GEO series

Cortical organoids reveal human-specific role of METTL5 in neurodevelopment via regulation of CHCHD2

GSE328362 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2026/06/10 Platform GPL34281

At a glance

Single-cell RNA-seq · human · 12 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: 12 samples: 3 × KOLF_rna vs 3 × KOLF_KO_rna vs 3 × KOLF_rpf vs 3 × KOLF_KO_rpfGroups 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.

Summary (written by the submitters)

METTL5 catalyzes N6-methyladenosine (m6A) modification on 18S rRNA. In humans, loss-of-function mutations in METTL5 cause severe microcephaly and intellectual disability, whereas Mettl5 knockout (KO) animal models display inconsistent and incomplete microcephaly phenotypes. To better model human disease, we generated METTL5-KO human induced pluripotent stem cell (hiPSC)-derived cortical organoids, which exhibited impaired neural progenitor cell (NPC) proliferation and differentiation, leading to reduced ventricle-like structures and more faithful recapitulation of patient phenotypes.

Read the full summary ↓

Mechanistically, Ribo-seq analysis revealed broad translational changes in METTL5-KO NPCs consistent with cellular stress responses rather than transcript-specific translational changes. Single-cell RNA-seq identified downregulation of CHCHD2, a mitochondrial regulator of oxidative metabolism. Reintroduction of CHCHD2 in METTL5-KO NPCs rescued proliferation and partially rescued oxidative metabolism defects. This suggests dysregulation of CHCHD2 is a driver of METTL5-mediated regulation of neurogenesis. These findings highlight a previously uncharacterized link between METTL5, CHCHD2, and cellular metabolism as essential for proper human brain development.

This dataset

Open GSE328362 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 GSE328362_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 PRJNA1454832 and SRA study SRP692709. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

3 × KOLF_rna vs 3 × KOLF_KO_rna vs 3 × KOLF_rpf vs 3 × KOLF_KO_rpf

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9679987 KOLF_rna_rep1 KOLF_rna
GSM9679988 KOLF_rna_rep2 KOLF_rna
GSM9679989 KOLF_rna_rep3 KOLF_rna
GSM9679990 KOLF_KO_rna_rep1 KOLF_KO_rna
GSM9679991 KOLF_KO_rna_rep2 KOLF_KO_rna
GSM9679992 KOLF_KO_rna_rep3 KOLF_KO_rna
GSM9679993 KOLF_rpf_rep1 KOLF_rpf
GSM9679994 KOLF_rpf_rep2 KOLF_rpf
GSM9679995 KOLF_rpf_rep3 KOLF_rpf
GSM9679996 KOLF_KO_rpf_rep1 KOLF_KO_rpf
GSM9679997 KOLF_KO_rpf_rep2 KOLF_KO_rpf
GSM9679998 KOLF_KO_rpf_rep3 KOLF_KO_rpf

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