Skip to main content
SpringerLink
Log in

Applications of Induced Pluripotent Stem Cell-Derived Glia in Brain Disease Research and Treatment

  • Chapter
  • First Online:
Human iPSC-derived Disease Models for Drug Discovery

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 281))

  • 345 Accesses

Abstract

Glia are integral components of neural networks and are crucial in both physiological functions and pathological processes of the brain. Many brain diseases involve glial abnormalities, including inflammatory changes, mitochondrial damage, calcium signaling disturbance, hemichannel opening, and loss of glutamate transporters. Induced pluripotent stem cell (iPSC)-derived glia provide opportunities to study the contributions of glia in human brain diseases. These cells have been used for human disease modeling as well as generating new therapies. This chapter introduces glial involvement in brain diseases, then summarizes different methods of generating iPSC-derived glia disease models of these cells. Finally, strategies for treating disease using iPSC-derived glia are discussed. The goal of this chapter is to provide an overview and shed light on the applications of iPSC-derived glia in brain disease research and treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA, Yeromin AV, Scarfone VM, Marsh SE, Fimbres C et al (2017) iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94:278–293.e279

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ager RR, Davis JL, Agazaryan A, Benavente F, Poon WW, LaFerla FM, Blurton-Jones M (2015) Human neural stem cells improve cognition and promote synaptic growth in two complementary transgenic models of Alzheimer's disease and neuronal loss. Hippocampus 25:813–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole GM, Cooper NR, Eikelenboom P, Emmerling M, Fiebich BL et al (2000) Inflammation and Alzheimer's disease. Neurobiol Aging 21:383–421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Albert K, Niskanen J, Kälvälä S, Lehtonen Š (2021) Utilising induced pluripotent stem cells in neurodegenerative disease research: focus on glia. Int J Mol Sci 22

    Google Scholar 

  • Ashpole NM, Chawla AR, Martin MP, Brustovetsky T, Brustovetsky N, Hudmon A (2013) Loss of calcium/calmodulin-dependent protein kinase II activity in cortical astrocytes decreases glutamate uptake and induces neurotoxic release of ATP. J Biol Chem 288:14599–14611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bahat-Stroomza M, Barhum Y, Levy YS, Karpov O, Bulvik S, Melamed E, Offen D (2009) Induction of adult human bone marrow mesenchymal stromal cells into functional astrocyte-like cells: potential for restorative treatment in Parkinson's disease. J Mol Neurosci 39:199–210

    Article  CAS  PubMed  Google Scholar 

  • Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S et al (2011) Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci U S A 108:14234–14239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bartzokis G (2011) Alzheimer's disease as homeostatic responses to age-related myelin breakdown. Neurobiol Aging 32:1341–1371

    Article  CAS  PubMed  Google Scholar 

  • Becerra-Calixto A, Cardona-Gómez GP (2017) Neuroprotection induced by transplanted CDK5 knockdown astrocytes in global cerebral ischemic rats. Mol Neurobiol 54:6681–6696

    Article  CAS  PubMed  Google Scholar 

  • Becerra-Calixto A, Posada-Duque R, Cardona-Gómez GP (2018) Recovery of neurovascular unit integrity by CDK5-KD astrocyte transplantation in a global cerebral ischemia model. Mol Neurobiol 55:8563–8585

    Article  CAS  PubMed  Google Scholar 

  • Benraiss A, Wang S, Herrlinger S, Li X, Chandler-Militello D, Mauceri J, Burm HB, Toner M, Osipovitch M, Xu QJ et al (2016) Human glia can both induce and rescue aspects of disease phenotype in Huntington disease. Nat Commun 7:11758

    Article  PubMed  PubMed Central  Google Scholar 

  • Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S et al (2013) Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 341:1233158

    Article  PubMed  Google Scholar 

  • Bigarreau J, Rouach N, Perrier AL, Mouthon F, Charvériat M (2022) Modeling and targeting neuroglial interactions with human pluripotent stem cell models. Int J Mol Sci 23

    Google Scholar 

  • Bohlen CJ, Bennett FC, Tucker AF, Collins HY, Mulinyawe SB, Barres BA (2017) Diverse requirements for microglial survival, specification, and function revealed by defined-medium cultures. Neuron 94:759–773.e758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bozoyan L, Khlghatyan J, Saghatelyan A (2012) Astrocytes control the development of the migration-promoting vasculature scaffold in the postnatal brain via VEGF signaling. J Neurosci 32:1687–1704

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Braak H, Sastre M, Del Tredici K (2007) Development of alpha-synuclein immunoreactive astrocytes in the forebrain parallels stages of intraneuronal pathology in sporadic Parkinson's disease. Acta Neuropathol 114:231–241

    Article  CAS  PubMed  Google Scholar 

  • Bradbury AM, Bongarzone ER, Sands MS (2021) Krabbe disease: new hope for an old disease. Neurosci Lett 752:135841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bradford J, Shin JY, Roberts M, Wang CE, Li XJ, Li S (2009) Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms. Proc Natl Acad Sci U S A 106:22480–22485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buchbinder D, Kelly DL, Duarte RF, Auletta JJ, Bhatt N, Byrne M, DeFilipp Z, Gabriel M, Mahindra A, Norkin M et al (2018) Neurocognitive dysfunction in hematopoietic cell transplant recipients: expert review from the late effects and Quality of Life Working Committee of the CIBMTR and complications and Quality of Life Working Party of the EBMT. Bone Marrow Transplant 53:535–555

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cai Q, Chen Z, Song P, Wu L, Wang L, Deng G, Liu B, Chen Q (2015) Co-transplantation of hippocampal neural stem cells and astrocytes and microvascular endothelial cells improve the memory in ischemic stroke rat. Int J Clin Exp Med 8:13109–13117

    CAS  PubMed  PubMed Central  Google Scholar 

  • Caiazzo M, Giannelli S, Valente P, Lignani G, Carissimo A, Sessa A, Colasante G, Bartolomeo R, Massimino L, Ferroni S et al (2015) Direct conversion of fibroblasts into functional astrocytes by defined transcription factors. Stem Cell Rep 4:25–36

    Article  CAS  Google Scholar 

  • Cameron B, Landreth GE (2010) Inflammation, microglia, and Alzheimer's disease. Neurobiol Dis 37:503–509

    Article  CAS  PubMed  Google Scholar 

  • Camp JG, Badsha F, Florio M, Kanton S, Gerber T, Wilsch-Bräuninger M, Lewitus E, Sykes A, Hevers W, Lancaster M et al (2015) Human cerebral organoids recapitulate gene expression programs of fetal neocortex development. Proc Natl Acad Sci U S A 112:15672–15677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Canals I, Ginisty A, Quist E, Timmerman R, Fritze J, Miskinyte G, Monni E, Hansen MG, Hidalgo I, Bryder D et al (2018) Rapid and efficient induction of functional astrocytes from human pluripotent stem cells. Nat Methods 15:693–696

    Article  CAS  PubMed  Google Scholar 

  • Chanoumidou K, Mozafari S, Baron-Van Evercooren A, Kuhlmann T (2020) Stem cell derived oligodendrocytes to study myelin diseases. Glia 68:705–720

    Article  PubMed  Google Scholar 

  • Chen S, Dong Z, Cheng M, Zhao Y, Wang M, Sai N, Wang X, Liu H, Huang G, Zhang X (2017) Homocysteine exaggerates microglia activation and neuroinflammation through microglia localized STAT3 overactivation following ischemic stroke. J Neuroinflammation 14:187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen D, Huang Y, Shi Z, Li J, Zhang Y, Wang K, Smith AD, Gong Y, Gao Y (2020) Demyelinating processes in aging and stroke in the central nervous system and the prospect of treatment strategy. CNS Neurosci Ther 26:1219–1229

    Article  PubMed  PubMed Central  Google Scholar 

  • Chlebanowska P, Tejchman A, Sułkowski M, Skrzypek K, Majka M (2020) Use of 3D organoids as a model to study idiopathic form of Parkinson's disease. Int J Mol Sci 21

    Google Scholar 

  • Choi I, Zhang Y, Seegobin SP, Pruvost M, Wang Q, Purtell K, Zhang B, Yue Z (2020) Microglia clear neuron-released α-synuclein via selective autophagy and prevent neurodegeneration. Nat Commun 11:1386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chu T, Zhou H, Li F, Wang T, Lu L, Feng S (2014) Astrocyte transplantation for spinal cord injury: current status and perspective. Brain Res Bull 107:18–30

    Article  CAS  PubMed  Google Scholar 

  • Clairembault T, Leclair-Visonneau L, Neunlist M, Derkinderen P (2015) Enteric glial cells: new players in Parkinson's disease? Mov Disord 30:494–498

    Article  PubMed  Google Scholar 

  • Colonna M, Butovsky O (2017) Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 35:441–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Correale J, Ysrraelit MC (2022) Multiple sclerosis and aging: the dynamics of demyelination and remyelination. ASN Neuro 14:17590914221118502

    Article  PubMed  PubMed Central  Google Scholar 

  • Czepiel M, Balasubramaniyan V, Schaafsma W, Stancic M, Mikkers H, Huisman C, Boddeke E, Copray S (2011) Differentiation of induced pluripotent stem cells into functional oligodendrocytes. Glia 59:882–892

    Article  PubMed  Google Scholar 

  • Dallérac G, Chever O, Rouach N (2013) How do astrocytes shape synaptic transmission? Insights from electrophysiology. Front Cell Neurosci 7:159

    Article  PubMed  PubMed Central  Google Scholar 

  • Davies JE, Huang C, Proschel C, Noble M, Mayer-Proschel M, Davies SJ (2006) Astrocytes derived from glial-restricted precursors promote spinal cord repair. J Biol 5:7

    Article  PubMed  PubMed Central  Google Scholar 

  • de Rus Jacquet A, Tancredi JL, Lemire AL, DeSantis MC, Li WP, O'Shea EK (2021) The LRRK2 G2019S mutation alters astrocyte-to-neuron communication via extracellular vesicles and induces neuron atrophy in a human iPSC-derived model of Parkinson's disease. Elife 10

    Google Scholar 

  • Delekate A, Füchtemeier M, Schumacher T, Ulbrich C, Foddis M, Petzold GC (2014) Metabotropic P2Y1 receptor signalling mediates astrocytic hyperactivity in vivo in an Alzheimer's disease mouse model. Nat Commun 5:5422

    Article  PubMed  Google Scholar 

  • Descalzi G (2021) Cortical astrocyte-neuronal metabolic coupling emerges as a critical modulator of stress-induced hopelessness. Neurosci Bull 37:132–134

    Article  PubMed  Google Scholar 

  • di Domenico A, Carola G, Calatayud C, Pons-Espinal M, Muñoz JP, Richaud-Patin Y, Fernandez-Carasa I, Gut M, Faella A, Parameswaran J et al (2019) Patient-specific iPSC-derived astrocytes contribute to non-cell-autonomous neurodegeneration in Parkinson's disease. Stem Cell Rep 12:213–229

    Article  Google Scholar 

  • Ding S (2014) Dynamic reactive astrocytes after focal ischemia. Neural Regen Res 9:2048–2052

    Article  PubMed  PubMed Central  Google Scholar 

  • Ding F, Liang S, Li R, Yang Z, He Y, Yang S, Duan Q, Zhang J, Lyu J, Zhou Z, Huang M, Wang H, Li J, Yang C, Wang Y, Gong M, Chen S, Jia H, Chen X, Liao X, Fu L, Zhang K (2022) Astrocytes exhibit diverse Ca2+ changes at subcellular domains during brain aging. Front Aging Neurosci

    Book  Google Scholar 

  • Douvaras P, Wang J, Zimmer M, Hanchuk S, O'Bara MA, Sadiq S, Sim FJ, Goldman J, Fossati V (2014) Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells. Stem Cell Rep 3:250–259

    Article  CAS  Google Scholar 

  • Dutta DJ, Woo DH, Lee PR, Pajevic S, Bukalo O, Huffman WC, Wake H, Basser PJ, SheikhBahaei S, Lazarevic V et al (2018) Regulation of myelin structure and conduction velocity by perinodal astrocytes. Proc Natl Acad Sci U S A 115:11832–11837

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Edgar JM, Garbern J (2004) The myelinated axon is dependent on the myelinating cell for support and maintenance: molecules involved. J Neurosci Res 76:593–598

    Article  CAS  PubMed  Google Scholar 

  • Ehrlich M, Mozafari S, Glatza M, Starost L, Velychko S, Hallmann AL, Cui QL, Schambach A, Kim KP, Bachelin C et al (2017) Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors. Proc Natl Acad Sci U S A 114:E2243–e2252

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Emdad L, D'Souza SL, Kothari HP, Qadeer ZA, Germano IM (2012) Efficient differentiation of human embryonic and induced pluripotent stem cells into functional astrocytes. Stem Cells Dev 21:404–410

