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Quick Coordinated and Authentic Reprogramming of Ribosome Biogenesis during iPSC Reprogramming

机译：在IPSC重新编程过程中快速协调和真实的核糖体生物生物重新编程

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摘要

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.
机译：诱导多能干细胞（IPSC）到OCT4（八寡发音子结合转录因子4），SOX2（SR Box 2），KLF4（Krüppel样因子4）和Myc（细胞髓细胞瘤，C-Myc或Myc）（集体OSKM ）是革命性的，但非常低效，缓慢和随机。它是未知的是，多步，多路径和低效IPSC重新编程的效力方面是什么。间充质 - 上皮（Met）转变被称为重新编程的最早途径。利用最近建立的重编程和重编程合法性的概念，作者首先证明核糖体生物发生（RB）在与成纤维细胞相比，在人胚胎干细胞方面全球富集，多能性重编程的流行的起始细胞。然后显示RB网络以协调的方式快速重新编程。人类IPSC也表现出更强大的核糖体生物发生。在来自不同供体的独立成纤维细胞线中也观察到核糖体生物发生的快速和全球重新编程。本研究另外表现出满足在适当的RB重新编程时没有显着发起。这种快速，协调和真实的RB通过OSKM重新编程因子重新编程为更强大的多能状态，显着造影了IPSC重新编程的总体低效率和长期延迟，并与低效OSKM重新编程的效力方面保持良好。

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