Regulation of Cell Fate Decisions in Early Mammalian Embryos

Early embryogenesis is characterized by the segregation of cell lineages that fulfill critical roles in the establishment of pregnancy and development of the fetus. The formation of the blastocyst marks the emergence of extraembryonic precursors, needed for implantation, and of pluripotent cells, which differentiate toward the major lineages of the adult organism. The coordinated emergence of these cell types shows that these processes are broadly conserved in mammals. However, developmental heterochrony and changes in gene regulatory networks highlight unique evolutionary adaptations that may explain the diversity in placentation and in the mechanisms controlling pluripotency in mammals. The incorporation of new technologies, including single-cell omics, imaging, and gene editing, is instrumental for comparative embryology. Broadening the knowledge of mammalian embryology will provide new insights into the mechanisms driving evolution and development. This knowledge can be readily translated into biomedical and biotechnological applications in humans and livestock, respectively

Pluripotent stem cells related to embryonic disc exhibit common self-renewal requirements in diverse livestock species

This is the author accepted manuscript. The final version is available from Palgrave Macmillan via the DOI in this record Data Availability: RNA-seq data generated in this study are deposited in Gene Expression Omnibus under accession number GSE172420 (reviewer token wjevsgycnnafbub).Despite four decades of effort, robust propagation of pluripotent stem cells from livestock animals remains challenging. The requirements for self-renewal are unclear and the relationship of cultured stem cells to pluripotent cells resident in the embryo uncertain. Here, we avoided using feeder cells or serum factors to provide a defined culture microenvironment. We show that the combination of activin A, fibroblast growth factor and the Wnt inhibitor XAV939 (AFX) supports establishment and continuous expansion of pluripotent stem cell lines from porcine, ovine and bovine embryos. Germ layer differentiation was evident in teratomas and readily induced in vitro. Global transcriptome analyses highlighted commonality in transcription factor expression across the three species, while global comparison with porcine embryo stages showed proximity to bilaminar disc epiblast. Clonal genetic manipulation and gene targeting were exemplified in porcine stem cells. We further demonstrated that genetically modified AFX stem cells gave rise to cloned porcine foetuses by nuclear transfer. In summary, for major livestock mammals, pluripotent stem cells related to the formative embryonic disc are reliably established using a common and defined signalling environment.Biotechnology and Biological Sciences Research CouncilBiotechnology and Biological Sciences Research CouncilEuropean Research CouncilMedical Research CouncilMedical Research CouncilJapan Society for the Promotion of ScienceJapan Society for the Promotion of ScienceJapan Agency for Medical Research and DevelopmentJapan Agency for Medical Research and DevelopmentWellcome TrustMedical Research Counci