Cyganek, Lukas

[["dc.bibliographiccitation.firstpage","975"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","991"],["dc.bibliographiccitation.volume","70"],["dc.contributor.author","Borchert, Thomas"],["dc.contributor.author","Hübscher, Daniela"],["dc.contributor.author","Guessoum, Celina I."],["dc.contributor.author","Lam, Tuan-Dinh D."],["dc.contributor.author","Ghadri, Jelena R."],["dc.contributor.author","Schellinger, Isabel N."],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Liaw, Norman Y."],["dc.contributor.author","Li, Yun"],["dc.contributor.author","Haas, Jan"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Huber, Mia A."],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Raaz, Uwe"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Meder, Benjamin"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Lüscher, Thomas F."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Templin, Christian"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.date.accessioned","2018-04-23T11:48:11Z"],["dc.date.available","2018-04-23T11:48:11Z"],["dc.date.issued","2017"],["dc.description.abstract","Background Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis. Objectives The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS. Methods Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function. Results Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate–dependent protein kinase A–mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β1-adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function. Conclusions Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype."],["dc.identifier.doi","10.1016/j.jacc.2017.06.061"],["dc.identifier.gro","3142333"],["dc.identifier.pmid","28818208"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16489"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13468"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/204"],["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 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.issn","0735-1097"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG Dressel"],["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 Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG Tiburcy (Stem Cell Disease Modeling)"],["dc.relation.workinggroup","RG Wollnik"],["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","Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy"],["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.contributor.author","Gönenc, Ipek Ilgin"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Schmidt, Julia"],["dc.contributor.author","Zibat, Arne"],["dc.contributor.author","Müller, Christian"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Argyriou, Loukas"],["dc.contributor.author","Räschle, Markus"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2022-02-23T16:37:14Z"],["dc.date.available","2022-02-23T16:37:14Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1101/2021.10.01.462717"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/100402"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/430"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","Single-cell transcription profiles in Bloom syndrome patients link BLM deficiency with altered condensin complex expression signatures"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1137"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1148"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Huang, Mengying"],["dc.contributor.author","Fan, Xuehui"],["dc.contributor.author","Yang, Zhen"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Yuecel, Goekhan"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Yingrui"],["dc.contributor.author","Wendel, Angela"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Borggrefe, Martin"],["dc.date.accessioned","2021-10-01T09:57:54Z"],["dc.date.available","2021-10-01T09:57:54Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Aims This study aimed to investigate possible roles and underlying mechanisms of alpha-adrenoceptor coupled signalling for the pathogenesis of Takotsubo syndrome (TTS). Methods and results Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with a toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) to mimic the setting of TTS. Patch-clamp technique, polymerase chain reaction (PCR) and Fluorescence-activated cell sorting (FACS) were employed for the study. High concentration Epi suppressed the depolarization velocity, prolonged duration of action potentials and induced arrhythmic events in hiPSC-CMs. The Epi effects were attenuated by an alpha-adrenoceptor blocker (phentolamine), suggesting involvement of alpha-adrenoceptor signalling in arrhythmogenesis related to QT interval prolongation in the setting of TTS. An alpha 1-adrenoceptor agonist (phenylephrine) but not an alpha 2-adrenoceptor agonist (clonidine) mimicked Epi effects. Epi enhanced ROS production, which could be attenuated by the alpha- adrenoceptor blocker. Treatment of cells with H2O2 (100 µM) mimicked the effects of Epi on action potentials and a reactive oxygen species (ROS)-blocker (N-acetyl-I-cysteine, 1 mM) prevented the Epi effects, indicating that the ROS signalling is involved in the alpha-adrenoceptor actions. Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidases were involved in alpha 1-adrenoceptor signalling. A protein kinase C (PKC) blocker suppressed the effects of Epi, phenylephrine and ROS as well, implying that PKC participated in alpha 1-adrenoceptor signalling and acted as a downstream factor of ROS. The abnormal action potentials resulted from alpha 1-adrenoceptor activation-induced dysfunctions of ion channels including the voltage-dependent Na+ and L-type Ca2+ channels. Conclusions Alpha 1-adrenoceptor signalling plays important roles for arrhythmogenesis of TTS. Alpha-adrenoceptor blockers might be clinically helpful for treating arrhythmias in patients with TTS."],["dc.identifier.doi","10.1093/europace/euab008"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89942"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-469"],["dc.relation.eissn","1532-2092"],["dc.relation.issn","1099-5129"],["dc.title","Alpha 1-adrenoceptor signalling contributes to toxic effects of catecholamine on electrical properties in cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","101560"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","STAR Protocols"],["dc.bibliographiccitation.volume","3"],["dc.contributor.author","Lyra-Leite, Davi M."],["dc.contributor.author","Gutiérrez-Gutiérrez, Óscar"],["dc.contributor.author","Wang, Meimei"],["dc.contributor.author","Zhou, Yang"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Burridge, Paul W."],["dc.date.accessioned","2022-08-24T05:30:58Z"],["dc.date.available","2022-08-24T05:30:58Z"],["dc.date.issued","2022"],["dc.description.abstract","The methods for the culture and cardiomyocyte differentiation of human embryonic stem cells, and later human induced pluripotent stem cells (hiPSC), have moved from a complex and uncontrolled systems to simplified and relatively robust protocols, using the knowledge and cues gathered at each step. HiPSC-derived cardiomyocytes have proven to be a useful tool in human disease modelling, drug discovery, developmental biology, and regenerative medicine. In this protocol review, we will highlight the evolution of protocols associated with hPSC culture, cardiomyocyte differentiation, sub-type specification, and cardiomyocyte maturation. We also discuss protocols for somatic cell direct reprogramming to cardiomyocyte-like cells."],["dc.identifier.doi","10.1016/j.xpro.2022.101560"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113149"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/543"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/443"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.issn","2666-1667"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.rights","CC BY-NC-ND 4.0"],["dc.title","A review of protocols for human iPSC culture, cardiac differentiation, subtype-specification, maturation, and direct reprogramming"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","527"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Lutter, Georg"],["dc.contributor.author","Puehler, Thomas"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Seiler, Jette"],["dc.contributor.author","Rogler, Anita"],["dc.contributor.author","Herberth, Tanja"],["dc.contributor.author","Knueppel, Philipp"],["dc.contributor.author","Gorb, Stanislav N."],["dc.contributor.author","Sathananthan, Janarthanan"],["dc.contributor.author","Sellers, Stephanie"],["dc.contributor.author","Haben, Irma"],["dc.date.accessioned","2022-04-01T10:03:18Z"],["dc.date.available","2022-04-01T10:03:18Z"],["dc.date.issued","2022"],["dc.description.abstract","Clinically used heart valve prostheses, despite their progress, are still associated with limitations. Biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds, as a matrix, were seeded with human endothelial colony-forming cells (ECFCs) and human induced-pluripotent stem cells-derived MSCs (iMSCs) for the generation of tissue-engineered heart valves. Cell adhesion, proliferation, and distribution, as well as the effects of coating PCL nanofibers, were analyzed by fluorescence microscopy and SEM. Mechanical properties of seeded PCL scaffolds were investigated under uniaxial loading. iPSCs were used to differentiate into iMSCs via mesoderm. The obtained iMSCs exhibited a comparable phenotype and surface marker expression to adult human MSCs and were capable of multilineage differentiation. EFCFs and MSCs showed good adhesion and distribution on PCL fibers, forming a closed cell cover. Coating of the fibers resulted in an increased cell number only at an early time point; from day 7 of colonization, there was no difference between cell numbers on coated and uncoated PCL fibers. The mechanical properties of PCL scaffolds under uniaxial loading were compared with native porcine pulmonary valve leaflets. The Young’s