# Mechanisms governing stem cell coordination by the niche

> **NIH NIH R01** · DREXEL UNIVERSITY · 2021 · $100,000

## Abstract

Project Summary / Abstract
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 the parent grant, we propose to interrogate
the specific mechanisms by which niche signals and somatic stem cells combine to regulate
GSC cytokinesis using molecular genetics and extended live imaging. Here, we request an
administrative supplement for the acquisition of fast and super-resolution laser scanning
confocal microscopy, which will improve the imaging capabilities, quality and data output
(productivity) of our R01-funded projects. The new instrumentation will enable imaging of fixed
and live testes faster and with less photodamage as well as unprecedented resolution (100 nm
lateral, 200 nm axial). This enhanced resolution will aid in identification of altered F-actin
structure at the intercellular bridge between GSC-daughter pairs investigated in Aim1 of the
parent grant. In our studies of temporal dynamics in abscission machinery localization to the
GSC-daughter intercellular bridge (Aim2 of parent grant), the new instrumentation will enable
tracking of ESCRT machinery with unprecedented spatiotemporal resolution in 2D and 3D using
detectors with superior quantum efficiency. Through the use of advanced modulations such as
dynamic enhancement and adaptive image quality determination and reconstruction, we will be
able to acquire high-quality time-lapse data with improved resolution. This is in conjunction with
the ability to acquire images from multiple (up to three) wavelengths simultaneously—an
essenti...

## Key facts

- **NIH application ID:** 10389225
- **Project number:** 3R01GM138705-02S2
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Kari Lenhart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $100,000
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10389225

## Citation

> US National Institutes of Health, RePORTER application 10389225, Mechanisms governing stem cell coordination by the niche (3R01GM138705-02S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10389225. Licensed CC0.

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