STAT3 is dispensable for maintenance of self-renewal in nonhuman primate embryonic stem cells
STAT3 is dispensable for maintenance of self-renewal in nonhuman primate embryonic stem cells
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DOI：
10.1634/stemcells.22-5-861
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发表时间：
2004-01-01
期刊：
影响因子：
5.2
通讯作者：
Suemori, H
中科院分区：
文献类型：
--
作者：
Sumi, T;Fujimoto, S;Suemori, H
白血病抑制因子（LIF）/糖蛋白130（gp 130）/信号转导和转录激活因子3（STAT 3）通路在维持小鼠胚胎干细胞（ES细胞）的自我更新和多能性中起着重要作用。然而，在灵长类动物的ES细胞中，包括来自人类和猴子的ES细胞，单独的LIF不足以维持自我更新。LIF/gp 130/STAT 3通路在灵长类ES细胞自我更新中的确切作用尚不清楚。在这项研究中，我们发现用LIF或白细胞介素（IL）-6/可溶性IL-6受体刺激食蟹猴ES细胞导致STAT 3磷酸化，这是以前在小鼠ES细胞中观察到的效果。伴随着这一概念，核转位和转录激活的STAT 3被观察到的LIF依赖性的方式。此外，对显性干扰突变体STAT 3F的分析表明，即使在LIF刺激后内源性STAT 3的磷酸化、核转位和转录激活通过在猴ES细胞中过表达STAT 3F而被完全废除，它们仍在未分化状态下继续增殖，保持其多能性。这些结果表明LIF/gp 130/STAT 3通路在食蟹猴ES细胞中起作用，但对于维持自我更新不是必需的。他们还表明，与鼠ES细胞不同，食蟹猴ES细胞通过LIF/gp 130/STAT 3非依赖性信号传导维持在未分化状态。
The leukemia inhibitory factor (LIF)/glycoprotein 130 (gp130)/signal transducer and activator of transcription 3 (STAT3) pathway plays an essential role in the maintenance of self-renewal and pluripotency in mouse embryonic stem (ES) cells. However, in primate ES cells, including those from humans and monkeys, LIF alone is not sufficient to maintain self-renewal. The precise role of the LIF/gp130/STAT3 pathway for self-renewal in primate ES cells is still unclear. In this study, we found that stimulation of cynomolgus monkey ES cells with LIF or interleukin (IL)-6/soluble IL-6 receptor leads to STAT3 phosphorylation, an effect seen previously in murine ES cells. Concomitant with this notion, nuclear translocalization and transcriptional activation of STAT3 were observed in a LIF-dependent manner. Moreover, the analysis of a dominant interfering mutant, STAT3F, showed that even though the phosphorylation, nuclear translocalization, and transcriptional activation of endogenous STAT3 after LIF stimulation were completely abrogated by overexpressing STAT3F in monkey ES cells, they continued to proliferate in an undifferentiated state, retaining their pluripotency. These results demonstrate that the LIF/gp130/STAT3 pathway functions in cynomolgus monkey ES cells but is not essential for the maintenance of self-renewal. They also suggest that cynomolgus monkey ES cells, unlike murine ES cells, are maintained in an undifferentiated state through LIF/gp130/STAT3-independent signaling.