Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA; Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Institute for Diabetes, Obesity & Metabolism, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Dev Cell. 2023 Nov 6;58(21):2195-2205.e5. doi: 10.1016/j.devcel.2023.08.003. Epub 2023 Aug 29.
Brown adipose tissue (BAT) is a thermogenic organ that protects animals against hypothermia and obesity. BAT derives from the multipotent paraxial mesoderm; however, the identity of embryonic brown fat progenitor cells and regulators of adipogenic commitment are unclear. Here, we performed single-cell gene expression analyses of mesenchymal cells during mouse embryogenesis with a focus on BAT development. We identified cell populations associated with the development of BAT, including Dpp4+ cells that emerge at the onset of adipogenic commitment. Immunostaining and lineage-tracing studies show that Dpp4+ cells constitute the BAT fascia and contribute minorly as adipocyte progenitors. Additionally, we identified the transcription factor GATA6 as a marker of brown adipogenic progenitor cells. Deletion of Gata6 in the brown fat lineage resulted in a striking loss of BAT. Together, these results identify progenitor and transitional cells in the brown adipose lineage and define a crucial role for GATA6 in BAT development.
棕色脂肪组织（BAT）是一种产热器官，可保护动物免受体温过低和肥胖的影响。BAT 源自多能轴旁中胚层；然而，胚胎棕色脂肪祖细胞的身份和脂肪生成承诺的调节因子尚不清楚。在这里，我们对胚胎发生过程中的间充质细胞进行了单细胞基因表达分析，重点是 BAT 的发育。我们确定了与 BAT 发育相关的细胞群，包括在脂肪生成承诺开始时出现的 Dpp4+细胞。免疫染色和谱系追踪研究表明，Dpp4+细胞构成 BAT 筋膜，并作为脂肪细胞祖细胞的贡献较小。此外，我们确定转录因子 GATA6 是棕色脂肪祖细胞的标志物。棕色脂肪谱系中 Gata6 的缺失导致 BAT 的惊人损失。总之，这些结果确定了棕色脂肪谱系中的祖细胞和过渡细胞，并定义了 GATA6 在 BAT 发育中的关键作用。
