TY - JOUR T1 - Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202000924 VL - 4 IS - 1 SP - e202000924 AU - Ruth Karlina AU - Dominik Lutter AU - Viktorian Miok AU - David Fischer AU - Irem Altun AU - Theresa Schöttl AU - Kenji Schorpp AU - Andreas Israel AU - Cheryl Cero AU - James W Johnson AU - Ingrid Kapser-Fischer AU - Anika Böttcher AU - Susanne Keipert AU - Annette Feuchtinger AU - Elisabeth Graf AU - Tim Strom AU - Axel Walch AU - Heiko Lickert AU - Thomas Walzthoeni AU - Matthias Heinig AU - Fabian J Theis AU - Cristina García-Cáceres AU - Aaron M Cypess AU - Siegfried Ussar Y1 - 2021/01/01 UR - https://www.life-science-alliance.org/content/4/1/e202000924.abstract N2 - 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. ER -