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Series GSE30802 Query DataSets for GSE30802
Status Public on Jul 11, 2012
Title Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming
Organism Homo sapiens
Experiment type Expression profiling by array
Summary 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.
 
Overall design 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
 
Contributor(s) Martens GA, Heimberg H
Citation(s) 22606327
Submission date Jul 19, 2011
Last update date Aug 10, 2018
Contact name Geert A. Martens
E-mail(s) geert.martens@vub.ac.be
Organization name Vrije Universiteit Brussel
Department Diabetes Research Center
Street address Laarbeeklaan 103
City Brussels
ZIP/Postal code 1090
Country Belgium
 
Platforms (2)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
GPL97 [HG-U133B] Affymetrix Human Genome U133B Array
Samples (26)
GSM764141 human duct cell, 3 days after transduction with AdGFP control vector, biological rep1 [HG133A]
GSM764142 human duct cell, 3 days after transduction with AdGFP control vector, biological rep2 [HG133A]
GSM764143 human duct cell, 3 days after transduction with AdGFP control vector, biological rep3 [HG133A]
Relations
BioProject PRJNA144451

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Supplementary file Size Download File type/resource
GSE30802_RAW.tar 86.0 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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