Details

Autor(en) / Beteiligte

• 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

Titel

Driving Neurogenesis in Neural Stem Cells with High Sensitivity Optogenetics

Ist Teil von

• Neuromolecular medicine, 2020-03, Vol.22 (1), p.139-149

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2020

Quelle

SpringerNature Journals

Beschreibungen/Notizen

• 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 Ca 2+ -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.