# Hair Follicle Dermal Stem Cell Functions and Potential

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $501,487

## Abstract

Project Summary
The hair cycle is an excellent model to study adult stem cell (SC) regulation by the microenvironment or niche,
as it involves bouts of hair follicle (HF) regression, rest and regrowth. During regression, most HF epithelial cells
die by apoptosis while the mesenchymal dermal papilla (DP) cell cluster survives and relocates from the HF
base to the SCs in the permanent upper follicle. During the resting phase, signals from the DP are critical for
activating the SCs to initiate regeneration of a growing HF. In contact with the DP and encasing growing HFs is
the dermal sheath (DS), which we recently reported is a specialized smooth muscle essential for DP relocation
and follicle regression. Within the DS, a non-smooth muscle cell subpopulation was recently discovered that also
survives regression and has the intriguing SC potential for regenerating the DS smooth muscle of re-growing
HFs and for contributing cells to the DP lineage during hair cycling. The cells were aptly named HF dermal SCs
(hfDSCs). However, the evidence for these potent cells has been largely indirect due to the lack of direct genetic
targeting for hfDSC cell ablation, labeling and tracing and for gene knockouts. Our immediate goal is to overcome
this roadblock for enabling direct functional hfDSC studies and answering several key questions: What is the
functional requirement of hfDSCs for HF regrowth? What is their lineage contribution to the DP during normal
unperturbed hair cycling? What is the hfDSC cell plasticity during wound healing? What are the molecular
mechanisms that control hfDSC identity and potency? Our long-term goal is to understand how hfDSCs and DP
niche cells govern SC functions and to provide a rational basis for developing future hair regenerative therapies.
We have recently isolated, transcriptome-wide characterized, genetically targeted and live imaged the mature
DS to uncover a key contractile role in follicle regression. We have now developed a genetic driver to study the
cellular and molecular functions of their progenitors, the hfDSCs. With our preliminary data we have established
the conditions to specifically and inducibly target for the first time the hfDSCs; explore their cellular dynamics;
define the functional requirement of hfDSC; purify for the first time hfDSCs in their quiescent and activated states;
define hfDSC-specific gene signatures; and interrogate the regulation of hfDSC identity and function. With these
studies we will rigorously test the hypothesis that hfDSCs constitute a potent mesenchymal progenitor population
of the HF niche. Overall, this work will establish genetic targeting of resting-phase hfDSCs, reveal their cellular
turnover and lineage potential for other hair and skin mesenchymal cells and provide molecular insight into
hfDSC gene regulation and function during the cycle.

## Key facts

- **NIH application ID:** 10880523
- **Project number:** 5R01AR079475-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Michael Rendl
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $501,487
- **Award type:** 5
- **Project period:** 2021-07-08 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10880523

## Citation

> US National Institutes of Health, RePORTER application 10880523, Hair Follicle Dermal Stem Cell Functions and Potential (5R01AR079475-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10880523. Licensed CC0.

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