Khadjeh, Sara

[["dc.bibliographiccitation.artnumber","149"],["dc.bibliographiccitation.journal","Journal of Translational Medicine"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Asif, Abdul R."],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Qasim, Mohamed"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Schott, Peter"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2017-09-07T11:44:53Z"],["dc.date.available","2017-09-07T11:44:53Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: Hemodynamic load leads to cardiac hypertrophy and heart failure. While afterload (pressure overload) induces concentric hypertrophy, elevation of preload (volume overload) yields eccentric hypertrophy and is associated with a better outcome. Here we analysed the proteomic pattern of mice subjected to short-term preload. Methods and Results: Female FVB/N mice were subjected to aortocaval shunt-induced volume overload that leads to an eccentric hypertrophy (left ventricular weight/tibia length +31 %) with sustained systolic heart function at 1 week after operation. Two-dimensional gel electrophoresis (2-DE) followed by mass spectrometric analysis showed alteration in the expression of 25 protein spots representing 21 different proteins. 64 % of these protein spots were up-regulated and 36 % of the protein spots were consistently down-regulated. Interestingly, alpha-1-antitrypsin was down-regulated, indicating higher elastin degradation and possibly contributing to the early dilatation. In addition to contractile and mitochondrial proteins, polymerase I and transcript release factor protein (PTRF) was also up-regulated, possibly contributing to the preload-induced signal transduction. Conclusions: Our findings reveal the proteomic changes of early-stage eccentric myocardial remodeling after volume overload. Induced expression of some of the respiratory chain enzymes suggests a metabolic shift towards an oxidative phosphorylation that might contribute to the favorable remodeling seen in early VO. Down-regulation of alpha-1-antitrypsin might contribute to extracellular matrix remodeling and left ventricular dilatation. We also identified PTRF as a potential signaling regulator of volume overload-induced cardiac hypertrophy."],["dc.identifier.doi","10.1186/s12967-016-0898-5"],["dc.identifier.gro","3141681"],["dc.identifier.isi","000377182700001"],["dc.identifier.pmid","27234427"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13299"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8784"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Research Foundation [SFB1002]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1479-5876"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Proteomic analysis of short-term preload-induced eccentric cardiac hypertrophy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","9"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","21"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Fomin, Andrey"],["dc.contributor.author","Luo, Xiaojing"],["dc.contributor.author","Li, Wener"],["dc.contributor.author","Fischer, Claudia"],["dc.contributor.author","Özcelik, Cemil"],["dc.contributor.author","Perrot, Andreas"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Vidal, Ramon Oliveira"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.date.accessioned","2018-04-23T11:49:17Z"],["dc.date.available","2018-04-23T11:49:17Z"],["dc.date.issued","2017"],["dc.description.abstract","The ability to generate patient-specific induced pluripotent stem cells (iPSCs) provides a unique opportunity for modeling heart disease in vitro. In this study, we generated iPSCs from a patient with dilated cardiomyopathy (DCM) caused by a missense mutation S635A in RNA-binding motif protein 20 (RBM20) and investigated the functionality and cell biology of cardiomyocytes (CMs) derived from patient-specific iPSCs (RBM20-iPSCs). The RBM20-iPSC-CMs showed abnormal distribution of sarcomeric α-actinin and defective calcium handling compared to control-iPSC-CMs, suggesting disorganized myofilament structure and altered calcium machinery in CMs of the RBM20 patient. Engineered heart muscles (EHMs) from RBM20-iPSC-CMs showed that not only active force generation was impaired in RBM20-EHMs but also passive stress of the tissue was decreased, suggesting a higher visco-elasticity of RBM20-EHMs. Furthermore, we observed a reduced titin (TTN) N2B-isoform expression in RBM20-iPSC-CMs by demonstrating a reduction of exon skipping in the PEVK region of TTN and an inhibition of TTN isoform switch. In contrast, in control-iPSC-CMs both TTN isoforms N2B and N2BA were expressed, indicating that the TTN isoform switch occurs already during early cardiogenesis. Using next generation RNA sequencing, we mapped transcriptome and splicing target profiles of RBM20-iPSC-CMs and identified different cardiac gene networks in response to the analyzed RBM20 mutation in cardiac-specific processes. These findings shed the first light on molecular mechanisms of RBM20-dependent pathological cardiac remodeling leading to DCM. Our data demonstrate that iPSC-CMs coupled with EHMs provide a powerful tool for evaluating disease-relevant functional