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1. The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition

Author

Glaser, Simone F., Heumüller, Andreas W., Tombor, Lukas, Hofmann, Patrick, Muhly-Reinholz, Marion, Fischer, Ariane, Gunther, Stefan, Kokot, Karoline E., Hassel, David, Kumar, Sandeep, Jo, Hanjoong, Boon, Reinier A., Abplanalp, Wesley, John, David, Boeckel, Jes-Niels, and Dimmeler, Stefanie

Published
2020

2. Leveraging chromatin state transitions for the identification of regulatory networks orchestrating heart regeneration

Author

Cordero, Julio, primary, Elsherbiny, Adel, additional, Wang, Yinuo, additional, Jürgensen, Lonny, additional, Constanty, Florian, additional, Günther, Stefan, additional, Boerries, Melanie, additional, Heineke, Joerg, additional, Beisaw, Arica, additional, Leuschner, Florian, additional, Hassel, David, additional, and Dobreva, Gergana, additional

Published
2024
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3. Fibronectin mediates mesendodermal cell fate decisions

Author

Cheng, Paul, Andersen, Peter, Hassel, David, Kaynak, Bogac L, Limphong, Pattraranee, Juergensen, Lonny, Kwon, Chulan, and Srivastava, Deepak

Subjects
Biochemistry and Cell Biology, Biological Sciences, Stem Cell Research, Stem Cell Research - Embryonic - Non-Human, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Animals, Cell Differentiation, Coculture Techniques, Embryo, Nonmammalian, Embryonic Induction, Embryonic Stem Cells, Endoderm, Extracellular Matrix, Fetal Proteins, Fibronectins, Gene Expression Regulation, Developmental, Integrin beta1, Mesoderm, Mice, RNA, Small Interfering, T-Box Domain Proteins, Wnt Signaling Pathway, Zebrafish, Zebrafish Proteins, beta Catenin, Fibronectin, Integrin-beta 1, Wnt, Integrin-β1, Medical and Health Sciences, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Non-cell-autonomous signals often play crucial roles in cell fate decisions during animal development. Reciprocal signaling between endoderm and mesoderm is vital for embryonic development, yet the key signals and mechanisms remain unclear. Here, we show that endodermal cells efficiently promote the emergence of mesodermal cells in the neighboring population through signals containing an essential short-range component. The endoderm-mesoderm interaction promoted precardiac mesoderm formation in mouse embryonic stem cells and involved endodermal production of fibronectin. In vivo, fibronectin deficiency resulted in a dramatic reduction of mesoderm accompanied by endodermal expansion in zebrafish embryos. This event was mediated by regulation of Wnt signaling in mesodermal cells through activation of integrin-β1. Our findings highlight the importance of the extracellular matrix in mediating short-range signals and reveal a novel function of endoderm, involving fibronectin and its downstream signaling cascades, in promoting the emergence of mesoderm.

Published
2013

4. miR-10 Regulates Angiogenesis through VEGF Signaling Titration

Author

Hassel, David, Katus, Hugo A, Stainier, Didier Y, and Srivastava, Deepak

Subjects
Vascular development, Angiogenesis, Cell signaling, Cardiovascular System & Hematology, Clinical Sciences, Cardiorespiratory Medicine and Haematology, Public Health and Health Services
Published
2012

5. MicroRNA-10 regulates the angiogenic behavior of zebrafish and human endothelial cells by promoting vascular endothelial growth factor signaling.

Author

Hassel, David, Cheng, Paul, White, Mark, Ivey, Kathryn, Kroll, Jens, Augustin, Hellmut, Katus, Hugo, Stainier, Didier, and Srivastava, Deepak

Subjects
Animals, Animals, Genetically Modified, Base Sequence, Cell Proliferation, Cells, Cultured, Endothelial Cells, Female, Gene Knockdown Techniques, Green Fluorescent Proteins, Human Umbilical Vein Endothelial Cells, Humans, Immunoblotting, Larva, Male, Mice, MicroRNAs, Microscopy, Confocal, Neovascularization, Physiologic, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Nucleic Acid, Signal Transduction, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2, Zebrafish
Abstract

