Comprehensive analysis of intercellular communication in thermogenic adipose niche

Abstract Brown adipose tissue (BAT) is responsible for regulating body temperature through adaptive thermogenesis. Cold exposure remodels BAT by increasing the number and function of brown adipocytes, expanding the network of blood vessels and sympathetic nerves, and changing the makeup and function of immune cells. Such synergistic adaptation requires extensive intercellular crosstalk in adipose niche to coordinate their responses. To understand the mechanisms of intercellular communication, 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 temperatures, we found that cold exposure enhances the interactions among the major cell types in BAT, including adipocytes, adipocyte progenitors, lymphatic and vascular endothelial cells, myelinated and non-myelinated Schwann cells, and immune cells. These interactions regulate the remodeling of the extracellular matrix, inflammatory response, angiogenesis, and neurite growth. Together, our integrative analysis of intercellular communications in BAT and their dynamic regulation establishes a holistic understanding of the mechanisms involved in BAT thermogenesis. The resources presented in this study provide a valuable platform for investigations of BAT development and thermogenesis.