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

• Published in: Cell stem cell Vol. 28; no. 3; pp. 550 - 567.e12
• Main Authors: Yu, Leqian, Wei, Yulei, Sun, Hai-Xi, Mahdi, Ahmed K., Pinzon Arteaga, Carlos A., Sakurai, Masahiro, Schmitz, Daniel A., Zheng, Canbin, Ballard, Emily D., Li, Jie, Tanaka, Noriko, Kohara, Aoi, Okamura, Daiji, Mutto, Adrian A., Gu, Ying, Ross, Pablo J., Wu, Jun
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04-03-2021
• Subjects: chimeras; formative pluripotency; horse embryonic stem cells; induced pluripotent stem cells; intermediate pluripotent stem cells; interspecies chimeras; Pluripotency; primoridial germ cells; chimeras; interspecies chimeras; intermediate pluripotent stem cells; induced pluripotent stem cells; formative pluripotency; primoridial germ cells; Pluripotency; horse embryonic stem cells
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2020.11.003

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 PSCs have demonstrated dual competency for chimera formation and direct responsiveness to primordial germ cell (PGC) specification, a unique functional feature of formative pluripotency. Here, by modulating fibroblast growth factor (FGF), transforming growth factor β (TGF-β), 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 and are capable of contributing to intra- or inter-species chimeras in vivo. XPSCs represent a pluripotency state between 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 the derivation of analogous stem cells from other mammalian species.
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•Derivation of intermediate XPSCs by modulating FGF, TGF-β, and WNT pathways•XPSCs can be generated from mice, horses, and humans•XPSCs harbor formative pluripotency features•XPSCs show chimera and primordial germ cell specification dual competency
Yu, Wu, and colleagues report the derivation of intermediate PSCs from mice, horses, and humans (designated as XPSCs) that are permissive for direct PGC-like cell induction in vitro and capable of contributing to intra- or inter-species chimeras in vivo. XPSCs harbor molecular, cellular, and phenotypic features characteristic of formative pluripotency.