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  4. MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1

MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1

International Journal of Oral Science, 2023 · DOI: https://doi.org/10.1038/s41368-023-00253-0 · Published: September 25, 2023

Spinal Cord InjuryRegenerative Medicine

Simple Explanation

This study explores how a protein called MLL1 affects the ability of stem cells from apical papilla (SCAPs) to turn into nerve cells. It finds that MLL1 normally inhibits this process. The study shows that when MLL1 is reduced in SCAPs, they are better able to form neuron-like cells and promote recovery in a rat model of spinal cord injury. MLL1 interacts with another protein, WDR5, to suppress the expression of a gene called HES1, which is important for nerve cell development. By reducing MLL1, the nerve-generating potential of SCAPs is enhanced.

Study Duration
5 weeks (in vivo behavioral testing)
Participants
Sprague-Dawley rats (female, aged 6-8 weeks)
Evidence Level
Not specified

Key Findings

  • 1
    Knockdown of MLL1 in SCAPs increases the expression of neural markers such as NeuroD, NCAM, TH, βIII-tubulin and Nestin, promoting neuron-like cell formation.
  • 2
    Depletion of MLL1 in SCAPs improves motor function recovery in a rat spinal cord injury model.
  • 3
    MLL1 interacts with WDR5 and represses HES1 expression by directly binding to HES1 promoters via regulating H3K4me3 methylation, inhibiting the neurogenic potential of SCAPs.

Research Summary

The study investigates the role of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs) and its impact on spinal cord injury recovery. The research demonstrates that MLL1 knockdown enhances the neurogenic potential of SCAPs, promoting the expression of neural markers and improving motor function in a rat SCI model. The study elucidates the molecular mechanism involving the interaction of MLL1 with WDR5 and the repression of HES1, offering a potential therapeutic target for SCI treatment.

Practical Implications

Therapeutic Target Identification

MLL1, WDR5, and HES1 are potential therapeutic targets for promoting functional recovery after SCI.

Stem Cell Therapy Enhancement

Genetically modified SCAPs with MLL1 knockdown can be used to enhance stem cell therapy for neurological injuries.

Understanding Neurogenesis

The study provides insights into the molecular mechanisms regulating neurogenesis in dental-MSCs.

Study Limitations

  • 1
    The study primarily uses a rat model, and further research is needed to confirm the findings in human subjects.
  • 2
    The long-term effects of MLL1 knockdown in SCAPs are not fully elucidated.
  • 3
    The specific signaling pathways downstream of HES1 in SCAPs require further investigation.

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