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Mis-splicing of mitotic regulators sensitizes SF3B1-mutated human HSCs to CHK1 inhibition [RNA-seq]

GSE263299 Homo sapiens (human) Single-cell RNA-seq 10 samples Submitted 2024/05/29 Platform GPL20795
At a glance

Single-cell RNA-seq · human · 10 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
10 samples: 8 distinct titles, 2 of them repeatedGroups 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
Mis-splicing of Mitotic Regulators Sensitizes SF3B1-Mutated Human HSCs to CHK1 InhibitionBlood cancer discovery · 2024
Summary (written by the submitters)
Splicing factor SF3B1 mutations are frequent somatic lesions in myeloid neoplasms that transform hematopoietic stem cells (HSCs) by inducing mis-splicing of target genes. However, the molecular and functional consequences of SF3B1 mutations in human HSCs remain unclear. Here, we identify the mis-splicing program in human HSCs as a targetable vulnerability by precise gene editing of SF3B1 K700E mutations in primary CD34+ cells.
Read the full summary ↓
Mutant SF3B1 induced pervasive mis-splicing and reduced expression of genes regulating mitosis in single cell transcriptomics, critically BUBR1 and CDC27, leading to altered differentiation and delayed G2/M progression. Mutant SF3B1 mis-splicing or reduced expression of BUBR1 and CDC27 was sufficient to delay G2/M transit, leading to activation of CHK1, sensitizing cells to CHK1 inhibition. Clinical CHK1 inhibitor prexasertib selectively targeted SF3B1-mutant HSCs and abrogated engraftment in vivo. These findings identify mis-splicing of mitotic regulators in SF3B1-mutant HSCs as a targetable vulnerability engaged by pharmacological CHK1 inhibition.
Published in
Mis-splicing of Mitotic Regulators Sensitizes SF3B1-Mutated Human HSCs to CHK1 Inhibition
Sarchi M, Clough CA, Crosse EI et al. · Blood cancer discovery 2024 · PMID 38856693 · doi:10.1158/2643-3230.BCD-23-0230
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 GSE263299_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: 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 PRJNA1096661 and SRA study SRP499974. Searching any of these in the dataset finder brings you back here.

Study design
8 distinct titles, 2 of them repeated
K562 WT ×2 K562 MUT ×2

Supports a case/control comparison: 3 samples read as cases, 5 as controls.

How we read this: Read from 10 sample titles: 8 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
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