# Nerve-stem cell interactions during skin homeostasis and wound repair

> **NIH NIH F32** · HARVARD UNIVERSITY · 2022 · $67,582

## Abstract

PROJECT ABSTRACT
The skin undergoes constant cycles of renewal and regeneration, depending on multiple stem cell populations
for the maintenance of its function as a barrier and environmental sensor. Situated at the environmental interface,
skin stem cells must be able to adapt to changes detected at the systemic level to preserve skin function. How
systemic information is integrated to regulate skin stem cell behavior remains poorly understood. The
sympathetic nervous system (SNS) densely innervates the skin, and forms connections with the three key stem
cell populations in the skin, providing a starting point for understanding how stem cell activity is directly influenced
by and integrated with systemic changes in the body. As both a local and systemic regulator, the SNS is uniquely
positioned to link changes sensed at the organismal level to changes in stems cell in the periphery. The SNS is
a branch of the autonomic nervous system, and is constantly active at a basal level to modulate physiological
processes such as heart rate and blood pressure, but becomes highly elevated under stress to trigger fight-or
flight responses. Traditionally, sympathetic neurons were thought to only directly regulate excitatory cells such
as muscle; however, pioneering studies in hematopoietic and skin stem cells indicate sympathetic activity has a
wider role governing physiology by directly regulating stem cells. Additionally, sympathetic neuropathy (loss of
innervation) in the skin is associated with prolonged wound healing, suggesting a vital role for sympathetic activity
in skin repair. The outermost layer of the skin consists of a continually renewing epidermis that depends on one
of the key skin stem cells, epidermal stem cells (EpSCs), for turnover and repair. EpSC activity must be
exceptionally regulated as they are extremely vulnerable to environmental carcinogens such as UV light that can
lead to development of some of the most prevalent types of skin cancer. Despite its importance, how EpSCs are
regulated by extrinsic signals, both at the local and systemic level, is poorly understood. Locally in the skin,
sympathetic neurons innervate EpSCs, with preliminary results indicating the sympathetic neurotransmitter,
norepinephrine, is able to stimulate EpSC proliferation. Given these results, I propose sympathetic activity
directly regulates EpSC behavior to govern epidermal renewal and repair following injury. I will utilize
pharmacological and chemogenetic tools in a mouse model that permits tracing of EpSCs and progeny to
determine how the sympathetic nervous system regulates EpSCs during epidermal renewal and repair. I will also
determine if this occurs directly through activation of the norepinephrine receptor, Adrb2, expressed by EpSCs
and identify the molecular pathways downstream of Adrb2 signaling. This proposal will elucidate the cellular
mechanisms by which the SNS regulates epidermal renewal and healing, and evaluate the therapeutic potential
of...

## Key facts

- **NIH application ID:** 10424395
- **Project number:** 5F32AR079252-02
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** Emily Rivkah Scott-Solomon
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $67,582
- **Award type:** 5
- **Project period:** 2021-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10424395

## Citation

> US National Institutes of Health, RePORTER application 10424395, Nerve-stem cell interactions during skin homeostasis and wound repair (5F32AR079252-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10424395. Licensed CC0.

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