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

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 the...

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Main Authors: Hagen Klett, Lonny Jürgensen, Patrick Most, Martin Busch, Fabian Günther, Gergana Dobreva, Florian Leuschner, David Hassel, Hauke Busch, Melanie Boerries
Format: Article
Language:English
Published: MDPI AG 2018-12-01
Series:Biomolecules
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Online Access:http://www.mdpi.com/2218-273X/9/1/11
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author Hagen Klett
Lonny Jürgensen
Patrick Most
Martin Busch
Fabian Günther
Gergana Dobreva
Florian Leuschner
David Hassel
Hauke Busch
Melanie Boerries
author_facet Hagen Klett
Lonny Jürgensen
Patrick Most
Martin Busch
Fabian Günther
Gergana Dobreva
Florian Leuschner
David Hassel
Hauke Busch
Melanie Boerries
author_sort Hagen Klett
collection DOAJ
description 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.
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spelling doaj.art-748016a256a94432a5f8e55313f74a122022-12-21T21:33:39ZengMDPI AGBiomolecules2218-273X2018-12-01911110.3390/biom9010011biom9010011Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart RegenerationHagen Klett0Lonny Jürgensen1Patrick Most2Martin Busch3Fabian Günther4Gergana Dobreva5Florian Leuschner6David Hassel7Hauke Busch8Melanie Boerries9Institute of Molecular Medicine and Cell Research, University of Freiburg, 79104 Freiburg, GermanyDepartment of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Anatomy and Developmental Biology, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, GermanyDepartment of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, GermanyDepartment of Cardiology, Angiology and Pneumology, University Hospital Heidelberg, 69120 Heidelberg, GermanyLuebeck Institute of Experimental Dermatology and Institute of Cardiogenetics, University of Luebeck, 23562 Luebeck, GermanyInstitute of Molecular Medicine and Cell Research, University of Freiburg, 79104 Freiburg, GermanyHeart 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.http://www.mdpi.com/2218-273X/9/1/11heart regenerationzebrafishcryoinjurydynamic transcriptomemiRNA
spellingShingle Hagen Klett
Lonny Jürgensen
Patrick Most
Martin Busch
Fabian Günther
Gergana Dobreva
Florian Leuschner
David Hassel
Hauke Busch
Melanie Boerries
Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
Biomolecules
heart regeneration
zebrafish
cryoinjury
dynamic transcriptome
miRNA
title Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
title_full Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
title_fullStr Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
title_full_unstemmed Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
title_short Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration
title_sort delineating the dynamic transcriptome response of mrna and microrna during zebrafish heart regeneration
topic heart regeneration
zebrafish
cryoinjury
dynamic transcriptome
miRNA
url http://www.mdpi.com/2218-273X/9/1/11
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