PUBLICATION

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

Authors
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.
ID
ZDB-PUB-160113-13
Date
2016
Source
Developmental Cell   36(1): 36-49 (Journal)
Registered Authors
Bakkers, Jeroen, Noël, Emily, Weidinger, Gilbert, Wu, Chi-Chung
Keywords
none
Datasets
GEO:GSE74652
MeSH Terms
  • Cell Differentiation
  • Regeneration/physiology*
  • Signal Transduction/genetics*
  • Bone Morphogenetic Proteins/genetics*
  • Bone Morphogenetic Proteins/metabolism
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism
  • Animals
  • Genome/genetics*
  • Gene Expression Regulation/genetics*
  • Cell Proliferation/genetics
(all 14)
PubMed
26748692 Full text @ Dev. Cell
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.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
No data available
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ae1TgTransgenic Insertion
    f2TgTransgenic Insertion
      fr13TgTransgenic Insertion
        fr14TgTransgenic Insertion
          hu4087
            		Point Mutation
            li3TgTransgenic Insertion
              pt510TgTransgenic Insertion
                sqet27EtTransgenic Insertion
                  twu34TgTransgenic Insertion
                    y1TgTransgenic Insertion
                      1 - 10 of 10
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                      Human Disease / Model
                      No data available
                      Sequence Targeting Reagents
                      No data available
                      Fish
                      No data available
                      Antibodies
                      Orthology
                      No data available
                      Engineered Foreign Genes
                      Marker Marker Type Name
                      DsRed2EFGDsRed2
                      EGFPEFGEGFP
                      GFPEFGGFP
                      1 - 3 of 3
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                      Mapping
                      No data available
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                      Citation
                      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. (2016) Spatially Resolved Genome-wide Transcriptional Profiling Identifies BMP Signaling as Essential Regulator of Zebrafish Cardiomyocyte Regeneration. Developmental Cell. 36(1):36-49.