Abstract
Stem cell technology can allow us to produce human neuronal cell types outside the body, but what exactly are stem cells, and what challenges are associated with their use? Stem cells are a kind of cell that has the capacity to self-renew to produce additional stem cells by mitosis, and also to differentiate into other – more mature – cell types. Stem cells are usually categorized as multipotent (able to give rise to multiple cells within a lineage), pluripotent (able to give rise to all cell types in an adult) and totipotent (able to give rise to all embryonic and adult lineages). Multipotent adult stem cells are found throughout the body, and they include neural stem cells. The challenge in utilizing adult stem cells for disease research is obtaining cells that are genetically matched to people with disease phenotypes, and being able to differentiate them into the appropriate cell types of interest. As adult neural stem cells reside in the brain, their isolation would require considerably invasive and dangerous procedures. In contrast, pluripotent stem cells are easy to obtain, due to the paradigm-shifting work on direct reprogramming of human skin fibroblasts into induced pluripotent stem cells. This work has enabled us to produce neurons that are genetically matched to individual patients. While we are able to isolate pluripotent stem cells from patients in a minimally invasive manner, we do not yet fully understand how to direct these cells to many of the medically important neuronal fates. Progress in this direction continues to be made, on multiple fronts, and it involves using small molecules and proteins to mimic developmentally important signals, as well as building on advances in "reprogramming" to directly convert one cell type into another by forced expression of sets of transcription factors. An additional challenge involves providing these cells with the appropriate environment to induce their normal behavior outside the body. Despite these challenges, the promise of producing human neuronal cell types in vitro gives opportunities for unique insights and is therefore worthwhile.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Chung YG et al (2014) Human somatic cell nuclear transfer using adult cells. Cell Stem Cell 14(6):777–780
Greber B et al (2010) Conserved and divergent roles of FGF signaling in mouse epiblast stem cells and human embryonic stem cells. Cell Stem Cell 6(3):215–226
Haidet-Phillips AM, Hester ME, Miranda CJ, Meyer K, Braun L, Frakes A, Song SW, Likhite S, Murtha MJ, Foust KD, Rao M, Eagle A, Kammesheidt A, Christensen A, Mendell JR, Burghes AHM, Kaspar BK (2011) Astrocytes from familial and sporadic ALS patients are toxic to motor neurons. Nat Biotechnol 29(9):824–828
Kriks S et al (2011) Dopamine neurons derived from human ES cells efficiently engraft in animal models of Parkinson’s disease. Nature 480(7378):547–551
Marchetto MC, Gage FH (2012) Modeling brain disease in a dish: really? Cell Stem Cell 10(6):642–645
Marchetto MC et al (2011) Induced pluripotent stem cells (iPSCs) and neurological disease modeling: progress and promises. Hum Mol Genet 20(R2):R109–R115
Merkle FT et al (2015) Generation of neuropeptidergic hypothalamic neurons from human pluripotent stem cells. Development 142(4):633–643
Nishioka N et al (2009) The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. Dev Cell 16(3):398–410
Schlaeger TM et al (2015) A comparison of non-integrating reprogramming methods. Nat Biotechnol 33(1):58–63
Schwartz SD et al (2012) Embryonic stem cell trials for macular degeneration: a preliminary report. Lancet 379(9817):713–720
Tabansky I et al (2013) Developmental bias in cleavage-stage mouse blastomeres. Curr Biol 23(1):21–31
Tabansky I, Stern JNH, Pfaff DW (2015) Implications of epigenetic variability within a cell population for “cell type” classification. Front Behav Neurosci 9:342. doi:10.3389/fnbeh.2015.00342
Tabar V, Studer L (2014) Pluripotent stem cells in regenerative medicine: challenges and recent progress. Nat Rev Genet 15(2):82–92
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676
Tesar PJ et al (2007) New cell lines from mouse epiblast share defining features with human embryonic stem cells. Nature 448(7150):196–199
Thomson JA (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147
Tsunemoto RK et al (2015) Forward engineering neuronal diversity using direct reprogramming. EMBO J 34(11):1445–1455. doi:10.15252/embj.201591402
Wang L et al (2015) Differentiation of hypothalamic-like neurons from human pluripotent stem cells. J Clin Invest 125(2):796–808
Wataya T et al (2008) Minimization of exogenous signals in ES cell culture induces rostral hypothalamic differentiation. Proc Natl Acad Sci U S A 105(33):11796–11801
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this entry
Cite this entry
Tabansky, I., Stern, J.N.H. (2016). Basics of Stem Cell Biology as Applied to the Brain. In: Pfaff, D., Volkow, N. (eds) Neuroscience in the 21st Century. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3474-4_130
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3474-4_130
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-3473-7
Online ISBN: 978-1-4939-3474-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences