Cellular trajectories and molecular mechanisms of iPSC reprogramming.
Cellular trajectories and molecular mechanisms of iPSC reprogramming.
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DOI：
10.1016/j.gde.2018.06.002
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发表时间：
2018-10
影响因子：
4
通讯作者：
Stadtfeld M
中科院分区：
文献类型：
--
作者：
Apostolou E;Stadtfeld M
诱导多能干细胞（iPSC）的发现巩固了转录因子作为控制细胞身份的主要参与者的概念，并提供了一个易于处理的工具来研究如何拆除体细胞身份并建立多能性。许多具有里程碑意义的研究通过描述转录、蛋白质和表观遗传变化的相对动力学，包括DNA甲基化和组蛋白修饰的改变，建立了iPSC形成的标志和路线图。最近，技术进步，如单细胞分析，高分辨率全基因组染色质测定和更有效的重编程系统已被用来挑战和完善我们对重编程过程的理解。在这里，我们将概述iPSC形成的分子机制的新见解，重点是核心重编程因子OCT4，KLF4，SOX 2和MYC（OKSM）如何驱动基因表达，染色质状态和3D基因组拓扑结构的变化。此外，我们还将讨论体外和体内系统中重编程因子表达的意外后果，这些结果可能指向iPSC技术的新应用。
The discovery of induced pluripotent stem cells (iPSCs) has solidified the concept of transcription factors as major players in controlling cell identity and provided a tractable tool to study how somatic cell identity can be dismantled and pluripotency established. A number of landmark studies have established hallmarks and roadmaps of iPSC formation by describing relative kinetics of transcriptional, protein and epigenetic changes, including alterations in DNA methylation and histone modifications. Recently, technological advancements such as single-cell analyses, high-resolution genome-wide chromatin assays and more efficient reprogramming systems have been used to challenge and refine our understanding of the reprogramming process. Here, we will outline novel insights into the molecular mechanisms underlying iPSC formation, focusing on how the core reprogramming factors OCT4, KLF4, SOX2 and MYC (OKSM) drive changes in gene expression, chromatin state and 3D genome topology. In addition, we will discuss unexpected consequences of reprogramming factor expression in in vitro and in vivo systems that may point towards new applications of iPSC technology.
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影响因子：
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Hawkins KE;Joy S;Delhove JM;Kotiadis VN;Fernandez E;Fitzpatrick LM;Whiteford JR;King PJ;Bolanos JP;Duchen MR;Waddington SN;McKay TR
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McKay TR
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影响因子：
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作者：
Banito, Ana;Rashid, Sheikh T.;Gil, Jesus
通讯作者：
Gil, Jesus