Epigenetic regulation of neural lineage elaboration: Implications for therapeutic reprogramming

NEUROBIOLOGY OF DISEASE

卷:148

Review

Stricker, Stefan H.^1,2,3  Goetz, Magdalena^1,2,4 

[1] Helmholtz Zentrum Muenchen, German Res Ctr Environm Hlth, Inst Stem Cell Res, D-82152 Planegg, Germany

[2] Ludwig Maximilians Univ Muenchen, Physiol Genom, Biomed Ctr BMC, D-82152 Munich, Germany

[3] Ludwig Maximilians Univ Munchen, MCN Jr Res Grp, Munich Ctr Neurosci, Biomed Ctr, Grosshaderner Str 9, D-82152 Planegg Martinsried, Germany

[4] Ludwig Maximilians Univ Muenchen, SYNERGY, Excellence Cluster Syst Neurol, BioMed Ctr BMC, D-82152 Munich, Germany

关键词: Direct reprogramming;    Epigenetics;    Neural lineage;   

DOI  :  10.1016/j.nbd.2020.105174

来源: Elsevier

【 摘 要 】

The vulnerability of the mammalian brain is mainly due to its limited ability to generate new neurons once fully matured. Direct conversion of non-neuronal cells to neurons opens up a new avenue for therapeutic intervention and has made great strides also for in vivo applications in the injured brain. These great achievements raise the issue of adequate identity and chromatin hallmarks of the induced neurons. This may be particularly important, as aberrant epigenetic settings may reveal their adverse effects only in certain brain activity states. Therefore, we review here the knowledge about epigenetic memory and partially resetting of chromatin hallmarks from other reprogramming fields, before moving to the knowledge in direct neuronal reprogramming, which is still limited. Most importantly, novel tools are available now to manipulate specific epigenetic marks at specific sites of the genome. Applying these will eventually allow erasing aberrant epigenetic memory and paving the way towards new therapeutic approaches for brain repair.