# Unraveling the interplay between metabolism, epigenetics and stem cell fate in the hair follicle

> **NIH NIH F32** · ROCKEFELLER UNIVERSITY · 2020 · $27,922

## Abstract

PROJECT SUMMARY
Emerging evidence has uncovered a critical role for cellular metabolism as stem cells (SCs) balance self-
renewal and differentiation to maintain tissue homeostasis. However, little is known mechanistically about how
SCs integrate metabolic stimuli during cell fate decisions within their in vivo niches. Furthermore, several
classes of metabolites are increasingly being recognized as able to influence epigenetic processes that control
chromatin remodeling, including highly plastic chromatin domains that direct key transcriptional programs to
maintain SC identity. Thus, achieving a better understanding of the complex crosstalk between metabolism,
epigenetics and SC function is critical to identify essential signaling cascades necessary to preserve SC-
mediated regenerative capacity. To achieve these goals, the murine hair follicle is an excellent system
because it naturally undergoes recurrent and synchronous cycles of tissue homeostasis and regeneration.
First, I will isolate and purify populations of hair follicle stem cells (HFSCs) during quiescence, activation and
following their transition to short-lived, proliferative progenitors. I will then perform in vivo metabolomic profiling
by directly measuring metabolite abundance using gas chromatography–mass spectrometry. Stable isotope
tracing will determine metabolite turnover rates and their relative contributions from several carbon sources,
including glucose sugars, fatty acids and the amino acid glutamine (Aim I). Next, I will engineer bioenergetic
sensors to monitor the metabolic dynamics of HFSCs throughout the hair cycle and within in vivo physiological
setting. This will be accomplished by exploiting my lab's powerful and rapid in utero lentiviral technology to
deliver these sensors specifically to the skin epithelium and hair follicle (Aim II). I will apply CRISPR-mediated
knockout strategies using the in utero lentiviral delivery platform to functionally assess the impact of metabolic
perturbations to the metabolism and behavior of HFSCs. And finally, I will measure the impact of these
interventions aimed at critical metabolic pathways on chromatin remodeling in HFSCs, clarifying the
mechanistic contributions played by metabolic adaptations during the epigenetic switch governing the transition
from self-renewal to lineage commitment and differentiation (Aim III). In total, this work will define the functional
consequences and epigenetic mechanisms underlying metabolic reprogramming in the regenerating hair
follicle, providing novel therapeutic targets that have the potential to help maintain long-term tissue
homeostasis in diseases affected by SC imbalance, ranging from aging to cancer.

## Key facts

- **NIH application ID:** 10266311
- **Project number:** 3F32AR073105-02S1
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Matthew Tierney
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $27,922
- **Award type:** 3
- **Project period:** 2018-08-01 → 2020-12-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10266311

## Citation

> US National Institutes of Health, RePORTER application 10266311, Unraveling the interplay between metabolism, epigenetics and stem cell fate in the hair follicle (3F32AR073105-02S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10266311. Licensed CC0.

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