Kornak, Uwe

[["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","2807"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Genetics in Medicine"],["dc.bibliographiccitation.lastpage","2814"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Hsieh, Tzung-Chien"],["dc.contributor.author","Mensah, Martin A"],["dc.contributor.author","Pantel, Jean T"],["dc.contributor.author","Aguilar, Dione"],["dc.contributor.author","Bar, Omri"],["dc.contributor.author","Bayat, Allan"],["dc.contributor.author","Becerra-Solano, Luis"],["dc.contributor.author","Bentzen, Heidi B"],["dc.contributor.author","Biskup, Saskia"],["dc.contributor.author","Borisov, Oleg"],["dc.contributor.author","Braaten, Oivind"],["dc.contributor.author","Ciaccio, Claudia"],["dc.contributor.author","Coutelier, Marie"],["dc.contributor.author","Cremer, Kirsten"],["dc.contributor.author","Danyel, Magdalena"],["dc.contributor.author","Daschkey, Svenja"],["dc.contributor.author","Eden, Hilda David"],["dc.contributor.author","Devriendt, Koenraad"],["dc.contributor.author","Wilson, Sandra"],["dc.contributor.author","Douzgou, Sofia"],["dc.contributor.author","Đukić, Dejan"],["dc.contributor.author","Ehmke, Nadja"],["dc.contributor.author","Fauth, Christine"],["dc.contributor.author","Fischer-Zirnsak, Björn"],["dc.contributor.author","Fleischer, Nicole"],["dc.contributor.author","Gabriel, Heinz"],["dc.contributor.author","Graul-Neumann, Luitgard"],["dc.contributor.author","Gripp, Karen W"],["dc.contributor.author","Gurovich, Yaron"],["dc.contributor.author","Gusina, Asya"],["dc.contributor.author","Haddad, Nechama"],["dc.contributor.author","Hajjir, Nurulhuda"],["dc.contributor.author","Hanani, Yair"],["dc.contributor.author","Hertzberg, Jakob"],["dc.contributor.author","Hoertnagel, Konstanze"],["dc.contributor.author","Howell, Janelle"],["dc.contributor.author","Ivanovski, Ivan"],["dc.contributor.author","Kaindl, Angela"],["dc.contributor.author","Kamphans, Tom"],["dc.contributor.author","Kamphausen, Susanne"],["dc.contributor.author","Karimov, Catherine"],["dc.contributor.author","Kathom, Hadil"],["dc.contributor.author","Keryan, Anna"],["dc.contributor.author","Knaus, Alexej"],["dc.contributor.author","Köhler, Sebastian"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Lavrov, Alexander"],["dc.contributor.author","Leitheiser, Maximilian"],["dc.contributor.author","Lyon, Gholson J"],["dc.contributor.author","Mangold, Elisabeth"],["dc.contributor.author","Reina, Purificación Marín"],["dc.contributor.author","Carrascal, Antonio Martinez"],["dc.contributor.author","Mitter, Diana"],["dc.contributor.author","Herrador, Laura Morlan"],["dc.contributor.author","Nadav, Guy"],["dc.contributor.author","Nöthen, Markus"],["dc.contributor.author","Orrico, Alfredo"],["dc.contributor.author","Ott, Claus-Eric"],["dc.contributor.author","Park, Kristen"],["dc.contributor.author","Peterlin, Borut"],["dc.contributor.author","Pölsler, Laura"],["dc.contributor.author","Raas-Rothschild, Annick"],["dc.contributor.author","Randolph, Linda"],["dc.contributor.author","Revencu, Nicole"],["dc.contributor.author","Fagerberg, Christina Ringmann"],["dc.contributor.author","Robinson, Peter Nick"],["dc.contributor.author","Rosnev, Stanislav"],["dc.contributor.author","Rudnik, Sabine"],["dc.contributor.author","Rudolf, Gorazd"],["dc.contributor.author","Schatz, Ulrich"],["dc.contributor.author","Schossig, Anna"],["dc.contributor.author","Schubach, Max"],["dc.contributor.author","Shanoon, Or"],["dc.contributor.author","Sheridan, Eamonn"],["dc.contributor.author","Smirin-Yosef, Pola"],["dc.contributor.author","Spielmann, Malte"],["dc.contributor.author","Suk, Eun-Kyung"],["dc.contributor.author","Sznajer, Yves"],["dc.contributor.author","Thiel, Christian T"],["dc.contributor.author","Thiel, Gundula"],["dc.contributor.author","Verloes, Alain"],["dc.contributor.author","Vrecar, Irena"],["dc.contributor.author","Wahl, Dagmar"],["dc.contributor.author","Weber, Ingrid"],["dc.contributor.author","Winter, Korina"],["dc.contributor.author","Wiśniewska, Marzena"],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Yeung, Ming W"],["dc.contributor.author","Zhao, Max"],["dc.contributor.author","Zhu, Na"],["dc.contributor.author","Zschocke, Johannes"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Horn, Denise"],["dc.contributor.author","Krawitz, Peter M"],["dc.date.accessioned","2020-06-23T14:53:50Z"],["dc.date.available","2020-06-23T14:53:50Z"],["dc.date.issued","2019"],["dc.description.abstract","Phenotype information is crucial for the interpretation of genomic variants. So far it has only been accessible for bioinformatics workflows after encoding into clinical terms by expert dysmorphologists."],["dc.identifier.doi","10.1038/s41436-019-0566-2"],["dc.identifier.pmid","31164752"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17059"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66689"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1530-0366"],["dc.relation.issn","1098-3600"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","PEDIA: prioritization of exome data by image analysis"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Genetics"],["dc.bibliographiccitation.lastpage","28"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Schnabel, Franziska"],["dc.contributor.author","Kornak, Uwe"],["dc.contributor.author","Wollnik, Bernd"],["dc.date.accessioned","2021-04-14T08:22:56Z"],["dc.date.available","2021-04-14T08:22:56Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Progeroid disorders make up a heterogeneous group of very rare hereditary diseases characterized by clinical signs that often mimic physiological aging in a premature manner. Apart from Hutchinson‐Gilford progeria syndrome, one of the best‐investigated progeroid disorders, a wide spectrum of other premature aging phenotypes exist, which differ significantly in their clinical presentation and molecular pathogenesis. Next‐generation sequencing (NGS)‐based approaches have made it feasible to determine the molecular diagnosis in the early stages of a disease. Nevertheless, a broad clinical knowledge on these disorders and their associated symptoms is still fundamental for a comprehensive patient management and for the interpretation of variants of unknown significance from NGS data sets. This review provides a detailed overview on characteristic clinical features and underlying molecular genetics of well‐known as well as only recently identified premature aging disorders and also highlights novel findings towards future therapeutic options."],["dc.description.abstract","image"],["dc.identifier.doi","10.1111/cge.13837"],["dc.identifier.pmid","32860237"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80743"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/158"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1399-0004"],["dc.relation.issn","0009-9163"],["dc.relation.workinggroup","RG Wollnik"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited."],["dc.title","Premature aging disorders: A clinical and genetic compendium"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","overview_ja"],["dspace.entity.type","Publication"]]