@article{dc09f90f1ce24adab263d89edf0de144,
title = "Derivation of Intermediate Pluripotent Stem Cells Amenable to Primordial Germ Cell Specification",
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",
author = "Leqian Yu and Yulei Wei and Sun, {Hai Xi} and Mahdi, {Ahmed K.} and {Pinzon Arteaga}, {Carlos A.} and Masahiro Sakurai and Schmitz, {Daniel A.} and Canbin Zheng and Ballard, {Emily D.} and Jie Li and Noriko Tanaka and Aoi Kohara and Daiji Okamura and Mutto, {Adrian A.} and Ying Gu and Ross, {Pablo J.} and Jun Wu",
note = "Funding Information: We would like to thank M. Saitou for providing the BVSC mESCs; K. Hinrichs and K. A. Rader for providing vitrified ICSI equine embryos; L. Zhang for technical support; X. Xu for preparing ChIP-seq libraries; X. Wang and C. Liang for helping with bioinformatics analysis; and E. Olson and M. Buszczak for critical reading of the manuscript. J.W. is a Virginia Murchison Linthicum Scholar in Medical Research and funded by Cancer Prevention & Research Institute of Texas (CPRIT no. RR170076 ). L.Y. is partially supported by a trainee fellowship from the Hamon Center for Regenerative Science & Medicine . H.-X.S., J.L., and Y.G. are supported by the Guangdong Provincial Key Laboratory of Genome Read and Write (no. 2017B030301011 ). A.A.M. is supported by Crestview Farm . This work was partially supported by the Asahi Glass Foundation . Funding Information: We would like to thank M. Saitou for providing the BVSC mESCs; K. Hinrichs and K. A. Rader for providing vitrified ICSI equine embryos; L. Zhang for technical support; X. Xu for preparing ChIP-seq libraries; X. Wang and C. Liang for helping with bioinformatics analysis; and E. Olson and M. Buszczak for critical reading of the manuscript. J.W. is a Virginia Murchison Linthicum Scholar in Medical Research and funded by Cancer Prevention & Research Institute of Texas (CPRIT no. RR170076). L.Y. is partially supported by a trainee fellowship from the Hamon Center for Regenerative Science & Medicine. H.-X.S. J.L. and Y.G. are supported by the Guangdong Provincial Key Laboratory of Genome Read and Write (no. 2017B030301011). A.A.M. is supported by Crestview Farm. This work was partially supported by the Asahi Glass Foundation. L.Y. P.J.R. and J.W. conceived the study. L.Y. and Y.W. derived FTW-ESC lines from mouse blastocysts. J.W. and L.Y. generated human FTW-iPSCs from HFFs. D.O. A.K. and N.T. tested FTW-ESC derivation from post-implantation epiblasts. J.W. L.Y. and C.A.P.A. derived horse FTW-ESC and FTW-iPSC lines. C.A.P.A. and D.A.S. generated horse NANOS3-EGFP reporter lines. Y.W. and M.S. performed mouse microinjection experiments. L.Y. and Y.W. designed and performed in vitro experiments. C.Z. and E.D.B. helped with in vitro experiments. H.-X.S. and J.L. performed bioinformatics analysis. Y.G. helped with project design and discussions. A.A.M. generated SCNT embryos. A.K.M. and P.J.R. performed microinjection of XPSCs from horse into sheep, goat, and pig embryos. L.Y. and J.W. wrote the manuscript, with input from all authors. L.Y. and J.W. are inventors on a patent application arising from this work. The other authors declare no competing interests.",
year = "2020",
doi = "10.1016/j.stem.2020.11.003",
language = "English (US)",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
}