Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas (FORTH), Heraklion, Crete 70013, Greece; Department of Molecular Biology and Genetics, Democritus University of Thrace, Dragana, Alexandroupolis, Evros 68100, Greece.
Stem Cell Reports. 2017 May 9;8(5):1366-1378. doi: 10.1016/j.stemcr.2017.03.006. Epub 2017 Apr 6.
Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state. During differentiation of embryoid bodies, PML influences cell-fate decisions between mesoderm and endoderm by controlling the expression of Tbx3. PML loss compromises the reprogramming ability of embryonic fibroblasts to induced pluripotent stem cells by inhibiting the transforming growth factor β pathway at the very early stages. Collectively, these results designate PML as a member of the regulatory network for ESC naive pluripotency and somatic cell reprogramming.
早幼粒细胞白血病蛋白（PML）是 PML 核体的主要组成部分，它在不同的细胞类型中调节着各种生理过程。然而，其在胚胎干细胞（ESC）中的功能知之甚少。在这里，我们报告 PML 通过控制细胞周期进程和维持关键多能性因子的表达，有助于 ESC 自我更新的维持。转录组分析和增益或缺失功能方法表明，PML 缺陷型 ESC 表现出与原始态和更接近初始态的形态、代谢和生长特性。在胚状体的分化过程中，PML 通过控制 Tbx3 的表达来影响中胚层和内胚层之间的细胞命运决定。PML 的缺失会通过在早期阶段抑制转化生长因子 β 途径来损害胚胎成纤维细胞向诱导多能干细胞的重编程能力。总的来说，这些结果表明 PML 是 ESC 原始态多能性和体细胞重编程的调控网络的成员。
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