The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression.
The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression.
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DOI：
10.1016/j.celrep.2015.03.008
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发表时间：
2015-04-07
期刊：
影响因子：
8.8
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Jiang W;Liu Y;Liu R;Zhang K;Zhang Y
长非编码RNA(LncRNAs)调控多种生物学过程，包括细胞谱系的确定。在这里，我们报告了使用纯化的细胞群体对人内胚层和胰腺细胞系进行转录组分析。通过对数据集的分析，可以识别出数百个表现出分化阶段特异性表达模式的lncRNA。作为鉴定这些lncRNAs的第一步，我们重点研究了一种内胚层特异的lncRNA DEANR1(确定的内皮细胞相关的长非编码RNA1)，并证明了它在人类内胚层分化中发挥着重要作用。DEANR1通过正向调节内胚层因子FOXA2的表达促进内胚层分化。重要的是，FOXA2的过表达能够修复DEANR1耗尽引起的内胚层分化缺陷。在机制上，DEANR1通过帮助Smad2/3募集到FOXA2启动子来促进FOXA2的激活。因此，我们的研究不仅揭示了一大组分化阶段特异性的lncRNA，而且还鉴定了一个对内胚层分化重要的新的lncRNA。
Long non-coding RNAs (lncRNAs) regulate diverse biological processes including cell lineage specification. Here we report transcriptome profiling of human endoderm and pancreatic cell lineages using purified cell populations. Analysis of the data sets allowed the identification of hundreds of lncRNAs exhibiting differentiation stage-specific expression patterns. As a first step in characterizing these lncRNAs, we focus on an endoderm-specific lncRNA DEANR1 (Definitive Endoderm Associated long Non-coding RNA1) and demonstrate that it plays an important role in human endoderm differentiation. DEANR1 contributes to endoderm differentiation by positively regulating endoderm factor FOXA2 expression. Importantly, overexpression of FOXA2 is able to rescue endoderm differentiation defects caused by DEANR1 depletion. Mechanistically, DEANR1 facilitates FOXA2 activation by helping SMAD2/3 recruitment to the FOXA2 promoter. Thus, our study not only reveals a large set of differentiation stage-specific lncRNAs, but also characterizes a novel lncRNA important for endoderm differentiation.
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