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A genome-wide CRISPR screen identifies the TNRC18 gene locus as a novel regulator of inflammatory signaling

GSE299089 Homo sapiens (human) RNA-seq (gene expression) 54 samples Submitted 2025/09/30 Platform GPL18573Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 54 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
54 samples: 18 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
A genome-wide CRISPR screen identifies the TNRC18 gene locus as a regulator of inflammatory signalingNature communications · 2025
Summary (written by the submitters)
Interleukin-1β (IL-1β) is dysregulated in chronic inflammatory diseases, yet the genetic factors influencing IL-1β production remain largely unknown. Myeloid-derived cells are the primary producers of IL-1β, which prompted a genome-wide CRISPR knockout screen in the human myeloid-derived U937 cell model treated with lipopolysaccharide (LPS) to mimic inflammatory conditions and sorted for high and low intracellular IL-1β levels.
Read the full summary ↓
A total of 295 genes were identified as regulators of IL-1β production, including known mediators such as TLR4, JAK-STAT and IL-10 receptor. Notably, 57 out of the 295 genes overlapped with loci associated with human inflammatory diseases, including the TNRC18 gene locus associated with multiple diseases in the Finnish population. U937 cells engineered with the Finnish-enriched rs748670681 risk allele demonstrated decreased levels of mRNA for TNRC18 and an adjacent gene WIPI2, reduction in LPS-dependent gene activation and cytokine production, but elevation of interferon-responsive gene programs. Transcriptomic profiles for individual knockouts of TNRC18 and WIPI2 attributed the loss of LPS-dependent signaling primarily to TNRC18, which occurs through the modulation of H3K27 acetylation around inflammatory regulatory regions via TNRC18 and its protein interaction network. In contrast, the loss of WIPI2 is characterized by an exacerbation of interferon signaling. Collectively, these findings delineate the global regulatory mechanisms of IL-1β production and provide molecular insights to the role of the rs748670681 variant as a pleiotropic risk factor for inflammatory diseases.
Published in
A genome-wide CRISPR screen identifies the TNRC18 gene locus as a regulator of inflammatory signaling
Rahimov F, Ghosh S, Petiwala S et al. · Nature communications 2025 · PMID 41285767 · doi:10.1038/s41467-025-65277-y
This dataset
Open GSE299089 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 GSE299089_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 PRJNA1272553 and SRA study SRP590157. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41285767) ↗
Study design
18 conditions, mostly in triplicate
U937 cells, non-template control, vehicle tre… ×3 U937 cells, non-template control, 24hr LPS tr… ×3 U937 cells, TNRC18 knockout, vehicle treatment ×3 U937 cells, TNRC18 knockout, 24hr LPS treatme… ×3 U937 cells, WT rep 1, vehicle treatment ×3 U937 cells, WT rep 1, 24hr LPS treatment ×3 U937 cells, WT rep 2, vehicle treatment ×3 U937 cells, WT rep 2, 24hr LPS treatment ×3 +10 more

Supports a case/control comparison: 6 samples read as cases, 36 as controls.

How we read this: 18 replicated groups read from 54 sample titles; they account for 54 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

+ 14 more — browse all 54 samples with per-sample file links →

Datasets on a similar topic

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