GEO series

HIFa isoform specific activation drives cell-type specificity of VHL-associated oncogenesis

GSE282887 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/08/15 Platform GPL30172

At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 12 samples: 6 conditions, mostly in duplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: HIFα isoform specific activities drive cell-type specificity of VHL-associated oncogenesisNature communications · 2025

Summary (written by the submitters)

Cancers arising from dysregulation of generally operative signaling pathways are commonly tissue specific, but the mechanisms underlying this paradox are poorly understood. Based on striking cell-type specificity, we postulated that these mechanisms must operate very early in cancer development and set out to study them in a model of von Hippel Lindau disease.

Read the full summary ↓

Biallelic mutation of the VHL ubiquitin ligase leads to constitutive activation of hypoxia inducible factors HIF1A and HIF2A and is often a truncal event in clear cell renal carcinoma. We used an oncogenic tagging strategy in which VHL-mutant cells are marked by tdTomato, enabling their observation, retrieval, and analysis early after VHL-inactivation. Our findings reveal markedly different consequences of HIF1A and HIF2A activation, but that both contribute to renal cell-type specific consequences of VHL-inactivation in the kidney. Early involvement of HIF2A in promoting proliferation within proximal tubular epithelium supports therapeutic targeting of HIF2A early in VHL disease.

Published in

HIFα isoform specific activities drive cell-type specificity of VHL-associated oncogenesis

Lima JDCC, Hooker M, Li R et al. · Nature communications 2025 · PMID 41102155 · doi:10.1038/s41467-025-64214-3

This dataset

Open GSE282887 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE282887_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1190947 and SRA study SRP547729. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41102155) ↗

Study design

6 conditions, mostly in duplicate

VHKO Male ×2 VHEKO Male ×2 VHKO Female ×2 VEKO Male ×2 VEKO Female ×2 VHEKO Female ×2

Supports a between-group comparison across 12 samples.

How we read this: 6 replicated groups read from 12 sample titles; they account for 12 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM8652187 VHKO Male 1 VHKO Male
GSM8652188 VHKO Male 2 VHKO Male
GSM8652189 VHEKO Male 1 VHEKO Male
GSM8652190 VHKO Female 1 VHKO Female
GSM8652191 VEKO Male 1 VEKO Male
GSM8652192 VEKO Male 2 VEKO Male
GSM8652193 VEKO Female 1 VEKO Female
GSM8652194 VEKO Female 2 VEKO Female
GSM8652195 VHEKO Male 2 VHEKO Male
GSM8652196 VHEKO Female 1 VHEKO Female
GSM8652197 VHKO Female 2 VHKO Female
GSM8652198 VHEKO Female 2 VHEKO Female

Datasets on a similar topic

GSE324375 Robust T cell activation kills tumors regardless of T cell specificity 39 samples shares specificity, activation, specific
GSE243942 Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing [RNA-seq] 125 samples shares activation, specific
GSE240689 Circadian-affected tissue specificity is linked to aging and longevity [sleep deprivation experiment] 96 samples shares specificity, specific
GSE236129 Activation of RAS/MEK/ERK signaling drives biliary differentiation in primary liver cancer [112UE] 80 samples shares activation, drives
GSE300925 Lyn expression in macrophages promotes TLR activation and restricts proliferation in an isoform-independent manner 48 samples shares activation, isoform
GSE279351 Liver-specific inactivation of Cideb improves metabolic profiles and ameliorates steatohepatitis and fibrosis in animal models for MASH 45 samples shares activation, specific
GSE327565 Sustained Yap/Taz activation promotes aberrant alveolar epithelial cell differentiation and drives persistent fibrotic remodeling 14 samples shares activation, drives
GSE243943 Spatio-temporal X-linked gene reactivation in the mouse germline reveals site-specific retention of epigenetic silencing 127 samples shares activation, specific

Search all mouse RNA-seq datasets in GEO →

Share this dataset

Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.