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iPSCs-Derived Neurons and Brain Organoids from Patients

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Human iPSC-derived Disease Models for Drug Discovery

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

Abstract

Induced pluripotent stem cells (iPSCs) can be differentiated into specific neurons and brain organoids by adding induction factors and small molecules in vitro, which carry human genetic information and recapitulate the development process of human brain as well as physiological, pathological, and pharmacological characteristics. Hence, iPSC-derived neurons and organoids hold great promise for studying human brain development and related nervous system diseases in vitro, and provide a platform for drug screening. In this chapter, we summarize the development of the differentiation techniques for neurons and brain organoids from iPSCs, and their applications in studying brain disease, drug screening, and transplantation.

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References

  • Almeida S et al (2012) Induced pluripotent stem cell models of progranulin-deficient frontotemporal dementia uncover specific reversible neuronal defects. Cell Rep 2(4):789–798

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ananiev G et al (2011) Isogenic pairs of wild type and mutant induced pluripotent stem cell (iPSC) lines from Rett syndrome patients as in vitro disease model. PloS One 6(9):e25255

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Andersen J et al (2020) Generation of functional human 3D Cortico-motor Assembloids. Cell 183(7):1913–1929 e26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Avior Y, Sagi I, Benvenisty N (2016) Pluripotent stem cells in disease modelling and drug discovery. Nat Rev Mol Cell Biol 17(3):170–182

    Article  CAS  PubMed  Google Scholar 

  • Bagley JA et al (2017) Fused cerebral organoids model interactions between brain regions. Nat Methods 14(7):743–751

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bamba Y et al (2016) In vitro characterization of neurite extension using induced pluripotent stem cells derived from lissencephaly patients with TUBA1A missense mutations. Mol Brain 9(1):70

    Article  PubMed  PubMed Central  Google Scholar 

  • Barker RA, Drouin-Ouellet J, Parmar M (2015) Cell-based therapies for Parkinson disease – past insights and future potential. Nat Rev Neurol 11(9):492–503

    Article  CAS  PubMed  Google Scholar 

  • Barmada SJ et al (2014) Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models. Nat Chem Biol 10(8):677–685

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benito-Kwiecinski S et al (2021) An early cell shape transition drives evolutionary expansion of the human forebrain. Cell 184(8):2084–2102.e19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bidinosti M et al (2016) CLK2 inhibition ameliorates autistic features associated with SHANK3 deficiency. Science 351(6278):1199–1203

    Article  CAS  PubMed  Google Scholar 

  • Birey F et al (2017) Assembly of functionally integrated human forebrain spheroids. Nature 545(7652):54–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Birey F et al (2022) Dissecting the molecular basis of human interneuron migration in forebrain assembloids from Timothy syndrome. Cell Stem Cell 29(2):248–264.e7

    Article  CAS  PubMed  Google Scholar 

  • Brennand KJ et al (2011) Modelling schizophrenia using human induced pluripotent stem cells. Nature 473(7346):221–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brennand K et al (2015) Phenotypic differences in hiPSC NPCs derived from patients with schizophrenia. Mol Psychiatry 20(3):361–368

    Article  CAS  PubMed  Google Scholar 

  • Byers B et al (2011) SNCA triplication Parkinson's patient's iPSC-derived DA neurons accumulate α-synuclein and are susceptible to oxidative stress. PloS One 6(11):e26159

    Article  PubMed  PubMed Central  Google Scholar 

  • Cakir B et al (2019) Engineering of human brain organoids with a functional vascular-like system. Nat Methods 16(11):1169–1175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cardoso T et al (2018) Target-specific forebrain projections and appropriate synaptic inputs of hESC-derived dopamine neurons grafted to the midbrain of Parkinsonian rats. J Comp Neurol 526(13):2133–2146

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen H et al (2014a) Modeling ALS with iPSCs reveals that mutant SOD1 misregulates neurofilament balance in motor neurons. Cell Stem Cell 14(6):796–809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen HM et al (2014b) Transcripts involved in calcium signaling and telencephalic neuronal fate are altered in induced pluripotent stem cells from bipolar disorder patients. Transl Psychiatry 4(3):e375

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Y et al (2016) Chemical control of grafted human PSC-derived neurons in a mouse model of Parkinson’s disease. Cell Stem Cell 18(6):817–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen X et al (2021) Modeling sporadic Alzheimer's disease in human brain organoids under serum exposure. Adv Sci (Weinh) 8(18):e2101462