RATIONALE: Formation and remodeling of the vasculature during development and disease involve a highly conserved and precisely regulated network of attractants and repellants. Various signaling pathways control the behavior of endothelial cells, but their posttranscriptional dose titration by microRNAs is poorly understood. OBJECTIVE: To identify microRNAs that regulate angiogenesis. METHODS AND RESULTS: We show that the highly conserved microRNA family encoding miR-10 regulates the behavior of endothelial cells during angiogenesis by positively titrating proangiogenic signaling. Knockdown of miR-10 led to premature truncation of intersegmental vessel growth in the trunk of zebrafish larvae, whereas overexpression of miR-10 promoted angiogenic behavior in zebrafish and cultured human umbilical venous endothelial cells. We found that miR-10 functions, in part, by directly regulating the level of fms-related tyrosine kinase 1 (FLT1), a cell-surface protein that sequesters vascular endothelial growth factor, and its soluble splice variant sFLT1. The increase in FLT1/sFLT1 protein levels upon miR-10 knockdown in zebrafish and in human umbilical venous endothelial cells inhibited the angiogenic behavior of endothelial cells largely by antagonizing vascular endothelial growth factor receptor 2 signaling. CONCLUSIONS: Our study provides insights into how FLT1 and vascular endothelial growth factor receptor 2 signaling is titrated in a microRNA-mediated manner and establishes miR-10 as a potential new target for the selective modulation of angiogenesis.

Published
2012

10. Nexilin mutations destabilize cardiac Z-disks and lead to dilated cardiomyopathy

Author

Hassel, David, Dahme, Tillman, Erdmann, Jeanette, Meder, Benjamin, Huge, Andreas, Stoll, Monika, Just, Steffen, Hess, Alexander, Ehlermann, Philipp, Weichenhan, Dieter, Grimmler, Matthias, Liptau, Henrike, Hetzer, Roland, Regitz-Zagrosek, Vera, Fischer, Christine, Nurnberg, Peter, Schunkert, Heribert, Katus, Hugo A., and Rottbauer, Wolfgang

Subjects
Gene mutations -- Analysis -- Genetic aspects -- Research, Heart diseases -- Genetic aspects -- Development and progression -- Research, Striated muscle -- Properties -- Analysis -- Genetic aspects -- Research, Molecular biology -- Research -- Analysis -- Genetic aspects, Medical genetics -- Research -- Analysis, Cardiomyopathy -- Genetic aspects -- Development and progression -- Research, Biological sciences, Health
Abstract

Z-disks, the mechanical integration sites of heart and skeletal muscle cells, link anchorage of myofilaments to force reception and processing. The key molecules that enable the Z-disk to persistently withstand the extreme mechanical forces during muscle contraction have not yet been identified. Here we isolated nexilin (encoded by NEXM as a novel Z-disk protein. Loss of nexilin in zebrafish led to perturbed Z-disk stability and heart failure. To evaluate the role of nexilin in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found several mutations in NEKN associated with the disease. Nexilin mutation carriers showed the same cardiac Z-disk pathology as observed in nexilin-deficient zebrafish. Expression in zebrafish of nexilin proteins encoded by NEXN mutant alleles induced Z-disk damage and heart failure, demonstrating a dominant-negative effect and confirming the disease-causing nature of these mutations. Increasing mechanical strain aggravated Z-disk damage in nexilin-deficient skeletal muscle, implying a unique role of nexilin in protecting Z-disks from mechanical trauma., In striated muscle cells, actin and myosin are aligned in arrays of thin and thick filaments to form sarcomeres. Thin filaments of adjacent sarcomeres are anchored in the Z-disk, which [...]

Published
2009

12. Erratum:The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition (Proceedings of the National Academy of Sciences of the United States of America (2020) 117 (4180-4187) DOI: 10.1073/pnas.1913481117)

Author

Glaser, Simone F., Heumüller, Andreas W., Tombor, Lukas, Hofmann, Patrick, Muhly-Reinholz, Marion, Fischer, Ariane, Günther, Stefan, Kokot, Karoline E., Okada, Hitoshi, Hassel, David, Kumar, Sandeep, Jo, Hanjoong, Boon, Reinier A., Abplanalp, Wesley, John, David, Boeckel, Jes Niels, and Dimmeler, Stefanie

