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Epithelial-Immune Metabolic Codependency Fuels Inflammatory Disease [Bulk RNA-seq]

GSE237767 Mus musculus (mouse) Single-cell RNA-seq 34 samples Submitted 2024/04/01 Platform GPL24676Platform GPL24247
At a glance

Single-cell RNA-seq · mouse · 34 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
Mus musculus (mouse)
Samples
34 samples: 8 conditions, mostly with about 4 replicates eachGroups 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
Metabolic coordination between skin epithelium and type 17 immunity sustains chronic skin inflammationImmunity · 2024
Summary (written by the submitters)
Inflammatory skin diseases are spurred by unchecked immune-epithelial circuits. Although the function of cytokine and chemokine signals in facilitating this crosstalk is well established, the specific metabolic mediators involved and their simultaneous contribution to dysregulation of these two distinct cellular compartments is unclear.
Read the full summary ↓
Here, we employed scRNA-seq, spatial transcriptomics, and immunofluorescence across multiple disease indications to elucidate a dysfunctional epithelial state marked by Hypoxia Inducible Factor 1 alpha (HIF1⍺). Ex vivo HIF1⍺ blockade of human Psoriasis (PsO) lesions led to a reduction in pathological gene expression via modulation of glucose metabolism. Epidermal-specific loss of HIF1⍺ or its transcriptional target, glucose transporter 1, curtailed both epidermal pathology and the cutaneous immune response in murine PsO. Glycolytic metabolism sustained epithelial hyperproliferation and differentiation, while lactate, its terminal product, was crucial for sustaining Type 17 response. Notably, inhibition of lactate dehydrogenase A or the lactate transporters MCT1/4 selectively attenuated the Type 17 response, underscoring a divergent requirement for glucose and lactate in epithelial and immune cells, respectively. Collectively, these findings identify therapeutically targetable immune-epithelial circuits by unveiling a remarkable coordination of metabolic processed between the epithelial and immune compartments in inflammatory skin disease.
Published in
Metabolic coordination between skin epithelium and type 17 immunity sustains chronic skin inflammation
Subudhi I, Konieczny P, Prystupa A et al. · Immunity 2024 · PMID 38772365 · doi:10.1016/j.immuni.2024.04.022
This dataset
Open GSE237767 in finder → Find more 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 GSE237767_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 PRJNA996578 and SRA study SRP450389. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38772365) ↗
Study design
8 conditions, mostly with about 4 replicates each
Imiquimod-treated WT murine skin, ×6 Psoriatic lesional skin, vehicle control, ×5 Imiquimod-treated HIF1⍺-epithelial specific K… ×5 Healthy skin, vehicle control, ×4 Psoriatic lesional skin, HIF1⍺ inhibitor, ×4 Psoriatic lesional skin, Standard of care, ×4 Healthy skin, HIF1⍺ inhibitor, ×3 Healthy skin, Standard of care, ×3

Supports a case/control comparison: 13 samples read as cases, 10 as controls.

How we read this: 8 replicated groups read from 34 sample titles; they account for 34 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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