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Disease-associated variant in LACC1, a Crohn’s risk gene, acts in T cells to alter gene expression, metabolism and T cell function

GSE272811 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/09/30 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 18 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
18 samples: 5 × Human Th0 cells, transduced with empty vector (EV), dono vs 5 × Human Th0 cells, transduced with shLACC1 (KD), dono vs 4 × Human induced Treg cells, transduced with empty vector (EV), dono vs 4 × Human induced Treg cells, transduced with shLACC1 (KD), donoGroups 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
Crohn's Disease-associated variant in laccase domain containing 1 (LACC1) modulates T cell gene expression, metabolism and T cell functionNature communications · 2025
Summary (written by the submitters)
Genome wide association studies (GWAS) identify a site near the metabolism gene laccase domain containing 1 (LACC1) as a risk for Crohn’s disease (CD). We previously found the Crohn’s disease risk allele near LACC1 correlates with decreased T lymphocyte LACC1 expression. Despite this, proof of this allelic effect, the mechanism by which gene expression is affected, and links to T cell function and inflammatory disease, remained unknown.
Read the full summary ↓
Here we identified sites in a promoter region in a haploblock that influenced LACC1 gene expression. Direct association of disease-risk variants with lower LACC1 mRNA was confirmed by comparing transcripts from each allele in LACC1 heterozygous human CD4+ T cells. Using gene editing, we validated the role of this promoter region in LACC1 expression in T cells. Human CD4+ T cells with LACC1 gene knockdown showed altered metabolism, including a reduced oxygen consumption rate, and reduced regulatory T cell differentiation. Therefore, our study provides a mechanism for this disease GWAS hit by linking promoter region alterations to changes in T cell metabolism and function.
Published in
Crohn's Disease-associated variant in laccase domain containing 1 (LACC1) modulates T cell gene expression, metabolism and T cell function
Li Y, Ascui G, Dicker M et al. · Nature communications 2025 · PMID 40089498 · doi:10.1038/s41467-025-57744-3
This dataset
Open GSE272811 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 GSE272811_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 PRJNA1138776 and SRA study SRP521447. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40089498) ↗
Study design
5 × Human Th0 cells, transduced with empty vector (EV), dono vs 5 × Human Th0 cells, transduced with shLACC1 (KD), dono vs 4 × Human induced Treg cells, transduced with empty vector (EV), dono vs 4 × Human induced Treg cells, transduced with shLACC1 (KD), dono

Supports a between-group comparison across 18 samples.

How we read this: 4 replicated groups read from 18 sample titles; they account for 18 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
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