Abstract/ Significance:

Systematic characterizations of adipose regulatory T (Treg) cell subsets and their phenotypes remain uncommon. Using single-cell ATAC-sequencing and paired single-cell RNA and T cell receptor (TCR) sequencing to map mouse adipose Treg cells, we identified CD73hiST2lo and CD73loST2hi subsets with distinct clonal expansion patterns. Analysis of TCR-sharing data implied a state transition between CD73hiST2lo and CD73loST2hi subsets. Mechanistically, we revealed that insulin signaling occurs through a HIF-1α–Med23–PPAR-γ axis to drive the transition of CD73hiST2lo into a CD73loST2hi adipose Treg cell subset. Treg cells deficient in insulin receptor, HIF-1α or Med23 have decreased PPAR-γ expression that in turn promotes accumulation of CD73hiST2lo adipose Treg cells and physiological adenosine production to activate beige fat biogenesis. We therefore unveiled a developmental trajectory of adipose Treg cells and its dependence on insulin signaling. Our findings have implications for understanding the dynamics of adipose Treg cell subsets in aged and obese contexts.

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In this study, Nt5efl/fl mice from GemPharmatech (strain ID, T009196) were crossed with Foxp3Cre us to ablate Ntfe in Tregs.

Find out more about GemPharmatech’s KOAP and their growing repository.

DOI:

https://doi.org/10.1038/s41590-021-01010-3

Tags: conditional knockout, cre/lox, CRISPR, Gene Editing, Genetically Modified Mouse Models, knockout, KOAP, mousemodels, Transgenic