Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics

Daniel Boon Loong Teh, Ankshita Prasad, Wenxuan Jiang, Nianchen Zhang, Yang Wu, Hyunsoo Yang, Sanyang Han, Zhigao Yi, Yanzhuang Yeo, Toru Ishizuka, Limsoon Wong, Nitish Thakor, Hiromu Yawo, Xiaogang Liu, Angelo All

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Optogenetic stimulation of neural stem cells (NSCs) enables their activity-dependent photo-modulation. This provides a spatio-temporal tool for studying activity-dependent neurogenesis and for regulating the differentiation of the transplanted NSCs. Currently, this is mainly driven by viral transfection of channelrhodopsin-2 (ChR2) gene, which requires high irradiance and complex in vivo/vitro stimulation systems. Additionally, despite the extensive application of optogenetics in neuroscience, the transcriptome-level changes induced by optogenetic stimulation of NSCs have not been elucidated yet. Here, we made transformed NSCs (SFO-NSCs) stably expressing one of the step-function opsin (SFO)-variants of chimeric channelrhodopsins, ChRFR(C167A), which is more sensitive to blue light than native ChR2, via a non-viral transfection system using piggyBac transposon. We set up a simple low-irradiance optical stimulation (OS)-incubation system that induced c-fos mRNA expression, which is activity-dependent, in differentiating SFO-NSCs. More neuron-like SFO-NCSs, which had more elongated axons, were differentiated with daily OS than control cells without OS. This was accompanied by positive/negative changes in the transcriptome involved in axonal remodeling, synaptic plasticity, and microenvironment modulation with the up-regulation of several genes involved in the Ca2+-related functions. Our approach could be applied for stem cell transplantation studies in tissue with two strengths: lower carcinogenicity and less irradiance needed for tissue penetration.

Original languageEnglish
Pages (from-to)139-149
Number of pages11
JournalNeuroMolecular Medicine
Issue number1
Publication statusPublished - Mar 2020

User-Defined Keywords

  • Calcium Signaling
  • Cell Line, Transformed
  • Channelrhodopsins/biosynthesis
  • DNA Transposable Elements
  • Gene Expression Regulation/radiation effects
  • Gene Ontology
  • Genes, Reporter
  • Genes, fos
  • Nerve Tissue Proteins/biosynthesis
  • Neural Stem Cells/cytology
  • Neurogenesis/radiation effects
  • Neuronal Plasticity/radiation effects
  • Optogenetics
  • RNA, Messenger/biosynthesis
  • Transcriptome/radiation effects
  • Up-Regulation/radiation effects


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