Establishment of LIF-dependent human iPS cells closely related to basic FGF-dependent authentic iPS cells.

Establishment of LIF-dependent human iPS cells closely related to basic FGF-dependent authentic iPS cells.
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DOI:
10.1371/journal.pone.0039022
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Kikyo N
Kikyo N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hirai H;Firpo M;Kikyo N

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人诱导多能干细胞(iPSCs)可分为白血病抑制因子(LIF)依赖的幼稚型和碱性成纤维细胞生长因子(bFGF)依赖的致敏型。虽然前者比后者更未分化,但它们需要信号转导抑制剂和用于iPSC生产的转基因的持续表达。我们使用转录增强型OCT 4来建立LIF依赖性人iPSC,而不使用抑制剂和持续的转基因表达。这些细胞属于致敏型多能干细胞,类似于bFGF依赖性iPSC。因此,iPSC生产所需的特定细胞因子并不一定像以前认为的那样定义干细胞表型。bFGF和LIF信号通路可能集中在未鉴定的OCT 4靶基因上。这些发现表明,我们的LIF依赖性人iPSCs可以提供一种新的模型来研究细胞因子信号传导在细胞重编程中的作用。
Human induced pluripotent stem cells (iPSCs) can be divided into a leukemia inhibitory factor (LIF)-dependent naïve type and a basic fibroblast growth factor (bFGF)-dependent primed type. Although the former are more undifferentiated than the latter, they require signal transduction inhibitors and sustained expression of the transgenes used for iPSC production. We used a transcriptionally enhanced version of OCT4 to establish LIF-dependent human iPSCs without the use of inhibitors and sustained transgene expression. These cells belong to the primed type of pluripotent stem cell, similar to bFGF-dependent iPSCs. Thus, the particular cytokine required for iPSC production does not necessarily define stem cell phenotypes as previously thought. It is likely that the bFGF and LIF signaling pathways converge on unidentified OCT4 target genes. These findings suggest that our LIF-dependent human iPSCs could provide a novel model to investigate the role of cytokine signaling in cellular reprogramming.
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