Investigating Human Adipocyte Heterogeneity

摘要 脂肪组织的实质细胞是白色脂肪细胞，它现在被理解为一种动态的 是代谢动态平衡的积极参与者。脂肪细胞根据需要储存和释放能量，他们 通过“脂肪因子”来协调整个身体的生理功能，它们 与人类疾病特征有关。了解人类脂肪细胞的多样性 这是一项具有挑战性的工作，因为处理大型、脆弱的细胞存在固有的技术困难。我们 现在已经使用先进的单核测序技术来绕过这个问题，并且现在已经 确定了人类白色脂肪细胞的七个不同亚群。有很多问题 剩余的，包括在不同的脂肪库中是否有更多的亚群，他们的 功能是，以及它们是如何发展的。在这份提案中，我们将结合以下几个方面解决这些问题 表型模式，结合信号分子和 预测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性疾病的特征联系起来。最后，一把钥匙 这项提议的成果是一个人类脂肪组织知识门户，它将吸收数据 并将其与其他组的数据集成，促进了实验的标准化 协议、数据分析和命名法。由此产生的数据库将是社区资源，并且 脂肪组织生物学新纪元的起点。

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.