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Biomolecules. 2018 Dec 28;9(1). pii: E11. doi: 10.3390/biom9010011.

Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration.

Author information

1
Institute of Molecular Medicine and Cell Research, University of Freiburg, 79104 Freiburg, Germany. hagen.klett@gmail.com.
2
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany. Lonny.Juergensen@med.uni-heidelberg.de.
3
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany. Lonny.Juergensen@med.uni-heidelberg.de.
4
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany. Patrick.Most@med.uni-heidelberg.de.
5
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany. Patrick.Most@med.uni-heidelberg.de.
6
Center for Translational Medicine, Jefferson University, Philadelphia, PA 19107, USA. Patrick.Most@med.uni-heidelberg.de.
7
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany. Martin.Busch@med.uni-heidelberg.de.
8
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany. Martin.Busch@med.uni-heidelberg.de.
9
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany. f.guenther@rbk.de.
10
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany. f.guenther@rbk.de.
11
Department of Anatomy and Developmental Biology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany. gergana.dobreva@medma.uni-heidelberg.de.
12
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany. Florian.Leuschner@med.uni-heidelberg.de.
13
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany. Florian.Leuschner@med.uni-heidelberg.de.
14
Department of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, Germany. david.hassel@gmail.com.
15
German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, 69120 Heidelberg, Germany. david.hassel@gmail.com.
16
Luebeck Institute of Experimental Dermatology and Institute of Cardiogenetics, University of Luebeck, 23562 Luebeck, Germany. hauke.busch@uni-luebeck.de.
17
Institute of Molecular Medicine and Cell Research, University of Freiburg, 79104 Freiburg, Germany. m.boerries@dkfz.de.
18
Comprehensive Cancer Center Freiburg (CCCF), University Medical Center, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany. m.boerries@dkfz.de.
19
German Cancer Consortium (DKTK), Partner Site Freiburg, 79104 Freiburg and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. m.boerries@dkfz.de.

Abstract

Heart diseases are the leading cause of death for the vast majority of people around the world, which is often due to the limited capability of human cardiac regeneration. In contrast, zebrafish have the capacity to fully regenerate their hearts after cardiac injury. Understanding and activating these mechanisms would improve health in patients suffering from long-term consequences of ischemia. Therefore, we monitored the dynamic transcriptome response of both mRNA and microRNA in zebrafish at 1⁻160 days post cryoinjury (dpi). Using a control model of sham-operated and healthy fish, we extracted the regeneration specific response and further delineated the spatio-temporal organization of regeneration processes such as cell cycle and heart function. In addition, we identified novel (miR-148/152, miR-218b and miR-19) and previously known microRNAs among the top regulators of heart regeneration by using theoretically predicted target sites and correlation of expression profiles from both mRNA and microRNA. In a cross-species effort, we validated our findings in the dynamic process of rat myoblasts differentiating into cardiomyocytes-like cells (H9c2 cell line). Concluding, we elucidated different phases of transcriptomic responses during zebrafish heart regeneration. Furthermore, microRNAs showed to be important regulators in cardiomyocyte proliferation over time.

KEYWORDS:

cryoinjury; dynamic transcriptome; heart regeneration; miRNA; zebrafish

PMID:
30597924
PMCID:
PMC6359357
DOI:
10.3390/biom9010011
[Indexed for MEDLINE]
Free PMC Article

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