Low oxygen enhances primitive and definitive neural stem cell colony formation by inhibiting distinct cell death pathways.
Low oxygen enhances primitive and definitive neural stem cell colony formation by inhibiting distinct cell death pathways.
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DOI：
10.1002/stem.96
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发表时间：
2009-08
期刊：
影响因子：
5.2
通讯作者：
van der Kooy, Derek
中科院分区：
文献类型：
--
作者：
Clarke, Laura;van der Kooy, Derek
神经干细胞（neural stem cells，NSCs）可以在缺乏指导因子的情况下从单个小鼠胚胎干细胞（embryonic stem cells，ESCs）中获得。首先形成克隆的原始NSC（pNSC）集落，然后产生克隆的成纤维细胞生长因子依赖性定形神经干细胞（dNSC）。我们测试了低氧培养作为减轻pNSC和dNSC中所见的广泛细胞死亡的潜在方法。在低氧（4%）中培养通过抑制凋亡诱导因子（AIF）依赖性细胞死亡促进pNSC的存活，尽管pNSC在20%氧中经历AIF和半胱天冬酶介导的细胞死亡。与此相反，通过抑制半胱天冬酶依赖性细胞死亡，dNSCs在低氧中的存活率增加。在常氧下，AIF参与促进dNSC存活。这两种生存效应都不依赖于缺氧的主要转录效应子，缺氧诱导因子1。低氧浓度可能通过在这些连续的pNSC和dNSC群体中通过不同途径抑制细胞死亡而参与早期NSC群体的扩增。干细胞2009;27：1879-1886
Neural stem cells (NSCs) can be derived from single mouse embryonic stem cells (ESCs) in the absence of instructive factors. Clonal primitive NSC (pNSC) colonies are formed first, and then give rise to clonal, fibroblast growth factor-dependent definitive neural stem cells (dNSCs). We tested low-oxygen culture as a potential method of alleviating the extensive cell death seen in pNSCs and dNSCs. Culture in low (4%) oxygen promoted survival of pNSCs by inhibiting apoptosis-inducing factor (AIF)-dependent cell death, although pNSCs undergo both AIF- and caspase-mediated cell death in 20% oxygen. In contrast, survival of dNSCs in low oxygen was increased by inhibition of caspase-dependent cell death. In normoxia, AIF is implicated in promoting dNSC survival. Neither survival effect was dependent on the main transcriptional effector of hypoxia, hypoxia-inducible factor 1. Low-oxygen concentrations may be involved in expansion of early NSC populations by inhibiting cell death through different pathways in these sequential pNSC and dNSC populations. Stem Cells 2009;27:1879–1886
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