    Article  PubMed  Google Scholar 

  • Cheng PH et al (2013) miR-196a ameliorates phenotypes of Huntington disease in cell, transgenic mouse, and induced pluripotent stem cell models. Am J Hum Genet 93(2):306–312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chiaradia I, Lancaster MA (2020) Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nat Neurosci 23(12):1496–1508

    Article  CAS  PubMed  Google Scholar 

  • Christian M et al (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186(2):757–761

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cong L et al (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339(6121):819–823

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cooper O et al (2012) Pharmacological rescue of mitochondrial deficits in iPSC-derived neural cells from patients with familial Parkinson's disease. Sci Transl Med 4(141):141ra90

    Article  PubMed  PubMed Central  Google Scholar 

  • Di Lullo E, Kriegstein AR (2017) The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci 18(10):573–584

    Article  PubMed  PubMed Central  Google Scholar 

  • Dimos JT et al (2008) Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321(5893):1218–1221

    Article  CAS  PubMed  Google Scholar 

  • Djuric U et al (2015) MECP2e1 isoform mutation affects the form and function of neurons derived from Rett syndrome patient iPS cells. Neurobiol Dis 76:37–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doers ME et al (2014) iPSC-derived forebrain neurons from FXS individuals show defects in initial neurite outgrowth. Stem Cells Dev 23(15):1777–1787

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doncheva NT et al (2021) Human pathways in animal models: possibilities and limitations. Nucleic Acids Res 49(4):1859–1871

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong X et al (2021) Human cerebral organoids establish subcortical projections in the mouse brain after transplantation. Mol Psychiatry 26(7):2964–2976

    Article  CAS  PubMed  Google Scholar 

  • Ebert AD et al (2009) Induced pluripotent stem cells from a spinal muscular atrophy patient. Nature 457(7227):277–280

    Article  CAS  PubMed  Google Scholar 

  • Egawa N et al (2012) Drug screening for ALS using patient-specific induced pluripotent stem cells. Sci Transl Med 4(145):145ra104

    Article  PubMed  Google Scholar 

  • Eichmüller OL et al (2022) Amplification of human interneuron progenitors promotes brain tumors and neurological defects. Science 375(6579):eabf5546

    Article  PubMed  PubMed Central  Google Scholar 

  • Eiraku M et al (2008) Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3(5):519–532

    Article  CAS  PubMed  Google Scholar 

  • Eiraku M et al (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472(7341):51–56

    Article  CAS  PubMed  Google Scholar 

  • Emborg ME et al (2013) Induced pluripotent stem cell-derived neural cells survive and mature in the nonhuman primate brain. Cell Rep 3(3):646–650

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flandin P et al (2011) Lhx6 and Lhx8 coordinately induce neuronal expression of Shh that controls the generation of interneuron progenitors. Neuron 70(5):939–950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giandomenico SL, Sutcliffe M, Lancaster MA (2021) Generation and long-term culture of advanced cerebral organoids for studying later stages of neural development. Nat Protoc 16(2):579–602

    Article  CAS  PubMed  Google Scholar 

  • Griesi-Oliveira K et al (2015) Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons. Mol Psychiatry 20(11):1350–1365

    Article  CAS  PubMed  Google Scholar 

  • Gunaseeli I et al (2010) Induced pluripotent stem cells as a model for accelerated patient- and disease-specific drug discovery. Curr Med Chem 17(8):759–766

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo X et al (2013) Inhibition of mitochondrial fragmentation diminishes Huntington's disease-associated neurodegeneration. J Clin Invest 123(12):5371–5388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • HD iPSC Consortium (2012) Induced pluripotent stem cells from patients with Huntington's disease show CAG-repeat-expansion-associated phenotypes. Cell Stem Cell 11(2):264–278

    Article  Google Scholar 

  • Hill RA (2012) Interaction of sex steroid hormones and brain-derived neurotrophic factor-tyrosine kinase B signalling: relevance to schizophrenia and depression. J Neuroendocrinol 24(12):1553–1561

