Cell stem cell, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Nature, Год журнала: 2021, Номер 591(7851), С. 620 - 626
Опубликована: Март 17, 2021
Язык: Английский
Процитировано
370
Nature, Год журнала: 2021, Номер 591(7851), С. 627 - 632
Опубликована: Март 17, 2021
Язык: Английский
Процитировано
282
Cell stem cell, Год журнала: 2021, Номер 28(6), С. 1016 - 1022.e4
Опубликована: Май 5, 2021
Human naive pluripotent cells can differentiate into extraembryonic trophectoderm and hypoblast. Here we describe a human embryo model (blastoid) generated by self-organization. Brief induction of leads to formation blastocyst-like structures within 3 days. Blastoids are composed three tissue layers displaying exclusive lineage markers, mimicking the natural blastocyst. Single-cell transcriptome analyses confirm segregation trophectoderm, hypoblast, epiblast with high fidelity embryo. This versatile scalable system provides robust experimental for research.
Язык: Английский
Процитировано
227
Nature Cell Biology, Год журнала: 2021, Номер 23(1), С. 49 - 60
Опубликована: Янв. 1, 2021
Язык: Английский
Процитировано
177
Nature Communications, Год журнала: 2021, Номер 12(1)
Опубликована: Сен. 21, 2021
Abstract Understanding human development is of fundamental biological and clinical importance. Despite its significance, mechanisms behind embryogenesis remain largely unknown. Here, we attempt to model early embryo with expanded pluripotent stem cells (EPSCs) in 3-dimensions. We define a protocol that allows us generate self-organizing cystic structures from EPSCs display some hallmarks embryogenesis. These mimic polarization cavitation characteristic pre-implantation leading blastocyst morphology formation the transition post-implantation-like organization upon extended culture. Single-cell RNA sequencing these reveals subsets bearing resemblance epiblast, hypoblast trophectoderm lineages. Nevertheless, significant divergences natural blastocysts persist key markers, signalling pathways point towards ways which transcriptional-level cell identities may diverge models embryo. Thus, this platform provides insights into design
Язык: Английский
Процитировано
144
Developmental Cell, Год журнала: 2022, Номер 57(2), С. 152 - 165
Опубликована: Янв. 1, 2022
Язык: Английский
Процитировано
124
Cell Discovery, Год журнала: 2021, Номер 7(1)
Опубликована: Сен. 7, 2021
Abstract Human blastocysts are comprised of the first three cell lineages embryo: trophectoderm, epiblast and primitive endoderm, all which essential for early development organ formation. However, due to ethical concerns restricted access human blastocysts, a comprehensive understanding embryogenesis is still lacking. To bridge this knowledge gap, reliable model system that recapitulates stages needed. Here we developed three-dimensional (3D), two-step induction protocol generating blastocyst-like structures (EPS-blastoids) from extended pluripotent stem (EPS) cells. Morphological single-cell transcriptomic analyses revealed EPS-blastoids contain key transcriptionally similar blastocysts. Furthermore, with embryos were cultured 8 or 10 days in vitro, terms embryonic structures, profiles. In conclusion, scalable mimic blastocyst development, can potentially facilitate study implantation failure induced by developmental defects at stage.
Язык: Английский
Процитировано
115
Cell stem cell, Год журнала: 2022, Номер 29(3), С. 400 - 418.e13
Опубликована: Фев. 9, 2022
Язык: Английский
Процитировано
98
Nature, Год журнала: 2023, Номер 622(7983), С. 574 - 583
Опубликована: Июнь 27, 2023
Abstract Investigating human development is a substantial scientific challenge due to the technical and ethical limitations of working with embryonic samples. In face these difficulties, stem cells have provided an alternative experimentally model inaccessible stages in vitro 1–13 . Here we show that pluripotent can be triggered self-organize into three-dimensional structures recapitulate some key spatiotemporal events early post-implantation development. Our system reproducibly captures spontaneous differentiation co-development epiblast-like extra-embryonic hypoblast-like lineages, establishes signalling hubs secreted modulators undergoes symmetry breaking-like events. Single-cell transcriptomics confirms diverse cell states perigastrulating embryo 14,15 without establishing placental types, including signatures epiblast, amniotic ectoderm, primitive streak, mesoderm, endoderm, as well initial yolk sac induction. Collectively, our features spanning from Carnegie stage 16 4–7, offering reproducible, tractable scalable experimental platform understand basic cellular molecular mechanisms underlie development, new opportunities dissect congenital pathologies high throughput.
Язык: Английский
Процитировано
86
Cell stem cell, Год журнала: 2022, Номер 29(10), С. 1445 - 1458.e8
Опубликована: Сен. 8, 2022
Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail capture the interactions between and extraembryonic tissues. To overcome this difficulty, we a ESC-based model that reconstitutes pluripotent ESC lineage two lineages post-implantation embryo by transcription-factor-mediated induction. This unified recapitulates developmental events day 5.5 8.5, including gastrulation; formation anterior-posterior axis, brain, beating heart structure; development tissues, yolk sac chorion. Comparing single-cell RNA sequencing individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across but also showed when where diverges program. Our findings demonstrate an extraordinary plasticity ESCs self-organize generate whole-embryo-like structure.
Язык: Английский
Процитировано
83