Here we describe the gene expression changes that occur as MGE-like cells are generated from hESCs. We performed extensive transcriptional profiling of subpopulation and single-cells using RNAseq at multiple timepoints to characterize the diversity and maturation status of these cells. We compared the transcriptomes of interneurons generated using this protocol to in vivo-derived human fetal interneurons using principal component analysis (PCA) to place them in temporal and developmental context. Our single-cell RNAseq (scRNA-seq) analysis revealed 41 distinct populations of progenitors, neurons and glia over the course of the differentiation protocol. We identified a set of genes associated with SST+ interneuron maturation. This study is the first to characterize the diversity and dynamic transcriptomic changes of human MGE progenitors and neurons generated in vitro at single-cell resolution, and the first transcriptomic comparison between human fetal interneurons and hESC-derived human interneurons.
