Moradi Sharif, Guenther Stefan, Soori Samira, Sharifi-Zarchi Ali, Kuenne Carsten, Khoddami Vahid, Tavakol Pouya, Kreutzer Susanne, Braun Thomas, Baharvand Hossein
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Department of Cardiac Development and Remodelling, Max-Planck Institute for Heart and Lung Research, Ludwigstr. 43, 61231, Bad Nauheim, Germany.
Stem Cell Rev Rep. 2023 Oct;19(7):2361-2377. doi: 10.1007/s12015-023-10582-6. Epub 2023 Jul 4.
Cells of the inner cell mass (ICM) acquire a unique ability for unlimited self-renewal during transition into embryonic stem cells (ESCs) in vitro, while preserving their natural multi-lineage differentiation potential. Several different pathways have been identified to play roles in ESC formation but the function of non-coding RNAs in this process is poorly understood. Here, we describe several microRNAs (miRNAs) that are crucial for efficient generation of mouse ESCs from ICMs. Using small-RNA sequencing, we characterize dynamic changes in miRNA expression profiles during outgrowth of ICMs in a high-resolution, time-course dependent manner. We report several waves of miRNA transcription during ESC formation, to which miRNAs from the imprinted Dlk1-Dio3 locus contribute extensively. In silico analyses followed by functional investigations reveal that Dlk1-Dio3 locus-embedded miRNAs (miR-541-5p, miR-410-3p, and miR-381-3p), miR-183-5p, and miR-302b-3p promote, while miR-212-5p and let-7d-3p inhibit ESC formation. Collectively, these findings offer new mechanistic insights into the role of miRNAs during ESC derivation.
在内细胞团（ICM）细胞体外转变为胚胎干细胞（ESC）的过程中，它们获得了无限自我更新的独特能力，同时保留了其自然的多谱系分化潜能。已经确定了几种不同的途径在ESC形成中发挥作用，但在此过程中非编码RNA的功能却知之甚少。在这里，我们描述了几种对从ICM高效生成小鼠ESC至关重要的微小RNA（miRNA）。使用小RNA测序，我们以高分辨率、时间进程依赖的方式表征了ICM生长过程中miRNA表达谱的动态变化。我们报告了ESC形成过程中几波miRNA转录，其中来自印记Dlk1-Dio3基因座的miRNA有广泛贡献。随后的功能研究通过计算机分析表明，Dlk1-Dio3基因座嵌入的miRNA（miR-541-5p、miR-410-3p和miR-381-3p）、miR-183-5p和miR-302b-3p促进ESC形成，而miR-212-5p和let-7d-3p则抑制ESC形成。总的来说，这些发现为miRNA在ESC衍生过程中的作用提供了新的机制见解。
