miR-185-5p regulates the proliferation and differentiation of neural stem/progenitor cells

Xuanran Feng; Xue Du; Xiaoyu Yang; Changqi Chen; Zhanping Liang; Xiaonan Xu; Yi Wang; Jialin C Zheng; Xiaohuan Xia; Jianhui Liu

doi:10.3389/fcell.2024.1510746

miR-185-5p regulates the proliferation and differentiation of neural stem/progenitor cells

Front Cell Dev Biol. 2024 Dec 5:12:1510746. doi: 10.3389/fcell.2024.1510746. eCollection 2024.

Authors

Xuanran Feng^#¹, Xue Du^#¹, Xiaoyu Yang¹, Changqi Chen¹, Zhanping Liang¹, Xiaonan Xu¹, Yi Wang², Jialin C Zheng^{1

3

4

5

6

7}, Xiaohuan Xia^{1

3

4

5

6}, Jianhui Liu^{1

3}

Affiliations

¹ Department of Anesthesiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
² Translational Research Center, Shanghai Yangzhi Rehabilitation Hospital, School of Medicine, Tongji University, Shanghai, China.
³ State Key Laboratory of Cardiovascular Diseases and Medical Innovation Center, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
⁴ Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
⁵ Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai, China.
⁶ Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
⁷ Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China.

^# Contributed equally.

Abstract

Background: MicroRNAs (miRNAs) have emerged as an essential regulator of the cell fate commitment of neural stem/progenitor cells (NPCs), although the impacts of certain miRNAs on NPCs remain vague. The aim of this study is to investigate the regulatory effects of miR-185-5p on the cell fate commitment of NPCs.

Methods: We investigated the impact of miR-185-5p on the proliferation and differentiation capacities of primary NPCs by manipulating the expression of miR-185-5p using specific mimics and inhibitors. The effects of miR-185-5p on NPCs was confirmed in vivo through stereotactic injection of miR-185-5p antagonists to the brains of mice at postnatal day 1 (P1).

Results: The expression levels of miR-185-5p kept increasing in the differentiation process of NPCs in vivo and in vitro. Perturbation of miR-185-5p's function showed that miR-185-5p inhibited NPCs' proliferation and promoted embryonic NPCs to differentiate more favorably to the glial lineage. We then validated the anti-proliferation and pro-glial roles of miR-185-5p using NPCs isolated from P1 mouse brains. In vivo study further showed enlarged NPCs pools and inhibited gliogenesis in the brains of P1 mice after animals received antagomir-185-5p.

Conclusion: Our study suggests miR-185-5p as an important regulator for the proliferation and glial fate commitment of NPCs.

Keywords: astrocytes; differentiation; miR-185-5p; neural stem/progenitor cells; proliferation.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by research grants from the National Natural Science Foundation of China (Nos. 82171194 and 82371204 to JL).