modulus and mean elongation at Fmax of unseeded PCL scaffolds were comparable to those of native leaflets (p = ns.). Colonization of PCL scaffolds with human ECFCs or iMSCs did not alter these properties (p = ns.). However, the native heart valves exhibited a maximum tensile stress at a force of 1.2 ± 0.5 N, whereas it was lower in the unseeded PCL scaffolds (0.6 ± 0.0 N, p < 0.05). A closed cell layer on PCL tissues did not change the values of Fmax (ECFCs: 0.6 ± 0.1 N; iMSCs: 0.7 ± 0.1 N). Here, a successful two-phase protocol, based on the timed use of differentiation factors for efficient differentiation of human iPSCs into iMSCs, was developed. Furthermore, we demonstrated the successful colonization of a biodegradable PCL nanofiber matrix with human ECFCs and iMSCs suitable for the generation of tissue-engineered heart valves. A closed cell cover was already evident after 14 days for ECFCs and 21 days for MSCs. The PCL tissue did not show major mechanical differences compared to native heart valves, which was not altered by short-term surface colonization with human cells in the absence of an extracellular matrix."],["dc.identifier.doi","10.3390/ijms23010527"],["dc.identifier.pii","ijms23010527"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106133"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1422-0067"],["dc.title","Biodegradable Poly-ε-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Open Journal of Bioresources"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Beuthner, Bo E. C."],["dc.contributor.author","Topci, Rodi"],["dc.contributor.author","Derks, Mareike"],["dc.contributor.author","Franke, Thomas"],["dc.contributor.author","Seelke, Sandra"],["dc.contributor.author","Puls, Miriam"],["dc.contributor.author","Schuster, Andreas"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Valentova, Miroslava"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zeisberg, Elisabeth M."],["dc.contributor.author","Jacobshagen, Claudius"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Nußbeck, Sara Y."],["dc.date.accessioned","2020-06-16T13:21:23Z"],["dc.date.available","2020-06-16T13:21:23Z"],["dc.date.issued","2020"],["dc.description.abstract","The bioresource (>265 patients with >27,600 biospecimens until December 2019; recruitment ongoing) on severe aortic stenosis is of vital importance to improve the still incomplete understanding of its etiology as well as its transition to heart failure. The bioresource contains various biospecimens, standardised clinical and imaging data sets including transthoracic echocardiography, computed tomography and magnetic resonance imaging of the heart. Biospecimen sampling follows the SOP-driven collection scheme of the German Center for Cardiovascular Research (DZHK) for venous blood and urine [1]. In addition, left-ventricular endomyocardial biopsies, rectal swabs and skin biopsies (for subsequent generation of induced pluripotent stem cells) are collected. Data management includes the use of a professional biospecimen management system as well as a Picture Archiving and Communication System (PACS) for imaging data. A Good Clinical Practice (GCP)-conform software for the management of clinical data and a trusted third party for the management of patient identifying data and pseudonyms are in place. Given these conditions, there is a high reuse-potential for biospecimens and data."],["dc.identifier.doi","10.5334/ojb.65"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66366"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/340"],["dc.language.iso","en"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation","SFB 1002 | INF: Unterstützung der SFB 1002 Forschungsdatenintegration, -visualisierung und -nachnutzung"],["dc.relation.issn","2056-5542"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.relation.workinggroup","RG E. Zeisberg (Kardiales Stroma)"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG Nußbeck"],["dc.relation.workinggroup","RG Toischer (Kardiales Remodeling)"],["dc.rights","CC BY 3.0"],["dc.title","Interdisciplinary Research on Aortic Valve Stenosis: A Longitudinal Collection of Biospecimens and Clinical Data of Patients Undergoing Transcatheter Aortic Valve Replacement"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","844441"],["dc.bibliographiccitation.journal","Frontiers in Cardiovascular Medicine"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Jakobi, Tobias"],["dc.contributor.author","Groß, Julia"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Doroudgar, Shirin"],["dc.date.accessioned","2022-07-01T07:35:28Z"],["dc.date.available","2022-07-01T07:35:28Z"],["dc.date.issued","2022"],["dc.description.abstract","Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has emerged as a major cause of morbidity and mortality worldwide, placing unprecedented pressure on healthcare. Cardiomyopathy is described in patients with severe COVID-19 and increasing evidence suggests that cardiovascular involvement portends a high mortality. To