A CCL2 + DPP4 + subset of mesenchymal stem cells expedites aberrant formation of creeping fat in humans.
Fengfei WuFangting WuQian ZhouXi LiuJieying FeiDa ZhangWeidong WangYi TaoYubing LinQiaoqiao LinXinghua PanKai SunFang XieLan BaiPublished in: Nature communications (2023)
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.
Keyphrases
- adipose tissue
- mesenchymal stem cells
- insulin resistance
- high fat diet
- fatty acid
- end stage renal disease
- ejection fraction
- newly diagnosed
- umbilical cord
- liver injury
- bone marrow
- prognostic factors
- systemic sclerosis
- dendritic cells
- anti inflammatory
- gene expression
- type diabetes
- idiopathic pulmonary fibrosis
- deep learning
- genome wide
- patient reported outcomes
- rna seq
- drug induced
- immune response