|
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)
|
|
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 |