# In vivo Identification of stem cells in MED12 mutant leiomyoma

> **NIH NIH R21** · OHIO STATE UNIVERSITY · 2020 · $234,000

## Abstract

PROJECT SUMMARY
Uterine leiomyoma (LM) is a benign smooth muscle tumor of the myometrium with an overall prevalence of over
70%. Symptoms of this tumor include heavy menstrual bleeding, pelvic pressure or pain, and often require
intervention. Since there is no effective non-surgical therapy for LMs, approximately a third of women with a
diagnosis of LM undergo hysterectomy, which imposes a significant physical and psychological burden. Surgery
also creates serious financial strain, with the annual cost for surgical management of LMs in the United States
estimated to be 829 million to 4.3 billion dollars. Hence, novel therapeutic options with long-term efficacy to
replace surgical management are urgently needed. In order to develop such medical options, a better
understanding of the cellular and molecular pathogenesis of LM is essential. Some studies suggest that stem
cells play a critical role in the pathogenesis, yet the identity and function of LM stem cells (LM-SCs) remain
ambiguous as different groups propose several incompatible stem cell models. This confusion is partially due to
faulty presumptions that all LMs are equivalent, and that all cells in a LM arise from a single progenitor cell.
Accumulating evidence indicates that LMs contain substantial non-tumor cells of independent cell lineages, and
the composition of tumor and non-tumor cells is distinctive between different LM subtypes. In this project, we will
focus on the MED12 mutant LM (MED12-LM), the most prevalent LM subtype accounting for ~70% of all LMs.
In MED12-LM, causal MED12 mutations are present only in tumor smooth muscle cell (T-SMC), which accounts
for ~60 % of total cell population. Tumor-associated fibroblast (TAF), which is negative for MED12 mutations, is
the second major cell type in MED12-LM, accounting for ~40% of total cells. Surprisingly, previous studies that
proposed LM-SC models did not recognize the presence of TAFs. In our analysis, the putative LM-SC fractions
primarily consisted of non-tumor cells. Accordingly, we seek to determine presence and characteristics of LM-
SC in MED12-LM utilizing the patient derived xenograft (PDX), the only research model that can replicate the
hormone-dependent growth of MED12-LMs. To identify LM-SCs, we will identify cell types that compose MED12-
LM by single cell RNA-seq (scRNA-seq) of PDXs. By comparing resting (no hormone) and growing (with
hormones) PDXs, we will identify cells and genes that control hormone-dependent growth of MED12-LMs. We
will also determine the growth kinetics of each cell type during regeneration of PDXs by a Pulse-Chase assay
with three thymidine analogs. Due to their infrequent proliferation, tissue stem cells are often identified as label-
retaining cells (LRCs). By this assay, we will identify LRCs as well as the first cells that undergo cell division in
response to hormones. Integration of scRNA-seq and Pulse-Chase assays will reveal the identity of cells and
signaling pathways that are essent...

## Key facts

- **NIH application ID:** 10050801
- **Project number:** 1R21HD102897-01
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Takeshi Kurita
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10050801

## Citation

> US National Institutes of Health, RePORTER application 10050801, In vivo Identification of stem cells in MED12 mutant leiomyoma (1R21HD102897-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10050801. Licensed CC0.

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