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

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.

Lymph vessels find a hairy niche

“…The timing of this study coincides nicely with recent findings that cutaneous blood vessels also contribute to regulation of HF cycling via angiocrine factors that maintain the quiescence of the stem cell population (Li et al , ). In line, various studies described vascular niches as important determinants for the development and maintenance of various tissue‐specific stem cell populations (Rafii et al , ).…”

The Hair Follicle as an Interdisciplinary Model for Biomedical Research: An Eclectic Literature Synthesis

“…Continuing on the theme of HF stem cell biology, some fascinating insights into the cross‐talk that occurs between the HFSCs and the skin vasculature, perifollicular immune cells, and dermal sheath have been published. [ 29–31 ] This is in addition to the recently identified communication between HF stem cell compartments and the lymphatic vasculature, described by two independent groups. [ 32,33 ] These vessels were shown to be crucial components of the HFSC niche; whereby secreted signals from the stem cells influence the dynamic behavior of the lymphatics and loss of lymph vessels perturbs HF growth.…”

An Intrinsic Oscillation of Gene Networks Inside Hair Follicle Stem Cells: An Additional Layer That Can Modulate Hair Stem Cell Activities

“…The HF bulge area is surrounded by blood vessels (part of dermal vasculature – superficial vascular plexus) that provide the nutritional and hormonal input into the hfSCs population, which was confirmed by recent research illustrating the connection between the bulge SCs and the perivascular niche ( Amoh et al, 2004 ; Xiao et al, 2013 ). Additional research has confirmed that the hair cycle depends on cutaneous angiogenesis and identified Bmp4 regulation as one of the main inhibitory factors of hfSCs anagen progression ( Mecklenburg et al, 2000 ; Li et al, 2019 ). Furthermore, the K15 negative upper bulge cells located adjacent to the vascular annulus express a signaling factor EGF-like domain- multiple 6 (Egfl6), which is involved in angiogenesis and the recruitment of vascular endothelial cells ( Xiao et al, 2013 ).…”