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ZFIN ID: ZDB-PUB-160113-13
Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration
Wu, C.C., Kruse, F., Vasudevarao, M.D., Junker, J.P., Zebrowski, D.C., Fischer, K., Noël, E.S., Grün, D., Berezikov, E., Engel, F.B., van Oudenaarden, A., Weidinger, G., Bakkers, J.
Date: 2016
Source: Developmental Cell   36(1): 36-49 (Journal)
Registered Authors: Bakkers, Jeroen, Noël, Emily, Weidinger, Gilbert, Wu, Chi-Chung
Keywords: none
Microarrays: GEO:GSE74652
MeSH Terms:
  • Animals
  • Bone Morphogenetic Proteins/genetics*
  • Bone Morphogenetic Proteins/metabolism
  • Cell Differentiation
  • Cell Proliferation/genetics
  • Gene Expression Regulation/genetics*
  • Genome/genetics*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Regeneration/physiology*
  • Signal Transduction/genetics*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism
PubMed: 26748692 Full text @ Dev. Cell
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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.
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