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Epigenetic Mechanisms Regulating the Transition from Embryonic Stem Cells Towards a Differentiated Neural Progeny

  • Marijn Schouten
  • Nik Papaloukas
  • Pascal Bielefeld
  • Silvina A. Fratantoni
  • Carlos P. FitzsimonsEmail author
Chapter
  • 790 Downloads

Abstract

Adult tissues preserve characteristic populations of self-renewing cells, which can give rise to various specialized cell types, and the brain is not an exception to this rule. The identification of neural stem cells (NSC) present in several areas of the adult brain has challenged conservative ideas regarding the applicability of regenerative medicine to the brain, creating a research field dedicated to unraveling the mechanisms of adult NSC self-renewal and differentiation, particularly within well defined tissue microenvironments termed neurogenic niches. Research over the past 50 years has revealed that NSC can give rise to different types of neural cells: neurons; astrocytes and oligodendrocytes; and recent observations have demonstrated that epigenetic mechanisms play a central role in the regulation of NSC self-renewal and differentiation under physiological and pathological conditions. In this chapter we review the literature describing these epigenetic mechanisms and discuss their possible implications for regenerative therapies for neurodegenerative disorders, which have been linked to alterations in the generation of new neurons from resident neural stem cells in the brain.

Keywords

Neurodegenerative disease DNA methylation MicroRNA Chromatin remodeling Histone modification 

Notes

Acknowledgments

We apologize to all colleagues whose work we have not included in this chapter due to space restrictions. This work has been supported by grants 864.09.016 Innovational Research Incentive Scheme VIDI from The Netherlands Organization for Scientific Research (NWO), and Project #14533, from the International Foundation for Alzheimer’s Research (ISAO), both to C.P.F.

References

  1. Altman J, Das GD (1965) Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 124:319–335PubMedCrossRefGoogle Scholar
  2. Ariff IM, Mitra A, Basu A (2012) Epigenetic regulation of self-renewal and fate determination in neural stem cells. J Neurosci Res 90:529–539. doi: 10.1002/jnr.22804 CrossRefGoogle Scholar
  3. Azim K, Fischer B, Hurtado-Chong A et al (2014) Persistent Wnt/β-catenin signaling determines dorsalization of the postnatal subventricular zone and neural stem cell specification into oligodendrocytes and glutamatergic neurons. Stem Cells 32:1301–1312. doi: 10.1002/stem.1639 PubMedCrossRefGoogle Scholar
  4. Balasubramaniyan V, Boddeke E, Bakels R et al (2006) Effects of histone deacetylation inhibition on neuronal differentiation of embryonic mouse neural stem cells. Neuroscience 143:939–951. doi: 10.1016/j.neuroscience.2006.08.082 PubMedCrossRefGoogle Scholar
  5. Ballas N, Grunseich C, Lu DD et al (2005) REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121:645–657. doi: 10.1016/j.cell.2005.03.013 PubMedCrossRefGoogle Scholar
  6. Barca-Mayo O, De Pietri TD (2014) Convergent microRNA actions coordinate neocortical development. Cell Mol Life Sci 71:2975–2995. doi: 10.1007/s00018-014-1576-5 PubMedPubMedCentralCrossRefGoogle Scholar
  7. Barroso-delJesus A, Romero-López C, Lucena-Aguilar G et al (2008) Embryonic stem cell-specific miR302-367 cluster: human gene structure and functional characterization of its core promoter. Mol Cell Biol 28:6609–6619. doi: 10.1128/MCB.00398-08 PubMedPubMedCentralCrossRefGoogle Scholar
