Single-Cell Transcriptional Profiling Reveals Sex and Age Diversity of Gene Expression in Mouse Endothelial Cells.
Single-Cell Transcriptional Profiling Reveals Sex and Age Diversity of Gene Expression in Mouse Endothelial Cells.
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DOI：
10.3389/fgene.2021.590377
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发表时间：
2021
影响因子：
3.7
通讯作者：
Nguyen PK
中科院分区：
文献类型：
--
作者：
Huang X;Shen W;Veizades S;Liang G;Sayed N;Nguyen PK
尽管众所周知，性别和年龄是调节内皮细胞（EC）功能的重要因素，但性别和年龄对内皮细胞基因表达的影响尚未在单细胞水平上进行系统分析。在这项研究中，我们对从 3 月龄和 18 月龄雄性和雌性 C57BL/6 小鼠中分离的五个主要器官（例如脂肪、心主动脉、肺、四肢肌肉和肾脏）的 EC 转录组进行了综合表征。在 3 个月和 18 个月亚组的女性和男性之间分别鉴定出 590 个和 252 个差异表达基因 (DEGS)。在年轻组和老年组中，脂肪分别为 177 度和 178 度，心脏/主动脉为 305 度和 469 度，肾脏为 22 度和 37 度，四肢肌肉为 26 度和 439 度，肺部为 880 度和 274 度。有趣的是，LARS2（一种参与线粒体编码基因翻译的线粒体亮氨酰 tRNA 合酶）在 3 个月组的雄性所有器官中与雌性相比差异表达，而 S100a8 和 S100a9（钙结合蛋白，在炎症和自身免疫状态下增加）在 18 个月时在雄性所有器官中表达上调。重要的是，RNAseq 的发现得到了 qPCR 和蛋白质印迹的证实。基因富集分析发现，3 个月时，雄性的基因在蛋白质靶向、分解代谢、线粒体电子传递、IL 1- 和 IL 2- 信号传导以及 Wnt 信号传导方面富集，而雌性的基因则在血管生成和趋化性方面富集。相比之下，18 个月时雄性和雌性的 EC 在涉及炎症和细胞凋亡的类似途径中上调。总而言之，我们的研究结果表明，两个年龄段的男性和女性之间的基因表达在很大程度上相似。然而，与年轻小鼠相比，老年小鼠内皮细胞炎症相关基因的表达增加，这可能会随着年龄的增长导致动脉粥样硬化、高血压和阿尔茨海默病等慢性非传染性疾病的发生。
Although it is well-known that sex and age are important factors regulating endothelial cell (EC) function, the impact of sex and age on the gene expression of ECs has not been systematically analyzed at the single cell level. In this study, we performed an integrated characterization of the EC transcriptome of five major organs (e.g., fat, heart-aorta, lung, limb muscle, and kidney) isolated from male and female C57BL/6 mice at 3 and 18 months of age. A total of 590 and 252 differentially expressed genes (DEGS) were identified between females and males in the 3- and 18-month subgroups, respectively. Within the younger and older group, there were 177 vs. 178 DEGS in fat, 305 vs. 469 DEGS in heart/aorta, 22 vs. 37 DEGS in kidney, 26 vs. 439 DEGS in limb muscle, and 880 vs. 274 DEGS in lung. Interestingly, LARS2, a mitochondrial leucyl tRNA synthase, involved in the translation of mitochondrially encoded genes was differentially expressed in all organs in males compared to females in the 3-month group while S100a8 and S100a9, which are calcium binding proteins that are increased in inflammatory and autoimmune states, were upregulated in all organs in males at 18 months. Importantly, findings from RNAseq were confirmed by qPCR and Western blot. Gene enrichment analysis found genes enriched in protein targeting, catabolism, mitochondrial electron transport, IL 1- and IL 2- signaling, and Wnt signaling in males vs. angiogenesis and chemotaxis in females at 3 months. In contrast, ECs from males and females at 18-months had up-regulation in similar pathways involved in inflammation and apoptosis. Taken together, our findings suggest that gene expression is largely similar between males and females in both age groups. Compared to younger mice, however, older mice have increased expression of genes involved in inflammation in endothelial cells, which may contribute to the development of chronic, non-communicable diseases like atherosclerosis, hypertension, and Alzheimer's disease with age.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
DOI：
10.1161/hypertensionaha.116.06602
发表时间：
2016-12
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Gillis EE;Sullivan JC
通讯作者：
Sullivan JC
影响因子：
7.7
作者：
Franco CA;Jones ML;Bernabeu MO;Vion AC;Barbacena P;Fan J;Mathivet T;Fonseca CG;Ragab A;Yamaguchi TP;Coveney PV;Lang RA;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
8.3
作者：
Cereda, Carlo W.;Tamisier, Renaud;Bassetti, Claudio L.
通讯作者：
Bassetti, Claudio L.
影响因子：
5
作者：
Donato AJ;Morgan RG;Walker AE;Lesniewski LA
通讯作者：
Lesniewski LA