MACanalyzeR: scRNA-seq Analysis Tool Reveals PPARγHI Lipid-Associated Macrophages Facilitate Thermogenic Expansion in BAT

Ninni, A.; Zaccaria, F.; Verteramo, L.; Sciarretta, F.; Silveira, L. S.; Rosa-Neto, J. C.; Grumati, P.; Rizzo, G.; Cochain, C.; Williams, J. W.; Ivanov, S.; Zhou, B.; Aquilano, K.; Lettieri-Barbato, D.

doi:10.1101/2024.07.29.605588

bioRxiv · 10.1101/2024.07.29.605588

MACanalyzeR: scRNA-seq Analysis Tool Reveals PPARγHI Lipid-Associated Macrophages Facilitate Thermogenic Expansion in BAT

Ninni, A.·Zaccaria, F.·Verteramo, L.·Sciarretta, F.·Silveira, L. S.·Rosa-Neto, J. C.·Grumati, P.·Rizzo, G.·Cochain, C.·Williams, J. W.·Ivanov, S.·Zhou, B.·Aquilano, K.·Lettieri-Barbato, D.

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Abstract

Macrophages in brown adipose tissue (BAT) play a complex role in regulating its activity. However, the role of macrophages in regulating BAT activation/deactivation has not yet been comprehensively characterized. To elucidate this, we developed MACanalyzeR, a scRNAseq-based tool specifically designed to explore the macrophage features at molecular and metabolic level. MACanalyzeR was applied in scRNA-seq datasets obtained from BAT with thermogenic loss (db/db mice) and activation (High Fat Diet, HFD). Our computational approach revealed that macrophages accumulating in BAT upon these conditions resemble lipid-associated macrophages (LAMs) with foaming-like features. BAT LAMs also show a significant enrichment of genes associated with mitochondria and lysosomes. Interestingly, LAMs identified in BAT from HFD mice positively correlate with thermogenic genes and exhibit an enrichment in PPAR{gamma} signaling pathway, with an activated mitochondrial metabolism. Cell dynamic strategy, revealed that LAM with high Pparg expression levels (PpargHIGH) progressively accumulate during skeletal muscle regeneration, suggesting a potential role for this LAM subcluster in maintaining tissue homeostasis. Our findings suggest PpargHIGH LAMs as a subclass of macrophages potentially contributing in preserving tissue homeostasis associated with high energy demand conditions such as thermogenic and regenerative stimuli.

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Ninni, A., Zaccaria, F., Verteramo, L., Sciarretta, F., Silveira, L. S., Rosa-Neto, J. C., Grumati, P., Rizzo, G., Cochain, C., Williams, J. W., Ivanov, S., Zhou, B., Aquilano, K., Lettieri-Barbato, D.. 2024-07-29. MACanalyzeR: scRNA-seq Analysis Tool Reveals PPARγHI Lipid-Associated Macrophages Facilitate Thermogenic Expansion in BAT. https://doi.org/10.1101/2024.07.29.605588

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