    Article  CAS  PubMed  Google Scholar 

  • Esposito G, Sarnelli G, Capoccia E, Cirillo C, Pesce M, Lu J, Calì G, Cuomo R, Steardo L (2016) Autologous transplantation of intestine-isolated glia cells improves neuropathology and restores cognitive deficits in β amyloid-induced neurodegeneration. Sci Rep 6:22605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fan C, Zheng Y, Cheng X, Qi X, Bu P, Luo X, Kim DH, Cao Q (2013) Transplantation of D15A-expressing glial-restricted-precursor-derived astrocytes improves anatomical and locomotor recovery after spinal cord injury. Int J Biol Sci 9:78–93

    Article  CAS  PubMed  Google Scholar 

  • Ferraiuolo L, Meyer K, Sherwood TW, Vick J, Likhite S, Frakes A, Miranda CJ, Braun L, Heath PR, Pineda R et al (2016) Oligodendrocytes contribute to motor neuron death in ALS via SOD1-dependent mechanism. Proc Natl Acad Sci U S A 113:E6496–e6505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferreira GS, Veening-Griffioen DH, Boon WPC, Moors EHM, van Meer PJK (2020) Levelling the translational gap for animal to human efficacy data. Animals 10

    Google Scholar 

  • Flynn RW, MacWalter RS, Doney AS (2008) The cost of cerebral ischaemia. Neuropharmacology 55:250–256

    Article  CAS  PubMed  Google Scholar 

  • Franklin RJ, Ffrench-Constant C (2008) Remyelination in the CNS: from biology to therapy. Nat Rev Neurosci 9:839–855

    Article  CAS  PubMed  Google Scholar 

  • Galiakberova AA, Surin AM, Bakaeva ZV, Sharipov RR, Zhang D, Dorovskoy DA, Shakirova KM, Fisenko AP, Dashinimaev EB (2022) IPSC-derived human neurons with GCaMP6s expression allow in vitro study of neurophysiological responses to neurochemicals. Neurochem Res 47:952–966

    Article  CAS  PubMed  Google Scholar 

  • Garcia VJ, Rushton DJ, Tom CM, Allen ND, Kemp PJ, Svendsen CN, Mattis VB (2019) Huntington's disease patient-derived astrocytes display electrophysiological impairments and reduced neuronal support. Front Neurosci 13:669

    Article  PubMed  PubMed Central  Google Scholar 

  • Ghatak S, Dolatabadi N, Trudler D, Zhang X, Wu Y, Mohata M, Ambasudhan R, Talantova M, Lipton SA (2019) Mechanisms of hyperexcitability in Alzheimer's disease hiPSC-derived neurons and cerebral organoids vs isogenic controls. Elife 8

    Google Scholar 

  • Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP et al (2005) A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet 365:415–416

    CAS  PubMed  Google Scholar 

  • Ginhoux F, Greter M, Leboeuf M, Nandi S, See P, Gokhan S, Mehler MF, Conway SJ, Ng LG, Stanley ER et al (2010) Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330:841–845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldman SA, Kuypers NJ (2015) How to make an oligodendrocyte. Development 142:3983–3995

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldman SA, Nedergaard M, Windrem MS (2012) Glial progenitor cell-based treatment and modeling of neurological disease. Science 338:491–495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gonzalez C, Armijo E, Bravo-Alegria J, Becerra-Calixto A, Mays CE, Soto C (2018) Modeling amyloid beta and tau pathology in human cerebral organoids. Mol Psychiatry 23:2363–2374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gordon A, Yoon SJ, Tran SS, Makinson CD, Park JY, Andersen J, Valencia AM, Horvath S, Xiao X, Huguenard JR et al (2021) Long-term maturation of human cortical organoids matches key early postnatal transitions. Nat Neurosci 24:331–342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gorzo KA, Gordon GR (2022) Photonics tools begin to clarify astrocyte calcium transients. Neurophotonics 9:021907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Greenamyre JT, Hastings TG (2004) Biomedicine. Parkinson's – divergent causes, convergent mechanisms. Science 304:1120–1122

    Article  CAS  PubMed  Google Scholar 

  • Griciuc A, Serrano-Pozo A, Parrado AR, Lesinski AN, Asselin CN, Mullin K, Hooli B, Choi SH, Hyman BT, Tanzi RE (2013) Alzheimer's disease risk gene CD33 inhibits microglial uptake of amyloid beta. Neuron 78:631–643

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu XL, Long CX, Sun L, Xie C, Lin X, Cai H (2010) Astrocytic expression of Parkinson's disease-related A53T alpha-synuclein causes neurodegeneration in mice. Mol Brain 3:12

    Article  PubMed  PubMed Central  Google Scholar 

  • Gunnarson E, Song Y, Kowalewski JM, Brismar H, Brines M, Cerami A, Andersson U, Zelenina M, Aperia A (2009) Erythropoietin modulation of astrocyte water permeability as a component of neuroprotection. Proc Natl Acad Sci U S A 106:1602–1607

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Halassa MM, Haydon PG (2010) Integrated brain circuits: astrocytic networks modulate neuronal activity and behavior. Annu Rev Physiol 72:335–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamilton J, Brustovetsky T, Sridhar A, Pan Y, Cummins TR, Meyer JS, Brustovetsky N (2020) Energy metabolism and mitochondrial superoxide anion production in pre-symptomatic striatal neurons derived from human-induced pluripotent stem cells expressing mutant huntingtin. Mol Neurobiol 57:668–684

    Article  CAS  PubMed  Google Scholar 

  • Hampton DW, Webber DJ, Bilican B, Goedert M, Spillantini MG, Chandran S (2010) Cell-mediated neuroprotection in a mouse model of human tauopathy. J Neurosci 30:9973–9983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han X, Chen M, Wang F, Windrem M, Wang S, Shanz S, Xu Q, Oberheim NA, Bekar L, Betstadt S et al (2013) Forebrain engraftment by human glial progenitor cells enhances synaptic plasticity and learning in adult mice. Cell Stem Cell 12:342–353

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Harry GJ (2013) Microglia during development and aging. Pharmacol Ther 139:313–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hastings N, Kuan WL, Osborne A, Kotter MRN (2022) Therapeutic potential of astrocyte transplantation. Cell Transplant 31:9636897221105499

    Article  PubMed  Google Scholar 

  • He T, Yang GY, Zhang Z (2022) Crosstalk of astrocytes and other cells during ischemic stroke. Life 12

    Google Scholar 

  • Heindl S, Gesierich B, Benakis C, Llovera G, Duering M, Liesz A (2018) Automated morphological analysis of microglia after stroke. Front Cell Neurosci 12:106

