Smorag, Lukasz Krzysztof

[["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.artnumber","6008"],["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.lastpage","11"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Xu, Xingbo"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Nakamura, Toshinobu"],["dc.contributor.author","Kimura, Tohru"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Fitzner, Antje"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Linke, Matthias"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, D.V. Krishna"],["dc.date.accessioned","2018-11-07T10:03:46Z"],["dc.date.available","2018-11-07T10:03:46Z"],["dc.date.issued","2015"],["dc.description.abstract","Reprogramming of mouse somatic cells into induced pluripotent stem cells (iPSCs) often generates partially reprogrammed iPSCs (pre-iPSCs), low-grade chimera forming iPSCs (lg-iPSCs) and fully reprogrammed, high-grade chimera production competent iPSCs (hg-iPSCs). Lg-iPSC transcriptome analysis revealed misregulated Dlk1-Dio3 cluster gene expression and subsequently the imprinting defect at the Dlk1-Dio3 locus. Here, we show that germ-cell marker Dppa3 is present only in lg-iPSCs and hg-iPSCs, and that induction with exogenous Dppa3 enhances reprogramming kinetics, generating all hg-iPSCs, similar to vitamin C (Vc). Conversely, Dppa3-null fibroblasts show reprogramming block at pre-iPSCs state and Dlk1-Dio3 imprinting defect. At the molecular level, we show that Dppa3 is associated with Dlk1-Dio3 locus and identify that Dppa3 maintains imprinting by antagonizing Dnmt3a binding. Our results further show molecular parallels between Dppa3 and Vc in Dlk1-Dio3 imprinting maintenance and suggest that early activation of Dppa3 is one of the cascades through which Vc facilitates the generation of fully reprogrammed iPSCs."],["dc.identifier.doi","10.1038/ncomms7008"],["dc.identifier.isi","000348812400009"],["dc.identifier.pmid","25613421"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11863"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38545"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/130"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Dressel"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Dppa3 expression is critical for generation of fully reprogrammed iPS cells and maintenance of Dlk1-Dio3 imprinting"],["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.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","677"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Biology of the Cell"],["dc.bibliographiccitation.lastpage","692"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Smorag, Lukasz"],["dc.contributor.author","Zheng, Y."],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:04:07Z"],["dc.date.available","2018-11-07T09:04:07Z"],["dc.date.issued","2012"],["dc.description.abstract","Background information Recently, it became apparent that microRNAs (miRNAs) can regulate gene expression post-transcriptionally. Despite the advances in identifying the testis-expressed miRNAs and their role in spermatogenesis, only few data are available showing the spatiotemporal expression of miRNAs during this process. Results To understand how different miRNAs can regulate germ cells differentiation, we generated a transgenic mouse model and purified pure populations of premeiotic (PrM) cells and primary spermatocytes (meiotic cells). We also established spermatogonial stem cell (SSC) culture using relatively simple and robust culture conditions. Comparison of global miRNA expression in these germ cell populations revealed 17 SSC-, 11 PrM- and 13 meiotic-specific miRNAs. We identified nine miRNAs as specific for both SSC and PrM cells and another nine miRNAs as specific for PrM and meiotic cells. Additionally, 45 miRNAs were identified as commonly expressed in all three cell types. Several of PrM- and meiotic-specific miRNAs were identified as exclusively/preferentially expressed in testis. We were able to identify the relevant target genes for many of these miRNAs. The luciferase reporter assays with SSC (miR-221)-, PrM (miR-203)- and meiotic (miR-34b-5p)-specific miRNAs and 3'-untranslated region constructs of their targets, c-Kit, Rbm44 and Cdk6, respectively, showed an approximately 30%40% decrease in reporter activity. Moreover, we observed a reduced expression of endogenous proteins, c-Kit and Cdk6, when the testis-derived cell lines, GC-1 and GC-4, were transfected with miRNA mimics for miR-221 and miR-34b-5p, respectively. Conclusions Taken together, we established the miRNA signature of SSC, PrM and meiotic cells and show evidence for their functional relevance during the process of spermatogenesis by target prediction and validation. Through our observations, we propose a working model in which the stage-specific miRNAs such as miR-221, -203 and -34b-5p coordinate the regulation of spermatogenesis."],["dc.identifier.doi","10.1111/boc.201200014"],["dc.identifier.isi","000310391100006"],["dc.identifier.pmid","22909339"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9536"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25040"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1768-322X"],["dc.relation.issn","0248-4900"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","MicroRNA signature in various cell types of mouse spermatogenesis: Evidence for stage-specifically expressed miRNA-221, -203 and -34b-5p mediated spermatogenesis regulation"],["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"]]