Notch2 Signaling Regulates the Proliferation of Murine Bone Marrow-Derived Mesenchymal Stem/Stromal Cells via c-Myc Expression.
Notch2 Signaling Regulates the Proliferation of Murine Bone Marrow-Derived Mesenchymal Stem/Stromal Cells via c-Myc Expression.
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DOI：
10.1371/journal.pone.0165946
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Matsuzaki Y
中科院分区：
文献类型：
--
作者：
Sato Y;Mabuchi Y;Miyamoto K;Araki D;Niibe K;Houlihan DD;Morikawa S;Nakagawa T;Nakajima T;Akazawa C;Hori S;Okano H;Matsuzaki Y
间充质干细胞/基质细胞（MSC）位于骨髓中，并在缺氧条件下保持其干细胞状态。然而，缺氧对MSC的影响的机制仍有待阐明。本研究试图揭示MSC增殖的信号通路。在低氧培养条件下，MSCs能长期保持其增殖和分化能力。Notch 2受体在低氧条件下在MSC中上调。Notch 2敲除（Notch 2-KD）的MSCs失去了细胞增殖能力，并显示低氧诱导转录因子（HIF）-1α、HIF-2α和c-Myc的基因表达降低。在Notch 2-KD MSC中过表达c-Myc基因允许细胞恢复其增殖能力。这些结果表明Notch 2信号传导与c-Myc表达相关，并且在MSC增殖的调节中起关键作用。我们的研究结果提供了重要的知识，阐明骨髓微环境中的MSC的自我复制能力。
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.
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DOI：
10.1084/jem.20091046
发表时间：
2009-10-26
期刊：
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5.9
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影响因子：
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DOI：
10.1016/s0360-3016(96)00539-1
发表时间：
1997-03-01
影响因子：
7
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Kennedy, AS;Raleigh, JA;Varia, MA
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Varia, MA