Recent studies have revealed the importance of long noncoding RNAs (lncRNAs) as tissue-specific regulators of gene expression. There is ample evidence that distinct types of vasculature undergo tight transcriptional control to preserve their structure, identity, and functions. We determined, for the first time, the global lineage-specific lncRNAome of human dermal blood and lymphatic endothelial cells (BECs and LECs), combining RNA-Seq and CAGE-Seq. A subsequent genome-wide antisense oligonucleotide-knockdown screen of a robust set of BEC- and LEC-specific lncRNAs identified LETR1 as a critical gatekeeper of the global LEC transcriptome. Deep RNA-DNA, RNA-protein, and phenotype rescue analyses revealed that LETR1 acts as a nuclear trans-acting lncRNA modulating, via key epigenetic factors, the expression of essential target genes, including KLF4 and SEMA3C, governing the growth and migratory ability of LECs. Together, our study provides new evidence supporting the intriguing concept that every cell type expresses precise lncRNA signatures to control lineage-specific regulatory programs.

中文翻译：

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LETR1是一种淋巴管内皮特异性lncRNA，通过KLF4和SEMA3C控制细胞增殖和迁移

最近的研究表明，长的非编码RNA（lncRNA）作为基因表达的组织特异性调节剂的重要性。有充分的证据表明，不同类型的脉管系统会受到严格的转录控制，以保持其结构，特性和功能。我们首次确定了人类真皮血液和淋巴内皮细胞（BEC和LEC）的全球谱系特异性lncRNAome，结合了RNA-Seq和CAGE-Seq。随后对一组强大的BEC和LEC特异性lncRNA进行全基因组反义寡核苷酸敲低筛选，将LETR1鉴定为全球LEC转录组的关键关守。深入的RNA-DNA，RNA-蛋白质和表型拯救分析表明，LETR1充当核反式lncRNA，它通过关键表观遗传因子调节必需靶基因的表达，包括KLF4和SEMA3C，它们控制着LEC的生长和迁移能力。总之，我们的研究提供了新的证据，支持了一个有趣的概念，即每种细胞类型均表达精确的lncRNA签名，以控制特定于谱系的调控程序。