# Mechanisms governing stem cell coordination by the niche

> **NIH NIH R01** · DREXEL UNIVERSITY · 2022 · $57,510

## Abstract

Project Summary / Abstract
The broad objective of this study is to understand the mechanism by which multiple stem cell populations are
controlled by the niche to coordinate daughter cell production. Coordination between adult stem cells is
essential to maintain tissue homeostasis and prevent tumorous overgrowth. Many structures, including the hair
follicle, hematopoietic network and developing ovary require tight control over stem cell proliferation and
coordination of daughter cell production from distinct stem cell lineages. In most cases, the molecular
mechanisms orchestrating this coordination are largely unknown. Leveraging the power of Drosophila genetics
and establishing a system for longitudinal (20+ hours) live imaging of stem cells within an endogenous niche
we have begun to reveal the mechanisms controlling stem cell coordination in the testis. Somatic stem cells
and germline stem cells (GSCs) of the testis must generate daughters in a precise 2:1 ratio for germ cells to
effectively differentiate into sperm. Our live imaging has revealed a modified cytokinesis program in GSCs as
the mechanism to coordinate release of one GSC daughter only after it correctly associates with two daughters
of the somatic stem cell lineage. This modified cytokinesis program is controlled at two stages—a pause
regulated by Jak/STAT signaling from the niche and a trigger for completion of cytokinesis derived from the
somatic stem cells. Both control points must be properly executed or stem cell cytokinesis fails, stem cell
tumors form and germ cells fail to differentiate. While we have identified the source of both the pause and
trigger, the mechanisms by which these signals control GSC cytokinesis remain unknown. In addition, the
degree to which soma and germline communicate to ensure that proper ratios of daughter cells are produced
is largely unexplored. This study uses molecular genetics and extended live imaging to interrogate the specific
mechanisms by which niche signals and somatic stem cells combine to regulate GSC cytokinesis to ensure
coordination between stem cells in the testis niche. By establishing a method for live imaging of both stem cell
populations, we can now also directly visualize stem cell coordination in real time and interrogate the cross-talk
between stem cell lineages that is essential for tissue homeostasis. Successful completion of the proposed
work will provide significant insight into stem cell-niche interactions and how these may become disrupted
during tumorigenesis, setting the foundation for future work aimed at identifying similar mechanisms at play in
other tissues and species.

## Key facts

- **NIH application ID:** 10616178
- **Project number:** 3R01GM138705-03S1
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Kari Lenhart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $57,510
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10616178

## Citation

> US National Institutes of Health, RePORTER application 10616178, Mechanisms governing stem cell coordination by the niche (3R01GM138705-03S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10616178. Licensed CC0.

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