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MiR-124 and Small Molecules Synergistically Regulate the Generation of Neuronal Cells from Rat Cortical Reactive Astrocytes

Zheng, Yangyang, Huang, Zhehao, Xu, Jinying, Hou, Kun, Yu, Yifei, Lv, Shuang, Chen, Lin, Li, Yulin, Quan, Chengshi, Chi, Guangfan·2021·Molecular Neurobiology
DOI 10.1007/s12035-021-02345-6
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Abstract

Irreversible neuron loss caused by central nervous system injuries usually leads to persistent neurological dysfunction. Reactive astrocytes, because of their high proliferative capacity, proximity to neuronal lineage, and significant involvement in glial scarring, are ideal starting cells for neuronal regeneration. Having previously identified several small molecules as important regulators of astrocyte-to-neuron reprogramming, we established herein that miR-124, ruxolitinib, SB203580, and forskolin could co-regulate rat cortical reactive astrocyte-to-neuron conversion. The induced cells had reduced astroglial properties, displayed typical neuronal morphologies, and expressed neuronal markers, reflecting 25.9% of cholinergic neurons and 22.3% of glutamatergic neurons. Gene analysis revealed that induced neuron gene expression patterns were more similar to that of primary neurons than of initial reactive astrocytes. On the molecular level, miR-124-driven neuronal differentiation of reactive astrocytes was via targeting of the SOX9-NFIA-HES1 axis to inhibit HES1 expression. In conclusion, we present a novel approach to inducing endogenous rat cortical reactive astrocytes into neurons through co-regulation involving miR-124 and three small molecules. Thus, our research has potential implications for inhibiting glial scar formation and promoting neuronal regeneration after central nervous system injury or disease.

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Metadata

Authors
Zheng, Y., Huang, Z., Xu, J., Hou, K., Yu, Y., Lv, S., Chen, L., Li, Y., Quan, C., & Chi, G.
Venue
Molecular Neurobiology
Publisher
Springer Science and Business Media LLC
Published
2021-03-16
Volume
58
Issue
5
Pages
2447-2464
ISSN
  • 0893-7648
  • 1559-1182
DOI
10.1007/s12035-021-02345-6
Cited by
24
References
5
Language
en
Licence
Funders
National Natural Science Foundation of China (81571199; 81870974)

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