Default Patterning Produces Pan-cortical Glutamatergic and CGE/LGE-like GABAergic Neurons from Human Pluripotent Stem Cells

Summary Default differentiation of human pluripotent stem cells has been promoted as a model of cortical development. In this study, a developmental transcriptome analysis of default-differentiated hPSNs revealed a gene expression program resembling in vivo CGE/LGE subpallial domains and GABAergic signaling. A combination of bioinformatic, functional, and immunocytochemical analysis further revealed that hPSNs consist of both cortical glutamatergic and CGE-like GABAergic neurons. This study provides a comprehensive characterization of the heterogeneous group of neurons produced by default differentiation and insight into future directed differentiation strategies.
Highlights • Multiple time point transcriptome analysis of default hPSC differentiation • Resultant neurons resemble a pan-cortical population with multiple layer markers • CGE/LGE-specific transcripts are expressed to near exclusion of MGE markers • Immunocytochemistry reveals CGE markers in hPSN subpopulation
Default differentiation of human pluripotent stem cell-derived neurons (hPSNs) is thought to be a model of cortical differentiation. The authors performed transcriptome, time-course analysis of developing and mature hPSNs. In addition to cortical glutamatergic neurons, default differentiation led to significant CGE/LGE-specific GABAergic patterning. This work comprehensively characterizes the heterogeneity of neurons produced by default differentiation.