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Notch1 signaling mediated dysfunction of bone marrow mesenchymal stem cells derived from cyanotic congenital heart disease.

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Wang T,Xing J,Ying Y,Tang H,Li J,Wei Y,Zhang H

doi

10.1016/j.bbrc.2020.04.129

subject

Has Abstract

pub_date

2020-07-05 00:00:00

pages

847-853

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(20)30869-X

journal_volume

527

pub_type

杂志文章

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