缺氧诱导定向细胞重新进入多能性。
Hypoxia induces re-entry of committed cells into pluripotency.
机构信息
Department of Biochemistry, University of Washington, Seattle, Washington, USA; Institute for Stem Cell and Regenerative Medicine University of Washington, Seattle, Washington, USA.
出版信息
Stem Cells. 2013 Sep;31(9):1737-48. doi: 10.1002/stem.1446.
Abstract
Adult stem cells reside in hypoxic niches, and embryonic stem cells (ESCs) are derived from a low oxygen environment. However, it is not clear whether hypoxia is critical for stem cell fate since for example human ESCs (hESCs) are able to self-renew in atmospheric oxygen concentrations as well. We now show that hypoxia can govern cell fate decisions since hypoxia alone can revert hESC- or iPSC-derived differentiated cells back to a stem cell-like state, as evidenced by re-activation of an Oct4-promoter reporter. Hypoxia-induced "de-differentiated" cells also mimic hESCs in their morphology, long-term self-renewal capacity, genome-wide mRNA and miRNA profiles, Oct4 promoter methylation state, cell surface markers TRA1-60 and SSEA4 expression, and capacity to form teratomas. These data demonstrate that hypoxia can influence cell fate decisions and could elucidate hypoxic niche function.
摘要
成体干细胞存在于低氧环境中，胚胎干细胞（ESCs）来源于低氧环境。然而，目前尚不清楚缺氧是否对干细胞命运至关重要，因为例如人胚胎干细胞（hESCs）在大气氧浓度下也能够自我更新。我们现在表明，缺氧可以控制细胞命运决定，因为单独的缺氧就可以将 hESC 或 iPSC 衍生的分化细胞逆转回类似于干细胞的状态，这可以通过重新激活 Oct4 启动子报告基因来证明。缺氧诱导的“去分化”细胞在形态、长期自我更新能力、全基因组 mRNA 和 miRNA 谱、Oct4 启动子甲基化状态、细胞表面标志物 TRA1-60 和 SSEA4 表达以及形成畸胎瘤的能力方面也类似于 hESCs。这些数据表明，缺氧可以影响细胞命运决定，并阐明低氧龛的功能。
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本文引用的文献
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