Single cell enhancer activity distinguishes GABAergic and cholinergic lineages in embryonic mouse basal ganglia

Abstract

Significance During brain development, neurons are generated by spatially and temporally distinct processes that remain to be fully characterized. The ganglionic eminences (GEs) in the embryonic subpallium give rise to GABAergic and cholinergic neuron lineages that form the basal ganglia or migrate to the cerebral cortex. Beyond a limited set of canonical RNA markers, the transcriptional states of GE progenitors and immature neurons cells remain poorly defined. We combine enhancer labeling, single-cell transcriptomics using transcription factor-anchored clustering, and integration with in situ hybridization data to distinguish emerging neuronal populations in embryonic mouse basal ganglia. Our results demonstrate the specificity of enhancer-based labeling at single-cell resolution and reveal developmental origins and specification processes of critical neuronal lineages.