Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity.
Single-cell profiling of vascular endothelial cells reveals progressive organ-specific vulnerabilities during obesity.
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DOI：
10.1038/s42255-022-00674-x
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发表时间：
2022-11
影响因子：
20.8
通讯作者：
Sheikh, Bilal N.
中科院分区：
文献类型：
--
作者：
Bondareva, Olga;Rodriguez-Aguilera, Jesus Rafael;Oliveira, Fabiana;Liao, Longsheng;Rose, Alina;Gupta, Anubhuti;Singh, Kunal;Geier, Florian;Schuster, Jenny;Boeckel, Jes-Niels;Buescher, Joerg M.;Kohli, Shrey;Kloeting, Nora;Isermann, Berend;Blueher, Matthias;Sheikh, Bilal N.
肥胖导致多种病理改变，包括动脉粥样硬化和痴呆，通常涉及血管缺陷和内皮细胞(EC)功能障碍。每个器官都有不同的EC亚型，但EC是否受到肥胖的不同影响尚不清楚。在这里，我们使用单细胞RNA测序来分析肥胖进行性阶段雄性小鼠七个器官中约375,000个内皮细胞的转录，以确定器官特异性易感性。我们发现，肥胖以器官和EC亚型特有的方式放松了基因表达网络的调控，包括脂质处理、代谢途径和AP1转录因子和炎症信号。随着持续的肥胖，转录异常会恶化，饮食干预和减肥只能部分缓解。例如，饮食干预大大减轻了肝脏的失调，但不能减轻肾脏和EC转录本的失调。通过与人类全基因组关联研究数据的整合，我们进一步确定了由肥胖诱导的血管疾病风险基因的子集。我们的工作对肥胖对内皮的影响进行了分类，构成了一个有用的资源，并揭示了作为潜在治疗目标的研究线索。Bondareva和Rodríguez-Aguera等人。使用scRNA-seq分析肥胖不同阶段雄性小鼠七个器官的375,000个内皮细胞的转录，以确定器官特有的脆弱性。
Obesity promotes diverse pathologies, including atherosclerosis and dementia, which frequently involve vascular defects and endothelial cell (EC) dysfunction. Each organ has distinct EC subtypes, but whether ECs are differentially affected by obesity is unknown. Here we use single-cell RNA sequencing to analyze transcriptomes of ~375,000 ECs from seven organs in male mice at progressive stages of obesity to identify organ-specific vulnerabilities. We find that obesity deregulates gene expression networks, including lipid handling, metabolic pathways and AP1 transcription factor and inflammatory signaling, in an organ- and EC-subtype-specific manner. The transcriptomic aberrations worsen with sustained obesity and are only partially mitigated by dietary intervention and weight loss. For example, dietary intervention substantially attenuates dysregulation of liver, but not kidney, EC transcriptomes. Through integration with human genome-wide association study data, we further identify a subset of vascular disease risk genes that are induced by obesity. Our work catalogs the impact of obesity on the endothelium, constitutes a useful resource and reveals leads for investigation as potential therapeutic targets. Bondareva and Rodríguez-Aguilera et al. use scRNA-seq to analyze transcriptomes of 375,000 endothelial cells from seven organs in male mice at various stages of obesity to identify organ-specific vulnerabilities.
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影响因子：
64.8
作者：
Gillich A;Zhang F;Farmer CG;Travaglini KJ;Tan SY;Gu M;Zhou B;Feinstein JA;Krasnow MA;Metzger RJ
通讯作者：
Metzger RJ
影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
4.3
作者：
Coutinho T;Turner ST;Kullo IJ
通讯作者：
Kullo IJ
DOI：
10.2215/cjn.00540107
发表时间：
2007-11-01
影响因子：
9.8
作者：
Ferris, Maria;Hogan, Susan L.;Jennette, J. Charles
通讯作者：
Jennette, J. Charles
影响因子：
14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen