Cortical Organoids Expose 10-Fold Rise in RGP Lineage Restriction as Division Timing Diverges
Updated
Updated · Nature.com · Aug 12
Cortical Organoids Expose 10-Fold Rise in RGP Lineage Restriction as Division Timing Diverges
3 articles · Updated · Nature.com · Aug 12
Summary
About one-third of radial glial progenitor clones in mouse cortical organoids were lineage-restricted, versus roughly 3% in vivo, showing sharply reduced diversity in excitatory neuron output.
MADM single-cell lineage tracing found organoid RGPs did not follow the brain’s usual stepwise program: proliferative, asymmetric neurogenic and small neurogenic clone types appeared concurrently, even at early stages.
That altered behavior was not explained by major transcriptional splits in progenitors; single-cell RNA sequencing showed a largely uniform RGP population and one main lineage trajectory from progenitors to neurons.
The organoids still reproduced broad corticogenesis features, including matched developmental stages and a later neurogenesis-to-gliogenesis switch, but clone sizes were smaller and temporal control was less strict than in vivo.
The study points to missing niche signals and other non-cell-autonomous cues in self-organizing organoids as key for faithful cortical lineage timing and full clonal cell-type diversity.