# Modeling Human Placentation via Single Cell RNA-Sequencing

> **NIH NIH R21** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $193,750

## Abstract

Abstract
Placental dysfunction leads to pregnancy-associated disorders, including intrauterine growth restriction
(IUGR) and preeclampsia, and also serves as a developmental cause for postnatal and adult diseases. Often,
the causal alterations in the placentation process, which lead to defective pregnancies, occur early in
gestation. However, due to ethical barriers and difficulties with the experimental systems, most of the
studies on human placental function are performed with samples obtained at term, thereby, limiting our
ability to understand placental development and function throughout gestation. Fortunately, the recent
advancement of single-nucleus RNA-sequencing (snRNA-seq) strategy and success in deriving true human
trophoblast stem cells (human TSCs) from villous cytotrophoblast cells (CTBs) have opened up new
strategies for direct assessment of early human placentation process.
 Chorionic villus sampling (CVS) is a standard health care procedure performed during latter stages
of the first trimester of pregnancy. Surplus tissue obtained via CVS represents a valuable source of
trophoblast cells for experimental analysis and thus, a unique opportunity to interrogate the early developing
placenta.
 Using gene knockout mouse models, we discovered that depletion of GATA family of transcription
factors, GATA2 and GATA3 in trophoblast progenitor cells leads to either loss of pregnancy or fetal growth
restriction. As part of our pursuit to define importance of these findings with respect to human placentation,
we have successfully performed scRNA-seq study with human chorionic villous samples and found that,
within a first-trimester placenta, GATA2 and GATA3 are broadly expressed in distinct cell types, including
CTBs, syncytioytrophoblasts (SynTs) and extravillous trophoblasts (EVTs). Furthermore, we have also
been able to establish human TSCs from CTBs, isolated from chorionic villi, and found that loss of GATA2
expression in human TSCs impairs both EVT and SynTB differentiation. These observations led us to the
central hypothesis of this proposal that single cell gene expression patterns, including expression of GATA
factors, in a first-trimester placenta could be predictive of pregnancy associated disorders during late
gestation. To test this hypothesis, we will use CVS to perform snRNA-seq and to establish patient-specific
human TSCs for subsequent functional studies. We will also monitor those pregnancies for pregnancy-
associated disorders, including intrauterine growth restriction and preeclampsia and collect term placental
samples for follow up analyses. Together, our proposed study, bolstered by modern technologies, will
illuminate previously unknown pathways, which underlie placental adaptation at a single cell level during
normative and pathological pregnancies.

## Key facts

- **NIH application ID:** 10448457
- **Project number:** 5R21HD102188-02
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Soumen Paul
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,750
- **Award type:** 5
- **Project period:** 2021-07-10 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448457

## Citation

> US National Institutes of Health, RePORTER application 10448457, Modeling Human Placentation via Single Cell RNA-Sequencing (5R21HD102188-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10448457. Licensed CC0.

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