The complexity of human neurobiology is influenced by its heterogeneity, reflected in both cell type diversity as well as genetic variations between individuals. Neural organoids are 3D developing neural tissues designed to mimic development of the nervous system; however, most currently fail to capture this diversity. Recent advances have focused on increasing complexity through self-organised multi-region organoids, assembloids and chimeroids. Here, we discuss these approaches, as well as the remaining lack of genetic and ethnic diversity in neural organoid research, its impact on the generalizability of findings, and strategies to address this gap. We provide a flowchart to guide the experimenter towards the choice of model and discuss applications of neural organoids that benefit from complexity or reliability.
Keywords: assembloids; brain development; chimeroids; disease modelling; genetic diversity; neural organoids; pluripotent stem cells; tissue complexity.
© 2026 MRC Laboratory of Molecular Biology. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.