Abstract

Correction for “The histone demethylase JMJD2B regulates endothelial-to-mesenchymal transition,” by Simone F. Glaser, Andreas W. Heumüller, Lukas Tombor, Patrick Hofmann, Marion Muhly-Reinholz, Ariane Fischer, Stefan Günther, Karoline E. Kokot, David Hassel, Sandeep Kumar, Hanjoong Jo, Reinier A. Boon, Wesley Abplanalp, David John, Jes-Niels Boeckel, and Stefanie Dimmeler, which was first published February 7, 2020; 10.1073/pnas.1913481117 (Proc. Natl. Acad. Sci. U.S.A. 117, 4180-4187). The authors note that Hitoshi Okada should be added to the author list between Karoline E. Kokot and David Hassel. Hitoshi Okada should be credited with providing mice. The corrected author line, affiliation line, and author contributions appear below. The online version has been corrected.

Published
2020
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14. miR-128a Acts as a Regulator in Cardiac Development by Modulating Differentiation of Cardiac Progenitor Cell Populations

Author

Hoelscher, Sarah C., primary, Stich, Theresia, additional, Diehm, Anne, additional, Lahm, Harald, additional, Dreßen, Martina, additional, Zhang, Zhong, additional, Neb, Irina, additional, Aherrahrou, Zouhair, additional, Erdmann, Jeanette, additional, Schunkert, Heribert, additional, Santamaria, Gianluca, additional, Cuda, Giovanni, additional, Gilsbach, Ralf, additional, Hein, Lutz, additional, Lange, Rüdiger, additional, Hassel, David, additional, Krane, Markus, additional, and Doppler, Stefanie A., additional

Published
2020
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16. The Zebrafish (Danio rerio) Is a Relevant Model for Studying Sex-Specific Effects of 17β-Estradiol in the Adult Heart

Author

Hein, Selina, Hassel, David, and Kararigas, Georgios

Subjects
sex differences, animal structures, cardiac, cardiovascular disease, estrogen, contractility, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
Abstract

Cardiovascular diseases are a major cause of morbidity and mortality, and there are significant sex differences therein. However, the underlying mechanisms are poorly understood. The steroid hormone 17β-estradiol (E2) is thought to play a major role in cardiovascular sex differences and to be protective, but this may not hold true for males. We aimed at assessing whether the zebrafish is an appropriate model for the study of E2 effects in the heart. We hypothesized that E2 regulates the cardiac contractility of adult zebrafish in a sex-specific manner. Male and female zebrafish were treated with vehicle (control) or E2 and the cardiac contractility was measured 0, 4, 7 and 14 days after treatment initiation using echocardiography. There was no significant effect on the heart rate by E2. Notably, there was a significant decrease in the ejection fraction of male zebrafish treated with E2 compared with controls. By contrast, there was no major difference in the ejection fraction between the two female groups. The dramatic effect in male zebrafish occurred as early as 4 days post treatment initiation. Although there was no significant difference in stroke volume and cardiac output between the two male groups, these were significantly higher in female zebrafish treated with E2 compared with controls. Gene expression analysis revealed that the levels of estrogen receptors were comparable among all groups. In conclusion, our data demonstrate that the adult zebrafish heart robustly responds to E2 and this occurs in a sex-specific manner. Given the benefits of using zebrafish as a model, new targets may be identified for the development of novel cardiovascular therapies for male and female patients. This would contribute towards the realization of personalized medicine.

Published
2019
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17. Semantic storage of climate data on object stores

