Quick, Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming.

Quick, Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming.
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iPSC重编程期间核糖体生物发生的快速,协调和真实重编程。

DOI:
10.3390/cells9112484
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发表时间:
2020-11-15
期刊:
影响因子:
6
通讯作者:
Hu K
Hu K
中科院分区:
生物学2区
文献类型:
--
作者:
Hu K

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通过OCT 4(八聚体结合转录因子4),SOX 2(SR box 2),KLF 4(Krüppel样因子4)和MYC(细胞性骨髓细胞瘤病,c-MYC或MYC)(统称为OSKM)诱导多能干细胞(iPSC)是革命性的,但效率非常低,缓慢且随机。尚不清楚多步骤、多途径和低效iPSC重编程的效力方面的基础是什么。间质-上皮(MET)转化被认为是最早的重编程途径。使用最近建立的概念的重编程和重编程的合法性,作者首次证明,核糖体生物合成(RB)是全球丰富的人类胚胎干细胞相比,成纤维细胞,流行的多能性重编程的起始细胞。然后,它表明,RB网络被重新编程迅速协调的方式。人类iPSC也表现出更强大的核糖体生物合成。在来自不同供体的独立成纤维细胞系中也观察到核糖体生物合成的快速和全局重编程。本研究还证明,MET在适当的RB重编程时基本上未启动。通过OSKM重编程因子将这种快速、协调和真实的RB重编程为更稳健的多能状态与iPSC重编程的整体低效率和长潜伏期形成鲜明对比,并且与低效OSKM重编程的效力方面很好地一致。
Induction of pluripotent stem cells (iPSC) by OCT4 (octamer-binding transcription factor 4), SOX2 (SR box 2), KLF4 (Krüppel-Like Factor 4), and MYC (cellular Myelocytomatosis, c-MYC or MYC) (collectively OSKM) is revolutionary, but very inefficient, slow, and stochastic. It is unknown as to what underlies the potency aspect of the multi-step, multi-pathway, and inefficient iPSC reprogramming. Mesenchymal-to-epithelial (MET) transition is known as the earliest pathway reprogrammed. Using the recently established concepts of reprogramome and reprogramming legitimacy, the author first demonstrated that ribosome biogenesis (RB) is globally enriched in terms of human embryonic stem cells in comparison with fibroblasts, the popular starting cells of pluripotency reprogramming. It is then shown that the RB network was reprogrammed quickly in a coordinated fashion. Human iPSCs also demonstrated a more robust ribosome biogenesis. The quick and global reprogramming of ribosome biogenesis was also observed in an independent fibroblast line from a different donor. This study additionally demonstrated that MET did not initiate substantially at the time of proper RB reprogramming. This quick, coordinated and authentic RB reprogramming to the more robust pluripotent state by the OSKM reprogramming factors dramatically contrasts the overall low efficiency and long latency of iPSC reprogramming, and aligns well with the potency aspect of the inefficient OSKM reprogramming.
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