Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA144453 | ENA |
REPOSITORIES: ENA
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Project description:Aims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. Methods: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. Results: Ngn3 stimulates duct cells to express a focused set of genes that are abundant in islet endocrine cells and/or neural tissues. This neuro-endocrine shift, however, covers a minor fraction (5%) of the estimated genome-wide transcriptome difference between duct and islet endocrine cells. Interestingly, transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. Conclusions/interpretation: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes. We used Affymetrix HG133A and HG133B to get a comprehensive view on the reprogramming potential in vitro of human pancreatic duct cell cultures (n=3-4) at 3 and 14/20 days after ectopic adenoviral expression of murine neurogenin 3 as compared to GFP-expressing control vectors.
2012-07-11 | GSE30802 | GEO
Project description:Aims/hypothesis: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3). In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. Methods: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. Results: Ngn3 stimulates duct cells to express a focused set of genes that are abundant in islet endocrine cells and/or neural tissues. This neuro-endocrine shift, however, covers a minor fraction (5%) of the estimated genome-wide transcriptome difference between duct and islet endocrine cells. Interestingly, transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. Conclusions/interpretation: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes. We used Affymetrix HG133A and HG133B to get a comprehensive view on the reprogramming potential in vitro of human pancreatic duct cell cultures (n=3-4) at 3 and 14/20 days after ectopic adenoviral expression of murine neurogenin 3 as compared to GFP-expressing control vectors. The microarray analysis was performed on 3 independent samples that each contained RNA extracted from a pool of 3 independent donor pancreata. The total number of non-selected donor organs is 9. Transcripts were considered as differentially regulated by Ngn3 when 1.5 fold (LCB, unpaired P < 0.05) up- or down-regulated in AdGFP-Ngn3 versus AdGFP controls, at 3 and/or 14 dpi. Transcripts that showed differential expression between day 3 and day 14 in AdGFP-Ngn3 duct cells but not in AdGFP control cells, were also considered Ngn3-regulated
2012-07-10 | E-GEOD-30802 | biostudies-arrayexpress
Project description:Aims: establishment of reference samples to investigate gene expression selective for endocrine or ductal-exocrine cells within the adult human pancreas. To this end, human islet endocrine cells, FACS-enriched in insulin+ cells, (n=3) and human exocrine ductal cells (n=2) are compared on Affymetrix HG133A platform with duplicate hybridizations of a panel of other primary human tissues. The microarray analysis was performed on 3 pools of human beta cell-enriched cell fractions, isolated from 10 non-selected donor organs, and 2 pools of duct cell-enriched fractions obtained from 6 non-selected donor pancreases. The cells were suspension-cultured for 2-3 weeks along standard procedures and with no specific treatment prior to FACS-sorting and RNA extraction. The average composition of human beta cell-preparations was 55 ± 13% insulin+ cells, 13±8% glucagon+ cells and 21 ±7% non-granulated cells. Pancreatic duct cells-enriched preparations contained 85 ±7% cytokeratin 19+ cells with 4 ± 1% insulin+ cells and 6 ±4% glucagon+ cells and were isolated as described by Heimberg H. et al.( Diabetes 2001,49: 571-579 ). Pancreatic cell mRNA profiles were compared to those of a panel of other human primary tissues (n=2 biological replicates). This dataset is part of the TransQST collection.
2011-07-21 | E-GEOD-30803 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to facilitate identification of novel tumor suppressor genes using an integrative genomics approach Genome wide DNA methylation profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to identify novel tumor suppressor genes Bisulphite converted DNA from the 21 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip
2012-11-01 | E-GEOD-40097 | biostudies-arrayexpress
Project description:RNA-Sequencing was performed on mechanically dissociated, epithelial-enriched samples, of human extrahepatic biliary tissue from Gallbladder, Common Bile Duct, and Pancreatic Duct tissues. Sequencing was also performed on in vitro cultures of Organoid cell lines at passage 5 that were derived from human Gallbladder, Common Bile Duct, Pancreatic Duct, or Intrahepatic Bile Ducts.
