Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration.
IF: 13.417
Cited by: 140


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.


Gene Expression

MeSH terms

Bone Morphogenetic Proteins
Cell Differentiation
Cell Proliferation
Gene Expression Regulation
Myocytes, Cardiac
Signal Transduction
Zebrafish Proteins


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

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