defects and for a deeper mechanistic understanding of alternative splicing-related cardiac diseases."],["dc.identifier.doi","10.1016/j.yjmcc.2017.09.008"],["dc.identifier.gro","3142517"],["dc.identifier.pmid","28941705"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16493"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13672"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/191"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.issn","0022-2828"],["dc.relation.workinggroup","RG Guan (Application of patient-specific induced pluripotent stem cells in disease modelling)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Severe DCM phenotype of patient harboring RBM20 mutation S635A can be modeled by patient-specific induced pluripotent stem cell-derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","362"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.lastpage","371"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Herwig, Melissa"],["dc.contributor.author","Linke, Wolfgang A."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Toischer, Karl"],["dc.date.accessioned","2017-09-07T11:54:33Z"],["dc.date.available","2017-09-07T11:54:33Z"],["dc.date.issued","2016"],["dc.description.abstract","AimWe have previously reported that early phase (1week) of experimental volume overload (VO) has an adaptive phenotype while wall stress-matched pressure overload (PO) is maladaptive. Here we investigate the transition from adaptation to heart failure (HF) in long-term VO. Methods and resultsFVB/N wild-type mice were subjected to VO induced by aortocaval shunt, and were followed by serial echocardiography until in vivo left ventricular ejection fraction was below <50% (13535days). Heart failure was evident from increased lung and liver weight and increased mortality compared with sham. Maladaptive remodelling resulted in significantly reduced sarcomeric titin phosphorylation (causing increased sarcomeric stiffness), whereas interstitial fibrosis was not increased. This was paralleled by re-expression of the fetal gene program, activation of calcium/calmodulin-dependent protein kinase II (CaMKII), decreased protein kinase B (Akt) phosphorylation, high oxidative stress, and increased apoptosis. Consistently, development of HF and mortality were significantly aggravated in Akt-deficient mice. ConclusionTransition to HF in VO is associated with decreased Akt and increased CaMKII signalling pathways together with increased oxidative stress and apoptosis. Lack of interstitial fibrosis together with sarcomeric titin hypophosphorylation indicates an increased stiffness at the sarcomeric but not matrix level in VO-induced HF (in contrast to PO). Transition to HF may result from myocyte loss and myocyte dysfunction owing to increased stiffness."],["dc.identifier.doi","10.1002/ejhf.465"],["dc.identifier.gro","3141701"],["dc.identifier.isi","000374308700005"],["dc.identifier.pmid","26694078"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/102"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Research Foundation DFG [SFB 1002, IRTG1816]"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A08: Translationale und posttranslationale Kontrolle trunkierter Titinproteine in Kardiomyozyten von Patienten mit dilatativer Kardiomyopathie"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Linke (Kardiovaskuläre Physiologie)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","Molecular and structural transition mechanisms in long-term volume overload"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","33853"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Volland, Cornelia"],["dc.contributor.author","Bremer, Sebastian"],["dc.contributor.author","Hellenkamp, Kristian"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Seidler, Tim"],["dc.date.accessioned","2017-09-07T11:44:37Z"],["dc.date.available","2017-09-07T11:44:37Z"],["dc.date.issued","2016"],["dc.description.abstract","TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity."],["dc.identifier.doi","10.1038/srep33853"],["dc.identifier.gro","3141617"],["dc.identifier.isi","000384478000002"],["dc.identifier.pmid","27667030"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13792"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1678"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Basic Research in Cardiology"],["dc.bibliographiccitation.volume","115"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Hindmarsh, Vanessa"],["dc.contributor.author","Weber, Frederike"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Vidal, Ramon O."],["dc.contributor.author","Torkieh, Setare"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Lbik, Dawid"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Mohamed, Belal A."],["dc.contributor.author","Bonn, Stefan"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.date.accessioned","2020-12-10T14:10:26Z"],["dc.date.available","2020-12-10T14:10:26Z"],["dc.date.issued","2020"],["dc.description.abstract","Heart failure is a major health problem worldwide with a significant morbidity and mortality rate. Although studied extensively in animal models, data from patients at the compensated disease stage