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

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 () and Lan Bai ()
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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

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41418-z

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