Mesh : Animals Fibrosis Single-Cell Analysis / methods Humans Fibroblasts / metabolism Transcriptome Mice Myocardium / metabolism pathology Myofibroblasts / metabolism pathology Gene Expression Profiling

来  源:   DOI:10.1126/sciadv.adk8501   PDF(Pubmed)

Abstract:
Single-cell technology has allowed researchers to probe tissue complexity and dynamics at unprecedented depth in health and disease. However, the generation of high-dimensionality single-cell atlases and virtual three-dimensional tissues requires integrated reference maps that harmonize disparate experimental designs, analytical pipelines, and taxonomies. Here, we present a comprehensive single-cell transcriptome integration map of cardiac fibrosis, which underpins pathophysiology in most cardiovascular diseases. Our findings reveal similarity between cardiac fibroblast (CF) identities and dynamics in ischemic versus pressure overload models of cardiomyopathy. We also describe timelines for commitment of activated CFs to proliferation and myofibrogenesis, profibrotic and antifibrotic polarization of myofibroblasts and matrifibrocytes, and CF conservation across mouse and human healthy and diseased hearts. These insights have the potential to inform knowledge-based therapies.
摘要:
单细胞技术使研究人员能够在健康和疾病方面以前所未有的深度探测组织的复杂性和动力学。然而,高维单细胞图集和虚拟三维组织的生成需要整合的参考图,以协调不同的实验设计,分析管道,和分类法。这里,我们提出了一个全面的心脏纤维化的单细胞转录组整合图,这是大多数心血管疾病的病理生理学基础。我们的发现揭示了心肌成纤维细胞(CF)身份和动态之间的相似性,在心肌病的缺血性和压力超负荷模型。我们还描述了激活的CFs对增殖和肌纤维形成的承诺的时间表,肌成纤维细胞和基质纤维细胞的促纤维化和抗纤维化极化,以及小鼠和人类健康和患病心脏的CF保护。这些见解有可能为基于知识的疗法提供信息。
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