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Astrocytes promote the proliferation of oligodendrocyte precursor cells through connexin 47-mediated LAMB2 secretion in exosomes

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Abstract

Background

Oligodendrocyte precursor cells (OPCs) can proliferate and differentiate into oligodendrocytes, the only myelin-forming cells in the central nervous system. Proliferating OPCs promotes remyelination in neurodegenerative diseases. Astrocytes (ASTs) are the most widespread cells in the brain and play a beneficial role in the proliferation of OPCs. Connexin 47 (Cx47) is the main component of AST-OPC gap junctions to regulate OPC proliferation. Nonetheless, the specific mechanism remains unclear.

Methods and results

This study investigates the proliferation mechanism of OPCs connected to ASTs via Cx47. Cx47 siRNA significantly inhibited OPCs from entering the proliferation cycle. Transcriptome sequencing of OPCs and gene ontology enrichment analysis revealed that ASTs enhanced the exosome secretion by OPCs via Cx47. Transmission electron microscopy, Western blot, and nanoparticle tracking analysis indicated that the OPC proliferation was related to extracellular exosomes. Cx47 siRNA decreased the OPC proliferation and exosome secretion in AST-OPC cocultures. Exogenous exosome supplementation alleviated the inhibitory effect of Cx47 siRNA and significantly improved OPC proliferation. Mass spectrometry revealed that LAMB2 was abundant in exosomes. The administration of exogenous LAMB2 induced DNA replication in the S phase in OPCs by activating cyclin D1.

Conclusions

Collectively, ASTs induce the secretion of exosomes that carry LAMB2 by OPCs via Cx47 to upregulate cyclin D1 thereby accelerating OPC proliferation.

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Data availability

The data of this study are available upon reasonable request.

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Funding

This study was supported by the Natural Science Foundation of China (NSFC 82171522) and the Chongqing Science and Technology Commission (No. cstc2019jcyj-msxmX0193).

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Authors and Affiliations

  1. Laboratory of Tissue Engineering and Stem Cell, Department of Histology and Embryology, Chongqing Medical University, Chongqing, People’s Republic of China

    Nannan Cheng, Yuanfeng Xiong, Wenjin Zhang, Xiaohong Wu, Zhongxiang Sun, Lei Zhang, Hong Wu, Yong Tang & Yan Peng

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  1. Nannan Cheng
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  2. Yuanfeng Xiong
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  3. Wenjin Zhang
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  4. Xiaohong Wu
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Contributions

NC made a key contribution to the experimental design, data analysis, and manuscript draft. YX and WZ participated in the experimental process. XW, ZS, LZ, and HW provided intellectual content. YT and YP guided the whole study and revised the manuscript. All authors approved the final manuscript.

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Correspondence to Yong Tang or Yan Peng.

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The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

Experimental animals in this study were provided by the Experimental Animal Center of Chongqing Medical University (Animal Use Approval No. SYXK YU 2018-0003). All animal experiments were approved by the Committee for Ethics in Animal Experimentation of Chongqing Medical University.

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Cheng, N., Xiong, Y., Zhang, W. et al. Astrocytes promote the proliferation of oligodendrocyte precursor cells through connexin 47-mediated LAMB2 secretion in exosomes. Mol Biol Rep 49, 7263–7273 (2022). https://doi.org/10.1007/s11033-022-07508-9

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