Retinal stem cells yield all retinal cell types, but their embryonic origin is elusive. Using a Zebrabow-based clonal analysis and in vivo lineage analyses, Tang et al. identify bipotent progenitors as the cell of origin of retinal stem cells.

Multidimensional landscapes of regulatory genes in neuronal phenotypes at whole-brain levels in the vertebrate remain elusive. We generated single-cell transcriptomes of ~67,000 region- and glutamatergic/neuromodulator-identifiable cells from larval zebrafish brains. Hierarchical clustering based on effector gene profiles ('terminal features') distinguished major brain cell types. Sister clusters at hierarchical termini displayed similar terminal features. It was further verified by a population-level statistical method. Intriguingly, glutamatergic/GABAergic sister clusters mostly expressed distinct transcriptional factor (TF) profiles ('convergent pattern'), whereas neuromodulator-type sister clusters predominantly expressed the same TF profiles ('matched pattern'). Interestingly, glutamatergic/GABAergic clusters with similar TF profiles could also display different terminal features ('divergent pattern'). It led us to identify a library of RNA-binding proteins that differentially marked divergent pair clusters, suggesting the post-transcriptional regulation of neuron diversification. Thus, our findings reveal multidimensional landscapes of transcriptional and post-transcriptional regulators in whole-brain neuronal phenotypes in the zebrafish brain.