Effects of hypoxia on pluripotency in murine iPS cells.
Effects of hypoxia on pluripotency in murine iPS cells.
复制标题
缺氧对小鼠 iPS 细胞多能性的影响。
DOI：
10.1002/jemt.22269
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发表时间：
2013
影响因子：
2.5
通讯作者：
Ishizaki H.
中科院分区：
文献类型：
--
作者：
Sugimoto K;Yoshizawa Y;Yamada S;Igawa K;Hayashi Y;Ishizaki H.
四种转录因子（Oct4, Sox2， Klf4和c‐Myc）或三种因子（c‐Myc除外）的逆转录转导已被证明可启动重编程过程，导致小鼠成纤维细胞向诱导多能干细胞（iPS）细胞转化，并且基于iPS细胞的临床前试验数量迅速增加。本研究评估了这些转录因子对缺氧条件下小鼠iPS细胞生长分化的影响。RT - PCR和茜素红S染色结果显示，不同转录因子组间诱导多能干细胞在缺氧条件下的生长分化和诱导多能干细胞向成骨细胞的分化均无统计学差异。此外，利用RT - PCR和Western blotting研究了缺氧诱导因子（hif）在小鼠iPS细胞中的功能与转录因子形态和表达的关系。HIF‐2α敲低组显示iPS细胞的集落大小减少。与对照组相比，HIF‐2α或‐3α敲低组的转录因子表达有统计学意义的降低。这些结果表明，HIF - 2α是维持小鼠iPS细胞多能性最具影响力的候选因子。科学通报，2013,36(6):1084 - 1092。©2013 Wiley期刊公司
Retroviral transduction of four transcription factors (Oct4, Sox2, Klf4 and c‐Myc) or three factors, excluding c‐Myc, has been shown to initiate a reprogramming process that results in the transformation of murine fibroblasts to induced pluripotent stem (iPS) cells, and there has been a rapid increase in the number of iPS cell‐based preclinical trials. In this study, the effects of these transcription factors were evaluated regarding the growth and differentiation of murine iPS cells under hypoxia. Based on the results of RT‐PCR and alizarin red S staining, there were no statistical differences in the growth and differentiation of iPS cells or the induction of iPS cells to osteoblasts under hypoxia between the transcription factor groups. Furthermore, the function of hypoxia inducible factors (HIFs) in murine iPS cells under hypoxia was investigated in relation to the morphology and expression of transcription factors using RT‐PCR and Western blotting. The HIF‐2α knockdown group exhibited a decrease in the colony size of the iPS cells. The HIF‐2α or ‐3α knockdown group demonstrated a statistically significant decrease in the transcription factor expression compared to that observed in the control group. These results demonstrate that HIF‐2α among HIFs is the most influential candidate for the maintenance of the pluripotency of murine iPS cells.Microsc. Res. Tech., 76:1084–1092, 2013. © 2013 Wiley Periodicals, Inc.