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

Stem Cell Reports. 2017 Nov 14;9(5):1463-1476. doi: 10.1016/j.stemcr.2017.09.023. Epub 2017 Oct 26.

Abstract

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.

Keywords: CALB2; CGE; COUPTFII; cortical neurons; development; human pluripotent stem cells; microarray; subpallium.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • COUP Transcription Factor II / genetics
  • COUP Transcription Factor II / metabolism
  • Calbindin 2 / genetics
  • Calbindin 2 / metabolism
  • Cells, Cultured
  • GABAergic Neurons / cytology*
  • GABAergic Neurons / metabolism
  • Gene Expression Regulation, Developmental*
  • Glutamic Acid / metabolism
  • Humans
  • Neurogenesis*
  • Pluripotent Stem Cells / cytology*
  • Pluripotent Stem Cells / metabolism
  • Transcriptome

Substances

  • CALB2 protein, human
  • COUP Transcription Factor II
  • Calbindin 2
  • NR2F2 protein, human
  • Glutamic Acid