Authors
Karel van Duijvenboden, Dennis EM de Bakker, Joyce CK Man, Rob Janssen, Marie Günthel, Matthew C Hill, Ingeborg B Hooijkaas, Ingeborg van der Made, Petra H van der Kraak, Aryan Vink, Esther E Creemers, James F Martin, Phil Barnett, Jeroen Bakkers, Vincent M Christoffels
Publication date
2019/9/3
Journal
Circulation
Volume
140
Issue
10
Pages
864-879
Publisher
Lippincott Williams & Wilkins
Description
Background
Surviving cells in the postinfarction border zone are subjected to intense fluctuations of their microenvironment. Recently, border zone cardiomyocytes have been specifically implicated in cardiac regeneration. Here, we defined their unique transcriptional and regulatory properties, and comprehensively validated new molecular markers, including Nppb, encoding B-type natriuretic peptide, after infarction.
Methods
Transgenic reporter mice were used to identify the Nppb-positive border zone after myocardial infarction. Transcriptome analysis of remote, border, and infarct zones and of purified cardiomyocyte nuclei was performed using RNA-sequencing. Top candidate genes displaying border zone spatial specificity were histologically validated in ischemic human hearts. Mice in which Nppb was deleted by genome editing were subjected to myocardial infarction. Chromatin accessibility landscapes of …
Total citations
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