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Series GSE253168 Query DataSets for GSE253168
Status Public on Jan 16, 2024
Title Onocgenic cell marking and single-cell transcriptomics reveal cell type and time-resolved actions of von Hippel Lindau inactivation in the kidney
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Defining the first events in oncogenesis and the cellular responses they entrain, even in advance of morphological abnormality, is a fundamental challenge in understanding cancer initiation. As a paradigm to address this we studied the tumor suppressor von Hippel Lindau (VHL), whose loss ultimately drives clear cell renal cancer. Vhl inactivation was directly coupled to activation of a tdTomato reporter within a single allele, allowing accurate visualization of affected cells in their native context and retrieval from the kidney for single-cell RNA sequencing. This strategy uncovered cell-type specific responses to Vhl inactivation, defined a novel proximal tubular class with oncogenic potential, and revealed longer term adaptive changes in the renal epithelium and the interstitium. Oncogenic cell marking also revealed markedly heterogeneous cellular effects including time-limited proliferation and elimination of specific cell types. Striking heterogeneity in these responses suggests that very early events define the tissue specificity of VHL tumor suppressor action.
 
Overall design Vhl(wt/flox) (Control) and Vhl(KO/flox) (KO) mice carrying the renal tubular epithelium specific Pax8-CreERT2 were dosed with 5x 2 mg tamoxifen and harvested either at an early (1-3 weeks) or late (4-12 months) timepoints after dosing. Cre-mediated recombination marked Vhl recombination with the expression of tdTomato. tdTomato-positve and tdTomato-negative cells were retrieved by FACS and subjected to scRNA-seq using the 10X Chromium NextGEM platform.
 
Contributor(s) Kurlekar S, Li R
Citation(s) 38502859
Submission date Jan 12, 2024
Last update date Jun 21, 2024
Contact name David Robert Mole
E-mail(s) david.mole@ndm.ox.ac.uk
Phone 0044 (0)1865 613956
Organization name University of Oxford
Department Nuffield Department of Medicine
Lab NDM Research Building
Street address Roosevelt Drive, Headington
City Oxford
ZIP/Postal code OX3 7FZ
Country United Kingdom
 
Platforms (2)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (31)
GSM8015436 Sorted renal cells, Control, Early, Female, tdTomato Negative, Rep 1
GSM8015437 Sorted renal cells, Control, Early, Female, tdTomato Negative, Rep 2
GSM8015438 Sorted renal cells, Control, Early, Female, tdTomato Negative, Rep 3
Relations
BioProject PRJNA1064144

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SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE253168_Vhl_Pax8_all_samples_seurat.rds.gz 10.9 Gb (ftp)(http) RDS
GSE253168_Vhl_Pax8_tdT_positive_samples_seurat.rds.gz 6.0 Gb (ftp)(http) RDS
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Raw data are available in SRA

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