GEO series

Xylosyltransferase-II deficiency rewires innate immune signaling and destabilizes polarization in human macrophages

GSE329556 Homo sapiens (human) RNA-seq (gene expression) 24 samples Submitted 2026/06/26 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 24 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: 24 samples: 24 samples, each with a distinct title — no replicated groupsGroups 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: Xylosyltransferase-II deficiency rewires innate immune signaling and destabilizes polarization in human macrophagesFrontiers in immunology · 2026

Summary (written by the submitters)

Xylosyltransferase-II (XT-II), encoded by XYLT2, catalyzes the rate-limiting step of proteoglycan biosynthesis, yet its role in macrophage biology and innate immune regulation remains poorly defined. Given the central role of macrophages in inflammatory signaling and tissue homeostasis, we investigated the transcriptional consequences of XYLT2 deficiency in human primary macrophages across distinct polarization states (M0, M1, M2).

Read the full summary ↓

Bulk mRNA sequencing revealed that XYLT2 deficiency induces a conserved and robust transcriptional reprogramming independent of polarization state. Differential expression analysis identified a shared interferon-associated gene signature, characterized by the upregulation of interferon-stimulated genes, including STAT1, IRF7, and multiple IFIT family members. Pathway enrichment analysis demonstrated significant activation of innate immune sensing pathways, including RIG-I-like, NOD-like, and Toll-like receptor signaling, alongside strong enrichment of JAK–STAT and cytokine signaling pathways. In parallel, pathways such as NF-κB, PI3K–Akt, and MAPK signaling exhibited bidirectional regulation, indicating complex network rewiring rather than uniform activation. Notably, osteoclast differentiation pathways were enriched among upregulated genes, suggesting a shift toward a pro-osteoclastogenic transcriptional state. Collectively, these findings demonstrate that XYLT2 deficiency drives a global, interferon-dominated transcriptional program associated with enhanced innate immune activation and altered macrophage functional identity, providing a mechanistic link between impaired proteoglycan biosynthesis and dysregulated immune signaling.

Published in

Xylosyltransferase-II deficiency rewires innate immune signaling and destabilizes polarization in human macrophages

Witt A, Ly TD, Kühle M et al. · Frontiers in immunology 2026 · PMID 42433371 · doi:10.3389/fimmu.2026.1850248

This dataset

Open GSE329556 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 GSE329556_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 PRJNA1459502. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42433371) ↗

Study design

24 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 12 samples read as cases, 12 as controls.

How we read this: Read from 24 sample titles: 24 distinct titles with little repetition. 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

GSM9706371 Donor1, M0 Macrophages, XYLT2-knockdown
GSM9706372 Donor1, M1 Macrophages, XYLT2-knockdown
GSM9706373 Donor1, M2 Macrophages, XYLT2-knockdown
GSM9706374 Donor2, M0 Macrophages, control
GSM9706375 Donor2, M1 Macrophages, control
GSM9706376 Donor2, M2 Macrophages, control
GSM9706377 Donor3, M0 Macrophages, control
GSM9706378 Donor3, M1 Macrophages, control
GSM9706379 Donor3, M2 Macrophages, control
GSM9706380 Donor4, M0 Macrophages, control
GSM9706381 Donor4, M1 Macrophages, control
GSM9706382 Donor4, M2 Macrophages, control
GSM9706383 Donor1, M0 Macrophages, control
GSM9706384 Donor1, M1 Macrophages, control
GSM9706385 Donor1, M2 Macrophages, control
GSM9706386 Donor2, M0 Macrophages, XYLT2-knockdown
GSM9706387 Donor2, M1 Macrophages, XYLT2-knockdown
GSM9706388 Donor2, M2 Macrophages, XYLT2-knockdown
GSM9706389 Donor3, M0 Macrophages, XYLT2-knockdown
GSM9706390 Donor3, M1 Macrophages, XYLT2-knockdown
GSM9706391 Donor3, M2 Macrophages, XYLT2-knockdown
GSM9706392 Donor4, M0 Macrophages, XYLT2-knockdown
GSM9706393 Donor4, M1 Macrophages, XYLT2-knockdown
GSM9706394 Donor4, M2 Macrophages, XYLT2-knockdown

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