Large-Scale Analysis of X Inactivation Variations between Primed and Naïve Human Embryonic Stem Cells

Abstract

X chromosome inactivation is a mammalian dosage compensation mechanism, where one of two X chromosomes is randomly inactivated in female cells. Previous studies have suggested that primed human embryonic stem cells (hESCs) maintain an eroded state of the X chromosome and do not express XIST, while in naïve transition, both XIST and the eroded X chromosome are reactivated. However, the pattern of chromosome X reactivation in naïve hESCs remains mainly unknown. In this study, we examine the variations in the status of X chromosome between primed and naïve hESCs by analyzing RNA sequencing samples from different studies. We show that most samples of naïve hESCs indeed reactivate XIST and there is an increase in gene expression levels on chromosome X. However, most of the naïve samples do not fully activate chromosome X in a uniform manner and present a distinct eroded pattern, probably as a result of XIST reactivation and initiation of re-inactivation of chromosome X. This large-scale analysis provides a higher-resolution description of the changes occurring in chromosome X during primed-to-naïve transition and emphasizes the importance of taking these variations into consideration when studying X inactivation in embryonic development.

Keywords

• human embryonic stem cells
• naive embryonic stem cells
• X inactivation
• large-scale analysis