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HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [ChIP-seq]

ABSTRACT: HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [ChIP-seq]

PROVIDER: PRJNA422594 | ENA |

REPOSITORIES: ENA

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HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [ChIP-seq]

Project description:The biological properties of pancreatic cancer stem cells (PCSCs) remain incompletely defined and the central regulators are unknown. By bioinformatic analysis of a PCSC-enriched gene signature, we identified the transcription factor HNF1A as a putative central regulator of PCSC function. Levels of HNF1A and its target genes were found to be elevated in PCSCs and tumorspheres, and depletion of HNF1A resulted in growth inhibition, apoptosis, impaired tumorsphere formation, PCSC depletion, and downregulation of OCT4 expression. Conversely, HNF1A overexpression increased PCSC numbers and tumorsphere formation in pancreatic cancer cells and drove PDA cell growth. Importantly, depletion of HNF1A in primary tumor xenografts impaired tumor growth and depleted PCSCs in vivo. Finally, we established an HNF1A-dependent gene signature in PDA cells that significantly correlated with reduced survivability in patients. These findings identify HNF1A as a central transcriptional regulator of the PCSC state and novel oncogene in pancreatic ductal adenocarcinoma.

2018-09-04 | GSE108150 | GEO

HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [Bru-seq]

2018-09-04 | GSE108149 | GEO

HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells

Project description:HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells

| PRJNA422591 | ENA

HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [Bru-seq]

Project description:HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells [Bru-seq]

| PRJNA422593 | ENA

HNF1A is a Novel Oncogene and Central Regulator of Pancreatic Cancer Stem Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-09-04 | GSE108151 | GEO

HNF1A is a novel oncogene that regulates human pancreatic cancer stem cell properties.

Project description: Not available

| S-EPMC6122955 | biostudies-literature

Human Pancreatic Islets Expressing HNF1A Variant Have Defective β cell Transcriptional Regulatory Networks

Project description:Using an integrated approach to characterize the pancreatic tissue and isolated islets from a 33-year-old with 17 years of type 1 diabetes (T1D), we found donor islets contained β cells without insulitis and lacked glucose-stimulated insulin secretion despite a normal insulin response to cAMP-evoked stimulation. With these unexpected findings for T1D, we sequenced the donor DNA and found a pathogenic heterozygous variant in hepatocyte nuclear factor 1 alpha (HNF1A). In one of the first studies of human pancreatic islets with a disease-causing HNF1A variant associated with the most common form of monogenic diabetes, we found that HNF1A dysfunction leads to insulin-insufficient diabetes reminiscent of T1D by impacting the regulatory processes critical for glucose-stimulated insulin secretion and suggest a rationale for a therapeutic alternative to current treatment.

2018-09-22 | GSE120299 | GEO

HNF1A, UTX, H3K27me3 and H3K27ac ChIP-seq in wild-type and UTX- or HNF1A-deficient mouse pancreas

Project description:HNF1A and UTX are putative tumor suppressors in pancreatic cancer. In this study, we have combined mouse genetics, transcriptomics and genome binding studies to link HNF1A and UTX in a molecular mechanism that suppresses pancreatic cancer. In this session, we have profiled UTX, HNF1A, H3K27me3 and H3K27ac in normal and UTX- or HNF1A-deficient mouse pancreas by ChIP-seq experiments. We show that HNF1A recruits UTX to its genomic targets in pancreatic acinar cells, which results in remodeling of the chromatin landscape and activation of a broad transcriptional program of differentiated acinar cells, which in turn indirectly suppresses tumor suppressor pathways.

2019-12-20 | E-MTAB-7944 | biostudies-arrayexpress

An HNF1A truncation associated with maturity-onset diabetes of the young impairs pancreatic progenitor differentiation by antagonising HNF1B function

Project description:Purpose: The goal of this study is to conduct and compare NGS-derived transcriptome profiling (RNA-seq) of progenitor lines derived from 3 HNF1A-WT and 3 HNF1A-CRISPR (with p291fsinsC mutation) human induced pluripotent stem cell lines. Methods: mRNA profiles of WT/CRISPR pancreatic progenitor cells obtained after in-vitro differentiation for 14 days were generated by deep sequencing using Illumina HiSeq 2000 sequencer. The raw RNA-sequencing read files were processed using the research computing facility at King’s College London, Rosalind (https://rosalind.kcl.ac.uk). RNA-sequencing reads were trimmed from adapters using Trimmomatic/0.39 (Bolger et al., 2014) and quality control was done using FASTQC/0.11.8 (Andrews, 2010). Reads were mapped to a concatenated genome sequence of human GRCh38/hg38 using STAR/2.4.2 (Dobin and Gingeras, 2015). Transcript abundance was measured using featureCount in Subread package (Liao et al., 2013). Results: The DESeq2 package (Love et al., 2014) was used to identify differentially expressed genes. We found 919 significantly regulated genes (271 upregulated, 648 downregulated), with 16 HNF1B targets and 19 HNF1A specific targets within the significantly dysregulated genes when comparing HNF1A-CRISPR versus HNF1A-WT groups. Conclusions: HNF1A and HNF1B gene targets are disturbed by the p291fsinsC mutation engineered in the CRISPR-Cas9 lines.

2022-01-25 | GSE166822 | GEO

Transcription profiling of pancreatic islets from Hnf1a-deficient and wild type mice

Project description:Pancreatic islets were isolated from Hnf1a (Hepatocyte nuclear factor 1 alpha) knockout and wild-type mice and cultured ex vivo for two days in RPMI medium with 10% FBS before RNA extraction. The transcription profiles were obtained using Affymetrix GeneChip Mouse Genome 430A 2.0 arrays [Mouse430A_2].

2009-03-21 | E-MEXP-1707 | biostudies-arrayexpress

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