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LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma

GSE311851 Homo sapiens (human) RNA-seq (gene expression) 114 samples Submitted 2025/12/02 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 114 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
Ewing sarcomaThis series is part of our curated briefing on it.
Samples
114 samples: 35 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
LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing SarcomabioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Lysine specific demethylase 1 (LSD1), encoded by the gene KDM1A, is overexpressed and correlates with poor patient prognosis in Ewing sarcoma. LSD1 colocalizes with the FET-fusion (EWSR::FLI1, EWS::ERG, etc) throughout the genome and has therefore been considered a critical co-regulator driving the progression of Ewing sarcoma. However therapeutic targeting of LSD1 by irreversible and noncompetitive inhibitors has yielded mixed results.
Read the full summary ↓
Irreversible, enzymatic inhibition seems ineffective, but reversible noncompetitive inhibition has predominant off target mechanisms, leaving open the question of LSD1 function in Ewing sarcoma. Here we take a robust approach through multiple methods of depletion in multiple cell lines to define LSD1 function, both enzymatic and nonenzymatic, in Ewing sarcoma cell lines. We define a core set of 22 genes that are commonly repressed by LSD1 in all cell lines and that repression of these genes downregulates synapse functioning and e-cadherin target genes. De-repression of these genes with LSD1 loss is an early and sustained genotype in all cell lines tested. Furthermore, we define distinct gene sets in each cell line that are regulated by the enzymatic and nonenzymatic functions of LSD1 and find repression of e-cadherin target genes to be nonenzymatically regulated. This finding supports the growing body of evidence that in addition to their canonical catalytic activity, enzymes serve essential noncanonical roles as well. Lastly, we uncovered evidence through use of the irreversible inhibitor OG-L002 that 2D cytotoxicity and proliferation assays may be insufficient to determine how Ewing sarcoma responds to LSD1 inhibition.
Published in
LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma
Dreher RD, Taslim C, Miller I et al. · bioRxiv : the preprint server for biology 2025 · PMID 41415396 · doi:10.64898/2025.12.04.692414
This dataset
Open GSE311851 in finder → Find more human RNA-seq datasets → Ewing sarcoma landscape →
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 GSE311851_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 PRJNA1371756 and SRA study SRP650013. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41415396) ↗
Study design
35 conditions, mostly in triplicate
a673_CRKO ×6 a673_CRWT ×6 a673_DMSO ×6 a673_iLSD1 ×3 a673_iLuc ×3 a673_DMSO_48hr ×3 a673_6hrUM ×3 a673_24hrUM ×3 +27 more

Supports a between-group comparison across 114 samples.

How we read this: 35 replicated groups read from 114 sample titles; they account for 114 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

+ 74 more — browse all 114 samples with per-sample file links →

More Ewing sarcoma datasets

Search all human RNA-seq datasets in GEO →

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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.