Capturing Cardiogenesis in Gastruloids

Cell stem cell, Год журнала: 2020, Номер 28(2), С. 230 - 240.e6

Опубликована: Ноя. 10, 2020

Язык: Английский

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Embryo model completes gastrulation to neurulation and organogenesis

Nature, Год журнала: 2022, Номер 610(7930), С. 143 - 153

Опубликована: Авг. 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.

Язык: Английский

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Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs

Cell, Год журнала: 2022, Номер 185(18), С. 3290 - 3306.e25

Опубликована: Авг. 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.

Язык: Английский

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Reconstructing aspects of human embryogenesis with pluripotent stem cells

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

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Generation of extracellular morphogen gradients: the case for diffusion

Nature Reviews Genetics, Год журнала: 2021, Номер 22(6), С. 393 - 411

Опубликована: Март 25, 2021

Язык: Английский

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Periodic formation of epithelial somites from human pluripotent stem cells

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Апрель 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.

Язык: Английский

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Reconstituting human somitogenesis in vitro

Nature, Год журнала: 2022, Номер 614(7948), С. 509 - 520

Опубликована: Дек. 21, 2022

Язык: Английский

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Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development

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

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Reconstruction and deconstruction of human somitogenesis in vitro

Nature, Год журнала: 2022, Номер 614(7948), С. 500 - 508

Опубликована: Дек. 21, 2022

Язык: Английский

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Modeling post-implantation stages of human development into early organogenesis with stem-cell-derived peri-gastruloids

Cell, Год журнала: 2023, Номер 186(18), С. 3776 - 3792.e16

Опубликована: Июль 20, 2023

Язык: Английский

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