# Role of VGLL1 in human placental development and trophoblast specification

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $467,055

## Abstract

Project Summary/Abstract
 Many placenta-associated pregnancy complications, including pre-eclampsia (PE) and intrauterine
growth restriction (IUGR), originate in the early stages of placental development, during the
establishment of trophoblast cells, the functional building blocks of the placenta. Due to the
inaccessibility of this early stage of human development, most of what we know about this process
comes from other species, in particular, from mice. Trophoblast specification in pre-implantation
mouse embryos is dependent upon the Tead4/Yap1 complex initiating a trophoblast-specific
transcriptional program. However, an increasing body of evidence, from our lab and others’, shows
significant species-specific differences in trophoblast lineage specification between mouse and human.
In a recent comparative placentation study, we identified the transcriptional co-factor vestigial-like
family member-1 (VGLL1) as a human-specific marker of early gestation cytotrophoblast (CTB), the
stem cell compartment of the human placenta. VGLL1 co-localizes with TEAD4 and TP63 in early
gestation CTB. Furthermore, expression of VGLL1 is induced very early during trophoblast
differentiation of human pluripotent stem cells (hPSCs) following BMP4 treatment, before induction of
TP63. Little is known about VGLL1 function, but interestingly, VGLL1 has been shown to bind TEAD4,
in a manner similar to the Tead4/Yap1 interaction, which is required for trophoblast lineage
specification in mice. This project aims to elucidate the role of VGLL1 as a human-specific
regulator of trophoblast lineage specification. We will manipulate VGLL1 expression in both newly-
established human trophoblast stem cell lines and in our established hPSC-based model of human
trophoblast lineage specification. We will assess the effects of such gene manipulation on trophoblast
maintenance, differentiation and function, as well as genome-wide changes in RNA expression. We
will validate our results by manipulation of VGLL1 in human primary CTB using the CRISPR/Cas9
technology. We will confirm the interaction between VGLL1 and TEAD4 in both systems and identify
direct downstream targets of the VGLL1-TEAD4 complex using ChIP-seq. We hypothesize that VGLL1
is a key player involved in trophoblast lineage specification in early human development, acting in
complex with TEAD4, to induce a TP63-based transcriptional program to establish and maintain
trophoblast stem cells in the human placenta.

## Key facts

- **NIH application ID:** 10102641
- **Project number:** 5R01HD096260-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Francesca Soncin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $467,055
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10102641

## Citation

> US National Institutes of Health, RePORTER application 10102641, Role of VGLL1 in human placental development and trophoblast specification (5R01HD096260-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10102641. Licensed CC0.

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