GEO series

The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation [RNA-seq]

GSE270648 Mus musculus (mouse) RNA-seq (gene expression) 19 samples Submitted 2026/05/20 Platform GPL19057

At a glance

RNA-seq (gene expression) · mouse · 19 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: 19 samples: 6 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: The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturationNature communications · 2026

Summary (written by the submitters)

Conventional type I dendritic cells (cDC1s) are characterized by their unique capacity to engulf and cross-present antigens from dead cells, in contrast to the closely related cDC2s. Recently, the engulfment of dead cells by cDC1s was found to initiate cDC1 homeostatic maturation and induction of cholesterol efflux pathways by inducing LXRb activity.

Read the full summary ↓

cDC1s are uniquely characterized by high basal activity of IRE1, a sensor of the unfolded protein response (UPR). IRE1 activity in cDC1s is unconventional because it does not induce a typical UPR gene signature and hence the role of IRE1 in cDC1s remains enigmatic. Here we show that IRE1 activity is critical for the survival of homeostatically matured cDC1s, not cDC2s, after engulfment of apoptotic cells. Mechanistically, we found that IRE1 becomes activated by the influx of dead-cell derived cholesterol, explaining its cDC1 subset specific activation. Following activation, IRE1’s endonuclease activity degrades miRNA-92a in a process termed Regulated IRE1 dependent decay (RIDD). miRNA-92a targets Abcg1 mRNA which is an essential cholesterol efflux transporter in cDC1s. Thus IRE1, together with LXRß which drives the expression of Abcg1 mRNA, coordinates cholesterol efflux in cDC1s after efferocytosis. Loss of IRE1 leads to cholesterol toxicity and cell death of mature cDC1s after engulfment of dead cells. This could be rescued by blocking miRNA synthesis or by enforcing cholesterol efflux with reconstituted high density lipoprotein treatment. In conclusion, these data highlight the central role of the endoplasmic reticulum and IRE1 as a sensor of cholesterol influx, extending IRE1’s function beyond its canonical role in protein folding. Furthermore, they underscore the tight control of lipid metabolism during cDC1 maturation, uncovering a second pathway to coordinate cholesterol efflux.

Published in

The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation

Bosteels V, Maréchal S, Cloots E et al. · Nature communications 2026 · PMID 42463662 · doi:10.1038/s41467-026-75716-z

This dataset

Open GSE270648 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 GSE270648_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 PRJNA1127635 and SRA study SRP515744. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42463662) ↗

Study design

6 conditions, mostly in triplicate

Spleen, WT, cDC2s, ×4 Spleen, WT, cDC1s, ×3 Spleen, Xbp1-Ire1 KO, cDC1s, ×3 Spleen, Xbp1-Ire1 KO, cDC2s, ×3 Spleen, Xbp1 KO, cDC1s, ×3 Spleen, Xbp1 KO, cDC2s, ×3

Supports a between-group comparison across 19 samples.

How we read this: 6 replicated groups read from 19 sample titles; they account for 19 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

GSM8349260 Spleen, WT, cDC1s, rep 1 Spleen, WT, cDC1s,
GSM8349261 Spleen, WT, cDC1s, rep 2 Spleen, WT, cDC1s,
GSM8349262 Spleen, WT, cDC2s, rep 1 Spleen, WT, cDC2s,
GSM8349263 Spleen, WT, cDC2s, rep 2 Spleen, WT, cDC2s,
GSM8349264 Spleen, Xbp1-Ire1 KO, cDC1s, rep 1 Spleen, Xbp1-Ire1 KO, c…
GSM8349265 Spleen, Xbp1-Ire1 KO, cDC1s, rep 2 Spleen, Xbp1-Ire1 KO, c…
GSM8349266 Spleen, Xbp1-Ire1 KO, cDC1s, rep 3 Spleen, Xbp1-Ire1 KO, c…
GSM8349267 Spleen, Xbp1-Ire1 KO, cDC2s, rep 1 Spleen, Xbp1-Ire1 KO, c…
GSM8349268 Spleen, Xbp1-Ire1 KO, cDC2s, rep 2 Spleen, Xbp1-Ire1 KO, c…
GSM8349269 Spleen, Xbp1-Ire1 KO, cDC2s, rep 3 Spleen, Xbp1-Ire1 KO, c…
GSM8349270 Spleen, WT, cDC1s, rep 3 Spleen, WT, cDC1s,
GSM8349271 Spleen, WT, cDC2s, rep 3 Spleen, WT, cDC2s,
GSM8349272 Spleen, WT, cDC2s, rep 4 Spleen, WT, cDC2s,
GSM8349273 Spleen, Xbp1 KO, cDC1s, rep 1 Spleen, Xbp1 KO, cDC1s,
GSM8349274 Spleen, Xbp1 KO, cDC1s, rep 2 Spleen, Xbp1 KO, cDC1s,
GSM8349275 Spleen, Xbp1 KO, cDC1s, rep 3 Spleen, Xbp1 KO, cDC1s,
GSM8349276 Spleen, Xbp1 KO, cDC2s, rep 1 Spleen, Xbp1 KO, cDC2s,
GSM8349277 Spleen, Xbp1 KO, cDC2s, rep 2 Spleen, Xbp1 KO, cDC2s,
GSM8349278 Spleen, Xbp1 KO, cDC2s, rep 3 Spleen, Xbp1 KO, cDC2s,

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