Single-cell profiling of lncRNAs and their cell lineage commitment roles via RNA-DNA-DNA triplex formation in mammary epithelium.,STEM CELLS

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Single-cell profiling of lncRNAs and their cell lineage commitment roles via RNA-DNA-DNA triplex formation in mammary epithelium.
STEM CELLS ( IF 4.0 ) Pub Date : 2020-09-15 , DOI: 10.1002/stem.3274
Haibo Xu _{1,

2,

3} , Xing Yang _{1,

4,

5} , Weiren Huang _{2,

3} , Yujie Ma ₁ , Hao Ke ₁ , Li Zou ₁ , Qin Yang ₁ , Baowei Jiao _{1,

6,

7}

Affiliation

Long noncoding RNAs (lncRNAs), which are crucial for organ development, exhibit cell‐specific expression. Thus, transcriptomic analysis based on total tissue (bulk‐seq) cannot accurately reflect the expression pattern of lncRNAs. Here, we used high‐throughput single‐cell RNA‐seq data to investigate the role of lncRNAs using the hierarchical model of mammary epithelium. With our comprehensive annotation of the mammary epithelium, lncRNAs showed much greater cell‐lineage specific expression than coding genes. The lineage‐specific lncRNAs were functionally correlated with lineage commitment through the coding genes via the cis‐ and trans‐effects of lncRNAs. For the working mechanism, lncRNAs formed a triplex structure with the DNA helix to regulate downstream lineage‐specific marker genes. We used lncRNA‐Carmn as an example to validate the above findings. Carmn, which is specifically expressed in mammary gland stem cells (MaSCs) and basal cells, positively regulated the Wnt signaling ligand Wnt10a through formation of a lncRNA‐DNA‐DNA triplex, and thus controlled the stemness of MaSCs. Our study suggests that lncRNAs play essential roles in cell‐lineage commitment and provides an approach to decipher lncRNA functions based on single‐cell RNA‐seq data.

中文翻译：

lncRNA 的单细胞分析及其通过乳腺上皮中 RNA-DNA-DNA 三链体形成的细胞谱系定型作用。

对器官发育至关重要的长非编码 RNA (lncRNA) 表现出细胞特异性表达。因此，基于全组织的转录组分析（bulk-seq）无法准确反映lncRNA的表达模式。在这里，我们使用高通量单细胞 RNA-seq 数据，利用乳腺上皮的分层模型来研究 lncRNA 的作用。通过对乳腺上皮的全面注释，lncRNA 显示出比编码基因更高的细胞谱系特异性表达。谱系特异性lncRNA通过编码基因通过lncRNA的顺式和反式效应与谱系定型在功能上相关。在工作机制上，lncRNA与DNA螺旋形成三链体结构来调节下游谱系特异性标记基因。我们以 lncRNA‐ Carmn为例来验证上述发现。 Carmn在乳腺干细胞（MaSCs）和基底细胞中特异性表达，通过形成lncRNA-DNA-DNA三链体，正向调节Wnt信号配体Wnt10a ，从而控制MaSCs的干性。我们的研究表明，lncRNA 在细胞谱系定型中发挥着重要作用，并提供了一种基于单细胞 RNA-seq 数据破译 lncRNA 功能的方法。

更新日期：2020-09-15

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