Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells.
Suppressing Nodal Signaling Activity Predisposes Ectodermal Differentiation of Epiblast Stem Cells.
复制标题
抑制节点信号活动促进外胚层干细胞的外胚层分化
DOI：
10.1016/j.stemcr.2018.05.019
复制
发表时间：
2018-07-10
影响因子：
5.9
通讯作者：
Jing N
中科院分区：
文献类型：
--
作者：
Liu C;Wang R;He Z;Osteil P;Wilkie E;Yang X;Chen J;Cui G;Guo W;Chen Y;Peng G;Tam PPL;Jing N
在这里，在一个基于干细胞的模型中，研究了小鼠原肠胚形成过程中外胚层（一种短暂的生殖层组织）特化的分子机制。我们通过抑制Nodal信号传导活性，从小鼠外胚层干细胞（EpiSC）中捕获了具有增强的外胚层潜能的自我更新细胞群。Nodal抑制的EpiSC的转录组类似于胚胎日龄（E）7.0和E7.5小鼠胚胎的前上胚层的转录组，其伴随着反映外胚层谱系相关基因表达的启动的染色质修饰。结节抑制的EpiSC在体外表现出增强的外胚层分化，并有助于植入后嵌合体中的神经外胚层和表面外胚层，但在体外和嵌合体中失去了中内胚层分化的倾向。我们的研究结果表明，外胚层祖细胞的特化是通过抑制Nodal信号活性而增强的，外胚层样干细胞为研究外胚层衍生的外胚层的分子特征提供了实验模型。自我更新的上胚层干细胞可以在Nodal抑制下维持Nodal抑制的上胚层干细胞和外胚层显示相似的转录组阻断Nodal将表观基因组改变为与外胚层潜能相关的表观基因组Nodal抑制的上胚层干细胞优先分化为外胚层细胞在这篇文章中，Liu及其同事表明，Nodal抑制的外胚层干细胞可以在体外自我更新，并显示出与晚幼粒细胞外胚层相似的转录组。原肠胚胚进一步的分析表明，Nodal信号传导的抑制使表观基因组倾向于外胚层相关状态。此外，这些Nodal抑制的上胚层干细胞有效地分化为外胚层细胞，但不是中内胚层谱系。
The molecular mechanism underpinning the specification of the ectoderm, a transient germ-layer tissue, during mouse gastrulation was examined here in a stem cell-based model. We captured a self-renewing cell population with enhanced ectoderm potency from mouse epiblast stem cells (EpiSCs) by suppressing Nodal signaling activity. The transcriptome of the Nodal-inhibited EpiSCs resembles that of the anterior epiblast of embryonic day (E)7.0 and E7.5 mouse embryo, which is accompanied by chromatin modifications that reflect the priming of ectoderm lineage-related genes for expression. Nodal-inhibited EpiSCs show enhanced ectoderm differentiation in vitro and contribute to the neuroectoderm and the surface ectoderm in postimplantation chimeras but lose the propensity for mesendoderm differentiation in vitro and in chimeras. Our findings show that specification of the ectoderm progenitors is enhanced by the repression of Nodal signaling activity, and the ectoderm-like stem cells provide an experimental model to investigate the molecular characters of the epiblast-derived ectoderm. Self-renewing epiblast stem cells can be maintained under Nodal inhibition Nodal-inhibited epiblast stem cells and the ectoderm display similar transcriptome Blocking Nodal changes the epigenome to that associated with ectoderm potency Nodal-inhibited epiblast stem cells differentiate preferentially to ectodermal cells In this article, Liu and colleagues show that Nodal-inhibited epiblast stem cells can self-renew in vitro and display similar transcriptome compared with the ectoderm of late-gastrula embryo. Further analysis shows that inhibition of Nodal signaling predisposes the epigenome to ectoderm-associated status. Moreover, these Nodal-inhibited epiblast stem cells efficiently differentiate to ectodermal cells but not mesendoderm lineages.
登录
查看更多内容
影响因子：
11.8
作者：
Rugg-Gunn, Peter J.;Cox, Brian J.;Lanner, Fredrik;Sharma, Parveen;Ignatchenko, Vladimir;McDonald, Angela C. H.;Garner, Jodi;Gramolini, Anthony O.;Rossant, Janet;Kislinger, Thomas
通讯作者：
Kislinger, Thomas
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
30.8
作者：
Liu, PT;Wakamiya, M;Bradley, A
通讯作者：
Bradley, A
影响因子：
64.8
作者：
Brennan, J;Lu, CC;Robertson, EJ
通讯作者：
Robertson, EJ
影响因子：
4.6
作者：
Mesnard, Daniel;Guzman-Ayala, Marcela;Constam, Daniel B.
通讯作者：
Constam, Daniel B.