title: Stress-mediated p38 activation promotes somatic cell reprogramming.
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.
authors.affiliation: Laboratory of Receptor-based Bio-medicine, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
authors.forename: Xinxiu
authors.initials: X
authors.lastname: Xu
authors.forename: Quan
authors.initials: Q
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Long
authors.forename: Ru
authors.initials: R
authors.lastname: Zhang
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Wei
authors.forename: Mingzhe
authors.initials: M
authors.lastname: Xing
authors.forename: Haifeng
authors.initials: H
authors.lastname: Gu
authors.forename: Xin
authors.initials: X
authors.lastname: Xie
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D065150:Cellular Reprogramming / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D004789:Enzyme Activation; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D012965:Sodium Chloride / Q000494:pharmacology; D013312:Stress, Physiological; D013724:Teratoma / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D014157:Transcription Factors; D012965:Sodium Chloride; D048051:p38 Mitogen-Activated Protein Kinases