RT Journal Article SR Electronic T1 Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000924 DO 10.26508/lsa.202000924 VO 4 IS 1 A1 Karlina, Ruth A1 Lutter, Dominik A1 Miok, Viktorian A1 Fischer, David A1 Altun, Irem A1 Schöttl, Theresa A1 Schorpp, Kenji A1 Israel, Andreas A1 Cero, Cheryl A1 Johnson, James W A1 Kapser-Fischer, Ingrid A1 Böttcher, Anika A1 Keipert, Susanne A1 Feuchtinger, Annette A1 Graf, Elisabeth A1 Strom, Tim A1 Walch, Axel A1 Lickert, Heiko A1 Walzthoeni, Thomas A1 Heinig, Matthias A1 Theis, Fabian J A1 García-Cáceres, Cristina A1 Cypess, Aaron M A1 Ussar, Siegfried YR 2021 UL http://www.life-science-alliance.org/content/4/1/e202000924.abstract AB Brown adipose tissue (BAT) plays an important role in the regulation of body weight and glucose homeostasis. Although increasing evidence supports white adipose tissue heterogeneity, little is known about heterogeneity within murine BAT. Recently, UCP1 high and low expressing brown adipocytes were identified, but a developmental origin of these subtypes has not been studied. To obtain more insights into brown preadipocyte heterogeneity, we use single-cell RNA sequencing of the BAT stromal vascular fraction of C57/BL6 mice and characterize brown preadipocyte and adipocyte clonal cell lines. Statistical analysis of gene expression profiles from brown preadipocyte and adipocyte clones identify markers distinguishing brown adipocyte subtypes. We confirm the presence of distinct brown adipocyte populations in vivo using the markers EIF5, TCF25, and BIN1. We also demonstrate that loss of Bin1 enhances UCP1 expression and mitochondrial respiration, suggesting that BIN1 marks dormant brown adipocytes. The existence of multiple brown adipocyte subtypes suggests distinct functional properties of BAT depending on its cellular composition, with potentially distinct functions in thermogenesis and the regulation of whole body energy homeostasis.