  8. Barski A, Cuddapah S, Cui K et al (2007) High-resolution profiling of histone methylations in the human genome. Cell 129:823–837. doi: 10.1016/j.cell.2007.05.009 PubMedCrossRefGoogle Scholar
  9. Bian S, Hong J, Li Q et al (2013) MicroRNA cluster miR-17-92 regulates neural stem cell expansion and transition to intermediate progenitors in the developing mouse neocortex. Cell Rep 3:1398–1406. doi: 10.1016/j.celrep.2013.03.037 PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bielefeld P, Van Vliet EA, Gorter JA et al (2013) Different subsets of newborn granule cells: a possible role in epileptogenesis? Eur J Neurosci 39(1):1–11. doi: 10.1111/ejn.12387, Epub 2013 Oct 16PubMedCrossRefGoogle Scholar
  11. Bird A (2007) Perceptions of epigenetics. Nature 447:396–398. doi: 10.1038/nature05913 PubMedCrossRefGoogle Scholar
  12. Boissart C, Nissan X, Giraud-Triboult K et al (2012) miR-125 potentiates early neural specification of human embryonic stem cells. Development 139:1247–1257. doi: 10.1242/dev.073627 PubMedCrossRefGoogle Scholar
  13. Boyer LA, Plath K, Zeitlinger J et al (2006) Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 441:349–353. doi: 10.1038/nature04733 PubMedCrossRefGoogle Scholar
  14. Brown M (2013) No ethical bypass of moral status in stem cell research. Bioethics 27:12–19. doi: 10.1111/j.1467-8519.2011.01891.x PubMedCrossRefGoogle Scholar
  15. Burgold T, Spreafico F, De Santa F et al (2008) The histone H3 lysine 27-specific demethylase Jmjd3 is required for neural commitment. PLoS ONE 3:e3034. doi: 10.1371/journal.pone.0003034 PubMedPubMedCentralCrossRefGoogle Scholar
  16. Burney MJ, Johnston C, Wong K-Y et al (2013) An epigenetic signature of developmental potential in neural stem cells and early neurons. Stem Cells 31:1868–1880. doi: 10.1002/stem.1431 PubMedCrossRefGoogle Scholar
  17. Card DAG, Hebbar PB, Li L et al (2008) Oct4/Sox2-regulated miR-302 targets cyclin D1 in human embryonic stem cells. Mol Cell Biol 28:6426–6438. doi: 10.1128/MCB.00359-08 PubMedCrossRefGoogle Scholar
  18. Chamberlain SJ, Yee D, Magnuson T (2008) Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency. Stem Cells 26:1496–1505. doi: 10.1634/stemcells.2008-0102 PubMedPubMedCentralCrossRefGoogle Scholar
  19. Chambers I, Tomlinson SR (2009) The transcriptional foundation of pluripotency. Development 136:2311–2322. doi: 10.1242/dev.024398 PubMedPubMedCentralCrossRefGoogle Scholar
  20. Conaco C, Otto S, Han J-J, Mandel G (2006) Reciprocal actions of REST and a microRNA promote neuronal identity. Proc Natl Acad Sci U S A 103:2422–2427. doi: 10.1073/pnas.0511041103 PubMedPubMedCentralCrossRefGoogle Scholar
  21. Cunningham M, Cho J-H, Leung A et al (2014) hPSC-derived maturing GABAergic interneurons ameliorate seizures and abnormal behavior in epileptic mice. Cell Stem Cell 15:559–573. doi: 10.1016/j.stem.2014.10.006 PubMedPubMedCentralCrossRefGoogle Scholar
  22. Dasgupta I, Bollinger J, Mathews DJH et al (2014) Patients’ attitudes toward the donation of biological materials for the derivation of induced pluripotent stem cells. Stem Cell 14:9–12. doi: 10.1016/j.stem.2013.12.006 Google Scholar
  23. Douglas T, Savulescu J (2009) Destroying unwanted embryos in research. Talking Point on morality and human embryo research. EMBO Rep 10:307–312. doi: 10.1038/embor.2009.54 PubMedPubMedCentralCrossRefGoogle Scholar
