Generation of Blastocyst-like Structures from Mouse Embryonic and Adult Cell Cultures

A single mouse blastomere from an embryo until the 8-cell stage can generate an entire blastocyst. Whether laboratory-cultured cells retain a similar generative capacity remains unknown. Starting from a single stem cell type, extended pluripotent stem (EPS) cells, we established a 3D differentiation...

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Veröffentlicht in:Cell Jg. 179; H. 3; S. 687
Hauptverfasser: Li, Ronghui, Zhong, Cuiqing, Yu, Yang, Liu, Haisong, Sakurai, Masahiro, Yu, Leqian, Min, Zheying, Shi, Lei, Wei, Yulei, Takahashi, Yuta, Liao, Hsin-Kai, Qiao, Jie, Deng, Hongkui, Nuñez-Delicado, Estrella, Rodriguez Esteban, Concepcion, Wu, Jun, Izpisua Belmonte, Juan Carlos
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 17.10.2019
Schlagworte:
Animals
Blastocyst - cytology
Blastocyst - metabolism
Cell Differentiation
Cell Line
Cell Lineage
Cells, Cultured
Cellular Reprogramming Techniques - methods
Embryo Implantation
Female
Humans
Induced Pluripotent Stem Cells - cytology
Induced Pluripotent Stem Cells - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mouse Embryonic Stem Cells - cytology
Mouse Embryonic Stem Cells - metabolism
Research Embryo Creation - methods
Transcriptome
blastoids
reprogramming
extended pluripotent stem cells
EPS-blastoid
implantation
blastocyst
EPS cells
totipotent
ISSN:1097-4172, 1097-4172
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Zusammenfassung:A single mouse blastomere from an embryo until the 8-cell stage can generate an entire blastocyst. Whether laboratory-cultured cells retain a similar generative capacity remains unknown. Starting from a single stem cell type, extended pluripotent stem (EPS) cells, we established a 3D differentiation system that enabled the generation of blastocyst-like structures (EPS-blastoids) through lineage segregation and self-organization. EPS-blastoids resembled blastocysts in morphology and cell-lineage allocation and recapitulated key morphogenetic events during preimplantation and early postimplantation development in vitro. Upon transfer, some EPS-blastoids underwent implantation, induced decidualization, and generated live, albeit disorganized, tissues in utero. Single-cell and bulk RNA-sequencing analysis revealed that EPS-blastoids contained all three blastocyst cell lineages and shared transcriptional similarity with natural blastocysts. We also provide proof of concept that EPS-blastoids can be generated from adult cells via cellular reprogramming. EPS-blastoids provide a unique platform for studying early embryogenesis and pave the way to creating viable synthetic embryos by using cultured cells.
Bibliographie:ObjectType-Article-1
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ISSN:1097-4172
1097-4172
DOI:10.1016/j.cell.2019.09.029