# Transcriptional regulation of skin stem cells and their niche

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $341,440

## Abstract

Project Summary:
The overarching goal of the proposed research is to understand how skin stem cells maintain
their identity when responding to cell intrinsic and extrinsic signals for self-renewal or
differentiation. Self-renewal of stem cells is achieved by either symmetrical or asymmetrical cell
division, through which new generations of stem cells are produced to replenish the stem cell
population. However, DNA replication and cell division of adult stem cells can also lead to
generation and accumulation of DNA mutations that compromise stem cell function and, in
some cases, tumorigenesis. In the skin, hair follicle stem cells acquire quiescence to minimize
cell turnover and division. However, it remains poorly understood how these stem cells
transition between self-renewing and quiescent phases and the requirement of quiescence for
long-term maintenance of stem cells. These questions have challenged investigators, because
these self-renewing and quiescent stem cells are rare and usually heterogeneous in most adult
tissues, making their isolation and characterization difficulty. In the skin of early adult mice, hair
follicle stem cells are highly synchronized for self-renewal and quiescence. This property makes
hair follicle stem cells an ideal system to investigate this fundamental question in stem cell
biology. Recently, we have identified a transcription factor, Foxc1, induced in self-renewing but
not quiescent hair follicle stem cells and their niche to reinforce quiescence. This finding
uncovers an adaptive response of quiescent stem cells to stem cell activation during self-
renewal and illuminates a path to further investigate mechanisms that control cellular state
transitions in adult stem cells. In this proposal, we will utilize our innovative genomic tools and
mouse models to understand adaptive control of stem cell quiescence and self-renewal
mediated by transcription factors. We will first determine how multiple transcription factors
regulate stem cell quiescence by coordinating transcriptional control of common and unique
targets. We will determine the requirement of quiescence for long-term maintenance of hair
follicle stem cells (Aim 1). We will then investigate the differences in open chromatin between
self-renewing and quiescent stem cells. We will examine how the BMP signaling is controlled by
transcription factors (Aim 2). Finally, we will investigate the mechanism of club hair anchorage
mediated by transcription factors (Aim 3). The knowledge gained from these studies will
enhance our understanding of quiescence control in hair follicle stem cells.

## Key facts

- **NIH application ID:** 10261535
- **Project number:** 5R01AR071435-06
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Rui Yi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $341,440
- **Award type:** 5
- **Project period:** 2017-07-28 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10261535

## Citation

> US National Institutes of Health, RePORTER application 10261535, Transcriptional regulation of skin stem cells and their niche (5R01AR071435-06). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10261535. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*