# Myometrial stem cells

> **NIH NIH R21** · MICHIGAN STATE UNIVERSITY · 2020 · $234,750

## 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 essentially 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
clonal, indicating a single cell of origin for each tumor. Our overarching hypothesis is that fibroids develop from
myometrial stem cells that have become dysregulated by either MED12 mutation or HMGA1/2 over-
expression. We have developed complementary models to study myometrial stems cells and determine the
mechanisms disrupted that lead to fibroid development or growth. We have identified and characterized label-
retaining cells (LRCs) in the mouse myometrium. These cells express putative stem cell markers, and divide in
response to postpartum repair, as would be expected for myometrial stem cells. We have also used side
population analysis and cell surface markers to identify human myometrial cells with stem cell properties.
However, none of these methods leads to a highly enriched, homogeneous population necessary for some of
the next generation sequencing approaches to study molecular mechanisms driving disease etiology and
progression. We propose to use establish RNA-seq profiles for these putative myometrial stem cells and map
them to single-cell sequencing clusters of myometrial cells to identify other cell surface markers to further
enrich for highly purified, human myometrial stem cells. Once these putative myometrial stem cells are
validated, we can then use them to study and better understand possible disrupted chromatin and epigenetic
mechanisms that lead to fibroid development and growth, with the ultimate goal of identifying targets for
therapeutic intervention.

## Key facts

- **NIH application ID:** 9986156
- **Project number:** 1R21HD100959-01A1
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** JOSE M. TEIXEIRA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,750
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986156

## Citation

> US National Institutes of Health, RePORTER application 9986156, Myometrial stem cells (1R21HD100959-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986156. Licensed CC0.

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