Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage development as well as underlying mechanisms remains obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling pathways synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast development and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights into human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.
基金:
National Key Ramp;D Program of China [2020YFA0112700, 2022YFA1103100, 2021YFA0805700]; National Natural Science Foundation of China [32130034, 82192874, 32100655, 82160294]; Major Basic Research Project of Science and Technology of Yunnan [202102AA100007, 202001BC070001, 2019FY002]; Joint Special Funds for the Department of Science and Technology of Yunnan Province-Kunming Medical University [202101AY070001-260, 202301AY070001-298]
第一作者机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming, Yunnan, Peoples R China[2]Yunnan Key Lab Primate Biomed Res, Kunming, Yunnan, Peoples R China[3]Yunnan Prov Acad Sci & Technol, Kunming, Yunnan, Peoples R China
共同第一作者:
通讯作者:
通讯机构:[1]Kunming Univ Sci & Technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming, Yunnan, Peoples R China[2]Yunnan Key Lab Primate Biomed Res, Kunming, Yunnan, Peoples R China[3]Yunnan Prov Acad Sci & Technol, Kunming, Yunnan, Peoples R China
推荐引用方式(GB/T 7714):
Ai Zongyong,Niu Baohua,Yin Yu,et al.Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids[J].CELL RESEARCH.2023,33(9):661-678.doi:10.1038/s41422-023-00846-8.
APA:
Ai, Zongyong,Niu, Baohua,Yin, Yu,Xiang, Lifeng,Shi, Gaohui...&Li, Tianqing.(2023).Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids.CELL RESEARCH,33,(9)
MLA:
Ai, Zongyong,et al."Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids".CELL RESEARCH 33..9(2023):661-678