  24. Dovey OM, Foster CT, Cowley SM (2010) Histone deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation. Proc Natl Acad Sci U S A 107:8242–8247. doi: 10.1073/pnas.1000478107 PubMedPubMedCentralCrossRefGoogle Scholar
  25. Dugas JC, Cuellar TL, Scholze A et al (2010) Dicer1 and miR-219 are required for normal oligodendrocyte differentiation and myelination. Neuron 65:597–611. doi: 10.1016/j.neuron.2010.01.027 PubMedPubMedCentralCrossRefGoogle Scholar
  26. Edlund T, Jessell TM (1999) Progression from extrinsic to intrinsic signaling in cell fate specification: a view from the nervous system. Cell 96:211–224PubMedCrossRefGoogle Scholar
  27. Fan G, Martinowich K, Chin MH et al (2005) DNA methylation controls the timing of astrogliogenesis through regulation of JAK-STAT signaling. Development 132:3345–3356. doi: 10.1242/dev.01912 PubMedCrossRefGoogle Scholar
  28. Feng J, Chang H, Li E, Fan G (2005) Dynamic expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b in the central nervous system. J Neurosci Res 79:734–746. doi: 10.1002/jnr.20404 PubMedCrossRefGoogle Scholar
  29. Fitzsimons CP, van Bodegraven E, Schouten M et al (2014) Epigenetic regulation of adult neural stem cells: implications for Alzheimer’s disease. Mol Neurodegener 9:25. doi: 10.1186/1750-1326-9-25 PubMedPubMedCentralCrossRefGoogle Scholar
  30. Gage FH (2000) Mammalian neural stem cells. Science 287:1433–1438PubMedCrossRefGoogle Scholar
  31. Gage FH, Kempermann G, Palmer TD et al (1998) Multipotent progenitor cells in the adult dentate gyrus. J Neurobiol 36:249–266. doi: 10.1002/(SICI)1097-4695(199808)36:2<249::AID-NEU11>3.0.CO;2-9 PubMedCrossRefGoogle Scholar
  32. Garg N, Po A, Miele E et al (2013) microRNA-17-92 cluster is a direct Nanog target and controls neural stem cell through Trp53inp1. EMBO J 32:2819–2832. doi: 10.1038/emboj.2013.214 PubMedPubMedCentralCrossRefGoogle Scholar
  33. Gifford CA, Ziller MJ, Gu H et al (2013) Transcriptional and epigenetic dynamics during specification of human embryonic stem cells. Cell 153:1149–1163. doi: 10.1016/j.cell.2013.04.037 PubMedPubMedCentralCrossRefGoogle Scholar
  34. Gjoneska E, Pfenning AR, Mathys H et al (2015) Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease. Nature 518:365–369. doi: 10.1038/nature14252 PubMedPubMedCentralCrossRefGoogle Scholar
  35. Goldstein LSB, Reyna S, Woodruff G (2015) Probing the secrets of Alzheimer’s disease using human-induced pluripotent stem cell technology. Neurotherapeutics 12:121–125. doi: 10.1007/s13311-014-0326-6 PubMedPubMedCentralCrossRefGoogle Scholar
  36. Grealish S, Diguet E, Kirkeby A et al (2014) Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson’s disease. Cell Stem Cell 15:653–665. doi: 10.1016/j.stem.2014.09.017 PubMedPubMedCentralCrossRefGoogle Scholar
  37. Grealish S, Heuer A, Cardoso T et al (2015) Monosynaptic tracing using modified rabies virus reveals early and extensive circuit integration of human embryonic stem cell-derived neurons. Stem Cell Rep 4:975–983. doi: 10.1016/j.stemcr.2015.04.011 CrossRefGoogle Scholar
  38. Hattiangady B, Rao MS, Shetty AK (2008) Grafting of striatal precursor cells into hippocampus shortly after status epilepticus restrains chronic temporal lobe epilepsy. Exp Neurol 212:468–481. doi: 10.1016/j.expneurol.2008.04.040 PubMedPubMedCentralCrossRefGoogle Scholar
  39. He F, Ge W, Martinowich K et al (2005) A positive autoregulatory loop of Jak-STAT signaling controls the onset of astrogliogenesis. Nat Neurosci 8:616–625. doi: 10.1038/nn1440 PubMedPubMedCentralCrossRefGoogle Scholar
