Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 32(1), P. 18 - 29
Published: Aug. 17, 2021
Language: Английский
Trends in Cell Biology, Journal Year: 2021, Volume and Issue: 32(1), P. 18 - 29
Published: Aug. 17, 2021
Language: Английский
Cell stem cell, Journal Year: 2020, Volume and Issue: 28(2), P. 230 - 240.e6
Published: Nov. 10, 2020
Language: Английский
Citations
232Nature, Journal Year: 2022, Volume and Issue: 610(7930), P. 143 - 153
Published: Aug. 25, 2022
Abstract Embryonic stem (ES) cells can undergo many aspects of mammalian embryogenesis in vitro 1–5 , but their developmental potential is substantially extended by interactions with extraembryonic cells, including trophoblast (TS) endoderm (XEN) and inducible XEN (iXEN) 6–11 . Here we assembled cell-derived embryos from mouse ES TS iXEN showed that they recapitulate the development whole natural embryo utero up to day 8.5 post-fertilization. Our model displays headfolds defined forebrain midbrain regions develops a beating heart-like structure, trunk comprising neural tube somites, tail bud containing neuromesodermal progenitors, gut tube, primordial germ cells. This complete within an yolk sac initiates blood island development. Notably, demonstrate neurulating Pax6 -knockout aggregated wild-type recapitulates ventral domain expansion occurs natural, ubiquitous embryos. Thus, these embryoids are powerful for dissecting roles diverse cell lineages genes results self-organization ability two types reconstitute through beyond gastrulation neurulation early organogenesis.
Language: Английский
Citations
192Cell, Journal Year: 2022, Volume and Issue: 185(18), P. 3290 - 3306.e25
Published: Aug. 2, 2022
In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether independently give rise entire gastrulating embryo-like structures and compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), both compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, ESCs transiently expressing Cdx2 Gata4 promote their priming toward trophectoderm primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key milestones, develop organ progenitors within complex similar E8.5 stage Our findings highlight the plastic potential pluripotent self-organize functionally reconstitute model beyond gastrulation.
Language: Английский
Citations
167Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)
Published: Sept. 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
Language: Английский
Citations
147Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(6), P. 393 - 411
Published: March 25, 2021
Language: Английский
Citations
108Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)
Published: April 28, 2022
Abstract During embryonic development, epithelial cell blocks called somites are periodically formed according to the segmentation clock, becoming foundation for segmental pattern of vertebral column. The process somitogenesis has recently been recapitulated with murine and human pluripotent stem cells. However, an in vitro model coupled clock epithelialization is still missing. Here, we report generation somitoids, organoids that form pairs somite-like structures. Somitoids display clear oscillations coincide presomitic mesoderm. resulting show anterior-posterior apical-basal polarities. Matrigel essential but dispensable differentiation into somite size rather constant, irrespective initial number. amount WNT signaling instructs proportion mesodermal lineages somitoids. provide a novel platform study somitogenesis.
Language: Английский
Citations
105Nature, Journal Year: 2022, Volume and Issue: 614(7948), P. 509 - 520
Published: Dec. 21, 2022
Language: Английский
Citations
86Cell stem cell, Journal Year: 2022, Volume and Issue: 29(10), P. 1445 - 1458.e8
Published: Sept. 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.
Language: Английский
Citations
84Nature, Journal Year: 2022, Volume and Issue: 614(7948), P. 500 - 508
Published: Dec. 21, 2022
Language: Английский
Citations
78Cell, Journal Year: 2023, Volume and Issue: 186(18), P. 3776 - 3792.e16
Published: July 20, 2023
Language: Английский
Citations
68