Cellular landscapes of non-diseased human cardiac valves from end-stage heart failure-explanted heart

Exploring the mechanisms of valvular heart disease (VHD) at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of non-diseased human cardiac valve leaflets remains unclear. The cellular landscapes of non-diseased human cardiac valve leaflets (five aortic valves, five pulmonary valves, five tricuspid valves, and three mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing (scRNA-seq) To identify the cellular composition of human cardiac valves, 18 valve specimens were collected from seven HTx recipients. Of these, five were AV samples, five were PV samples, five were TV samples, and three were MV samples. The determination of each sample’s non-diseased state was based on the clinical history, echocardiography, and histological characterization of the corresponding valves. The freshly collected valves were digested enzymatically to prepare the single-cell suspension, and scRNA-seq was performed using the 10x Genomics Chromium platform. Then, the sequencing reads were demultiplexed, mapped to the GRCh38 human genome, and counted by unique molecular identifier. >>>Submitter states: Raw sequence data were provided at China Genomic Sequence Archive (GSA) at accession no. HRA002977.<<<

在细胞层面探究心脏瓣膜病（valvular heart disease, VHD）的发病机制，或有助于识别全新治疗靶点；然而目前人类非病变心脏瓣膜小叶的完整细胞图谱仍不明确。本研究针对接受心脏移植的终末期心力衰竭患者的非病变心脏瓣膜小叶（含5个主动脉瓣（aortic valve, AV）、5个肺动脉瓣（pulmonary valve, PV）、5个三尖瓣（tricuspid valve, TV）及3个二尖瓣（mitral valve, MV）），采用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）探究其细胞图谱。为明确人类心脏瓣膜的细胞组成，研究团队从7名心脏移植（heart transplantation, HTx）受者体内采集了18份瓣膜标本，其中5份为主动脉瓣（aortic valve, AV）样本、5份为肺动脉瓣（pulmonary valve, PV）样本、5份为三尖瓣（tricuspid valve, TV）样本、3份为二尖瓣（mitral valve, MV）样本。每份样本的非病变状态均通过对应瓣膜的临床病史、超声心动图及组织学特征进行确认。将新鲜采集的瓣膜经酶解制备单细胞悬液，并采用10x Genomics Chromium平台开展单细胞RNA测序。随后对测序reads进行解复用，将序列比对至GRCh38人类参考基因组，并通过唯一分子标识符（unique molecular identifier, UMI）完成计数。提交者声明：原始测序数据已上传至中国基因组序列档案库（China Genomic Sequence Archive, GSA），登录号为HRA002977。