  40. Hemmati-Brivanlou A, Melton DA (1994) Inhibition of activin receptor signaling promotes neuralization in Xenopus. Cell 77:273–281PubMedCrossRefGoogle Scholar
  41. Hime GR, Abud HE (2013) The stem cell state. Adv Exp Med Biol 786:1–4. doi: 10.1007/978-94-007-6621-1_1 PubMedCrossRefGoogle Scholar
  42. Hirabayashi Y, Gotoh Y (2010) Epigenetic control of neural precursor cell fate during development. Nat Rev Neurosci 11:377–388. doi: 10.1038/nrn2810 PubMedCrossRefGoogle Scholar
  43. Hirabayashi Y, Suzki N, Tsuboi M et al (2009) Polycomb limits the neurogenic competence of neural precursor cells to promote astrogenic fate transition. Neuron 63:600–613. doi: 10.1016/j.neuron.2009.08.021 PubMedCrossRefGoogle Scholar
  44. Holoch D, Moazed D (2015) RNA-mediated epigenetic regulation of gene expression. Nat Rev Genet 16:71–84. doi: 10.1038/nrg3863 PubMedPubMedCentralCrossRefGoogle Scholar
  45. Hong S, Heo J, Lee S et al (2008) Methyltransferase-inhibition interferes with neuronal differentiation of P19 embryonal carcinoma cells. Biochem Biophys Res Commun 377:935–940. doi: 10.1016/j.bbrc.2008.10.089 PubMedCrossRefGoogle Scholar
  46. Hsieh J, Nakashima K, Kuwabara T et al (2004) Histone deacetylase inhibition-mediated neuronal differentiation of multipotent adult neural progenitor cells. Proc Natl Acad Sci U S A 101:16659–16664. doi: 10.1073/pnas.0407643101 PubMedPubMedCentralCrossRefGoogle Scholar
  47. Hunt RF, Girskis KM, Rubenstein JL et al (2013) GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior. Nat Neurosci 16:692–697. doi: 10.1038/nn.3392 PubMedPubMedCentralCrossRefGoogle Scholar
  48. Hyun I (2014) Policy: regulate embryos made for research. Nature 509:27–28. doi: 10.1038/509027a PubMedCrossRefGoogle Scholar
  49. Israel MA, Yuan SH, Bardy C et al (2012) Probing sporadic and familial Alzheimer’s disease using induced pluripotent stem cells. Nature 482:216–220. doi: 10.1038/nature10821 PubMedPubMedCentralGoogle Scholar
  50. Jeltsch A, Jurkowska RZ (2014) New concepts in DNA methylation. Trends Biochem Sci 39:310–318. doi: 10.1016/j.tibs.2014.05.002 PubMedCrossRefGoogle Scholar
  51. Jepsen K, Solum D, Zhou T et al (2007) SMRT-mediated repression of an H3K27 demethylase in progression from neural stem cell to neuron. Nature 450:415–419. doi: 10.1038/nature06270 PubMedCrossRefGoogle Scholar
  52. Kempermann G (2004) Functional significance of adult neurogenesis. Curr Opin Neurobiol 14:186–191. doi: 10.1016/j.conb.2004.03.001 PubMedCrossRefGoogle Scholar
  53. Kim H, Lee G, Ganat Y et al (2011) miR-371-3 expression predicts neural differentiation propensity in human pluripotent stem cells. Cell Stem Cell 8:695–706. doi: 10.1016/j.stem.2011.04.002 PubMedCrossRefGoogle Scholar
  54. Kim JA, Ha S, Shin KY et al (2015) Neural stem cell transplantation at critical period improves learning and memory through restoring synaptic impairment in Alzheimer's disease mouse model. Cell Death Dis 6, e1789. doi: 10.1038/cddis.2015.138 PubMedPubMedCentralCrossRefGoogle Scholar
  55. Kohyama J, Sanosaka T, Tokunaga A et al (2010) BMP-induced REST regulates the establishment and maintenance of astrocytic identity. J Cell Biol 189:159–170. doi: 10.1083/jcb.200908048 PubMedPubMedCentralCrossRefGoogle Scholar
  56. LaSalle JM, Powell WT, Yasui DH (2013) Epigenetic layers and players underlying neurodevelopment. Trends Neurosci 36:460–470. doi: 10.1016/j.tins.2013.05.001 PubMedPubMedCentralCrossRefGoogle Scholar
  57. Laurent L, Wong E, Li G et al (2010) Dynamic changes in the human methylome during differentiation. Genome Res 20:320–331. doi: 10.1101/gr.101907.109 PubMedPubMedCentralCrossRefGoogle Scholar
