GSE185671
Diversification of multipotential postmitotic mouse retinal  Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
The genesis of broad neuronal classes from multipotential neural progenitor cells has been extensively studied, but less is known about the diversification of a single neuronal class into multiple types. We used single-cell RNA-seq to study how newly-born (postmitotic) mouse retinal ganglion cell (RGC) precursors diversify into ~45 discrete types. Computational analysis provides evidence that RGC type identity is not specified at mitotic exit, but acquired by gradual, asynchronous fate restriction of postmitotic multipotential precursors. Some types are not identifiable until a week after they are generated. Immature RGCs may be specified to project ipsilaterally or contralaterally to the rest of the brain before their type identity has been determined. Optimal transport inference identifies groups of RGC precursors with largely non-overlapping fates, distinguished by selectively expressed transcription factors that could act as fate determinants. Our study provides a framework for investigating the molecular diversification of discrete types within a neuronal class. Overall design: We profiled and analyzed RGCs at 5 developing stages: E13 and E14 (during the period of peak RGC genesis), E16 (by which time RGCs axons are reaching target retinorecipient areas), P0 (as dendrite elaboration begins), and P5 (shortly after RGCs begin to receive synapses).