# Regulation of Epidermal Development and Differentiation

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2020 · $563,882

## Abstract

Project Summary
Our global objective 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 to determine how transcription
factors act in concert to specify stem cell behavior, and to ascertain how stem cells respond to
stimulating signals from their microenvironment to remodel their chromatin landscape and
activate a new program of gene expression to make tissue. Past AR31737 research led to the
identification of transcription factors that are selectively expressed by hair follicle (HF) stem
cells, and through mouse genetics, we elucidated the consequences of missing each factor.
Although each had differential roles in suppressing tissue lineages, the cohort displayed a
common function in controlling stemness. This past research now sets the foundation to
tackle a series of important questions: (1) What key stemness genes are co-regulated by the
cohort of HF stem cell factors and how does their chromatin become remodeled when faced
with dramatically changing transcriptional landscapes during lineage progression? Can we
exploit this information to develop paradigms for understanding transcriptional control of gene
expression in other skin stem cells and/or their progeny? (2) What are the mechanisms
controlling how key genes switch between repressed and active states during lineage
determination and progression? Do certain transcription factors function as pioneers in initiating
these switches, and if so how? (3) How do external niche signals, e.g. WNTs and BMPs, impact
transcriptional regulation of adult HF stem cells? (4) Which signaling pathways govern the
establishment of stem cells during skin development? To answer these questions, we'll use in
vivo FACS, single cell/RNA-seq, ChIP-seq, powerful in vivo RNAi screens, and devise new
tools and technologies to explore transcriptional governance of skin stem cells and their
tissues. In so doing, we expect to advance our knowledge of tissue homeostasis and to
understand stem cell plasticity, namely how stem cells survive when faced with new
environments in wound-repair and malignant progression.

## Key facts

- **NIH application ID:** 9966705
- **Project number:** 5R01AR031737-38
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** ELAINE FUCHS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $563,882
- **Award type:** 5
- **Project period:** 1983-01-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9966705

## Citation

> US National Institutes of Health, RePORTER application 9966705, Regulation of Epidermal Development and Differentiation (5R01AR031737-38). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9966705. Licensed CC0.

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