Small RNA 测序揭示 Dlk1-Dio3 基因簇内 microRNAs 作为多能性干细胞干性维持的主要调控因子。
Small RNA Sequencing Reveals Dlk1-Dio3 Locus-Embedded MicroRNAs as Major Drivers of Ground-State Pluripotency.
机构信息
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, Iran; Department of Developmental Biology, University of Science and Culture, Tehran, Iran.
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Banihashem Square, Banihashem Street, Ressalat Highway, Tehran 1665659911, Iran; Computer Engineering Department, Sharif University of Technology, Tehran, Iran.
出版信息
Stem Cell Reports. 2017 Dec 12;9(6):2081-2096. doi: 10.1016/j.stemcr.2017.10.009. Epub 2017 Nov 9.
Ground-state pluripotency is a cell state in which pluripotency is established and maintained through efficient repression of endogenous differentiation pathways. Self-renewal and pluripotency of embryonic stem cells (ESCs) are influenced by ESC-associated microRNAs (miRNAs). Here, we provide a comprehensive assessment of the "miRNome" of ESCs cultured under conditions favoring ground-state pluripotency. We found that ground-state ESCs express a distinct set of miRNAs compared with ESCs grown in serum. Interestingly, most "ground-state miRNAs" are encoded by an imprinted region on chromosome 12 within the Dlk1-Dio3 locus. Functional analysis revealed that ground-state miRNAs embedded in the Dlk1-Dio3 locus (miR-541-5p, miR-410-3p, and miR-381-3p) promoted pluripotency via inhibition of multi-lineage differentiation and stimulation of self-renewal. Overall, our results demonstrate that ground-state pluripotency is associated with a unique miRNA signature, which supports ground-state self-renewal by suppressing differentiation.
胚胎干细胞（ESCs）的自我更新和多能性受到 ESC 相关 microRNAs（miRNAs）的影响。在这里，我们对有利于胚胎干细胞多能性的条件下培养的胚胎干细胞的“miRNome”进行了全面评估。我们发现，与在血清中生长的胚胎干细胞相比，胚胎干细胞表达了一组独特的 miRNAs。有趣的是，大多数“胚胎干细胞 miRNAs”是由 12 号染色体上 Dlk1-Dio3 基因座内的印记区域编码的。功能分析表明，位于 Dlk1-Dio3 基因座内的胚胎干细胞 miRNAs（miR-541-5p、miR-410-3p 和 miR-381-3p）通过抑制多能性分化和刺激自我更新来促进多能性。总的来说，我们的研究结果表明，胚胎干细胞多能性与独特的 miRNA 特征相关，通过抑制分化来支持胚胎干细胞的多能性自我更新。
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