# Cellular Atlas of the Human Placenta: Structure-Function Relationships and their Implications for Placental Dysfunction

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $525,399

## Abstract

Project Summary/Abstract
Little is known about structure-function relationships in the human placenta. As pathologists, we can view
the placenta only after delivery, and correlate our findings to clinical and prenatal course, as well as
neonatal outcome. At best, however, we have lesions which correlate with disease, but have yet to be
validated, either directly, through molecular analysis, or indirectly, through manipulation and functional
analysis of in vitro models. Placental dysfunction, manifested clinically as preeclampsia (PE) with or
without fetal growth restriction (FGR), is associated with histopathologic lesions of maternal vascular
malperfusion (MVM) and fetal vascular malperfusion (FVM). These lesions differentially affect the three
trophoblast compartments: cytotrophoblast (CTB, the putative stem cell), syncytiotrophoblast (STB, the
cell type responsible for gas/nutrient exchange), and extravillous trophoblast (EVT, the invasive cell type
at the maternal-fetal interface). Nevertheless, our understanding of these lesions is limited to morphology
and immunolocalization of a few markers. Over the past few years, multiple groups, including ours, have
used scRNAseq to characterize cellular heterogeneity within both normal and diseased placentae;
however, these studies remain mostly descriptive, lacking both spatial context of the molecular data and
functional evaluation of the distinct cell types. We therefore propose to apply novel technologies, including
digital spatial profiling (DSP) and tissue decellularization followed by extracellular matrix (ECM)-specific
mass spectrometry, as discovery-based approaches to better characterize specific MVM and FVM lesions
at the molecular level. We will then use primary term CTB, to reproducibly model these phenotypes and
to perform functional validation as part of a targeted evaluation approach. We will test the hypothesis that
late gestation CTB respond to specific cell- and ECM-derived signals to proliferate and/or differentiate into
either STB or EVT, thus identifying potential regenerative capacity in this unique transient organ.
We will also probe the cellular and ECM origins of PE-associated placental dysfunction, testing the
hypothesis that this disease originates from alterations in ECM composition and paracrine signaling from
both placental and decidual (maternal) cells. Successful completion of this proposal will establish a
detailed cellular and matrix atlas of the human placenta, with validated structure-function
relationships, laying the groundwork for probing placental regenerative capacity in the setting of
placental dysfunction.

## Key facts

- **NIH application ID:** 10367204
- **Project number:** 1R01HD104805-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Mana M Parast
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $525,399
- **Award type:** 1
- **Project period:** 2021-09-17 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10367204

## Citation

> US National Institutes of Health, RePORTER application 10367204, Cellular Atlas of the Human Placenta: Structure-Function Relationships and their Implications for Placental Dysfunction (1R01HD104805-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10367204. Licensed CC0.

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