x chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming

x chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming

;Kun-Yong Kim;Eriona Hysolli;Yoshiaki Tanaka;Brandon Wang;Yong-Wook Jung;Xinghua Pan;Sherman Morton Weissman;In-Hyun Park
nature reviews gastroenterology & hepatology 2014 Vol. 2 pp. 896-909
191
kim2014stemx

Abstract

Induced pluripotent stem cells (iPSCs) acquire embryonic stem cell (ESC)-like epigenetic states, including the X chromosome. Previous studies reported that human iPSCs retain the inactive X chromosome of parental cells, or acquire two active X chromosomes through reprogramming. Most studies investigated the X chromosome states in established human iPSC clones after completion of reprogramming. Thus, it is still not fully understood when and how the X chromosome reactivation occurs during reprogramming. Here, we report a dynamic change in the X chromosome state throughout reprogramming, with an initial robust reactivation of the inactive X chromosome followed by an inactivation upon generation of nascent iPSC clones. iPSCs with two active X chromosomes or an eroded X chromosome arise in passaging iPSCs. These data provide important insights into the plasticity of the X chromosome of human female iPSCs and will be crucial for the future application of such cells in cell therapy and X-linked disease modeling.

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