TY - JOUR
T1 - Transcriptional and epigenetic mechanisms underlying astrocyte identity
AU - Pavlou, Maria Angeliki S.
AU - Grandbarbe, Luc
AU - Buckley, Noel J.
AU - Niclou, Simone P.
AU - Michelucci, Alessandro
N1 - Funding Information:
M.A.S.P. and L.G. were supported by the University of Luxembourg (IRP ASTROSYS) . A.M. was supported by the Luxembourg Institute of Health and the Luxembourg Centre for Systems Biomedicine (MIGLISYS) .
Publisher Copyright:
© 2019 The Authors
PY - 2019/3
Y1 - 2019/3
N2 - Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation capacities that range from their transition towards reactive astrocytes to their ability to undergo reprogramming, thereby revealing their potential to retain latent features of neural progenitor cells. We propose that the mechanisms underlying reactive astrogliosis or astrocyte reprogramming provide an opportunity for initiating neuronal regeneration, a process that is notably reduced in the mammalian nervous system throughout evolution. Conversely, this plasticity may also affect normal astrocytic functions resulting in pathologies ranging from neurodevelopmental disorders to neurodegenerative diseases and brain tumors. We postulate that epigenetic mechanisms linking extrinsic cues and intrinsic transcriptional programs are key factors to maintain astrocyte identity and function, and critically, to control the balance of regenerative and degenerative activity. Here, we will review the main evidences supporting this concept. We propose that unravelling the epigenetic and transcriptional mechanisms underlying the acquisition of astrocyte identity and plasticity, as well as understanding how these processes are modulated by the local microenvironment under specific threatening or pathological conditions, may pave the way to new therapeutic avenues for several neurological disorders including neurodegenerative diseases and brain tumors of astrocytic lineage.
AB - Astrocytes play a significant role in coordinating neural development and provide critical support for the function of the CNS. They possess important adaptation capacities that range from their transition towards reactive astrocytes to their ability to undergo reprogramming, thereby revealing their potential to retain latent features of neural progenitor cells. We propose that the mechanisms underlying reactive astrogliosis or astrocyte reprogramming provide an opportunity for initiating neuronal regeneration, a process that is notably reduced in the mammalian nervous system throughout evolution. Conversely, this plasticity may also affect normal astrocytic functions resulting in pathologies ranging from neurodevelopmental disorders to neurodegenerative diseases and brain tumors. We postulate that epigenetic mechanisms linking extrinsic cues and intrinsic transcriptional programs are key factors to maintain astrocyte identity and function, and critically, to control the balance of regenerative and degenerative activity. Here, we will review the main evidences supporting this concept. We propose that unravelling the epigenetic and transcriptional mechanisms underlying the acquisition of astrocyte identity and plasticity, as well as understanding how these processes are modulated by the local microenvironment under specific threatening or pathological conditions, may pave the way to new therapeutic avenues for several neurological disorders including neurodegenerative diseases and brain tumors of astrocytic lineage.
KW - Astrocyte differentiation
KW - Epigenetic modifications
KW - Reactive astrogliosis
KW - Transcriptional mechanisms
UR - http://www.scopus.com/inward/record.url?scp=85059701030&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/30599178
U2 - 10.1016/j.pneurobio.2018.12.007
DO - 10.1016/j.pneurobio.2018.12.007
M3 - Review article
C2 - 30599178
AN - SCOPUS:85059701030
SN - 0301-0082
VL - 174
SP - 36
EP - 52
JO - Progress in Neurobiology
JF - Progress in Neurobiology
ER -