facilitate fast development of antiviral interventions, drugs initially developed to treat other diseases are currently being repurposed as COVID-19 treatments. While it has been shown that SARS-CoV-2 invades cells through the angiotensin-converting enzyme 2 receptor (ACE2), the effect of drugs currently repurposed to treat COVID-19 on the heart requires further investigation. Methods Human induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) were treated with five repurposed drugs (remdesivir, lopinavir/ritonavir, lopinavir/ritonavir/interferon beta (INF-β), hydroxychloroquine, and chloroquine) and compared with DMSO controls. Transcriptional profiling was performed to identify global changes in gene expression programs. Results RNA sequencing of hiPSC-CMs revealed significant changes in gene programs related to calcium handling and the endoplasmic reticulum stress response, most prominently for lopinavir/ritonavir and lopinavir/ritonavir/interferon-beta. The results of the differential gene expression analysis are available for interactive access at https://covid19drugs.jakobilab.org . Conclusion Transcriptional profiling in hiPSC-CMs treated with COVID-19 drugs identified unfavorable changes with lopinavir/ritonavir and lopinavir/ritonavir/INF-β in key cardiac gene programs that may negatively affect heart function."],["dc.identifier.doi","10.3389/fcvm.2022.844441"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112179"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2297-055X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Transcriptional Effects of Candidate COVID-19 Treatments on Cardiac Myocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1928"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1929"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:19:09Z"],["dc.date.available","2020-12-10T18:19:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1093/europace/euz274"],["dc.identifier.eissn","1532-2092"],["dc.identifier.issn","1099-5129"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75144"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","‘Mature’ resting membrane potentials in hiPSC-CMs: fact or artefact?—Authors’ reply"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1621"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Journal of Bone and Mineral Research"],["dc.bibliographiccitation.lastpage","1635"],["dc.bibliographiccitation.volume","36"],["dc.contributor.affiliation","Rössler, Uta; 1\r\nBIH Center for Regenerative Therapies (BCRT)\r\nCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health\r\nBerlin Germany"],["dc.contributor.affiliation","Stelzer, Nina; 1\r\nBIH Center for Regenerative Therapies (BCRT)\r\nCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health\r\nBerlin Germany"],["dc.contributor.affiliation","Bose, Shroddha; 6\r\nInstitute of Chemistry and Biochemistry\r\nFreie Universität Berlin\r\nBerlin Germany"],["dc.contributor.affiliation","Kopp, Johannes; 1\r\nBIH Center for Regenerative Therapies (BCRT)\r\nCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health\r\nBerlin Germany"],["dc.contributor.affiliation","Søe, Kent; 8\r\nClinical Cell Biology, Department of Pathology\r\nOdense University Hospital\r\nOdense C Denmark"],["dc.contributor.affiliation","Cyganek, Lukas; 11\r\nStem Cell Unit, Clinic for Cardiology and Pneumology\r\nUniversity Medical Center Göttingen\r\nGöttingen Germany"],["dc.contributor.affiliation","Zifarelli, Giovanni; 13\r\nIstituto di Biofisica, CNR\r\nGenoa Italy"],["dc.contributor.affiliation","Ali, Salaheddine; 1\r\nBIH Center for Regenerative Therapies (BCRT)\r\nCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health\r\nBerlin Germany"],["dc.contributor.affiliation","von der Hagen, Maja; 14\r\nAbteilung Neuropädiatrie, Medizinische Fakultät Carl Gustav Carus\r\nTechnische Universität Dresden\r\nDresden Germany"],["dc.contributor.affiliation","Strässler, Elisabeth Tamara; 15\r\nDepartment of Cardiology\r\nCharité ‐ Universitätsmedizin Berlin, Campus Benjamin Franklin\r\nBerlin Germany"],["dc.contributor.affiliation","Hahn, Gabriele; 17\r\nInstitut und Poliklinik für Radiologische Diagnostik\r\nMedizinische Fakultät Carl Gustav Carus Technische Universität Dresden\r\nDresden Germany"],["dc.contributor.affiliation","Pusch, Michael; 13\r\nIstituto di Biofisica, CNR\r\nGenoa Italy"],["dc.contributor.affiliation","Stauber, Tobias; 6\r\nInstitute of Chemistry and Biochemistry\r\nFreie Universität Berlin\r\nBerlin Germany"],["dc.contributor.affiliation","Izsvák, Zsuzsanna; 19\r\nMax‐Delbrück‐Center for Molecular Medicine (MDC), Helmholtz Association\r\nBerlin Germany"],["dc.contributor.affiliation","Gossen, Manfred; 20\r\nBerlin‐Brandenburg Center for Regenerative Therapies\r\nCharité Virchow Campus\r\nBerlin Germany"],["dc.contributor.affiliation","Stachelscheid, Harald; 22\r\nCharité ‐ Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt‐Universität zu Berlin, and Berlin Institute of Health\r\nBerlin