Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level.
Aortic heterogeneity across segments and under high fat/salt/glucose conditions at the single-cell level.
复制标题
单细胞水平上跨节段和高脂肪/盐/葡萄糖条件下的主动脉异质性
DOI：
10.1093/nsr/nwaa038
复制
发表时间：
2020-05
影响因子：
20.6
通讯作者：
Ma X
中科院分区：
文献类型：
--
作者：
He D;Mao A;Zheng CB;Kan H;Zhang K;Zhang Z;Feng L;Ma X
摘要主动脉包括升、弓、胸、腹四个部分，对心跳作出反应，感知代谢物并将血液分配到身体的各个部位。然而，尚不清楚主动脉节段的异质性以及代谢病理学如何改变它。在这里，使用单细胞RNA测序分析了正常条件下或高血糖水平、高饮食盐或高脂肪摄入的小鼠腹主动脉、主动脉弓、胸段和腹段的共216612个单个细胞。我们生成了10种不同细胞类型的纲要，主要是内皮细胞（EC）、平滑肌细胞（SMC）、基质细胞和免疫细胞。不同细胞的分布和它们之间的相互联系受到解剖节段的血流动力学微环境的影响，EC和SMC的空间异质性可能有助于通过钢丝肌造影测量的差异性血管扩张和收缩。重要的是，主动脉细胞的组成、其基因表达谱及其调节细胞间网络因高脂肪/盐/葡萄糖条件而发生广泛变化。值得注意的是，腹主动脉显示出细胞组成的最显著变化，特别是涉及EC、成纤维细胞和具有心血管风险因子相关调节子和基因表达网络的骨髓细胞。我们的研究阐明了主动脉细胞多样性的性质和范围，并对代谢性疾病的治疗产生了影响。
Abstract The aorta, with ascending, arch, thoracic and abdominal segments, responds to the heartbeat, senses metabolites and distributes blood to all parts of the body. However, the heterogeneity across aortic segments and how metabolic pathologies change it are not known. Here, a total of 216 612 individual cells from the ascending aorta, aortic arch, and thoracic and abdominal segments of mouse aortas under normal conditions or with high blood glucose levels, high dietary salt, or high fat intake were profiled using single-cell RNA sequencing. We generated a compendium of 10 distinct cell types, mainly endothelial (EC), smooth muscle (SMC), stromal and immune cells. The distributions of the different cells and their intercommunication were influenced by the hemodynamic microenvironment across anatomical segments, and the spatial heterogeneity of ECs and SMCs may contribute to differential vascular dilation and constriction that were measured by wire myography. Importantly, the composition of aortic cells, their gene expression profiles and their regulatory intercellular networks broadly changed in response to high fat/salt/glucose conditions. Notably, the abdominal aorta showed the most dramatic changes in cellular composition, particularly involving ECs, fibroblasts and myeloid cells with cardiovascular risk factor-related regulons and gene expression networks. Our study elucidates the nature and range of aortic cell diversity, with implications for the treatment of metabolic pathologies.
登录
查看更多内容
影响因子：
20.1
作者：
Dai, Guohao;Vaughn, Saran;Gimbrone, Michael A., Jr.
通讯作者：
Gimbrone, Michael A., Jr.
影响因子：
1.5
作者：
Deng, Yaqi;Kim, BongWoo;He, Xuelian;Kim, Sunja;Lu, Changqing;Wang, Haibo;Cho, Ssang-Goo;Hou, Yiping;Li, Jianrong;Zhao, Xianghui;Lu, Q. Richard
通讯作者：
Lu, Q. Richard
内皮细胞，成纤维细胞和血管炎。
DOI：
10.1093/rheumatology/keh542
发表时间：
2005-07
期刊：
Rheumatology (Oxford, England)
影响因子：
--
作者：
Buckley CD;Rainger GE;Nash GB;Raza K
通讯作者：
Raza K
影响因子：
20.3
作者：
Dekker, RJ;van Soest, S;Horrevoets, AJG
通讯作者：
Horrevoets, AJG
影响因子：
1.5
作者：
Doerflinger, NH;Macklin, WB;Popko, B
通讯作者：
Popko, B