Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration

Chi-Chung Wu, Fabian Kruse, Mohankrishna Dalvoy Vasudevarao, Jan Philipp Junker, David C Zebrowski, Kristin Fischer, Emily S Noël, Dominic Grün, Eugene Berezikov, Felix B Engel, Alexander van Oudenaarden, Gilbert Weidinger, Jeroen Bakkers

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

Samenvatting

In contrast to mammals, zebrafish regenerate heart injuries via proliferation of cardiomyocytes located near the wound border. To identify regulators of cardiomyocyte proliferation, we used spatially resolved RNA sequencing (tomo-seq) and generated a high-resolution genome-wide atlas of gene expression in the regenerating zebrafish heart. Interestingly, we identified two wound border zones with distinct expression profiles, including the re-expression of embryonic cardiac genes and targets of bone morphogenetic protein (BMP) signaling. Endogenous BMP signaling has been reported to be detrimental to mammalian cardiac repair. In contrast, we find that genetic or chemical inhibition of BMP signaling in zebrafish reduces cardiomyocyte dedifferentiation and proliferation, ultimately compromising myocardial regeneration, while bmp2b overexpression is sufficient to enhance it. Our results provide a resource for further studies on the molecular regulation of cardiac regeneration and reveal intriguing differential cellular responses of cardiomyocytes to a conserved signaling pathway in regenerative versus non-regenerative hearts.

Originele taal-2Engels
Pagina's (van-tot)36-49
Aantal pagina's14
TijdschriftDevelopmental Cell
Volume36
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 11 jan 2016

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