Kosinsky, Robyn Laura

[["dc.bibliographiccitation.firstpage","705"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Calcified Tissue International"],["dc.bibliographiccitation.lastpage","719"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Saul, D."],["dc.contributor.author","Harlas, B."],["dc.contributor.author","Ahrabi, A."],["dc.contributor.author","Kosinsky, R. L."],["dc.contributor.author","Hoffmann, D. B."],["dc.contributor.author","Wassmann, M."],["dc.contributor.author","Wigger, R."],["dc.contributor.author","Böker, K. O."],["dc.contributor.author","Sehmisch, S."],["dc.contributor.author","Komrakova, M."],["dc.date.accessioned","2020-06-10T14:22:48Z"],["dc.date.available","2020-06-10T14:22:48Z"],["dc.date.issued","2017"],["dc.description.abstract","Osteoporosis is often accompanied by sarcopenia. The effect of strontium ranelate (SR) on muscle tissue has not been investigated sufficiently. In this study, the effect of different SR treatments on muscle was studied. Additionally, the lumbar vertebrae were analyzed. Three-month-old female rats were divided into five groups (n = 12): Group 1: untreated (NON-OVX); Group 2: ovariectomized and left untreated (OVX); Group 3: SR after OVX until the study ended (13 weeks, SR prophylaxis and therapy = pr+th); Group 4: OVX and SR for 8 weeks (SR prophylaxis = pr); Group 5: SR for 5 weeks from the 8 week after OVX (SR therapy = SR th). SR was applied in food (630 mg/kg body weight). The size of muscle fibers, capillary density, metabolic enzymes, and mRNA expression were assessed in soleus, gastrocnemius, and longissimus muscles. The vertebral bodies underwent micro-CT, biomechanical, and ashing analyses. In general, SR did not alter the muscle histological parameters. The changes in fiber size and capillary ratio were related to the body weight. Myostatin mRNA was decreased in Sr pr+th; protein expression was not changed. SR th led to increase in mRNA expression of vascular endothelial growth factor (Vegf-B). In lumbar spine, SR pr+th enhanced biomechanical properties, bone mineral density, trabecular area, density, and thickness and cortical density. The reduced calcium/phosphate ratio in the SR pr+th group indicates the replacement of calcium by strontium ions. SR has no adverse effects on muscle tissue and it shows a favorable time-dependent effect on vertebrae. A functional analysis of muscles could verify these findings."],["dc.identifier.doi","10.1007/s00223-017-0374-0"],["dc.identifier.pmid","29242963"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66222"],["dc.language.iso","en"],["dc.relation.eissn","1432-0827"],["dc.relation.issn","0171-967X"],["dc.title","Effect of Strontium Ranelate on the Muscle and Vertebrae of Ovariectomized Rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","401"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Saul, Dominik; \t\t \r\n\t\t Kogod Center on Aging and Division of Endocrinology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA, Saul.Dominik@mayo.edu\t\t \r\n\t\t Department of Trauma, Orthopedics and Reconstructive Surgery, Georg-August-University of Goettingen, 37075 Goettingen, Germany, Saul.Dominik@mayo.edu"],["dc.contributor.affiliation","Kosinsky, Robyn Laura; \t\t \r\n\t\t Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA, Kosinsky.RobynLaura@mayo.edu"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.date.accessioned","2021-04-14T08:29:43Z"],["dc.date.available","2021-04-14T08:29:43Z"],["dc.date.issued","2021"],["dc.date.updated","2022-09-06T08:44:48Z"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.description.sponsorship","Deutsche Krebshilfe"],["dc.identifier.doi","10.3390/ijms22010401"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82970"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Epigenetics of Aging and Aging-Associated Diseases"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3126"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.date.accessioned","2021-12-01T09:23:03Z"],["dc.date.available","2021-12-01T09:23:03Z"],["dc.date.issued","2021"],["dc.description.abstract","The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies."],["dc.description.abstract","The human aging process is associated with molecular changes and cellular degeneration, resulting in a significant increase in cancer incidence with age. Despite their potential correlation, the relationship between cancer- and ageing-related transcriptional changes is largely unknown. In this study, we aimed to analyze aging-associated transcriptional patterns in publicly available bulk mRNA-seq and single-cell RNA-seq (scRNA-seq) datasets for chronic myelogenous leukemia (CML), colorectal cancer (CRC), hepatocellular carcinoma (HCC), lung cancer (LC), and pancreatic ductal adenocarcinoma (PDAC). Indeed, we detected that various aging/senescence-induced genes (ASIGs) were upregulated in malignant diseases compared to healthy control samples. To elucidate the importance of ASIGs during cell development, pseudotime analyses were performed, which revealed a late enrichment of distinct cancer-specific ASIG signatures. Notably, we were able to demonstrate that all cancer entities analyzed in this study comprised cell populations expressing ASIGs. While only minor correlations were detected between ASIGs and transcriptome-wide changes in PDAC, a high proportion of ASIGs was induced in CML, CRC, HCC, and LC samples. These unique cellular subpopulations could serve as a basis for future studies on the role of aging and senescence in human malignancies."