  58. Lee JT (2012) Epigenetic regulation by long noncoding RNAs. Science 338:1435–1439. doi: 10.1126/science.1231776 PubMedCrossRefGoogle Scholar
  59. Lee TI, Jenner RG, Boyer LA et al (2006) Control of developmental regulators by Polycomb in human embryonic stem cells. Cell 125:301–313. doi: 10.1016/j.cell.2006.02.043 PubMedPubMedCentralCrossRefGoogle Scholar
  60. Letzen BS, Liu C, Thakor NV et al (2010) MicroRNA expression profiling of oligodendrocyte differentiation from human embryonic stem cells. PLoS ONE 5:e10480. doi: 10.1371/journal.pone.0010480 PubMedPubMedCentralCrossRefGoogle Scholar
  61. Li J-Y, Pu M-T, Hirasawa R et al (2007) Synergistic function of DNA methyltransferases Dnmt3a and Dnmt3b in the methylation of Oct4 and Nanog. Mol Cell Biol 27:8748–8759. doi: 10.1128/MCB.01380-07 PubMedPubMedCentralCrossRefGoogle Scholar
  62. Li X, Barkho BZ, Luo Y et al (2008) Epigenetic regulation of the stem cell mitogen Fgf-2 by Mbd1 in adult neural stem/progenitor cells. J Biol Chem 283:27644–27652. doi: 10.1074/jbc.M804899200 PubMedPubMedCentralCrossRefGoogle Scholar
  63. Liebers R, Rassoulzadegan M, Lyko F (2014) Epigenetic regulation by heritable RNA. PLoS Genet 10(4):e1004296. doi:  10.1371/journal.pgen.1004296. eCollection 2014 Apr reviewGoogle Scholar
  64. Lim DA, Huang Y-C, Swigut T et al (2009) Chromatin remodelling factor Mll1 is essential for neurogenesis from postnatal neural stem cells. Nature 458:529–533. doi: 10.1038/nature07726 PubMedPubMedCentralCrossRefGoogle Scholar
  65. Lipchina I, Studer L, Betel D (2012) The expanding role of miR-302-367 in pluripotency and reprogramming. Cell Cycle 11:1517–1523. doi: 10.4161/cc.19846 PubMedCrossRefGoogle Scholar
  66. Ma DK, Marchetto MC, Guo JU et al (2010) Epigenetic choreographers of neurogenesis in the adult mammalian brain. Nat Neurosci 13:1338–1344. doi: 10.1038/nn.2672 PubMedPubMedCentralCrossRefGoogle Scholar
  67. MacDonald JL, Roskams AJ (2008) Histone deacetylases 1 and 2 are expressed at distinct stages of neuro-glial development. Dev Dyn 237:2256–2267. doi: 10.1002/dvdy.21626 PubMedCrossRefGoogle Scholar
  68. Maisano X, Litvina E, Tagliatela S et al (2012) Differentiation and functional incorporation of embryonic stem cell-derived GABAergic interneurons in the dentate gyrus of mice with temporal lobe epilepsy. J Neurosci 32:46–61. doi: 10.1523/JNEUROSCI.2683-11.2012 PubMedPubMedCentralCrossRefGoogle Scholar
  69. Marks H, Kalkan T, Menafra R et al (2012) The transcriptional and epigenomic foundations of ground state pluripotency. Cell 149:590–604. doi: 10.1016/j.cell.2012.03.026 PubMedPubMedCentralCrossRefGoogle Scholar
  70. Matsumoto S, Banine F, Struve J et al (2006) Brg1 is required for murine neural stem cell maintenance and gliogenesis. Dev Biol 289:372–383. doi: 10.1016/j.ydbio.2005.10.044 PubMedCrossRefGoogle Scholar
  71. Mazur-Kolecka B, Golabek A, Nowicki K et al (2006) Amyloid-beta impairs development of neuronal progenitor cells by oxidative mechanisms. Neurobiol Aging 27:1181–1192. doi: 10.1016/j.neurobiolaging.2005.07.006 PubMedCrossRefGoogle Scholar
  72. Melton C, Judson RL, Blelloch R (2010) Opposing microRNA families regulate self-renewal in mouse embryonic stem cells. Nature 463:621–626. doi: 10.1038/nature08725 PubMedPubMedCentralCrossRefGoogle Scholar
  73. Mohn F, Weber M, Rebhan M et al (2008) Lineage-specific polycomb targets and de novo DNA methylation define restriction and potential of neuronal progenitors. Mol Cell 30:755–766. doi: 10.1016/j.molcel.2008.05.007 PubMedCrossRefGoogle Scholar
