snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis

• Published in: Nature (London) 2020-11, Vol.587 (7832), p.98-102
• Main Authors: Sun, Wenfei, Dong, Hua, Balaz, Miroslav, Slyper, Michal, Drokhlyansky, Eugene, Colleluori, Georgia, Giordano, Antonio, Kovanicova, Zuzana, Stefanicka, Patrik, Balazova, Lucia, Ding, Lianggong, Husted, Anna Sofie, Rudofsky, Gottfried, Ukropec, Jozef, Cinti, Saverio, Schwartz, Thue W., Regev, Aviv, Wolfrum, Christian
• Format: Article
• Language: English
• Subjects: 13/106; 13/109; 13/31; 13/51; 13/62; 13/89; 14; 14/1; 14/19; 14/28; 631/80/304; 692/163/2743; 692/308/575; Acetates - metabolism; Adipocytes; Adipocytes - metabolism; Adipose Tissue, Brown - cytology; Adipose Tissue, Brown - metabolism; Adult; Aged; Aldehyde Dehydrogenase 1 Family - genetics; Aldehyde Dehydrogenase 1 Family - metabolism; Animals; Biomarkers; Cell Nucleus - genetics; Cell Separation; Cold; Cytochrome P-450 CYP2E1 - genetics; Cytochrome P-450 CYP2E1 - metabolism; Energy Metabolism; Exposure; Female; Fluorescence; Gene sequencing; Genes; Genomics; Humanities and Social Sciences; Humans; Male; Metabolism; Mice; Middle Aged; multidisciplinary; Nuclei; Nuclei (cytology); Paracrine Communication; Population; Preadipocytes; Red fluorescent protein; Retinal Dehydrogenase - genetics; Retinal Dehydrogenase - metabolism; RNA-Seq; Room temperature; Science; Science (multidisciplinary); Single-Cell Analysis; snRNA; Stromal cells; Subpopulations; Thermogenesis; Thermogenesis - genetics; Transgenic mice; Young Adult
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2856-x

Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite) 1 . It is an important regulator of systemic metabolism, as shown by the fact that dysfunctional adipose tissue in obesity leads to a variety of secondary metabolic complications 2 , 3 . In addition, adipose tissue functions as a signalling hub that regulates systemic metabolism through paracrine and endocrine signals 4 . Here we use single-nucleus RNA-sequencing (snRNA-seq) analysis in mice and humans to characterize adipocyte heterogeneity. We identify a rare subpopulation of adipocytes in mice that increases in abundance at higher temperatures, and we show that this subpopulation regulates the activity of neighbouring adipocytes through acetate-mediated modulation of their thermogenic capacity. Human adipose tissue contains higher numbers of cells of this subpopulation, which could explain the lower thermogenic activity of human compared to mouse adipose tissue and suggests that targeting this pathway could be used to restore thermogenic activity. Single-nucleus RNA sequencing in mouse and human adipose tissue identifies a subpopulation of adipocytes that regulates thermogenesis in neighbouring adipocytes in a paracrine manner by modulating acetate signalling.