Smorag, Lukasz Krzysztof

[["dc.bibliographiccitation.firstpage","527"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Wiley Interdisciplinary Reviews - RNA"],["dc.bibliographiccitation.lastpage","535"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:38:38Z"],["dc.date.available","2018-11-07T09:38:38Z"],["dc.date.issued","2014"],["dc.description.abstract","RNA-binding proteins play an important role in the regulation of gene expression by modulating translation and localization of specific messenger RNAs (mRNAs) during early development and gametogenesis. The DAZ (Deleted in Azoospermia) family of proteins, which includes DAZ, DAZL, and BOULE, are germ cell-specific RNA-binding proteins that are implicated in translational regulation of several transcripts. Of particular importance is DAZL, which is present in vertebrates and arose from the duplication of the ancestral BOULE during evolution. Identification of DAZL target mRNAs and characterization of the RNA-binding sequence through in vitro binding assays and crystallographic studies revealed that DAZL binds to GUU triplets in the 3' untranslated region of target mRNAs. Although there is compelling evidence for the role of DAZL in translation stimulation of target mRNAs, recent studies indicate that DAZL can also function in translational repression and transport of specific mRNAs. Furthermore, apart from the well-characterized function of DAZL in gametogenesis, recent data suggest its role in early embryonic development and differentiation of pluripotent stem cells toward functional gametes. In light of the mounting evidence for the role of DAZL in various cellular and developmental processes, we summarize the currently characterized biological functions of DAZL in RNA biology and development. (C) 2014 John Wiley & Sons, Ltd."],["dc.identifier.doi","10.1002/wrna.1228"],["dc.identifier.isi","000337627700006"],["dc.identifier.pmid","24715697"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33108"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1757-7012"],["dc.relation.issn","1757-7004"],["dc.title","The roles of DAZL in RNA biology and development"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","793"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","MHR Basic science of reproductive medicine"],["dc.bibliographiccitation.lastpage","803"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Zovoilis, Athanasios"],["dc.contributor.author","Pantazi, Angeliki"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Salinas Riester, Gabriela"],["dc.contributor.author","Wolf, Marieke"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Holubowska, Anna"],["dc.contributor.author","Stewart, Colin L."],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T08:37:42Z"],["dc.date.available","2018-11-07T08:37:42Z"],["dc.date.issued","2010"],["dc.description.abstract","Cells originating from the germ cell lineage retain the remarkable property under special culture conditions to give rise to cells with embryonic stem cell (ESC) properties, such as the multipotent adult germline stem cells (maGSCs) derived from adult mouse testis. To get an insight into the mechanisms that control pluripotency and differentiation in these cells, we studied how differences observed during in vitro differentiation between ESCs and maGSCs are associated with differences at the level of microRNAs (miRNAs). In this work, we provide for a first time a connection between germ cell origin of maGSCs and their specific miRNA expression profile. We found that maGSCs express higher levels of germ cell markers characteristic for primordial germ cells (PGCs) and spermatogonia compared with ESCs. Retained expression of miR-290 cluster has been previously reported in maGSCs during differentiation and it was associated with higher Oct-4 levels. Here, we show that this property is also shared by another pluripotent cell line originating from the germ line, the embryonic germ cells. In addition, we provide proof that the specific miRNA expression profile of maGSCs has an impact on their differentiation potential. Low levels of miR-302 in maGSCs during the first 10 days of leukaemia inhibitory factor deprivation are shown to be necessary for the maintenance of high levels of early germ cell markers."],["dc.identifier.doi","10.1093/molehr/gaq053"],["dc.identifier.isi","000283679900002"],["dc.identifier.pmid","20566704"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18598"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1360-9947"],["dc.title","Embryonic stem cell-related miRNAs are involved in differentiation of pluripotent cells originating from the germ line"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","69"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","Differentiation"],["dc.bibliographiccitation.lastpage","78"],["dc.bibliographiccitation.volume","78"],["dc.contributor.author","Zovoilis, Athanasios"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Pantazi, Angeliki"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T11:24:40Z"],["dc.date.available","2018-11-07T11:24:40Z"],["dc.date.issued","2009"],["dc.description.abstract","We report the biological effects of miR-290 cluster via gain-of-function or loss-of-function experiments in mouse embryonic stem cells (ESCs) cultured under differentiation conditions. Under these conditions we found that overexpression of miR-290 cluster in ESCs cannot prevent downregulation of Oct-4, but inhibition results in earlier down regulation of Oct-4 compared with the negative control. In consistence with previous findings that report ectopic expression of Brachyury during gastrulation in Argonaute-2 KO mice due to impaired miRNA function, we show that miR-290 cluster regulates negatively differentiation of ESCs towards mesodermal and germ cell lineage. These results suggest that although incapable to maintain pluripotent state alone, miR-290 cluster inhibits ESC differentiation and it is involved in the pathways controlling mesoderm and primordial germ cell differentiation. Finally, we provide proofs that members of this cluster target Dkk-1 gene, a Wnt pathway inhibitor, and affect this pathway, which can partially explain why miR-290 cluster favours pluripotency against differentiation. