Activated astrocytes enhance the dopaminergic differentiation of stem cells and promote brain repair through bFGF

Fan Yang, Yunhui Liu, Jie Tu, Jun Wan, Jie Zhang, Bifeng Wu, Shanping Chen, Jiawei Zhou, Yangling Mu and Liping Wang ()
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Fan Yang: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Yunhui Liu: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Jie Tu: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Jun Wan: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Jie Zhang: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Bifeng Wu: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Shanping Chen: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Jiawei Zhou: State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Yangling Mu: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences
Liping Wang: Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences

Nature Communications, 2014, vol. 5, issue 1, 1-14

Abstract: Abstract Astrocytes provide neuroprotective effects against degeneration of dopaminergic (DA) neurons and play a fundamental role in DA differentiation of neural stem cells. Here we show that light illumination of astrocytes expressing engineered channelrhodopsin variant (ChETA) can remarkably enhance the release of basic fibroblast growth factor (bFGF) and significantly promote the DA differentiation of human embryonic stem cells (hESCs) in vitro. Light activation of transplanted astrocytes in the substantia nigra (SN) also upregulates bFGF levels in vivo and promotes the regenerative effects of co-transplanted stem cells. Importantly, upregulation of bFGF levels, by specific light activation of endogenous astrocytes in the SN, enhances the DA differentiation of transplanted stem cells and promotes brain repair in a mouse model of Parkinson’s disease (PD). Our study indicates that astrocyte-derived bFGF is required for regulation of DA differentiation of the stem cells and may provide a strategy targeting astrocytes for treatment of PD.

Date: 2014
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DOI: 10.1038/ncomms6627

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