Development of the human placenta

Development, Journal Year: 2019, Volume and Issue: 146(22)

Published: Nov. 15, 2019

ABSTRACT The placenta is essential for normal in utero development mammals. In humans, defective placental formation underpins common pregnancy disorders such as pre-eclampsia and fetal growth restriction. great variation types across mammals means that animal models have been of limited use understanding human development. However, new tools studying development, including 3D organoids, stem cell culture systems single RNA sequencing, brought insights into this field. Here, we review the morphological, molecular functional aspects formation, with a focus on defining – trophoblast.

Language: Английский

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A developmental landscape of 3D-cultured human pre-gastrulation embryos

Nature, Journal Year: 2019, Volume and Issue: 577(7791), P. 537 - 542

Published: Dec. 12, 2019

Language: Английский

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Human blastoids model blastocyst development and implantation

Nature, Journal Year: 2021, Volume and Issue: 601(7894), P. 600 - 605

Published: Dec. 2, 2021

Abstract One week after fertilization, human embryos implant into the uterus. This event requires embryo to form a blastocyst consisting of sphere encircling cavity lodging proper. Stem cells can model that we called blastoid 1 . Here show naive pluripotent stem cultured in PXGL medium 2 and triply inhibited for Hippo, TGF-β ERK pathways efficiently (with more than 70% efficiency) blastoids generating blastocyst-stage analogues three founding lineages (more 97% trophectoderm, epiblast primitive endoderm) according sequence timing development. Blastoids spontaneously first axis, observe induces local maturation polar thereby endowing with capacity directionally attach hormonally stimulated endometrial cells, as during implantation. Thus, propose such is faithful, scalable ethical investigating implantation development 3,4

Language: Английский

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Human naive epiblast cells possess unrestricted lineage potential

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(6), P. 1040 - 1056.e6

Published: April 7, 2021

Classic embryological experiments have established that the early mouse embryo develops via sequential lineage bifurcations. The first segregated is trophectoderm, essential for blastocyst formation. Mouse naive epiblast and derivative embryonic stem cells are restricted accordingly from producing trophectoderm. Here we show, in contrast, human readily make trophectoderm descendant trophoblast cell types. Trophectoderm was induced rapidly efficiently by inhibition of ERK/mitogen-activated protein kinase (MAPK) Nodal signaling. Transcriptome comparison with substantiated direct formation subsequent differentiation into syncytiotrophoblast, cytotrophoblast, downstream cells. During pluripotency progression potential switches to amnion. Live-cell tracking revealed also able produce Thus, paradigm developmental specification coupled restriction does not apply humans. Instead, plasticity regeneration retained until implantation.

Language: Английский

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Reconstituting the transcriptome and DNA methylome landscapes of human implantation

Nature, Journal Year: 2019, Volume and Issue: 572(7771), P. 660 - 664

Published: Aug. 21, 2019

Language: Английский

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Derivation of trophoblast stem cells from naïve human pluripotent stem cells

eLife, Journal Year: 2020, Volume and Issue: 9

Published: Feb. 12, 2020

Naïve human pluripotent stem cells (hPSCs) provide a unique experimental platform of cell fate decisions during pre-implantation development, but their lineage potential remains incompletely characterized. As naïve hPSCs share transcriptional and epigenomic signatures with trophoblast cells, it has been proposed that the state may have enhanced predisposition for differentiation along this extraembryonic lineage. Here we examined isogenic primed hPSCs. We found can directly give rise to (hTSCs) undergo further into both extravillous syncytiotrophoblast. In contrast, do not support hTSC derivation, non-self-renewing cytotrophoblasts in response BMP4. Global transcriptome chromatin accessibility analyses indicate hTSCs derived from are similar blastocyst-derived acquire features post-implantation trophectoderm. The derivation will enable elucidation early mechanisms govern normal development associated pathologies.

Language: Английский

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Chemical reprogramming of human somatic cells to pluripotent stem cells

Nature, Journal Year: 2022, Volume and Issue: 605(7909), P. 325 - 331

Published: April 13, 2022

Language: Английский

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Naive stem cell blastocyst model captures human embryo lineage segregation

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(6), P. 1016 - 1022.e4

Published: May 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.

Language: Английский

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Capturing human trophoblast development with naive pluripotent stem cells in vitro

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(6), P. 1023 - 1039.e13

Published: April 7, 2021

Language: Английский

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Deconstructing and reconstructing the mouse and human early embryo

Nature Cell Biology, Journal Year: 2018, Volume and Issue: 20(8), P. 878 - 887

Published: July 19, 2018

Language: Английский

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