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2021"],["dc.identifier.doi","10.3390/cells10113126"],["dc.identifier.pii","cells10113126"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/94549"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-478"],["dc.relation.eissn","2073-4409"],["dc.relation.orgunit","Klinik für Unfallchirurgie, Orthopädie und Plastische Chirurgie"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Single-Cell Transcriptomics Reveals the Expression of Aging- and Senescence-Associated Genes in Distinct Cancer Cell Populations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","unpublished"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1000191"],["dc.bibliographiccitation.issue","01"],["dc.bibliographiccitation.journal","Journal of Osteoporosis and Physical Activity"],["dc.bibliographiccitation.volume","05"],["dc.contributor.author","Saul, D."],["dc.contributor.author","Schilling, A. F."],["dc.contributor.author","Kosinsky, R. L."],["dc.date.accessioned","2019-07-09T11:43:26Z"],["dc.date.available","2019-07-09T11:43:26Z"],["dc.date.issued","2017"],["dc.description.abstract","In an aging population, the decline in muscle mass and strength in combination with a high prevalence of osteoporosis and cancer leads to a multitude of clinical manifestations. In the recent years, mouse models of wasting in cancer and inflammation, including xenograft, genetic and chemically induced models, allowed to uncover several key mechanisms underlying muscle loss. These include inflammation, hormone alterations and deregulated protein degradation. Inflammation is associated with increased expression of tumor necrosis factor α (TNF-α), nuclear factor κB (NF-κB), and interleukin (IL)-6 and is therefore linked to inflammatory bowel diseases or chronic obstructive pulmonary disease (COPD). Moreover, active NF-κB signaling and IL-6 secretion commonly occurs in malignancies and cancer-induced cachexia. The ubiquitin proteasome-mediated degradation of proteins represents a second pathway underlying sarcopenia and is partially initiated by inflammatory signaling. Consequently, increased levels of the E3 ligases Muscle RING-Finger Protein-1 (MuRF1), Atrogin-1/Muscle Atrophy F-box (MAFbx), and tumor necrosis factor α receptor adaptor protein 6 (TRAF6) are associated with high rates of protein degradation. Furthermore, hormonal alterations, such as the aging-related decline of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), lead to a reduction of muscle mass. Interestingly, experimental targeting of several of those sarcopenia-associated factors in vivo resulted in a rescue of muscle mass and function. While therapeutic options nowadays still need to be evaluated regarding their clinical practicability, IL-6 antibodies, inhibition of cyclooxygenases and inhibitors of myostatin appear promising."],["dc.identifier.doi","10.4172/2329-9509.1000191"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14528"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58888"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2329-9509"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Why Age Matters: Inflammation, Cancer and Hormones in the Development of Sarcopenia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Atkinson, Elizabeth J."],["dc.contributor.author","Doolittle, Madison L."],["dc.contributor.author","Zhang, Xu"],["dc.contributor.author","LeBrasseur, Nathan K."],["dc.contributor.author","Pignolo, Robert J."],["dc.contributor.author","Robbins, Paul D."],["dc.contributor.author","Niedernhofer, Laura J."],["dc.contributor.author","Ikeno, Yuji"],["dc.contributor.author","Khosla, Sundeep"],["dc.date.accessioned","2022-09-01T09:50:03Z"],["dc.date.available","2022-09-01T09:50:03Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Although cellular senescence drives multiple age-related co-morbidities through the senescence-associated secretory phenotype, in vivo senescent cell identification remains challenging. Here, we generate a gene set (SenMayo) and validate its enrichment in bone biopsies from two aged human cohorts. We further demonstrate reductions in SenMayo in bone following genetic clearance of senescent cells in mice and in adipose tissue from humans following pharmacological senescent cell clearance. We next use SenMayo to identify senescent hematopoietic or mesenchymal cells at the single cell level from human and murine bone marrow/bone scRNA-seq data. Thus, SenMayo identifies senescent cells across tissues and species with