GEO series

Threonine Phosphorylation of STAT1 Restricts Interferon Signaling and Promotes Innate Inflammatory Responses

GSE261824 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2024/03/18 Platform GPL17021

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples: 8 conditions, mostly in duplicateGroups 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: Threonine phosphorylation of STAT1 restricts interferon signaling and promotes innate inflammatory responsesProceedings of the National Academy of Sciences of the United States of America · 2024

Summary (written by the submitters)

Since its discovery over three decades ago, signal transducer and activator of transcription 1 (STAT1) has been extensively studied as a central mediator for interferons (IFNs) signaling and antiviral defense. Here, using genetic and biochemical assays, we unveil Thr748 as a conserved IFN-independent phosphorylation switch in Stat1, which restricts IFN signaling and promotes innate inflammatory responses following the recognition of the bacterial-derived toxin lipopolysaccharide (LPS).

Read the full summary ↓

Genetically-engineered mice expressing phospho-deficient threonine748–to-alanine (T748A) mutant Stat1 are resistant to LPS–induced lethality. Of note, T748A mice exhibited undisturbed IFN signaling, as well as total expression of Stat1. Further, the T748A point-mutation of Stat1 recapitulates the safeguard effect of the genetic ablation of Stat1 following LPS-induced lethality, indicating that the Thr748 phosphorylation contributes inflammatory functionalities of Stat1. Mechanistically, LPS-induced Toll-like receptor 4 endocytosis activates a cell-intrinsic IκB kinase (IKK)–mediated Thr748 phosphorylation of Stat1, which promotes macrophages inflammatory response while restricting the IFN and anti-inflammatory responses. Depletion of macrophages restores the sensitivity of the T748A mice to LPS-induced lethality. Together, our study indicates a phosphorylation-dependent functional dichotomy of Stat1 in innate immune responses: IFN phospho-tyrosine dependent, and inflammatory phospho-threonine dependent. Better understanding of the Thr748 phosphorylation of Stat1 may uncover novel pharmacologically targetable molecules and offer better treatment modalities for sepsis, a disease that claims millions of lives annually.

Published in

Threonine phosphorylation of STAT1 restricts interferon signaling and promotes innate inflammatory responses

Metwally H, Elbrashy MM, Ozawa T et al. · Proceedings of the National Academy of Sciences of the United States of America 2024 · PMID 38621137 · doi:10.1073/pnas.2402226121

This dataset

Open GSE261824 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 GSE261824_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 PRJNA1089167 and SRA study SRP496146. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38621137) ↗

Study design

8 conditions, mostly in duplicate

BMDMs Wt, LPS 0 hr # ×2 BMDMs T748A, LPS 0 hr # ×2 BMDMs Wt, LPS 4 hr # ×2 BMDMs T748A, LPS 4 hr # ×2 PCMs Wt, LPS 0 hr # ×2 PCMs T748A, LPS 0 hr # ×2 PCMs Wt, LPS 4 hr # ×2 PCMs T748A, LPS 4 hr # ×2

Supports a between-group comparison across 16 samples.

How we read this: 8 replicated groups read from 16 sample titles; they account for 16 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

GSM8152583 BMDMs Wt, LPS 0 hr #1 BMDMs Wt, LPS 0 hr #
GSM8152584 BMDMs Wt, LPS 0 hr #2 BMDMs Wt, LPS 0 hr #
GSM8152585 BMDMs T748A, LPS 0 hr #1 BMDMs T748A, LPS 0 hr #
GSM8152586 BMDMs T748A, LPS 0 hr #2 BMDMs T748A, LPS 0 hr #
GSM8152587 BMDMs Wt, LPS 4 hr #1 BMDMs Wt, LPS 4 hr #
GSM8152588 BMDMs Wt, LPS 4 hr #2 BMDMs Wt, LPS 4 hr #
GSM8152589 BMDMs T748A, LPS 4 hr #1 BMDMs T748A, LPS 4 hr #
GSM8152590 BMDMs T748A, LPS 4 hr #2 BMDMs T748A, LPS 4 hr #
GSM8152591 PCMs Wt, LPS 0 hr #1 PCMs Wt, LPS 0 hr #
GSM8152592 PCMs Wt, LPS 0 hr #2 PCMs Wt, LPS 0 hr #
GSM8152593 PCMs T748A, LPS 0 hr #1 PCMs T748A, LPS 0 hr #
GSM8152594 PCMs T748A, LPS 0 hr #2 PCMs T748A, LPS 0 hr #
GSM8152595 PCMs Wt, LPS 4 hr #1 PCMs Wt, LPS 4 hr #
GSM8152596 PCMs Wt, LPS 4 hr #2 PCMs Wt, LPS 4 hr #
GSM8152597 PCMs T748A, LPS 4 hr #1 PCMs T748A, LPS 4 hr #
GSM8152598 PCMs T748A, LPS 4 hr #2 PCMs T748A, LPS 4 hr #

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