Transcriptome and proteome analysis of human brain organoids

During development of the human cerebral cortex, multipotent neural progenitors generate excitatory neurons and glial cells. Investigations of the transcriptome and epigenome have revealed important gene regulatory networks underlying this crucial developmental event. However, the post-transcriptional control of gene expression and protein abundance during human corticogenesis remains poorly understood. We addressed this issue by using a dual reporter cell line to isolate neural progenitors and neurons from the telencephalic brain organoid tissue and performed cell type and developmental stage-specific transcriptome and proteome analysis. Integrating the two datasets revealed temporal modules of gene expression during human corticogenesis, both at RNA and protein level. Our multiomics approach reveals novel posttranscriptional regulatory mechanisms crucial for fidelity of cortical development.