high fidelity. Using this senescence panel, we are able to characterize senescent cells at the single cell level and identify key intercellular signaling pathways. SenMayo also represents a potentially clinically applicable panel for monitoring senescent cell burden with aging and other conditions as well as in studies of senolytic drugs."],["dc.description.sponsorship"," Dr. Mildred Scheel Stiftung für Krebsforschung https://doi.org/10.13039/501100005973"],["dc.description.sponsorship"," Foundation for the National Institutes of Health https://doi.org/10.13039/100000009"],["dc.identifier.doi","10.1038/s41467-022-32552-1"],["dc.identifier.pii","32552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113610"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","4"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nutrition & Metabolism"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Weber, Marie"],["dc.contributor.author","Zimmermann, Marc Hendrik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Hoffmann, Daniel Bernd"],["dc.contributor.author","Menger, Björn"],["dc.contributor.author","Taudien, Stefan"],["dc.contributor.author","Lehmann, Wolfgang"],["dc.contributor.author","Komrakova, Marina"],["dc.contributor.author","Sehmisch, Stephan"],["dc.date.accessioned","2019-07-09T11:49:50Z"],["dc.date.accessioned","2020-06-09T07:03:29Z"],["dc.date.available","2019-07-09T11:49:50Z"],["dc.date.available","2020-06-09T07:03:29Z"],["dc.date.issued","2019"],["dc.description.abstract","Background Osteoporosis is one of the world’s major medical burdens in the twenty-first century. Pharmaceutical intervention currently focusses on decelerating bone loss, but phytochemicals such as baicalein, which is a lipoxygenase inhibitor, may rescue bone loss. Studies evaluating the effect of baicalein in vivo are rare. Methods We administered baicalein to sixty-one three-month-old female Sprague-Dawley rats. They were divided into five groups, four of which were ovariectomized (OVX) and one non-ovariectomized (NON-OVX). Eight weeks after ovariectomy, bilateral tibial osteotomy with plate osteosynthesis was performed and bone formation quantified. Baicalein was administered subcutaneously using three doses (C1: 1 mg/kg BW; C2: 10 mg/kg BW; and C3: 100 mg/kg BW) eight weeks after ovariectomy for four weeks. Finally, femora and tibiae were collected. Biomechanical tests, micro-CT, ashing, histological and gene expression analyses were performed. Results Biomechanical properties were unchanged in tibiae and reduced in femora. In tibiae, C1 treatment enhanced callus density and cortical width and decreased callus area. In the C3 group, callus formation was reduced during the first 3 weeks after osteotomy, correlating to a higher mRNA expression of Osteocalcin, Tartrate-resistant acid phosphatase and Rankl. In femora, baicalein treatments did not alter bone parameters. Conclusions Baicalein enhanced callus density and cortical width but impaired early callus formation in tibiae. In femora, it diminished the biomechanical properties and calcium-to-phosphate ratio. Thus, it is not advisable to apply baicalein to treat early bone fractures. To determine the exact effects on bone healing, further studies in which baicalein treatments are started at different stages of healing are needed."],["dc.identifier.doi","10.1186/s12986-018-0327-2"],["dc.identifier.pmid","30651746"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15789"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59640"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66212"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1743-7075"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Effect of the Lipoxygenase Inhibitor Baicalein on Bone Tissue and Bone Healing in Ovariectomized Rats"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Cell Death and Differentiation"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Zerche, Maria"],["dc.contributor.author","Kutschat, Ana Patricia"],["dc.contributor.author","Nair, Asha"],["dc.contributor.author","Ye, Zhenqing"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","von Heesen, Maximilian"],["dc.contributor.author","Friton, Jessica J."],["dc.contributor.author","Schwarzer, Ana Carolina"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2021-07-05T15:00:28Z"],["dc.date.available","2021-07-05T15:00:28Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract Despite the identification of several genetic factors linked to increased susceptibility to inflammatory bowel disease (IBD), underlying molecular mechanisms remain to be elucidated in detail. The ubiquitin ligases RNF20 and RNF40 mediate the monoubiquitination of histone H2B at lysine 120 (H2Bub1) and were shown to play context-dependent roles in the development of inflammation. Here, we aimed to examine the function of the RNF20/RNF40/H2Bub1 axis in intestinal inflammation in IBD patients and mouse models. For this purpose, intestinal sections from IBD patients were immunohistochemically stained for