Investigating Human Adipocyte Heterogeneity

研究人类脂肪细胞异质性

基本信息

批准号：
10632169
负责人：
Orr Ashenberg
金额：
$ 223.59万
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 2028-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10632169
关键词：
ATAC-seq Abdomen Address Adipocytes Adipose tissue Affect Automobile Driving Binding Biology Blood Vessels Bone Marrow CRISPR-mediated transcriptional activation Catalogs Categories Cell Nucleus Cell Ontogeny Cell physiology Cells Chromatin Communities Complex Data Data Analyses Data Set Databases Development Disease Exhibits Fatty acid glycerol esters Functional disorder Gene Expression Genes Grant Health Heterogeneity Histologic Homeostasis Human Hyperlipidemia Image Immune In Vitro Individual Kidney Knowledge Knowledge Portal Lymphedema Metabolic Metabolic Diseases Metabolic dysfunction Metabolism Modality Modeling Mus Nerve Nodal Nomenclature Non-Insulin-Dependent Diabetes Mellitus Nuclear Obesity Participant Pathway interactions Phase Phenotype Physiological Physiology Population Predictive Factor Predisposing Factor Prevalence Proteomics Protocols documentation Resources Signaling Molecule Standardization System Techniques Technology Testing Untranslated RNA Variant Visceral Waist-Hip Ratio Work adipokines cell type gene regulatory network genome-wide human disease intercellular communication lipidomics metabolomics multiple omics novel outreach polygenic risk score programs screening single nucleus RNA-sequencing spatial relationship subcutaneous trait transcription factor transcriptome sequencing web based interface web portal

项目摘要

ABSTRACT The parenchymal cell of adipose tissue is the white adipocyte, which is now understood to be a dynamic and active participant in metabolic homeostasis. Adipocytes store and release energy as needed, they coordinate physiological functions throughout the body via the elaboration of “adipokines”, and they have associations with human disease traits. Understanding the diversity of human adipocytes has been challenging, because of the technical difficulties inherent in working with large, fragile cells. We have now used advanced single nuclear sequencing techniques to circumvent this issue, and have now identified seven distinct subpopulations of human white adipocytes. There are many questions remaining, including whether there are more subpopulations in different adipose depots, what their functions are, and how they develop. In this proposal we will address these issues using a combination of phenotyping modalities, combined with experimental manipulations of signaling molecules and transcription factors that are predicted to affect adipocyte subpopulation development and function. Furthermore, we will associate these subpopulations with human metabolic disease traits. Finally, a key deliverable of this proposal is a Human Adipose Tissue Knowledge Portal, which will assimilate the data generated here and integrate it with data from other groups, facilitating standardization of experimental protocols, data analysis, and nomenclature. The resulting database will be a community resource and the starting point for a new era of adipose tissue biology.

抽象的脂肪组织的实质细胞是白色脂肪细胞，现在被认为是一种动态的脂肪细胞根据需要储存和释放能量，并积极参与代谢稳态。通过“脂肪因子”的阐述来协调整个身体的生理功能，并且它们了解人类脂肪细胞的多样性与人类疾病特征有关。由于处理大而脆弱的细胞固有的技术困难，我们一直在挑战。现在已经使用先进的单核测序技术来规避这个问题，并且现在已经确定了人类七种白色脂肪细胞的不同亚群还有很多问题。剩余的，包括不同脂肪库中是否有更多的亚群，他们的功能是什么，以及它们如何发展。在本提案中，我们将使用组合来解决这些问题。表型分析模式，结合信号分子的实验操作和预计会影响脂肪细胞亚群发育和功能的转录因子。此外，我们将把这些亚群与人类代谢疾病特征联系起来。该提案的可交付成果是人类脂肪组织知识门户，它将吸收数据在这里生成并将其与其他组的数据集成，促进实验的标准化协议、数据分析和命名法所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。