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Single-cell profiling uncovers regulatory programs of pathogenic Th2 cells in allergic asthma

GSE280390 Mus musculus (mouse) Single-cell RNA-seq 24 samples Submitted 2025/01/30 Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 24 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism
Mus musculus (mouse)
Samples
24 samples: 8 conditions, mostly in triplicateGroups 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
Single-cell and chromatin accessibility profiling reveals regulatory programs of pathogenic Th2 cells in allergic asthmaNature communications · 2025
Summary (written by the submitters)
Lung pathogenic T helper type 2 (pTh2) cells are important drivers of allergic asthma, but fundamental questions remain regarding their regulation and heterogeneity. The differentiation and effector functions of immune cells are tightly regulated by epigenetic processes. Histone deacetylase 1 (HDAC1) is an important epigenetic regulator of T cells, however, its role in pTh2 cells is yet to be determined.
Read the full summary ↓
Here we investigate immune regulation in allergic asthma by single-cell RNA sequencing (scRNA-seq) in mice challenged with house dust mite, in the presence and absence of HDAC1 function. Our analyses reveal two distinct subsets of lung pTh2 cells: pathogenic effector Th2 (peTh2) and pathogenic Th2 tissue-resident memory (Th2 Trm) cells. Both pTh2 cell subsets are highly proinflammatory and exhibit distinct transcriptional and phenotypic signatures as compared with other lung Th subsets. Based on our scRNA-seq analysis, we identify conditions to generate pTh2 cells in vitro and confirm that these in vitro generated pTh2 cells have a similar transcriptional profile as lung peTh2 cells. Using our new in vitro model, we demonstrate that the p38 mitogen-activated protein kinase pathway is critical for interleukin-5 (IL-5) and IL-13 expression in pTh2 cells. Our data further underline the importance of HDAC1 in limiting the pathogenicity of lung and in vitro pTh2 cells and in the formation of lung Th2 Trm cells. In summary, we have generated novel insights into pTh2 cell biology and established a new in vitro model for investigating pTh2 cells that will be useful for discovering molecular mechanisms involved in pTh2-mediated allergic asthma.
Published in
Single-cell and chromatin accessibility profiling reveals regulatory programs of pathogenic Th2 cells in allergic asthma
Khan M, Alteneder M, Reiter W et al. · Nature communications 2025 · PMID 40089475 · doi:10.1038/s41467-025-57590-3
This dataset
Open GSE280390 in finder → Find more mouse ChIP / ATAC / CUT&Tag 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 GSE280390_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 PRJNA1178293 and SRA study SRP541435. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40089475) ↗
Study design
8 conditions, mostly in triplicate
HDAC1fl/fl Th2 cells, after 24h in culture, s… ×3 HDAC1fl/fl pTh2 cells, after 24h in culture, … ×3 HDAC1fl/fl Cd4 Cre Th2 cells, after 24h in cu… ×3 HDAC1fl/fl Cd4 Cre pTh2 cells, after 24h in c… ×3 HDAC1fl/fl Th2 cells, after 48h in culture, s… ×3 HDAC1fl/fl pTh2 cells, after 48h in culture, … ×3 HDAC1fl/fl Cd4 Cre Th2 cells, after 48h in cu… ×3 HDAC1fl/fl Cd4 Cre pTh2 cells, after 48h in c… ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 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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