{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328362/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":[" Other","Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328362"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Cortical organoids reveal human-specific role of METTL5 in neurodevelopment via regulation of CHCHD2","description":"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. 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.","dates":{"publication":"2026/06/10"},"accession":"GSE328362","cross_references":{"GSM":["GSM9679993","GSM9679992","GSM9679991","GSM9679990","GSM9679997","GSM9679996","GSM9679995","GSM9679994","GSM9679989","GSM9679988","GSM9679998","GSM9679987"],"GPL":["34281"],"GSE":["328362"],"taxon":["Homo sapiens"]}}