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单细胞测序揭示冠状动脉疾病保护机制
来源:小柯机器人 发布时间:2019/8/13 13:26:27

美国斯坦福大学医学院Thomas Quertermous研究组取得新进展。他们利用单细胞测序揭示了平滑肌细胞表型转化与疾病基因TCF21在动脉粥样硬化过程中的保护作用。2019年8月,国际知名学术期刊《自然—医学》发表了这一成果。

使用单细胞RNA测序,研究人员在小鼠和人动脉的动脉粥样硬化病变中全面表征了血管平滑肌细胞(SMC)体内表型转化的转录组,并发现这些细胞转化为独特的成纤维细胞样细胞,被命名为“fibromyocyte”,而不是经典的巨噬细胞表型。SMC中特异性敲除TCF21(一个导致CAD的基因)能够显著抑制小鼠中的SMC表型转化,从而导致病变内以及病变的保护性纤维帽内存在较少的fibromyocyte。此外,TCF21表达与患者冠状动脉中的SMC表型转化显著相关,并且较高水平的TCF21表达与人CAD相关组织中降低的CAD风险相关。这些结果确立了TCF21和SMC表型转化在该疾病中的保护作用。

据介绍,为响应各种刺激,血管平滑肌细胞(SMC)可以去分化、增殖和迁移,这一过程被称为表型转化。然而,动脉粥样硬化时SMC的体内表型转化以及该过程对冠状动脉疾病(CAD)风险的影响尚不明确。

附:英文原文

Title: Atheroprotective roles of smooth muscle cell phenotypic modulation and the TCF21 disease gene as revealed by single-cell analysis

Author: Robert C. Wirka, Dhananjay Wagh, David T. Paik, Milos Pjanic, Trieu Nguyen, Clint L. Miller, Ramen Kundu, Manabu Nagao, John Coller, Tiffany K. Koyano, Robyn Fong, Y. Joseph Woo, Boxiang Liu, Stephen B. Montgomery, Joseph C. Wu, Kuixi Zhu, Rui Chang, Melissa Alamprese, Michelle D. Tallquist, Juyong B. Kim, Thomas Quertermous

Issue&Volume: Volume 25 Issue 8, August 2019

Abstract: In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transform into unique fibroblast-like cells, termed fibromyocytes, rather than into a classical macrophage phenotype. SMC-specific knockout of TCF21a causal CAD genemarkedly inhibited SMC phenotypic modulation in mice, leading to the presence of fewer fibromyocytes within lesions as well as within the protective fibrous cap of the lesions. Moreover, TCF21 expression was strongly associated with SMC phenotypic modulation in diseased human coronary arteries, and higher levels of TCF21 expression were associated with decreased CAD risk in human CAD-relevant tissues. These results establish a protective role for both TCF21 and SMC phenotypic modulation in this disease.

DOI: 10.1038/s41591-019-0512-5

Source: https://www.nature.com/articles/s41591-019-0512-5

期刊信息

Nature Medicine:《自然—医学》,创刊于1995年。隶属于施普林格·自然出版集团,最新IF:30.641
官方网址:https://www.nature.com/nm/
投稿链接:https://mts-nmed.nature.com/cgi-bin/main.plex


本期文章:《自然—医学》:Volume 25 Issue 8