LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels

Stem Cell Research & Therapy, 2021 · DOI: https://doi.org/10.1186/s13287-021-02452-0 · Published: January 31, 2021

Spinal Cord Injury Neurology Regenerative Medicine & Stem Cells

Simple Explanation

Spinal cord injury (SCI) can result in permanent functional impairment. Promoting the differentiation of neural stem and progenitor cells (NSPCs) into neurons is a promising approach for SCI treatment. LINGO-1 is a protein that inhibits axon regeneration, neuron survival, and oligodendrocyte differentiation. Inhibiting LINGO-1 could promote NSPC differentiation into neurons. This study revealed a LINGO-1/miR-15b-3p/Wnt5a pathway which can modulate spinal cord-derived NSPC differentiation, potentially contributing to SCI treatment.

Study Duration

5 Weeks

Participants

Female adult C57/BL6 mice

Evidence Level

Not specified

Key Findings

1
LINGO-1 shRNA increased neuronal differentiation of spinal cord-derived NSPCs while decreasing astrocyte differentiation.
2
These effects were accompanied by elevated Wnt5a protein expression, but unexpectedly, no changes in Wnt5a mRNA levels.
3
Transplantation of LINGO-1 shRNA-treated sp-NSPCs into SCI mice promoted neural differentiation, wound compaction, and motor function recovery.

Research Summary

This study examined the effects of LINGO-1 on spinal cord-derived NSPC (sp-NSPC) differentiation, its mechanisms, and functional recovery in mice after cell transplantation. LINGO-1 shRNA promotes neural differentiation of sp-NSPCs and Wnt5a expression, probably by downregulating miR-15b-3p. Transplantation of LINGO-1 shRNA-treated NSPCs promotes recovery of motor function after SCI, highlighting its potential as a target for SCI treatment.

Practical Implications

Therapeutic Target for SCI

LINGO-1 downregulation can be a promising therapeutic strategy for promoting functional recovery after SCI.

NSPC Differentiation

Manipulation of LINGO-1 expression can effectively modulate NSPC differentiation towards neuronal lineages.

Wnt5a Regulation

Understanding the LINGO-1/miR-15b-3p/Wnt5a pathway provides insights into post-transcriptional regulation of Wnt signaling.

Study Limitations

1
The internal microenvironment is more complex, and other factors may negatively affect the differentiation of sp-NSPCs.
2
More details may still need to be elucidated.
3
Not specified

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