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

小鼠和人类脂肪组织细胞图谱的生成

• 批准号: 9906217
• 负责人: DIANE J MATHIS
• 金额: $ 172.49万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-23 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9906217
• 关键词: Address; Adipocytes; Adipose tissue; Affect; Age; Anatomy; Anterior; Atlases; Behavior; Biological Assay; Biology; Biopsy; Body Weight decreased; Cell Communication; Cell Separation; Cell physiology; Cells; Cellular Structures; Coculture Techniques; Communities; Complex; Computational Technique; Cytokine Receptors; Data; Databases; Development; Disease; Endothelial Cells; Fasting; Fatty acid glycerol esters; Fibroblasts; Fractionation; Future; Gastric Bypass; Generations; Genes; Goals; Growth; Health; Heterogeneity; High Fat Diet; Human; Immune; Individual; Individual Differences; Knowledge; Location; Mesentery; Metabolic; Metabolism; Modeling; Mus; Nutritional; Obesity; Organism; Pathway Analysis; Pathway interactions; Play; Population; Resolution; Resources; Role; Stress; Structure; Surface; T-Cell Activation; Techniques; Technology; Thinness; Tissues; Visceral; Weight Gain; bariatric surgery; base; cell type; cost effective; differential expression; experimental study; feeding; genome wide association study; human subject; in vivo; lipid biosynthesis; macrophage; man; men; metabolic abnormality assessment; network models; next generation; novel; response; sex; single cell sequencing; single-cell RNA sequencing; subcutaneous; thermal stress; transcriptome

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.

摘要 脂肪组织在调节全身代谢中起关键作用。脂肪储存库本身 是细胞类型的异质混合物，包括免疫细胞、前脂肪细胞、基质细胞、 除了脂肪细胞本身之外，还包括成纤维细胞、内皮细胞等。的相对 已知这些细胞的比例以及它们的激活状态在以下变化中不同： 营养状态尽管长期以来人们认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， 不幸的是，这些细胞亚群的身份是不完全的。在这里，我们建议使用单细胞 用于鉴定小鼠不同脂肪库内的新细胞亚群的测序技术 还有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， 如禁食、高脂肪饮食、胃旁路术和热应激。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 计算技术来表征细胞类型之间发生的相互作用。所得 数据库将是一个社区资源和脂肪组织生物学新时代的起点。