Dressel, Ralf

[["dc.bibliographiccitation.artnumber","e22413"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Luehrig, Sandra"],["dc.contributor.author","Tan, Xiaoying"],["dc.contributor.author","Khromov, Tatjana"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Zechner, Ulrich"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2018-11-07T08:54:13Z"],["dc.date.available","2018-11-07T08:54:13Z"],["dc.date.issued","2011"],["dc.description.abstract","Embryonic stem cells (ESCs) generated from the in-vitro culture of blastocyst stage embryos are known as equivalent to blastocyst inner cell mass (ICM) in-vivo. Though several reports have shown the expression of germ cell/pre-meiotic (GC/PrM) markers in ESCs, their functional relevance for the pluripotency and germ line commitment are largely unknown. In the present study, we used mouse as a model system and systematically analyzed the RNA and protein expression of GC/PrM markers in ESCs and found them to be comparable to the expression of cultured pluripotent cells originated from the germ line. Further, siRNA knockdown experiments have demonstrated the parallel maintenance and independence of pluripotent and GC/PrM networks in ESCs. Through chromatin immunoprecipitation experiments, we observed that pluripotent cells exhibit active chromatin states at GC marker genes and a bivalent chromatin structure at PrM marker genes. Moreover, gene expression analysis during the time course of iPS cells generation revealed that the expression of GC markers precedes pluripotency markers. Collectively, through our observations we hypothesize that the chromatin state and the expression of GC/PrM markers might indicate molecular parallels between in-vivo germ cell specification and pluripotent stem cell generation."],["dc.identifier.doi","10.1371/journal.pone.0022413"],["dc.identifier.isi","000293172900028"],["dc.identifier.pmid","21799849"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8198"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22620"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Stage-Specific Germ-Cell Marker Genes Are Expressed in All Mouse Pluripotent Cell Types and Emerge Early during Induced Pluripotency"],["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"]]

[["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","2164"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","The FASEB journal"],["dc.bibliographiccitation.lastpage","2177"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Novota, Peter"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Streckfuss-Boemeke, Katrin"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Jaenisch, Rudolf"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2017-09-07T11:45:57Z"],["dc.date.available","2017-09-07T11:45:57Z"],["dc.date.issued","2010"],["dc.description.abstract","Multipotent adult germ-line stem cells (maGSCs) and induced pluripotent stem cells (iPSCs) could be used to generate autologous cells for therapeutic purposes, which are expected to be tolerated by the recipient. However, effects of the immune system on these cells have not been investigated. We have compared the susceptibility of maGSC lines to IL-2-activated natural killer (NK) cells with embryonic stem cell (ESC) lines, iPSCs, and F9 teratocarcinoma cells. The killing of pluripotent cell lines by syngeneic, allogeneic, and xenogeneic killer cells ranged between 48 and 265% in chromium release assays when compared to YAC-1 cells, which served as highly susceptible reference cells. With the exception of 2 maGSC lines, they expressed ligands for the activating NK receptor NKG2D that belong to the RAE-1 family, and killing could be inhibited by soluble NKG2D, demonstrating a functional role of these molecules. Furthermore, ligands of the activating receptor DNAM-1 were frequently expressed. The susceptibility to NK cells might constitute a common feature of pluripotent cells. It could result in rejection after transplantation, as suggested by a reduced teratoma growth after NK cell activation in vivo, but it might also offer a strategy to deplete contaminating pluripotent cells before grafting of differentiated cells.-Dressel, R., Nolte, J., Elsner, L., Novota, P., Guan, K., Streckfuss-Bomeke, K., Hasenfuss, G., Jaenisch, R., Engel, W. Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells. FASEB J. 24, 2164-2177 (2010). www.fasebj.org"],["dc.identifier.doi","10.1096/fj.09-134957"],["dc.identifier.gro","3142896"],["dc.identifier.isi","000279343600004"],["dc.identifier.pmid","20145206"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6231"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/351"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.relation.issn","0892-6638"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Pluripotent stem cells are highly susceptible targets for syngeneic, allogeneic, and xenogeneic natural killer cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","61"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Stem Cell Research"],["dc.bibliographiccitation.lastpage","74"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Nyamsuren, Gunsmaa"],["dc.contributor.author","Kata, Aleksandra"],["dc.contributor.author","Xu, X."],["dc.contributor.author","Raju, Priyadharsini"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.contributor.author","Adham, Ibrahim M."],["dc.date.accessioned","2018-11-07T09:37:55Z"],["dc.date.available","2018-11-07T09:37:55Z"],["dc.date.issued","2014"],["dc.description.abstract","Pelota (Pelo) is ubiquitously expressed, and its genetic deletion in mice leads to embryonic lethality at an early post-implantation stage. In the present study, we conditionally deleted Pelo and showed that PELO deficiency did not markedly affect the self-renewal of embryonic stem cells (ESCs) or their capacity to differentiate in teratoma assays. However, their differentiation into extraembryonic endoderm (ExEn) in embryoid bodies (EBs) was severely compromised. Conversely, forced expression of Pelo in ESCs resulted in spontaneous differentiation toward the ExEn lineage. Failure of Pelo-deficient ESCs to differentiate into ExEn was accompanied by the retained expression of pluripotency-related genes and alterations in expression of components of the bone morphogenetic protein (BMP) signaling pathway. Further experiments have also revealed that attenuated activity of BMP signaling is responsible for the impaired development of ExEn. The recovery of ExEn and down-regulation of pluripotent genes in BMP4-treated Pelo-null EBs indicate that the failure of mutant cells to down-regulate pluripotency-related genes in EBs is not a result of autonomous defect, but rather to failed signals from surrounding ExEn lineage that induce the differentiation program. In vivo studies showed the presence of ExEn in Pelo-null embryos at E6.5, yet embryonic lethality at E7.5, suggesting that PELO is not required for the induction of ExEn development, but rather for ExEn maintenance or for terminal differentiation toward functional visceral endoderm which provides the embryos with growth factors required for further development. Moreover, Pelo-null fibroblasts failed to reprogram toward induced pluripotent stem cells (iPSCs) due to inactivation of BMP signaling and impaired mesenchymal-to-epithelial transition. Thus, our results indicate that PELO plays an important role in the establishment of pluripotency and differentiation of ESCs into ExEn lineage through activation of BMP signaling. (C) 2014 The Authors. Published by Elsevier B.V."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2014"],["dc.identifier.doi","10.1016/j.scr.2014.04.011"],["dc.identifier.isi","000342287000006"],["dc.identifier.pmid","24835669"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10452"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32951"],["dc.notes.intern","Merged from goescholar"],["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.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Pelota regulates the development of extraembryonic endoderm through activation of bone morphogenetic protein (BMP) signaling"],["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"]]

[["dc.bibliographiccitation.artnumber","31"],["dc.bibliographiccitation.journal","Biology Direct"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","Nayernia, Karim"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Engel, Wolfgang"],["dc.date.accessioned","2017-09-07T11:46:52Z"],["dc.date.available","2017-09-07T11:46:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Background: Multipotent adult germ-line stem cells (maGSCs) represent a new pluripotent cell type that can be derived without genetic manipulation from spermatogonial stem cells (SSCs) present in adult testis. Similarly to induced pluripotent stem cells (iPSCs), they could provide a source of cellular grafts for new transplantation therapies of a broad variety of diseases. To test whether these stem cells can be rejected by the recipients, we have analyzed whether maGSCs and iPSCs can become targets for cytotoxic T lymphocytes (CTL) or whether they are protected, as previously proposed for embryonic stem cells (ESCs). Results: We have observed that maGSCs can be maintained in prolonged culture with or without leukemia inhibitory factor and/or feeder cells and still retain the capacity to form teratomas in immunodeficient recipients. They were, however, rejected in immunocompetent allogeneic recipients, and the immune response controlled teratoma growth. We analyzed the susceptibility of three maGSC lines to CTL in comparison to ESCs, iPSCs, and F9 teratocarcinoma cells. Major histocompatibility complex (MHC) class I molecules were not detectable