Global transcriptional analysis of human extended pluripotent stem cells, human primed pluripotent stem cells, mouse extended pluripotent stem cells, and mouse embryonic stem cells by RNA-seq

All mammals develop from embryonic founder cells with the ability to generate all of the differentiated cells that constitute the organism. Capture of stem cells with such developmental potential in vitro has been a major challenge in stem cell biology. Here, we show that a chemical cocktail enables the derivation of a new stem cell type from both mice and humans, designated as extended pluripotent stem (EPS) cells. A single human or mouse EPS cell is able to contribute to both embryonic and extraembryonic lineages in inter- and intra-species chimeric mouse conceptuses respectively. Compared to known pluripotent stem cells, EPS cells show upregulation of gene modules marking embryonic cells from early preimplantation development. Further analysis shows that PARP1 inhibition is required for maintaining EPS potency. Our findings constitute a first step towards capturing authentic mammalian totipotency in vitro, and open new avenues for basic and translational research. Total of 10 samples were analyzed, which included human extended pluripotent stem cells, human primed pluripotent stem cells, mouse extended pluripotent stem cells, and mouse embryonic stem cells. For human primed pluripotent stem cells, one cell line H1 was analyzed, which included two samples. For human extended pluripotent stem cells, two cell lines were analyzed, which included ES1-EPS (2 samples) and H1-EPS (2 samples). For mouse extended pluripotent stem cells, two cell lines were analyzed, which included mc6-1 (1 sample) and OG6-3 (1 sample). For mouse embryonic stem cells, two cell lines were analyzed, which included mc2i (1 sample) and OG-2i (1 sample).