Studies of Direct Pluripotent Stem Cell Programming

 描述(申请人提供)：直接多能干细胞编程的研究。众所周知，胚胎发育过程中细胞命运的诱导是通过生长因子(1)等发育信号的作用来调控的。适当地暴露在这些信号下会导致胚胎的正常构型和生长。我们最近提出，这种信号传递的一个结果，细胞类型分化，除了涉及其他因素外，还涉及到 转录或表观遗传状态，它决定了要指定的细胞类型；2.它是适当的“细胞周期”状态，影响分化速度(2)。在一定限度内，t有可能扰乱正常的分化过程，并通过非自然发生的途径更快地达到分化状态。这种对正常分化过程的改变的研究有助于我们理解细胞命运所需的要素，而不是只研究正常的胚胎分化。此外，这些改变的分化途径可能会为再生医学带来有用的方法。这一建议的目的是发展和更好地了解分化的途径独立性以及转录调节和细胞周期调节的特殊作用。我们将解决三个重要问题：1.改变分化途径背后的潜在分子变化；2.就不同的细胞类型而言，我们开发的方法有多广泛；3.在小鼠ES细胞中的这些发现能否在人类身上得到证实。

 DESCRIPTION (provided by applicant): Studies of Direct Pluripotent Stem Cell Programming. It is widely known that the induction of cell fates during embryogenesis is orchestrated through the action of developmental signals, such as growth factors (1). Proper exposure to these signals leads to the normal patterning and growth of the embryo. We recently proposed that one outcome of this signaling, cell type differentiation, involves among other factors alignment of the transcriptional or epigenetic state, which determines the cell type to be specified, and 2. It's appropriate "cell cycle" state, which affects the rate of differentiation (2). Within some limits, t may be possible to perturb the normal process of differentiation and achieve differentiated states more rapidly and through pathways that do not occur naturally. This study of the alteration of the normal differentiation process helps us understand the elements required for cell fate and cannot be understood by studying only normal embryonic differentiation. Furthermore, these altered pathways of differentiation could lead to useful approaches for regenerative medicine. The aim of this proposal is to develop and to better understand the pathway independence of differentiation and the special role of transcriptional regulators and cell cycle regulation. We will address three important issues: 1. What are the underlying molecular changes that underlie altered pathways of differentiation, 2. In terms of different cell types, how widely applicable are the methods we developed, and 3. Can these discoveries in mouse ES cells be demonstrated in human.