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Single‐cell RNA sequencing of preadipocytes reveals the cell fate heterogeneity induced by melatonin
Journal of Pineal Research ( IF 8.3 ) Pub Date : 2021-02-23 , DOI: 10.1111/jpi.12725
Zhenhui Li 1, 2, 3 , Ming Zheng 1, 3 , Jiawei Mo 1, 3 , Kan Li 1, 3 , Xin Yang 1, 3 , Lijin Guo 1, 3 , Xiquan Zhang 1, 3 , Bahareldin Ali Abdalla 1, 3 , Qinghua Nie 1, 3
Affiliation  

Obesity is a global epidemic health disorder and associated with several diseases. Body weight–reducing effects of melatonin have been reported; however, no investigation toward examining whether the beneficial effects of melatonin are associated with preadipocyte heterogeneity has been reported. In this study, we profiled 25 071 transcriptomes of normal and melatonin‐treated preadipocytes using scRNA‐seq. By tSNE analysis, we present a cellular‐state landscape for melatonin‐treated preadipocytes that covers multiple‐cell subpopulations, defined as cluster 0 to cluster 13. Cluster 0 and cluster 1 were the largest components of normal and melatonin‐treated preadipocytes, respectively. G0S2, an inhibitor of adipose triglyceride lipase (ATGL), was significantly upregulated in cluster 0 and downregulated in cluster 1. We redefined cluster 0 as the G0S2‐positive cluster (G0S2+) and cluster 1 as the G0S2‐negative cluster (G0S2). Through pseudotime analysis, the G0S2 cluster cell differentiation trajectory was divided into three major structures, that is, the prebranch, the lipid catabolism branch, and the cell fate 2 branch. In vitro, G0S2 knockdown enhanced the expression levels of ATGL, BAT markers and fatty acid oxidation–related genes, but inhibited C/EBPα and PPARγ expression. In vivo, knockdown of G0S2 reduced the body weight gain in high‐fat‐fed mice. The beneficial effects of the G0S2 cell cluster in promoting lipolysis and inhibiting adipogenesis are dependent on two major aspects: first, downregulation of the G0S2 gene in the G0S2 cluster, resulting in activation of ATGL, which is responsible for the bulk of triacylglycerol hydrolase activity; and second, upregulation of FABP4 in the G0S2 cluster, resulting in inhibition of PPARγ and further reducing adipogenesis.

中文翻译:

前脂肪细胞的单细胞 RNA 测序揭示了褪黑激素诱导的细胞命运异质性

肥胖是一种全球流行的健康障碍,并与多种疾病有关。已经报道了褪黑激素的体重减轻作用;然而,尚无关于检查褪黑激素的有益作用是否与前脂肪细胞异质性相关的调查报告。在这项研究中,我们使用 scRNA-seq 分析了正常和褪黑激素处理的前脂肪细胞的 25 071 个转录组。通过 tSNE 分析,我们展示了褪黑激素处理的前脂肪细胞的细胞状态图,涵盖了多细胞亚群,定义为集群 0 到集群 13。集群 0 和集群 1 分别是正常和褪黑激素处理的前脂肪细胞的最大组成部分。G0S2,脂肪甘油三酯脂肪酶(ATGL)抑制剂),在簇 0 中显着上调,在簇 1 中下调。我们将簇 0 重新定义为 G0S2 阳性簇 (G0S2 + ),将簇 1重新定义为 G0S2 阴性簇 (G0S2 )。通过pseudotime分析,GOS2启动-簇细胞的分化轨迹分为三个主要的结构,也就是prebranch,脂质代谢科,以及细胞命运2分支。在体外,G0S2敲低增强了ATGL、BAT 标志物和脂肪酸氧化相关基因的表达水平,但抑制了C/EBPαPPARγ 的表达。在体内,G0S2 的敲低减少高脂肪喂养小鼠的体重增加。的GOS2启动的有益效果-小区组中促进脂肪分解和抑制脂肪形成都依赖于两个主要方面:第一,下调GOS2启动的GOS2启动基因-簇,导致活化ATGL,这是负责大部分的甘油三酯水解酶活动; 和第二,上调FABP4的GOS2启动在-簇,从而抑制的PPARγ和进一步降低脂肪生成。
更新日期:2021-03-29
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