Enhancing the Potency of Mouse Embryonic Stem Cells [BS-Seq]

Mouse naïve pluripotent stem cells (ESC) can contribute to all embryonic tissues and the germline, but rarely to the extra-embryonic tissues in chimeric embryos. Here we describe a novel advanced pluripotent stem cell (ASC) with higher potency, since a single ASC contributes very efficiently to the fetus, germline, yolk sac and the placental labyrinth in chimeras. ASCs were derived from blastocysts in two steps in a chemically defined medium with Activin A (ActA) and basic fibroblast growth factor (bFGF), followed by Wnt and BMP. Notably, ASCs exhibit a distinct transcriptome with the expression of both naïve pluripotent genes, as well as mesodermal somatic genes; Eomes, Eras, Tdgf1, Evx1, hand1, Wnt5a, and distinct repetitive elements. Established ESCs can also be readily and directly to ASCs. Importantly, ASCs exhibit a stable hypermethylated epigenome unlike the hypomethylated epiblast in blastocysts and naïve ESCs, indicating that ASCs might represent a state in between the naïve and primed states of pluripotency.