Functional control of transplantable human ESC-derived neurons via optogenetic targeting

Jason P. Weick, Michael Johnson, Steven P. Skroch, Justin C. Williams, Karl Deisseroth, Su Chun Zhang

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Current methods to examine and regulate the functional integration and plasticity of human ESC (hESC)-derived neurons are cumbersome and technically challenging. Here, we engineered hESCs and their derivatives to express the light-gated channelrhodopsin-2 (ChR2) protein to overcome these deficiencies. Optogenetic targeting of hESC-derived neurons with ChR2 linked to the mCherry fluorophore allowed reliable cell tracking as well as light-induced spiking at physiological frequencies. Optically induced excitatory and inhibitory postsynaptic currents could be elicited in either ChR2+ or ChR2 - neurons in vitro and in acute brain slices taken from transplanted severe combined immunodeficient (SCID) mice. Furthermore, we created a clonal hESC line that expresses ChR2-mCherry under the control of the synapsin-1 promoter. On neuronal differentiation, ChR2-mCherry expression was restricted to neurons and was stably expressed for at least 6 months, providing more predictable light-induced currents than transient infections. This pluripotent cell line will allow both in vitro and in vivo analysis of functional development as well as the integration capacity of neuronal populations for cell-replacement strategies.

Original languageEnglish (US)
Pages (from-to)2008-2016
Number of pages9
JournalStem Cells
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2010
Externally publishedYes

Keywords

  • AMPA
  • Channelrhodopsin-2
  • GABA
  • Human embryonic stem cells
  • Neurodegeneration
  • Synapsin-1
  • Transplantation

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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