Design principles of pluripotency.

Design principles of pluripotency.
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DOI:
10.1002/emmm.200900035
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发表时间:
2009-08
影响因子:
11.1
通讯作者:
Smith, Austin
Smith, Austin
中科院分区:
医学1区
文献类型:
--
作者:
Smith, Austin

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多能性是个体细胞在胚胎或细胞培养环境中的信号指导下以灵活的方式启动成熟生物体的所有谱系的能力。它是哺乳动物发育和胚胎干细胞(ES)生物学的基石。多能细胞没有预先设定的程序,它是一张白纸。这种不受限制的细胞状态的设计原理是什么?遗传和细胞生物学研究指出转录因子命令而不是表观遗传治理(Niwa,2007; Silva & Smith,2008)。对这一观点的令人信服的支持来自Shinya Yamanaka的显着发现,即多能性可以通过转录因子诱导的重编程从体细胞中重建(Takahashi & Yamanaka,2006)。那么,这种独特的状态是如何获得的,如何保持它,以及如何路由到已提交的血统祖先的退出路径?这是我的实验室正在解决的一些问题。以下是对多能性和谱系决定的基本设计原则的个人看法。
Pluripotency is the capacity of individual cells to initiate all lineages of the mature organism in a flexible manner directed by signals in the embryo or cell culture environment. It is the keystone of mammalian development and of embryonic stem cell (ES) biology. A pluripotent cell has no predetermined programme; it is a blank slate. What are the design principles of this unrestricted cell state? Genetic and cell biological studies point to transcription factor command rather than epigenetic governance (Niwa, 2007; Silva & Smith, 2008). Persuasive support for this view comes from the remarkable discovery of Shinya Yamanaka that pluripotency can be recreated from somatic cells through transcription factor induced reprogramming (Takahashi & Yamanaka, 2006). So how is this unique status acquired, how can it be maintained, and how is the exit path (s) to committed lineage progenitors routed? These are some of the questions that my laboratory is addressing. What follows here is a personal perception of the underlying design principles of pluripotency and lineage determination.
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