Effects of ionizing radiation on self-renewal and pluripotency of human embryonic stem cells.
Effects of ionizing radiation on self-renewal and pluripotency of human embryonic stem cells.
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电离辐射对人类胚胎干细胞自我更新和多能性的影响。
DOI：
10.1158/0008-5472.can-09-4238
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发表时间：
2010-07-01
期刊：
影响因子：
11.2
通讯作者：
Wu JC
中科院分区：
文献类型：
--
作者：
Wilson KD;Sun N;Huang M;Zhang WY;Lee AS;Li Z;Wang SX;Wu JC
人胚胎干细胞（hESCs）为在体外研究电离辐射对早期胚胎细胞的反应提供了一个新的平台。到目前为止，还没有研究分析hESC对电离辐射的全基因组转录反应，也没有任何研究评估它们形成畸胎瘤的能力，这是多能性的决定性测试。在这项研究中，我们使用微阵列分析低（0.4戈伊），中（2戈伊），高（4戈伊）剂量照射后的hESC的整体基因表达的变化。我们在每种辐射剂量下确定了参与细胞死亡，p53信号传导，细胞周期，癌症，胚胎和器官发育等的基因和途径。使用基因集富集分析（GSEA），我们还表明，一套全面的核心胚胎转录因子的表达不会改变辐射在任何剂量。将辐照过的hESC移植到免疫缺陷小鼠中导致所有剂量辐照过的hESC形成畸胎瘤，这是多能性的明确证据。此外，使用生物发光成像技术，我们发现辐射导致hESC在移植后最初死亡，但存活的细胞在两周内迅速恢复到与对照组相似的水平。综上所述，我们证明了与体细胞相似，照射后的人胚胎干细胞遭受显著的死亡和凋亡。然而，它们继续保持多能性，并能够形成所有三个胚层。像这样的研究将有助于确定孕妇的辐射暴露限制，以及用于跟踪细胞再生疗法的放射性示踪剂报告探针。
Human embryonic stem cells (hESCs) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs, nor has any study assessed their ability to form teratomas, the definitive test of pluripotency. In this study, we use microarrays to analyze the global gene expression changes in hESCs after low (0.4 Gy), medium (2 Gy), and high (4 Gy) dose irradiation. We identify genes and pathways at each radiation dose that are involved in cell death, p53 signaling, cell cycling, cancer, embryonic and organ development, and others. Using Gene Set Enrichment Analysis (GSEA), we also show that the expression of a comprehensive set of core embryonic transcription factors is not altered by radiation at any dose. Transplantation of irradiated hESCs to immune-deficient mice results in teratoma formation from hESCs irradiated at all doses, definitive proof of pluripotency. Further, using a bioluminescence imaging technique, we have found that irradiation causes hESCs to initially die after transplantation, but the surviving cells quickly recover by two weeks to levels similar to control. To conclude, we demonstrate that similar to somatic cells, irradiated hESCs suffer significant death and apoptosis after irradiation. However, they continue to remain pluripotent and are able to form all three embryonic germ layers. Studies such as this will help define the limits for radiation exposure for pregnant women and also radiotracer reporter probes for tracking cellular regenerative therapies.