# Genetic Analysis of MicroRNA Functions in Skin Stem Cells In Vivo

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2022 · $456,046

## Abstract

Project Summary:
Mammalian skin and its appendages function as the outermost barrier of the body to protect
inner organs from environmental hazards and keep essential fluids within the body.
Homeostasis and integrity of mammalian skin are maintained by multiple progenitor and stem
cell populations residing in distinct skin compartments such as basal cells in the interfollicular
epidermis and bulge stem cells in hair follicles. In epithelial cells, cell adhesion, migration and
proliferation are fundamental properties that are controlled by many mechanisms. Among key
regulators, microRNAs (miRNAs) are a class of small, noncoding RNAs that take essential roles
in mammalian gene regulation in diverse cell types and tissues. Despite modest regulation of
individual targets, miRNAs broadly modulate a large number (60%) of genes and play important
roles in a wide range of biological processes. In mammalian skin, the critical functions of the
entire miRNA pathway in both embryonic skin development and maintenance of adult HF
lineages have been well appreciated. In contrast, the knowledge of individual miRNAs for their
targets and function remains scarce. Importantly, similar to other regulators, how miRNAs
regulate cell migration and proliferation has not been examined in the context of intact skin in
live animals. To address these important issues, we have developed techniques to directly
capture miRNA and their targeted mRNA fragments and to image cell migration and proliferation
as well as cytoskeleton dynamics in intact skin of live animals. Using these state-of-art tools
together with our mouse models, we find that miR-205, the most highly expressed miRNA in
epithelial stem cells, promotes cell migration by targeting components of adherens junctions,
actin cytoskeleton and mechanosensing genes in both epidermis and hair follicles. In this
project, we will further examine how miR-205-regulated cell migration alters the balance
between epidermal proliferation and differentiation in the epidermis (Aim 1); how miR-205-
induced cell migration triggers hair follicle growth in young and aged mice and how enhanced
hair follicle growth affects hair follicle stem cells (Aim 2); and probe how the loss of Piezo1, a
mechanically activated ion channel and a new miR-205 target, governs the quiescence of hair
follicle stem/progenitor cells (Aim 3). Taken together, studies proposed here, if successful, will
significantly enhance our knowledge about mechanisms mediated by individual miRNAs that
govern cell migration and proliferation in live animals. The knowledge gained from these studies
under normal and stressed conditions will pave the way to manipulate miRNAs and utilize
epithelial stem cells for regenerative medicine.

## Key facts

- **NIH application ID:** 10358643
- **Project number:** 5R01AR066703-09
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Rui Yi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $456,046
- **Award type:** 5
- **Project period:** 2014-07-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10358643

## Citation

> US National Institutes of Health, RePORTER application 10358643, Genetic Analysis of MicroRNA Functions in Skin Stem Cells In Vivo (5R01AR066703-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10358643. Licensed CC0.

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