Generation and characterization of human emryonic stem cells with increased expression of HIF-2a

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The HIF-2 a subunit is involved in regulation of transcription factors, controlling the self-renewal of human pluripotent stem cells, embryonic development of the cardiovascular system and the regulation of angiogenesis by transcriptional activation of angiogenic cascades in physiological and pathological processes. Currently, modulation of HIF-2a expression is considered as a promising strategy for the treatment of ischemic and cancer diseases. However, the problem of choosing the optimal methods of effective regulation of HIF-2a remains. The aim of this study is to obtain human embryonic stem cells with increased expression of HIF-2a at normal oxygen concentration due to silencing of INT6, the regulator of HIF-2a. In this study, we obtained genetically modified human embryonic stem cells with increased expression of HIF-2a under atmospheric oxygen conditions. The approach used is based on a CRISPR/Cas9-mediated deletion of a part of the INT6 gene, an HIF-2a inhibitor. A study of the resulting genetically modified human embryonic stem cells will contribute to an understanding of the connection between hypoxia and pluripotency. Obtaining endothelial derivatives of pluripotent stem cells with increased expression of HIF-2a and enhanced regenerative potential may become the basis for the development of promising strategies for treatment of ischemic diseases.

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About the authors

M. K Zhiven

Institute of Cytology and Genetics, the Siberian Branch of the RAS; E.N. Meshalkin National Medical Research Center


I. S Zakharova

Institute of Cytology and Genetics, the Siberian Branch of the RAS; E.N. Meshalkin National Medical Research Center

A. I Shevchenko

Institute of Cytology and Genetics, the Siberian Branch of the RAS; E.N. Meshalkin National Medical Research Center

E. A Elisaphenko

Institute of Cytology and Genetics, the Siberian Branch of the RAS; E.N. Meshalkin National Medical Research Center

K. E Orishchenko

Institute of Cytology and Genetics, the Siberian Branch of the RAS

S. M Zakian

Institute of Cytology and Genetics, the Siberian Branch of the RAS; E.N. Meshalkin National Medical Research Center


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