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A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans

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Listed:
  • Fengfei Wu

    (Southern Medical University)

  • Fangting Wu

    (Southern Medical University)

  • Qian Zhou

    (Southern Medical University)

  • Xi Liu

    (Southern Medical University)

  • Jieying Fei

    (Southern Medical University)

  • Da Zhang

    (Southern Medical University)

  • Weidong Wang

    (Southern Medical University)

  • Yi Tao

    (Southern Medical University)

  • Yubing Lin

    (Southern Medical University)

  • Qiaoqiao Lin

    (Southern Medical University)

  • Xinghua Pan

    (Southern Medical University, and Guangdong Provincial Key Laboratory of Single Cell Technology and Application)

  • Kai Sun

    (Southern Medical University)

  • Fang Xie

    (Southern Medical University)

  • Lan Bai

    (Southern Medical University)

Abstract

Creeping fat is a typical feature of Crohn’s disease. It refers to the expansion of mesenteric adipose tissue around inflamed and fibrotic intestines and is associated with stricture formation and intestinal obstruction. In this study, we characterize creeping fat as pro-adipogenic and pro-fibrotic. Lipidomics analysis of Crohn’s disease patients (sixteen males, six females) and healthy controls (five males, ten females) reveals abnormal lipid metabolism in creeping fat. Through scRNA-seq analysis on mesenteric adipose tissue from patients (five males, one female) and healthy controls (two females), we identify a CCL2+DPP4+ subset of mesenchymal stem cells that expands in creeping fat and expedites adipogenic differentiation into dystrophic adipocytes in response to CCL20+CD14+ monocytes and IL-6, leading to the formation of creeping fat. Ex vivo experiments (tissues from five males, one female) confirm that both CCL20+CD14+ monocytes and IL-6 activate DPP4+ mesenchymal stem cells towards a pro-adipogenic phenotype. This study provides a comprehensive investigation of creeping fat formation and offers a conceptual framework for discovering therapeutic targets for treatment of Crohn’s disease.

Suggested Citation

  • Fengfei Wu & Fangting Wu & Qian Zhou & Xi Liu & Jieying Fei & Da Zhang & Weidong Wang & Yi Tao & Yubing Lin & Qiaoqiao Lin & Xinghua Pan & Kai Sun & Fang Xie & Lan Bai, 2023. "A CCL2+DPP4+ subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41418-z
    DOI: 10.1038/s41467-023-41418-z
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    1. Shikha Nayar & Joshua K. Morrison & Mamta Giri & Kyle Gettler & Ling-shiang Chuang & Laura A. Walker & Huaibin M. Ko & Ephraim Kenigsberg & Subra Kugathasan & Miriam Merad & Jaime Chu & Judy H. Cho, 2021. "A myeloid–stromal niche and gp130 rescue in NOD2-driven Crohn’s disease," Nature, Nature, vol. 593(7858), pages 275-281, May.
    2. Petra C. Schwalie & Hua Dong & Magda Zachara & Julie Russeil & Daniel Alpern & Nassila Akchiche & Christian Caprara & Wenfei Sun & Kai-Uwe Schlaudraff & Gianni Soldati & Christian Wolfrum & Bart Depla, 2018. "A stromal cell population that inhibits adipogenesis in mammalian fat depots," Nature, Nature, vol. 559(7712), pages 103-108, July.
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