Extraembryonic Endoderm (XEN) Cells Capable of Contributing to Embryonic Chimeras Established from Pig Embryos

Chi-Hun Park; Young-Hee Jeoung; Kyung-Jun Uh; Ki-Eun Park; Jessica Bridge; Anne Powell; Jie Li; Laramie Pence; Luhui Zhang; Tianbin Liu; Hai-Xi Sun; Ying Gu; Yue Shen; Jun Wu; Juan-Carlos Izpisua Belmonte; Bhanu P Telugu

doi:10.1016/j.stemcr.2020.11.011

Extraembryonic Endoderm (XEN) Cells Capable of Contributing to Embryonic Chimeras Established from Pig Embryos

Stem Cell Reports. 2021 Jan 12;16(1):212-223. doi: 10.1016/j.stemcr.2020.11.011. Epub 2020 Dec 17.

Authors

Chi-Hun Park¹, Young-Hee Jeoung², Kyung-Jun Uh³, Ki-Eun Park⁴, Jessica Bridge², Anne Powell⁵, Jie Li⁶, Laramie Pence², Luhui Zhang⁷, Tianbin Liu⁸, Hai-Xi Sun⁸, Ying Gu⁸, Yue Shen⁹, Jun Wu¹⁰, Juan-Carlos Izpisua Belmonte¹¹, Bhanu P Telugu¹²

Affiliations

¹ Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Animal Bioscience and Biotechnology Laboratory, USDA, ARS, Beltsville, MD 20705, USA. Electronic address: chpark@umd.edu.
² Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Animal Bioscience and Biotechnology Laboratory, USDA, ARS, Beltsville, MD 20705, USA.
³ Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.
⁴ Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Animal Bioscience and Biotechnology Laboratory, USDA, ARS, Beltsville, MD 20705, USA; RenOVAte Biosciences Inc, Reisterstown, MD 21136, USA.
⁵ Animal Bioscience and Biotechnology Laboratory, USDA, ARS, Beltsville, MD 20705, USA; RenOVAte Biosciences Inc, Reisterstown, MD 21136, USA.
⁶ BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; BGI-Shenzhen, Shenzhen, 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, 518120, China; Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, Guangdong, China.
⁷ Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA.
⁸ BGI-Shenzhen, Shenzhen, 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, 518120, China; Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, Guangdong, China.
⁹ BGI Education Center, University of Chinese Academy of Sciences, Shenzhen 518083, China; BGI-Shenzhen, Shenzhen, 518083, China; Guangdong Provincial Key Laboratory of Genome Read and Write, Shenzhen, 518120, China; Guangdong Provincial Academician Workstation of BGI Synthetic Genomics, BGI-Shenzhen, Guangdong, China; Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, Shenzhen, 518120, China.
¹⁰ 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.
¹¹ Salk Institute, La Jolla, San Diego, CA 92037, USA.
¹² Animal and Avian Sciences, University of Maryland, College Park, MD 20742, USA; Animal Bioscience and Biotechnology Laboratory, USDA, ARS, Beltsville, MD 20705, USA; RenOVAte Biosciences Inc, Reisterstown, MD 21136, USA. Electronic address: btelugu@umd.edu.

Abstract

Most of our current knowledge regarding early lineage specification and embryo-derived stem cells comes from studies in rodent models. However, key gaps remain in our understanding of these developmental processes from nonrodent species. Here, we report the detailed characterization of pig extraembryonic endoderm (pXEN) cells, which can be reliably and reproducibly generated from primitive endoderm (PrE) of blastocyst. Highly expandable pXEN cells express canonical PrE markers and transcriptionally resemble rodent XENs. The pXEN cells contribute both to extraembryonic tissues including visceral yolk sac as well as embryonic gut when injected into host blastocysts, and generate live offspring when used as a nuclear donor in somatic cell nuclear transfer (SCNT). The pXEN cell lines provide a novel model for studying lineage segregation, as well as a source for genome editing in livestock.

Keywords: Cloning; SCNT; XEN; embryonic chimera; extra-embryonic cells; gut endoderm; pig/porcine; primitive endoderm; stem cell; yolk sac.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blastocyst / cytology
Blastocyst / metabolism
CRISPR-Cas Systems / genetics
Cell Lineage
Chimera
Collagen Type I, alpha 1 Chain / genetics
Embryo, Mammalian / cytology*
Embryo, Mammalian / metabolism
Endoderm / cytology*
Endoderm / metabolism
Gene Editing
Mice
Swine

Substances

Collagen Type I, alpha 1 Chain

Grants and funding

R01 HD092304/HD/NICHD NIH HHS/United States