Degeneration and dysfunction of dopaminergic (DA) neurons are involved in Parkinson’s disease (PD), and direct differentiation of embryonic stem cells (ESCs) into DA neurons may provide a source of cell transplantation therapy for PD. Emerging studies have demonstrated that astrocytes play important roles in midbrain DA neuron development and secreting trophic factors, such as  basic fibroblast growth factor (bFGF), to protect DA neurons. It remains unclear that astrocyte-derived bFGF is sufficient to induce DA differentiation of stem cells and thereby enhance brain repair in a PD model.

A research group led by Prof WANG Liping at Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences used an optogenetic tool to investigate the effects of specific activation of individual astrocyte populations on the DA differentiation of stem cells and the underlying mechanisms. They found that the light-activated astrocytes upregulated the synthesis of bFGF in a tissue-specific manner and significantly promoted the DA differentiation of the hESCs. Most importantly, specific activation of endogenous astrocytes in the SN through an optogenetic approach promoted the astrocyte specific bFGF release in situ, which substantially enhanced the DA differentiation of transplanted stem cells and promoted the regenerative effects in a mouse model of PD. These results were published in Nature Communications ( 2014. DOI: 10.1038/ncomms6627.)

This study first discovered that the specific activation of midbrain astrocytes increased the synthesis and release of bFGF, which directed the differentiation of the transplanted hESCs to DA neurons. Using the optogenetic approach to regulate astrocytes in a tissue-specific manner would also be helpful to dissect the elaborate interactions between astrocytes and neurons in PD, which will contribute to the further understanding the biological role of the astrocytes in neural degenerative disease.

The work was supported by the National Natural Sciences Foundation of China, the National Basic Research Program of China (973 program), and the Chinese Academy of Sciences.

Schematic drawing for the molecular mechanism of the light induced bFGF release to enhance the neural/dopaminergic differentiation of human embryonic stem cells (Image by SIAT)

Contact:
WANG Liping, Ph. D.
Shenzhen Key Lab of Neuropsychiatric Modulation, CAS Center for Excellence in Brain Science, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China
Tel: 0755-86392218, Email: lp.wang@siat.ac.cn