Department of Genome Regulation, Max Planck Institute for Molecular Genetics, Berlin, Germany.
Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, Germany.
Elife. 2023 Jan 31;12:e83077. doi: 10.7554/eLife.83077.
Long non-coding RNAs (lncRNAs) have emerged as fundamental regulators in various biological processes, including embryonic development and cellular differentiation. Despite much progress over the past decade, the genome-wide annotation of lncRNAs remains incomplete and many known non-coding loci are still poorly characterized. Here, we report the discovery of a previously unannotated lncRNA that is transcribed 230 kb upstream of the gene and located within the same topologically associating domain. We termed it (ranscript egulating ndoderm and activated by so) and show that it is induced following SOX17 activation but its expression is more tightly restricted to early definitive endoderm. Loss of affects crucial functions independent of SOX17 and leads to an aberrant endodermal transcriptome, signaling pathway deregulation and epithelial to mesenchymal transition defects. Consequently, cells lacking the lncRNA cannot further differentiate into more mature endodermal cell types. Taken together, our study identified and characterized as a transiently expressed and essential non-coding regulator in early human endoderm differentiation.
长非编码 RNA（lncRNA）已成为多种生物过程的基本调控因子，包括胚胎发育和细胞分化。尽管在过去十年中取得了很大进展，但 lncRNA 的全基因组注释仍然不完整，许多已知的非编码基因座仍未得到很好的描述。在这里，我们报告了一种以前未注释的 lncRNA 的发现，该 lncRNA 转录于 基因上游 230kb 处，位于相同的拓扑关联域内。我们将其命名为 （ranscript egulating ndoderm and activated by so），并表明它在 SOX17 激活后被诱导，但它的表达更严格地局限于早期确定性内胚层。缺失 会影响独立于 SOX17 的关键功能，并导致异常的内胚层转录组、信号通路失调和上皮到间充质转化缺陷。因此，缺乏该 lncRNA 的细胞不能进一步分化为更成熟的内胚层细胞类型。总之，我们的研究鉴定并表征了 作为早期人内胚层分化中瞬时表达和必需的非编码调控因子。
