Regulation of differentiation potential of human mesenchymal stem cells by intracytoplasmic delivery of coactivator-associated arginine methyltransferase 1 protein using cell-penetrating peptide.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Recent studies suggest that epigenetic modifications, such as DNA methylation and histone modification, can alter the differentiation potential of stem cells or progenitor cells. Specifically, coactivator-associated arginine methyltransferase 1 (CARM1) is known to act as a coactivator for various transcription factors and to regulate gene expression by chromatin remodeling through histone methylation. Here, for the first time, we have used direct protein delivery of CARM1 using cell-penetrating peptide (CPP) to regulate the differentiation potential of human mesenchymal stem cells (hMSCs). Immunofluorescence showed that the CPP-CARM1 protein is successfully delivered into the nuclei of hMSCs. Further experiments using immunofluorescence and Western blotting showed that the delivered CARM1 protein can effectively methylate the arginine 17 residue of histone H3 in both bone marrow (BM)- and adipose-derived (AD)-hMSCs, thus suggesting that the CARM1 protein delivered by the CPP system is biologically active in hMSCs. Chromatin immunoprecipitation (ChIP) assay and genome-wide gene expression profiling supported the result that delivered CARM1 protein can cause chromatin remodeling through histone methylation. Finally, the CPP-CARM1 protein efficiently elevated the differentiation efficiency of BM-hMSCs and AD-hMSCs into adipogenic, osteogenic, and myogenic cell lineages in vitro. A

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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