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Histone Demethylases KDM4A and KDM4C Regulate Differentiation of Embryonic Stem Cells to Endothelial Cells.

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journal contribution
posted on 27.01.2016, 00:00 by L. Wu, KK Wary, S. Revskoy, X. Gao, K. Tsang, YA Komarova, J. Rehman, AB Malik
Understanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead to increased efficiency of generation of vessel wall endothelial cells needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an indispensable but independent role in mediating the expression of fetal liver kinase (Flk)1 and VE-cadherin, respectively, and thereby the transition of mouse ESCs (mESCs) to endothelial cells. KDM4A was shown to bind to histones associated with the Flk1 promoter and KDM4C to bind to histones associated with the VE-cadherin promoter. KDM4A and KDM4C were also both required for capillary tube formation and vasculogenesis in mice. We observed in zebrafish that KDM4A depletion induced more severe vasculogenesis defects than KDM4C depletion, reflecting the early involvement of KDM4A in specifying endothelial cell fate. These findings together demonstrate the essential role of KDM4A and KDM4C in orchestrating mESC differentiation to endothelial cells through the activation of Flk1 and VE-cadherin promoters, respectively.


The studies were supported by National Heart, Lung, and Blood Institute grants T32-HL007829 and HL090152 to A.B.M., HL118068 to A.B.M. and J.R., GM094220 to J.R., HL103922 to Y.A.K., and HL079356 to K.K.W


Publisher Statement

This is the copy of an article published in Stem Cell Reports © 2015 Elsevier Publications. http://dx.doi.org/10.1016/j.stemcr.2015.05.016


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