Single-cell long-read sequencing in human cerebral organoids uncovers cell-type-specific and autism-associated exons.

ABSTRACT: Dysregulation of alternative splicing has been repeatedly associated with neurodevelopmental disorders, but the extent of cell-type-specific splicing in human neural development remains largely uncharted. Here, single-cell long-read sequencing in induced pluripotent stem cell (iPSC)-derived cerebral organoids identifies over 31,000 uncatalogued isoforms and 4,531 cell-type-specific splicing events. Long reads uncover coordinated splicing and cell-type-specific intron retention events, which are challenging to study with short reads. Retained neuronal introns are enriched in RNA splicing regulators, showing shorter lengths, higher GC contents, and weaker 5' splice sites. We use this dataset to explore the biological processes underlying neurological disorders, focusing on autism. In compari

SUBMITTER: Yang Y 

PROVIDER: S-EPMC10842930 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature