RT Journal Article SR Electronic T1 Chimera-competent eXtra-Embryonic eNdoderm (XEN) cells established from pig embryos JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.02.892802 DO 10.1101/2020.01.02.892802 A1 Chi Park A1 Young Jeoung A1 Jun Uh A1 Kieun Park A1 Jessica Bridge A1 Anne Powell A1 Jie Li A1 Laramie Pence A1 Tianbin Liu A1 Hai-Xi Sun A1 Ying Gu A1 Yue Shen A1 Jun Wu A1 Juan-Carlos Izpisua Belmonte A1 Bhanu P. Telugu YR 2020 UL http://biorxiv.org/content/early/2020/01/23/2020.01.02.892802.abstract AB In this article, we report for the first time the derivation and characterization of extra-embryonic endoderm (XEN) cells from primitive endoderm (PrE) of porcine (p) embryos. The pXEN cells can be reliably and reproducibly generated from parthenote, in vitro and in vivo derived embryos. The pXEN cells retained all the hallmarks of PrE including expression of canonical PrE and XEN cell markers (GATA4, GATA6, SOX17, SALL4, FOXA2, and HNF4A). Transcriptome analysis further confirmed their XEN cell origin. The pXEN cells when introduced into blastocyst stage embryo contributed to wide-spread chimerism including visceral yolk sac, chorion, as well as embryonic gut and liver primordium in the fetus. The pXEN cells were shown to be an efficient nuclear donor for generating cloned offspring. Taken together, pXEN cells fulfil a longstanding need for a stable, chimera-competent, and nuclear transfer-compatible porcine embryonic cells with applications for agriculture and medicine.Significance Statement We report for the first time, the derivation and characterization of extraembryonic endoderm (XEN) stem cells from porcine (p) embryos. The pXEN cells can be reliably and reproducibly derived from primitive endoderm precursors. When injected into blastocyst-stage embryos, the pXEN cells have contributed to wide-spread chimerism including visceral yolk sac, chorion of the extraembryonic membranes, as well as definitive endoderm of the fetus, primarily the embryonic gut and liver primordium. Additionally, these XEN cells have proven to be an efficient nuclear donor for generating cloned offspring. These newly discovered stem cells provide a novel model for studying lineage segregation, as well as a source for interspecies chimeras for generating endodermal organs, and for genome editing in livestock.