西亚试剂优势供应上万种化学试剂产品，欢迎各位新老客户咨询、选购！
中国
联系我们
联系方式：400-990-3999 / 邮箱：sales@xiyashiji.com
西亚试剂 —— 品质可靠，值得信赖
HIF-2α Suppresses p53 to Enhance the Stemness and Regenerative Potential of Human Embryonic Stem Cells
Bikul Das, Reza Bayat-Mokhtari, Micky Tsui, Shamim Lotfi, Rika Tsuchida, Dean W. Felsher, Herman Yeger
Human Embryonic Stem Cells (hESCs) have been reported to exert cytoprotective activity in the area of tissue injury. However, hypoxia/oxidative stress prevailing in the area of injury could activate p53, leading to death and differentiation of hESCs. Here we report that when exposed to hypoxia/oxidative stress, a small fraction of hESCs, namely the SSEA3+/ABCG2+ fraction undergoes a transient state of reprogramming to a low p53 and high HIF-2α state of transcriptional activity. This state can be sustained for a period of two-weeks and is associated with enhanced transcriptional activity of Oct-4 and Nanog, concomitant with high teratomagenic potential. Conditioned medium (CM) obtained from the post-hypoxia SSEA3+/ABCG2+ hESCs showed cytoprotection both in vitro and in vivo. We termed this phenotype as the “enhanced stemness” state. We then demonstrated that the underlying molecular mechanism of this transient phenotype of “enhanced stemness” involved high Bcl-2, FGF-2 and MDM2 expression, and an altered state of the p53/MDM2 oscillation system. Specific silencing of HIF-2α and p53 resisted the reprogramming of SSEA3+/ABCG2+ to the “enhanced stemness” phenotype. Thus, our studies have uncovered a unique transient reprogramming activity in hESCs, the “enhanced stemness” reprogramming where a highly cytoprotective and undifferentiated state is achieved by transiently suppressing p53 activity. We suggest that this transient reprogramming is a form of stem cell altruism that benefits the surrounding tissues during the process of tissue regeneration.
