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

基本信息

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
项目类别：
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

项目摘要

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.

抽象的脂肪组织在调节全身代谢中起着至关重要的作用。脂肪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。亲戚已知这些细胞的比例以及它们的激活状态随着以下变化而变化营养状态。尽管长期以来人们认识到脂肪组织的行为是决定性的通过脂肪垫内各种组成细胞类型之间的相互作用，我们对脂肪垫的了解不幸的是，这些细胞亚群的身份是不完整的。这里我们建议使用单细胞测序技术识别小鼠不同脂肪库内的新细胞亚群和人类。我们将评估这些不同的细胞如何随性别、年龄和代谢扰动而变化，例如禁食、高脂肪饮食、胃绕道手术和热应激。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表征细胞类型之间发生的相互作用的计算技术。由此产生的数据库将成为社区资源和脂肪组织生物学新时代的起点。