GEO series

Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer (scRNA-Seq)

GSE247451 Mus musculus (mouse) Single-cell RNA-seq 21 samples Submitted 2024/09/06 Platform GPL21273Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 21 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: 21 samples: 21 samples, each with a distinct title — no replicated groupsGroups 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: Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancerNature genetics · 2024

Summary (written by the submitters)

Carriers of germline BRCA1 mutations face a high risk of developing breast cancer; however, the mechanisms underlying this tumor predisposition are not completely understood. Here, using a newly developed genetically engineered mouse model for germline Brca1 heterozygosity that allows spatiotemporal control of full Brca1 inactivation, we demonstrate that the early tumor onset in a Brca1-heterozygous background cannot be fully explained by the conventional “two-hit” hypothesis.

Read the full summary ↓

Specifically, when both Brca1-heterozygous and wild-type conditional mice are induced to Brca1 nullizygosity simultaneously, heterozygous mice develop tumors sooner, suggesting the existence of inherent tumor-promoting alterations in the Brca1-heterozygous state prior to tumor formation. Single-cell RNA-seq and ATAC-seq analyses uncover a unique set of differentially accessible chromatin regions in ostensibly normal Brca1-heterozygous mammary epithelial cells, distinct from wild-type cells and partially mimicking the chromatin and RNA-level changes in tumor cells, thereby pointing to an epigenetic priming mechanism for promoting early tumor onset in the Brca1-heterozygous background. Transcription factor analyses of the altered chromatin regions identify loss of ELF5 and gain of AP-1 binding sites in association with these epigenetically primed chromatin regions, and in vivo experiment reveals that Brca1-heterozygous mice are reliant on the AP-1 pathway for accelerated tumorigenesis. Finally, analysis of downstream target genes identifies Wnt10a as a candidate driver of early tumor onset, and functional experiments demonstrate that it activates the WNT pathway and is sufficient to substantially accelerate tumor formation. Taken together, these findings provide the first in vivo demonstration of a role of BRCA1 haploinsufficiency in accelerating tumor formation and implicate AP-1 and WNT10A as promoters of tumor formation in BRCA1-related breast cancer, advancing our understanding of the disease and informing potential strategies for therapeutic intervention.

Published in

Brca1 haploinsufficiency promotes early tumor onset and epigenetic alterations in a mouse model of hereditary breast cancer

Li CM, Cordes A, Oliphant MUJ et al. · Nature genetics 2024 · PMID 39528827 · doi:10.1038/s41588-024-01958-6

This dataset

Open GSE247451 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 GSE247451_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 PRJNA1037578 and SRA study SRP471174. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39528827) ↗

Study design

21 samples, each with a distinct title — no replicated groups

Supports a case/control comparison: 4 samples read as cases, 7 as controls.

How we read this: Read from 21 sample titles: 21 distinct titles with little repetition. 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

GSM7890131 Tumor_WT_a
GSM7890132 Tumor_WT_b
GSM7890133 Tumor_WT_c
GSM7890134 Tumor_HET_a
GSM7890135 Tumor_HET_b
GSM7890136 Tumor_HET_c
GSM7890137 Tumor_HET_d
GSM7890138 Young_WT_a
GSM7890139 Young_WT_b
GSM7890140 Young_WT_c
GSM7890141 Young_HET_a
GSM7890142 Young_HET_b
GSM7890143 Young_HET_c
GSM7890144 Aged_WT_a
GSM7890145 Aged_WT_b
GSM7890146 Aged_WT_c
GSM7890147 Aged_WT_d
GSM7890148 Aged_HET_a
GSM7890149 Aged_HET_b
GSM7890150 Aged_HET_c
GSM7890151 Aged_HET_d

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