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Comparative single-cell transcriptomics of human neuroblastoma and preclinical models reveal conservation of adrenergic cell state

GSE280892 Mus musculus (mouse) Single-cell RNA-seq 14 samples Submitted 2024/11/02 Platform GPL19057

At a glance

Single-cell RNA-seq · mouse · 14 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Mus musculus (mouse)
Samples: 14 samples: 5 × Hemizygous vs 5 × Homozygous vs 2 × Homozygous 4 Tumoroids Passage vs 2 × Homozygous 5 Tumoroids PassageGroups 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.

Summary (written by the submitters)

Transgenic mice and organoid models, such as three-dimensional tumoroid cultures, have emerged as powerful tools for investigating cancer development and targeted therapies. Yet, the extent to which these preclinical models recapitulate the cellular identity of heterogeneous malignancies, such as neuroblastoma (NB), remains to be validated.

Read the full summary ↓

Here we characterize the transcriptional landscape of TH-MYCN tumors by single-cell RNA sequencing (scRNA-seq) and developed novel ex vivo tumoroids. We provide a comparative analysis with murine fetal adrenal gland and human NB, to decipher the heterogeneity, cell-cell interactions, and clinical relevance of these models. Integrated analysis with fetal adrenal samples confirmed that both TH-MYCN tumors and tumoroids closely mirror the cellular profiles of normal embryonic sympathoblasts and chromaffin cells. Comprehensive comparison between tumors from NB patients and TH-MYCN mice demonstrated similarities in adrenergic tumor cell composition. Through ex vivo tumoroid cultures, we demonstrated histological resemblance, and shared transcriptional profiles with originating TH-MYCN tumors and human NB. Importantly, we identified subpopulations within tumoroids that exhibit gene expression associated with poor NB patient survival. Notably, recurrent observations of a low-proliferative chromaffin phenotype connected to the highly proliferative sympathetic phenotype may suggest that pushing sympathoblasts into a chromaffin-like state may offer an interesting therapeutic strategy for NB. Together, this study not only deepens our understanding of the widely used transgenic mouse model but also introduces a novel ex vivo model that maintains critical adrenergic cell state identity, thereby enhancing its translational potential for NB research.

This dataset

Open GSE280892 in finder → Find more mouse 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 GSE280892_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 PRJNA1180995 and SRA study SRP542655. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

5 × Hemizygous vs 5 × Homozygous vs 2 × Homozygous 4 Tumoroids Passage vs 2 × Homozygous 5 Tumoroids Passage

Supports a between-group comparison across 14 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 14 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

GSM8607149 Hemizygous 1 Hemizygous
GSM8607150 Hemizygous 2 Hemizygous
GSM8607151 Hemizygous 3 Hemizygous
GSM8607152 Hemizygous 4 Hemizygous
GSM8607153 Hemizygous 5 Hemizygous
GSM8607154 Homozygous 1 Homozygous
GSM8607155 Homozygous 2 Homozygous
GSM8607156 Homozygous 3 Homozygous
GSM8607157 Homozygous 4 Homozygous
GSM8607158 Homozygous 5 Homozygous
GSM8607159 Homozygous 4 Tumoroids Passage 0 Homozygous 4 Tumoroids …
GSM8607160 Homozygous 4 Tumoroids Passage 5 Homozygous 4 Tumoroids …
GSM8607161 Homozygous 5 Tumoroids Passage 0 Homozygous 5 Tumoroids …
GSM8607162 Homozygous 5 Tumoroids Passage 5 Homozygous 5 Tumoroids …

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