Single-Cell RNA Sequencing of the Rat Carotid Arteries Uncovers Potential Cellular Targets of Neointimal Hyperplasia.
Single-Cell RNA Sequencing of the Rat Carotid Arteries Uncovers Potential Cellular Targets of Neointimal Hyperplasia.
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大鼠颈动脉的单细胞 RNA 测序揭示了新内膜增生的潜在细胞靶点
DOI：
10.3389/fcvm.2021.751525
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发表时间：
2021
影响因子：
3.6
通讯作者：
Chen SL
中科院分区：
文献类型：
--
作者：
Gao XF;Chen AQ;Wang ZM;Wang F;Luo S;Chen SY;Gu Y;Kong XQ;Zuo GF;Chen Y;Ge Z;Zhang JJ;Chen SL
目的：支架内再狭窄(ISR)仍然是药物洗脱支架的一个致命弱点，尽管在设备和操作技术上取得了进步。新生内膜增生(NIH)是ISR最重要的病理生理过程。本研究绘制了正常动脉和狭窄动脉的图谱，以揭示新生内膜增生的潜在细胞靶点。方法和结果：通过比较大鼠左(对照)和右(球囊损伤)颈动脉，我们定位了正常动脉的11个簇和对照组和实验组的11个相互的簇。不同的细胞群分为血管平滑肌细胞(VSMCs)、成纤维细胞、内皮细胞(ECs)、巨噬细胞、未知细胞和其他6种细胞类型。通过假时间分析，将同时表达VSMC和成纤维细胞标志的异常细胞类型称为移行细胞。由于VSMC的比例较高，我们将其分为6个簇，并分析了它们与VSMC表型转换的关系。此外，N-肉豆蔻酰基转移酶1(NMT1)被证实是一种可靠的VSMC合成表型标记。最后，我们通过疾病易感基因分析，提出了几个新的靶基因，如Cyp7a1和CDK4，有待于进一步的研究验证。结论：通过单细胞RNA测序确定了颈动脉内异质细胞分布图，揭示了ISR模型中多种细胞类型及其内在联系。这项研究强调了VSMC表型转换在新生内膜增生进展中的关键作用，并为NIH的潜在机制提供了线索。
Aims: In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia. Methods and Results: By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis. Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies. Conclusion: Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.
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影响因子：
10.8
作者：
Durham AL;Speer MY;Scatena M;Giachelli CM;Shanahan CM
通讯作者：
Shanahan CM
影响因子：
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作者：
Huaman, Jeannette;Ogunwobi, Olorunseun O.
通讯作者：
Ogunwobi, Olorunseun O.
影响因子：
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作者：
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Pu Jun
影响因子：
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作者：
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通讯作者：
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影响因子：
16.6
作者：
Liang, Jiyong;Xu, Zhi-Xiang;Mills, Gordon B.
通讯作者：
Mills, Gordon B.