Epigenetic Mechanisms Regulating the Transition from Embryonic Stem Cells Towards a Differentiated Neural Progeny
- 790 Downloads
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.
KeywordsNeurodegenerative disease DNA methylation MicroRNA Chromatin remodeling Histone modification
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.
- 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
- 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
- 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