The Forkhead box transcription factor FOXM1 is required for the maintenance of cell proliferation and protection against oxidative stress in human embryonic stem cells
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AbstractHuman embryonic stem cells (hESCs) exhibit unique cell cycle structure, self-renewal and pluripotency. The Forkhead box transcription factor M1 (FOXM1) is critically required for the maintenance of pluripotency in mouse embryonic stem cells and mouse embryonal carcinoma cells, but its role in hESCs remains unclear. Here, we show that FOXM1 expression was enriched in undifferentiated hESCs and was regulated in a cell cycle-dependent manner with peak levels detected at the G2/M phase. Expression of FOXM1 did not correlate with OCT4 and NANOG during in vitro differentiation of hESCs. Importantly, knockdown of FOXM1 expression led to aberrant cell cycle distribution with impairment in mitotic progression but showed no profound effect on the undifferentiated state. Interestingly, FOXM1 depletion sensitized hESCs to oxidative stress. Moreover, genome-wide analysis of FOXM1 targets by ChIP-seq identified genes important for M phase including CCNB1 and CDK1, which were subsequently confirmed by ChIP and RNA interference analyses. Further peak set comparison against a differentiating hESC line and a cancer cell line revealed a substantial difference in the genomic binding profile of FOXM1 in hESCs. Taken together, our findings provide the first evidence to support FOXM1 as an important regulator of cell cycle progression and defense against oxidative stress in hESCs. (C) 2016 The Authors. Published by Elsevier B.V.
All Author(s) ListKwok CTD, Leung MH, Qin J, Qin Y, Wang J, Lee YL, Yao KM
Journal nameStem Cell Research
Volume Number16
Issue Number3
Pages651 - 661
LanguagesEnglish-United Kingdom
KeywordsCell proliferation; Chromatin immunoprecipitation-sequencing; FOXM1; Human embryonic stem cells; Oxidative stress; Pluripotency
Web of Science Subject CategoriesBiotechnology & Applied Microbiology; Cell & Tissue Engineering; Cell Biology

Last updated on 2021-18-09 at 00:28