Single Cell Analysis Reveals Partial Reactivation of X-chromosome Instead of chromosome wide dampening in Naive Human Pluripotent Stem Cells

Abstract

Recently, a unique form of X-chromosome dosage compensation has been demonstrated in human preimplantation embryos, which happens through the dampening of X-linked gene expression from both X-chromosomes. Subsequently, X-chromosome dampening has also been demonstrated in female human pluripotent stem cells (hPSCs) during the transition from primed to naive state. However, the existence of dampened X-chromosomes remains controversial in both embryos and hPSCs. Specifically, in preimplantation embryos it has been shown that there is inactivation of X-chromosome instead of dampening. Here, we have performed allelic analysis of X-linked genes at the single cell level in hPSCs and found that there is partial reactivation of the inactive X-chromosome instead of chromosome-wide dampening upon conversion from primed to naive state. In addition, our analysis suggests that the reduced X-linked gene expression in naive hPSCs might be the consequence of erasure of active X-chromosome upregulation.