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Crosstalk in Skin: Loss of Desmoglein 1 in Keratinocytes Inhibits BRAFV600E-induced Cellular Senescence in Human Melanocytes

GSE255546 Homo sapiens (human) RNA-seq (gene expression) 18 samples Submitted 2024/11/18 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)
Topic
MelanomaThis series is part of our curated briefing on it.
Samples
18 samples: 6 conditions, mostly in triplicateGroups 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
Crosstalk in Skin: Loss of Desmoglein 1 in Keratinocytes Inhibits BRAF(V600E)-Induced Cellular Senescence in Human MelanocytesThe Journal of investigative dermatology · 2025
Summary (written by the submitters)
Melanoma arises from transformation of melanocytes in the basal layer of the epidermis where they are surrounded by keratinocytes, with which they interact through cell contact and paracrine communication. Although research focuses on how the accumulation of oncogene and tumor suppressor gene mutations in melanocytes drive melanoma development, how alterations in keratinocytes serve as extrinsic drivers of melanoma initiation and progression is poorly understood.
Read the full summary ↓
We recently identified keratinocyte desmoglein 1 (Dsg1) as an important mediator of keratinocyte:melanoma crosstalk. Here we address the extent to which Dsg1 loss, which occurs in response to acute environmental stress such as ultraviolet radiation, affects early steps in melanomagenesis. RNA-Seq analysis revealed that paracrine signals from Dsg1-deficient keratinocytes mediate a transcriptional switch from a differentiated to undifferentiated cell state in melanocytes expressing BRAFV600E. Of 221 differentially expressed genes in BRAFV600E cells treated with Dsg1-deficient conditioned media (CM), the laminin superfamily member NTN4/Netrin-4, which inhibits senescence in endothelial cells, stood out. Indeed, while BRAFV600E melanocytes treated with Dsg1-deficient CM showed signs of senescence bypass, knockdown of NTN4 reversed these effects. These results suggest that Dsg1 loss in keratinocytes provides an extrinsic signal to push melanocytes towards oncogenic transformation once an initial mutation has been introduced.
Published in
Crosstalk in Skin: Loss of Desmoglein 1 in Keratinocytes Inhibits BRAF(V600E)-Induced Cellular Senescence in Human Melanocytes
Tong X, Burks HE, Ren Z et al. · The Journal of investigative dermatology 2025 · PMID 39581457 · doi:10.1016/j.jid.2024.10.608
This dataset
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.

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 GSE255546_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1075335 and SRA study SRP489250. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly in triplicate
Control melanocytes in shCTL CM # ×3 Control melanocytes in shDsg1 CM # ×3 Melanocytes with wild type BRAF in shCTL CM # ×3 Melanocytes with wild type BRAF in shDsg1 CM # ×3 Melanocytes with mutant BRAFV600E in shCTL CM… ×3 Melanocytes with mutant BRAFV600E in shDsg1 C… ×3

Supports a case/control comparison: 3 samples read as cases, 12 as controls.

How we read this: 6 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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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.