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 journalArticle

Abstract

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 (US)
JournalNeuromolecular medicine
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Optogenetics
Neural Stem Cells
Neurogenesis
Opsins
Transcriptome
Transfection
Neuronal Plasticity
Stem Cell Transplantation
Neurosciences
Genes
Axons
Up-Regulation
Neurons
Light
Messenger RNA

Keywords

  • Microarray genomic
  • Neural stem cells
  • Neurogenesis
  • Optogenetics stimulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics. / Teh, Daniel Boon Loong; Prasad, Ankshita; Jiang, Wenxuan; Zhang, Nianchen; Wu, Yang; Yang, Hyunsoo; Han, Sanyang; Yi, Zhigao; Yeo, Yanzhuang; Ishizuka, Toru; Wong, Limsoon; Thakor, Nitish; Yawo, Hiromu; Liu, Xiaogang; All, Angelo.

In: Neuromolecular medicine, 01.01.2019.

Research output: Contribution to journalArticle

Teh, DBL, Prasad, A, Jiang, W, Zhang, N, Wu, Y, Yang, H, Han, S, Yi, Z, Yeo, Y, Ishizuka, T, Wong, L, Thakor, N, Yawo, H, Liu, X & All, A 2019, 'Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics', Neuromolecular medicine. https://doi.org/10.1007/s12017-019-08573-3
Teh, Daniel Boon Loong ; Prasad, Ankshita ; Jiang, Wenxuan ; Zhang, Nianchen ; Wu, Yang ; Yang, Hyunsoo ; Han, Sanyang ; Yi, Zhigao ; Yeo, Yanzhuang ; Ishizuka, Toru ; Wong, Limsoon ; Thakor, Nitish ; Yawo, Hiromu ; Liu, Xiaogang ; All, Angelo. / Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics. In: Neuromolecular medicine. 2019.
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AU - Wong, Limsoon

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