Gene expression responses to oxygen challenge in a panel of human brain organoids

The human brain is highly sensitive to oxygen availability, and hypoxia is a common risk factor for neurological and cognitive traits throughout life. Hypoxia exerts distinct effects on different brain cell types, many of which involve changes in gene expression. We used brain organoids derived from genotyped human iPSC lines to characterize gene expression at single-cell resolutions under normoxic conditions and both hypoxic and hyperoxic challenges. Brain organoids were differentiated from 21 Yoruba iPSC lines. After 7 weeks of in vitro culture, organoids were adapted to normoxic (10% oxygen) conditions for one week prior to sample collection. After 8 weeks in culture, organoids were acutely exposed to 24 hours of hypoxia (1% oxygen) or hyperoxia (atmospheric 21% oxygen). Organoids were then dissociated and lines were pooled for single-cell RNA-seq processing using the 10x Genomics HT v3.1 kit. Data collection was performed in two separate batches, with 16 lines in batch 1, 7 lines in batch 2, and 2 lines common to both.