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.diff.2009.06.003"],["dc.identifier.isi","000274532300003"],["dc.identifier.pmid","19628328"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56456"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Sci Ltd"],["dc.relation.issn","0301-4681"],["dc.title","Members of the miR-290 cluster modulate in vitro differentiation of mouse embryonic stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1045"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Stem Cell Research"],["dc.bibliographiccitation.lastpage","1059"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Elkenani, Manar"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:17:54Z"],["dc.date.available","2018-11-07T09:17:54Z"],["dc.date.issued","2013"],["dc.description.abstract","Pluripotency is maintained by both known and unknown transcriptional regulatory networks. In the present study, we have identified Zfp819, a KRAB-zinc finger protein, as a novel pluripotency-related factor and characterized its role in pluripotent stem cells. We show that Zfp819 is expressed highly in various types of pluripotent stem cells but not in their differentiated counterparts. We identified the presence of non-canonical nuclear localization signals in particular zinc finger motifs and identified them as responsible for the nuclear localization of Zfp819. Analysis of the Zfp819 promoter region revealed the presence of a transcriptionally active chromatin signature. Moreover, we confirmed the binding of pluripotency-related factors, Oct4, Sox2, and Nanog to the distal promoter region of Zfp819, indicating that the expression of this gene is regulated by a pluripotency transcription factor network. We found that the expression of endogenous retroviral elements (ERVs) such as Intracisternal A Particle (IAP) retrotransposons, Long Interspersed Nuclear Elements (LINE1), and Short Interspersed Nuclear Elements (SINE B1) is significantly upregulated in Zfp819-knockdown (Zfp819_KD) cells. In line with the activation of ERVs, we observed the occurrence of spontaneous DNA damage in Zfp819_KD cells. Furthermore, we tested whether Zfp819 can interact with KAP1, a KRAB-associated protein with a transcriptional repression function, and found the interaction between these two proteins in both in vitro and in vivo experiments. The challenging of Zfp819_KD cells with DNA damaging agent revealed that these cells are inefficient in repairing the damaged DNA, as cells showed presence of gamma H2A.X foci for a prolonged time. Collectively, our study identified Zfp819 as a novel pluripotency-related factor and unveiled its function in genomic integrity maintenance mechanisms of mouse embryonic stem cells. (C) 2013 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.scr.2013.07.006"],["dc.identifier.isi","327905300008"],["dc.identifier.pmid","23954693"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28283"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","1876-7753"],["dc.relation.issn","1873-5061"],["dc.title","Zfp819, a novel KRAB-zinc finger protein, interacts with KAP1 and functions in genomic integrity maintenance of mouse embryonic stem cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","833"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","843"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Ehmke, Nadja"],["dc.contributor.author","Graul-Neumann, Luitgard"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Koenig, Rainer"],["dc.contributor.author","Segebrecht, Lara"],["dc.contributor.author","Magoulas, Pilar"],["dc.contributor.author","Scaglia, Fernando"],["dc.contributor.author","Kilic, Esra"],["dc.contributor.author","Hennig, Anna F."],["dc.contributor.author","Adolphs, Nicolai"],["dc.contributor.author","Saha, Namrata"],["dc.contributor.author","Fauler, Beatrix"],["dc.contributor.author","Kalscheuer, Vera M."],["dc.contributor.author","Hennig, Friederike"],["dc.contributor.author","Altmüller, Janine"],["dc.contributor.author","Netzer, Christian"],["dc.contributor.author","Thiele, Holger"],["dc.contributor.author","Nürnberg, Peter"],["dc.contributor.author","Yigit, Gökhan"],["dc.contributor.author","Jäger, Marten"],["dc.contributor.author","Hecht, Jochen"],["dc.contributor.author","Krüger, Ulrike"],["dc.contributor.author","Mielke, Thorsten"],["dc.contributor.author","Krawitz, Peter M."],["dc.contributor.author","Horn, Denise"],["dc.contributor.author","Schuelke, Markus"],["dc.contributor.author","Mundlos, Stefan"],["dc.contributor.author","Bacino, Carlos A."],["dc.contributor.author","Bonnen, Penelope