2019-01-20 | E-MTAB-7569 | biostudies-arrayexpress
Project description:The remarkable differentiation capacity of pluripotent stem cells into any adult cell types have enabled researchers to model human embryonic development and disease process in dishes, as well as deriving specialized cells for replacing damaged tissues. Type 1 diabetes is a degenerative disease characterized by autoimmune destruction of the insulin-producing beta islet cells in the pancreas. Recent advances have led to the establishment of different methods to direct differentiation of human or mouse pluripotent stem cells toward beta cell lineages. However, existing strategies have not yet succeeded in generating fully functional beta cells in vitro. Thus, it remains a major challenge to identify novel regulators of beta cell differentiation and maturation, and the islet-specific genetic and epigenetic regulatory networks are logical targets. To obtain a comprehensive view of the mRNA expression pattern during in vitro directed differentiation of hPSC into pancreatic beta islet cells, we collected 16 samples of 6 stages of differentiated derivatives, 2 samples of human fetal pancreas and 5 samples of purified human beta islet cells for analysis. With these samples, we performed genome-wide mRNA expression profiling using the Illumina Infinium HT-12 v4 Gene Expression BeadArray.
2012-11-07 | E-GEOD-42094 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to facilitate identification of novel tumor suppressor genes using an integrative genomics approach Genome wide DNA methylation profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to identify novel tumor suppressor genes
2012-11-01 | GSE40097 | GEO
Project description:Creating in vitro models of diseases of the pancreatic ductal compartment requires a comprehensive understanding of the developmental trajectories of pancreas-specific cell types. Here, we report the single-cell characterization of the differentiation of pancreatic duct-like organoids (PDLOs) from human induced pluripotent stem cells (hiPSCs) on a microwell chip that facili-tates the uniform aggregation and chemical induction of hiPSC-derived pancreatic progenitors. Using time-resolved single-cell transcriptional profiling and immunofluorescence imaging of the forming PDLOs, we identified differentiation routes from pan-creas progenitors through ductal intermediates to two types of mature duct-like cell and a few non-ductal cell types. PDLO subpopulations expressed either mucins or the cystic fibrosis transmembrane conductance regulator, and resembled human adult duct cells. We also used the chip to uncover ductal markers relevant to pancreatic carcinogenesis, and to establish PDLO co-cultures with stellate cells, which allowed for the study of epithelial–mesenchymal signalling. The PDLO microsystem could be used to establish patient-specific pancreatic duct models.
2021-07-08 | GSE162547 | GEO
Project description:Genome wide expression profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to facilitate identification of novel tumor suppressor genes using an integrative genomics approach Genome wide expression profiling of 20 PDAC cell lines and an immortalized non-malignant pancreatic duct cell line (HPDE) to facilitate identification of novel tumor suppressor genes using an integrative genomics approach
2012-11-01 | GSE40098 | GEO
Project description:The adult pancreas is capable of limited regeneration after injury, but has no defined stem cell population. The cell types and molecular signals that govern the production of new pancreatic tissue are not well understood. Here we show that inactivation of the SCF-type E3 ubiquitin ligase substrate recognition component Fbw7 induces pancreatic ductal cells to reprogram into β-cells. The induced β-cells resemble islet β-cells in morphology and histology, express genes essential for β-cell function, and release insulin upon glucose challenge. Thus, loss of Fbw7 appears to reawaken an endocrine developmental differentiation program in adult pancreatic ductal cells. Our study highlights the plasticity of seemingly differentiated adult cells, identifies Fbw7 as a master regulator of cell fate decisions in the pancreas, and reveals adult pancreatic duct cells as a latent multipotent cell type. We used microarray to compare adult mouse fbw7 knock out ductal cells with bonafide beta cells
2014-08-07 | GSE58969 | GEO