Expanding the genetic code to generate human brain organoids with vasculature and microglia

It has not been fully explored in 3D tissues or organoids. Here, we presented a new strategy leveraging GCE-T to generate vascularized human cerebral organoids (vhCOs) containing resident microglia.

By reassigning a premature termination codon in ETV2, a targeted noncanonical amino acid was incorporated to drive endothelial differentiation in hPSCs at the translational level. Strikingly, the generated vhCOs exhibited coordinated differentiation of functional vasculature, blood brain barrier feature and microglia. single-nucleus transcriptomic analysis revealed multiple brain regional distribution, marked neurogenesis, and neuro-vascular-immune network in vhCOs, resembling human fetal brain.