Wang T, Xing J, Ying Y, Tang H, Li J, Wei Y, Zhang H.Biochem Biophys Res Commun. 2020 Jul 5;527(4):847-853. doi: 10.1016/j.bbrc.2020.04.129. Epub 2020 May 16.PMID: 32430170
Bone marrow mesenchymal stem cells (BMSCs) derived from cyanotic congenital heart disease (CCHD) exhibit deficient multi-lineage differentiation potential due to the abnormal accumulation of D-galactose. However, the underlying mechanisms have not yet been explored. Here, the multi-lineage differentiation potential of the BMSCs from CCHD and non-CCHD (NCHD) patients were assessed. BMSCs from CCHD patients exhibited inferior multi-lineage differentiation potential with reduced Notch1 protein and mRNA level. Bisulfite sequencing PCR results showed the methylation level of Notch1 promoter was raised, which inhibited the binding of NF-Ya. Exposure BMSCs from NCHD patients with D-galactose under hypoxia (4% O2) decreased the expression of Notch1. And activating Notch1 partially restored the deficient BMSCs of CCHD patients. In conclusion, the impaired multi-lineage differentiation potential of BMSCs from CCHD patients is owing to the decreased Notch1 level with a remarkable hypermethylation in its promoter region. Activated Notch1 signaling pathway could partially restore the deficient BMSCs in the CCHD patients, which may provide a new method on cell therapy in patients with CCHD.