GEO series

IRE1α Regulates Macrophage Phagocytosis In Immune Thrombocytopenia Through NR1D1 mRNA Decay And Lysosomal Biogenesis

GSE305695 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/02/05 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 12 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: 12 samples: 3 × Blank_WT vs 3 × R300_WT vs 3 × Blank_KO vs 3 × R300_KOGroups 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: IRE1α regulates macrophage phagocytosis in immune thrombocytopenia through NR1D1 mRNA decay and lysosomal biogenesisCell reports · 2026

Summary (written by the submitters)

Macrophage phagocytosis is essential for immune homeostasis but must be tightly constrained to prevent pathological tissue damage. How cellular stress pathways enforce phagocytic homeostasis remains incompletely understood. Here, we show that phagocytosis selectively activates the endoplasmic reticulum stress sensor IRE1α in macrophages, which functions as a negative regulator of lysosome-driven phagocytic amplification.

Read the full summary ↓

Using myeloid-specific IRE1α-deficient mice and pharmacological inhibition, we demonstrate that loss of IRE1α RNase activity leads to excessive phagocytosis through unchecked lysosomal biogenesis. Mechanistically, phagocytosis-activated IRE1α directly degrades Nr1d1 mRNA via regulated IRE1α-dependent decay (RIDD), thereby restraining NR1D1-driven lysosomal expansion. Disruption of this IRE1α-NR1D1 axis exacerbates macrophage-mediated platelet clearance and accelerates disease progression of immune thrombocytopenia (ITP). Reduced ERN1 expression and IRE1α activity are observed in monocytes from patients with ITP. Pharmacological inhibition of NR1D1 or lysosomal activity rescues thrombocytopenia. Together, these findings establish the IRE1α-NR1D1-lysosome axis as a therapeutically actionable pathway in phagocytosis-driven diseases.

Published in

IRE1α regulates macrophage phagocytosis in immune thrombocytopenia through NR1D1 mRNA decay and lysosomal biogenesis

Xu Y, Zhao F, Lin M et al. · Cell reports 2026 · PMID 41824452 · doi:10.1016/j.celrep.2026.117083

This dataset

Open GSE305695 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 GSE305695_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 PRJNA1307484 and SRA study SRP609762. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41824452) ↗

Study design

3 × Blank_WT vs 3 × R300_WT vs 3 × Blank_KO vs 3 × R300_KO

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9181871 Blank_WT1 Blank_WT
GSM9181872 Blank_WT2 Blank_WT
GSM9181873 Blank_WT3 Blank_WT
GSM9181874 R300_WT1 R300_WT
GSM9181875 R300_WT2 R300_WT
GSM9181876 R300_WT3 R300_WT
GSM9181877 Blank_KO1 Blank_KO
GSM9181878 Blank_KO2 Blank_KO
GSM9181879 Blank_KO3 Blank_KO
GSM9181880 R300_KO1 R300_KO
GSM9181881 R300_KO2 R300_KO
GSM9181882 R300_KO3 R300_KO

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