Human basal radial glia morphotypes are transcriptionally distinct and exhibit different cell fate determination
Basal radial glia (bRG) are key neural progenitors driving human neocortical expansion. They are characterized by remarkable morphological heterogeneity, yet how stable different morphotypes are and how they relate to cellular identity remains unclear. Using human cortical organoids combined with long-term live imaging and morphology-resolved spatial transcriptomics, CellShape-seq, we show that bRG morphotypes exhibit distinct morphodynamic behaviors, proliferative capacities and transcriptional profiles. While multipolar and monopolar bRG inherit mother cell's morphology, bifurcated cells generate morphologically diverse progeny. Instead, in interphase multipolar cells display morphological flexibility while other morphotypes remain stable. Multipolar cells further show the greatest proliferative capacity and the transcriptional signature related to progenitor state. Bifurcated bRG have the lowest proliferative capacity and are characterized by expression of RNA- and chromatin-associated YBX1. Pharmacological inhibition of YBX1 depleted bifurcated bRG and promoted glial commitment. Our findings link progenitor morphology, gene expression and fate, providing a new framework for understanding the cellular logic of human cortical development.