RRC ID 6188
Author Kohyama J, Kojima T, Takatsuka E, Yamashita T, Namiki J, Hsieh J, Gage FH, Namihira M, Okano H, Sawamoto K, Nakashima K.
Title Epigenetic regulation of neural cell differentiation plasticity in the adult mammalian brain.
Journal Proc Natl Acad Sci U S A
Abstract 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.
Volume 105(46)
Pages 18012-7
Published 2008-11-18
DOI 10.1073/pnas.0808417105
PII 0808417105
PMID 19004774
PMC PMC2584744
MeSH Animals Astrocytes / cytology Astrocytes / metabolism Brain / cytology* Brain / metabolism* Cell Differentiation / genetics* Epigenesis, Genetic* Female Green Fluorescent Proteins / metabolism Methyl-CpG-Binding Protein 2 / metabolism Mice Neuronal Plasticity / genetics* Neurons / cytology* Neurons / metabolism* Oligodendroglia / cytology Oligodendroglia / metabolism Organ Specificity Rats STAT Transcription Factors / metabolism
IF 9.412
Times Cited 58
DNA material pCALNL5 (RDB01862)