H2Bub1. Rnf20 or Rnf40 were conditionally deleted in the mouse intestine and mice were monitored for inflammation-associated symptoms. Using mRNA-seq and chromatin immunoprecipitation (ChIP)-seq, we analyzed underlying molecular pathways in primary intestinal epithelial cells (IECs) isolated from these animals and confirmed these findings in IBD resection specimens using ChIP-seq.The majority (80%) of IBD patients displayed a loss of H2Bub1 levels in inflamed areas and the intestine-specific deletion of Rnf20 or Rnf40 resulted in spontaneous colorectal inflammation in mice. Consistently, deletion of Rnf20 or Rnf40 promoted IBD-associated gene expression programs, including deregulation of various IBD risk genes in these animals. Further analysis of murine IECs revealed that H3K4me3 occupancy and transcription of the Vitamin D Receptor ( Vdr ) gene and VDR target genes is RNF20/40-dependent. Finally, these effects were confirmed in a subgroup of Crohn’s disease patients which displayed epigenetic and expression changes in RNF20/40-dependent gene signatures. Our findings reveal that loss of H2B monoubiquitination promotes intestinal inflammation via decreased VDR activity thereby identifying RNF20 and RNF40 as critical regulators of IBD."],["dc.description.abstract","Abstract Despite the identification of several genetic factors linked to increased susceptibility to inflammatory bowel disease (IBD), underlying molecular mechanisms remain to be elucidated in detail. The ubiquitin ligases RNF20 and RNF40 mediate the monoubiquitination of histone H2B at lysine 120 (H2Bub1) and were shown to play context-dependent roles in the development of inflammation. Here, we aimed to examine the function of the RNF20/RNF40/H2Bub1 axis in intestinal inflammation in IBD patients and mouse models. For this purpose, intestinal sections from IBD patients were immunohistochemically stained for H2Bub1. Rnf20 or Rnf40 were conditionally deleted in the mouse intestine and mice were monitored for inflammation-associated symptoms. Using mRNA-seq and chromatin immunoprecipitation (ChIP)-seq, we analyzed underlying molecular pathways in primary intestinal epithelial cells (IECs) isolated from these animals and confirmed these findings in IBD resection specimens using ChIP-seq.The majority (80%) of IBD patients displayed a loss of H2Bub1 levels in inflamed areas and the intestine-specific deletion of Rnf20 or Rnf40 resulted in spontaneous colorectal inflammation in mice. Consistently, deletion of Rnf20 or Rnf40 promoted IBD-associated gene expression programs, including deregulation of various IBD risk genes in these animals. Further analysis of murine IECs revealed that H3K4me3 occupancy and transcription of the Vitamin D Receptor ( Vdr ) gene and VDR target genes is RNF20/40-dependent. Finally, these effects were confirmed in a subgroup of Crohn’s disease patients which displayed epigenetic and expression changes in RNF20/40-dependent gene signatures. Our findings reveal that loss of H2B monoubiquitination promotes intestinal inflammation via decreased VDR activity thereby identifying RNF20 and RNF40 as critical regulators of IBD."],["dc.identifier.doi","10.1038/s41418-021-00808-w"],["dc.identifier.pii","808"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87834"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.eissn","1476-5403"],["dc.relation.issn","1350-9047"],["dc.title","RNF20 and RNF40 regulate vitamin D receptor-dependent signaling in inflammatory bowel disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3082"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","23"],["dc.contributor.affiliation","Saul, Dominik; 1Division of Endocrinology, Mayo Clinic, Rochester, MN 55905, USA"],["dc.contributor.affiliation","Leite Barros, Luísa; 4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; barros.luisa@mayo.edu (L.L.B.); wixom.alexander@mayo.edu (A.Q.W.); gibbons.hunter@mayo.edu (H.R.G.); faubion.william@mayo.edu (W.A.F.)"],["dc.contributor.affiliation","Wixom, Alexander Q.; 4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; barros.luisa@mayo.edu (L.L.B.); wixom.alexander@mayo.edu (A.Q.W.); gibbons.hunter@mayo.edu (H.R.G.); faubion.william@mayo.edu (W.A.F.)"],["dc.contributor.affiliation","Gellhaus, Benjamin; 3Department of Trauma, Orthopedics and Reconstructive Surgery, Georg-August-University of Göttingen, 37075 Göttingen, Germany; benjamin.gellhaus@stud.uni-goettingen.de"],["dc.contributor.affiliation","Gibbons, Hunter R.; 4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; barros.luisa@mayo.edu (L.L.B.); wixom.alexander@mayo.edu (A.Q.W.); gibbons.hunter@mayo.edu (H.R.G.); faubion.william@mayo.edu (W.A.F.)"],["dc.contributor.affiliation","Faubion, William A.; 4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; barros.luisa@mayo.edu (L.L.B.); wixom.alexander@mayo.edu (A.Q.W.); gibbons.hunter@mayo.edu (H.R.G.); faubion.william@mayo.edu (W.A.F.)"],["dc.contributor.affiliation","Kosinsky, Robyn Laura; 4Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA; barros.luisa@mayo.edu (L.L.B.); wixom.alexander@mayo.edu (A.Q.W.); gibbons.hunter@mayo.edu (H.R.G.); faubion.william@mayo.edu (W.A.F.)"