Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure

DOI：

10.1161/atvbaha.122.318314

发表时间：

2022-10

期刊：

Arteriosclerosis, Thrombosis, and Vascular Biology

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Songren Shu (舒松仁);Mengxia Fu (付梦霞);Xiao Chen (陈晓);Ningning Zhang (张宁宁);Ruojin Zhao (赵若瑾);Yuan Chang (常远);Hao Cui (崔皓);Zirui Liu (刘子睿);Xiaohu Wang (王小虎);Xiumeng Hua (花秀猛);Yuan Li (李源);Xin Wang (王欣);Xianqiang Wang (王现强);Wei Feng (凤玮);Jiangping Song (宋江平)

背景：在细胞水平探索瓣膜性心脏病的机制可能有助于确定新的治疗靶点；然而，未患病的人类心脏瓣膜小叶的综合细胞景观仍不清楚。方法：使用单细胞 RNA 测序来探索接受心脏移植的终末期心力衰竭患者的未患病人类心脏瓣膜小叶（5 个主动脉瓣、5 个肺动脉瓣、5 个三尖瓣和 3 个二尖瓣）的细胞景观。生物信息学用于识别细胞类型、描述细胞功能并研究细胞发育轨迹和相互作用。总结了4种心脏瓣膜在细胞水平上的差异。进行病理染色以验证单细胞 RNA 测序的主要发现。对我们的单细胞数据和已发表的基于全基因组关联研究和基于批量 RNA 测序的数据进行综合分析，提供了对钙化主动脉瓣疾病的细胞特异性贡献的见解。结果：在来自未患病人类心脏瓣膜小叶的 128 412 个细胞中鉴定出了 6 种细胞类型。瓣膜间质细胞是最大的群体，其次是骨髓细胞、淋巴细胞、瓣膜内皮细胞、肥大细胞和肌成纤维细胞。 4 种类型的心脏瓣膜具有不同的细胞组成。细胞间通讯分析显示瓣膜间质细胞位于通讯网络的中心。我们的单细胞 RNA 测序数据的综合分析揭示了参与钙化主动脉瓣疾病发病机制的关键细胞亚群。结论：4 种类型的未患病心脏瓣膜的细胞景观存在差异，这可能解释了它们对病理重塑和瓣膜性心脏病的易感性差异。

Background: Exploring the mechanisms of valvular heart disease at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of nondiseased human cardiac valve leaflets remains unclear. Methods: The cellular landscapes of nondiseased human cardiac valve leaflets (5 aortic valves, 5 pulmonary valves, 5 tricuspid valves, and 3 mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing. Bioinformatics was used to identify the cell types, describe the cell functions, and investigate cellular developmental trajectories and interactions. Differences among the 4 types of cardiac valves at the cellular level were summarized. Pathological staining was performed to validate the key findings of single-cell RNA sequencing. An integrative analysis of our single-cell data and published genome-wide association study-based and bulk RNA sequencing-based data provided insights into the cell-specific contributions to calcific aortic valve diseases. Results: Six cell types were identified among 128 412 cells from nondiseased human cardiac valve leaflets. Valvular interstitial cells were the largest population, followed by myeloid cells, lymphocytes, valvular endothelial cells, mast cells, and myofibroblasts. The 4 types of cardiac valve had distinct cellular compositions. The intercellular communication analysis revealed that valvular interstitial cells were at the center of the communication network. The integrative analysis of our single-cell RNA sequencing data revealed key cellular subpopulations involved in the pathogenesis of calcific aortic valve diseases. Conclusions: The cellular landscape differed among the 4 types of nondiseased cardiac valve, which might explain their differences in susceptibility to pathological remodeling and valvular heart disease.

Cellular Landscapes of Nondiseased Human Cardiac Valves From End-Stage Heart Failure–Explanted Heart

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