{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301365/"]},"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=GSE301365"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell analysis of human iPSC-derived midbrain organoids generated with triphasic Wnt modulation combined with a dynamic bioreactor","description":"Human midbrain organoids (hMOs) derived from induced pluripotent stem cells offer a promising platform to model Parkinson’s disease (PD), but current systems often fall short in generating mature, regionally specified dopaminergic (DA) neurons that reflect disease-relevant vulnerabilities. Here, we present a refined differentiation strategy that combines tri-phasic WNT signaling modulation with dynamic bioreactor cultivation to enhance DA neuron yield, specification, and maturation within hMOs. This approach generated DA neurons with enriched substantia nigra-like identity (GIRK2⁺, ALDH1A1⁺), elevated dopamine release, and robust functional activity. Single cell transcriptomic profiling revealed upregulation of synaptic, metabolic, and neuroprotective pathways within the DA neuron cluster, while stress-related and pro-apoptotic programs were suppressed. Importantly, these hMOs exhibited selective vulnerability upon challenge with α-synuclein preformed fibrils (aSyn-PFFs), modeling PD-relevant neurodegeneration. Together, our findings establish a scalable, physiologically relevant platform for investigating PD mechanisms, therapeutic screening and advancing the development of cell replacement strategies.","dates":{"publication":"2026/06/03"},"accession":"GSE301365","cross_references":{"GSM":["GSM9081661","GSM9081662","GSM9081640","GSM9081641","GSM9081663","GSM9081664","GSM9081642","GSM9081665","GSM9081643","GSM9081644","GSM9081645","GSM9081646","GSM9081647","GSM9081648","GSM9081649","GSM9081650","GSM9081651","GSM9081652","GSM9081653","GSM9081654","GSM9081655","GSM9081656","GSM9081657","GSM9081658","GSM9081636","GSM9081659","GSM9081637","GSM9081638","GSM9081639","GSM9081660"],"GPL":["34281"],"GSE":["301365"],"taxon":["Homo sapiens"]}}