    Article  PubMed  PubMed Central  Google Scholar 

  • Helman G, Van Haren K, Bonkowsky JL, Bernard G, Pizzino A, Braverman N, Suhr D, Patterson MC, Ali Fatemi S, Leonard J et al (2015) Disease specific therapies in leukodystrophies and leukoencephalopathies. Mol Genet Metab 114:527–536

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC et al (2013) NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493:674–678

    Article  CAS  PubMed  Google Scholar 

  • Henneberger C, Papouin T, Oliet SH, Rusakov DA (2010) Long-term potentiation depends on release of D-serine from astrocytes. Nature 463:232–236

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT, Close JL, Long B, Johansen N, Penn O et al (2019) Conserved cell types with divergent features in human versus mouse cortex. Nature 573:61–68

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ip CW, Kroner A, Bendszus M, Leder C, Kobsar I, Fischer S, Wiendl H, Nave KA, Martini R (2006) Immune cells contribute to myelin degeneration and axonopathic changes in mice overexpressing proteolipid protein in oligodendrocytes. J Neurosci 26:8206–8216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeyakumar M, Dwek RA, Butters TD, Platt FM (2005) Storage solutions: treating lysosomal disorders of the brain. Nat Rev Neurosci 6:713–725

    Article  PubMed  Google Scholar 

  • Jiang R, Diaz-Castro B, Looger LL, Khakh BS (2016) Dysfunctional calcium and glutamate Signaling in striatal astrocytes from Huntington's disease model mice. J Neurosci 36:3453–3470

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jo J, Xiao Y, Sun AX, Cukuroglu E, Tran HD, Göke J, Tan ZY, Saw TY, Tan CP, Lokman H et al (2016) Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell 19:248–257

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juopperi TA, Kim WR, Chiang CH, Yu H, Margolis RL, Ross CA, Ming GL, Song H (2012) Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington's disease patient cells. Mol Brain 5:17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim H, Park HJ, Choi H, Chang Y, Park H, Shin J, Kim J, Lengner CJ, Lee YK, Kim J (2019a) Modeling G2019S-LRRK2 sporadic Parkinson's disease in 3D midbrain organoids. Stem Cell Rep 12:518–531

    Article  CAS  Google Scholar 

  • Kim Y, Park J, Choi YK (2019b) The role of astrocytes in the central nervous system focused on BK channel and heme oxygenase metabolites: a review. Antioxidants 8

    Google Scholar 

  • Kimoff RJ, Kaminska M, Trojan D (2022) Multiple sclerosis and related disorders. Handb Clin Neurol 189:177–200

    Article  PubMed  Google Scholar 

  • Kliot M, Smith GM, Siegal JD, Silver J (1990) Astrocyte-polymer implants promote regeneration of dorsal root fibers into the adult mammalian spinal cord. Exp Neurol 109:57–69

    Article  CAS  PubMed  Google Scholar 

  • Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711–715

    Article  CAS  PubMed  Google Scholar 

  • Krencik R, Zhang SC (2011) Directed differentiation of functional astroglial subtypes from human pluripotent stem cells. Nat Protoc 6:1710–1717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krencik R, Weick JP, Liu Y, Zhang ZJ, Zhang SC (2011) Specification of transplantable astroglial subtypes from human pluripotent stem cells. Nat Biotechnol 29:528–534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krivit W (2002) Stem cell bone marrow transplantation in patients with metabolic storage diseases. Adv Pediatr 49:359–378

    PubMed  Google Scholar 

  • Kuan WL, Kasis A, Yuan Y, Mason SL, Lazar AS, Barker RA, Goncalves J (2015) Modelling the natural history of Huntington's disease progression. J Neurol Neurosurg Psychiatry 86:1143–1149

    Article  CAS  PubMed  Google Scholar 

  • Kuchibhotla KV, Lattarulo CR, Hyman BT, Bacskai BJ (2009) Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice. Science 323:1211–1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuga N, Sasaki T, Takahara Y, Matsuki N, Ikegaya Y (2011) Large-scale calcium waves traveling through astrocytic networks in vivo. J Neurosci 31:2607–2614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar M, Nguyen NTP, Milanese M, Bonanno G (2022) Insights into human-induced pluripotent stem cell-derived astrocytes in neurodegenerative disorders. Biomol Ther 12

    Google Scholar 

  • Kwak TH, Kang JH, Hali S, Kim J, Kim KP, Park C, Lee JH, Ryu HK, Na JE, Jo J et al (2020) Generation of homogeneous midbrain organoids with in vivo-like cellular composition facilitates neurotoxin-based Parkinson's disease modeling. Stem Cells 38:727–740

    Article  CAS  PubMed  Google Scholar 

  • Lalancette-Hébert M, Gowing G, Simard A, Weng YC, Kriz J (2007) Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 27:2596–2605

    Article  PubMed  PubMed Central  Google Scholar 

  • Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013) Cerebral organoids model human brain development and microcephaly. Nature 501:373–379

    Article  CAS  PubMed  Google Scholar 

  • Lee JP, Jeyakumar M, Gonzalez R, Takahashi H, Lee PJ, Baek RC, Clark D, Rose H, Fu G, Clarke J et al (2007) Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease. Nat Med 13:439–447

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Suk JE, Patrick C, Bae EJ, Cho JH, Rho S, Hwang D, Masliah E, Lee SJ (2010) Direct transfer of alpha-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies. J Biol Chem 285:9262–9272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee Y, Morrison BM, Li Y, Lengacher S, Farah MH, Hoffman PN, Liu Y, Tsingalia A, Jin L, Zhang PW et al (2012) Oligodendroglia metabolically support axons and contribute to neurodegeneration. Nature 487:443–448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lester DB, Rogers TD, Blaha CD (2010) Acetylcholine-dopamine interactions in the pathophysiology and treatment of CNS disorders. CNS Neurosci Ther 16:137–162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li H, Jiang H, Zhang B, Feng J (2018) Modeling Parkinson's disease using patient-specific induced pluripotent stem cells. J Parkinsons Dis 8:479–493

    Article  PubMed  PubMed Central  Google Scholar 

  • Li L, Li R, Zacharek A, Wang F, Landschoot-Ward J, Chopp M, Chen J, Cui X (2020a) ABCA1/ApoE/HDL signaling pathway facilitates myelination and oligodendrogenesis after stroke. Int J Mol Sci 21

    Google Scholar 

  • Li X, Liao Y, Dong Y, Li S, Wang F, Wu R, Yuan Z, Cheng J (2020b) Mib2 deficiency inhibits microglial activation and alleviates ischemia-induced brain injury. Aging Dis 11:523–535

