Long-term adaptation to hypoxia preserves hematopoietic stem cell function.

Long-term adaptation to hypoxia preserves hematopoietic stem cell function.
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长期适应缺氧可保留造血干细胞功能。

DOI:
10.1016/j.exphem.2016.04.010
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发表时间:
2016-09
影响因子:
2.6
通讯作者:
Hwang PM
Hwang PM
中科院分区:
医学4区
文献类型:
--
作者:
Chen J;Kang JG;Keyvanfar K;Young NS;Hwang PM

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分子氧维持有氧生活,但它也作为氧化应激的底物,与疾病的发病机制和衰老有关。与在常氧(21%O2)中饲养的小鼠相比,将环境氧气减少到10%O2(缺氧)导致造血干细胞功能增加,如通过骨髓(BM)细胞移植到致死辐射受体中所测量的。在缺氧小鼠中,BM c-Kit+ Sca 1 +Lin−(KSL)细胞以及具有其他造血干细胞和祖细胞标志物的细胞数量增加,而BM细胞集落形成能力保持不变。来自缺氧小鼠的KSL细胞显示氧化应激水平降低,转录因子Gata 1和细胞因子受体c-Mpl表达增加,与红细胞生成增加和造血干细胞植入增强的观察结果一致。这些观察结果证明了低氧造血干细胞生态位的益处,并表明低氧条件可以进一步优化以保持体内干细胞的完整性。
Molecular oxygen sustains aerobic life but it also serves as the substrate for oxidative stress that has been associated with the pathogenesis of disease and with aging. Compared to mice housed in normoxia (21% O2), reducing ambient oxygen to 10% O2 (hypoxia) resulted in increased hematopoietic stem cell function as measured by bone marrow (BM) cell engraftment into lethally-irradiated recipients. The number of BM c-Kit+Sca1+Lin− (KSL) cells, as well as cells with other hematopoietic stem and progenitor cell markers, were increased in hypoxia mice while BM cell colony forming capacity remained unchanged. KSL cells from hypoxia mice showed a decreased level of oxidative stress and increased expression of transcription factor Gata1 and cytokine receptor c-Mpl, consistent with the observations of increased erythropoiesis and enhanced hematopoietic stem cell engraftment. These observations demonstrate the benefit of a hypoxic hematopoietic stem cell niche and suggest that hypoxic conditions can be further optimized to preserve stem cell integrity in vivo.
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