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GATA2 deficiency drives a profibrotic program and metabolic dysfunction in alveolar macrophages

GSE298755 Mus musculus (mouse) RNA-seq (gene expression) 14 samples Submitted 2025/06/30 Platform GPL30172
At a glance

RNA-seq (gene expression) · mouse · 14 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
14 samples: 5 × AM, GATA2 fl/fl, PBS, 0 hour, vs 4 × AM, GATA2 -/-, IL33, 24 hour, vs 3 × AM, GATA2 -/-, PBS, 0 hour, vs 2 × AM, GATA2 fl/fl, IL33, 24 hour,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.
Summary (written by the submitters)
Alveolar macrophages (AMs) have homeostatic, anti-inflammatory programming to limit tissue damage in response to minor challenge and the distinct, lung-specific function of catabolizing lipid-rich pulmonary surfactant to support gas exchange. GATA transcription factors (TFs) have been well established to cooperate with and antagonize other TFs to shape immune cell fates and GATA2 is expressed in a lung-specific manner in macrophages.
Read the full summary ↓
Both mutations and lung macrophage downregulation of GATA2 have been associated with chronic pulmonary pathologies in humans, but the role of GATA2 in shaping AM function is not well defined. Using mice with myeloid-specific deletion of the GATA2 DNA binding C-terminal zinc finger domain, we show that GATA2 deficiency promotes a profibrotic state and metabolic dysfunction in AMs in response to type 2 stimuli. While homeostatic functions of AMs remained largely intact, GATA2 deficiency increased expression of genes associated with pulmonary fibrosis in response to IL-33-induced inflammation. Coincident with GATA2-dependent expression of genes in metabolic pathways, seahorse metabolic flux analysis suggests that AM metabolism is compromised, likely due to mitochondrial dysregulation, in the absence of GATA2. AM GATA2-dependent gene networks are enriched for targets of TFs previously demonstrated to interact with GATA2 in other cellular contexts, including PU.1, PPARγ, and other TFs that regulate AM homeostatic and inflammatory function. Thus, GATA2 mediates AM metabolic and transcriptomic programming to limit responses that support the development pulmonary fibrosis.
This dataset
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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 GSE298755_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 PRJNA1271057 and SRA study SRP589406. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
5 × AM, GATA2 fl/fl, PBS, 0 hour, vs 4 × AM, GATA2 -/-, IL33, 24 hour, vs 3 × AM, GATA2 -/-, PBS, 0 hour, vs 2 × AM, GATA2 fl/fl, IL33, 24 hour,

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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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