期刊
DEVELOPMENT
卷 142, 期 18, 页码 3151-U115出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.123547
关键词
Human; Mouse; Epiblast; Trophectoderm; Embryonic stem cells; RNA-sequencing
资金
- Francis Crick Institute
- Cancer Research UK
- UK Medical Research Council [MC_UP_1202/9]
- Wellcome Trust
- March of Dimes Foundation [FY11-436]
- Agency for Science Technology and Research (A-STAR), Singapore
- MRC [MC_UP_1202/9] Funding Source: UKRI
- Medical Research Council [MC_UP_1202/9] Funding Source: researchfish
- The Francis Crick Institute [10120] Funding Source: researchfish
Here, we provide fundamental insights into early human development by single-cell RNA-sequencing of human and mouse preimplantation embryos. We elucidate conserved transcriptional programs along with those that are human specific. Importantly, we validate our RNA-sequencing findings at the protein level, which further reveals differences in human and mouse embryo gene expression. For example, we identify several genes exclusively expressed in the human pluripotent epiblast, including the transcription factor KLF17. Key components of the TGF-beta signalling pathway, including NODAL, GDF3, TGFBR1/ALK5, LEFTY1, SMAD2, SMAD4 and TDGF1, are also enriched in the human epiblast. Intriguingly, inhibition of TGF-beta signalling abrogates NANOG expression in human epiblast cells, consistent with a requirement for this pathway in pluripotency. Although the key trophectoderm factors Id2, Elf5 and Eomes are exclusively localized to this lineage in the mouse, the human orthologues are either absent or expressed in alternative lineages. Importantly, we also identify genes with conserved expression dynamics, including Foxa2/FOXA2, which we show is restricted to the primitive endoderm in both human and mouse embryos. Comparison of the human epiblast to existing embryonic stem cells (hESCs) reveals conservation of pluripotency but also additional pathways more enriched in hESCs. Our analysis highlights significant differences in human preimplantation development compared with mouse and provides a molecular blueprint to understand human embryogenesis and its relationship to stem cells.
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