PDF(Pubmed)
Abstract：
UNASSIGNED: Despite the critical role of the cardiovascular system, our understanding of its cellular and transcriptional diversity remains limited. We therefore sought to characterize the cellular composition, phenotypes, molecular pathways, and communication networks between cell types at the tissue and sub-tissue level across the cardiovascular system of the healthy Wistar rat, an important model in preclinical cardiovascular research. We obtained high quality tissue samples under controlled conditions that reveal a level of cellular detail so far inaccessible in human studies.
UNASSIGNED: We performed single nucleus RNA-sequencing 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 (PV), which produced an aggregate map of 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, including a number of rare cell types such as PV cardiomyocytes and non-myelinating Schwann cells (NMSCs), and unique groups of vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and fibroblasts (FBs), which gave rise to a detailed cell type distribution across tissues. We demonstrated differences in the cellular composition across different cardiac regions and tissue-specific differences in transcription for each cell type, highlighting the molecular diversity and complex tissue architecture of the cardiovascular system. Specifically, we observed great transcriptional heterogeneities among ECs and FBs. Importantly, several cell subtypes had a unique regional localization such as a subtype of VSMCs enriched in the large vasculature. We found the cellular makeup of PV tissue is closer to heart tissue than to the large arteries. We further explored the ligand-receptor repertoire across cell clusters and tissues, and observed tissue-enriched cellular communication networks, including heightened Nppa - Npr1/2/3 signaling in the sinoatrial node.
UNASSIGNED: Through a large single nucleus sequencing effort encompassing over 500,000 nuclei, we broadened our understanding of cellular transcription in the healthy cardiovascular system. The existence of tissue-restricted cellular phenotypes suggests regional regulation of cardiovascular physiology. The overall conservation in gene expression and molecular pathways across rat and human cell types, together with our detailed transcriptional characterization of each cell type, offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease.
UNASSIGNED: We performed single nucleus RNA-sequencing 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 (PV), which produced an aggregate map of 505,835 nuclei. We identified 26 distinct cell types and additional subtypes, including a number of rare cell types such as PV cardiomyocytes and non-myelinating Schwann cells (NMSCs), and unique groups of vascular smooth muscle cells (VSMCs), endothelial cells (ECs) and fibroblasts (FBs), which gave rise to a detailed cell type distribution across tissues. We demonstrated differences in the cellular composition across different cardiac regions and tissue-specific differences in transcription for each cell type, highlighting the molecular diversity and complex tissue architecture of the cardiovascular system. Specifically, we observed great transcriptional heterogeneities among ECs and FBs. Importantly, several cell subtypes had a unique regional localization such as a subtype of VSMCs enriched in the large vasculature. We found the cellular makeup of PV tissue is closer to heart tissue than to the large arteries. We further explored the ligand-receptor repertoire across cell clusters and tissues, and observed tissue-enriched cellular communication networks, including heightened Nppa - Npr1/2/3 signaling in the sinoatrial node.
UNASSIGNED: Through a large single nucleus sequencing effort encompassing over 500,000 nuclei, we broadened our understanding of cellular transcription in the healthy cardiovascular system. The existence of tissue-restricted cellular phenotypes suggests regional regulation of cardiovascular physiology. The overall conservation in gene expression and molecular pathways across rat and human cell types, together with our detailed transcriptional characterization of each cell type, offers the potential to identify novel therapeutic targets and improve preclinical models of cardiovascular disease.
摘要：
■尽管心血管系统的关键作用，我们对其细胞和转录多样性的理解仍然有限。因此，我们试图表征细胞组成，表型，分子途径，以及健康Wistar大鼠心血管系统中组织和亚组织水平的细胞类型之间的通讯网络，临床前心血管研究的重要模型。我们在受控条件下获得了高质量的组织样本，这些样本揭示了迄今为止在人类研究中无法获得的细胞细节水平。
■我们在10个不同区域的78个样本中进行了单核RNA测序，包括心脏的四个腔室。室间隔,窦房结,房室结,主动脉,肺动脉,和肺静脉（PV），产生了505,835个原子核的聚集图。我们确定了26种不同的细胞类型和其他亚型，包括许多罕见的细胞类型，如PV心肌细胞和非髓鞘雪旺细胞（NMSC），和独特的血管平滑肌细胞（VSMC），内皮细胞（ECs）和成纤维细胞（FBs），这导致了整个组织中详细的细胞类型分布。我们证明了不同心脏区域的细胞组成差异以及每种细胞类型转录的组织特异性差异。强调心血管系统的分子多样性和复杂的组织结构。具体来说,我们观察到ECs和FBs之间存在很大的转录异质性。重要的是,几种细胞亚型具有独特的区域定位,例如富集在大脉管系统中的VSMC亚型.我们发现PV组织的细胞组成比大动脉更接近心脏组织。我们进一步探索了跨细胞簇和组织的配体-受体库，并观察到组织富集的细胞通信网络，包括窦房结Nppa-Npr1/2/3信号增强。
■通过包含超过500,000个细胞核的大型单核测序工作，我们拓宽了我们对健康心血管系统中细胞转录的理解。组织限制性细胞表型的存在表明心血管生理学的区域调节。大鼠和人类细胞类型的基因表达和分子途径的总体保守性，以及我们对每种细胞类型的详细转录表征，提供了确定新的治疗靶点和改善心血管疾病临床前模型的潜力。
■我们在10个不同区域的78个样本中进行了单核RNA测序，包括心脏的四个腔室。室间隔,窦房结,房室结,主动脉,肺动脉,和肺静脉（PV），产生了505,835个原子核的聚集图。我们确定了26种不同的细胞类型和其他亚型，包括许多罕见的细胞类型，如PV心肌细胞和非髓鞘雪旺细胞（NMSC），和独特的血管平滑肌细胞（VSMC），内皮细胞（ECs）和成纤维细胞（FBs），这导致了整个组织中详细的细胞类型分布。我们证明了不同心脏区域的细胞组成差异以及每种细胞类型转录的组织特异性差异。强调心血管系统的分子多样性和复杂的组织结构。具体来说,我们观察到ECs和FBs之间存在很大的转录异质性。重要的是,几种细胞亚型具有独特的区域定位,例如富集在大脉管系统中的VSMC亚型.我们发现PV组织的细胞组成比大动脉更接近心脏组织。我们进一步探索了跨细胞簇和组织的配体-受体库，并观察到组织富集的细胞通信网络，包括窦房结Nppa-Npr1/2/3信号增强。
■通过包含超过500,000个细胞核的大型单核测序工作，我们拓宽了我们对健康心血管系统中细胞转录的理解。组织限制性细胞表型的存在表明心血管生理学的区域调节。大鼠和人类细胞类型的基因表达和分子途径的总体保守性，以及我们对每种细胞类型的详细转录表征，提供了确定新的治疗靶点和改善心血管疾病临床前模型的潜力。
