Mapping the molecular and structural specialization of the skin basement membrane for inter-tissue interactions

Ko Tsutsui,Ritsuko Morita,Hiroki Machida,Asako Nakagawa,Kiyotoshi Sekiguchi,Jeffrey H Miner,Kyungmin Ahn,Hironobu Fujiwara

doi:10.1038/s41467-021-22881-y

Abstract

Inter-tissue interaction is fundamental to multicellularity. Although the basement membrane (BM) is located at tissue interfaces, its mode of action in inter-tissue interactions remains poorly understood, mainly because the molecular and structural details of the BM at distinct inter-tissue interfaces remain unclear. By combining quantitative transcriptomics and immunohistochemistry, we systematically identify the cellular origin, molecular identity and tissue distribution of extracellular matrix molecules in mouse hair follicles, and reveal that BM composition and architecture are exquisitely specialized for distinct inter-tissue interactions, including epithelial–fibroblast, epithelial–muscle and epithelial–nerve interactions. The epithelial–fibroblast interface, namely, hair germ–dermal papilla interface, makes asymmetrically organized side-specific heterogeneity in the BM, defined by the newly characterized interface, hook and mesh BMs. One component of these BMs, laminin α5, is required for hair cycle regulation and hair germ–dermal papilla anchoring. Our study highlights the significance of BM heterogeneity in distinct inter-tissue interactions.

Highlights

Our study provides the comprehensive overview of the extracellular matrix (ECM) landscape within the adult hair follicle (HF) and highlights how basement membrane (BM) composition and structure are exquisitely tailored for individual inter-tissue interactions
Our study further reveals remarkable molecular complexity and spatial specialization of BMs in the hair germ (HG)–dermal papilla (DP) interface, which is involved in HF regeneration and HG–DP anchoring
Just before catagen entry, their deposition levels were again increased and they formed hook-like structures in regressing HFs. β1 integrin was tightly associated with the hook and interface BMs. These results demonstrate that hook BM components emerge and increase only when HG–DP interface decreases in size from late catagen to telogen, suggesting the functional importance of hook BMs and their interaction with integrins in anchoring the HG and DP

Summary

Introduction

Mouse hair follicle (HF) is an excellent model to investigate the formation and function of spatiotemporally specialized ECMs because this mini-organ is tiny, yet has clear epithelial and dermal compartments associated with specific tissue architecture and functions (Fig. 1a)[10,11]. Another prominent feature of the HF is its regenerative ability. HFs undergo cycles of regeneration (anagen), regression (catagen) and resting (telogen) phases during hair regeneration to continuously supply new hairs[12] This regenerative process is underpinned by epithelial stem cells residing in the basal layer around the HF bulge region. The BM at the HG–DP interface could be critical in the HF regeneration cycle, its molecular identities and functions, as for other regions of the HF, remain largely unknown

Methods

Results

Conclusion