# Stem cell epigenetics in uterine fibroids

> **NIH NIH R21** · MICHIGAN STATE UNIVERSITY · 2021 · $205,542

## Abstract

Project Summary
Uterine fibroids (also known as leiomyomas) are the most common tumors in the female reproductive tract.
Some estimates indicate that up to 75% of American women have uterine fibroids, depending on race and
ethnicity. There is a significant disparity in the incidence of fibroids since African-American women are 2-3
times more likely to develop fibroids, often with earlier onset and greater severity of symptoms. These tumors
can be very painful and are the leading cause of hysterectomies in the US. Despite the healthcare burden
caused by uterine fibroids, their etiology and pathophysiology are unknown. The vast majority of fibroids either
have mutations in Mediator Complex protein 12 (MED12) gene or over-express high mobility group AT hooks
(HMGA)1/2 transcription factors, but the molecular mechanism that are disrupted and lead to tumor
development or growth are unknown. Another well known characteristic of fibroids is that they are mostly
clonal, indicating a single cell of origin for each tumor. Our overarching hypothesis is that the vast majority of
uterine fibroids develop from myometrial stem/progenitor cells that have become dysregulated by either
MED12 mutation or HMGA1/2 over-expression. Using SUSD2 as a marker, we have enriched for a population
of perivascular myometrial cells with all the characteristics of mesenchymal stem cells from both human
myometrial and fibroid specimens. The perivascular niche is the most common site for mesenchymal stem
cells in many tissues. We have compelling evidence that chromatin compartmentalization is changed in
uterine fibroids compared to normal myometrium, which leads to homeotic transformation of the stem cell into
a more cervical phenotype. We propose to determine how the epigenetic landscape of the myometrial and
fibroid stem cells affects compartmentalization in the stem cells. Once these mechanisms are understood, we
will have a better understanding of how disruption of key pathways affect their behavior, with the ultimate goal
of identifying targets for therapeutic intervention.

## Key facts

- **NIH application ID:** 10200875
- **Project number:** 5R21HD102907-02
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** JOSE M. TEIXEIRA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $205,542
- **Award type:** 5
- **Project period:** 2020-07-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200875

## Citation

> US National Institutes of Health, RePORTER application 10200875, Stem cell epigenetics in uterine fibroids (5R21HD102907-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10200875. Licensed CC0.

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