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Leite Barros, Luísa"],["dc.contributor.author","Wixom, Alexander Q."],["dc.contributor.author","Gellhaus, Benjamin"],["dc.contributor.author","Gibbons, Hunter R."],["dc.contributor.author","Faubion, William A."],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.date.accessioned","2022-04-01T10:02:06Z"],["dc.date.available","2022-04-01T10:02:06Z"],["dc.date.issued","2022"],["dc.date.updated","2022-09-03T13:38:32Z"],["dc.description.abstract","Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.3390/ijms23063082"],["dc.identifier.pii","ijms23063082"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105824"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","1422-0067"],["dc.rights","CC BY 4.0"],["dc.title","Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer"],["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","izz127"],["dc.bibliographiccitation.firstpage","56"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Inflammatory Bowel Diseases"],["dc.bibliographiccitation.lastpage","65"],["dc.bibliographiccitation.volume","26"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.date.accessioned","2019-07-31T10:24:19Z"],["dc.date.accessioned","2020-06-10T14:46:29Z"],["dc.date.available","2019-07-31T10:24:19Z"],["dc.date.available","2020-06-10T14:46:29Z"],["dc.date.issued","2019"],["dc.description.abstract","Recent studies implicate that 42% of inflammatory bowel disease (IBD) patients suffer from sarcopenia, the loss of muscle mass and strength, increasing the risk of falls and fall-related injuries. To determine the impact and molecular basis of IBD-associated sarcopenia, we sought to establish and characterize an experimental model for IBD-associated sarcopenia in vivo."],["dc.identifier.doi","10.1093/ibd/izz127"],["dc.identifier.pmid","31228348"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66225"],["dc.language.iso","en"],["dc.relation.eissn","1536-4844"],["dc.relation.issn","1078-0998"],["dc.title","Dextran Sodium Sulfate-induced Colitis as a Model for Sarcopenia in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","362"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Crohn's and Colitis"],["dc.bibliographiccitation.lastpage","373"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Chua, Robert Lorenz"],["dc.contributor.author","Qui, Martin"],["dc.contributor.author","Saul, Dominik"],["dc.contributor.author","Mehlich, Dawid"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Faubion, William A."],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-06-09T07:16:37Z"],["dc.date.available","2020-06-09T07:16:37Z"],["dc.date.issued","2019"],["dc.description.abstract","Background and aims: Inflammatory bowel diseases are linked to an increased risk of developing colorectal cancer [CRC]. Previous studies suggested that the H2B ubiquitin ligase RING finger protein-20 [RNF20] inhibited inflammatory signaling mediated by the nuclear factor kappa-light-chain-enhancer of activated B cells [NF-κB]. However, the role of RNF40, the obligate heterodimeric partner of RNF20, in the context of inflammation and CRC has not been addressed. Here, we examined the effect of RNF40 loss on CRC cells in vitro and on inflammation and inflammatory signaling in vitro and in vivo. Methods: We evaluated H2Bub1 levels in human and murine colorectal tumors by immunohistochemistry. Moreover, we correlated H2Bub1 and RNF40 levels in vivo and assessed the consequences of RNF40 depletion on cellular phenotype and gene expression in CRC cells in vitro. Finally, we examined the effect of a colon-specific loss of Rnf40 in a murine model of colitis, and assessed both local and systemic inflammation-associated consequences. Results: In vitro studies revealed that the tumorigenic phenotype of CRC cells decreased after RNF40 depletion and displayed gene expression changes related to chromosome segregation and DNA replication, as well as decreased induction of several NF-κB-associated cytokines. This effect was associated with decreased nuclear localization of NF-κB following tumor necrosis factor alpha treatment. Consistently, the colon-specific loss of Rnf40 exerted a protective local, as well as systemic, effect following acute colitis. Conclusions: Our findings suggest that RNF40 plays a central role in the maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity."],["dc.identifier.doi","10.1093/ecco-jcc/jjy165"],["dc.identifier.isi","WOS:000464942000013"],["dc.identifier.pmid","30321325"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/66214"],["dc.identifier.url","https://publons.com/publon/28102253/"],["dc.language.iso","en"],["dc.publisher","Oxford University Press ({OUP})"],["dc.relation.issn","1873-9946"],["dc.title","Loss of RNF40 Decreases NF-B Activity in Colorectal Cancer Cells and Reduces Colitis Burden in Mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]