An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells
Authors
Boroviak, Thorsten
Chen, Yutong
Siriwardena, Dylan
Pavlinek, Adam
Penfold, Christopher A
Journal Title
Development
ISSN
0950-1991
Publisher
The Company of Biologists
Type
Article
This Version
AM
Metadata
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Boroviak, T., Chen, Y., Siriwardena, D., Pavlinek, A., & Penfold, C. A. An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells. Development https://doi.org/10.17863/CAM.84540
Abstract
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, yet, 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 a 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.
Sponsorship
Wellcome Trust (206684/Z/17/Z)
Royal Society (IEC\R3\183044)
Embargo Lift Date
2025-05-12
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.84540
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337121
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