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Learn MoreDespite morphological similarities, relatively little is known about conserved developmental processes in human and mouse pre-implantation embryos. Here we provide the first comprehensive single-cell RNA-sequencing comparison of human and mouse embryos from the zygotic to the blastocyst stage. We establish a robust computational pipeline allowing us to elucidate human-specific transcriptional Programs. Importantly, we validate our RNA-sequencing findings by Immunofluorescence analysis, which further reveals differences in human and mouseembryo gene expression. For example, although key trophectoderm factors Id2, Elf5, Eomes and Tcfap2c/Ap2 are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we identify several genes exclusively expressed in the human pluripotent epiblast including the transcription factor KLF17 and key components of the TGF- signaling pathway LEFTY1, LEFTY2, NODAL and ACVRL1/ALK1 whose expression is absent from the mouse inner cell mass. Conversely, we also identify genes with conserved expression dynamics including Foxa2/FOXA2, which we show for the first time is restricted to the primitive endoderm in both human and mouse embryos. Our analysis highlights significant differences in human pre-implantation development compared to mouse and provides a molecular blueprint to understand human embryogenesis. SOURCE: paul blakeley (blakeleyp@gmail.com) - Crick Institute
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