Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Effects on the transcriptome of adult mouse pancreas (principally acinar cells) by the inactivation of the Ptf1a gene in vivo

ABSTRACT: RNA-seq analysis documented mRNA changes in total pancreatic RNA preparations 14 days after Ptf1a inactivation. pancreas mRNA profiles of Tamoxifen treated adult control mice [Ptf1a(CreER/+)] and Ptf1a conditional knockout mice [Ptf1a(CreER/fl)] were generated by deep sequencing using an Illumina Hiseq 2500.

ORGANISM(S): Mus musculus

SUBMITTER: Galvin Swift

PROVIDER: E-GEOD-70542 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma.

Krah Nathan M NM De La O Jean-Paul JP Swift Galvin H GH Hoang Chinh Q CQ Willet Spencer G SG Chen Pan Fong F Cash Gabriela M GM Bronner Mary P MP Wright Christopher Ve CV MacDonald Raymond J RJ Murtaugh L Charles LC

eLife 20150707

Understanding the initiation and progression of pancreatic ductal adenocarcinoma (PDAC) may provide therapeutic strategies for this deadly disease. Recently, we and others made the surprising finding that PDAC and its preinvasive precursors, pancreatic intraepithelial neoplasia (PanIN), arise via reprogramming of mature acinar cells. We therefore hypothesized that the master regulator of acinar differentiation, PTF1A, could play a central role in suppressing PDAC initiation. In this study, we de ...[more]

PMID: 26151762

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Project description:The Ptf1a gene has essential functions during several stages of pancreas development. It is expressed in the naM-CM-/ve endoderm and required pancreas cell fate specification; it is also required later in the differentiation and maintenance of acinar cells. To identify the regulatory genetic program downstream of Ptf1a required for early pancreatic fate acquisition, we used microarrays to perform a comprehensive gene expression analysis of Ptf1a overexpressing endodermal tissue at NF32 and NF36. The results revealed an up-regulation on 1142 probe sets over 2-fold. Additional analyses, by in situ hybridizations, identified 9 genes that were endodermally expressed after the onset of endogenous Ptf1a; STXBP1, putative transmembrane protein TA-2, C25H, IGFBP1, IRF1, HALPN3, Hey1, sestrin 1, syndecan-4. These results provide insight into the regulatory network activated by Ptf1a during early pancreas development. In order to identify downstream targets of Ptf1a, two microarrays were performed at different time-points. The two microarrays compared control pancreatic tissue (GFP) and pancreatic tissue over-expressing Ptf1a (Ptf1a+GFP). The first microarray was performed at NF32, hence renamed MA32, 8 hours after the initial expression of endogenous Ptf1a. A second microarray was performed at NF36 (MA36), 8 hours after the first one. Ptf1a+gfp mRNA or gfp mRNA alone was injected into the two dorso-vegetal blastomeres of eight-cell embryos, targeting the anterior endoderm, and 40/48 hours later the anterior endoderm was dissected out. Approximated 15 endoderm explants were pooled for each RNA preparation, and both control and experimental samples were collected from the same batch of embryos; this was done in triplicate at NF32 and in quadruplicate at NF36 (Fig. 1A). For the NF32 microarray, we used the Affymetrix 3M-bM-^@M-^Y Xenopus laevis Genome 2.0 GeneChip, whereas for the NF36 microarray we used the Affymetrix 3M-bM-^@M-^Y Xenopus laevis Genome 1.0 GeneChip; the NF36 microarray was performed prior to the release of the 2.0 GeneChip.

Dataset Information

Effects on the transcriptome of adult mouse pancreas (principally acinar cells) by the inactivation of the Ptf1a gene in vivo

Publications

The acinar differentiation determinant PTF1A inhibits initiation of pancreatic ductal adenocarcinoma.

Similar Datasets

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