Pluto Bioinformatics

GSE123055: Formative transition of human nave pluripotent stem cells

Bulk RNA sequencing

Human nave pluripotent stem cells (PSC) share features with pre-implantation epiblast. They thus provide an unmatched opportunity for characterising the developmental programme of pluripotency in Homo sapiens. Here we confirm that nave PSC do not respond directly to germ layer induction, but must first acquire competence. Capacitation for multi-lineage differentiation occurs without exogenous growth factor stimulation and is facilitated by inhibition of Wnt signalling. Whole transcriptome profiling during this formative transition highlights dynamic changes in gene expression, affecting many cellular properties, including metabolism and epithelialisation. Notably, nave pluripotency factors are exchanged for post-implantation factors, but competent cells remain devoid of lineage primed transcription. The gradual pace of transition for human nave PSC is consistent with the timespan of primate development from blastocyst to gastrulation. Transcriptome trajectory during in vitro capacitation of human nave cells tracks the progression of epiblast during embryogenesis in Macaca fascicularis, but shows greater divergence from mouse development. Thus the formative transition of nave PSC in a simple culture system may recapitulate essential and specific features of pluripotency dynamics during an inaccessible period of human embryogenesis. SOURCE: Giuliano,Giuseppe,Stirparo (giulianostirparo@gmail.com) - University of Cambridge