    Article  CAS  PubMed  Google Scholar 

  • Hockemeyer D, Jaenisch R (2016) Induced pluripotent stem cells meet genome editing. Cell Stem Cell 18(5):573–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hockemeyer D et al (2009) Efficient targeting of expressed and silent genes in human ESCs and iPSCs using zinc-finger nucleases. Nat Biotechnol 27(9):851–857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hockemeyer D et al (2011) Genetic engineering of human pluripotent cells using TALE nucleases. Nat Biotechnol 29(8):731–734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu BY, Zhang SC (2009) Differentiation of spinal motor neurons from pluripotent human stem cells. Nat Protoc 4(9):1295–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu BY et al (2010) Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci U S A 107(9):4335–4340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu D et al (2021) Small-molecule suppression of calpastatin degradation reduces neuropathology in models of Huntington's disease. Nat Commun 12(1):5305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huo HQ et al (2018) Modeling down syndrome with patient iPSCs reveals cellular and migration deficits of GABAergic neurons. Stem Cell Rep 10(4):1251–1266

    Article  CAS  Google Scholar 

  • Iakoucheva LM, Muotri AR, Sebat J (2019) Getting to the cores of autism. Cell 178(6):1287–1298

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Israel MA et al (2012) Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature 482(7384):216–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang H et al (2012) Parkin controls dopamine utilization in human midbrain dopaminergic neurons derived from induced pluripotent stem cells. Nat Commun 3:668

    Article  PubMed  Google Scholar 

  • Jin M et al (2022) Type-I-interferon signaling drives microglial dysfunction and senescence in human iPSC models of down syndrome and Alzheimer's disease. Cell Stem Cell 29(7):1135–1153.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jo J et al (2021) Lewy body-like inclusions in human midbrain organoids carrying glucocerebrosidase and α-synuclein mutations. Ann Neurol 90(3):490–505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalia LV, Lang AE (2015) Parkinson's disease. Lancet 386(9996):896–912

    Article  CAS  PubMed  Google Scholar 

  • Kang Y et al (2021) A human forebrain organoid model of fragile X syndrome exhibits altered neurogenesis and highlights new treatment strategies. Nat Neurosci 24(10):1377–1391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Karumbayaram S et al (2009) Directed differentiation of human-induced pluripotent stem cells generates active motor neurons. Stem Cells 27(4):806–811

    Article  CAS  PubMed  Google Scholar 

  • Kelley KW, Pasca SP (2022) Human brain organogenesis: toward a cellular understanding of development and disease. Cell 185(1):42–61

    Article  CAS  PubMed  Google Scholar 

  • Kikuchi T et al (2017) Human iPS cell-derived dopaminergic neurons function in a primate Parkinson’s disease model. Nature 548(7669):592–596

    Article  CAS  PubMed  Google Scholar 

  • Kim KY, Hysolli E, Park IH (2011) Neuronal maturation defect in induced pluripotent stem cells from patients with Rett syndrome. Proc Natl Acad Sci U S A 108(34):14169–14174

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirkeby A et al (2012) Generation of regionally specified neural progenitors and functional neurons from human embryonic stem cells under defined conditions. Cell Rep 1(6):703–714

    Article  CAS  PubMed  Google Scholar 

  • Kondo T et al (2013) Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness. Cell Stem Cell 12(4):487–496

    Article  CAS  PubMed  Google Scholar 

  • Kumari D et al (2015) High-throughput screening to identify compounds that increase fragile X mental retardation protein expression in neural stem cells differentiated from fragile X syndrome patient-derived induced pluripotent stem cells. Stem Cells Transl Med 4(7):800–808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lancaster MA, Knoblich JA (2014) Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 9(10):2329–2340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lancaster MA et al (2013) Cerebral organoids model human brain development and microcephaly. Nature 501(7467):373–379

    Article  CAS  PubMed  Google Scholar 

  • Laursen TM (2011) Life expectancy among persons with schizophrenia or bipolar affective disorder. Schizophr Res 131(1–3):101–104

    Article  PubMed  Google Scholar 

  • Lee G et al (2009) Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature 461(7262):402–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lefrère J, Berche P (2010) Doctor Brown-Sequard’s therapy. In: Annales D’endocrinologie

    Google Scholar 

  • Li XJ, Li S (2012) Influence of species differences on the neuropathology of transgenic Huntington's disease animal models. J Genet Genomics 39(6):239–245

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li XJ et al (2005) Specification of motoneurons from human embryonic stem cells. Nat Biotechnol 23(2):215–221

    Article  PubMed  Google Scholar 

  • Li XJ et al (2008) Directed differentiation of ventral spinal progenitors and motor neurons from human embryonic stem cells by small molecules. Stem Cells 26(4):886–893

    Article  CAS  PubMed  Google Scholar 

  • Lichtenstein P et al (2009) Common genetic determinants of schizophrenia and bipolar disorder in Swedish families: a population-based study. Lancet 373(9659):234–239

