Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of Heterogeneous Identities in Embryonic Stem Cells.
Functional Antagonism between OTX2 and NANOG Specifies a Spectrum of Heterogeneous Identities in Embryonic Stem Cells.
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DOI：
10.1016/j.stemcr.2017.09.019
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发表时间：
2017-11-14
影响因子：
5.9
通讯作者：
Simeone A
中科院分区：
文献类型：
--
作者：
Acampora D;Di Giovannantonio LG;Garofalo A;Nigro V;Omodei D;Lombardi A;Zhang J;Chambers I;Simeone A
在白血病抑制因子（LIF）和胎牛血清（FBS）中培养的胚胎干细胞（ESCs）在初始转录因子和引物转录因子的表达上表现出异质性。这种异质性反映了ESCs的动态状态，以及它们对促进初始或引物多能性的信号效应物迅速作出反应的多功能性。在这里，我们报道了缺乏Nanog或过表达Otx2的ESCs在LIF + FBS中表现出早期的启动身份，并且不能转化为2i诱导的初始状态。相反，Otx2-null的ESCs在LIF + FBS中具有与nanog -过表达的ESCs相似的幼稚身份特征，并且很难转化为fgf诱导的早期启动状态。当Nanog和Otx2同时失活时，在LIF + FBS中培养的ESCs表现出启动身份和向幼稚状态转化的能力减弱。这些数据表明，通过相互拮抗，NANOG和OTX2指明了在LIF + FBS中培养的ESCs的异质特性，并单独使它们对初始或启动的诱导因子做出最佳反应。Nanog或Otx2过表达缺失可诱导LIF培养的ESCs的启动身份Nanog或Otx2过表达缺失影响初始转化Otx2缺失的LIF ESCs表现出初始身份并异常转化为启动状态缺乏Otx2和Nanog的ESCs表现出启动身份并转化为初始状态和启动状态Simeone等研究了控制LIF + FBS培养的ESCs异质性和柔性身份的分子机制。他们分析了一系列携带不同剂量OTX2和/或NANOG的ESC系。他们发现OTX2和NANOG拮抗调节网络之间的协同作用指定了LIF + FBS中ESCs的身份。
Embryonic stem cells (ESCs) cultured in leukemia inhibitory factor (LIF) plus fetal bovine serum (FBS) exhibit heterogeneity in the expression of naive and primed transcription factors. This heterogeneity reflects the dynamic condition of ESCs and their versatility to promptly respond to signaling effectors promoting naive or primed pluripotency. Here, we report that ESCs lacking Nanog or overexpressing Otx2 exhibit an early primed identity in LIF + FBS and fail to convert into 2i-induced naive state. Conversely, Otx2-null ESCs possess naive identity features in LIF + FBS similar to Nanog-overexpressing ESCs and convert poorly into FGF-induced early primed state. When both Nanog and Otx2 are inactivated, ESCs cultured in LIF + FBS exhibit primed identity and weakened ability to convert into naive state. These data suggest that, through mutual antagonism, NANOG and OTX2 specify the heterogeneous identity of ESCs cultured in LIF + FBS and individually predispose them for optimal response to naive or primed inducing factors. Loss of Nanog or Otx2 overexpression induces primed identity in ESCs cultured in LIF Loss of Nanog or Otx2 overexpression affects naive conversion Otx2 null ESCs in LIF show naive identity and abnormal conversion into primed state ESCs lacking Otx2 and Nanog show primed identity and convert into naive and primed states In this article, Simeone and colleagues study the molecular mechanism controlling the heterogeneous and flexible identity of ESCs cultured in LIF + FBS. They analyze a series of ESC lines carrying different dosages of OTX2 and/or NANOG. They find that synergism between the OTX2 and NANOG antagonistic regulatory networks specifies the identity of ESCs in LIF + FBS.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
DOI：
10.1098/rstb.2013.0540
发表时间：
2014-12-05
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
--
作者：
Kalkan T;Smith A
通讯作者：
Smith A
影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
影响因子：
23.9
作者：
Nichols, Jennifer;Smith, Austin
通讯作者：
Smith, Austin
影响因子：
23.9
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
通讯作者：
Surani MA