Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo

Abstract

5High-resolution molecular programs delineating the cellular foundations of and then of epiblast and hypoblast in late blastocysts. We detected distinct 3 3 pluripotent states, first as a short 'naïve' state followed by a protracted primed state. comprehending early human development and a foundation for further studies of 3 7 human pluripotent stem cell differentiation in pig interspecies chimeras. . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/347823 doi: bioRxiv preprint first posted online Jun. 20, 2018; 3 Pre-gastrulation embryo development shows broad similarities between mammals, although 4 0 species-specific differences in early lineage segregation, the establishment of pluripotency, 4 1 and X chromosome inactivation have been reported [1][2][3] . Mouse embryos, which are widely 4 2 used as a model for mammalian development, transit rapidly through early development 4 3 (E3.5-E5.5, i.e. ~2 days), followed by development of the characteristic cup-shaped post- inaccessible, we are beginning to investigate relatively more accessible pig embryos. 8Notably both human and pig embryos evidently form a flat embryonic disc before the onset 4 9 of gastrulation 4 . Thus, the pig embryo can broaden our understanding of the pre-gastrulation 5 0development of large mammals with protracted development. 1Segregation of trophectoderm (TE) and hypoblast, and the emergence of pluripotency arewell established in mice 5,6 , but require detailed studies in other mammals at the resolution of lineage segregation have however emerged in reports between monkey and human, large mammalian species, are therefore highly desirable. 7In mouse embryos a distinct transcriptional signature of naïve pluripotency in the inner cell humans, has been challenging, suggesting possible biological differences 9,10 . Indeed, mouse embryonic naïve cells are not apparently detected in human embryos 9,11 . By contrast, . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/347823 doi: bioRxiv preprint first posted online Jun. 20, 2018; 4 KLF17 is expressed in the human but not mouse ICM 9,11,12 . Also, while Jak-Stat3 and WNT 6 7 signalling are detected in the early mouse ICM 13 , many TGFβ signalling components are 6 8 present in marmoset, human and pig ICM 11,12,14,15 , indicating that the emergence and been studied 12,16 . 5Here we report lineage segregation, the establishment of pluripotency, and X-chromosomeinactivation during the entire peri-gastrulation period in the pig embryo using single cell RNA-seq (scRNA-seq). This comprehensive analysis provides new understanding of the the early human developmen...

Histone demethylase complexes KDM3A and KDM3B cooperate with OCT4/SOX2 to construct pluripotency gene regulatory network

“…S7C). The expression pattern was similar to SOX2, suggesting that a similar interaction mechanism might exist in Epiblast [35]. Our results also reveal that the overexpression of KDM3A can significantly improve the proliferation and anti-apoptosis ability of pluripotent stem cells, but that of KDM3B leads to a decline in cell proliferation.…”

“…Several studies on pig early embryos have indicated that OCT4 is generic expressed in ICM and TE, which differs from that in humans and mice (Fig. S7C) [35]. The regulatory mechanism of endogenous OCT4 in pigs may be unique.…”

Human–Monkey Chimeras for Modeling Human Disease: Opportunities and Challenges

“…This could be because naive pluripotency has not been appropriately instated in donor cells [17,27]. In contrast, host blastocysts at the time of embryo injection may not be developmentally synchronized with putative donor naive cells [28]. In this regard, the nature of chimera competency in primates may fundamentally differ from the rodent paradigm, such that currently defined ''naivete'' does not correspond to chimera-forming ability.…”