biostudies-literaturePflug FGEU Horizon 2020Austrian Science Fund FWFAustrian Academy of SciencesVienna BioCentere1012054https://www.ebi.ac.uk/biostudies/studies/S-EPMC11065252biostudies-literatureUnknown20(4)Neural organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progenies arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This high variability exceeds what can be explained by existing stochastic models of corticogenesis and indicates the existence of an additional source of stochasticity. To explain this variability, we introduce the SAN model which distinguishes Symmetrically diving, Asymmetrically dividing, and Non-proliferating cells. In the SAN model, the additional source of stochasticity is the survival time of a lineage's pool of symmetrically dividing cells. These survival times result from neutraPLoS computational biologyNeutral competition explains the clonal composition of neural organoids.PMC11065252SFB-F7811-BDoctoral Program874769SFB-F7804-BKnoblich JAEsk CLindenhofer DHaendeler SPflug FGvon Haeseler AfalseNeutral competition explains the clonal composition of neural organoids.Neural organoids model the development of the human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed the number of progenies arising from each initial stem cell to be highly diverse, with lineage sizes ranging from one to more than 20,000 cells. This high variability exceeds what can be explained by existing stochastic models of corticogenesis and indicates the existence of an additional source of stochasticity. To explain this variability, we introduce the SAN model which distinguishes Symmetrically diving, Asymmetrically dividing, and Non-proliferating cells. In the SAN model, the additional source of stochasticity is the survival time of a lineage's pool of symmetrically dividing cells. These survival times result from neutra2024-01-01T00:00:00Z2024 Apr2026-06-02T08:35:56.474Z2026-05-26T03:06:58.235ZS-EPMC110652523864825010.1371/journal.pcbi.1012054