    Article  PubMed  PubMed Central  Google Scholar 

  • Lin YT, Seo J, Gao F, Feldman HM, Wen HL, Penney J, Cam HP, Gjoneska E, Raja WK, Cheng J et al (2018) APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC-derived brain cell types. Neuron 98:1294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lippmann ES, Williams CE, Ruhl DA, Estevez-Silva MC, Chapman ER, Coon JJ, Ashton RS (2015) Deterministic HOX patterning in human pluripotent stem cell-derived neuroectoderm. Stem Cell Rep 4:632–644

    Article  CAS  Google Scholar 

  • Luo C, Lancaster MA, Castanon R, Nery JR, Knoblich JA, Ecker JR (2016) Cerebral organoids recapitulate epigenomic signatures of the human Fetal brain. Cell Rep 17:3369–3384

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lutz SE, Zhao Y, Gulinello M, Lee SC, Raine CS, Brosnan CF (2009) Deletion of astrocyte connexins 43 and 30 leads to a dysmyelinating phenotype and hippocampal CA1 vacuolation. J Neurosci 29:7743–7752

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maezawa I, Zimin PI, Wulff H, Jin LW (2011) Amyloid-beta protein oligomer at low nanomolar concentrations activates microglia and induces microglial neurotoxicity. J Biol Chem 286:3693–3706

    Article  CAS  PubMed  Google Scholar 

  • Mariani JN, Zou L, Goldman SA (2019) Human glial chimeric mice to define the role of glial pathology in human disease. Methods Mol Biol 1936:311–331

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marin MA, Carmichael ST (2019) Mechanisms of demyelination and remyelination in the young and aged brain following white matter stroke. Neurobiol Dis 126:5–12

    Article  CAS  PubMed  Google Scholar 

  • Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL (2015) Alzheimer's disease. Nat Rev Dis Primers 1:15056

    Article  PubMed  Google Scholar 

  • McGraw P, Liang L, Escolar M, Mukundan S, Kurtzberg J, Provenzale JM (2005) Krabbe disease treated with hematopoietic stem cell transplantation: serial assessment of anisotropy measurements – initial experience. Radiology 236:221–230

    Article  PubMed  Google Scholar 

  • Meyer DA, Torres-Altoro MI, Tan Z, Tozzi A, Di Filippo M, DiNapoli V, Plattner F, Kansy JW, Benkovic SA, Huber JD et al (2014) Ischemic stroke injury is mediated by aberrant Cdk5. J Neurosci 34:8259–8267

    Article  PubMed  PubMed Central  Google Scholar 

  • Micu I, Plemel JR, Caprariello AV, Nave KA, Stys PK (2018) Axo-myelinic neurotransmission: a novel mode of cell signalling in the central nervous system. Nat Rev Neurosci 19:49–58

    Article  CAS  PubMed  Google Scholar 

  • Miller JD, Ganat YM, Kishinevsky S, Bowman RL, Liu B, Tu EY, Mandal PK, Vera E, Shim JW, Kriks S et al (2013) Human iPSC-based modeling of late-onset disease via progerin-induced aging. Cell Stem Cell 13:691–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mirzaei N, Davis N, Chau TW, Sastre M (2022) Astrocyte reactivity in Alzheimer's disease: therapeutic opportunities to promote repair. Curr Alzheimer Res 19:1–15

    Article  CAS  PubMed  Google Scholar 

  • Moehle MS, Webber PJ, Tse T, Sukar N, Standaert DG, DeSilva TM, Cowell RM, West AB (2012) LRRK2 inhibition attenuates microglial inflammatory responses. J Neurosci 32:1602–1611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Monzel AS, Hemmer K, Kaoma T, Smits LM, Bolognin S, Lucarelli P, Rosety I, Zagare A, Antony P, Nickels SL et al (2020) Machine learning-assisted neurotoxicity prediction in human midbrain organoids. Parkinsonism Relat Disord 75:105–109

    Article  PubMed  Google Scholar 

  • Mozafari S, Baron-Van Evercooren A (2021) Human stem cell-derived oligodendrocytes: from humanized animal models to cell therapy in myelin diseases. Semin Cell Dev Biol 116:53–61

    Article  PubMed  Google Scholar 

  • Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S, Bakiasi G, Tsai LH, Aubourg P, Ransohoff RM et al (2016) Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med 22:1358–1367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nahirney PC, Reeson P, Brown CE (2016) Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice. J Cereb Blood Flow Metab 36:413–425

    Article  PubMed  Google Scholar 

  • Najm FJ, Lager AM, Zaremba A, Wyatt K, Caprariello AV, Factor DC, Karl RT, Maeda T, Miller RH, Tesar PJ (2013) Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nat Biotechnol 31:426–433

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Najm R, Zalocusky KA, Zilberter M, Yoon SY, Hao Y, Koutsodendris N, Nelson M, Rao A, Taubes A, Jones EA et al (2020) In vivo chimeric Alzheimer's disease modeling of apolipoprotein E4 toxicity in human neurons. Cell Rep 32:107962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nasrabady SE, Rizvi B, Goldman JE, Brickman AM (2018) White matter changes in Alzheimer's disease: a focus on myelin and oligodendrocytes. Acta Neuropathol Commun 6:22

    Article  PubMed  PubMed Central  Google Scholar 

  • Neher JJ, Emmrich JV, Fricker M, Mander PK, Théry C, Brown GC (2013) Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc Natl Acad Sci U S A 110:E4098–E4107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neher JJ, Neniskyte U, Hornik T, Brown GC (2014) Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo. Glia 62:1463–1475

    Article  PubMed  PubMed Central  Google Scholar 

  • Neufeld EF (1991) Lysosomal storage diseases. Annu Rev Biochem 60:257–280

    Article  CAS  PubMed  Google Scholar 

  • Nguyen HN, Byers B, Cord B, Shcheglovitov A, Byrne J, Gujar P, Kee K, Schüle B, Dolmetsch RE, Langston W et al (2011) LRRK2 mutant iPSC-derived DA neurons demonstrate increased susceptibility to oxidative stress. Cell Stem Cell 8:267–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oksanen M, Petersen AJ, Naumenko N, Puttonen K, Lehtonen Š, Gubert Olivé M, Shakirzyanova A, Leskelä S, Sarajärvi T, Viitanen M et al (2017) PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer's disease. Stem Cell Rep 9:1885–1897

    Article  CAS  Google Scholar 

  • Olabarria M, Noristani HN, Verkhratsky A, Rodríguez JJ (2010) Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease. Glia 58:831–838

    Article  PubMed  Google Scholar 

  • Olby NJ, Blakemore WF (1996) Reconstruction of the glial environment of a photochemically induced lesion in the rat spinal cord by transplantation of mixed glial cells. J Neurocytol 25:481–498

