# Lipid mediated regulation of stem cell behavior and tissue homeostasis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $442,284

## Abstract

Project Summary
 Tissue stem cells provide for the maintenance and regeneration of organs and tissues throughout life. The
ability of stem cells to contribute to tissue homeostasis depends on their unique ability to generate new stem
cells (self-renewal), as well as specialized cell types (differentiation). Stem cell behavior is influenced by the
integration of intrinsic factors with extrinsic cues provided by the local microenvironment (or “niche”) and
circulating, systemic factors. Thus, identification and characterization of the mechanisms that are involved in
regulating stem cell behavior holds significant promise for the maintenance, manipulation and expansion of stem
cells for use in regenerative medicine.
 The capacity of stem cells to self-renew or differentiate has been attributed to distinct metabolic states. Our
lab recently found that an increase in triacylglycerides (TAG) in the form of lipid droplets (LDs), either through
disruption of fatty acid oxidation (FAO) or stimulation of lipid anabolism, correlates with a loss of germline stem
cell (GSC) fate in the Drosophila testis. Genetic or pharmacologic enhancement of lipid catabolism rescued the
loss of GSCs, indicating that GSCs are sensitive to the levels of intracellular lipids. Here, we propose to identify
the mechanism(s) by which ectopic lipid accumulation leads to loss of GSC identity and to use the well-
characterized Drosophila male germline as a model to uncover mechanisms used to tightly regulate lipid
metabolism in GSCs to maintain tissue homeostasis through the following Specific Aims:
Aim 1: To characterize mechanisms by which increased intracellular lipids contribute to loss of GSCs
Aim 2: To investigate the role of phosphatidic acid (PA) metabolism in the Drosophila testis
Aim 3: To characterize the role of the phosphatidic acid phosphatase (PAP) dLipin in the Drosophila
testis
 Taken together, these Aims will contribute to a better understanding of how lipid metabolism can influence
tissue homeostasis by influencing stem cell behavior. Furthermore, our work will provide a genetic model to
characterize mechanisms that cells in non-adipose tissues use to manage ectopic lipids to avoid lipotoxicity.
Finally, our findings will provide important insights into how stem cell and/or germ cell function may be altered in
individuals suffering from metabolic disorders, such as obesity and/or type 2 diabetes, leading to strategies to
regulate stem cell function, in vivo, in patients by modulating metabolic pathways pharmacologically or through
diet.

## Key facts

- **NIH application ID:** 9998567
- **Project number:** 1R01GM135767-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** DANA LEANNE JONES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $442,284
- **Award type:** 1
- **Project period:** 2020-06-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9998567

## Citation

> US National Institutes of Health, RePORTER application 9998567, Lipid mediated regulation of stem cell behavior and tissue homeostasis (1R01GM135767-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9998567. Licensed CC0.

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