Disruption of ADNP-KDM1A-GTF2I complex drives neural differentiation imbalance in Helsmoortel-Van der Aa syndrome [multi-omic]

Here, to characterize HVDAS in a developmental setting, we generated cortical brain organoids of 5 control and 5 HVDAS lines and profiled them by single-cell RNA- and ATAC-seq. Organoids were grown for 30 days using the protocol 10.1016/j.stem.2019.08.002. To reduce batch effects and costs, and maximize coverage in terms of cell number and detected genes, we performed 3 downstream multiplexing 10.1038/s41592-024-02555-5. We grew each line independently, then single-cell dissociated 3 organoids per line, than mixed the cells and performed multiomic (10x GEX+ATAC) on 3 pools of multiple individuals. In silico sample deconvolution was performed by using ScanSNP on bulk RNA-seq from E-MTAB-15963.