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首页> 外文期刊>Radiotherapy and oncology: Journal of the European Society for Therapeutic Radiology and Oncology >Sensing radiosensitivity of human epidermal stem cells.
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Sensing radiosensitivity of human epidermal stem cells.

机译：人类表皮干细胞的放射敏感性。

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PURPOSE: Radiosensitivity of stem cells is a matter of debate. For mouse somatic stem cells, both radiosensitive and radioresistant stem cells have been described. By contrast, the response of human stem cells to radiation has been poorly studied. As epidermis is a radiosensitive tissue, we evaluated in the present work the radiosensitivity of cell populations enriched for epithelial stem cells of human epidermis. METHODS AND MATERIALS: The total keratinocyte population was enzymatically isolated from normal human skin. We used flow cytometry and antibodies against cell surface markers to isolate basal cell populations from human foreskin. Cell survival was measured after a dose of 2Gy with the XTT assay at 72h after exposure and with a clonogenic assay at 2 weeks. Transcriptome analysis using oligonucleotide microarrays was performed to assess the genomic cell responses to radiation. RESULTS: Cell sorting based on two membrane proteins, alpha6 integrin and the transferrin receptor CD71, allowed isolation of keratinocyte populations enriched for the two types of cells found in the basal layer of epidermis: stem cells and progenitors. Both the XTT assay and the clonogenic assay showed that the stem cells were radioresistant whereas the progenitors were radiosensitive. We made the hypothesis that upstream DNA damage signalling might be different in the stem cells and used microarray technology to test this hypothesis. The stem cells exhibited a much more reduced gene response to a dose of 2Gy than the progenitors, as we found that 6% of the spotted genes were regulated in the stem cells and 20% in the progenitors. Using Ingenuity Pathway Analysis software, we found that radiation exposure induced very specific pathways in the stem cells. The most striking responses were the repression of a network of genes involved in apoptosis and the induction of a network of cytokines and growth factors. CONCLUSION: These results show for the first time that keratinocyte populations enriched for stem cells from human epidermis are radioresistant. Based on both repressed and induced genes, we found that the major response of the irradiated stem cell population was the regulation of genes functionally related to cell death, cell survival and apoptosis.
机译：目的：干细胞的放射敏感性尚有争议。对于小鼠体干细胞，已经描述了放射敏感性和放射抗性干细胞。相比之下，人类干细胞对辐射的反应研究很少。由于表皮是放射敏感性组织，因此我们在当前工作中评估了富含人表皮上皮干细胞的细胞群体的放射敏感性。方法和材料：从人体正常皮肤中酶分离总的角质形成细胞。我们使用流式细胞仪和抗细胞表面标志物的抗体从人包皮中分离出基底细胞群。剂量为2Gy后，在暴露后72h用XTT测定，在2周时用克隆形成测定，测量细胞存活率。使用寡核苷酸微阵列进行转录组分析以评估基因组细胞对辐射的反应。结果：基于两种膜蛋白，即α6整合素和转铁蛋白受体CD71的细胞分选，可以分离富含在表皮基底层中发现的两种类型的细胞的角质形成细胞群：干细胞和祖细胞。 XTT分析和克隆形成分析均显示干细胞具有放射抗性，而祖细胞具有放射敏感性。我们提出了一个假设，即干细胞中上游DNA损伤的信号传导可能有所不同，并使用微阵列技术测试了这一假设。干细胞在剂量为2Gy时比祖细胞表现出大大降低的基因响应，因为我们发现在干细胞中有6％的斑点基因受到调控，而在祖细胞中则有20％。使用Ingenuity Pathway Analysis软件，我们发现辐射暴露诱导了干细胞中非常特定的途径。最显着的反应是细胞凋亡相关基因网络的抑制以及细胞因子和生长因子网络的诱导。结论：这些结果首次表明富集人表皮干细胞的角质形成细胞群具有放射抗性。基于受抑制和诱导的基因，我们发现辐照的干细胞群体的主要反应是与细胞死亡，细胞存活和细胞凋亡功能相关的基因的调节。

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