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METTL3/MYCN cooperation drives neural crest differentiation and provides therapeutic vulnerability in neuroblastoma

GSE244473 Homo sapiens (human) ChIP-seq / ATAC-seq (genome binding and open chromatin) 55 samples Submitted 2024/09/30 Platform GPL28038Platform GPL30173
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · human · 55 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Homo sapiens (human)
Topic
NeuroblastomaThis series is part of our curated briefing on it.
Samples
55 samples: 15 conditions, mostly in duplicateGroups 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
METTL3/MYCN cooperation drives neural crest differentiation and provides therapeutic vulnerability in neuroblastomaThe EMBO journal · 2024
Summary (written by the submitters)
Neuroblastoma (NB) is a childhood cancer. Improper differentiation of developing trunk neural crest cells (tNCC) cause NB tumor formation in sympathetic nervous system. N6-methyladenosine (m6A) epitranscriptomic modification control post-transcriptional gene expression but the mechanism which recruit m6A methyltransferase complex to specific locus is less characterized.
Read the full summary ↓
We explored if m6A epitranscriptome could fine tune gene regulation in migrating/differentiating tNCC. We uncovered m6A epitranscriptome based regulation of HOX gene expression in tNCC which contributes in their timely differentiation to sympathetic neurons. Posterior HOX genes are m6A modified in MYCN NB cells and tumors. We provided evidence that sustained overexpression of MYCN oncogene could drive METTL3 recruitment in subset of genes to create an undifferentiated state in tNCC. Our study suggests oncogenic transcription factor mediated modulation of m6A epitranscriptome could be a prevalent mechanism in other cancers. METTL3 depletion/inhibition induces DNA damage and differentiation in MYCN overexpressed cells. METTL3 inhibition increases vulnerability to the chemotherapeutic drug in MYCN-amplified Patient-derived xenografts (PDX) cells, suggesting METTL3 inhibition could be a potential therapeutic approach for NB.
Published in
METTL3/MYCN cooperation drives neural crest differentiation and provides therapeutic vulnerability in neuroblastoma
Thombare K, Vaid R, Pucci P et al. · The EMBO journal 2024 · PMID 39528654 · doi:10.1038/s44318-024-00299-8
This dataset
Open GSE244473 in finder → Find more human RNA-seq datasets → Neuroblastoma 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 GSE244473_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1023241 and SRA study SRP464260. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39528654) ↗
Study design
15 conditions, mostly in duplicate
h9_hESC_Input ×2 h9_NCSC_day14_Input ×2 h9_NCSC_day7_Input ×2 C8_SN_MYCN_minusDOX ×2 C8_SN_MYCN_plusDOX ×2 ES_stable_Controlsh_NCSC_day7 ×2 ES_stable_METTL3KD_812sh_NCSC_day7 ×2 tNCC_Controlsh ×2 +32 more

Supports a case/control comparison: 4 samples read as cases, 10 as controls.

How we read this: 15 replicated groups read from 55 sample titles; they account for 30 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

+ 15 more — browse all 55 samples with per-sample file links →

More Neuroblastoma datasets

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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.