GEO series

Patient TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome

GSE264590 Homo sapiens (human) DNA methylation 10 samples Submitted 2024/06/26 Platform GPL24676

At a glance

DNA methylation · human · 10 samples

What it is: DNA methylationChemical marks on DNA that help switch genes on or off.
Organism: Homo sapiens (human)
Samples: 10 samples
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: Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA MethylomebioRxiv : the preprint server for biology · 2024

Summary (written by the submitters)

Tuberous Sclerosis Complex (TSC) is a debilitating developmental disorder characterized by a variety of clinical manifestations. While benign tumors in the heart, lungs, kidney, and brain are all hallmarks of the disease, often the most severe symptoms of TSC are neurological, including seizures, autism, psychiatric disorders, and intellectual disabilities.

Read the full summary ↓

TSC is caused by a heterozygous loss of function mutation in TSC1 or TSC2 and consequent dysregulation of signaling via mechanistic Target of Rapamycin Complex 1 (mTORC1). While TSC neurological phenotypes are well-documented, it is not yet known how early in neural development TSC1/2-mutant cells diverge from the typical developmental trajectory, and whether such phenotypes are seen in the heterozygous-mutant populations comprising the vast majority of cells in patient tissues. Using TSC patient-derived isogenic induced pluripotent stem cells (iPSCs), we observed aberrant early neurodevelopment in vitro, including misexpression of key transcription factors associated with lineage commitment and premature electrical activity. These alterations in differentiation were coincident with widespread changes in DNA methylation, including at loci associated with key genes in neurodevelopment. Collectively, these data suggest that mutation or loss of TSC2 affects gene regulation and expression at earlier timepoints than previously appreciated, with implications for whether and how prenatal treatment should be pursued.

Published in

Human TSC2 Mutant Cells Exhibit Aberrations in Early Neurodevelopment Accompanied by Changes in the DNA Methylome

Chalkley ML, Guerin LN, Iyer T et al. · bioRxiv : the preprint server for biology 2024 · PMID 38895266 · doi:10.1101/2024.06.04.597443

This dataset

Open GSE264590 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 GSE264590_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 beta-value tables or raw IDAT files among the supplementary files.

Also filed as BioProject PRJNA1103201 and SRA study SRP503388. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 38895266) ↗

Samples in this study

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+ 10 more — browse all 10 samples with per-sample file links →

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