Lobular architecture of human adipose tissue defines the niche and fate of progenitor cells

D Estève,Y Veeranagouda,A Briot,M Didier,C Dani,A Zakaroff-Girard,N Boulet,C Belles,S Ledoux,A Remaury,P Decaunes,A Bouloumié,J C Guillemot,J Galitzky

doi:10.1038/s41467-019-09992-3

Abstract

Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. Here we report that lobules are composed of two extracellular matrix compartments, i.e., septa and stroma, delineating niches of CD45−/CD34+/CD31− progenitor subsets characterized by MSCA1 (ALPL) and CD271 (NGFR) expression. MSCA1+ adipogenic subset is enriched in stroma while septa contains mainly MSCA1−/CD271− and MSCA1−/CD271high progenitors. CD271 marks myofibroblast precursors and NGF ligand activation is a molecular relay of TGFβ-induced myofibroblast conversion. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. Thus, the human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks.

Highlights

Human adipose tissue is constituted of structural units termed lobules, the organization of which remains to be defined
Adipogenesis is a sequential cellular event starting from immature mesenchymal progenitor cells that once committed into preadipocytes differentiate into adipocytes
Immunostaining of COLLAGEN 1 (COL1) underlined both compartments with a marked accumulation of COLLAGEN 1 in the septa compared with the stroma, while CD34 immunostaining revealed the presence of

Summary

Introduction

Human adipose tissue (hAT) is constituted of structural units termed lobules, the organization of which remains to be defined. In human subcutaneous (SC) and visceral (VS) AT, the progenitor subset repartition is different, modulated by obesity and in favor of adipocyte and myofibroblast fate, respectively. Lobules exhibit depot-specific architecture with marked fibrous septa containing mesothelial-like progenitor cells in VSAT. The human AT lobule organization in specific progenitor subset domains defines the fat depot intrinsic capacity to remodel and may contribute to obesity-associated cardiometabolic risks. The intrinsic property of a fat depot to handle lipids in excess (or its expandability) is determined by the metabolic fitness of mature adipocytes and its capacity to produce new adipocytes by adipogenesis[5]. In addition to commitment into an adipogenic lineage, human AT progenitor cells exhibit a myofibroblastic potential in response to TGFβ1 stimulation and are suspected to be involved in fibrosis[13,14]

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