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Mechanisms of Differential Signaling by IFNLR1 Variants

GSE329545 Homo sapiens (human) RNA-seq (gene expression) 48 samples Submitted 2026/04/30 Platform GPL34284
At a glance

RNA-seq (gene expression) · human · 48 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
48 samples: 20 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
Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 VariantsJournal of innate immunity · 2026
Summary (written by the submitters)
Introduction: Lambda interferons signal through the interferon lambda receptor-1 (IFNLR1) and IL10RB heterodimer to induce interferon stimulated genes (ISGs). We previously showed that proteins derived from distinct IFNLR1 splice isoforms uniquely influence gene expression and HBV replication in stem cell-derived hepatocytes (iHeps). Here, we evaluated the mechanisms of signal transduction by full-length IFNLR1 (variant 1) and a truncated variant missing part of the cytoplasmic JAK1-interacting domain (variant 2).
Read the full summary ↓
Methods: We evaluated HEK293T cells, wild-type (WT), and IFNLR1 knock-out (KO) iHeps with doxycycline-inducible expression FLAG-tagged IFNLR1 variants using the Duolink proximity ligation assay, ImageStream flow cytometry, western blotting of JAK-STAT proteins, susceptibility to JAK1 and TYK2 inhibitors, and gene expression profiling. Results: Each variant demonstrated IFNL-induced colocalization with IL10RB, but variant 1 was more rapidly and extensively internalized. In WT iHeps with intact endogenous IFNLR1, overexpression of either variant 1 or variant 2 enabled higher IFNL-induced JAK1, TYK2, STAT1 and STAT2 phosphorylation, yet variant 2 supported less robust ISG induction than variant 1. In iHeps with abrogated endogenous IFNLR1 expression, variant 2 supported less JAK1 and TYK2 phosphorylation and ISG induction than variant 1 yet was not deficient in supporting STAT1 and STAT2 phosphorylation. Select ISGs had differential constitutive expression in IFNL-untreated variant-expressing iHeps. In iHeps expressing variant 1, WT-iHeps were more resistant than KO-iHeps to TYK2-inhibition of antiviral ISG induction yet conversely were more susceptible to TYK2-inhibition of proinflammatory ISG induction, suggesting endogenously produced noncanonical variants influence the TYK2-dependence of IFNL signaling. Conclusions: IFNLR1 variants promote differential utilization of signaling mediators to influence IFNL-induced gene expression patterns, indicating a putative role in pathway regulation.
Published in
Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants
Novotny LA, Martinez-Morant C, Duncan SA et al. · Journal of innate immunity 2026 · PMID 42213608 · doi:10.1159/000552360
This dataset
Open GSE329545 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 GSE329545_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 PRJNA1459475 and SRA study SRP696093. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42213608) ↗
Study design
20 conditions, mostly in duplicate
WT+Iso1 -dox +IFNL3 ×2 WT+Iso1 +dox +IFNL3 ×2 WT+EV -dox -IFNL3 ×2 WT+EV +dox -IFNL3 ×2 WT+Iso2 -dox -IFNL3 ×2 WT+Iso2 -dox +IFNL3 ×2 WT+Iso2 +dox -IFNL3 ×2 WT+Iso2 +dox +IFNL3 ×2 +20 more

Supports a between-group comparison across 40 samples.

How we read this: 20 replicated groups read from 48 sample titles; they account for 40 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

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