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Series GSE77410 Query DataSets for GSE77410
Status Public on Dec 11, 2017
Title c-Myc down-regulation is required for pre-acinar to acinar maturation in the pancreas (RNA-Seq)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Multipotent pancreatic progenitors (MPC) are defined as Ptf1a+, Mychigh, Cpa+ cells. During the transition from MPC to unipotent acinar progenitors, c-Myc is down-regulated whereas Ptf1a is up-regulated, leading to the deployment of the acinar program. Here, we show that c-Myc and Ptf1a interact directly and c-Myc binds to, and represses, the transcriptional activity of the PTF1 complex in vitro and in vivo. Using Ela1-Myc mice, in which c-Myc is overexpressed in acinar cells starting at E14.5, we find that acinar cells fail to undergo normal maturation at P1 and this is followed by a massive subsequent repression of the acinar programme. Lineage tracing with Ptf1aCreERT2;Rosa26YFP and Ela1-Myc;Ptf1aCreERT2;Rosa26YFP mice receiving TMX at E15.5 and analyzed at E18.5 revealed that c-Myc overexpression is associated with activation of a hepatic programme but not with pancreatic lineage misspecification At 8 weeks, the silencing of the acinar program is associated with increased expression of the PRC2 complex in a c-Myc dependent manner. Genome wide studies show that Ptf1a and c-Myc display partially overlapping chromatin occupancy patterns and DNA binding competition. We conclude that c-Myc down-regulation during development is crucial for the maturation of pre-acinar to acinar cells. c-Myc overexpression may contribute to pancreatic carcinogenesis by restraining cell differentiation and rendering cells susceptible to transformation.
 
Overall design Pancreas mRNA profiles of 8-week old wild type (WT) and ELA1-MYC mice were generated by deep sequencing, in triplicate, using Illumina GAIIx.
 
Contributor(s) Sánchez-Arévalo Lobo VJ, Carrillo de Santa Pau E, Real FX
Citation(s)
  • Sánchez-Arévalo Lobo VJ, Fernández LC, Carrillo-de-Santa-Pau E, Richart L et al. c-Myc downregulation is required for preacinar to acinar maturation and pancreatic homeostasis. Gut 2018 Apr;67(4):707-718. PMID: 28159836
Submission date Jan 29, 2016
Last update date May 15, 2019
Contact name Enrique Carrillo de Santa Pau
E-mail(s) enrique.carrillo@imdea.org
Organization name Spanish National Cancer Research Centre (CNIO)
Department Cancer Cell Biology Programme
Lab Epithelial Carcinogenesis group
Street address C/ Melchor Fernández Almagro, 3
City Madrid
ZIP/Postal code 28029
Country Spain
 
Platforms (1)
GPL11002 Illumina Genome Analyzer IIx (Mus musculus)
Samples (6)
GSM2051456 ASF00611_WT
GSM2051457 ASF00615_WT
GSM2051458 ASF00616_WT
This SubSeries is part of SuperSeries:
GSE77411 c-Myc down-regulation is required for pre-acinar to acinar maturation in the pancreas
Relations
BioProject PRJNA310236
SRA SRP069082

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE77410_RAW.tar 19.9 Mb (http)(custom) TAR (of TXT, WIG)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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