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Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi-compartmental alterations in gene expression and signaling cross-talk

GSE274068 Homo sapiens (human) Spatial transcriptomics 12 samples Submitted 2025/01/27 Platform GPL24676
At a glance

Spatial transcriptomics · human · 12 samples

What it is
Spatial transcriptomicsGene activity measured with its position in a tissue section.
Organism
Homo sapiens (human)
Samples
12 samples: 3 × N/TERT-2G keratinocytes, negative control, vs 3 × N/TERT-2G keratinocytes, APOE knockdown, vs 3 × N/TERT-2G keratinocytes, ATF3 knockdown, vs 3 × N/TERT-2G keratinocytes, CXCL14 knockdown,Groups 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
Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi-compartmental alterations in gene expression and signaling cross-talkbioRxiv : the preprint server for biology · 2024
Summary (written by the submitters)
Vulvar diseases are a critical but often overlooked issue in women's health, impacting many women and frequently causing long-term physical and emotional challenges. Lichen sclerosus (LS) is a chronic inflammatory skin disease that causes scarring of the vulva and is associated with an increased risk of malignancy. The molecular pathogenesis of vulvar LS (VLS) is not well understood, preventing development of any FDA-approved therapies.
Read the full summary ↓
Here, we utilize single-cell and spatial transcriptomics to analyze lesional and non-lesional skin from VLS patients, as well as healthy control vulvar skin. Our studies, which reveal histologic, cellular, and molecular heterogeneities within VLS, also identify unifying molecular changes across fibroblasts, immune cells, keratinocytes, and melanocytes in lesional skin. The findings depict a scenario of cellular stress and damage affecting both fibroblasts and keratinocytes, along with a complex immune landscape indicating enhanced CD8+ T cell cytotoxicity but also signs of exhaustion. They further suggest aberrant cell-cell signaling across, and increased activation of IFN, JAK/STAT and p53 pathways in, specific cell types. Using monolayer and organotypic culture models, we demonstrate that the depletion of select genes, which are downregulated in VLS lesional skin keratinocytes, partially recapitulates VLS-like stress-associated changes. Collectively, these data provide novel insights into the pathogenesis of VLS, identifying potential biomarkers and therapeutic targets for future research.
Published in
Single-cell and spatial transcriptomics of vulvar lichen sclerosus reveal multi-compartmental alterations in gene expression and signaling cross-talk
Sun P, Kraus CN, Zhao W et al. · bioRxiv : the preprint server for biology 2024 · PMID 39211101 · doi:10.1101/2024.08.14.607986
This dataset
Open GSE274068 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 GSE274068_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: Spatial studies usually ship Space Ranger style folders (count matrix plus tissue images). Look for them among the supplementary files.

Also filed as BioProject PRJNA1144887 and SRA study SRP524616. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39211101) ↗
Study design
3 × N/TERT-2G keratinocytes, negative control, vs 3 × N/TERT-2G keratinocytes, APOE knockdown, vs 3 × N/TERT-2G keratinocytes, ATF3 knockdown, vs 3 × N/TERT-2G keratinocytes, CXCL14 knockdown,

Supports a case/control comparison: 9 samples read as cases, 3 as controls.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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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