Self-patterning of human stem cells into post-implantation lineages

Nature, Journal Year: 2023, Volume and Issue: 622(7983), P. 574 - 583

Published: June 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.

Language: Английский

---

Derivation of totipotent-like stem cells with blastocyst-like structure forming potential

Cell Research, Journal Year: 2022, Volume and Issue: 32(6), P. 513 - 529

Published: May 4, 2022

Abstract It is challenging to derive totipotent stem cells in vitro that functionally and molecularly resemble from embryos. Here, we report a chemical cocktail enables the derivation of totipotent-like cells, designated as potential (TPS) 2-cell mouse embryos extended pluripotent these TPS can be stably maintained long term vitro. shared features with terms totipotency markers, transcriptome, chromatin accessibility DNA methylation patterns. In vivo chimera formation assays show have embryonic extraembryonic developmental potentials at single-cell level. Moreover, induced into blastocyst-like structures resembling preimplantation blastocysts. Mechanistically, inhibition HDAC1/2 DOT1L activity activation RARγ signaling are important for inducing maintaining cells. Our study opens up new path toward fully capturing

Language: Английский

---

Induction of mouse totipotent stem cells by a defined chemical cocktail

Nature, Journal Year: 2022, Volume and Issue: 617(7962), P. 792 - 797

Published: June 21, 2022

Language: Английский

---

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

Cell, Journal Year: 2023, Volume and Issue: 186(18), P. 3776 - 3792.e16

Published: July 20, 2023

Language: Английский

---

Cynomolgus monkey embryo model captures gastrulation and early pregnancy

Cell stem cell, Journal Year: 2023, Volume and Issue: 30(4), P. 362 - 377.e7

Published: April 1, 2023

Language: Английский

---