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 Regenerative Medicine Neurology

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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