GEO series

Sustained NF-kB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiation [Expt2]

GSE247504 Mus musculus (mouse) Single-cell RNA-seq 10 samples Submitted 2025/02/19 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 10 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 10 samples: 5 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: Sustained NF-κB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiationCell stem cell · 2025

Summary (written by the submitters)

Tissue homeostasis relies on meticulously coordinated fate determination by resident stem cells through a tissue-wide feedback loop. Dysregulation of this process is closely associated with tumorigenesis, yet the mechanisms distinguishing these phenomena remain in question. Here, we integrate comparative analyses of in vivo large-scale quantitative clonal dynamics and single-cell transcriptomics to unveil a key evolutionary trajectory within a single alveolar type II (AT2) stem cell, driving tissue-wide neoplastic transformation in the lung.

Read the full summary ↓

Tracking thousands of AT2 clones throughout murine adulthood uncovers two independent homeostatic AT2 subpopulation scharacterised by unique cellular kinetics. Notably, a small AT2 subset undergoes substantial clonal expansion upon KrasG12D activation. The mutant AT2 cells follow a differentiation trajectory via emergent regenerative cell states, yet exhibit remarkable cell state equivalency with stochastic fate transitions, driving abnormal expansion with halted differentiation into mature AT1 cells. The genetic deletion of Il1r1 signalling impedes oncogenic expansion by disrupting this reprogramming trajectory, underscoring its significance in tumour initiation. Significantly, our analysis of oncogene-associated multi-colour reporter mouse models reveals a tissue- wide systemic injury response elicited by oncogenic clones in neighbouring wildtype AT2 cells, modulating their fitness programme. Moreover, we identify sustained NF-kB activation in reprogrammed cell states, setting neoplastic transformation apart from normal regeneration by preventing oncogenic exit into the differentiated AT1 state. Collectively, this work delineates the common mechanisms governing lineage infidelity across diverse tissues and proposes a compelling target amenable to therapeutic manipulation.

Published in

Sustained NF-κB activation allows mutant alveolar stem cells to co-opt a regeneration program for tumor initiation

England FJ, Bordeu I, Ng ME et al. · Cell stem cell 2025 · PMID 39978341 · doi:10.1016/j.stem.2025.01.011

This dataset

Open GSE247504 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 GSE247504_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1039247 and SRA study SRP477551. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39978341) ↗

Study design

5 conditions, mostly in duplicate

Expt2_Confetti RFP ×2 Expt2_2w het RFP ×2 Expt2_2w hom RFP ×2 Expt2_12w het RFP ×2 Expt2_12w hom RFP ×2

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 10 sample titles; they account for 10 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

GSM7890839 Expt2_Confetti RFP r1 Expt2_Confetti RFP
GSM7890840 Expt2_Confetti RFP r2 Expt2_Confetti RFP
GSM7890841 Expt2_2w het RFP r1 Expt2_2w het RFP
GSM7890842 Expt2_2w het RFP r2 Expt2_2w het RFP
GSM7890843 Expt2_2w hom RFP r1 Expt2_2w hom RFP
GSM7890844 Expt2_2w hom RFP r2 Expt2_2w hom RFP
GSM7890845 Expt2_12w het RFP r1 Expt2_12w het RFP
GSM7890846 Expt2_12w het RFP r2 Expt2_12w het RFP
GSM7890847 Expt2_12w hom RFP r1 Expt2_12w hom RFP
GSM7890848 Expt2_12w hom RFP r2 Expt2_12w hom RFP

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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.