MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1.
10.1038/s41368-023-00253-0
- Author:
Chen ZHANG
1
;
Weilong YE
1
;
Mengyao ZHAO
1
;
Lujue LONG
1
;
Dengsheng XIA
2
;
Zhipeng FAN
3
Author Information
1. Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
2. Department of Dental Emergency, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China.
3. Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, China. zpfan@ccmu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
Humans;
Rats;
Cell Differentiation;
Intracellular Signaling Peptides and Proteins/therapeutic use*;
Leukemia/metabolism*;
Mesenchymal Stem Cells;
Neurogenesis;
Stem Cells;
Transcription Factor HES-1/metabolism*
- From:
International Journal of Oral Science
2023;15(1):48-48
- CountryChina
- Language:English
-
Abstract:
Mesenchymal stem cell (MSC)-based therapy has emerged as a promising treatment for spinal cord injury (SCI), but improving the neurogenic potential of MSCs remains a challenge. Mixed lineage leukemia 1 (MLL1), an H3K4me3 methyltransferases, plays a critical role in regulating lineage-specific gene expression and influences neurogenesis. In this study, we investigated the role and mechanism of MLL1 in the neurogenesis of stem cells from apical papilla (SCAPs). We examined the expression of neural markers, and the nerve repair and regeneration ability of SCAPs using dynamic changes in neuron-like cells, immunofluorescence staining, and a SCI model. We employed a coimmunoprecipitation (Co-IP) assay, real-time RT-PCR, microarray analysis, and chromatin immunoprecipitation (ChIP) assay to investigate the molecular mechanism. The results showed that MLL1 knock-down increased the expression of neural markers, including neurogenic differentiation factor (NeuroD), neural cell adhesion molecule (NCAM), tyrosine hydroxylase (TH), βIII-tubulin and Nestin, and promoted neuron-like cell formation in SCAPs. In vivo, a transplantation experiment showed that depletion of MLL 1 in SCAPs can restore motor function in a rat SCI model. MLL1 can combine with WD repeat domain 5 (WDR5) and WDR5 inhibit the expression of neural markers in SCAPs. MLL1 regulates Hairy and enhancer of split 1 (HES1) expression by directly binds to HES1 promoters via regulating H3K4me3 methylation by interacting with WDR5. Additionally, HES1 enhances the expression of neural markers in SCAPs. Our findings demonstrate that MLL1 inhibits the neurogenic potential of SCAPs by interacting with WDR5 and repressing HES1. These results provide a potential therapeutic target for promoting the recovery of motor function in SCI patients.
