Pluto Bioinformatics

GSE138012: Nave human pluripotency stem cells respond to Wnt, Nodal and LIF signalling to produce expandable nave extra-embryonic endoderm

Bulk RNA sequencing

Embryonic stem cells (ESCs) can exist in at least two states that transcriptionally resemble different stages of embryonic development. Nave ESCs resemble peri-implantation stages and primed ESCs the pre-gastrulation epiblast. In mouse, primed ESCs give rise to definitive endoderm in response to pathways downstream of Nodal and Wnt signalling. However, when these cytokines are applied to nave ESCs, they differentiate to a cell type that approximates early primitive endoderm (PrE), the blastocyst stage progenitor layer that gives rise to the extra-embryonic endoderm. Here, we apply this context dependency to human ESCs, showing that these cytokines drive the differentiation of nave pluripotent cells to generate extra-embryonic PrE, or hypoblast, and, as in mouse, expanded as an in vitro model for nave extra-embryonic endoderm (nEnd) in defined conditions. Consistent with observations made in mouse, human PrE differentiation is dependent on FGF signalling in vitro, and we show, that by inhibiting FGF receptor signalling, we could simplify nave pluripotent culture such that inhibitor requirements closer resembled those used in mouse. These nEnd cultures represent stable extra-embryonic endoderm, or human hypoblast, cell lines. SOURCE: Josh,M,Brickman (joshua.brickman@sund.ku.dk) - Brickman Copenhagen University