Author

Massey, Neil, Hassel, David, Jones, Matt, Kershaw, Phil, and Lawrence, Bryan

Abstract

High performance computers, data analysis systems and data centres typically use large (often parallel) POSIX filesystems. However, with the advent of exascale climate data, such filesystems cannot deliver price/performance across all aspects of the workflow from simulation to analysis. Alternative methods of storing large amounts of data are necessary, potentially as part of tiered storage environments. One alternative option is object storage, which potentially addresses many of the challenges of managing data at exascale, including decoupling from traditional POSIX semantics for user management and presenting a universal interface for access from inside the data centre and remotely across wide area networks. In particular, using the Amazon S3 interface allows hosting data more easily on public cloud or adopting hybrid-cloud scenarios. However, this approach raises a number of problems: 1) Determining a means of storage for large files that will facilitate efficient access; 2) Enabling meaningful search of data, when the data is distributed across objects rather than in a hierarchical file system; 3) Supporting existing applications which depend on POSIX semantics; and 4) Managing the distributed objects. To address these issues large data sets can be broken into "fragments" stored as objects, each fragment containing a subset of the data. This allows for parallel access to the fragments, improving the performance of reading the data across a network - particularly if the application and storage have semantic information about the nature of the objects. Here we present a new method of splitting netCDF files into subarray fragments and storing each fragment as an object in an object storage system with an S3 interface. The metadata and domain for each climate variable are stored in a master array file, as well as the location in the master array and URI of each subarray fragment. This master array file can be written to a location not within the object storage, for example a POSIX file system on a SSD. It allows for fast search and indexing of the metadata without having to reassemble the subarray fragments. Each subarray fragment is stored as a self-contained netCDF file within the object storage, complete with the metadata and subdomain for that subarray, allowing reconstruction of the data, if the master file is lost, using standard climate data tools. The method is implemented in Python and Cython as the S3-netCDF4-python package, which is a subclass of the standard netCDF4-python package. This allows any improvements in the standard package, and lower software stack, to be automatically included in S3-netCDF4-python. Also, as a subclass of netCDF4-python, S3-netCDF4- python presents a well-known interface and data model to the scientist, hiding the physical location of the files and allowing scientists to continue using existing workflows based on netCDF4-python. We conclude by providing some examples and presenting some performance metrics to compare with storing netCDF files on other disk systems or using other interfaces such as OPeNDAP. Some limited comparison with other object store approaches such as the HDF Groups’s Highly Scalable Data Server will also be included.

Published
2018
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19. Biallelic Variants in ASNA1 , Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy

Author

Verhagen, Judith M.A., primary, van den Born, Myrthe, additional, van der Linde, Herma C., additional, G.J. Nikkels, Peter, additional, Verdijk, Rob M., additional, Kivlen, Maryann H., additional, van Unen, Leontine M.A., additional, Baas, Annette F., additional, ter Heide, Henriette, additional, van Osch-Gevers, Lennie, additional, Hoogeveen-Westerveld, Marianne, additional, Herkert, Johanna C., additional, Bertoli-Avella, Aida M., additional, van Slegtenhorst, Marjon A., additional, Wessels, Marja W., additional, Verheijen, Frans W., additional, Hassel, David, additional, Hofstra, Robert M.W., additional, Hegde, Ramanujan S., additional, van Hasselt, Peter M., additional, van Ham, Tjakko J., additional, and van de Laar, Ingrid M.B.H., additional

Published
2019
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20. Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy

Author

Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., van de Laar, Ingrid M.B.H., Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., and van de Laar, Ingrid M.B.H.

Published
2019

21. Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy

Author

UMC Utrecht, Pathologie Pathologen staf, Cancer, Genetica Klinische Genetica, Circulatory Health, Cardiologie patientenzorg, Child Health, Cluster C, Metabole ziekten patientenzorg, Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., van de Laar, Ingrid M.B.H., UMC Utrecht, Pathologie Pathologen staf, Cancer, Genetica Klinische Genetica, Circulatory Health, Cardiologie patientenzorg, Child Health, Cluster C, Metabole ziekten patientenzorg, Verhagen, Judith M.A., van den Born, Myrthe, van der Linde, Herma C., G J Nikkels, Peter, Verdijk, Rob M., Kivlen, Maryann H., van Unen, Leontine M.A., Baas, Annette F., Ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C., Bertoli-Avella, Aida M., van Slegtenhorst, Marjon A., Wessels, Marja W., Verheijen, Frans W., Hassel, David, Hofstra, Robert M.W., Hegde, Ramanujan S., van Hasselt, Peter M., van Ham, Tjakko J., and van de Laar, Ingrid M.B.H.