Germany"],["dc.contributor.author","Rössler, Uta"],["dc.contributor.author","Hennig, Anna Floriane"],["dc.contributor.author","Stelzer, Nina"],["dc.contributor.author","Bose, Shroddha"],["dc.contributor.author","Kopp, Johannes"],["dc.contributor.author","Søe, Kent"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zifarelli, Giovanni"],["dc.contributor.author","Ali, Salaheddine"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Pusch, Michael"],["dc.contributor.author","von der Hagen, Maja"],["dc.contributor.author","Strässler, Elisabeth Tamara"],["dc.contributor.author","Hahn, Gabriele"],["dc.contributor.author","Stauber, Tobias"],["dc.contributor.author","Izsvák, Zsuzsanna"],["dc.contributor.author","Gossen, Manfred"],["dc.contributor.author","Stachelscheid, Harald"],["dc.date.accessioned","2021-06-01T09:41:55Z"],["dc.date.available","2021-06-01T09:41:55Z"],["dc.date.issued","2021"],["dc.date.updated","2022-02-09T13:20:40Z"],["dc.description.abstract","ABSTRACT Human induced pluripotent stem cells (hiPSCs) hold great potential for modeling human diseases and the development of innovative therapeutic approaches. Here, we report on a novel, simplified differentiation method for forming functional osteoclasts from hiPSCs. The three‐step protocol starts with embryoid body formation, followed by hematopoietic specification, and finally osteoclast differentiation. We observed continuous production of monocyte‐like cells over a period of up to 9 weeks, generating sufficient material for several osteoclast differentiations. The analysis of stage‐specific gene and surface marker expression proved mesodermal priming, the presence of monocyte‐like cells, and of terminally differentiated multinucleated osteoclasts, able to form resorption pits and trenches on bone and dentine in vitro. In comparison to peripheral blood mononuclear cell (PBMC)‐derived osteoclasts hiPSC‐derived osteoclasts were larger and contained a higher number of nuclei. Detailed functional studies on the resorption behavior of hiPSC‐osteoclasts indicated a trend towards forming more trenches than pits and an increase in pseudoresorption. We used hiPSCs from an autosomal recessive osteopetrosis (ARO) patient (BIHi002‐A, ARO hiPSCs) with compound heterozygous missense mutations p.(G292E) and p.(R403Q) in CLCN7, coding for the Cl−/H+‐exchanger ClC‐7, for functional investigations. The patient's leading clinical feature was a brain malformation due to defective neuronal migration. Mutant ClC‐7 displayed residual expression and retained lysosomal co‐localization with OSTM1, the gene coding for the osteopetrosis‐associated transmembrane protein 1, but only ClC‐7 harboring the mutation p.(R403Q) gave strongly reduced ion currents. An increased autophagic flux in spite of unchanged lysosomal pH was evident in undifferentiated ARO hiPSCs. ARO hiPSC‐derived osteoclasts showed an increased size compared to hiPSCs of healthy donors. They were not able to resorb bone, underlining a loss‐of‐function effect of the mutations. In summary, we developed a highly reproducible, straightforward hiPSC‐osteoclast differentiation protocol. We demonstrated that osteoclasts differentiated from ARO hiPSCs can be used as a disease model for ARO and potentially also other osteoclast‐related diseases. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)."],["dc.description.sponsorship","Berlin Institute of Health"],["dc.description.sponsorship","BCRT crossfield project GenoPro"],["dc.description.sponsorship","BIH Center for Regenerative Therapies"],["dc.description.sponsorship","European Community's Seventh Framework Programme"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.identifier.doi","10.1002/jbmr.4322"],["dc.identifier.pmid","33905594"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85075"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/394"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","1523-4681"],["dc.relation.issn","0884-0431"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made."],["dc.title","Efficient generation of osteoclasts from human induced pluripotent stem cells and functional investigations of lethal CLCN7 ‐related osteopetrosis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Stem Cells International"],["dc.bibliographiccitation.lastpage","14"],["dc.bibliographiccitation.volume","2018"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Buljubasic, Fanis"],["dc.contributor.author","Sattler, Katherine"],["dc.contributor.author","Yücel, Gökhan"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiao-Bo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:37:41Z"],["dc.date.available","2020-12-10T18:37:41Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1155/2018/6067096"],["dc.identifier.pmid","29535773"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77065"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/325"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Ion Channel Expression and Characterization in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]