are lacking. We sampled myocardium biopsies from aortic stenosis patients with compensated hypertrophy and moderate heart failure and used transcriptomics to study the transition to failure. Sequencing and comparative analysis of analogous samples of mice with transverse aortic constriction identified 25 candidate genes with similar regulation in response to pressure overload, reflecting highly conserved molecular processes. The gene cysteine-rich secretory protein LCCL domain containing 1 (CRISPLD1) is upregulated in the transition to failure in human and mouse and its function is unknown. Homology to ion channel regulatory toxins suggests a role in Ca2+ cycling. CRISPR/Cas9-mediated loss-of-function leads to dysregulated Ca2+ handling in human-induced pluripotent stem cell-derived cardiomyocytes. The downregulation of prohypertrophic, proapoptotic and Ca2+-signaling pathways upon CRISPLD1-KO and its upregulation in the transition to failure implicates a contribution to adverse remodeling. These findings provide new pathophysiological data on Ca2+ regulation in the transition to failure and novel candidate genes with promising potential for therapeutic interventions."],["dc.identifier.doi","10.1007/s00395-020-0784-4"],["dc.identifier.pmid","32146539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70757"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/350"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D04: Bedeutung der Methylierung von RNA (m6A) und des Histons H3 (H3K4) in der Herzinsuffizienz"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 4.0"],["dc.title","CRISPLD1: a novel conserved target in the transition to human heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","BMC Evolutionary Biology"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Turetzek, Natascha"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Schomburg, Christoph"],["dc.contributor.author","Prpic, Nikola-Michael"],["dc.date.accessioned","2019-07-09T11:44:23Z"],["dc.date.available","2019-07-09T11:44:23Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1186/s12862-017-1013-0"],["dc.identifier.pmid","28709396"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14734"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58999"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Rapid diversification of homothorax expression patterns after gene duplication in spiders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1002342"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Pechmann, Matthias"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Turetzek, Natascha"],["dc.contributor.author","McGregor, Alistair P."],["dc.contributor.author","Damen, Wim G. M."],["dc.contributor.author","Prpic, Nikola-Michael"],["dc.date.accessioned","2018-11-07T08:51:00Z"],["dc.date.available","2018-11-07T08:51:00Z"],["dc.date.issued","2011"],["dc.description.abstract","Despite many aspects of the regulation of segmentation being conserved among arthropods, the evolution of novel gene functions has played an important role in the evolution of developmental regulation and the emergence of new segmental structures. Moreover the study of such novel gene functions can be informative with respect to the patterns and direction of evolutionary changes in developmental programs. The homeobox gene Distal-less (Dll) is known for its conserved function in appendage development in metazoans. In arthropods, Dll is required for the specification of distal appendage structures. Here we describe a novel and unexpected role of Dll in the spider Achaearanea tepidariorum. We detect At-Dll transcripts not only in the appendages, but unexpectedly also in an anterior domain during early development, prior to the specification of the limb primordia. A similar early Dll domain is present in the distantly related spider Pholcus phalangioides. In A. tepidariorum this early At-Dll expression is required for head segmentation. RNA interference results in spiders that lack either the first or the first and the second walking leg segments. The early At-Dll expression is also required for the activation of the segment polarity genes engrailed and hedgehog in this region. Our work identifies the Distal-less gene as a novel factor in anterior spider segmentation with a gap gene-like function. This novel role of Dll is interesting because Dll expression is reduced in this region in crustaceans and the homologous insect segment, the mandible segment, does not express Dll and does not require this gene for patterning. We therefore discuss the possible implications of our results for understanding the evolution and diversification of the mandible segment."],["dc.identifier.doi","10.1371/journal.pgen.1002342"],["dc.identifier.isi","000296665400041"],["dc.identifier.pmid","22028676"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8016"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/21829"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7390"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Novel Function of Distal-less as a Gap Gene during Spider Segmentation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1804"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","1819"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Iyer, Lavanya