Rebs, Sabine

[["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","101901"],["dc.bibliographiccitation.journal","Stem Cell Research"],["dc.bibliographiccitation.volume","47"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Sedaghat-Hamedani, Farbod"],["dc.contributor.author","Kayvanpour, Elham"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2021-04-14T08:24:33Z"],["dc.date.available","2021-04-14T08:24:33Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.scr.2020.101901"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81329"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","1873-5061"],["dc.title","Generation of pluripotent stem cell lines and CRISPR/Cas9 modified isogenic controls from a patient with dilated cardiomyopathy harboring a RBM20 p.R634W mutation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","12230"],["dc.bibliographiccitation.firstpage","12230"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","23"],["dc.contributor.affiliation","Sedaghat-Hamedani, Farbod; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Rebs, Sabine; 4Department of Cardiology and Pneumology, Georg-August-University Göttingen, 37073 Göttingen, Germany"],["dc.contributor.affiliation","Kayvanpour, Elham; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Zhu, Chenchen; 7Department of Genetics, Stanford University, Stanford, CA 94305, USA"],["dc.contributor.affiliation","Amr, Ali; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Müller, Marion; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Haas, Jan; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Wu, Jingyan; 7Department of Genetics, Stanford University, Stanford, CA 94305, USA"],["dc.contributor.affiliation","Steinmetz, Lars M.; 2DZHK (German Centre for Cardiovascular Research), Partner Site Heidelberg and Mannheim, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Ehlermann, Philipp; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Streckfuss-Bömeke, Katrin; 4Department of Cardiology and Pneumology, Georg-August-University Göttingen, 37073 Göttingen, Germany"],["dc.contributor.affiliation","Frey, Norbert; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.affiliation","Meder, Benjamin; 1Institute for Cardiomyopathies Heidelberg (ICH), University Hospital Heidelberg, 69120 Heidelberg, Germany"],["dc.contributor.author","Sedaghat-Hamedani, Farbod"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Kayvanpour, Elham"],["dc.contributor.author","Zhu, Chenchen"],["dc.contributor.author","Amr, Ali"],["dc.contributor.author","Müller, Marion"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Wu, Jingyan"],["dc.contributor.author","Steinmetz, Lars M."],["dc.contributor.author","Ehlermann, Philipp"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.editor","Chandra Janga, Sarath"],["dc.date.accessioned","2022-12-01T08:31:40Z"],["dc.date.available","2022-12-01T08:31:40Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:12:19Z"],["dc.description.abstract","Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and is of familial origin in 20–40% of cases. Genetic testing by next-generation sequencing (NGS) has yielded a definite diagnosis in many cases; however, some remain elusive. In this study, we used a combination of NGS, human-induced pluripotent-stem-cell-derived cardiomyocytes (iPSC-CMs) and nanopore long-read sequencing to identify the causal variant in a multi-generational pedigree of DCM. A four-generation family with familial DCM was investigated. Next-generation sequencing (NGS) was performed on 22 family members. Skin biopsies from two affected family members were used to generate iPSCs, which were then differentiated into iPSC-CMs. Short-read RNA sequencing was used for the evaluation of the target gene expression, and long-read RNA nanopore sequencing was used to evaluate the relevance of the splice variants. The pedigree suggested a highly penetrant, autosomal dominant mode of inheritance. The phenotype of the family was suggestive of laminopathy, but previous genetic testing using both Sanger and panel sequencing only yielded conflicting evidence for LMNA p.R644C (rs142000963), which was not fully segregated. By re-sequencing four additional affected family members, further non-coding LMNA variants could be detected: rs149339264, rs199686967, rs201379016, and rs794728589. To explore the roles of these variants, iPSC-CMs were generated. RNA sequencing showed the LMNA expression levels to be significantly lower in the iPSC-CMs of the LMNA variant carriers. We demonstrated a dysregulated sarcomeric structure and altered calcium homeostasis in the iPSC-CMs of the LMNA variant carriers. Using targeted nanopore long-read sequencing, we revealed the biological significance of the variant c.356+1G>A, which generates a novel 5′ splice site in exon 1 of the cardiac isomer of LMNA, causing a nonsense mRNA product with almost complete RNA decay and haploinsufficiency. Using novel molecular analysis and nanopore technology, we demonstrated the pathogenesis of the rs794728589 (c.356+1G>A) splice variant in LMNA. This study highlights the importance of precise diagnostics in the clinical management and workup of cardiomyopathies."],["dc.identifier.doi","10.3390/ijms232012230"],["dc.identifier.pii","ijms232012230"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118233"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.publisher","MDPI"],["dc.relation.eissn","1422-0067"],["dc.rights","Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)."],["dc.title","Genotype Complements the Phenotype: Identification of the Pathogenicity of an LMNA Splice Variant by Nanopore Long-Read Sequencing in a Large DCM Family"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","129"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Genomics, Proteomics & Bioinformatics"],["dc.bibliographiccitation.lastpage","146"],["dc.bibliographiccitation.volume","20"],["dc.contributor.author","Boeckel, Jes-Niels"],["dc.contributor.author","Möbius-Winkler, Maximilian"],["dc.contributor.author","Müller, Marion"],["dc.contributor.author","Rebs, Sabine"],["dc.contributor.author","Eger, Nicole"],["dc.contributor.author","Schoppe, Laura"],["dc.contributor.author","Tappu, Rewati"],["dc.contributor.author","Kokot, Karoline E."],["dc.contributor.author","Kneuer, Jasmin M."],["dc.contributor.author","Gaul, Susanne"],["dc.contributor.author","Meder, Benjamin"],["dc.date.accessioned","2022-12-01T08:30:36Z"],["dc.date.available","2022-12-01T08:30:36Z"],["dc.date.issued","2022"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100003042 Else Kroner-Fresenius-Stiftung"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100004937 BMBF Berlin"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100005970 Deutsche Stiftung für Herzforschung"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100007316 Klaus Tschira Foundation"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/501100013811 University of Leipzig Faculty of Medicine"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/100010447 DZHK"],["dc.description.sponsorship"," http://dx.doi.org/10.13039/100011272 European Commission Seventh Framework Programme for Research and Technological Development Health"],["dc.identifier.doi","10.1016/j.gpb.2021.01.006"],["dc.identifier.pii","S1672022921001467"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117929"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.issn","1672-0229"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","SLM2 Is A Novel Cardiac Splicing Factor Involved in Heart Failure due to Dilated Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]