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

Leqian Yu, Yulei Wei, Hai Xi Sun, Ahmed K. Mahdi, Carlos A. Pinzon Arteaga, Masahiro Sakurai, Daniel A. Schmitz, Canbin Zheng, Emily D. Ballard, Jie Li, Noriko Tanaka, Aoi Kohara, Daiji Okamura, Adrian A. Mutto, Ying Gu, Pablo J. Ross, Jun Wu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalCell Stem Cell
DOIs
StateAccepted/In press - 2020

Keywords

  • Pluripotency
  • chimeras
  • formative pluripotency
  • horse embryonic stem cells
  • induced pluripotent stem cells
  • intermediate pluripotent stem cells
  • interspecies chimeras
  • primoridial germ cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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