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Altered extracellular matrix structure and elevated stiffness in a brain organoid model for disease

GSE228926 Homo sapiens (human) Non-coding RNA profiling 31 samples Submitted 2025/01/25 Platform GPL24676
At a glance

Non-coding RNA profiling · human · 31 samples

What it is
Non-coding RNA profilingLevels of RNAs that do not code for proteins, such as miRNA or lncRNA.
Organism
Homo sapiens (human)
Samples
31 samples: 8 conditions, mostly with about 4 replicates eachGroups 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
Altered extracellular matrix structure and elevated stiffness in a brain organoid model for diseaseNature communications · 2025
Summary (written by the submitters)
Mutations in Lissencephaly 1 (LIS1) result in various human brain developmental diseases, such as changes in brain structure, lissencephaly, and epilepsy. RNA-sequencing data from on-chip organoids derived from human embryonic stem cells (hESCs) revealed significant changes in the expression of extracellular matrix (ECM) – related genes in LIS1+/- samples.
Read the full summary ↓
This project examined the biomechanical properties of LIS1+/- mutated and healthy hESCs-derived cortical organoids. A rheological test using the pipette aspiration technique revealed that LIS1+/- cortical organoids are stiffer than control organoids. The increased stiffness of the LIS1+/- cortices was proportional to an increased expression of the nuclear mechano-sensing protein, Lamin A, highlighting the adverse cellular and nuclear changes underlying the stiffening of LIS1+/- organoids. To delineate the ECM composition associated with the stiffening effect in LIS1+/-, healthy and mutated hippocampal and cortical organoids were examined at the protein, mRNA, and miRNA levels. Whole RNA sequencing showed altered expression of multiple collagen-related pathways, including the 'collagens containing ECM' and the 'Collagen trimer' pathways. Differential mRNA expression has inversely correlated with the expression of their targeting miRNAs in the LIS1+/- organoids. This inverse miRNA-mRNA expression was most pronounced in genes associated with the ECM-receptor signalling pathway. At the protein level, the mutated hippocampal organoids showed unilateral, substantial increased expression of collagens and proteins involved in collagen synthesis, modification, and remodelling. Following a collagenolytic treatment with the catalytic domain of the MMP9 enzyme, the stiffness levels in the LIS1+/- organoids were reduced to control values. Overall, this work provides new information about the role of LIS1 in controlling collagen expression and the abnormal mechanical properties associated with mutation to the LIS1 gene in the development of the human cortex and hippocampus.
Published in
Altered extracellular matrix structure and elevated stiffness in a brain organoid model for disease
Karlinski Zur M, Bhattacharya B, Solomonov I et al. · Nature communications 2025 · PMID 40312467 · doi:10.1038/s41467-025-59252-w
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 GSE228926_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.

Also filed as BioProject PRJNA952199 and SRA study SRP430842. Searching any of these in the dataset finder brings you back here.

Study design
8 conditions, mostly with about 4 replicates each
RNA-seq - Wild type organoid day 105, repeat # ×4 RNA-seq - LIS1+/- organoid day 105, repeat # ×4 small RNA-seq - Wild type organoid day 105, r… ×4 small RNA-seq - LIS1+/- organoid day 105, rep… ×4 RNA-seq - Wild type Cntrl organoid day 18, re… ×4 RNA-seq - LIS1+/- Cntrl organoid day 18, repe… ×4 RNA-seq - LIS1+/- MMP9 Treated organoid day 1… ×4 RNA-seq - Wild type MMP9 Treated organoid day… ×3

Supports a case/control comparison: 4 samples read as cases, 12 as controls.

How we read this: 8 replicated groups read from 31 sample titles; they account for 31 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
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