Abstract
Mesenchymal stem/stromal cells (MSCs) reside in the bone marrow and maintain their stemness under hypoxic conditions. However, the mechanism underlying the effects of hypoxia on MSCs remains to be elucidated. This study attempted to uncover the signaling pathway of MSC proliferation. Under low-oxygen culture conditions, MSCs maintained their proliferation and differentiation abilities for a long term. The Notch2 receptor was up-regulated in MSCs under hypoxic conditions. Notch2-knockdown (Notch2-KD) MSCs lost their cellular proliferation ability and showed reduced gene expression of hypoxia-inducible transcription factor (HIF)-1α, HIF-2α, and c-Myc. Overexpression of the c-Myc gene in Notch2-KD MSCs allowed the cells to regain their proliferation capacity. These results suggested that Notch2 signaling is linked to c-Myc expression and plays a key role in the regulation of MSC proliferation. Our findings provide important knowledge for elucidating the self-replication competence of MSCs in the bone marrow microenvironment.
Highlights
Mesenchymal stem/stromal cells (MSCs) have self-renewal and multipotent differentiation abilities in vitro and are an attractive candidate for regenerative medicine strategies [1]
We demonstrated that the PDGFRα+stem cell antigen 1 (Sca-1)+ (PαS) cell population is significantly enriched for murine MSCs [29, 30]
These results suggested that PDGFRα+Sca-1+ MSCs (PαS-MSCs) reside under hypoxic conditions in the bone marrow (BM)
Summary
Mesenchymal stem/stromal cells (MSCs) have self-renewal and multipotent differentiation abilities in vitro and are an attractive candidate for regenerative medicine strategies [1]. Several clinical studies utilizing MSCs in degenerative diseases are underway all over the world. MSCs were identified in the bone marrow (BM) [2], dental pulp [3], adipose tissue [4], PLOS ONE | DOI:10.1371/journal.pone.0165946. MSCs were identified in the bone marrow (BM) [2], dental pulp [3], adipose tissue [4], PLOS ONE | DOI:10.1371/journal.pone.0165946 November 17, 2016
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