@article{22753,
  abstract     = {Radial glial progenitors (RGPs) produce all excitatory neurons in the developing cerebral cortex. Mosaic analysis with double markers (MADM)-based lineage tracing in vivo has revealed a quantitative framework of RGP lineage progression1. Here we established MADM technology2,3 in mouse embryonic stem cells to probe RGP lineage progression in a self-organizing cortical organoid system. We found that RGPs exhibit a high level of plasticity in proliferative potential in organoids rather than strict temporally stereotyped lineage progression as observed in vivo. RGPs in organoids showed increased lineage restriction, diminishing cell-type diversity in clones of cortical projection neurons, despite uniform single-cell transcriptional signatures of RGPs and a unitary lineage trajectory. Thus, critical non-cell-autonomous cues that are absent in self-organizing systems and/or the genuine stem cell niche are essential for faithful temporal control of RGP lineage progression and the generation of clonal cortical cell-type diversity.},
  author       = {Stouffer, Melissa A and Miranda, Osvaldo and Pauler, Florian and Pipicelli, Fabrizia and Streicher, Carmen and Cheung, Giselle T and Hippenmeyer, Simon},
  issn         = {1476-4687},
  journal      = {Nature},
  publisher    = {Springer Nature},
  title        = {{Temporal uncoupling of radial glia lineage progression in cortical organoids}},
  doi          = {10.1038/s41586-026-10916-7},
  year         = {2026},
}