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

doi:10.1016/j.stem.2020.11.003

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

Cell Stem Cell. 2021 Mar 4;28(3):550-567.e12. doi: 10.1016/j.stem.2020.11.003. Epub 2020 Dec 2.

Authors

Leqian Yu¹, Yulei Wei², Hai-Xi Sun³, Ahmed K Mahdi⁴, Carlos A Pinzon Arteaga⁵, Masahiro Sakurai⁵, Daniel A Schmitz⁵, Canbin Zheng⁶, Emily D Ballard⁵, Jie Li³, Noriko Tanaka⁷, Aoi Kohara⁷, Daiji Okamura⁷, Adrian A Mutto⁸, Ying Gu³, Pablo J Ross⁴, Jun Wu⁹

Affiliations

¹ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China; International Healthcare Innovation Institute, Jiangmen 529040, China.
³ Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen 518083, China; China National GeneBank, BGI-Shenzhen, Shenzhen 518120, China.
⁴ Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.
⁵ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁶ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Microsurgery, Orthopaedic Trauma and Hand Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
⁷ Department of Advanced Bioscience, Graduate School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
⁸ Instituto de Investigaciones Biotecnológicas IIB-INTECH Dr. Rodolfo Ugalde, UNSAM-CONICET, Buenos Aires 1650, Argentina.
⁹ Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: jun2.wu@utsouthwestern.edu.

PMID: 33271070
DOI: 10.1016/j.stem.2020.11.003

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.

Keywords: Pluripotency; chimeras; formative pluripotency; horse embryonic stem cells; induced pluripotent stem cells; intermediate pluripotent stem cells; interspecies chimeras; primoridial germ cells.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cell Differentiation
Chimera
Germ Cells
Horses
Mice
Pluripotent Stem Cells*