  74. Montgomery RL, Hsieh J, Barbosa AC et al (2009) Histone deacetylases 1 and 2 control the progression of neural precursors to neurons during brain development. Proc Natl Acad Sci U S A 106:7876–7881. doi: 10.1073/pnas.0902750106 PubMedPubMedCentralCrossRefGoogle Scholar
  75. Mountford JC (2008) Human embryonic stem cells: origins, characteristics and potential for regenerative therapy. Transfus Med 18:1–12. doi: 10.1111/j.1365-3148.2007.00807.x PubMedCrossRefGoogle Scholar
  76. Muñoz-Sanjuán I, Brivanlou AH (2002) Neural induction, the default model and embryonic stem cells. Nat Rev Neurosci 3:271–280. doi: 10.1038/nrn786 PubMedCrossRefGoogle Scholar
  77. Ono T, Galanopoulou AS (2012) Epilepsy and epileptic syndrome. Adv Exp Med Biol 724:99–113. doi: 10.1007/978-1-4614-0653-2_8 PubMedCrossRefGoogle Scholar
  78. Pawlak M, Jaenisch R (2011) De novo DNA methylation by Dnmt3a and Dnmt3b is dispensable for nuclear reprogramming of somatic cells to a pluripotent state. Genes Dev 25:1035–1040PubMedPubMedCentralCrossRefGoogle Scholar
  79. Pereira M, Pfisterer U, Rylander D et al (2014) Highly efficient generation of induced neurons from human fibroblasts that survive transplantation into the adult rat brain. Sci Rep 4:6330. doi: 10.1038/srep06330 PubMedPubMedCentralCrossRefGoogle Scholar
  80. Petit GH, Olsson TT, Brundin P (2014) The future of cell therapies and brain repair: Parkinson’s disease leads the way. Neuropathol Appl Neurobiol 40:60–70. doi: 10.1111/nan.12110 PubMedCrossRefGoogle Scholar
  81. Ptashne M (2007) On the use of the word “epigenetic”. Curr Biol 17:R233–R236. doi: 10.1016/j.cub.2007.02.030 PubMedCrossRefGoogle Scholar
  82. Ptashne M (2013) Epigenetics: core misconcept. Proc Natl Acad Sci U S A 110(18):7101–7103. doi: 10.1073/pnas.1305399110, Epub 2013 Apr 12PubMedPubMedCentralCrossRefGoogle Scholar
  83. Rago L, Beattie R, Taylor V, Winter J (2014) miR379-410 cluster miRNAs regulate neurogenesis and neuronal migration by fine-tuning N-cadherin. EMBO J 33:906–920. doi: 10.1002/embj.201386591 PubMedPubMedCentralCrossRefGoogle Scholar
  84. Ramalho-Santos M, Willenbring H (2007) On the origin of the term “stem cell”. Stem Cell 1:35–38. doi: 10.1016/j.stem.2007.05.013 Google Scholar
  85. Ringrose L, Paro R (2004) Epigenetic regulation of cellular memory by the Polycomb and Trithorax group proteins. Annu Rev Genet 38:413–443. doi: 10.1146/annurev.genet.38.072902.091907 PubMedCrossRefGoogle Scholar
  86. Roadmap Epigenomics Consortium, Kundaje A, Meuleman W et al (2015) Integrative analysis of 111 reference human epigenomes. Nature 518:317–330. doi: 10.1038/nature14248 PubMedCentralCrossRefGoogle Scholar
  87. Rubin LL (2008) Stem cells and drug discovery: the beginning of a new era? Cell 132:549–552. doi: 10.1016/j.cell.2008.02.010 PubMedCrossRefGoogle Scholar
  88. Rüschenschmidt C, Koch PG, Brüstle O, Beck H (2005) Functional properties of ES cell-derived neurons engrafted into the hippocampus of adult normal and chronically epileptic rats. Epilepsia 46(5):174–183. doi: 10.1111/j.1528-1167.2005.01028.x PubMedCrossRefGoogle Scholar
  89. Sawai T (2014) The moral value of induced pluripotent stem cells: a Japanese bioethics perspective on human embryo research. J Med Ethics 40:766–769. doi: 10.1136/medethics-2013-101838 PubMedCrossRefGoogle Scholar
