Transcriptional characterization of visceral adipose tissue (VAT) mesenchymal stromal cell (mSC) subtypes in male and female C57BL/6 mice.

Regulatory T cells (Tregs) are key brakes on the VAT inflammation that regulates local and systemic metabolic tenor. The cytokine, IL-33, expands and sustains the unique Treg population residing within VAT. Making use of single-cell RNA sequencing, we identified the major IL-33 producers in VAT to be particular mSC subtypes, related to but distinct from adipocyte progenitor cells. We further characterize these subsets by individually isolating them and performing bulk-RNA sequencing. We explored modulation of the VAT-mSC (VmSC) landscape with physiologic variables such as age and sex, as well as pathogenic states like obesity. We uncovered a VAT Treg:stromal-cell negative regulatory loop that keeps the potent effect of IL-33 under rein. Overall design: Gene expression profiles of VmSC subtypes from young male and female mice. 2-4 mice were pooled for each biological replicate and at least 2 biological replicates were obtained per VmSC subtype.

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Spallanzani RG, Zemmour D, Xiao T, Jayewickreme T, Li C, Bryce PJ, Benoist C, Mathis D