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S1P/S1PR4 Promotes the Differentiation of CD8+TRM Cells Aggravating Bile Duct Injury in Biliary Atresia

GSE300457 Homo sapiens (human) Single-cell RNA-seq 45 samples Submitted 2025/12/19 Platform GPL24676
At a glance

Single-cell RNA-seq · human · 45 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
45 samples: 25 × LB vs 20 × LHGroups 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
S1P/S1PR4 promotes the differentiation of CD8(+) tissue-resident memory T cells aggravating bile duct injury in biliary atresiaJournal of hepatology · 2026
Summary (written by the submitters)
BACKGROUND AND AIMS: Biliary atresia (BA) is the most common and serious neonatal biliary disease, characterized by progressive biliary inflammation and fibrosis. We aim to comprehensively and systematically investigate the complex pathological process of BA from multiple molecular dimensions, combining transcriptomics, proteomics, metabolomics, and single-cell RNA sequencing.
Read the full summary ↓
METHODS: Integration of multi-omics data detected and localized aberrant metabolite regulation in immune cells of BA liver tissue. By flow cytometry sorting of specific immune cell subsets and in vitro experiments, we verified the role and mechanism of the aberrant metabolite signaling pathway in the progression of BA. In vivo experiments confirmed the effect of inhibiting the aberrant signaling pathway in alleviating bile duct injury and fibrosis. RESULTS: Based on multi-omics data, the sphingolipid metabolism pathway was abnormally activated in the S1 subtype of BA, a molecular subtype characterized by abnormal immune inflammation and poor prognosis. By integrating single-cell RNA profiling, Sphingosine-1-Phosphate Receptor 4 (S1PR4), a receptor of Sphingosine-1-Phosphate (S1P), was primarily expressed in CX3CR1+CD8+effector T (Teff) cells. In vitro, S1P/S1PR4 signaling promoted the migration of CX3CR1+CD8+Teff cells, and facilitated the differentiation of CX3CR1+CD8+Teff cells into CD8+ tissue-resident memory T (TRM) cells. Co-culture of CD8+TRM cells and cholangiocytes could induce the apoptosis of cholangiocytes. In vivo, S1PR4 inhibitor could alleviate liver inflammation and fibrosis by inhibiting the accumulation of CD8+TRM cells. CONCLUSIONS: Our study revealed that activation of the S1P/S1PR4 signaling pathway promotes the differentiation of CD8+ TRM cells, which subsequently induces cholangiocyte injury. Targeting the activation of the S1P/S1PR4 signaling pathway is a promising therapeutic strategy for BA, especially for patients with the S1 subtype.
Published in
S1P/S1PR4 promotes the differentiation of CD8(+) tissue-resident memory T cells aggravating bile duct injury in biliary atresia
Sun D, Wang D, Jia L et al. · Journal of hepatology 2026 · PMID 40915360 · doi:10.1016/j.jhep.2025.08.036
This dataset
Open GSE300457 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 GSE300457_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1280989 and SRA study SRP594079. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40915360) ↗
Study design
25 × LB vs 20 × LH

Supports a between-group comparison across 45 samples.

How we read this: 2 replicated groups read from 45 sample titles; they account for 45 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

+ 5 more — browse all 45 samples with per-sample file links →

Datasets on a similar topic

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