  90. Schouten M, Buijink MR, Lucassen PJ, Fitzsimons CP (2012) New neurons in aging brains: molecular control by small non-coding RNAs. Front Neurosci 6:25. doi: 10.3389/fnins.2012.00025 PubMedPubMedCentralCrossRefGoogle Scholar
  91. Schwartz YB, Pirrotta V (2013) A new world of Polycombs: unexpected partnerships and emerging functions. Nat Rev Genet 14:853–864. doi: 10.1038/nrg3603 PubMedCrossRefGoogle Scholar
  92. Setoguchi H, Namihira M, Kohyama J et al (2006) Methyl-CpG binding proteins are involved in restricting differentiation plasticity in neurons. J Neurosci Res 84:969–979. doi: 10.1002/jnr.21001 PubMedCrossRefGoogle Scholar
  93. Shakèd M, Weissmüller K, Svoboda H et al (2008) Histone deacetylases control neurogenesis in embryonic brain by inhibition of BMP2/4 signaling. PLoS ONE 3:e2668. doi: 10.1371/journal.pone.0002668 PubMedPubMedCentralCrossRefGoogle Scholar
  94. Sher F, Boddeke E, Olah M, Copray S (2012) Dynamic changes in Ezh2 gene occupancy underlie its involvement in neural stem cell self-renewal and differentiation towards oligodendrocytes. PLoS ONE 7:e40399. doi: 10.1371/journal.pone.0040399 PubMedPubMedCentralCrossRefGoogle Scholar
  95. Sinkkonen L, Hugenschmidt T, Berninger P et al (2008) MicroRNAs control de novo DNA methylation through regulation of transcriptional repressors in mouse embryonic stem cells. Nat Struct Mol Biol 15:259–267. doi: 10.1038/nsmb.1391 PubMedCrossRefGoogle Scholar
  96. Smrt RD, Eaves-Egenes J, Barkho BZ et al (2007) Mecp2 deficiency leads to delayed maturation and altered gene expression in hippocampal neurons. Neurobiol Dis 27:77–89. doi: 10.1016/j.nbd.2007.04.005 PubMedPubMedCentralCrossRefGoogle Scholar
  97. Soldati C, Bithell A, Johnston C et al (2012) Repressor element 1 silencing transcription factor couples loss of pluripotency with neural induction and neural differentiation. Stem Cells 30:425–434. doi: 10.1002/stem.1004 PubMedCrossRefGoogle Scholar
  98. Steffen PA, Ringrose L (2014) What are memories made of? How Polycomb and Trithorax proteins mediate epigenetic memory. Nat Rev Mol Cell Biol 15:340–356. doi: 10.1038/nrm3789 PubMedCrossRefGoogle Scholar
  99. Suh M-R, Lee Y, Kim JY et al (2004) Human embryonic stem cells express a unique set of microRNAs. Dev Biol 270:488–498. doi: 10.1016/j.ydbio.2004.02.019 PubMedCrossRefGoogle Scholar
  100. Sun J, Sun J, Ming G-L, Song H (2011) Epigenetic regulation of neurogenesis in the adult mammalian brain. Eur J Neurosci 33:1087–1093. doi: 10.1111/j.1460-9568.2011.07607.x PubMedPubMedCentralCrossRefGoogle Scholar
  101. Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126:663–676. doi: 10.1016/j.cell.2006.07.024 PubMedCrossRefGoogle Scholar
  102. Tan S-L, Nishi M, Ohtsuka T et al (2012) Essential roles of the histone methyltransferase ESET in the epigenetic control of neural progenitor cells during development. Development 139:3806–3816. doi: 10.1242/dev.082198 PubMedCrossRefGoogle Scholar
  103. Tang K, Peng G, Qiao Y et al (2015) Intrinsic regulations in neural fate commitment. Develop Growth Differ 57:109–120. doi: 10.1111/dgd.12204 CrossRefGoogle Scholar
  104. Taupin P (2006) Adult neural stem cells, neurogenic niches, and cellular therapy. Stem Cell Rev 2:213–219. doi: 10.1007/s12015-006-0049-0 PubMedCrossRefGoogle Scholar
  105. Thomson JA, Itskovitz-Eldor J, Shapiro SS et al (1998) Embryonic stem cell lines derived from human blastocysts. Science 282:1145–1147PubMedCrossRefGoogle Scholar
  106. Tong LM, Djukic B, Arnold C et al (2014) Inhibitory interneuron progenitor transplantation restores normal learning and memory in ApoE4 knock-in mice without or with Aβ accumulation. J Neurosci 34:9506–9515. doi: 10.1523/JNEUROSCI.0693-14.2014 PubMedPubMedCentralCrossRefGoogle Scholar
