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.

中文翻译：

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C57BL/6J 小鼠不同棕色脂肪细胞亚型的鉴定和表征。

棕色脂肪组织 (BAT) 在调节体重和葡萄糖稳态中起重要作用。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 内的异质性知之甚少。最近，鉴定了 UCP1 高表达和低表达的棕色脂肪细胞，但尚未研究这些亚型的发育起源。为了更深入地了解棕色前脂肪细胞异质性，我们使用 C57/BL6 小鼠 BAT 基质血管部分的单细胞 RNA 测序，并表征棕色前脂肪细胞和脂肪细胞克隆细胞系。来自棕色前脂肪细胞和脂肪细胞克隆的基因表达谱的统计分析确定了区分棕色脂肪细胞亚型的标记。我们使用标记物 EIF5、TCF25、和 BIN1。我们还证明了损失Bin1增强 UCP1 表达和线粒体呼吸，表明 BIN1 标记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 的不同功能特性取决于其细胞组成，在产热和全身能量稳态调节方面具有潜在的不同功能。