An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.
The Company of Biologists
MetadataShow full item record
Chen, Y., Siriwardena, D., Penfold, C., Pavlinek, A., & Boroviak, T. E. (2022). An integrated atlas of human placental development delineates essential regulators of trophoblast stem cells.. Development https://doi.org/10.1242/dev.200171
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.
Wellcome Trust (206684/Z/17/Z)
Royal Society (IEC\R3\183044)
External DOI: https://doi.org/10.1242/dev.200171
This record's URL: https://www.repository.cam.ac.uk/handle/1810/337121
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/