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| Status |
Public on Feb 11, 2022 |
| Title |
Obesity-induced senescent macrophages activate a fibrotic transcriptional program in adipocyte progenitors |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Adipose tissue fibrosis is regulated by the chronic and progressive metabolic imbalance caused by differences in caloric intake and energy expenditure. By exploring the cellular heterogeneity within fibrotic adipose tissue, we demonstrate that early adipocyte progenitor cells expressing both platelet derived growth factor receptor (PDGFR) α and β are the major contributors to extracellular matrix deposition. We show that the fibrotic program is promoted by senescent macrophages. These macrophages were enriched in the fibrotic stroma and exhibit a distinct expression profile. Furthermore, we demonstrate that these cells display a blunted phagocytotic capacity and acquire a senescence-associated secretory phenotype. Finally, we determined that osteopontin, which was expressed by senescent macrophages in the fibrotic environment promoted progenitor cell proliferation, fibrotic gene expression, and inhibited adipogenesis. Our work reveals that obesity promotes macrophage senescence and provides a conceptual framework for the discovery of rational therapeutic targets for metabolic and inflammatory disease associated with obesity.
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| Overall design |
Single cell of the stromal vascular fraction from mice epididymal adipose tissue following 24 weeks of either high fat or low fat diet feeding
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| Contributor(s) |
Rabhi N, Desevin K, Belkina AC, Desevin K, Tilston-Lunel A, Varelas X, Layne MD, Farmer SR |
| Citation(s) |
35181634 |
| Submission date |
Jan 25, 2022 |
| Last update date |
Mar 15, 2022 |
| Contact name |
Nabil Rabhi |
| E-mail(s) |
rabhi@bu.edu
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| Phone |
8572659274
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| Organization name |
Boston University
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| Department |
Biochemistry
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| Lab |
Farmer Lab
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| Street address |
Silvio Conte Building, 72 E. Concord St
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| City |
Boston |
| State/province |
Massachusetts |
| ZIP/Postal code |
02118 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA800421 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE194399_RAW.tar |
17.5 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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