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Zhang SC (2010) Human stem cells as a model of motoneuron development and diseases. Ann N Y Acad Sci 1198:192–200

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y et al (2013a) Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc 8(9):1670–1679

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Y et al (2013b) Medial ganglionic eminence-like cells derived from human embryonic stem cells correct learning and memory deficits. Nat Biotechnol 31(5):440–447

    Article  PubMed  PubMed Central  Google Scholar 

  • Lu J et al (2013) Generation of integration-free and region-specific neural progenitors from primate fibroblasts. Cell Rep 3(5):1580–1591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu J et al (2016) Generation of serotonin neurons from human pluripotent stem cells. Nat Biotechnol 34(1):89–94

    Article  CAS  PubMed  Google Scholar 

  • Ma L et al (2012) Human embryonic stem cell-derived GABA neurons correct locomotion deficits in quinolinic acid-lesioned mice. Cell Stem Cell 10(4):455–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maetzel D et al (2014) Genetic and chemical correction of cholesterol accumulation and impaired autophagy in hepatic and neural cells derived from Niemann-Pick type C patient-specific iPS cells. Stem Cell Rep 2(6):866–880

    Article  CAS  Google Scholar 

  • Mansour AA et al (2018) An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol 36(5):432–441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marchetto MC et al (2010) A model for neural development and treatment of Rett syndrome using human induced pluripotent stem cells. Cell 143(4):527–539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mariani J et al (2012) Modeling human cortical development in vitro using induced pluripotent stem cells. Proc Natl Acad Sci U S A 109(31):12770–12775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maroof AM et al (2013) Directed differentiation and functional maturation of cortical interneurons from human embryonic stem cells. Cell Stem Cell 12(5):559–572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez-Losa M et al (2018) Nav1. 1-overexpressing interneuron transplants restore brain rhythms and cognition in a mouse model of Alzheimer’s disease. Neuron 98(1):75–89. e5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mertens J et al (2015) Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder. Nature 527(7576):95–99

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyoshi G et al (2021) FoxG1 regulates the formation of cortical GABAergic circuit during an early postnatal critical period resulting in autism spectrum disorder-like phenotypes. Nat Commun 12(1):3773

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Montine TJ et al (2012) National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 123(1):1–11

    Article  CAS  PubMed  Google Scholar 

  • Nicholas CR et al (2013) Functional maturation of hPSC-derived forebrain interneurons requires an extended timeline and mimics human neural development. Cell Stem Cell 12(5):573–586

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oksanen M et al (2017) PSEN1 mutant iPSC-derived model reveals severe astrocyte pathology in Alzheimer's disease. Stem Cell Rep 9(6):1885–1897

    Article  CAS  Google Scholar 

  • Paquet D et al (2016) Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9. Nature 533(7601):125–129

    Article  CAS  PubMed  Google Scholar 

  • Park IH et al (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park B, Yoo KH, Kim C (2015) Hematopoietic stem cell expansion and generation: the ways to make a breakthrough. Blood Res 50(4):194

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • PaÅŸca SP et al (2011) Using iPSC-derived neurons to uncover cellular phenotypes associated with Timothy syndrome. Nat Med 17(12):1657–1662

    Article  PubMed  PubMed Central  Google Scholar 

  • Perez-Pinera P et al (2013) RNA-guided gene activation by CRISPR-Cas9-based transcription factors. Nat Methods 10(10):973–976

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pinson A et al (2022) Human TKTL1 implies greater neurogenesis in frontal neocortex of modern humans than Neanderthals. Science 377(6611):eabl6422

    Article  CAS  PubMed  Google Scholar 

  • Pollen AA et al (2019) Establishing cerebral organoids as models of human-specific brain evolution. Cell 176(4):743–756.e17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prakash N et al (2006) A Wnt1-regulated genetic network controls the identity and fate of midbrain-dopaminergic progenitors in vivo. Development 133(1):89–98

    Article  CAS  PubMed  Google Scholar 

  • Qian X et al (2016) Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell 165(5):1238–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian X et al (2018) Generation of human brain region-specific organoids using a miniaturized spinning bioreactor. Nat Protoc 13(3):565–580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raja WK et al (2016) Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer's disease phenotypes. PloS One 11(9):e0161969

    Article  PubMed  PubMed Central  Google Scholar 

  • Rallu M et al (2002) Dorsoventral patterning is established in the telencephalon of mutants lacking both Gli3 and Hedgehog signaling. Development 129(21):4963–4974

