De-erosion of X chromosome dosage compensation by the editing of XIST regulatory regions restores the differentiation potential in hPSCs.

ABSTRACT: Human pluripotent stem cells (hPSCs) regularly and irreversibly show the erosion of X chromosome inactivation (XCI) by long non-coding RNA (lncRNA) XIST silencing, causing challenges in various applications of female hPSCs. Here, we report reliable methods to reactivate XIST with monoallelic expression in female hPSCs. Surprisingly, we find that the editing of XIST regulatory regions by Cas9-mediated non-homologous end joining is sufficient for the reactivation of XIST by endogenous systems. Proliferated hPSCs with XIST reactivation show XCI from an eroded X chromosome, suggesting that hPSCs with normal dosage compensation might lead to a growth advantage. Furthermore, the use of targeting vectors, including the XIST regulatory region sequences and

SUBMITTER: Motosugi N 

PROVIDER: S-EPMC9795333 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature