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

Wu CC, Kruse F, Vasudevarao MD, Junker JP, Zebrowski D, Fischer K, Noel ES, Grun D, Berezikov E, Engel F, Van Oudenaarden A, Weidinger G, Bakkers J (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Developmental Cell Elsevier (Cell Press)

Book Volume: 36

Pages Range: 36-49

Journal Issue: 1

DOI: 10.1016/j.devcel.2015.12.010

Abstract

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.

Authors with CRIS profile

Felix Engel Department of Nephropathology

Involved external institutions

Universität Ulm DE Germany (DE) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL) Technische Universität Dresden DE Germany (DE) University of Groningen / Rijksuniversiteit Groningen NL Netherlands (NL)

How to cite

APA:

Wu, C.-C., Kruse, F., Vasudevarao, M.D., Junker, J.P., Zebrowski, D., Fischer, K.,... Bakkers, J. (2016). Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration. Developmental Cell, 36(1), 36-49. https://doi.org/10.1016/j.devcel.2015.12.010

MLA:

Wu, Chi-Chung, et al. "Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration." Developmental Cell 36.1 (2016): 36-49.

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