Efficient generation of region-specific forebrain neurons from human pluripotent stem cells under highly defined condition

Fang Yuan, Kai-Heng Fang, Shi-Ying Cao, Zhuang-Yin Qu, Qi Li, Robert Krencik, Min Xu, Anita Bhattacharyya, Yu-Wen Su, Dong-Ya Zhu, Yan Liu

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Human pluripotent stem cells (hPSCs) have potential to differentiate to unlimited number of neural cells, which provide powerful tools for neural regeneration. To date, most reported protocols were established with an animal feeder system. However, cells derived on this system are inappropriate for the translation to clinical applications because of the introduction of xenogenetic factors. In this study, we provided an optimized paradigm to generate region-specific forebrain neurons from hPSCs under a defined system. We assessed five conditions and found that a vitronectin-coated substrate was the most efficient method to differentiate hPSCs to neurons and astrocytes. More importantly, by applying different doses of purmorphamine, a small-molecule agonist of sonic hedgehog signaling, hPSCs were differentiated to different region-specific forebrain neuron subtypes, including glutamatergic neurons, striatal medium spiny neurons, and GABA interneurons. Our study offers a highly defined system without exogenetic factors to produce human neurons and astrocytes for translational medical studies, including cell therapy and stem cell-based drug discovery.

Original languageEnglish (US)
Pages (from-to)18550
JournalScientific Reports
Volume5
DOIs
StatePublished - Dec 16 2015

Keywords

  • Cell Culture Techniques
  • Cell Differentiation
  • Cell Line
  • Humans
  • Neurons
  • Pluripotent Stem Cells
  • Prosencephalon
  • Journal Article

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