# Transcriptional regulation of skin stem cells and their niche

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $539,773

## Abstract

Project Summary:
 The overarching goal of the proposed research is to understand the mechanism of hair
follicle stem cell (HF-SC) maintenance and aging. HF-SCs reside in an anatomically distinct
region, called the bulge. During the lifespan, HF-SCs go through a multi-stage process, called
the hair cycle, to generate hair shaft and self-renew. During the anagen phase of hair cycle, HF-
SCs and their hair germ progenitors give rise to a large number of transit-amplifying cells in the
Matrix of hair bulb, where precursors to terminally differentiated hair shaft are produced, to fuel
hair growth. During the catagen phase, most cells in the lower portion of hair follicles, including
the Matrix, undergo apoptosis but a few cells survive and move upward to help to form the new
bulge compartment. Upon the formation of the new bulge compartment, HF-SCs usually rest in
the quiescent telogen phase before initiating the next anagen hair growth. Although many
studies have examined mechanisms that regulate self-renewal and differentiation of HF-SCs, it
remains poorly understood how these stem cells quantitatively control hair growth and how their
functions decline during aging. In the first funding cycle, we have established skin specific,
Foxc1 and Nfatc1 double knockout as a premature aging model for HFs and revealed the
escape of HF-SCs from their bulge niche as a new mechanism for the reduction of HF-SCs and
HF miniaturization. In our preliminary study, we have generated a hair cycle stage-specific
single-cell atlas and a longitudinal single-cell atlas during aging. These rich single-cell
transcriptomic datasets have identified a unique cell population of migratory niche (migNiche).
Using intravital live imaging to track the duration of hair growth for individual HFs across multiple
hair cycles in our mutant model, we have obtained experimental evidence that the size of HF-
SC bulge controls the duration of anagen hair growth and the size of HFs and, in turn, define the
size of the next-generation bulge. In this proposal, we will utilize our innovative intravital
imaging, single-cell genomic tools and genetically engineered mouse models to understand cell
extrinsic and cell intrinsic mechanisms of hair follicle stem cell maintenance. We will Investigate
the formation of new HF-SC compartment and its effect on hair growth (Aim 1). We will then
elucidate FOXC1/NFATC1-mediated gene expression control in the migratory niche (Aim 2).
Finally, we will elucidate the mechanism and consequence of HF-SC escape (Aim 3). Together,
our renewal application will provide conceptual and mechanistic insights into the maintenance of
HF-SCs through a cell extrinsic mechanism mediated by migNiche and a cell intrinsic
mechanism controlled by HF-SC adhesion.

## Key facts

- **NIH application ID:** 10833207
- **Project number:** 5R01AR071435-08
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Rui Yi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $539,773
- **Award type:** 5
- **Project period:** 2017-07-28 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833207

## Citation

> US National Institutes of Health, RePORTER application 10833207, Transcriptional regulation of skin stem cells and their niche (5R01AR071435-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10833207. Licensed CC0.

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