Hypoxia-enhanced Derivation of iPSCs from Human Dental Pulp Cells
Hypoxia-enhanced Derivation of iPSCs from Human Dental Pulp Cells
复制标题
DOI：
10.1177/0022034513502204
复制
发表时间：
2013-10-01
影响因子：
7.6
通讯作者：
Tezuka, K.
中科院分区：
文献类型：
--
作者：
Iida, K.;Takeda-Kawaguchi, T.;Tezuka, K.
缺氧增强人真皮成纤维细胞的重编程效率以成为诱导多能干细胞（iPSC）。因为我们之前表明缺氧有利于人牙髓细胞（DPC）的分离和维持，所以我们在这里检查了它是否促进DPC重新编程成为iPSC。与真皮成纤维细胞不同，与常氧（21% O-2）相比，早期和短暂缺氧（3% O-2）诱导DPC向iPSC转变为3.3至5.1倍。通过形态学和干细胞标志物的表达判断，所产生的iPSC与胚胎干细胞以及常氧条件下产生的iPSC非常相似。然而，持续缺氧强烈抑制iPSC集落的出现并改变其形态，抗氧化剂未能抑制这种作用。短暂缺氧增加了NANOG和CDH 1的表达水平，并调节了许多基因的表达，包括那些编码趋化因子及其受体的基因。因此，我们得出结论，当针对细胞类型进行优化时，缺氧是增强体细胞重编程成为iPSC的简单而有用的工具。
Hypoxia enhances the reprogramming efficiency of human dermal fibroblasts to become induced pluripotent stem cells (iPSCs). Because we showed previously that hypoxia facilitates the isolation and maintenance of human dental pulp cells (DPCs), we examined here whether it promotes the reprogramming of DPCs to become iPSCs. Unlike dermal fibroblasts, early and transient hypoxia (3% O-2) induced the transition of DPCs to iPSCs by 3.3- to 5.1-fold compared with normoxia (21% O-2). The resulting iPSCs closely resembled embryonic stem cells as well as iPSCs generated in normoxia, as judged by morphology and expression of stem cell markers. However, sustained hypoxia strongly inhibited the appearance of iPSC colonies and altered their morphology, and anti-oxidants failed to suppress this effect. Transient hypoxia increased the expression levels of NANOG and CDH1 and modulated the expression of numerous genes, including those encoding chemokines and their receptors. Therefore, we conclude that hypoxia, when optimized for cell type, is a simple and useful tool to enhance the reprogramming of somatic cells to become iPSCs.