by flow cytometry on these stem cell lines, apart from low levels on one maGSC line (maGSC Stra8 SSC5). However, using a quantitative real time PCR analysis H2K and B2m transcripts were detected in all pluripotent stem cell lines. All pluripotent stem cell lines were killed in a peptide-dependent manner by activated CTLs derived from T cell receptor transgenic OT-I mice after pulsing of the targets with the SIINFEKL peptide. Conclusion: Pluripotent stem cells, including maGSCs, ESCs, and iPSCs can become targets for CTLs, even if the expression level of MHC class I molecules is below the detection limit of flow cytometry. Thus they are not protected against CTL-mediated cytotoxicity. Therefore, pluripotent cells might be rejected after transplantation by this mechanism if specific antigens are presented and if specific activated CTLs are present. Our results show that the adaptive immune system has in principle the capacity to kill pluripotent and teratoma forming stem cells. This finding might help to develop new strategies to increase the safety of future transplantations of in vitro differentiated cells by exploiting a selective immune response against contaminating undifferentiated cells. Reviewers: This article was reviewed by Bhagirath Singh, Etienne Joly and Lutz Walter."],["dc.identifier.doi","10.1186/1745-6150-4-31"],["dc.identifier.gro","3143070"],["dc.identifier.isi","000270223400001"],["dc.identifier.pmid","19715575"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/5748"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/543"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1745-6150"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Multipotent adult germ-line stem cells, like other pluripotent stem cells, can be killed by cytotoxic T lymphocytes despite low expression of major histocompatibility complex class I molecules"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e48869"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Khromov, Tatjana"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Siamishi, Iliana"],["dc.contributor.author","Nolte, Jessica"],["dc.contributor.author","Opitz, Lennart"],["dc.contributor.author","Engel, Wolfgang"],["dc.contributor.author","Pantakani, Dasaradha Venkata Krishna"],["dc.date.accessioned","2018-11-07T09:03:34Z"],["dc.date.available","2018-11-07T09:03:34Z"],["dc.date.issued","2012"],["dc.description.abstract","Stem cells in the developing embryo proliferate and differentiate while maintaining genomic integrity, failure of which may lead to accumulation of mutations and subsequent damage to the embryo. Embryonic stem cells (ESCs), the in vitro counterpart of embryo stem cells are highly sensitive to genotoxic stress. Defective ESCs undergo either efficient DNA damage repair or apoptosis, thus maintaining genomic integrity. However, the genotoxicity- and apoptosis-related processes in germ-line derived pluripotent cells, multipotent adult germ-line stem cells (maGSCs), are currently unknown. Here, we analyzed the expression of apoptosis-related genes using OligoGEArray in undifferentiated maGSCs and ESCs and identified a similar set of genes expressed in both cell types. We detected the expression of intrinsic, but not extrinsic, apoptotic pathway genes in both cell types. Further, we found that apoptosis-related gene expression patterns of differentiated ESCs and maGSCs are identical to each other. Comparative analysis revealed that several pro-and antiapoptotic genes are expressed specifically in pluripotent cells, but markedly downregulated in the differentiated counterparts of these cells. Activation of the intrinsic apoptotic pathway cause approximately similar to 35% of both ESCs and maGSCs to adopt an early-apoptotic phenotype. Moreover, we performed transcriptome studies using early-apoptotic cells to identify novel pluripotency- and apoptosis-related genes. From these transcriptome studies, we selected Fgf4 (Fibroblast growth factor 4) and Mnda (Myeloid cell nuclear differentiating antigen), which are highly downregulated in early-apoptotic cells, as novel candidates and analyzed their roles in apoptosis and genotoxicity responses in ESCs. Collectively, our results show the existence of common molecular mechanisms for maintaining the pristine stem cell pool of both ESCs and maGSCs."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2012"],["dc.identifier.doi","10.1371/journal.pone.0048869"],["dc.identifier.isi","000311935800158"],["dc.identifier.pmid","23145002"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8319"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24921"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Apoptosis-Related Gene Expression Profiles of Mouse ESCs and maGSCs: Role of Fgf4 and Mnda in Pluripotent Cell Responses to Genotoxicity"],["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"]]