Skin vasculature and hair follicle cross-talking associated with stem cell activation and tissue homeostasis

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Abstract

Skin vasculature cross-talking with hair follicle stem cells (HFSCs) is poorly understood. Skin vasculature undergoes dramatic remodeling during adult mouse hair cycle. Specifically, a horizontal plexus under the secondary hair germ (HPuHG) transiently neighbors the HFSC activation zone during the quiescence phase (telogen). Increased density of HPuHG can be induced by reciprocal mutations in the epithelium (Runx1) and endothelium (Alk1) in adult mice, and is accompanied by prolonged HFSC quiescence and by delayed entry and progression into the hair growth phase (anagen). Suggestively, skin vasculature produces BMP4, a well-established HFSC quiescence-inducing factor, thus contributing to a proliferation-inhibitory environment near the HFSC. Conversely, the HFSC activator Runx1 regulates secreted proteins with previously demonstrated roles in vasculature remodeling. We suggest a working model in which coordinated remodeling and molecular cross-talking of the adult epithelial and endothelial skin compartments modulate timing of HFSC activation from quiescence for proper tissue homeostasis of adult skin.

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All data generated or analysed during this study are included in the manuscript and supporting files

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Kefei Nina Li

Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States

Competing interests
The authors declare that no competing interests exist.
Prachi Jain

Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States

Competing interests
The authors declare that no competing interests exist.
Catherine Hua He

Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States

Competing interests
The authors declare that no competing interests exist.
Flora Chae Eun

Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States

Competing interests
The authors declare that no competing interests exist.
Sangjo Kang

Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States

Competing interests
The authors declare that no competing interests exist.
Tudorita Tumbar

Molecular Biology and Genetics, Cornell University, Ithaca, Ithaca, United States

For correspondence
tt252@cornell.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-2273-1889

Funding

National Institute of Arthritis and Musculoskeletal and Skin Diseases (RO1 AR070157)

Tudorita Tumbar

NYSTEM (DOH01-C30293GG-3450000)

Prachi Jain

National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR073806)

Tudorita Tumbar

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Mouse work followed the Cornell University Institutional Animal Care and Use Committee guidelines. IACUC protocol # 2007-0125.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.