# Control of Stem Cell Dynamics by a Niche at Steady-State and During Aging

> **NIH NIH R35** · UNIVERSITY OF PENNSYLVANIA · 2021 · $418,928

## Abstract

Stem cells are necessary for tissue homeostasis, and are often localized to specialized niches that
control their function. In this manner, niches control virtually all aspects of stem cell dynamics, and
these properties of stem cells are essential to tissue maintenance. Recent work has shown that
precise cellular architecture is important in order for a niche to communicate with fidelity to the stem
cells it controls. A major issue is that the field does not understand how niches are initially formed in a
tissue, nor the key cell biological steps that constitute stem cell dynamics., and how these are
regulated by niche signals. Our lab made significant advances on these questions over the past five
years of GM funding.
First, after identifying key signals and transcriptional regulators of niche cell specification, we revealed
the dynamics of niche formation by live-imaging. This enabled us to suggest mechanisms underlying
niche morphogenesis that are so central to its function. We pursue the underlying mechanisms in this
proposal, capitalizing on our knowledge of cytoskeletal control over cell-cell organization, and in
particular the involvement of actomyosin contractility and RhoA signaling.
Second, we discovered that the niche imposes precise control over fundamental cellular processes
such as abscission and midbody inheritance in order to regulate stem cell dynamics during tissue
homeostasis and upon stresses, such as aging. We found that dysregulations of either of these
fundamental cell biological processes compromises tissue function. Furthermore, the control of
midbody inheritance as detailed in the proposal should have an impact generally on our
understanding of how normal and cancer cells deal with defects in centrosome number.
To address our hyptheses, we combine the powerful genetic and molecalur approaches available in
using Drosohila, with state-of-the-art assays in cellualr mechanics, which include high spatial and
temporal live-imaging, FRAP and laser ablation.
Collectively, our approaches should reveal the undelying mechnics that establish a niche properly,
and reveal important cellular features that allow stem cells to maintain tissues.
!

## Key facts

- **NIH application ID:** 10159958
- **Project number:** 5R35GM136270-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** STEPHEN Francis DINARDO
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,928
- **Award type:** 5
- **Project period:** 2020-06-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159958

## Citation

> US National Institutes of Health, RePORTER application 10159958, Control of Stem Cell Dynamics by a Niche at Steady-State and During Aging (5R35GM136270-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10159958. Licensed CC0.

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