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- Title
Dnmt3a regulates both proliferation and differentiation of mouse neural stem cells.
- Authors
Wu, Zhourui; Huang, Kevin; Yu, Juehua; Le, Thuc; Namihira, Masakasu; Liu, Yupeng; Zhang, Jun; Xue, Zhigang; Cheng, Liming; Fan, Guoping
- Abstract
DNA methylation is known to regulate cell differentiation and neuronal function in vivo. Here we examined whether deficiency of a de novo DNA methyltransferase, Dnmt3a, affects in vitro differentiation of mouse embryonic stem cells (mESCs) to neuronal and glial cell lineages. Early-passage neural stem cells (NSCs) derived from Dnmt3a-deficient ESCs exhibited a moderate phenotype in precocious glial differentiation compared with wild-type counterparts. However, successive passaging to passage 6 (P6), when wild-type NSCs become gliogenic, revealed a robust phenotype of precocious astrocyte and oligodendrocyte differentiation in Dnmt3a(-/-) NSCs, consistent with our previous findings in the more severely hypomethylated Dnmt1(-/-) NSCs. Mass spectrometric analysis revealed that total levels of methylcytosine in Dnmt3a(-/-) NSCs at P6 were globally hypomethylated. Moreover, the Dnmt3a(-/-) NSC proliferation rate was significantly increased compared with control from P6 onward. Thus, our work revealed a novel role for Dnmt3a in regulating both the timing of neural cell differentiation and the cell proliferation in the paradigm of mESC-derived-NSCs.
- Publication
Journal of neuroscience research, 2012, Vol 90, Issue 10, p1883
- ISSN
1097-4547
- Publication type
Journal Article
- DOI
10.1002/jnr.23077