An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.
Human development
Human trophoblast stem cells
Placenta development
Self-renewal
Trophoblast
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
01 07 2022
01 07 2022
Historique:
received:
09
09
2021
accepted:
12
05
2022
entrez:
6
7
2022
pubmed:
7
7
2022
medline:
9
7
2022
Statut:
ppublish
Résumé
The trophoblast lineage safeguards fetal development by mediating embryo implantation, immune tolerance, nutritional supply and gas exchange. Human trophoblast stem cells (hTSCs) provide a platform to study lineage specification of placental tissues; however, the regulatory network controlling self-renewal remains elusive. Here, we present a single-cell atlas of human trophoblast development from zygote to mid-gestation together with single-cell profiling of hTSCs. We determine the transcriptional networks of trophoblast lineages in vivo and leverage probabilistic modelling to identify a role for MAPK signalling in trophoblast differentiation. Placenta- and blastoid-derived hTSCs consistently map between late trophectoderm and early cytotrophoblast, in contrast to blastoid-trophoblast, which correspond to trophectoderm. We functionally assess the requirement of the predicted cytotrophoblast network in an siRNA-screen and reveal 15 essential regulators for hTSC self-renewal, including MAZ, NFE2L3, TFAP2C, NR2F2 and CTNNB1. Our human trophoblast atlas provides a powerful analytical resource to delineate trophoblast cell fate acquisition, to elucidate transcription factors required for hTSC self-renewal and to gauge the developmental stage of in vitro cultured cells.
Identifiants
pubmed: 35792865
pii: 275917
doi: 10.1242/dev.200171
pmc: PMC9340556
pii:
doi:
Substances chimiques
Basic-Leucine Zipper Transcription Factors
0
NFE2L3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 206684/Z/17/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT RG89228
Pays : United Kingdom
Informations de copyright
© 2022. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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