Published
2019

24. Retinoic acid catabolizing enzymeCYP26C1 is a genetic modifier inSHOXdeficiency

Author

Montalbano, Antonino, primary, Juergensen, Lonny, additional, Roeth, Ralph, additional, Weiss, Birgit, additional, Fukami, Maki, additional, Fricke‐Otto, Susanne, additional, Binder, Gerhard, additional, Ogata, Tsutomu, additional, Decker, Eva, additional, Nuernberg, Gudrun, additional, Hassel, David, additional, and Rappold, Gudrun A, additional

Published
2016
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30. Regulation of β1 Integrin-Klf2-Mediated Angiogenesis by CCM Proteins

Author

Renz, Marc, primary, Otten, Cécile, additional, Faurobert, Eva, additional, Rudolph, Franziska, additional, Zhu, Yuan, additional, Boulday, Gwénola, additional, Duchene, Johan, additional, Mickoleit, Michaela, additional, Dietrich, Ann-Christin, additional, Ramspacher, Caroline, additional, Steed, Emily, additional, Manet-Dupé, Sandra, additional, Benz, Alexander, additional, Hassel, David, additional, Vermot, Julien, additional, Huisken, Jan, additional, Tournier-Lasserve, Elisabeth, additional, Felbor, Ute, additional, Sure, Ulrich, additional, Albiges-Rizo, Corinne, additional, and Abdelilah-Seyfried, Salim, additional

Published
2015
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32. Functional missense and splicing variants in the retinoic acid catabolizing enzyme CYP26C1in idiopathic short stature

Author

Montalbano, Antonino, Juergensen, Lonny, Fukami, Maki, Thiel, Christian, Hauer, Nadine, Roeth, Ralph, Weiss, Birgit, Naiki, Yasuhiro, Ogata, Tsutomu, Hassel, David, and Rappold, Gudrun

Abstract

Height is a complex quantitative trait with a high heritability. Short stature is diagnosed when height is significantly below the average of the general population for that person’s age and sex. We have recently found that the retinoic acid degrading enzyme CYP26C1 modifies SHOX deficiency phenotypes toward more severe clinical manifestations. Here, we asked whether damaging variants in CYP26C1alone could lead to short stature. We performed exome and Sanger sequencing to analyze 856 individuals with short stature where SHOX deficiency was previously excluded. Three different damaging missense variants and one splicing variant were identified in six independent individuals; the functional significance of the identified variants was tested in vitro or in vivo using zebrafish as a model. The genetic and functional data reported here indicate that CYP26C1represents a novel gene underlying growth disorders and that damaging variants in the absence of SHOXvariants can lead to short stature.

Published
2018
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33. Stress maximum and steady extensional flow of branched polymer melts

Author

Huang, Qian, Skov, Anne Ladegaard, Rasmussen, Henrik K., Hoyle, David M., McLeish, Thomas C., Harlen, Oliver, Hassel, David, Lord, Tim D., Mackley, Malcolm R., Hassager, Ole, Huang, Qian, Skov, Anne Ladegaard, Rasmussen, Henrik K., Hoyle, David M., McLeish, Thomas C., Harlen, Oliver, Hassel, David, Lord, Tim D., Mackley, Malcolm R., and Hassager, Ole

Published
2011

38. The myosin-interacting protein SMYD1 is essential for sarcomere organization

Author

Just, Steffen, primary, Meder, Benjamin, additional, Berger, Ina M., additional, Etard, Christelle, additional, Trano, Nicole, additional, Patzel, Eva, additional, Hassel, David, additional, Marquart, Sabine, additional, Dahme, Tillman, additional, Vogel, Britta, additional, Fishman, Mark C., additional, Katus, Hugo A., additional, Strähle, Uwe, additional, and Rottbauer, Wolfgang, additional

Published
2011
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39. A dual role for ErbB2 signaling in cardiac trabeculation

Author

Liu, Jiandong, primary, Bressan, Michael, additional, Hassel, David, additional, Huisken, Jan, additional, Staudt, David, additional, Kikuchi, Kazu, additional, Poss, Kenneth D., additional, Mikawa, Takashi, additional, and Stainier, Didier Y. R., additional

Published
2010
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43. Deficient Zebrafish Ether-à-Go-Go –Related Gene Channel Gating Causes Short-QT Syndrome in Zebrafish Reggae Mutants

Author

Hassel, David, primary, Scholz, Eberhard P., additional, Trano, Nicole, additional, Friedrich, Oliver, additional, Just, Steffen, additional, Meder, Benjamin, additional, Weiss, Daniel L., additional, Zitron, Edgar, additional, Marquart, Sabine, additional, Vogel, Britta, additional, Karle, Christoph A., additional, Seemann, Gunnar, additional, Fishman, Mark C., additional, Katus, Hugo A., additional, and Rottbauer, Wolfgang, additional

