{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE278nnn/GSE278954/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE278954"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Liver Disease Reveals KIF12 as a Critical Regulator of Organelle Localization","description":"Kinesin family member 12 (KIF12) has been implicated in liver disease requiring transplantation in pediatric patients. Single cell RNA-sequencing shows KIF12 expression selectively in biliary cells in healthy human liver. Here, we generated a human KIF12-disease model by introducing a homozygous KIF12 p.Arg219* mutation in induced pluripotent stem cells. These cells were differentiated into 2D cholangiocyte-like cells (iCCs) and 3D biliary organoids. Pioneering single-molecule fluorescence microscopy in live iCCs, we observed wild-type KIF12 co-localizing with microtubules, consistent with prediction of being a microtubule associated motor protein. KIF12 deficiency causes perinuclear clustering of mitochondria and lysosomes, along with aberrant cilia localization. These defects were rescued by viral delivery of wild-type KIF12. Collectively, these findings uncovered a mechanistic link between KIF12 dysfunction, mitochondria, lysosomes, and cilia mispositioning, and biliary pathology. Our study expands the knowledge of kinesins beyond neuronal function and provides a foundation for development of targeted genetic therapies for kinesinopathies.","dates":{"publication":"2026/09/23"},"accession":"GSE278954","cross_references":{"GSM":["GSM8558815","GSM8558814","GSM8558823","GSM8558819","GSM8558818","GSM8558817","GSM8558816","GSM8558822","GSM8558821","GSM8558820"],"GPL":["24676"],"GSE":["278954"],"taxon":["Homo sapiens"],"PMID":["[42727250]"]}}