# Skin Stem Cells and Their Niche Interactions

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2024 · $410,337

## Abstract

Project Summary/Abstract
The global objective of this research is to elucidate the mechanisms underlying tissue homeostasis and
regeneration in mammalian skin and to understand how this process goes awry in human disorders, including
cancers. Central to achieving this goal is the characterization of the different stem cells (SCs) within skin,
determining their relative contributions to tissue homeostasis and wound-repair, and elucidating how changes in
their niche microenvironments impact these events. Past AR050452 research led to purification of hair follicle
(HF) bulge and basal inter-follicular epidermal (Epd) cells and established them as long-lived, self-renewing SCs
that function in tissue regeneration and wound-repair. However, both in their biology and their tissue regenerative
tasks, these SCs display distinct behaviors predicated by their unique microenvironments (niches). The field still
lacks a comprehensive knowledge of the constituents of these niches, the nature of SC:niche interactions, and
how they help SCs cope with stressful situations. Past AR050452 research set the foundations to tackle the next
key questions: (1). What are dynamics in bulge niche components that drive HFSC behavior during the hair
cycle? (2) What are the key niche:HFSC interactions that maintain quiescence and drive tissue (hair)
regeneration and how do they differ from the niche: short-lived progeny interactions that drive hair differentiation?
(3) How are HFSCs spared during the destructive phase of the cycle when hair growth ceases and most follicle
cells below the bulge apoptose? Does eating confer increased SC fitness? (4) How do HFSC:niche interactions
change when skin is injured and the SCs become repurposed to repair the wound? How do SCs protect
themselves against immune/pathogen attack so that they can orchestrate the re-epithelialization process? (5)
How does the natural process of wound-repair differ from the behavior of a SC when it acquires an oncogenic
mutation that will ultimately lead it down a path to cancer? To answer these questions, we'll use FACS, single
cell spatial transcriptomics and chromatin landscaping, conditional gene knockout and RNAi screens in vivo and
employ these methods to explore skin stem cells in their native, wound-induced and tumorigenic environments.

## Key facts

- **NIH application ID:** 10801260
- **Project number:** 2R01AR050452-21
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** ELAINE FUCHS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $410,337
- **Award type:** 2
- **Project period:** 2004-02-26 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10801260

## Citation

> US National Institutes of Health, RePORTER application 10801260, Skin Stem Cells and Their Niche Interactions (2R01AR050452-21). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10801260. Licensed CC0.

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