    Article  CAS  PubMed  Google Scholar 

  • Rash BG, Grove EA (2007) Patterning the dorsal telencephalon: a role for sonic hedgehog? J Neurosci 27(43):11595–11603

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Real R et al (2018) In vivo modeling of human neuron dynamics and down syndrome. Science 362(6416)

    Google Scholar 

  • Renton AE, Chiò A, Traynor BJ (2014) State of play in amyotrophic lateral sclerosis genetics. Nat Neurosci 17(1):17–23

    Article  CAS  PubMed  Google Scholar 

  • Revah O et al (2022) Maturation and circuit integration of transplanted human cortical organoids. Nature 610(7931):319–326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ross CA, Tabrizi SJ (2011) Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol 10(1):83–98

    Article  CAS  PubMed  Google Scholar 

  • Ryan SD et al (2013) Isogenic human iPSC Parkinson's model shows nitrosative stress-induced dysfunction in MEF2-PGC1α transcription. Cell 155(6):1351–1364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salero E, Hatten ME (2007) Differentiation of ES cells into cerebellar neurons. Proc Natl Acad Sci U S A 104(8):2997–3002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sances S et al (2016) Modeling ALS with motor neurons derived from human induced pluripotent stem cells. Nat Neurosci 19(4):542–553

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shahsavani M et al (2018) An in vitro model of lissencephaly: expanding the role of DCX during neurogenesis. Mol Psychiatry 23(7):1674–1684

    Article  CAS  PubMed  Google Scholar 

  • Shcheglovitov A et al (2013) SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion syndrome patients. Nature 503(7475):267–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sheridan SD et al (2011) Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PloS One 6(10):e26203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith C et al (2014) Whole-genome sequencing analysis reveals high specificity of CRISPR/Cas9 and TALEN-based genome editing in human iPSCs. Cell Stem Cell 15(1):12–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith M et al (2019) Organ donation after circulatory death: current status and future potential. Intensive Care Med 45(3):310–321

    Article  PubMed  Google Scholar 

  • Snow JP et al (2020) Neuronal modeling of alternating hemiplegia of childhood reveals transcriptional compensation and replicates a trigger-induced phenotype. Neurobiol Dis 141:104881

    Article  CAS  PubMed  Google Scholar 

  • Stern S et al (2018) Neurons derived from patients with bipolar disorder divide into intrinsically different sub-populations of neurons, predicting the patients' responsiveness to lithium. Mol Psychiatry 23(6):1453–1465

    Article  CAS  PubMed  Google Scholar 

  • Sun XY et al (2022) Generation of vascularized brain organoids to study neurovascular interactions. elife 11:e76707

    Article  CAS  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(4):663–676

    Article  CAS  PubMed  Google Scholar 

  • Takahashi K et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872

    Article  CAS  PubMed  Google Scholar 

  • Tanaka T et al (2009) In vitro pharmacologic testing using human induced pluripotent stem cell-derived cardiomyocytes. Biochem Biophys Res Commun 385(4):497–502

    Article  CAS  PubMed  Google Scholar 

  • Tang XY et al (2021) DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with down syndrome. J Clin Invest 131(12)

    Google Scholar 

  • Tang XY et al (2022) Human organoids in basic research and clinical applications. Signal Transduct Target Ther 7(1):168

    Article  PubMed  PubMed Central  Google Scholar 

  • Tao Y et al (2021) Autologous transplant therapy alleviates motor and depressive behaviors in parkinsonian monkeys. Nat Med 27(4):632–639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Telias M et al (2015) Functional deficiencies in fragile X neurons derived from human embryonic stem cells. J Neurosci 35(46):15295–15306

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thomson JA et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147

    Article  CAS  PubMed  Google Scholar 

  • Urbach A et al (2010) Differential modeling of fragile X syndrome by human embryonic stem cells and induced pluripotent stem cells. Cell Stem Cell 6(5):407–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vadodaria KC et al (2016) Generation of functional human serotonergic neurons from fibroblasts. Mol Psychiatry 21(1):49–61

    Article  CAS  PubMed  Google Scholar 

  • Vadodaria KC et al (2019a) Altered serotonergic circuitry in SSRI-resistant major depressive disorder patient-derived neurons. Mol Psychiatry 24(6):808–818

    Article  PubMed  PubMed Central  Google Scholar 

  • Vadodaria KC et al (2019b) Serotonin-induced hyperactivity in SSRI-resistant major depressive disorder patient-derived neurons. Mol Psychiatry 24(6):795–807

