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Genetic background and transient prenatal disruption of vitamin A signaling determine susceptibility to airway hyperresponsiveness in mice [RNA-Seq]

GSE307576 Mus musculus (mouse) Single-nucleus RNA-seq 16 samples Submitted 2026/01/28 Platform GPL34290
At a glance

Single-nucleus RNA-seq · mouse · 16 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
16 samples: 4 × e14.5 lung B6 control vs 4 × e14.5 lung B6 BMS vs 4 × e14.5 lung AJ control vs 3 × e14.5 lung AJ BMSGroups 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
Genetic background and transient prenatal disruption of vitamin A signaling determine susceptibility to airway hyperresponsiveness in micebioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Airway structural changes and hyperresponsiveness (AHR), hallmarks of asthma, are crucially influenced by genetic variations and adverse exposures. While intrauterine environmental perturbations leading to dysfunctional lung development have been linked to adult pulmonary disease, still little is known about the developmental events leading to these postnatal abnormalities.
Read the full summary ↓
Here, we provide evidence of genetic background playing a key role in this process. Using A/J and C57BL/6J mice known for their distinct susceptibility to AHR, we show that A/J but not C57BL/6J develop an aberrant airway smooth muscle (SM) program and AHR in adulthood when exposed transiently to a vitamin A/retinoic acid (RA)-disrupted intrauterine environment in vivo by a maternal BMS493 administration. Single nuclei multiomics analysis identified a subpopulation of mesenchymal cells that overactivated TGFβ targets in response to BMS selectively in A/J, but not C57BL/6J, embryonic lungs. These cells, localized to sites of airway SM initiation, exhibited robust BMS-mediated upregulation of SMAD2/3 targets, including regulators of SM program Pdgfra and Tnc, and showed stable cell proportions despite the marked transcriptional rewiring following RA disruption. These findings identify TGFβ-activating mesenchymal cells as a critical niche responsive to RA signaling and reveal how genetic background determines developmental susceptibility to micronutrient perturbations with long-term impact on airway function.
Published in
Genetic background and transient prenatal disruption of vitamin A signaling determine susceptibility to airway hyperresponsiveness in mice
Otoshi T, Kameshwar AKS, Kotton BD et al. · bioRxiv : the preprint server for biology 2025 · PMID 41279414 · doi:10.1101/2025.10.31.685835
This dataset
Open GSE307576 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 GSE307576_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 PRJNA1322313 and SRA study SRP618726. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41279414) ↗
Study design
4 × e14.5 lung B6 control vs 4 × e14.5 lung B6 BMS vs 4 × e14.5 lung AJ control vs 3 × e14.5 lung AJ BMS

Supports a between-group comparison across 15 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 15 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
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