# Epigenetic barriers to trophoblast differentiation from pluripotent stem cells

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $326,088

## Abstract

PROJECT SUMMARY
Murine trophoblast stem cells (TSCs) are cells isolated from blastocyst stage mouse embryos that are
capable of differentiation into multiple trophoblast cell types in vitro and can colonize the placenta in utero.
These cells have greatly advanced the study of trophoblast development, due to the ability to expand TSCs
and differentiate them in vitro, facilitating cytological, biochemical, and epigenomic studies. However, no
well-validated human TSCs have been described, limiting these studies to mouse models. One potential
solution that has been pursued by multiple groups is the trans-differentiation of pluripotent stem cells
(PSCs), which encompass both embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs),
into trophoblast. Although PSCs can trans-differentiate into cells with many features of TSCs, these cells,
called trophoblast stem-like cells (TS-LCs), do not have the developmental potential or self-renewal
capacity of TSCs. Consequently, TS-LCs are limited as models for trophoblast function. These findings
reveal there is an epigenetic block to trans-differentiation that must be overcome to produce bona fide
induced trophoblast sem cells (iTSCs) from PSCs. We propose three Aims, two of which will characterize
epigenetic features in PSCs that contribute to the trans-differentiation barrier. In the third Aim, we propose
to use a combination of genome engineering and a novel hybrid differentiation/trans-differentiation protocol
to overcome this barrier and produce bona fide iTSCs. Successful completion of these studies will provide
considerable insight into the epigenetic barriers to trans-differentiation, and potentially the first bona fide
iTSC lines derived from human PSCs.

## Key facts

- **NIH application ID:** 9823887
- **Project number:** 5R01HD093783-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Feixia Chu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $326,088
- **Award type:** 5
- **Project period:** 2017-12-02 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9823887

## Citation

> US National Institutes of Health, RePORTER application 9823887, Epigenetic barriers to trophoblast differentiation from pluripotent stem cells (5R01HD093783-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9823887. Licensed CC0.

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