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IL-6/gp130 signaling in CD4+ T cells drives the pathogenesis of pulmonary hypertension

GSE255994 Mus musculus (mouse) RNA-seq (gene expression) 22 samples Submitted 2024/04/12 Platform GPL19057Platform GPL20084
At a glance

RNA-seq (gene expression) · mouse · 22 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
22 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
IL-6/gp130 signaling in CD4(+) T cells drives the pathogenesis of pulmonary hypertensionProceedings of the National Academy of Sciences of the United States of America · 2024
Summary (written by the submitters)
Pulmonary arterial hypertension (PAH) is characterized by stenosis and occlusions of small pulmonary arteries, leading to elevated pulmonary arterial pressure and right heart failure. Although accumulating evidence shows the importance of interleukin (IL)-6 in the pathogenesis of PAH, the target cells of IL-6 are poorly understood. Using mice harboring the floxed allele of gp130, a subunit of IL-6 receptor, we found substantial Cre recombination in all hematopoietic cell lineages from the primitive hematopoietic stem cell level in SM22α-Cre mice.
Read the full summary ↓
We also revealed that a CD4+ cell-specific gp130 deletion ameliorated the phenotype of hypoxia-induced pulmonary hypertension in mice. Disruption of IL-6 signaling via deletion of gp130 in CD4+ T cells inhibited phosphorylation of signal transducer and activator of transcription 3 (STAT3) and suppressed the hypoxia-induced increase in T helper 17 cells. To further examine the role of IL-6/gp130 signaling in more severe PH models, we developed Il6 knockout (KO) rats using the CRISPR/Cas9 system and showed that IL-6 deficiency could improve the pathophysiology in hypoxia-, monocrotaline-, and Sugen5416/hypoxia (SuHx)-induced rat PH models. Phosphorylation of STAT3 in CD4+ cells was also observed around the vascular lesions in the lungs of SuHx rat model, but not in Il6 KO rats. Blockade of IL-6 signaling had an additive effect on conventional PAH therapeutics, such as endothelin receptor antagonist (macitentan) and soluble guanylyl cyclase stimulator (BAY41-2272). These findings suggest that IL-6/gp130 signaling in CD4+ cells plays a critical role in the pathogenesis of PAH.
Published in
IL-6/gp130 signaling in CD4(+) T cells drives the pathogenesis of pulmonary hypertension
Ishibashi T, Inagaki T, Okazawa M et al. · Proceedings of the National Academy of Sciences of the United States of America 2024 · PMID 38602915 · doi:10.1073/pnas.2315123121
This dataset
Open GSE255994 in finder → Find more 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 GSE255994_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: 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 PRJNA1077362 and SRA study SRP490075. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38602915) ↗
Study design
8 conditions, mostly in triplicate
Total Lung Tissue WT SuHx 56d ×3 Total Lung Tissue IL6KO SuHx 56d ×3 Total Lung Tissue WT SuHx 7d ×3 Total Lung Tissue IL6KO SuHx 7d ×3 tdTomato-positive CD4-positive cell from sple… ×3 tdTomato-negative CD4-positive cell from sple… ×3 Lung CD4-positive cell WT SuHx 7d ×2 Lung CD4-positive cell IL6KO SuHx 7d ×2

Supports a between-group comparison across 22 samples.

How we read this: 8 replicated groups read from 22 sample titles; they account for 22 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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