Ptf1a was identified as the essential transcription factor which controls pancreatic exocrine enzyme expression. With lineage tracing eperiments Ptf1a was recognized as an important pancreatic progenitor transcription factor and Ptf1a null mice do not develop a pancreas.
RNA profiling and chromatin immunoprecipitation-sequencing reveal that PTF1a stabilizes pancreas progenitor identity via the control of MNX1/HLXB9 and a network of other transcription factors.
Specimen part
View SamplesRegulation of mRNA stability by RNA-protein interactions contributes significantly to quantitative aspects of gene expression. We have identified potential mRNA targets of the AU-rich element binding protein AUF1. Myc-tagged AUF1 p42 was induced in mouse NIH-3T3 cells and RNA-protein complexes isolated using anti-myc tag antibody beads. Bound mRNAs were analyzed with Affymetrix microarrays. We have identified 508 potential target mRNAs that were at least 3-fold enriched compared to control cells without myc-AUF1. 22.3% of the enriched mRNAs had an AU-rich cluster in the ARED Organism database, against 16.3% of non-enriched control mRNAs. The enrichment towards AU-rich elements was also visible by AREScore with an average value of 5.2 in the enriched mRNAs versus 4.2 in the control group. Yet, many mRNAs were enriched without a high ARE score suggesting that AUF1 has a broader binding spectrum than standard AUUUA repeats. AUF1 did not preferentially bind to unstable mRNAs. Still, some enriched mRNAs were highly unstable, as those of TNFSF11 (known as RANKL), KLF10, HES1, CCNT2, SMAD6, and BCL6. We have mapped some of the instability determinants. HES1 mRNA appeared to have a coding region determinant. Detailed analysis of the RANKL and BCL6 3UTR revealed for both that full instability required two elements, which are conserved in evolution. In RANKL mRNA both elements are AU-rich and separated by 30 bases, while in BCL6 mRNA one is AU-rich and 60 bases from a non AU-rich element that potentially forms a stem-loop structure.
Short-lived AUF1 p42-binding mRNAs of RANKL and BCL6 have two distinct instability elements each.
Cell line
View SamplesHuman Immunodeficiency Virus (HIV) associated nephropathy (HIVAN) is characterized clinically by both nephrosis and by rapidly progressive kidney dysfunction. HIVAN is characterized histologically by both collapsing focal segmental glomerulosclerosis and prominent tubular damage. Neutrophil Gelatinase Associated Lipocalin (NGAL) is known to be rapidly expressed in distal segments of the nephron at the onset of different types of acute kidney injury, but few studies have examined NGAL in chronic kidney disease models. We found that urinary NGAL (uNGAL) was highly expressed by patients with biopsy proven HIVAN, whereas HIV+ patients without HIVAN demonstrated lower levels. uNGAL was also highly expressed in the TgFVB mouse model of HIVAN, which demonstrated NGAL gene expression in dilated, microcystic segments of the nephron. These data show that NGAL is markedly upregulated in the setting of HIVAN, and suggest that uNGAL levels may provide a non-invasive screening test to detect HIVAN related tubular disease.
Urinary NGAL marks cystic disease in HIV-associated nephropathy.
No sample metadata fields
View SamplesThe goal was to determine how IL-12 affects gene expression by murine CTL.
IL-12 enhances CTL synapse formation and induces self-reactivity.
No sample metadata fields
View SamplesFoxp1 is expressed throughout B cell development, but the physiological functions in mature B lymphocytes are unknown. We therefore evaluated differential gene expression in Foxp1-deficient B cells, with or
Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells.
Specimen part
View SamplesHearts Lacking Caveolin-1 Develop Hypertrophy with Normal Cardiac Substrate Metabolism
Hearts lacking caveolin-1 develop hypertrophy with normal cardiac substrate metabolism.
No sample metadata fields
View SamplesLong non-coding RNAs (lncRNAs) regulate diverse biological pathways. Unlike protein coding genes, where methods to comprehensibly study their functional roles in cellular systems are available, techniques to systematically investigate lncRNAs have largely remained unexplored. Here, we report a technology for combined Knockdown and Localization Analysis of Non-coding RNAs (c-KLAN) that merges phenotypic characterization and localization approaches to study lncRNAs. Using a library of endoribonuclease prepared short interfering RNAs (esiRNAs) coupled with a pipeline for synthesizing labeled riboprobes for RNA fluorescence in situ hybridization (FISH), we demonstrate the utility of c-KLAN by identifying a novel transcript Panct1 (Pluripotency associated non-coding transcript 1) that regulates embryonic stem cell identity. We postulate that c-KLAN should be generally useful in the discovery of lncRNAs implicated in various biological processes.
Combined RNAi and localization for functionally dissecting long noncoding RNAs.
Specimen part
View SamplesThe insulin-like growth factor (IGF) axis is an important signaling pathway in the growth and survival of many cell types and has been implicated in multiple aspects of cancer progression from tumorigenesis to metastasis. The multiple roles of IGF signaling in cancer suggest that selective inhibition of the pathway might yield clinically effective therapeutics. Here we describe A-928605, a novel small molecule inhibitor of the receptor tyrosine kinase responsible for IGF signal transduction. This small molecule is able to abrogate activation of the pathway as shown by effects on the target and downstream effectors and is shown to be effective at inhibiting the proliferation of an oncogene addicted tumor model cell line (CD8-IGF1R 3T3) both in vitro and in vivo.
Reversal of oncogene transformation and suppression of tumor growth by the novel IGF1R kinase inhibitor A-928605.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Divergence of RNA localization between rat and mouse neurons reveals the potential for rapid brain evolution.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Type I and type III interferons drive redundant amplification loops to induce a transcriptional signature in influenza-infected airway epithelia.
Specimen part
View Samples