    Article  CAS  PubMed  Google Scholar 

  • Osakada F, Takahashi M (2011) Neural induction and patterning in Mammalian pluripotent stem cells. CNS Neurol Disord Drug Targets 10:419–432

    Article  CAS  PubMed  Google Scholar 

  • Osborn LM, Kamphuis W, Wadman WJ, Hol EM (2016) Astrogliosis: an integral player in the pathogenesis of Alzheimer's disease. Prog Neurobiol 144:121–141

    Article  CAS  PubMed  Google Scholar 

  • Ouyang YB, Voloboueva LA, Xu LJ, Giffard RG (2007) Selective dysfunction of hippocampal CA1 astrocytes contributes to delayed neuronal damage after transient forebrain ischemia. J Neurosci 27:4253–4260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ouyang YB, Xu L, Liu S, Giffard RG (2014) Role of astrocytes in delayed neuronal death: GLT-1 and its novel regulation by MicroRNAs. Adv Neurobiol 11:171–188

    Article  PubMed  PubMed Central  Google Scholar 

  • Palpagama TH, Waldvogel HJ, Faull RLM, Kwakowsky A (2019) The role of microglia and astrocytes in Huntington's disease. Front Mol Neurosci 12:258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parajuli B, Koizumi S (2022) Strategies for manipulating microglia to determine their role in the healthy and diseased brain. Neurochem Res

    Google Scholar 

  • Parajuli B, Sonobe Y, Horiuchi H, Takeuchi H, Mizuno T, Suzumura A (2013) Oligomeric amyloid β induces IL-1β processing via production of ROS: implication in Alzheimer's disease. Cell Death Dis 4:e975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paşca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, Kim CH, Park JY, O'Rourke NA, Nguyen KD et al (2015) Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods 12:671–678

    Article  PubMed  PubMed Central  Google Scholar 

  • Pihlaja R, Koistinaho J, Malm T, Sikkilä H, Vainio S, Koistinaho M (2008) Transplanted astrocytes internalize deposited beta-amyloid peptides in a transgenic mouse model of Alzheimer's disease. Glia 56:154–163

    Article  PubMed  Google Scholar 

  • Platt FM, d'Azzo A, Davidson BL, Neufeld EF, Tifft CJ (2018) Lysosomal storage diseases. Nat Rev Dis Primers 4:27

    Article  PubMed  Google Scholar 

  • Popko B (2010) Myelin maintenance: axonal support required. Nat Neurosci 13:275–277

    Article  CAS  PubMed  Google Scholar 

  • Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I (2004) Where is the evidence that animal research benefits humans? BMJ 328:514–517

    Article  PubMed  PubMed Central  Google Scholar 

  • Proschel C, Stripay JL, Shih CH, Munger JC, Noble MD (2014) Delayed transplantation of precursor cell-derived astrocytes provides multiple benefits in a rat model of Parkinsons. EMBO Mol Med 6:504–518

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin H, He W, Yang C, Li J, Jian T, Liang S, Chen T, Feng H, Chen X, Liao X et al (2020) Monitoring astrocytic Ca(2+) activity in freely behaving mice. Front Cell Neurosci 14:603095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Radde R, Bolmont T, Kaeser SA, Coomaraswamy J, Lindau D, Stoltze L, Calhoun ME, Jäggi F, Wolburg H, Gengler S et al (2006) Abeta42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology. EMBO Rep 7:940–946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raja WK, Mungenast AE, Lin YT, Ko T, Abdurrob F, Seo J, Tsai LH (2016) Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer's disease phenotypes. PloS One 11:e0161969

    Article  PubMed  PubMed Central  Google Scholar 

  • Renner M, Lancaster MA, Bian S, Choi H, Ku T, Peer A, Chung K, Knoblich JA (2017) Self-organized developmental patterning and differentiation in cerebral organoids. EMBO J 36:1316–1329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Revah O, Gore F, Kelley KW, Andersen J, Sakai N, Chen X, Li MY, Birey F, Yang X, Saw NL et al (2022) Maturation and circuit integration of transplanted human cortical organoids. Nature 610:319–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Robertson JM (2018) The Gliocentric brain. Int J Mol Sci 19

    Google Scholar 

  • Rosati G (2001) The prevalence of multiple sclerosis in the world: an update. Neurol Sci 22:117–139

    Article  CAS  PubMed  Google Scholar 

  • Sailor KA, Agoranos G, López-Manzaneda S, Tada S, Gillet-Legrand B, Guerinot C, Masson JB, Vestergaard CL, Bonner M, Gagnidze K et al (2022) Hematopoietic stem cell transplantation chemotherapy causes microglia senescence and peripheral macrophage engraftment in the brain. Nat Med 28:517–527

    Article  CAS  PubMed  Google Scholar 

  • Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ransohoff RM, Greenberg ME, Barres BA, Stevens B (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheiblich H, Dansokho C, Mercan D, Schmidt SV, Bousset L, Wischhof L, Eikens F, Odainic A, Spitzer J, Griep A et al (2021) Microglia jointly degrade fibrillar alpha-synuclein cargo by distribution through tunneling nanotubes. Cell 184:5089–5106.e5021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, Van der Flier WM (2016) Alzheimer's disease. Lancet 388:505–517

    Article  CAS  PubMed  Google Scholar 

  • Semyanov A, Henneberger C, Agarwal A (2020) Making sense of astrocytic calcium signals – from acquisition to interpretation. Nat Rev Neurosci 21:551–564

    Article  CAS  PubMed  Google Scholar 

  • Serrano-Pozo A, Mielke ML, Gómez-Isla T, Betensky RA, Growdon JH, Frosch MP, Hyman BT (2011) Reactive glia not only associates with plaques but also parallels tangles in Alzheimer's disease. Am J Pathol 179:1373–1384

    Article  PubMed  PubMed Central  Google Scholar 

  • Shaltouki A, Peng J, Liu Q, Rao MS, Zeng X (2013) Efficient generation of astrocytes from human pluripotent stem cells in defined conditions. Stem Cells 31:941–952

    Article  CAS  PubMed  Google Scholar 

  • Silva M, Daheron L, Hurley H, Bure K, Barker R, Carr AJ, Williams D, Kim HW, French A, Coffey PJ et al (2015) Generating iPSCs: translating cell reprogramming science into scalable and robust biomanufacturing strategies. Cell Stem Cell 16:13–17

    Article  CAS  PubMed  Google Scholar 

  • Simons M, Nave KA (2015) Oligodendrocytes: myelination and axonal support. Cold Spring Harb Perspect Biol 8:a020479

