Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency

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Title
Unveiling the critical role of REX1 in the regulation of human stem cell pluripotency
Author(s)
Mi Young Son; Hoonsung Choi; Y M Han; Yee Sook Cho
Bibliographic Citation
Stem Cells, vol. 31, no. 11, pp. 2374-2387
Publication Year
2013
Abstract
Reduced expression 1 (REX1) is a widely used pluripotency marker, but little is known about its roles in pluripotency. Here, we show that REX1 is functionally important in the reacquisition and maintenance of pluripotency. REX1-depleted human pluripotent stem cells (hPSCs) lose their self-renewal capacity and full differentiation potential, especially their mesoderm lineage potential. Cyclin B1/B2 expression was found to parallel that of REX1. REX1 positively regulates the transcriptional activity of cyclin B1/B2 through binding to their promoters. REX1 induces the phosphorylation of DRP1 at Ser616 by cyclin B/CDK1, which leads to mitochondrial fission and appears to be important for meeting the high-energy demands of highly glycolytic hPSCs. During reprogramming to pluripotency by defined factors (OCT4, SOX2, KLF4, and c-MYC), the reprogramming kinetics and efficiency are markedly improved by adding REX1 or replacing KLF4 with REX1. These improvements are achieved by lowering reprogramming barriers (growth arrest and apoptosis), by enhancing mitochondrial fission, and by conversion to glycolytic metabolism, dependent on the cyclin B1/B2-DRP1 pathway. Our results show that a novel pluripotency regulator, REX1, is essential for pluripotency and reprogramming.
Keyword
Cyclin BHuman embryonic stem cellHuman induced pluripotent stem cellPluripotencyReprogrammingREX1
ISSN
1066-5099
Publisher
Wiley
DOI
http://dx.doi.org/10.1002/stem.1509
Type
Article
Appears in Collections:
Division of Research on National Challenges > Stem Cell Convergenece Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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