Single-Cell RNA-Seq Reveals Cellular Heterogeneity of Pluripotency Transition and X Chromosome Dynamics during Early Mouse Development

摘要

Following implantation, the epiblast (EPI) cells transitfrom the naive to primed pluripotency, accompaniedby dynamic changes in X chromosome activity in females.To investigate the molecular attributes of thisprocess, we performed single-cell RNA-seq analysisof 1,724 cells of E5.25, E5.5, E6.25, and E6.5 mouseembryos. We identified three cellular states in theEPI cells that capture the transition along the pluripotencycontinuum and the acquisition of primitivestreak propensity. The transition of three EPI stateswas driven by inductive signaling activity emanatingfrom the visceral endoderm (VE). In the EPI of femaleembryos, X chromosome reactivation (XCR) wasinitiated prior to the completion of imprinted X chromosomeinactivation (XCI), and the ensuing randomXCI was highly asynchronous. Moreover, imprintedpaternal XCI proceeded faster in the VE than theextraembryonic ectoderm. Our study has provideda detailed molecular roadmap of the emergent lineagecommitment before gastrulation and characterizedX chromosome dynamics during early mousedevelopment.