# Mechanisms of stem cell specification in the male germline

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $471,757

## Abstract

PROJECT SUMMARY/ABSTRACT
 The germline provides an eternal cellular link between generations and in metazoan a
male's genetic contribution to the next generation is delivered via sperm. Thus, the genesis of
sperm (i.e. spermatogenesis) is critical for the continuity and diversity of a species.
 This project is designed to advance our understanding of the developmental origins of the
sperm producing (i.e. spermatogenic) lineage. In particular, it seeks to uncover a cell autonomous
trigger driving formation of the foundational spermatogonial stem cell (SSC) pool which is required
for continuity of spermatogenesis and male fertility in adulthood. In mammals, the SSC pool is
known to arise in early postnatal life from a subset of the prospermatogonial precursor
population but the mechanism underpinning the process is grossly undefined. Indeed, no single
molecule as has been identified, to date, to be obligatory for this process.
 Understanding how the foundational SSC pool is built from prospermatogonial precursors
is scientifically and clinically important. Progress in this area of study has been limited because
the tools for investigating the process in fine detail have been lacking. Over the past several years,
we discovered genes that are expressed by SSCs (e.g. Id4) and generated multi-transgenic
reporter mouse models to label germ cell subsets through fetal and neonatal development. Using
these tools, we have been able to describe the kinetics underlying the building of the foundational
SSC pool, determine that the process is triggered at a defined age point in neonatal development
(P0-3 in mice), and profile transcriptome dynamics as the single cell level. Outcomes of these
studies uncovered a unique expression profile for the transcription factor Msx1; temporal
induction in a subset of the prospermatogonial population at P0 that based on trajectory
predictions from scRNA-seq analyses are fated to become SSCs. The current project is designed
to define the potency of temporal Msx1 expression on SSC fate specification and explore the
mechanism of action for Msx1 in prospermatogonia. Results are expected to provide a wealth of
information from which we can define how SSC fate is triggered in a subset of prospermatogonia
during neonatal development. This information may be clinically and scientifically useful for
understanding the etiology of male infertility, and through transient ectopic expression approaches
to reprogram somatic cells to adopt an SSC fate or rejuvenate stem cell capacity in aged or
imperfect SSCs.

## Key facts

- **NIH application ID:** 10064366
- **Project number:** 1R01HD101223-01A1
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** Jon M Oatley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $471,757
- **Award type:** 1
- **Project period:** 2020-09-11 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10064366

## Citation

> US National Institutes of Health, RePORTER application 10064366, Mechanisms of stem cell specification in the male germline (1R01HD101223-01A1). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10064366. Licensed CC0.

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