E."],["dc.contributor.author","Wollnik, Bernd"],["dc.contributor.author","Fischer-Zirnsak, Björn"],["dc.contributor.author","Kornak, Uwe"],["dc.date.accessioned","2018-04-23T11:49:09Z"],["dc.date.available","2018-04-23T11:49:09Z"],["dc.date.issued","2017"],["dc.description.abstract","Gorlin-Chaudhry-Moss syndrome (GCMS) is a dysmorphic syndrome characterized by coronal craniosynostosis and severe midface hypoplasia, body and facial hypertrichosis, microphthalmia, short stature, and short distal phalanges. Variable lipoatrophy and cutis laxa are the basis for a progeroid appearance. Using exome and genome sequencing, we identified the recurrent de novo mutations c.650G>A (p.Arg217His) and c.649C>T (p.Arg217Cys) in SLC25A24 in five unrelated girls diagnosed with GCMS. Two of the girls had pronounced neonatal progeroid features and were initially diagnosed with Wiedemann-Rautenstrauch syndrome. SLC25A24 encodes a mitochondrial inner membrane ATP-Mg/Pi carrier. In fibroblasts from affected individuals, the mutated SLC25A24 showed normal stability. In contrast to control cells, the probands’ cells showed mitochondrial swelling, which was exacerbated upon treatment with hydrogen peroxide (H2O2). The same effect was observed after overexpression of the mutant cDNA. Under normal culture conditions, the mitochondrial membrane potential of the probands’ fibroblasts was intact, whereas ATP content in the mitochondrial matrix was lower than that in control cells. However, upon H2O2 exposure, the membrane potential was significantly elevated in cells harboring the mutated SLC25A24. No reduction of mitochondrial DNA copy number was observed. These findings demonstrate that mitochondrial dysfunction with increased sensitivity to oxidative stress is due to the SLC25A24 mutations. Our results suggest that the SLC25A24 mutations induce a gain of pathological function and link mitochondrial ATP-Mg/Pi transport to the development of skeletal and connective tissue."],["dc.identifier.doi","10.1016/j.ajhg.2017.09.016"],["dc.identifier.gro","3142499"],["dc.identifier.pmid","29100093"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13652"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/193"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D02: Neue Mechanismen der genomischen Instabilität bei Herzinsuffizienz"],["dc.relation.issn","0002-9297"],["dc.relation.workinggroup","RG Wollnik"],["dc.title","De Novo Mutations in SLC25A24 Cause a Craniosynostosis Syndrome with Hypertrichosis, Progeroid Appearance, and Mitochondrial Dysfunction"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","813"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Human Genetics"],["dc.bibliographiccitation.lastpage","826"],["dc.bibliographiccitation.volume","135"],["dc.contributor.author","Jakubiczka-Smorag, Joanna"],["dc.contributor.author","Santamaria-Araujo, Jose Angel"],["dc.contributor.author","Metz, Imke"],["dc.contributor.author","Kumar, Avadh"],["dc.contributor.author","Hakroush, Samy"],["dc.contributor.author","Brueck, Wolfgang"],["dc.contributor.author","Schwarz, Guenter"],["dc.contributor.author","Burfeind, Peter"],["dc.contributor.author","Reiss, Jochen"],["dc.contributor.author","Smorag, Lukasz"],["dc.date.accessioned","2018-11-07T10:12:30Z"],["dc.date.available","2018-11-07T10:12:30Z"],["dc.date.issued","2016"],["dc.description.abstract","Molybdenum cofactor (MoCo) deficiency is a rare, autosomal-recessive disorder, mainly caused by mutations in MOCS1 (MoCo deficiency type A) or MOCS2 (MoCo deficiency type B) genes; the absence of active MoCo results in a deficiency in all MoCo-dependent enzymes. Patients with MoCo deficiency present with neonatal seizures, feeding difficulties, severe developmental delay, brain atrophy and early childhood death. Although substitution therapy with cyclic pyranopterin monophosphate (cPMP) has been successfully used in both Mocs1 knockout mice and in patients with MoCo deficiency type A, there is currently no Mocs2 knockout mouse and no curative therapy for patients with MoCo deficiency type B. Therefore, we generated and characterized a Mocs2-null mouse model of MoCo deficiency type B. Expression analyses of Mocs2 revealed a ubiquitous expression pattern; however, at the cellular level, specific cells show prominent Mocs2 expression, e.g., neuronal cells in cortex, hippocampus and brainstem. Phenotypic analyses demonstrated that Mocs2 knockout mice failed to thrive and died within 11 days after birth. None of the tested MoCo-dependent enzymes were active in Mocs2-deficient mice, leading to elevated concentrations of purines, such as hypoxanthine and xanthine, and non-detectable levels of uric acid in the serum and urine. Moreover, elevated concentrations of S-sulfocysteine were measured in the serum and urine. Increased levels of xanthine resulted in bladder and kidney stone formation, whereas increased concentrations of toxic sulfite triggered neuronal apoptosis. In conclusion, Mocs2-deficient mice recapitulate the severe phenotype observed in humans and can now serve as a model for preclinical therapeutic approaches for MoCo deficiency type B."],["dc.identifier.doi","10.1007/s00439-016-1676-4"],["dc.identifier.isi","000377364300012"],["dc.identifier.pmid","27138983"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40249"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1432-1203"],["dc.relation.issn","0340-6717"],["dc.title","Mouse model for molybdenum cofactor deficiency type B recapitulates the phenotype observed in molybdenum cofactor deficient patients"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]