Generation of a Cellular Atlas of Adipose Tissue in Mouse and Man

摘要 脂肪组织在调节全身新陈代谢中起着关键作用。脂肪库本身 是多种细胞类型的混合物，包括免疫细胞、前脂肪细胞、基质细胞 成纤维细胞、内皮细胞和其他细胞，以及脂肪细胞本身。相对的 这些细胞的比例以及它们的激活状态已知在以下情况下有所不同 营养状况。尽管长期以来人们意识到脂肪组织的行为是由 通过脂肪垫内各种组成细胞类型之间的相互作用，我们对 可悲的是，这些细胞亚群的身份是不完整的。在这里，我们建议使用单电池 利用测序技术鉴定小鼠不同脂肪库中新的细胞亚群 和人类。我们将评估这些不同的细胞如何随性别、年龄和代谢紊乱而变化， 比如禁食、高脂饮食、胃旁路和热应激。此外，我们将确定激活 这些细胞在这些不同条件下的状态，并将利用各种实验和 描述细胞类型之间相互作用的计算技术。由此产生的 数据库将是一种社区资源，是脂肪组织生物学新时代的起点。

ABSTRACT Adipose tissue plays a critical role in regulating systemic metabolism. The adipose depots themselves are heterogeneous mixtures of cell types that include immune cells, preadipocytes, stromal fibroblasts, endothelial cells, and others, in addition to the adipocytes themselves. The relative proportions of these cells, as well as their activation state, is known to differ following changes in nutritional state. Despite a longstanding realization that the behavior of adipose tissue is determined by interactions between the various component cell types within the fat pad, our knowledge of the identity of these cellular sub-populations is woefully incomplete. Here we propose to use single cell sequencing technology to identify novel subpopulations of cells within different adipose depots of mice and humans. We will assess how these different cells vary with sex, age, and metabolic perturbations, like fasting, high fat diet, gastric bypass, and thermal stress. Further, we will determine the activation state of these cells under these different conditions, and will utilize a variety of experimental and computational techniques to characterize the interactions that occur between cell types. The resulting database will be a community resource and the starting point for a new era of adipose tissue biology.