Long Non-coding RNAs in Adipogenesis

描述(申请人提供)：哺乳动物基因组表达大量的长非编码RNA(LncRNAs)。然而，只有一小部分人被研究过。已知的lncRNAs在细胞中有不同的作用，主要是在细胞核中，如染色质重塑、转录和RNA加工。脂肪生成是由前体细胞产生脂肪细胞的过程，前体细胞对人类疾病有许多影响，如糖尿病和心血管疾病。虽然蛋白质编码基因在脂肪形成中的调控已经被很好地研究，但lncRNAs的作用完全不清楚。我们已经对人类和小鼠脂肪生成细胞的转录本进行了测序，测序达到了前所未有的深度。我们的初步分析表明，一组lncRNAs在脂肪形成过程中受到高度调控，表明它们在这一过程中发挥着功能作用。在这项资助中，我们计划研究已知的和新的在脂肪形成中调节的lncRNAs在前体细胞向成熟脂肪细胞分化中的作用。 公共卫生相关性：脂肪细胞与人类疾病有许多关联。脂肪细胞数量的异常导致肥胖，肥胖正迅速成为世界范围内一个严重的公共卫生问题，并与其他常见疾病有关，如II型糖尿病和心血管疾病。脂肪生成是从前体细胞生成脂肪细胞的过程，它涉及一系列信号事件，导致对在细胞增殖和分化中发挥作用的基因的调节。在这项授权中，我们将识别和研究长的非编码RNA(LncRNAs)，它们越来越多地被发现与细胞中的各种关键功能有关。然而，它们在脂肪形成中的作用完全不清楚。

DESCRIPTION (provided by applicant): The mammalian genomes express a large number of long noncoding RNAs (lncRNAs). Only a handful of them, however, have been studied. The known lncRNAs have diverse roles in the cell, mostly in the nucleus, such as chromatin remodeling, transcription, and RNA processing. Adipogenesis is the process that generates adipocytes from precursor cells, which have many implications for human diseases, such as diabetes and cardiovascular diseases. While regulation of protein-coding genes in adipogenesis has been well studied, the role of lncRNAs is completely unclear. We have sequenced the transcriptomes of human and mouse cells undergoing adipogenesis to an unprecedented depth. Our preliminary analysis indicates that a set of lncRNAs are highly regulated during adipogenesis, suggesting their functional roles in the process. In this grant, we plan to examine known and novel lncRNAs that are regulated in adipogenesis for their roles in differentiation of precursor cells into mature adipocytes. PUBLIC HEALTH RELEVANCE: Adipocytes have many implications for human diseases. Aberration in fat cell number leads to obesity, which is rapidly becoming a serious public health problem around the world, and is related to other common diseases, such as type II diabetes and cardiovascular diseases. Adipogenesis is the process that generates adipocytes from precursor cells, which involves a cascade of signaling events leading to regulation of genes that play roles in cell proliferation and differentiation. In this grant, we will identify and examine long noncoding RNAs (lncRNAs), which are increasingly found to be associated with various key functions in the cell. However, their roles in adipogenesis are completely unclear.