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Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling.

GSE262710 Homo sapiens (human) Single-nucleus RNA-seq 46 samples Submitted 2024/10/02 Platform GPL24676Platform GPL22790
At a glance

Single-nucleus RNA-seq · human · 46 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). 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
46 samples: 12 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
Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modellingMolecular autism · 2024
Summary (written by the submitters)
Background: SETBP1 Haploinsufficiency Disorder (SETBP1-HD) is characterised by mild to moderate intellectual disability, speech and language impairment, mild motor developmental delay, behavioural issues, hypotonia, mild facial dysmorphisms, and vision impairment. Despite a clear link between SETBP1 mutations and neurodevelopmental disorders the precise role of SETBP1 in neural development remains elusive.
Read the full summary ↓
We investigate three SETBP1 genetic variants including two pathogenic mutations p.Glu545Ter and SETBP1 p.Tyr1066Ter, resulting in removal of SKI and/or SET domains, and a point mutation p.Thr1387Met in the SET domain. Methods: Genetic variants were introduced into induced pluripotent stem cells (iPSCs) and subsequently differentiated into neurons to model the disease. We measured changes in cellular differentiation, SETBP1 protein localisation, and gene expression changes. Results: The data indicated a change in the WNT pathway, RNA polymerase II pathway and identified GATA2 as a central transcription factor in disease perturbation. In addition, the genetic variants altered the expression of gene sets related to neural forebrain development matching characteristics typical of the SETBP1-HD phenotype. Limitations: The study investigates changes in cellular function in differentiation of iPSC to neural progenitor cells as a human model of SETBP1 HD disorder. Future studies may provide additional information relevant to disease on further neural cell specification, to derive mature neurons, neural forebrain cells, or brain organoids. Conclusions: We developed a human SETBP1-HD model and identified perturbations to the WNT and POL2RA pathway, genes regulated by GATA2. Strikingly neural cells for both the SETBP1 truncation mutations and the single nucleotide variant displayed a SETBP1-HD-like phenotype.
Published in
Identifying SETBP1 haploinsufficiency molecular pathways to improve patient diagnosis using induced pluripotent stem cells and neural disease modelling
Shaw NC, Chen K, Farley KO et al. · Molecular autism 2024 · PMID 39350244 · doi:10.1186/s13229-024-00625-1
This dataset
Open GSE262710 in finder → Find more human 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 GSE262710_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 PRJNA1093043 and SRA study SRP498476. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39350244) ↗
Study design
12 conditions, mostly in triplicate
KOLF2 cells, SETBP1_WT, Day 0, biol ×6 KOLF2 cells, SETBP1_WT, Day 24, biol ×6 WT ×6 KOLF2 cells, SETBP1_VUS2, Day 0, biol ×4 KOLF2 cells, SETBP1_VUS2, Day 24, biol ×4 KOLF2 cells, SETBP1_PATH2, Day 0, biol ×3 KOLF2 cells, SETBP1_PATH2, Day 24, biol ×3 KOLF2 cells, SETBP1_PATH3, Day 0, biol ×3 +4 more

Supports a between-group comparison across 46 samples.

How we read this: 12 replicated groups read from 46 sample titles; they account for 46 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

+ 6 more — browse all 46 samples with per-sample file links →

Datasets on a similar topic

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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.