Neutral competition explains the clonal composition of neural organoids

• DOI: 10.1371/journal.pcbi.1012054
• Publication Date: 2024-04-22T17:30:55Z
• Authors: Florian G. Pflug; Simon Haendeler; Christopher Esk; Dominik Lindenhofer; Jürgen A. Knoblich; Arndt von Haeseler
• Keywords: Organoid; Lineage (genetic); Cell lineage; Corticogenesis

Neural organoids model the development of human brain and are an indispensable tool for studying neurodevelopment. Whole-organoid lineage tracing has revealed number progenies arising from each initial stem cell to be highly diverse, with sizes ranging one more than 20,000 cells. This high variability exceeds what can explained by existing stochastic models corticogenesis indicates existence additional source stochasticity. To explain this variability, we introduce SAN which distinguishes Symmetrically diving, Asymmetrically dividing, Non-proliferating In model, stochasticity is survival time a lineage’s pool symmetrically dividing These times result neutral competition within sub-population all We demonstrate that our explains experimentally observed derive quantitative relationship between size. also show implies regulatory mechanism keeps size population constant. Our results provide insight into clonal composition neural how it arises. relevant many applications organoids, similar processes may occur in other developing tissues both vitro vivo .