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

Kefei Nina Li,Catherine Hua He,Prachi Jain,Tudorita Tumbar,Flora Chae Eun,Sangjo Kang

doi:10.7554/elife.45977

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.

Highlights

Stem cell (SC) maintenance and function depend on signals from their local microenvironment, the SC niche
To understand in detail how the skin vasculature is remodeled near the hair follicle stem cells (HFSCs) activation zone in the hair germ during hair cycle, we sacrificed C57BL/6 wild type mice at late catagen (PD19), telogen (PD20), early anagen (PD21) and anagen (PD28) (Figure 1 and Figure 1—figure supplement 1)
We provide the first evidence for reciprocal communication that exists between vasculature and HFSCs in the hair germ during late quiescence stages of hair cycle, a stage, skin location, and specific question not examined by previous work of vasculature in the skin (Mecklenburg et al, 2000; Xiao et al, 2013; Yano et al, 2001; Zhuang et al, 2018)

Summary

Introduction

Stem cell (SC) maintenance and function depend on signals from their local microenvironment, the SC niche. Mesenchymal, and hematopoietic SCs neighbor the vasculature, which supplies oxygen and nutrients and provides molecular signals to the stem cells (Goldberg and Hirschi, 2009; Gomez-Gaviro et al, 2012; Oh and Nor, 2015; Waldau, 2015), through endothelial cells (Azevedo et al, 2017; Gao et al, 2018; Perlin et al, 2017). We proposed a hypothetical model in which adult epithelial HFSCs cluster in their tissue residence (the bulge) to produce gradients of signaling molecules that might remodel the surrounding microenvironment (Fuchs et al, 2004; Tumbar et al, 2004)

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