Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain.
Neural stem/progenitor cells (NSCs/NPCs) give rise to neurons, astrocytes, and oligodendrocytes. It has become apparent that intracellular epigenetic modification including DNA methylation, in concert with extracellular cues such as cytokine signaling, is deeply involved in fate specification of NSCs/NPCs by defining cell-type specific gene expression. However, it is still unclear how differentiated neural cells retain their specific attributes by repressing cellular properties characteristic of other lineages. In previous work we have shown that methyl-CpG binding protein transcriptional repressors (MBDs), which are expressed predominantly in neurons in the central nervous system, inhibit astrocyte-specific gene expression by binding to highly methylated regions of their target genes. Here we report that oligodendrocytes, which do not express MBDs, can transdifferentiate into astrocytes both in vitro (cytokine stimulation) and in vivo (ischemic injury) through the activation of the JAK/STAT signaling pathway. These findings suggest that differentiation plasticity in neural cells is regulated by cell-intrinsic epigenetic mechanisms in collaboration with ambient cell-extrinsic cues.
Kohyama
Jun
J
Laboratory of Molecular Neuroscience, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 630-0101, Japan.
Kojima
Takuro
T
Takatsuka
Eriko
E
Yamashita
Toru
T
Namiki
Jun
J
Hsieh
Jenny
J
Gage
Fred H
FH
Namihira
Masakazu
M
Okano
Hideyuki
H
Sawamoto
Kazunobu
K
Nakashima
Kinichi
K
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics*; D044127:Epigenesis, Genetic; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity / Q000235:genetics*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D050791:STAT Transcription Factors / Q000378:metabolism
D051783:Methyl-CpG-Binding Protein 2; D050791:STAT Transcription Factors; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins