Transcriptional profile of the rat cardiovascular system at single-cell resolution

We sought to characterize cellular composition across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We performed snRNA-seq in 78 samples in 10 distinct regions including the four chambers of the heart, ventricular septum, sinoatrial node, atrioventricular node, aorta, pulmonary artery, and pulmonary veins, which produced 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, with different cellular composition across cardiac regions and tissue-specific transcription for each cell type. Several cell subtypes were region-specific, including a subtype of vascular smooth muscle cells enriched in the large vasculature. We observed tissue-enriched cellular communication networks, including heightened Nppa - Npr1/2/3 signaling in the sinoatrial node. The existence of tissue-restricted cell types suggests regional regulation of cardiovascular physiology. Our detailed transcriptional characterization of each cell type offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease. 78 samples which passed QC are included here. All samples are from healthy Wistar rat cardiovascular tissue, collected from specific tissue regions. The rats are all male 17 week old animals. Multiple tissue region samples were collected from each individual rat, and a total of 16 individual rats were used to collect the snRNA-seq data in this study. Nuclei were isolated from each sample and were used to prepare a 10x 3' v2 library for snRNA-seq.

本研究旨在系统解析健康Wistar大鼠（Wistar rat）心血管系统的细胞组成，该大鼠是心血管临床前研究中的经典实验模型。本研究针对涵盖心脏四腔、室间隔、窦房结、房室结、主动脉、肺动脉及肺静脉在内的10个不同区域的78个样本，开展了单细胞核RNA测序（snRNA-seq），最终获得505,835个细胞核。研究共鉴定出26种明确的细胞类型及多种亚型，不同心脏区域的细胞组成存在显著差异，且每种细胞类型均具备组织特异性转录特征。部分细胞亚型具有区域特异性，例如在大血管中富集的血管平滑肌细胞亚型。本研究还观察到组织富集的细胞通讯网络，如窦房结中Nppa-Npr1/2/3信号通路的激活水平显著升高。组织限制性细胞类型的存在提示心血管生理功能存在区域特异性调控机制。本研究针对每种细胞类型的详细转录组特征解析，可为新型治疗靶点的发掘及心血管疾病临床前模型的优化提供重要支撑。本数据集纳入了全部通过质量控制（QC）的78个样本，所有样本均采自健康Wistar大鼠的心血管组织，且来自特定的组织区域。实验大鼠均为17周龄的雄性个体。每只实验大鼠可获取多个组织区域的样本，本研究共使用16只个体大鼠完成了单细胞核RNA测序数据的采集。从每个样本中分离得到细胞核，并用于构建10x 3' v2测序文库以开展单细胞核RNA测序。