# Delineating spatiotemporal dynamics of hair follicle dermal niche specification at the single-cell level

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $368,500

## Abstract

SUMMARY
The hair follicle (HF) is composed of an epithelial and dermal population and is a classic model to study the
epithelial-mesenchymal interactions governing appendage development. During HF development, the first
morphologically distinct dermal population is the dermal condensate (DC), a dense cluster of specialized cells
that matures into the dermal papilla (DP). As the DP holds the revered capacity to induce new HF growth, large
efforts have been made to program undifferentiated fibroblasts into differentiated DC/DP cells but met with
limited efficacy. The principal challenge has been the inability to assess molecular differences between cells
before they are morphologically apparent. As such, we lack a molecular “roadmap” of the transition states that
direct lineage commitment and morphogenesis that could guide faithful methods to recapitulate these events in
vitro. To meet this challenge, we recently used an unbiased diffusion map technique to systemize single-cell
RNA sequencing (scRNA-seq) data from mouse embryonic skin. Using this technique, we identified a
molecular DC differentiation trajectory, an inferred pathway of transcriptional states through which DC cells
pass, before and during HF morphogenesis. Guided by this map, we showed that dermal Wnt/-catenin
signaling is required to progress to an intermediate phase of DC cell differentiation and that DC cells are
immediate quiescent progeny of a molecularly distinct (Dkk1+), highly proliferative population. Currently, the
critical transition steps that Dkk1+ cells pass through and the signals that regulate them remain unknown.
Combining innovative computational methods and mouse models, our preliminary data reveal that Dkk1+
progenitors utilize two molecular pathways to generate DC cells that distinguishes DC initiation from DC
expansion processes prior to morphogenesis. We hypothesize that DC formation is a dynamic process wherein
DC initiation and DC expansion utilize distinct molecular pathways to generate DC cells and that signals that
regulate the transition from proliferation to quiescence are essential for DC differentiation by Dkk1+
progenitors. In this grant, we use an integrative approach to build a temporospatial map of DC transition states
that govern DC formation. In Aim 1, we will couple transcriptional kinetic scRNA-seq data (RNA velocity) with
in vivo lineage tracing to define transition steps that lead to DC initiation and DC expansion, coupled with live
imaging and quantitative FISH to spatially locate critical transition steps. Using this same approach, we will
define how local epithelial signals regulate key transition states within distinct DC paths. In Aim 2, we will
examine the role of local proliferation in DC formation and signals (e.g. YAP/TAZ) that regulate the transition
between proliferation and quiescence using genetic mouse models. This complementary approach will
overcome major challenges in dissecting the early events that lead to DC cell fate. T...

## Key facts

- **NIH application ID:** 10051158
- **Project number:** 1R01AR076420-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Peggy S Myung
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $368,500
- **Award type:** 1
- **Project period:** 2020-07-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051158

## Citation

> US National Institutes of Health, RePORTER application 10051158, Delineating spatiotemporal dynamics of hair follicle dermal niche specification at the single-cell level (1R01AR076420-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10051158. Licensed CC0.

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