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Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinom

GSE267731 Mus musculus (mouse) Single-nucleus RNA-seq 14 samples Submitted 2025/12/31 Platform GPL24247
At a glance

Single-nucleus RNA-seq · mouse · 14 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). 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
14 samples: 10 × K:TG vs 2 × TGGroups 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.
Summary (written by the submitters)
Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with extensive biological heterogeneity, such as varying cells of origin from alveolar epithelial cells (AECs) in the distal lung. The predominant types of AECs include surfactant-producing alveolar epithelial type II (AT2) cells and large, delicate alveolar epithelial type I (AT1) cells, which are responsible for facilitating gas exchange.
Read the full summary ↓
Although AT1 cells have been thought to be terminally differentiated and consequently unable to proliferate, we, and others, have previously reported that Gramd2+ AT1 cells can give rise to a histologically-defined LUAD1,2 on transgenic mouse model. Immunotherapy has shown a major impact on treatment of solid tumors over the past 10 years, particularly on LUAD, where it significantly improves patients’ survival rates3. However, because of the largely unknown immunosuppressive states of LUAD, there is considerable variability in patient response to therapy across LUAD patients, making immunotherapeutic treatment challenging. To determine whether cells of origin for LUAD reprogram differently tumor immune microenvironment (TIME) landscape, we employed single nucleus RNA sequencing (snRNA-Seq) on mouse KRASG12D-overexpressing Gramd2+ AT1 cell and Sftpc+ AT2 cell-derived LUADs to comprehensively characterize transcriptomic, molecular, and cellular aberrations within the TIME. We demonstrate that myeloid cells within the AT1-LUAD TIME manifest a disordered cell composition and disrupted transcriptome: increased cell number of inflammatory monocytes and macrophages but decreased cell number of myeloid-derived suppressor cells (MDSCs) were observed in AT1-LUAD TIME compared with its AT2 counterpart. In addition, a series of bioinformatic analyses, gene set enrichment analysis (GSEA), ingenuity pathway analysis (IPA) and cell-cell communication (CCC) analysis, along with immunostaining confirmed LUAD TIME derived from different cells of origin exhibits altered suppressive gene expression patterns and disparate pro-inflammatory signaling activities. Taken together, AT1-LUAD presents a proinflammatory, immunoreactive TIME, while the TIME of AT2-LUAD is relatively immunosuppressive. This study suggests that LUAD cell of origin is associated with transcriptomic aberrations and immune landscape changes that may inform ongoing translational work to improve patient responses.
This dataset
Open GSE267731 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 GSE267731_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 PRJNA1112733 and SRA study SRP508330. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
10 × K:TG vs 2 × TG

Supports a between-group comparison across 12 samples.

How we read this: 2 replicated groups read from 14 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
Datasets on a similar topic

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