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| Status |
Public on Feb 05, 2024 |
| Title |
Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
Foxp3+CD4+ regulatory T (Treg) cells found within tissues regulate local immunity, inflammation and homeostasis. Tregs in epididymal visceral adipose tissue (eVAT) are critical regulators of local and systemic inflammation and metabolism. During aging and under obesogenic conditions, eVAT Tregs undergo transcriptional and phenotypic changes and are important for containing inflammation and normalizing metabolic indices. We have employed single-cell RNA sequencing, single-cell Tra and Trb sequencing, adoptive transfers, photoconvertible mice, cellular interaction analyses and in vitro cultures to dissect the evolving heterogeneity of eVAT Tregs with aging and obesity. Distinct Treg subtypes with distinguishable gene-expression profiles and functional roles were enriched at differing ages and with differing diets. Like those in lean mice, eVAT Tregs in obese mice were not primarily recruited from the circulation but instead underwent local expansion and had a distinct and diversified T cell receptor repertoire. The different eVAT-Treg subtypes specialized in different functions; for example, the subtypes enriched in lean, but not obese, mice suppressed adipogenesis. The existence of functionally divergent eVAT-Treg subtypes in response to obesogenic conditions presents possibilities for precision therapeutics in the context of obesity.
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| Overall design |
We investigated how the heterogeneity of the eVAT SVF and Treg compartments evolved with aging and obesity. 14-wk-old Foxp3-GFP mice were placed on a low-fat or high-fat diet for 16 weeks. For scRNA-seq, the total SVF and Tregs sorted from eVAT of the mice, hashed by individual groups, and encapsulated with the Chromium 3' v3 platform. For joint scRNA-seq and scTra/b-seq, Tregs sorted from eVAT and spleen of lean and obese mice were encapsulated using the Chromium Single Cell 5' v2 and V(D)J platform (10X Genomics). Data from two independent experiments.
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| Contributor(s) |
Muñoz-Rojas AR, Benoist C, Mathis D |
| Citation missing |
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| Submission date |
Nov 22, 2023 |
| Last update date |
Feb 06, 2024 |
| Contact name |
CBDM Lab |
| E-mail(s) |
cbdm@hms.harvard.edu
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| Phone |
617-432-7747
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| Organization name |
Harvard Medical School
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| Department |
Microbiology and Immunobiology
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| Lab |
CBDM
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| Street address |
77 Avenue Louis Pasteur
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (10)
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| GSM7914417 |
GEX:eVAT SVF 14wk LFD and eVAT SVF 14/16wk LFD/LFD and eVAT SVF 14/16wk LFD/HFD (exp1) |
| GSM7914418 |
GEX:eVAT SVF 14wk LFD and eVAT SVF 14/16wk LFD/LFD and eVAT SVF 14/16wk LFD/HFD (exp2) |
| GSM7914419 |
GEX:eVAT Tregs 14wk LFD and eVAT Tregs 14/16wk LFD/LFD and eVAT Tregs 14/16wk LFD/HFD (exp1) |
| GSM7914420 |
GEX:eVAT Tregs 14wk LFD and eVAT Tregs 14/16wk LFD/LFD and eVAT Tregs 14/16wk LFD/HFD (exp2) |
| GSM7914421 |
GEX:eVAT Lean and eVAT Obese and Spleen Lean and Spleen Obese (exp3) |
| GSM7914422 |
GEX:eVAT Lean and eVAT Obese and Spleen Lean and Spleen Obese (exp4) |
| GSM7914423 |
FBC:eVAT Lean and eVAT Obese and Spleen Lean and Spleen Obese (exp3) |
| GSM7914424 |
FBC:eVAT Lean and eVAT Obese and Spleen Lean and Spleen Obese (exp4) |
| GSM7914425 |
TCR:eVAT Lean and eVAT Obese and Spleen Lean and Spleen Obese (exp3) |
| GSM7914426 |
TCR:eVAT Lean and eVAT Obese and Spleen Lean and Spleen Obese (exp4) |
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| Relations |
| BioProject |
PRJNA1044014 |
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