    Article  CAS  PubMed  Google Scholar 

  • Wang ZB, Zhang X, Li XJ (2013) Recapitulation of spinal motor neuron-specific disease phenotypes in a human cell model of spinal muscular atrophy. Cell Res 23(3):378–393

    Article  CAS  PubMed  Google Scholar 

  • Wang Y-K et al (2018) Human clinical-grade parthenogenetic ESC-derived dopaminergic neurons recover locomotive defects of nonhuman primate models of Parkinson's disease. Stem Cell Rep 11(1):171–182

    Article  CAS  Google Scholar 

  • Wen Z et al (2014) Synaptic dysregulation in a human iPS cell model of mental disorders. Nature 515(7527):414–418

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wernig M et al (2008) Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci U S A 105(15):5856–5861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Williams EC et al (2014) Mutant astrocytes differentiated from Rett syndrome patients-specific iPSCs have adverse effects on wild-type neurons. Hum Mol Genet 23(11):2968–2980

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiang Y et al (2019) hESC-derived thalamic organoids form reciprocal projections when fused with cortical organoids. Cell Stem Cell 24(3):487–497 e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiang Y et al (2020) Dysregulation of BRD4 function underlies the functional abnormalities of MeCP2 mutant neurons. Mol Cell 79(1):84–98.e9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu M et al (2016) Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med 22(10):1101–1107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu R et al (2019) OLIG2 drives abnormal neurodevelopmental phenotypes in human iPSC-based organoid and chimeric mouse models of down syndrome. Cell Stem Cell 24(6):908–926.e8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu L et al (2022) Abnormal mitochondria in down syndrome iPSC-derived GABAergic interneurons and organoids. Biochim Biophys Acta Mol Basis Dis 1868(6):166388

    Article  CAS  PubMed  Google Scholar 

  • Yagi T et al (2011) Modeling familial Alzheimer's disease with induced pluripotent stem cells. Hum Mol Genet 20(23):4530–4539

    Article  CAS  PubMed  Google Scholar 

  • Yahata N et al (2011) Anti-Aβ drug screening platform using human iPS cell-derived neurons for the treatment of Alzheimer's disease. PloS One 6(9):e25788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamanaka S (2008) Induction of pluripotent stem cells from mouse fibroblasts by four transcription factors. Cell Prolif 41:51–56

    Article  PubMed  Google Scholar 

  • Yan Y et al (2005) Directed differentiation of dopaminergic neuronal subtypes from human embryonic stem cells. Stem Cells 23(6):781–790

    Article  CAS  PubMed  Google Scholar 

  • Yang D et al (2008) Human embryonic stem cell-derived dopaminergic neurons reverse functional deficit in parkinsonian rats. Stem Cells 26(1):55–63

    Article  CAS  PubMed  Google Scholar 

  • Yu J et al (2007) Induced pluripotent stem cell lines derived from human somatic cells. Science 318(5858):1917–1920

    Article  CAS  PubMed  Google Scholar 

  • Yuan F et al (2018) Induction of human somatostatin and parvalbumin neurons by expressing a single transcription factor LIM homeobox 6. eLife:7

    Google Scholar 

  • Zhang BZ et al (2020) SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res 30(10):928–931

    Article  CAS  PubMed  Google Scholar 

  • Zhao J et al (2020) APOE4 exacerbates synapse loss and neurodegeneration in Alzheimer's disease patient iPSC-derived cerebral organoids. Nat Commun 11(1):5540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu W et al (2022) Dysfunction of vesicular storage in young-onset Parkinson’s patient-derived dopaminergic neurons and organoids revealed by single cell electrochemical cytometry. Chem Sci 13(21):6217–6223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou J et al (2009) Gene targeting of a disease-related gene in human induced pluripotent stem and embryonic stem cells. Cell Stem Cell 5(1):97–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. School of Pharmacy, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China

    Wanying Zhu, Lei Xu, Xinrui Li, Hao Hu, Shuning Lou & Yan Liu

Authors
  1. Wanying Zhu
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  2. Lei Xu
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  3. Xinrui Li
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  4. Hao Hu
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  5. Shuning Lou
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  6. Yan Liu
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Corresponding author

Correspondence to Yan Liu .

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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

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Zhu, W., Xu, L., Li, X., Hu, H., Lou, S., Liu, Y. (2023). iPSCs-Derived Neurons and Brain Organoids from Patients. 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_657

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