Heterogeneous Nuclear Ribonucleoprotein A2/B1 Regulates the Self‐Renewal and Pluripotency of Human Embryonic Stem Cells Via the Control of the G1/S Transition. (December 2013)

• Record Type: Journal Article
• Authors: Choi, Hong Seo; Lee, Hyun Min; Jang, Young‐Joo; Kim, Cheorl‐Ho; Ryu, Chun Jeih
• Is Part Of: Stem cells. Volume 31:Number 12(2013:Dec.)
• Page Start: 2647
• Page End: 2658
• Publication Date: 2013-12
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1366
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Self‐renewal and pluripotency of human embryonic stem cells (hESCs) are a complex biological process for maintaining hESC stemness. However, the molecular mechanisms underlying these special properties of hESCs are not fully understood. Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) is a multifunctional RNA‐binding protein whose expression is related to cell proliferation and carcinogenesis. In this study, we found that hnRNP A2/B1 expression was localized to undifferentiated hESCs and decreased upon differentiation of hESCs. hnRNP A2/B1 knockdown reduced the number of alkaline phosphatase‐positive colonies in hESCs and led to a decrease in the expression of pluripotency‐associated transcription factors OCT4, NANOG, and SOX2, indicating that hnRNP A2/B1 is essential for hESC self‐renewal and pluripotency. hnRNP A2/B1 knockdown increased the expression of gene markers associated with the early development of three germ layers, and promoted the process of epithelial‐mesenchymal transition, suggesting that hnRNP A2/B1 is required for maintaining the undifferentiated and epithelial phenotypes of hESCs. hnRNP A2/B1 knockdown inhibited hESC proliferation and induced cell cycle arrest in the G0/G1 phase before differentiation via degradation of cyclin D1, cyclin E, and Cdc25A. hnRNP A2/B1 knockdown increased p27 expression and induced phosphorylation of p53 and Chk1, suggesting that hnRNP A2/B1 also regulates the G1/S transition of hESC cell cycle through the control of p27 expression and p53 and Chk1 activity. Analysis of signaling molecules further revealed that hnRNP A2/B1 regulated hESC proliferation in a PI3K/Akt‐dependent manner. These findings provide for the first time mechanistic insights into how hnRNP A2/B1 regulates hESC self‐renewal and pluripotency. S<sc>TEM</sc> C<sc>ells</sc><italic>2013;31:2647–2658</italic></p> </abstract>