Mazloom Amin R, Xu Huilei, Reig-Palou Jaume, Vasileva Ana, Román Angel-Carlos, Mulero-Navarro Sonia, Lemischka Ihor R, Sevilla Ana
Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, United States.
Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.
Front Cell Dev Biol. 2022 May 16;10:820255. doi: 10.3389/fcell.2022.820255. eCollection 2022.
Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to play a relevant role in cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these early stages of embryonic stem cell (ESC) differentiation remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of stem cells that incorporate protein-coding and miRNA genes based on miRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific stem cell miRNA expression program and integrates dynamic changes of feed-forward loops contributing to the early stages of cell differentiation upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in embryonic stem cells.
多能状态的特征是细胞既能自我更新又能分化，且多能性会不可逆丧失，这是发育生物学中的重要研究领域。尽管微小RNA（miRNA）已被证明在细胞分化中发挥相关作用，但整合到基因调控网络中的miRNA的作用及其在胚胎干细胞（ESC）分化早期阶段的动态变化仍不清楚。在这里，我们基于miRNA阵列表达以及雌激素相关受体β（Esrrb）下调后短转录本的定量测序，描述了包含蛋白质编码和miRNA基因的干细胞动态转录调控电路。数据揭示了关键干细胞转录因子Esrrb如何调节特定的干细胞miRNA表达程序，并整合前馈环的动态变化，这些变化在其下调时有助于细胞分化的早期阶段。这些发现共同为胚胎干细胞中转录后转录调控网络的结构提供了新见解。
