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Direct Reprogramming of Astrocytes into Functional Serotonergic Neurons

66 Pages Posted: 12 Oct 2018 Sneak Peek Status: Under Review

See all articles by Sue Han

Sue Han

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Yi Wang

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Yueguang Liu

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Guangdun Peng

Chinese Academy of Sciences (CAS), Shanghai Institutes for Biological Sciences, Institute of Biochemistry and Cell Biology, State Key Laboratory of Cell Biology

Guizhong Cui

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

Jiehui Chen

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

Yudong Hu

Jiangnan University - School of Biotechnology

Wenliang Wang

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Sanlan Li

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Zhiping Rao

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Fei Liu

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Yuhan Shi

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Yijie Zhang

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Feng Zhu

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Jiacheng Yuan

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Junlan Geng

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Naihe Jing

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

Leping Cheng

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

More...

Abstract

Serotonergic neurons project widely in the central nervous system and regulate a variety of behaviors. Obtaining induced serotonergic neurons (iSNs) iscritical for disease modeling, drug screening and cell therapy. Here, we found that a combination of transcription factors Ascl1, Nkx2.2, Gata2, Foxa2, and Lmx1b could convert postnatal astrocytes into functional serotonergic neurons. We further found that the iSNs expressed serotonergic neuron-specific markers and exhibited similar electrophysiological properties with native serotonergic neurons. More importantly, using an optogenetic stimulation protocol, we demonstrated that the iSNs could form synaptic connections with co-cultured neurons in dishes. Last, after transplanted into the mouse brain, astrocyte-derived iSNs survived, expressed appropriate molecular markers, and matured gradually in vivo. Taken together, our results showed that defined transcription factors were able to convert astrocytes into functional serotonergic neurons andthus provided an alternative option for generate sufficient numbers of a new neuronal subtype for therapeutic therapy.

Suggested Citation

Han, Sue and Wang, Yi and Liu, Yueguang and Peng, Guangdun and Cui, Guizhong and Chen, Jiehui and Hu, Yudong and Wang, Wenliang and Li, Sanlan and Rao, Zhiping and Liu, Fei and Shi, Yuhan and Zhang, Yijie and Zhu, Feng and Yuan, Jiacheng and Geng, Junlan and Jing, Naihe and Cheng, Leping, Direct Reprogramming of Astrocytes into Functional Serotonergic Neurons (October 11, 2018). Available at SSRN: https://ssrn.com/abstract=3264941 or http://dx.doi.org/10.2139/ssrn.3264941
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Sue Han

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Yi Wang

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Yueguang Liu

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Guangdun Peng

Chinese Academy of Sciences (CAS), Shanghai Institutes for Biological Sciences, Institute of Biochemistry and Cell Biology, State Key Laboratory of Cell Biology

Shanghai
China

Guizhong Cui

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

320 Yue Yang Road
Shanghai, 200031
China

Jiehui Chen

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

320 Yue Yang Road
Shanghai, 200031
China

Yudong Hu

Jiangnan University - School of Biotechnology

China

Wenliang Wang

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Sanlan Li

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Zhiping Rao

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Fei Liu

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Yuhan Shi

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Yijie Zhang

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Feng Zhu

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Jiacheng Yuan

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Junlan Geng

Chinese Academy of Sciences (CAS) - Institute of Neuroscience

Wuhan, 430071
China

Naihe Jing

Chinese Academy of Sciences (CAS) - Institute of Biochemistry and Cell Biology

320 Yue Yang Road
Shanghai, 200031
China

Leping Cheng (Contact Author)

Chinese Academy of Sciences (CAS) - Institute of Neuroscience ( email )

Wuhan, 430071
China

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