# Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin

> **NIH NIH R56** · CORNELL UNIVERSITY · 2022 · $397,841

## Abstract

Skin vasculature cross-talking with hair follicle stem cells (HFSCs) during hair cycle may control key steps of
adult skin homeostasis but is poorly understood. We have described a novel vasculature structure composed
primarily of blood vessels that undergoes remarkable remodeling during hair cycle in both mouse and human
skin. In particular, a horizontal(H) plexus(P) located under(u) the secondary hair(H) germ(G) at telogen might
enforces mouse HFSC quiescence. This may potentially occur through cell signaling from endothelial cells
towards the primed HFSC in the hair germ. If true, this finding would prove for the first time the skin endothelial
cells as novel dermal signaling niches for HFSCs. The cell signals at play in the communication between
endothelial cells and HFSC, as well as the nature and regulation of hair cycle vasculature remodeling, remain
currently unknown. Here we will rigorously address these questions in two specific and complementary aims,
with special emphasis on our novel vasculature structure, the HPuHG. First, we will examine distribution and
dynamic remodeling of different endothelial cell lineages and vascular structures during the hair cycle and
explore the genetic control of this remodeling (Aim1). Furthermore, we will systematically characterize the
molecular makeup of EC lineages and identify putative pathways of cross-talking with the hair follicle
epithelium. In particular, we will focus on the HPuHG interaction with the hair germ harboring the primed
HFSCs, which initiate the new hair growth cycle. Second, we will explore the mechanisms at play in the
communication from skin endothelial cells towards HFSCs by exploiting a relevant mouse model (the Alk1
endothelial-specific knockout) novel to hair cycle regulation (Aim2). We showed that in this mouse model the
vasculature near the hair germ (in the HPuHG) is increased at telogen and this is accompanied by delayed
HFSC activation. These phenotypes rationalize the exceptional fitness of this mouse model for further inquiry
into the nature of the cross-talking between endothelial cells and HFSCs. Using a candidate as well as an
unbiased approach we will explore mechanisms downstream of Alk1 in endothelial cells that may influence
HFSC activation timing. Collectively, this work will characterize remodeling of skin vasculature in hair cycle and
illuminate the communication between skin endothelial cells and HFSCs to coordinate tissue homeostasis. It
will have future broad relevance for human skin regeneration studies and for more in depth understanding of
skin vasculature disease.

## Key facts

- **NIH application ID:** 10696346
- **Project number:** 1R56AR081021-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Tudorita Tumbar
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $397,841
- **Award type:** 1
- **Project period:** 2022-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696346

## Citation

> US National Institutes of Health, RePORTER application 10696346, Investigating the coordinated endothelial-epithelial interactions in adult hair cycle of mouse skin (1R56AR081021-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10696346. Licensed CC0.

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