TY - JOUR
T1 - Reprogramming neurons for regeneration
T2 - The fountain of youth
AU - Yang, Shu Guang
AU - Wang, Xue Wei
AU - Qian, Cheng
AU - Zhou, Feng Quan
N1 - Publisher Copyright:
© 2022 The Authors
PY - 2022/7
Y1 - 2022/7
N2 - Neurons in the central nervous system (CNS) are terminally differentiated cells that gradually lose their ability to support regeneration during maturation due to changes in transcriptomic and chromatin landscape. Similar transcriptomic changes also occur during development when stem cells differentiate into different types of somatic cells. Importantly, differentiated cells can be reprogrammed back to induced pluripotent stems cells (iPSCs) via global epigenetic remodeling by combined overexpression of pluripotent reprogramming factors, including Oct4, Sox2, Klf4, c-Myc, Nanog, and/or Lin28. Moreover, recent findings showed that many proneural transcription factors were able to convert non-neural somatic cells into neurons bypassing the pluripotent stage via direct reprogramming. Interestingly, many of these factors have recently been identified as key regulators of CNS neural regeneration. Recent studies indicated that these factors could rejuvenate mature CNS neurons back to a younger state through cellular state reprogramming, thus favoring regeneration. Here we will review some recent findings regarding the roles of genetic cellular state reprogramming in regulation of neural regeneration and explore the potential underlying molecular mechanisms. Moreover, by using newly emerging techniques, such as multiomics sequencing with big data analysis and Crispr-based gene editing, we will discuss future research directions focusing on better revealing cellular state reprogramming-induced remodeling of chromatin landscape and potential translational application.
AB - Neurons in the central nervous system (CNS) are terminally differentiated cells that gradually lose their ability to support regeneration during maturation due to changes in transcriptomic and chromatin landscape. Similar transcriptomic changes also occur during development when stem cells differentiate into different types of somatic cells. Importantly, differentiated cells can be reprogrammed back to induced pluripotent stems cells (iPSCs) via global epigenetic remodeling by combined overexpression of pluripotent reprogramming factors, including Oct4, Sox2, Klf4, c-Myc, Nanog, and/or Lin28. Moreover, recent findings showed that many proneural transcription factors were able to convert non-neural somatic cells into neurons bypassing the pluripotent stage via direct reprogramming. Interestingly, many of these factors have recently been identified as key regulators of CNS neural regeneration. Recent studies indicated that these factors could rejuvenate mature CNS neurons back to a younger state through cellular state reprogramming, thus favoring regeneration. Here we will review some recent findings regarding the roles of genetic cellular state reprogramming in regulation of neural regeneration and explore the potential underlying molecular mechanisms. Moreover, by using newly emerging techniques, such as multiomics sequencing with big data analysis and Crispr-based gene editing, we will discuss future research directions focusing on better revealing cellular state reprogramming-induced remodeling of chromatin landscape and potential translational application.
KW - Aging
KW - Axon regeneration
KW - Cellular state reprogramming
KW - Epigenetic regulation
KW - Optic nerve
KW - Regeneration
UR - http://www.scopus.com/inward/record.url?scp=85129725016&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85129725016&partnerID=8YFLogxK
U2 - 10.1016/j.pneurobio.2022.102284
DO - 10.1016/j.pneurobio.2022.102284
M3 - Review article
C2 - 35533809
AN - SCOPUS:85129725016
SN - 0301-0082
VL - 214
JO - Progress in Neurobiology
JF - Progress in Neurobiology
M1 - 102284
ER -