研究人员利用单细胞基因表达、染色质可及性和空间转录组分析，对心肌梗死患者和对照组的心肌在不同时间点的多个生理区进行了综合的高分辨率人类心脏重塑图谱。多模式的数据整合使研究人员能够以更高的分辨率评估心脏细胞类型的组成，并通过识别损伤、修复和重塑的不同组织结构，产生对心脏转录组和表观基因组变化的洞察力。研究人员确定并验证了主要细胞类型的疾病特异性心脏细胞状态，并在其空间背景下进行分析，评估其对其他细胞类型的依赖性。这些数据阐明了人类心肌组织的分子原理，再现了缺血性损伤后心肌细胞和骨髓细胞的渐变过程。总之，这项研究提供了人类心肌梗死的综合分子图谱，代表了该领域的重要参考，为心脏疾病的高级机制和治疗研究铺平了道路。
据悉，心肌梗死是全世界死亡的主要原因之一。虽然在急性期治疗方面取得了进展，但对重塑过程的不完全了解限制了减少晚期死亡率的治疗效果。
附：英文原文
Title: Spatial multi-omic map of human myocardial infarction
Author: Kuppe, Christoph, Ramirez Flores, Ricardo O., Li, Zhijian, Hayat, Sikander, Levinson, Rebecca T., Liao, Xian, Hannani, Monica T., Tanevski, Jovan, Wnnemann, Florian, Nagai, James S., Halder, Maurice, Schumacher, David, Menzel, Sylvia, Schfer, Gideon, Hoeft, Konrad, Cheng, Mingbo, Ziegler, Susanne, Zhang, Xiaoting, Peisker, Fabian, Kaesler, Nadine, Saritas, Turgay, Xu, Yaoxian, Kassner, Astrid, Gummert, Jan, Morshuis, Michiel, Amrute, Junedh, Veltrop, Rogier J. A., Boor, Peter, Klingel, Karin, Van Laake, Linda W., Vink, Aryan, Hoogenboezem, Remco M., Bindels, Eric M. J., Schurgers, Leon, Sattler, Susanne, Schapiro, Denis, Schneider, Rebekka K., Lavine, Kory, Milting, Hendrik, Costa, Ivan G., Saez-Rodriguez, Julio, Kramann, Rafael
Issue&Volume: 2022-08-10
Abstract: Myocardial infarction is a leading cause of death worldwide1. Although advances have been made in acute treatment, an incomplete understanding of remodelling processes has limited the effectiveness of therapies to reduce late-stage mortality2. Here we generate an integrative high-resolution map of human cardiac remodelling after myocardial infarction using single-cell gene expression, chromatin accessibility and spatial transcriptomic profiling of multiple physiological zones at distinct time points in myocardium from patients with myocardial infarction and controls. Multi-modal data integration enabled us to evaluate cardiac cell-type compositions at increased resolution, yielding insights into changes of the cardiac transcriptome and epigenome through the identification of distinct tissue structures of injury, repair and remodelling. We identified and validated disease-specific cardiac cell states of major cell types and analysed them in their spatial context, evaluating their dependency on other cell types. Our data elucidate the molecular principles of human myocardial tissue organization, recapitulating a gradual cardiomyocyte and myeloid continuum following ischaemic injury. In sum, our study provides an integrative molecular map of human myocardial infarction, represents an essential reference for the field and paves the way for advanced mechanistic and therapeutic studies of cardiac disease.
DOI: 10.1038/s41586-022-05060-x
Source: https://www.nature.com/articles/s41586-022-05060-x
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
