Comprehensive analysis of intercellular communication in thermogenic adipose niche

Abstract

Brown adipose tissue (BAT) is responsible for regulating body temperature through adaptive thermogenesis. The ability of thermogenic adipocytes to dissipate chemical energy as heat counteracts weight gain and has gained considerable attention as a strategy against obesity. BAT undergoes major remodeling in a cold environment. This remodeling results from changes in the number and function of brown adipocytes, expanding the network of blood vessels and sympathetic nerves, and changes in the makeup and function of immune cells. All these processes are essential for enhanced BAT thermogenesis to maintain euthermia in the cold. Such synergistic adaptation requires extensive crosstalk between the individual cells in tissues to coordinate their responses. To understand the mechanisms of intercellular communication in BAT, we applied the CellChat algorithm to single-cell transcriptomic data of mouse BAT. We constructed an integrative network of ligand-receptor interactome in BAT and identified the major signaling input and output of each cell type. By comparing the ligand-receptor interactions in BAT of mice housed at different environmental temperatures, we found that cold exposure enhances the intercellular interactions among the major cell types in BAT, including adipocytes, adipocyte progenitors, lymphatic and vascular endothelial cells, myelinated Schwann cells (MSC), nonmyelinated Schwann cells (NMSC), and immune cells. Furthermore, we identified the ligands and receptors that are regulated at the transcriptional level by temperature. These interactions are predicted to regulate the remodeling of extracellular matrix (ECM), inflammatory response, angiogenesis, and neurite growth. Together, our integrative analysis of intercellular communications in BAT and their dynamic regulation in response to housing temperatures establishes a holistic understanding of the mechanisms involved in BAT thermogenesis. The resources presented in this study provide a valuable platform for future investigations of BAT development and thermogenesis.