Regionally distinct trophoblast regulate barrier function and invasion in the human placenta

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Data availability
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Abstract

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.

Data availability

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.

The following data sets were generated

The following previously published data sets were used

1. Vento-Tormo
2. R
3. et al
(2018) Reconstructing the human first trimester fetal-maternal interface using single cell transcriptomics - 10x data
EMBL-EBI, E-MTAB-6701.

https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-6701/
1. Roger Pique-Regi
2. et al
(2019) Single Cell Transcriptional Signatures of the Human Placenta in Term and Preterm Parturition
NIH dpGAP, phs001886.v1.p1.

https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001886.v1.p1

Article and author information

Author details

Bryan Marsh

Department of Urology, University of California, San Francisco, San Francisco, United States

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-4979-5233
Yan Zhou

Department of Obstetrics, Gynecology and Reproductive Sciences, Center for Reproductive Sciences, Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, United States

Competing interests
No competing interests declared.
Mirhan Kapidzic

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell, University of California, San Francisco, San Francisco, United States

Competing interests
No competing interests declared.
Susan Fisher

The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell, University of California, San Francisco, San Francisco, United States

For correspondence
susan.fisher@ucsf.edu

Competing interests
Susan Fisher, is a consultant for Novo Nordisk. All other authors declare no competing interests..
Robert Blelloch

Department of Urology, University of California, San Francisco, San Francisco, United States

For correspondence
robert.blelloch@ucsf.edu

Competing interests
No competing interests declared.

"This ORCID iD identifies the author of this article:" 0000-0002-1975-0798

Funding

National Institutes of Health (P50 HD055764)

Bryan Marsh
Robert Blelloch

National Institutes of Health (R37 HD076253)

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.

Ethics

Human subjects: The University of California, San Francisco (UCSF) Institutional Review Board approved this study (11-05530). All donors gave informed consent.

Copyright

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.