    Article  PubMed  Google Scholar 

  • Singh A, Tetreault L, Kalsi-Ryan S, Nouri A, Fehlings MG (2014) Global prevalence and incidence of traumatic spinal cord injury. Clin Epidemiol 6:309–331

    PubMed  PubMed Central  Google Scholar 

  • Smits LM, Reinhardt L, Reinhardt P, Glatza M, Monzel AS, Stanslowsky N, Rosato-Siri MD, Zanon A, Antony PM, Bellmann J et al (2019) Modeling Parkinson's disease in midbrain-like organoids. NPJ Parkinson's Dis 5:5

    Article  Google Scholar 

  • Snyder EY, Taylor RM, Wolfe JH (1995) Neural progenitor cell engraftment corrects lysosomal storage throughout the MPS VII mouse brain. Nature 374:367–370

    Article  CAS  PubMed  Google Scholar 

  • Sompol P, Norris CM (2018) Ca(2+), astrocyte activation and calcineurin/NFAT signaling in age-related neurodegenerative diseases. Front Aging Neurosci 10:199

    Article  PubMed  PubMed Central  Google Scholar 

  • Song JJ, Oh SM, Kwon OC, Wulansari N, Lee HS, Chang MY, Lee E, Sun W, Lee SE, Chang S et al (2018) Cografting astrocytes improves cell therapeutic outcomes in a Parkinson's disease model. J Clin Invest 128:463–482

    Article  PubMed  Google Scholar 

  • Stahon KE, Bastian C, Griffith S, Kidd GJ, Brunet S, Baltan S (2016) Age-related changes in axonal and mitochondrial ultrastructure and function in white matter. J Neurosci 36:9990–10001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Steinman MQ, Gao V, Alberini CM (2016) The role of lactate-mediated metabolic coupling between astrocytes and neurons in long-term memory formation. Front Integr Neurosci 10:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Su SC, Tsai LH (2011) Cyclin-dependent kinases in brain development and disease. Annu Rev Cell Dev Biol 27:465–491

    Article  CAS  PubMed  Google Scholar 

  • Suga M, Kondo T, Inoue H (2019) Modeling neurological disorders with human pluripotent stem cell-derived astrocytes. Int J Mol Sci 20

    Google Scholar 

  • Suzuki K, Suzuki Y (1970) Globoid cell leucodystrophy (Krabbe's disease): deficiency of galactocerebroside beta-galactosidase. Proc Natl Acad Sci U S A 66:302–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swanson RA, Ying W, Kauppinen TM (2004) Astrocyte influences on ischemic neuronal death. Curr Mol Med 4:193–205

    Article  CAS  PubMed  Google Scholar 

  • Szabó Z, Héja L, Szalay G, Kékesi O, Füredi A, Szebényi K, Dobolyi Á, Orbán TI, Kolacsek O, Tompa T et al (2017) Extensive astrocyte synchronization advances neuronal coupling in slow wave activity in vivo. Sci Rep 7:6018

    Article  PubMed  PubMed Central  Google Scholar 

  • Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K, Okita K, Nakagawa M, Yamanaka S (2007) Induction of pluripotent stem cells from fibroblast cultures. Nat Protoc 2:3081–3089

    Article  CAS  PubMed  Google Scholar 

  • Takata K, Kozaki T, Lee CZW, Thion MS, Otsuka M, Lim S, Utami KH, Fidan K, Park DS, Malleret B et al (2017) Induced-pluripotent-stem-cell-derived primitive macrophages provide a platform for modeling tissue-resident macrophage differentiation and function. Immunity 47:183–198.e186

    Article  CAS  PubMed  Google Scholar 

  • Tchieu J, Calder EL, Guttikonda SR, Gutzwiller EM, Aromolaran KA, Steinbeck JA, Goldstein PA, Studer L (2019) NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells. Nat Biotechnol 37:267–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tcw J, Wang M, Pimenova AA, Bowles KR, Hartley BJ, Lacin E, Machlovi SI, Abdelaal R, Karch CM, Phatnani H et al (2017) An efficient platform for astrocyte differentiation from human induced pluripotent stem cells. Stem Cell Rep 9:600–614

    Article  CAS  Google Scholar 

  • Tieng V, Stoppini L, Villy S, Fathi M, Dubois-Dauphin M, Krause KH (2014) Engineering of midbrain organoids containing long-lived dopaminergic neurons. Stem Cells Dev 23:1535–1547

    Article  CAS  PubMed  Google Scholar 

  • Tornatore C, Baker-Cairns B, Yadid G, Hamilton R, Meyers K, Atwood W, Cummins A, Tanner V, Major E (1996) Expression of tyrosine hydroxylase in an immortalized human fetal astrocyte cell line; in vitro characterization and engraftment into the rodent striatum. Cell Transplant 5:145–163

    CAS  PubMed  Google Scholar 

  • Tremblay M, Lowery RL, Majewska AK (2010) Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8:e1000527

    Article  PubMed  PubMed Central  Google Scholar 

  • Tse KH, Herrup K (2017) DNA damage in the oligodendrocyte lineage and its role in brain aging. Mech Ageing Dev 161:37–50

    Article  CAS  PubMed  Google Scholar 

  • Tsuchiya T, Park KC, Toyonaga S, Yamada SM, Nakabayashi H, Nakai E, Ikawa N, Furuya M, Tominaga A, Shimizu K (2005) Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma. J Neuroimmunol 160:210–218

    Article  CAS  PubMed  Google Scholar 

  • Villa A, Gelosa P, Castiglioni L, Cimino M, Rizzi N, Pepe G, Lolli F, Marcello E, Sironi L, Vegeto E et al (2018) Sex-specific features of microglia from adult mice. Cell Rep 23:3501–3511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volterra A, Liaudet N, Savtchouk I (2014) Astrocyte Ca2+ signalling: an unexpected complexity. Nat Rev Neurosci 15:327–335

    Article  CAS  PubMed  Google Scholar 

  • von Bartheld CS, Bahney J, Herculano-Houzel S (2016) The search for true numbers of neurons and glial cells in the human brain: a review of 150 years of cell counting. J Comp Neurol 524:3865–3895

    Article  Google Scholar 

  • Waldvogel HJ, Kim EH, Tippett LJ, Vonsattel JP, Faull RL (2015) The neuropathology of Huntington's disease. Curr Top Behav Neurosci 22:33–80

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, Maherali N, Studer L, Hochedlinger K, Windrem M et al (2013) Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell 12:252–264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang M, Zhang L, Gage FH (2020) Modeling neuropsychiatric disorders using human induced pluripotent stem cells. Protein Cell 11:45–59

