Stress-mediated p38 activation promotes somatic cell reprogramming View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-10-09

AUTHORS

Xinxiu Xu, Quan Wang, Yuan Long, Ru Zhang, Xiaoyuan Wei, Mingzhe Xing, Haifeng Gu, Xin Xie

ABSTRACT

Environmental stress-mediated adaptation plays essential roles in the evolution of life. Cellular adaptation mechanisms usually involve the regulation of chromatin structure, transcription, mRNA stability and translation, which eventually lead to efficient changes in gene expression. Global epigenetic change is also involved in the reprogramming of somatic cells into induced pluripotent stem (iPS) cells by defined factors. Here we report that environmental stress such as hyperosmosis not only facilitates four factor-mediated reprogramming, but also enhances two or one factor-induced iPS cell generation. Hyperosmosis-induced p38 activation plays a critical role in this process. Constitutive active p38 mimics the positive effect of hyperosmosis, while dominant negative p38 and p38 inhibitor block the effect of hyperosmosis. Further study indicates stress-mediated p38 activation may promote reprogramming by reducing the global DNA methylation level and enhancing the expression of pluripotency genes. Our results demonstrate how simple environmental stress like hyperosmosis helps to alter the fate of cells via intracellular signaling and epigenetic modulation. More... »

PAGES

131-141

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cr.2012.143

DOI

http://dx.doi.org/10.1038/cr.2012.143

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053268375

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23044805


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