The human placenta contains two specialized regions: the villous chorion where gases and nutrients are exchanged between maternal and fetal blood, and the smooth chorion which surrounds more than 70% of the developing fetus but whose cellular composition and function is poorly understood. Here, we use single cell RNA sequencing to compare the cell types and molecular programs between these two regions in the second trimester human placenta. Each region consists of progenitor cytotrophoblasts (CTBs) and extravillous trophoblasts (EVTs) with similar gene expression programs. While CTBs in the villous chorion differentiate into syncytiotrophoblasts, they take an alternative trajectory in the smooth chorion producing a previously unknown CTB population which we term smooth-chorion-specific CTBs (SC-CTBs). Marked by expression of region-specific cytokeratins, the SC-CTBs form a stratified epithelium above a basal layer of progenitor CTBs. They express epidermal and metabolic transcriptional programs consistent with a primary role in defense against physical stress and pathogens. Additionally, we show that SC-CTBs closely associate with EVTs and secrete factors that inhibit the migration of the EVTs. This restriction of EVT migration is in striking contrast to the villous region where EVTs migrate away from the chorion and invade deeply into the decidua. Together, these findings greatly expand our understanding of CTB differentiation in these distinct regions of the human placenta. This knowledge has broad implications for studies of the development, functions, and diseases of the human placenta.
Sequencing data have been deposited in GEO under the accession code GSE198373Processed data have been deposited on Figshare at https://figshare.com/projects/Regionally_distinct_trophoblast_regulate_barrier_function_and_invasion_in_the_human_placenta/135191.Code to generate the processed data have been deposited on GitHub at https://github.com/marshbp/Regionally-distinct-trophoblast-regulate-barrier-function-and-invasion-in-the-human-placenta.
Regionally distinct trophoblast regulate barrier function and invasion in the human placentaNCBI Gene Expression Omnibus, GSE198373.
Single Cell Transcriptional Signatures of the Human Placenta in Term and Preterm ParturitionNIH dpGAP, phs001886.v1.p1.
- Bryan Marsh
- Robert Blelloch
- Yan Zhou
- Mirhan Kapidzic
- Susan Fisher
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: The University of California, San Francisco (UCSF) Institutional Review Board approved this study (11-05530). All donors gave informed consent.
- Claudia Gerri, Max Planck Institute of Molecular Cell Biology and Genetics
© 2022, Marsh et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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