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Theranostics 2024; 14(4):1701-1719. doi:10.7150/thno.92700 This issue Cite

Research Paper

Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling

Guodong Wang1,2*, Dandan Zhang1*, Liangshan Qin1,2, Quanhui Liu1,2, Wenkui Tang1,2, Mingxing Liu1,2, Fan Xu1, Fen Tang1, Leping Cheng3, Huiming Mo3, Xiang Yuan1, Zhiqiang Wang1, Ben Huang1✉

1. Guangxi Key Laboratory of Eye Health, Department of Technical Support, The People's Hospital of Guangxi Zhuang Autonomous Region, Guangxi Academy of Medical Sciences, Nanning, 530021, China.
2. School of Animal Science and Technology, Guangxi University, Nanning, 530005, Guangxi, China.
3. Key Laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education, Guangxi-ASEAN Collaborative Innovation Center for Major Disease Prevention and Treatment, and Guangxi Key Laboratory of Regenerative Medicine, Center for Translational Medicine, Guangxi Medical University, Nanning, 530021, China.
*Guodong Wang and Dandan Zhang contributed equally to this study.

✉ Corresponding author: E-mail addresses: benhuangedu.cn/bhuangorg.cn (B. Huang); Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Ben Huang.

Citation:
Wang G, Zhang D, Qin L, Liu Q, Tang W, Liu M, Xu F, Tang F, Cheng L, Mo H, Yuan X, Wang Z, Huang B. Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling. Theranostics 2024; 14(4):1701-1719. doi:10.7150/thno.92700. https://www.thno.org/v14p1701.htm
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Abstract

Graphic abstract

Human somatic cells can be reprogrammed into neuron cell fate through regulation of a single transcription factor or application of small molecule cocktails.

Methods: Here, we report that forskolin efficiently induces the conversion of human somatic cells into induced neurons (FiNs).

Results: A large population of neuron-like phenotype cells was observed as early as 24-36 h post-induction. There were >90% TUJ1-, >80% MAP2-, and >80% NEUN-positive neurons at 5 days post-induction. Multiple subtypes of neurons were present among TUJ1-positive cells, including >60% cholinergic, >20% glutamatergic, >10% GABAergic, and >5% dopaminergic neurons. FiNs exhibited typical neural electrophysiological activity in vitro and the ability to survive in vitro and in vivo more than 2 months. Mechanistically, forskolin functions in FiN reprogramming by regulating the cAMP-CREB1-JNK signals, which upregulates cAMP-CREB1 expression and downregulates JNK expression.

Conclusion: Overall, our studies identify a safer and efficient single-small-molecule-driven reprogramming approach for induced neuron generation and reveal a novel regulatory mechanism of neuronal cell fate acquisition.

Keywords: Chemically induced neurons (ciNs), Somatic cell transdifferentiation, Forskolin, CREB1-JNK, Regulatory network

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APA
Wang, G., Zhang, D., Qin, L., Liu, Q., Tang, W., Liu, M., Xu, F., Tang, F., Cheng, L., Mo, H., Yuan, X., Wang, Z., Huang, B. (2024). Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling. Theranostics, 14(4), 1701-1719. https://doi.org/10.7150/thno.92700.

ACS
Wang, G.; Zhang, D.; Qin, L.; Liu, Q.; Tang, W.; Liu, M.; Xu, F.; Tang, F.; Cheng, L.; Mo, H.; Yuan, X.; Wang, Z.; Huang, B. Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling. Theranostics 2024, 14 (4), 1701-1719. DOI: 10.7150/thno.92700.

NLM
Wang G, Zhang D, Qin L, Liu Q, Tang W, Liu M, Xu F, Tang F, Cheng L, Mo H, Yuan X, Wang Z, Huang B. Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling. Theranostics 2024; 14(4):1701-1719. doi:10.7150/thno.92700. https://www.thno.org/v14p1701.htm

CSE
Wang G, Zhang D, Qin L, Liu Q, Tang W, Liu M, Xu F, Tang F, Cheng L, Mo H, Yuan X, Wang Z, Huang B. 2024. Forskolin-driven conversion of human somatic cells into induced neurons through regulation of the cAMP-CREB1-JNK signaling. Theranostics. 14(4):1701-1719.

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