Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification

LEQIAN YU; WU J; MUTTO ADRIAN; ROSS JUAN PABLO

Cell Stem Cell

Cell Press

Año: 2020

Dynamic pluripotent stem cell (PSC) states are in vitro adaptations of pluripotency continuum in vivo. Previous studies have generated a number of PSCs with distinct properties. To date, however, no known PSCshave demonstrated dual competency for chimera formation and direct responsiveness to primordial germcell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblastgrowth factor (FGF), transforming growth factor b (TGF-b), and WNT pathways, we derived PSCs from mice,horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro andare capable of contributing to intra- or inter-species chimeras in vivo. XPSCs represent a pluripotency statebetween naive and primed pluripotency and harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency. XPSCs open new avenues for studying mammalian pluripotency and dissecting the molecular mechanisms governing PGC specification. Our method may be broadly applicable for thederivation of analogous stem cells from other mammalian species.