# Spatially Resolved, Functional Dissection of the Human Spermatogonial Stem Cell Niche

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $337,627

## Abstract

PROJECT SUMMARY
The functions of human spermatogonial stem cells (SSCs), including self-renewal and differentiation, are
required for the constant production of male gametes over a long reproductive lifespan; imbalances in this
process directly contribute to infertility or germ cell-derived cancers. Despite this wide range of healthcare
implications, the cellular and molecular regulation of human SSCs is poorly understood, in particular with
respect to the microenvironment in which SSCs reside, termed the niche. Despite research efforts, a major gap
in knowledge remains, i.e., how does the SSC niche influence the functions of human SSCs? Our long-term
goal is to understand the molecular mechanisms that regulate human SSCs. Unlike rodents, for which genetic
models are routinely used to evaluate the roles of the niche in regulating SSC functions in vivo, functional
dissection of the human SSC niche has been challenging largely due to a lack of experimental tools. Single cell
omics has enabled a molecular catalogue of human testicular cell types but falls short on providing insights into
the spatial and functional interactions between SSCs and the niche due to tissue disassociation.
We have recently established a spatial transcriptomics (ST) approach that successfully recapitulates many
aspects of the mouse and human spermatogenesis. This approach quantifies genome-wide gene expression
of individual testicular cells within intact tissue sections. Using this ST approach, coupled with a series of
functional, cellular, and molecular analyses, we will test our central hypothesis that human SSCs are
functionally regulated by the niche through a selective set of ligand-receptor (LR) interactions. First, we will
perform a systematic characterization of LR interactions at the human SSC niche. Second, we will
comparatively study the human and mouse SSC niches under the hypothesis that human specific LR pairs
may be crucial to human SSC functions. Finally, we will examine the contribution of germline cells to the
functions of human SSC niche. The successful completion of the proposed work will significantly enhance our
mechanistic understanding of the functional role of the niche in regulating human SSC activities. It will also
provide much needed insights into the etiology of male infertility, fertility preservation for cancer patients, and
the successful establishment of in vitro spermatogenesis.

## Key facts

- **NIH application ID:** 10856959
- **Project number:** 1R01HD114698-01
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Haiqi Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $337,627
- **Award type:** 1
- **Project period:** 2024-04-04 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856959

## Citation

> US National Institutes of Health, RePORTER application 10856959, Spatially Resolved, Functional Dissection of the Human Spermatogonial Stem Cell Niche (1R01HD114698-01). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10856959. Licensed CC0.

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