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Loss of Tbx4 Affects Postnatal Lung Development and Predisposes to Pulmonary Hypertension

GSE289897 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/04/11 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 12 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Mus musculus (mouse)
Samples
12 samples: 3 × mouse lung, Control, P36, vs 3 × mouse lung, CKO, P36, vs 3 × mouse lung, Control, P14, vs 3 × mouse lung, CKO, P14,Groups 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
Loss of Tbx4 Affects Postnatal Lung Development and Predisposes to Pulmonary HypertensionAmerican journal of respiratory cell and molecular biology · 2025
Summary (written by the submitters)
Pulmonary arterial hypertension (PAH) is a progressive vascular disease characterized by remodeling of the precapillary pulmonary arteries. Genomic variation within the T-box 4 (TBX4) transcription factor is the second most common genetic cause of PAH, and can also cause severe lung developmental disorders with neonatal PH. Currently, the effect of TBX4 loss-of-function on later stages of lung development and predisposition to lung disease, including PH, is not well understood.
Read the full summary ↓
Therefore, we have generated Tbx4 conditional knockout (Tbx4-CKO) mice in which Cre recombinase deletes exon 5 of Tbx4 within the embryonic lung mesenchyme to create a null allele. We harvested lungs from these mice at various timepoints to examine alveologenesis, vascularization, vascular remodeling, lung cellular composition, and disruption of transcriptional activity compared with control lungs. Right ventricular systolic pressure (RVSP) was measured in six-month-old mice to evaluate for PH. Tbx4-CKO lungs show enlargement of airspaces, as confirmed by an increase in mean linear intercept at P14 (24.9%), P36 (31.5%), and P180 (49.6%). These lungs also show a 39.3% decrease in von Willebrand Factor-positive vessels and a 14.2% increase in vessel wall thickness. Consistent with these results, Tbx4-CKO mice show a statistically significant increase of 15.7% in RVSP and 16.3% in the Fulton index. Bulk-RNA sequencing analysis revealed enrichment of pathways and genes relevant to lung alveologenesis, angiogenesis, and PH. Our results show that disruption of Tbx4 expression during early lung development is sufficient to disrupt postnatal lung development and circulation.
Published in
Loss of Tbx4 Affects Postnatal Lung Development and Predisposes to Pulmonary Hypertension
Maldonado-Velez G, Mickler EA, Cook TG et al. · American journal of respiratory cell and molecular biology 2025 · PMID 40106779 · doi:10.1165/rcmb.2024-0459OC
This dataset
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.

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 GSE289897_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1225272 and SRA study SRP564707. Searching any of these in the dataset finder brings you back here.

Study design
3 × mouse lung, Control, P36, vs 3 × mouse lung, CKO, P36, vs 3 × mouse lung, Control, P14, vs 3 × mouse lung, CKO, P14,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 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
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