  107. Torper O, Pfisterer U, Wolf DA et al (2013) Generation of induced neurons via direct conversion in vivo. Proc Natl Acad Sci U S A 110:7038–7043. doi: 10.1073/pnas.1303829110 PubMedPubMedCentralCrossRefGoogle Scholar
  108. Tropepe V, Hitoshi S, Sirard C et al (2001) Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism. Neuron 30:65–78PubMedCrossRefGoogle Scholar
  109. Tsujimura K, Abematsu M, Kohyama J et al (2009) Neuronal differentiation of neural precursor cells is promoted by the methyl-CpG-binding protein MeCP2. Exp Neurol 219:104–111. doi: 10.1016/j.expneurol.2009.05.001 PubMedCrossRefGoogle Scholar
  110. Villasante A, Piazzolla D, Li H et al (2011) Epigenetic regulation of Nanog expression by Ezh2 in pluripotent stem cells. Cell Cycle 10:1488–1498PubMedPubMedCentralCrossRefGoogle Scholar
  111. Visvanathan J, Lee S, Lee B et al (2007) The microRNA miR-124 antagonizes the anti-neural REST/SCP1 pathway during embryonic CNS development. Genes Dev 21:744–749. doi: 10.1101/gad.1519107 PubMedPubMedCentralCrossRefGoogle Scholar
  112. Waldau B, Hattiangady B, Kuruba R, Shetty AK (2010) Medial ganglionic eminence-derived neural stem cell grafts ease spontaneous seizures and restore GDNF expression in a rat model of chronic temporal lobe epilepsy. Stem Cells 28:1153–1164. doi: 10.1002/stem.446 PubMedPubMedCentralGoogle Scholar
  113. Whyte WA, Bilodeau S, Orlando DA et al (2012) Enhancer decommissioning by LSD1 during embryonic stem cell differentiation. Nature 482:221–225. doi: 10.1038/nature10805 PubMedPubMedCentralGoogle Scholar
  114. Wu Z, Huang K, Yu J et al (2012) Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells. J Neurosci Res 90:1883–1891. doi: 10.1002/jnr.23077 PubMedPubMedCentralCrossRefGoogle Scholar
  115. Yu IT, Park J-Y, Kim SH et al (2009) Valproic acid promotes neuronal differentiation by induction of proneural factors in association with H4 acetylation. Neuropharmacology 56:473–480. doi: 10.1016/j.neuropharm.2008.09.019 PubMedCrossRefGoogle Scholar
  116. Zhang Z, Jones A, Sun C-W et al (2011) PRC2 complexes with JARID2, MTF2, and esPRC2p48 in ES cells to modulate ES cell pluripotency and somatic cell reprogramming. Stem Cells 29:229–240. doi: 10.1002/stem.578 PubMedPubMedCentralCrossRefGoogle Scholar
  117. Zheng K, Li H, Zhu Y et al (2010) MicroRNAs are essential for the developmental switch from neurogenesis to gliogenesis in the developing spinal cord. J Neurosci 30:8245–8250. doi: 10.1523/JNEUROSCI.1169-10.2010 PubMedPubMedCentralCrossRefGoogle Scholar
  118. Zipori D (2009) Multipotency and tissue-specific stem cells. In: Zipori D (ed) Biology of stem cells and the molecular basis of the stem state. Humana Press, Totowa, pp 39–55CrossRefGoogle Scholar
  119. Zovoilis A, Smorag L, Pantazi A, Engel W (2009) Members of the miR-290 cluster modulate in vitro differentiation of mouse embryonic stem cells. Differentiation 78:69–78. doi: 10.1016/j.diff.2009.06.003 PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Marijn Schouten
    • 1
  • Nik Papaloukas
    • 1
  • Pascal Bielefeld
    • 1
  • Silvina A. Fratantoni
    • 2
  • Carlos P. Fitzsimons
    • 1
    Email author
  1. 1.Neuroscience Program, Swammerdam Institute for Life SciencesUniversity of AmsterdamAmsterdamThe Netherlands
  2. 2.BioFocus DPI Limited, A Charles River CompanyLeidenThe Netherlands

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