Inhibition of Human Y Chromosome Gene, SRY, Promotes Naïve State of Human Pluripotent Stem Cells

Although males and females have a variety of sexually dimorphic features related to hormonal effects, the genetic basis of dimorphism relies on early embryo development. Two pluripotent states, naive and primed, emerge during early mammalian development. Identification of signaling pathways that induce differences between these two states can help to modulate conversion of primed cells to naive cells. Naive cells have a shorter doubling time and longer survival than their primed counterparts when passaged as single cells. In this study, we sought to explore the role of Y chromosome genes on human pluripotent stem cells (hPSCs) by investigating differential expressions of the male-specific region of the Y chromosome (MSY) genes in primed and naive cells. Interestingly, we found that several MSY genes, including SRY, showed higher expression levels in primed compared to naive human embryonic stem cells (hESCs). We hypothesize that SRY prevents WNT/β-catenin signaling by its interaction and inhibition of β-cat...