M."],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Schoger, Eric"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Wagner, Eva"],["dc.contributor.author","Woelfer, Monique"],["dc.contributor.author","Zafiriou, Maria-Patapia"],["dc.contributor.author","Milting, Hendrik"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Zelarayán, Laura C."],["dc.date.accessioned","2020-12-10T14:24:44Z"],["dc.date.available","2020-12-10T14:24:44Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1016/j.jacc.2019.07.076"],["dc.identifier.pmid","31582141"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16513"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/72339"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/283"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C04: Fibroblasten-Kardiomyozyten Interaktion im gesunden und erkrankten Herzen: Mechanismen und therapeutische Interventionen bei Kardiofibroblastopathien"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.relation.workinggroup","RG Zimmermann (Engineered Human Myocardium)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","KLF15-Wnt–Dependent Cardiac Reprogramming Up-Regulates SHISA3 in the Mammalian Heart"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2850"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","2867"],["dc.bibliographiccitation.volume","46"],["dc.contributor.author","Iyer, Lavanya M"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Woelfer, Monique"],["dc.contributor.author","Schoger, Eric"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Zafiriou, Maria Patapia"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Pang, Sze Ting"],["dc.contributor.author","Weber, Tobias"],["dc.contributor.author","Rathjens, Franziska S."],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Noack, Claudia"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Zelarayán, Laura C."],["dc.date.accessioned","2018-04-23T11:47:57Z"],["dc.date.available","2018-04-23T11:47:57Z"],["dc.date.issued","2018"],["dc.description.abstract","Chromatin remodelling precedes transcriptional and structural changes in heart failure. A body of work suggests roles for the developmental Wnt signalling pathway in cardiac remodelling. Hitherto, there is no evidence supporting a direct role of Wnt nuclear components in regulating chromatin landscapes in this process. We show that transcriptionally active, nuclear, phosphorylated(p)Ser675-β-catenin and TCF7L2 are upregulated in diseased murine and human cardiac ventricles. We report that inducible cardiomyocytes (CM)-specific pSer675-β-catenin accumulation mimics the disease situation by triggering TCF7L2 expression. This enhances active chromatin, characterized by increased H3K27ac and TCF7L2 occupancies to cardiac developmental and remodelling genes in vivo. Accordingly, transcriptomic analysis of β-catenin stabilized hearts shows a strong recapitulation of cardiac developmental processes like cell cycling and cytoskeletal remodelling. Mechanistically, TCF7L2 co-occupies distal genomic regions with cardiac transcription factors NKX2–5 and GATA4 in stabilized-β-catenin hearts. Validation assays revealed a previously unrecognized function of GATA4 as a cardiac repressor of the TCF7L2/β-catenin complex in vivo, thereby defining a transcriptional switch controlling disease progression. Conversely, preventing β-catenin activation post-pressure-overload results in a downregulation of these novel TCF7L2-targets and rescues cardiac function. Thus, we present a novel role for TCF7L2/β-catenin in CMs-specific chromatin modulation, which could be exploited for manipulating the ubiquitous Wnt pathway."],["dc.description.sponsorship","Open-Access-Publikatinsfonds 2018"],["dc.identifier.doi","10.1093/nar/gky049"],["dc.identifier.gro","3142314"],["dc.identifier.pmid","29394407"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15089"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13447"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/201"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A11: Absolute Arrhythmie bei Vorhofflimmern - ein neuer Mechanismus, der zu einer Störung von Ca2+-Homöostase und elektrischer Stabilität in der Transition zur Herzinsuffizienz führt"],["dc.relation","SFB 1002 | C07: Kardiomyozyten Wnt/β-catenin Komplex Aktivität im pathologischen Herz-Remodeling - als gewebespezifischer therapeutischer Ansatz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation","SFB 1002 | S02: Hochauflösende Fluoreszenzmikroskopie und integrative Datenanalyse"],["dc.relation","SFB 1002 | INF: Unterstützung der SFB 1002 Forschungsdatenintegration, -visualisierung und -nachnutzung"],["dc.relation.issn","0305-1048"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.relation.workinggroup","RG Zelarayán-Behrend (Developmental Pharmacology)"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","A context-specific cardiac β-catenin and GATA4 interaction influences TCF7L2 occupancy and remodels chromatin driving disease progression in the adult heart"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]