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<p>Adipose tissue homeostasis depends on an intact vascular network that ensures adequate nutrient delivery and immune regulation. In obesity, vascular dysfunction, particularly within endothelial cells (ECs), contributes to inflammation and metabolic disease progression, yet the cellular organization of the human adipose vasculature remains poorly defined. Here we show, using single-cell RNA sequencing of nearly 70,000 vascular cells from human subcutaneous adipose tissue of 65 individuals, that the adipose vasculature is highly heterogeneous and consists of seven canonical EC subtypes. In addition, we identify a distinct population of ECs that display mixed endothelial, mesenchymal, adipocytic and immune transcriptional features. Computational analyses and whole-mount imaging support their presence and suggest that they emerge through endothelial-to-mesenchymal transition. Comparative analyses further reveal inflammatory and fibrotic vascular signatures in obesity and type 2 diabetes. Together, this atlas delineates the cellular complexity of the human adipose vasculature and highlights its contribution to metabolic disease.</p>

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Defining the vascular niche of human adipose tissue across metabolic states

  • 期刊论文

  • 发表日期：

    2026年3月12日

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  • Ibrahim AlZaim,
  • Mohamed N. Hassan,
  • Maja Schröter,
  • Luca Mannino,
  • Katarina Dragicevic,
  • Marie Balle Sjogaard,
  • Joseph Festa,
  • Lolita Dokshokova,
  • Sophie Weinbrenner,
  • Blanca Tardajos Ayllon,
  • Bettina Hansen,
  • Rikke Kongsgaard Rasmussen,
  • Julie N. Christensen,
  • Olivia Wagman,
  • Ruby Schipper,
  • Min Cai,
  • Wouter Dheedene,
  • Anja Bille Bohn,
  • Jean Farup,
  • Lin Lin,
  • Samuele Soraggi,
  • Anna Dalsgaard Thorsen,
  • Amanda Bæk,
  • Henrik Holm Thomsen,
  • Maximilian von Heesen,
  • Lena-Christin Conradi,
  • Paul Evans,
  • Carolina E. Hagberg,
  • Joerg Heeren,
  • Margo Emont,
  • Evan D. Rosen,
  • Aernout Luttun,
  • Anders Etzerodt,
  • Lucas Massier,
  • Mikael Rydén,
  • Niklas Mejhert,
  • Matthias Blüher,
  • Konstantin Khodosevich,
  • Robert A. Fenton,
  • Bilal N. Sheikh,
  • Niels Jessen,
  • Laura P.M.H. de Rooij,
  • Joanna Kalucka

摘要

Adipose tissue homeostasis depends on an intact vascular network that ensures adequate nutrient delivery and immune regulation. In obesity, vascular dysfunction, particularly within endothelial cells (ECs), contributes to inflammation and metabolic disease progression, yet the cellular organization of the human adipose vasculature remains poorly defined. Here we show, using single-cell RNA sequencing of nearly 70,000 vascular cells from human subcutaneous adipose tissue of 65 individuals, that the adipose vasculature is highly heterogeneous and consists of seven canonical EC subtypes. In addition, we identify a distinct population of ECs that display mixed endothelial, mesenchymal, adipocytic and immune transcriptional features. Computational analyses and whole-mount imaging support their presence and suggest that they emerge through endothelial-to-mesenchymal transition. Comparative analyses further reveal inflammatory and fibrotic vascular signatures in obesity and type 2 diabetes. Together, this atlas delineates the cellular complexity of the human adipose vasculature and highlights its contribution to metabolic disease.