Single cell analysis reveals immune cell–adipocyte crosstalk regulating the transcription of thermogenic adipocytes
Prashant Rajbhandari,
Douglas Arneson,
Sydney K Hart,
In Sook Ahn,
Graciel Diamante,
Luis C Santos,
Nima Zaghari,
An-Chieh Feng,
Brandon J Thomas,
Laurent Vergnes,
Stephen D Lee,
Abha K Rajbhandari,
Karen Reue,
Stephen T Smale,
Xia Yang,
Peter Tontonoz
Affiliations
Prashant Rajbhandari
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States; Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, United States
Douglas Arneson
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States
Sydney K Hart
Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, United States
In Sook Ahn
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States
Graciel Diamante
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States
Luis C Santos
Diabetes, Obesity, and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, United States
Nima Zaghari
Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States
An-Chieh Feng
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Brandon J Thomas
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States
Laurent Vergnes
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States
Stephen D Lee
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States
Abha K Rajbhandari
Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, United States
Karen Reue
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
Stephen T Smale
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
Xia Yang
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, United States; Bioinformatics Interdepartmental Program, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States
Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, United States; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States; Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States
Immune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.
