ArticleStem cell research & therapy2015
Activation of Notch1 signalling promotes multi-lineage differentiation of c-Kit(POS)/NKX2.5(POS) bone marrow stem cells: implication in stem cell translational medicine.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- S-Nitrosylation of NOTCH1 Regulates Mesenchymal Stem Cells Differentiation Into Hepatocyte-Like Cells by Inhibiting Notch Signalling Pathway.Journal of cellular and molecular medicine · 2024Article
- Application and challenges of stem cells in cardiovascular aging.Regenerative therapy · 2024Review
- PSME4 Degrades Acetylated YAP1 in the Nucleus of Mesenchymal Stem Cells.Pharmaceutics · 2022Article
- Intervention effects of traditional Chinese medicine on stem cell therapy of myocardial infarction.Frontiers in pharmacology · 2022Review
- SETD4 in the Proliferation, Migration, Angiogenesis, Myogenic Differentiation and Genomic Methylation of Bone Marrow Mesenchymal Stem Cells.Stem cell reviews and reports · 2021Article
- Inhibition of Notch Signaling Promotes the Differentiation of Epicardial Progenitor Cells into Adipocytes.Stem cells international · 2021Article
- Pathologic role of peptidyl-prolyl isomerase Pin1 in pulmonary artery remodeling.American journal of translational research · 2021Article
- The therapeutic potential of mesenchymal stem cells for cardiovascular diseases.Cell death & disease · 2020Review
- Macrophage-derived MMP-8 determines smooth muscle cell differentiation from adventitia stem/progenitor cells and promotes neointima hyperplasia.Cardiovascular research · 2020Article
- Mechanisms supporting potential use of bone marrow-derived mesenchymal stem cells in psychocardiology.American journal of translational research · 2019Review
- Combination ofEvidence-based complementary and alternative medicine : eCAM · 2019Article
- Hypoxia-stressed cardiomyocytes promote early cardiac differentiation of cardiac stem cells through HIF-1Acta pharmaceutica Sinica. B · 2018Article
- The cardiac niche role in cardiomyocyte differentiation of rat bone marrow-derived stromal cells: comparison between static and microfluidic cell culture methods.EXCLI journal · 2018Article
- Thioredoxin-1 Protects Bone Marrow-Derived Mesenchymal Stromal Cells from Hyperoxia-Induced Injury In Vitro.Oxidative medicine and cellular longevity · 2018Article
- A brief review: the therapeutic potential of bone marrow mesenchymal stem cells in myocardial infarction.Stem cell research & therapy · 2017Review
- High glucose promotes vascular smooth muscle cell proliferation by upregulating proto-oncogene serine/threonine-protein kinase Pim-1 expression.Oncotarget · 2017Article
- Single-cell analysis of the fate of c-kit-positive bone marrow cells.NPJ Regenerative medicine · 2017Article
- Key transcription factors in the differentiation of mesenchymal stem cells.Differentiation; research in biological diversityReview
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Authors and funding
9 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
introductionTransplantation of bone marrow mesenchymal stem cells (BMSCs) can repair injured hearts. However, whether BMSC populations contain cells with cardiac stem cell characteristics is ill-defined. We report here that Notch signalling can promote differentiation of c-Kit(POS)/NKX2.5(POS) BMSCs into cardiomyocyte-like cells.
methodsTotal BMSCs were isolated from Sprague-Dawley rat femurs and c-Kit(POS) cells were purified. c-Kit(POS)/NKX2.5(POS) cells were isolated by single-cell cloning, and the presence of cardiomyocyte, smooth muscle cell (SMC), and endothelial cell differentiation markers assessed by immunofluorescence staining and semi-quantitative reverse-transcription polymerase chain reaction (RT-PCR) analysis. Levels of c-Kit and Notch1-4 in total BMSCs and c-Kit(POS)/NKX2.5(POS) BMSCs were quantitated by flow cytometry. Following infection with an adenovirus over-expressing Notch1 intracellular domain (NICD), total BMSCs and c-Kit(POS)/NKX2.5(POS) cells were assessed for differentiation to cardiomyocyte, SMC, and endothelial cell lineages by immunofluorescence staining and real-time quantitative RT-PCR. Total BMSCs and c-Kit(POS)/NKX2.5(POS) cells were treated with the Notch1 ligand Jagged1 and markers of cardiomyocyte, SMC, and endothelial cell differentiation were examined by immunofluorescence staining and real-time quantitative RT-PCR analysis.
resultsc-Kit(POS)/NKX2.5(POS) cells were present among total BMSC populations, and these cells did not express markers of adult cardiomyocyte, SMC, or endothelial cell lineages. c-Kit(POS)/NKX2.5(POS) BMSCs exhibited a multi-lineage differentiation potential similar to total BMSCs. Following sorting, the c-Kit level in c-Kit(POS)/NKX2.5(POS) BMSCs was 84.4%. Flow cytometry revealed that Notch1 was the predominant Notch receptor present in total BMSCs and c-Kit(POS)/NKX2.5(POS) BMSCs. Total BMSCs and c-Kit(POS)/NKX2.5(POS) BMSCs overexpressing NICD had active Notch1 signalling accompanied by differentiation into cardiomyocyte, SMC, and endothelial cell lineages. Treatment of total BMSCs and c-Kit(POS)/NKX2.5(POS) BMSCs with exogenous Jagged1 activated Notch1 signalling and drove multi-lineage differentiation, with a tendency towards cardiac lineage differentiation in c-Kit(POS)/NKX2.5(POS) BMSCs.
conclusionsc-Kit(POS)/NKX2.5(POS) cells exist in total BMSC pools. Activation of Notch1 signalling contributed to multi-lineage differentiation of c-Kit(POS)/NKX2.5(POS) BMSCs, favouring differentiation into cardiomyocytes. These findings suggest that modulation of Notch1 signalling may have potential utility in stem cell translational medicine.
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