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Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages

GSE272396 Homo sapiens (human) RNA-seq (gene expression) 36 samples Submitted 2024/07/17 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 36 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
Homo sapiens (human)
Samples
36 samples: 12 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
Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophagesCell reports · 2024
Summary (written by the submitters)
A wide variety of electrophilic derivatives of the Kreb’s cycle-derived metabolite, itaconate, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages.
Read the full summary ↓
Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production. Endogenous itaconate directly targets cysteine 13 in IRAK4 disrupting IRAK4 autophosphorylation and activation, drives the degradation of NFκB, and modulates global ubiquitination patterns. As a result, cells unable to make itaconate overproduce inflammatory cytokines such as TNFα, IL6, and IL-1β in response to these innate activators. In contrast, the production of IFNβ, downstream of LPS, requires the production of itaconate. These data demonstrate that itaconate is a critical arbiter of inflammatory cytokine production downstream of multiple innate signaling pathways laying the groundwork for the development of itaconate mimetics for the treatment of autoimmunity.
Published in
Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages
Bourner LA, Chung LA, Long H et al. · Cell reports 2024 · PMID 39093697 · doi:10.1016/j.celrep.2024.114570
This dataset
Open GSE272396 in finder → Find more human 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 GSE272396_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 PRJNA1136566 and SRA study SRP520333. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39093697) ↗
Study design
12 conditions, mostly in triplicate
THP-1, WT, Vehicle, 6Hr, ×3 THP-1, WT, LPS&IFNg Stimulated, 6Hr, ×3 THP-1, IRG1 KO, Vehicle, 6Hr, ×3 THP-1, IRG1 KO, LPS&IFNg Stimulated, 6Hr, ×3 THP-1, WT, Vehicle, 12Hr, ×3 THP-1, WT, LPS&IFNg Stimulated, 12Hr, ×3 THP-1, IRG1 KO, Vehicle, 12Hr, ×3 THP-1, IRG1 KO, LPS&IFNg Stimulated, 12Hr, ×3 +4 more

Supports a case/control comparison: 9 samples read as cases, 18 as controls.

How we read this: 12 replicated groups read from 36 sample titles; they account for 36 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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