Published
2008
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44. Cardiac Myosin Light Chain-2

Author

Rottbauer, Wolfgang, primary, Wessels, Georgia, additional, Dahme, Tillman, additional, Just, Steffen, additional, Trano, Nicole, additional, Hassel, David, additional, Burns, Charles Geoffrey, additional, Katus, Hugo A., additional, and Fishman, Mark C., additional

Published
2006
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45. Identification and functional characterization of zebrafish K2P10.1 (TREK2) two-pore-domain K+ channels

Author

Gierten, Jakob, Hassel, David, Schweizer, Patrick A., Becker, Rüdiger, Katus, Hugo A., and Thomas, Dierk

Subjects
*ZEBRA danio, *POTASSIUM channels, *MEMBRANE proteins, *ELECTROPHYSIOLOGY, *COMPLEMENTARY DNA, *FISH genetics, *ARACHIDONIC acid
Abstract

Abstract: Two-pore-domain potassium (K2P) channels mediate K+ background currents that stabilize the resting membrane potential and contribute to repolarization of action potentials in excitable cells. The functional significance of K2P currents in cardiac electrophysiology remains poorly understood. Danio rerio (zebrafish) may be utilized to elucidate the role of cardiac K2P channels in vivo. The aim of this work was to identify and functionally characterize a zebrafish otholog of the human K2P10.1 channel. K2P10.1 orthologs in the D. rerio genome were identified by database analysis, and the full zK2P10.1 coding sequence was amplified from zebrafish cDNA. Human and zebrafish K2P10.1 proteins share 61% identity. High degrees of conservation were observed in protein domains relevant for structural integrity and regulation. K2P10.1 channels were heterologously expressed in Xenopus oocytes, and currents were recorded using two-electrode voltage clamp electrophysiology. Human and zebrafish channels mediated K+ selective background currents leading to membrane hyperpolarization. Arachidonic acid, an activator of hK2P10.1, induced robust activation of zK2P10.1. Activity of both channels was reduced by protein kinase C. Similar to its human counterpart, zK2P10.1 was inhibited by the antiarrhythmic drug amiodarone. In summary, zebrafish harbor K2P10.1 two-pore-domain K+ channels that exhibit structural and functional properties largely similar to human K2P10.1. We conclude that the zebrafish represents a valid model to study K2P10.1 function in vivo. [Copyright &y& Elsevier]

Published
2012
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47. Delineating the Dynamic Transcriptome Response of mRNA and microRNA during Zebrafish Heart Regeneration.

Author

Klett, Hagen, Jürgensen, Lonny, Most, Patrick, Busch, Martin, Günther, Fabian, Dobreva, Gergana, Leuschner, Florian, Hassel, David, Busch, Hauke, and Boerries, Melanie

Subjects
TRANSCRIPTOMES, MESSENGER RNA, CARDIAC regeneration
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. [ABSTRACT FROM AUTHOR]

Published
2019
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48. Abstract 12239: Biallelic Variants in ASNA1 Cause Rapidly Progressive Pediatric Cardiomyopathy.

Author

Verhagen, Judith M, van den Born, Myrthe, van der Linde, Herma C, Nikkels, Peter G, Verdijk, Rob M, van Unen, Leontine M, Baas, Annette F, ter Heide, Henriette, van Osch-Gevers, Lennie, Hoogeveen-Westerveld, Marianne, Herkert, Johanna C, van Slegtenhorst, Marjon A, Wessels, Marja W, Verheijen, Frans W, Hassel, David M, Hofstra, Robert M, Hegde, Ramanujan S, van Ham, Tjakko J, van Hasselt, Peter M, and van de Laar, Ingrid M

Published
2018

49. A dual role for ErbB2 signaling in cardiac trabeculation.

Author

Jiandong Liu, Bressan, Michael, Hassel, David, Huisken, Jan, Staudt, David, Kikuchi, Kazu, Poss, Kenneth D., Mikawa, Takashi, and Stainier, Didier Y. R.

Subjects
HEART cells
Abstract

An abstract of an article on the role of ErbB2 signaling in cardiac trabeculation is presented.

Published
2010
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