Hesx1 enhances pluripotency by working downstream of multiple pluripotency-associated signaling pathways
Hesx1 enhances pluripotency by working downstream of multiple pluripotency-associated signaling pathways
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Hesx1 通过作用于多个多能性相关信号通路的下游来增强多能性
DOI：
10.1016/j.bbrc.2015.07.074
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发表时间：
2015-08-28
影响因子：
3.1
通讯作者：
Zhang, Yong
中科院分区：
文献类型：
--
作者：
Li, Wen-Zhong;Wang, Zhi-Wei;Zhang, Yong
Hesx1是一种在胚胎干细胞(ESCs)中表达的同源盒基因，与控制多能性状态的核心转录因子有关。然而，关于Hesx1如何参与维持多能性的潜在机制的数据仍然很少。在这项研究中，我们发现Hesx1对多种多潜能相关的途径抑制剂以及LIF刺激都有反应。特别是，Hesx1的表达很容易被糖原合成酶激酶3和丝裂原活化蛋白激酶的双重抑制(2I)所诱导。强迫表达Hesx1可以部分补偿LIF或2i的每一组分的取消。我们还证明了LIF和2I的每个抑制剂都可以相互独立地诱导Hesx1。我们初步提出Hesx1是LIF和2I介导的自我更新信号通路的共同下游靶点，在维持ESC同一性方面发挥重要作用。我们的研究扩展了确定建立胚胎干细胞多能性中缺失的关键因素的方法。(C)2015 Elsevier Inc.保留所有权利。
Hesx1, a homeobox gene expressed in embryonic stem cells (ESCs), has been implicated in the core transcription factors governing the pluripotent state. However, data about the underlying mechanism of how Hesx1 is involved in maintaining pluripotency is still scarce. In this study, we find Hesx1 responds to multiple pluripotency-related pathway inhibitors as well as LIF stimulation. Particularly, the expression of Hesx1 can be readily induced by dual inhibition (2i) of glycogen synthase kinase 3 and mitogen-activated protein kinase. Forced expression of Hesx1 can partially compensate for the withdrawal of either LIF or each component of 2i. We also demonstrate that LIF and each inhibitor of 2i can induce Hesx1 independent of one another. We tentatively put forward that Hesx1 is a common downstream target of LIF- and 2i-mediated self-renewal signaling pathways and plays an important role in maintaining ESC identity. Our study extends the methods of identifying the missing crucial factors in establishing ESC pluripotency. (C) 2015 Elsevier Inc. All rights reserved.