    Article  CAS  PubMed  Google Scholar 

  • Wang Q, Lu M, Zhu X, Gu X, Zhang T, Xia C, Yang L, Xu Y, Zhou M (2022) The role of microglia immunometabolism in neurodegeneration: focus on molecular determinants and metabolic intermediates of metabolic reprogramming. Biomed Pharmacother 153:113412

    Article  CAS  PubMed  Google Scholar 

  • Weinstock-Guttman B, Ramanathan M (2012) Multiple sclerosis in 2011: advances in therapy, imaging and risk factors in MS. Nat Rev Neurol 8:66–68

    Article  CAS  PubMed  Google Scholar 

  • Wilkins A, Majed H, Layfield R, Compston A, Chandran S (2003) Oligodendrocytes promote neuronal survival and axonal length by distinct intracellular mechanisms: a novel role for oligodendrocyte-derived glial cell line-derived neurotrophic factor. J Neurosci 23:4967–4974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Windrem MS, Roy NS, Wang J, Nunes M, Benraiss A, Goodman R, McKhann GM 2nd, Goldman SA (2002) Progenitor cells derived from the adult human subcortical white matter disperse and differentiate as oligodendrocytes within demyelinated lesions of the rat brain. J Neurosci Res 69:966–975

    Article  CAS  PubMed  Google Scholar 

  • Windrem MS, Schanz SJ, Guo M, Tian GF, Washco V, Stanwood N, Rasband M, Roy NS, Nedergaard M, Havton LA et al (2008) Neonatal chimerization with human glial progenitor cells can both remyelinate and rescue the otherwise lethally hypomyelinated shiverer mouse. Cell Stem Cell 2:553–565

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Winship IR, Plaa N, Murphy TH (2007) Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J Neurosci 27:6268–6272

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu JL, Gao TM (2022) Monitoring the activity of astrocytes in learning and memory. Neurosci Bull 38:1117–1120

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu L, Li J, Chen L, Zhang H, Yuan L, Davies SJ (2013) Combined transplantation of GDAs(BMP) and hr-decorin in spinal cord contusion repair. Neural Regen Res 8:2236–2248

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wyndaele M, Wyndaele JJ (2006) Incidence, prevalence and epidemiology of spinal cord injury: what learns a worldwide literature survey? Spinal Cord 44:523–529

    Article  CAS  PubMed  Google Scholar 

  • Xin W, Chan JR (2020) Myelin plasticity: sculpting circuits in learning and memory. Nat Rev Neurosci 21:682–694

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yandava BD, Billinghurst LL, Snyder EY (1999) "Global" cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci U S A 96:7029–7034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Jalal FY, Thompson JF, Walker EJ, Candelario-Jalil E, Li L, Reichard RR, Ben C, Sang QX, Cunningham LA et al (2011) Tissue inhibitor of metalloproteinases-3 mediates the death of immature oligodendrocytes via TNF-α/TACE in focal cerebral ischemia in mice. J Neuroinflammation 8:108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, Hawkins JS, Geissler R, Barres BA, Wernig M (2013) Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol 31:434–439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Z, Gong M, Jian T, Li J, Yang C, Ma Q, Deng P, Wang Y, Huang M, Wang H et al (2022) Engrafted glial progenitor cells yield long-term integration and sensory improvement in aged mice. Stem Cell Res Ther 13:285

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yeh CY, Vadhwana B, Verkhratsky A, Rodríguez JJ (2011) Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease. ASN Neuro 3:271–279

    Article  CAS  PubMed  Google Scholar 

  • Yin J, VanDongen AM (2021) Enhanced neuronal activity and asynchronous calcium transients revealed in a 3D organoid model of Alzheimer's disease. ACS Biomater Sci Eng 7:254–264

    Article  CAS  PubMed  Google Scholar 

  • Yin YN, Hu J, Wei YL, Li ZL, Luo ZC, Wang RQ, Yang KX, Li SJ, Li XW, Yang JM et al (2021) Astrocyte-derived lactate modulates the passive coping response to behavioral challenge in male mice. Neurosci Bull 37:1–14

    Article  CAS  PubMed  Google Scholar 

  • Yu G, Zhang Y, Ning B (2021) Reactive astrocytes in central nervous system injury: subgroup and potential therapy. Front Cell Neurosci 15:792764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeiss CJ (2015) Improving the predictive value of interventional animal models data. Drug Discov Today 20:475–482

    Article  PubMed  Google Scholar 

  • Zhang K, Chen X (2017) Sensory response in host and engrafted astrocytes of adult brain in vivo. Glia 65:1867–1884

    Article  PubMed  Google Scholar 

  • Zhang K, Chen C, Yang Z, He W, Liao X, Ma Q, Deng P, Lu J, Li J, Wang M et al (2016) Sensory response of transplanted astrocytes in adult mammalian cortex in vivo. Cereb Cortex 26:3690–3704

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang K, Förster R, He W, Liao X, Li J, Yang C, Qin H, Wang M, Ding R, Li R et al (2021) Fear learning induces α7-nicotinic acetylcholine receptor-mediated astrocytic responsiveness that is required for memory persistence. Nat Neurosci 24:1686–1698

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Brain Research Center and State Key Laboratory of Trauma and Chemical Poisoning, Third Military Medical University, Chongqing, China

    Zhiqi Yang, Mingyue Gong, Chuanyan Yang & Kuan Zhang

  2. Department of Occupational Health, Third Military Medical University, Chongqing, China

    Chunhai Chen

Authors
  1. Zhiqi Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mingyue Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chuanyan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunhai Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kuan Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kuan Zhang .

Editor information

Editors and Affiliations

  1. Center for Prevention and Treatment of Visual Loss; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA, USA

    Markus H. Kuehn

  2. School of Pharmacy, Qingdao University, Qingdao, Shandong, China

    Wei Zhu

Ethics declarations

We thank Jia Lou for technical assistance.

Funding

This work was supported by the National Key R&D Program of China (no. 2018YFA0109600) and the National Natural Science Foundation of China (no. 81771175).

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yang, Z., Gong, M., Yang, C., Chen, C., Zhang, K. (2023). Applications of Induced Pluripotent Stem Cell-Derived Glia in Brain Disease Research and Treatment. In: Kuehn, M.H., Zhu, W. (eds) Human iPSC-derived Disease Models for Drug Discovery. Handbook of Experimental Pharmacology, vol 281. Springer, Cham. https://doi.org/10.1007/164_2023_697

Download citation

Publish with us

Policies and ethics

Search

Navigation