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Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the self-renewal and pluripotency of human embryonic stem cells via the control of the G1/S transition.
Stem Cells. 2013 Dec; 31(12):2647-58.SC

Abstract

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.

Authors+Show Affiliations

Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23495120

Citation

Choi, Hong Seo, et al. "Heterogeneous Nuclear Ribonucleoprotein A2/B1 Regulates the Self-renewal and Pluripotency of Human Embryonic Stem Cells Via the Control of the G1/S Transition." Stem Cells (Dayton, Ohio), vol. 31, no. 12, 2013, pp. 2647-58.
Choi HS, Lee HM, Jang YJ, et al. Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the self-renewal and pluripotency of human embryonic stem cells via the control of the G1/S transition. Stem Cells. 2013;31(12):2647-58.
Choi, H. S., Lee, H. M., Jang, Y. J., Kim, C. H., & Ryu, C. J. (2013). Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the self-renewal and pluripotency of human embryonic stem cells via the control of the G1/S transition. Stem Cells (Dayton, Ohio), 31(12), 2647-58. https://doi.org/10.1002/stem.1366
Choi HS, et al. Heterogeneous Nuclear Ribonucleoprotein A2/B1 Regulates the Self-renewal and Pluripotency of Human Embryonic Stem Cells Via the Control of the G1/S Transition. Stem Cells. 2013;31(12):2647-58. PubMed PMID: 23495120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Heterogeneous nuclear ribonucleoprotein A2/B1 regulates the self-renewal and pluripotency of human embryonic stem cells via the control of the G1/S transition. AU - Choi,Hong Seo, AU - Lee,Hyun Min, AU - Jang,Young-Joo, AU - Kim,Cheorl-Ho, AU - Ryu,Chun Jeih, PY - 2012/09/17/received PY - 2013/02/15/accepted PY - 2013/3/16/entrez PY - 2013/3/16/pubmed PY - 2015/1/16/medline KW - G1/S transition KW - Human embryonic stem cells KW - PI3K/Akt KW - Pluripotency KW - Self-renewal KW - hnRNP A2/B1 SP - 2647 EP - 58 JF - Stem cells (Dayton, Ohio) JO - Stem Cells VL - 31 IS - 12 N2 - 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. SN - 1549-4918 UR - https://www.unboundmedicine.com/medline/citation/23495120/Heterogeneous_nuclear_ribonucleoprotein_A2/B1_regulates_the_self_renewal_and_pluripotency_of_human_embryonic_stem_cells_via_the_control_of_the_G1/S_transition_ L2 - https://doi.org/10.1002/stem.1366 DB - PRIME DP - Unbound Medicine ER -