Trace elements during primordial plexiform network formation in human cerebral organoids

Systematic studies of micronutrients during brain formation are hindered by restrictions to animal models and adult post-mortem tissues. Recently, advances in stem cell biology have enabled recapitulation of the early stages of human telencephalon development. In the present work, we exposed cerebral organoids derived from human pluripotent stem cells to synchrotron radiation in order to measure how biologically valuable micronutrients are incorporated and distributed in the exogenously developing brain. Our findings indicate that elemental inclusion in organoids is consistent with human brain tissue and involves calcium, iron, phosphorus, potassium, sulfur, and zinc. Local trends in concentrations suggest a switch from passive to actively mediated transport across cell membranes. Finally, correlational analysis for pairs of elements shows spatially conserved patterns, suggesting they may physically associate, be stored in similar compartments or used in related biological processes. These findings might reflect which trace elements are important during human brain development and will support studies aimed to unravel the consequences of disrupted metal homeostasis for neurodevelopmental diseases, including those manifested in adulthood.