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人类动脉粥样硬化斑块中的单细胞RNA测序揭示了一种具有多分化潜能并塑造微环境的新型平滑肌细胞亚型。

Single-cell RNA sequencing in human atherosclerotic plaques reveals a novel smooth muscle cell subtype that possesses multi differentiation potential and shapes the microenvironment.

作者信息

Ye Weijie, Chen Zhibing, Xia Zhiwei, Li Dongjie

机构信息

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan, China.

出版信息

Clin Exp Med. 2025 Jul 16;25(1):251. doi: 10.1007/s10238-025-01735-7.

Abstract

Smooth muscle cells (SMCs) play a crucial role in atherosclerosis, undergoing proliferation, migration, and transdifferentiation into other cell types. Multiple SMC subsets exist, each with distinct roles that are increasingly being elucidated. To investigate the heterogeneity of SMC subsets in lesion, we integrated three single-cell RNA sequencing datasets. Bioinformatics analysis was conducted to evaluate the effects of the immune microenvironment, biological function, metabolic interactions, and differentiation potential of different SMC subsets. Atherosclerotic plaques from ApoE mice were used for validation. We employed pySCENIC to predict the transcription factors associated with different SMC subsets and used bulk RNA sequencing data to identify the function of the_C5 marker gene (ALDOA). We identified a unique smooth muscle cell cluster 5 (SMC_C5) in human coronary plaques and confirmed its presence in aortic plaques of ApoE mice. SMC_C5 interacts with macrophages and monocytes, influencing the microenvironment and participating in various pathways and metabolic processes. Additionally, SMC_C5 cells exhibit pluripotent differentiation potential. Mechanistically, we found a strong association of SMC_C5 and the transcription factor GA binding protein 1 (GABP1). The SMC_C5 marker gene (ALDOA) was involved in regulating metabolism, hypoxia response, and the immune microenvironment. This investigation provides novel insights into the complex biology of SMCs and reveals novel functions of SMC_C5 in atherogenesis.

摘要

平滑肌细胞(SMCs)在动脉粥样硬化中起关键作用,会经历增殖、迁移并转分化为其他细胞类型。存在多个平滑肌细胞亚群,每个亚群都有不同的作用,且这些作用正越来越多地被阐明。为了研究病变中平滑肌细胞亚群的异质性,我们整合了三个单细胞RNA测序数据集。进行了生物信息学分析,以评估不同平滑肌细胞亚群的免疫微环境、生物学功能、代谢相互作用和分化潜能的影响。使用载脂蛋白E(ApoE)小鼠的动脉粥样硬化斑块进行验证。我们使用pySCENIC预测与不同平滑肌细胞亚群相关的转录因子,并使用批量RNA测序数据来确定C5标记基因(ALDOA)的功能。我们在人类冠状动脉斑块中鉴定出一个独特的平滑肌细胞簇5(SMC_C5),并在ApoE小鼠的主动脉斑块中证实了其存在。SMC_C5与巨噬细胞和单核细胞相互作用,影响微环境并参与各种途径和代谢过程。此外,SMC_C5细胞表现出多能分化潜能。从机制上讲,我们发现SMC_C5与转录因子GA结合蛋白1(GABP1)有很强的关联。SMC_C5标记基因(ALDOA)参与调节代谢、缺氧反应和免疫微环境。这项研究为平滑肌细胞的复杂生物学提供了新的见解,并揭示了SMC_C5在动脉粥样硬化发生中的新功能。

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