Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature.
Single-Cell RNA Sequencing Reveals Novel Genes Regulated by Hypoxia in the Lung Vasculature.
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DOI：
10.1159/000522340
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发表时间：
2022
影响因子：
1.7
通讯作者：
Lilly, Brenda
中科院分区：
文献类型：
--
作者：
Thomas, Shelby;Manivannan, Sathiyanarayanan;Garg, Vidu;Lilly, Brenda
肺动脉高压（PAH）是一种慢性进行性疾病，具有显著的发病率和死亡率。该疾病的特征在于血管重塑，其包括远端血管的肌化增加和与细胞外基质沉积的变化相关的血管硬化。在人类中，慢性缺氧会导致PAH，多年来，缺氧诱导的PAH啮齿动物模型一直用于研究该疾病。随着单细胞RNA测序技术的发展，现在可以在细胞特异性水平上检测体内缺氧依赖的转录变化。在这项研究中，我们使用单细胞RNA测序来比较暴露于缺氧28天的野生型小鼠的肺和正常氧处理的对照小鼠的肺。我们还检查了Notch3缺陷的小鼠，Notch3是一种与PAH相关的平滑肌富集基因。数据分析表明，缺氧促进了肺内免疫和内皮细胞类型的细胞数量变化，激活了先天免疫途径，并导致血管细胞基因表达的特异性变化。令人惊讶的是，我们发现与野生型对照相比，Notch3缺陷小鼠的肺差异有限。这些发现为慢性缺氧暴露对体内基因表达和细胞表型的影响提供了新的见解，并确定了血管系统细胞的独特变化。
Pulmonary arterial hypertension (PAH) is a chronic progressive disease with significant morbidity and mortality. The disease is characterized by vascular remodeling that includes increased muscularization of distal blood vessels and vessel stiffening associated with changes in extracellular matrix deposition. In humans, chronic hypoxia causes PAH, and hypoxia-induced rodent models of PAH have been used for years to study the disease. With the development of single-cell RNA sequencing technology, it is now possible to examine hypoxia-dependent transcriptional changes in vivo at a cell-specific level. In this study, we used single-cell RNA sequencing to compare lungs from wild-type mice exposed to hypoxia for 28 days to normoxia-treated control mice. We additionally examined mice deficient for Notch3, a smooth muscle-enriched gene linked to PAH. Data analysis revealed that hypoxia promoted cell number changes in immune and endothelial cell types in the lung, activated the innate immunity pathway, and resulted in specific changes in gene expression in vascular cells. Surprisingly, we found limited differences in lungs from mice deficient for Notch3 compared to wild-type controls. These findings provide novel insight into the effects of chronic hypoxia exposure on gene expression and cell phenotypes in vivo and identify unique changes to cells of the vasculature.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
调节肺动脉高压中肺血管平滑肌收缩力：对治疗的影响。
影响因子：
4
作者：
Lyle MA;Davis JP;Brozovich FV
通讯作者：
Brozovich FV
影响因子：
2.6
作者：
Das M;Fessel J;Tang H;West J
通讯作者：
West J
影响因子：
5.4
作者：
Horita H;Furgeson SB;Ostriker A;Olszewski KA;Sullivan T;Villegas LR;Levine M;Parr JE;Cool CD;Nemenoff RA;Weiser-Evans MC
通讯作者：
Weiser-Evans MC
影响因子：
20.3
作者：
Manalo, DJ;Rowan, A;Semenza, GL
通讯作者：
Semenza, GL