Macrophages are essential immune cells present in all tissues, and are vital for maintaining tissue homeostasis, immune surveillance, and immune responses. Considerable efforts have identified shared and tissue-specific gene programs for macrophages across organs during homeostasis. This information has dramatically enhanced our understanding of tissue-restricted macrophage programming and function. However, few studies have addressed the overlapping and tissue-specific responses of macrophage subsets following inflammatory responses. One subset of macrophages that has been observed across several studies, lipid-associated macrophages (LAMs), have gained interest due to their unique role in lipid metabolism and potential as a therapeutic target. LAMs have been associated with regulating disease outcomes in metabolically related disorders including atherosclerosis, obesity, and nonalcoholic fatty liver disease (NAFLD). In this study, we utilized single-cell RNA sequencing (scRNAseq) data to profile LAMs across multiple tissues and sterile inflammatory conditions in mice and humans. Integration of data from various disease models revealed that LAMs share a set of conserved transcriptional profiles, including Trem2 and Lpl, but also identified key sets of tissue-specific LAM gene programs. Importantly, the shared LAM markers were highly conserved with human LAM populations that also emerge in chronic inflammatory settings. Overall, this analysis provides a detailed transcriptional landscape of tissue-restricted and shared LAM gene programs and offers insights into their roles in metabolic and chronic inflammatory diseases. These data may help instruct appropriate targets for broad or tissue-restricted therapeutic interventions to modulate LAM populations in disease.
