Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice.
Identification and characterization of distinct brown adipocyte subtypes in C57BL/6J mice.
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DOI：
10.26508/lsa.202000924
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发表时间：
2021-01
影响因子：
4.4
通讯作者：
Ussar S
中科院分区：
文献类型：
--
作者：
Karlina R;Lutter D;Miok V;Fischer D;Altun I;Schöttl T;Schorpp K;Israel A;Cero C;Johnson JW;Kapser-Fischer I;Böttcher A;Keipert S;Feuchtinger A;Graf E;Strom T;Walch A;Lickert H;Walzthoeni T;Heinig M;Theis FJ;García-Cáceres C;Cypess AM;Ussar S
采用多种细胞生物学和统计学方法，我们鉴定并表征了EIF5、TCF25和BIN1作为C57BL/6J小鼠棕色脂肪细胞亚型的标记物。褐色脂肪组织（BAT）在调节体重和葡萄糖稳态中起着重要作用。尽管越来越多的证据支持白色脂肪组织的异质性，但对小鼠BAT的异质性知之甚少。最近，发现了UCP1高表达和低表达的棕色脂肪细胞，但这些亚型的发育起源尚未得到研究。为了进一步了解棕色前脂肪细胞的异质性，我们对C57/BL6小鼠的BAT间质血管部分进行了单细胞RNA测序，并对棕色前脂肪细胞和脂肪细胞克隆细胞系进行了表征。对棕色前脂肪细胞和脂肪细胞克隆的基因表达谱进行统计分析，确定区分棕色脂肪细胞亚型的标记。我们使用EIF5、TCF25和BIN1标记物确认了体内存在不同的棕色脂肪细胞群。我们还证明，Bin1的缺失增强了UCP1的表达和线粒体呼吸，这表明Bin1标志着休眠的棕色脂肪细胞。多种棕色脂肪细胞亚型的存在表明，BAT根据其细胞组成具有不同的功能特性，在产热和调节全身能量稳态方面可能具有不同的功能。
Using a number of cell biological and statistical methods we identify and characterize EIF5, TCF25 and BIN1 as markers for individual brown adipocyte subtypes in C57BL/6J mice. 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.