# Elucidating the Role of TCF21+ Mesenchymal Cells in Testis Tissue  Homeostasis and Regeneration

> **NIH NIH F30** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2020 · $31,871

## Abstract

Abstract
Male fertility is dependent on the successful production of both reproductive hormones and mature sperm,
which requires the concerted activity of germ cells, supporting somatic cells, and the hypothalamic-pituitary
axis. The diversity of cell types involved in these processes in the testis has largely been defined histologically,
but our molecular understanding of somatic populations is largely limited by the availability of transgenic lines.
Therefore, to achieve an unbiased analysis of the somatic compartment and molecular cell types, I have
applied single cell RNA-seq to the adult mouse testis. Transcriptome analysis of ~5000 single-cells identified
all major somatic cell types, and a previously unappreciated interstitial cell population (Tcf21+ cells). Clustering
and principle component analyses suggest that the novel cell population is related to both myoid and Leydig
cells. Marker gene analysis of this population is consistent with this population being a mesenchymal stem cell
(MSC). In other organs, MSCs are known for their regenerative and immunomodulatory potential, but whether
this cell population is capable of supporting testicular tissue homeostasis and regeneration in the adult testis,
or serving as the cell of origin myiod or Leydig cells, remains unknown. Therefore, this proposal aims to
explore the functional role of Tcf21+ cells in the embryonic and adult testis. Based on my preliminary data and
previous genetic studies demonstrating a key role for Tcf21 in testis differentiation and development, I
hypothesize that Tcf21+ cells are precursors for myoid and Leydig cells, and serve as a reserve somatic stem
cell in the adult testis. To address these questions, I will use a combination of genetic lineage tracing,
immunohistochemical and functional characterization, and in vivo targeted cell ablation. These studies will
elucidate the development and homeostatic function of interstitial cells in the testis, and will provide new
evidence for a reserve somatic stem cell population, which could be used to inform new therapeutic
approaches for patients with hypoandrogenism and/or infertility. Additionally, completion of this work will
provide me with critical scientific, technical, and medical training, as outlined in my training plan, which will be
foundational for a successful career as a physician scientist studying the intrinsic and extrinsic regulation of
spermatogenesis and male fertility.

## Key facts

- **NIH application ID:** 10003038
- **Project number:** 5F30HD097961-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Adrienne Niederriter Shami
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $31,871
- **Award type:** 5
- **Project period:** 2018-09-30 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10003038

## Citation

> US National Institutes of Health, RePORTER application 10003038, Elucidating the Role of TCF21+ Mesenchymal Cells in Testis Tissue  Homeostasis and Regeneration (5F30HD097961-03). Retrieved via AI Analytics 2026-06-03 from https://api.ai-analytics.org/grant/nih/10003038. Licensed CC0.

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