Epigenetic Plasticity of Hematopoietic Cells

In recent years significant evidence was provided for the concept that the developmental potential is engraved in the chromatin of stem cells. This is indicated by low-level expression of lineage specific genes and also by epigenetic alterations that occur prior to gene locus activation. In turn, cell lineage specification involves not only the activation, but also the epigenetic silencing of different genetic programmes. In this article, I will summarise recent data from my laboratory that indicate that (i) at the epigenetic level developmental processes occur in a step-wise fashion and (ii) that developmental windows exist, which are associated with a specific chromatin structure, in which such decisions can be reversed.     

原始生殖细胞发生的机制

生殖细胞的发生是发育和遗传的基础。在几乎所有哺乳动物中,原始生殖细胞（primordial germ cell,PGC）均由近端上胚层体细胞在周边细胞特定的信号诱导下特化而成。目前的研究已经发现一些与生殖细胞特化有关的信号分子和关键转录调控元件,以及特化后生殖细胞获得的与体细胞不同的生物特性。生殖细胞的特化是一个结合了体细胞发育程序的抑制、细胞多能性程序的启动和全基因组表观遗传重编程三个方面的动态的复杂过程。多能性干细胞（胚胎干细胞或诱导型多能干细胞）具有发育全能性,能分化为机体任何一种细胞类型,包括生殖细胞。利用多能性干细胞体外分化形成生殖细胞有助于深入系统地研究配子发生的调控机制,为干细胞在不育症治疗方面的应用带来新希望。     

Temporal and epigenetic regulation of neurodevelopmental plasticity

The anticipated therapeutic uses of neural stem cells depend on their ability to retain a certain level of developmental plasticity. In particular, cells must respond to developmental manipulations designed to specify precise neural fates. Studies in vivo and in vitro have shown that the developmental potential of neural progenitor cells changes and becomes progressively restricted with time. For in vitro cultured neural progenitors, it is those derived from embryonic stem cells that exhibit the greatest developmental potential. It is clear that both extrinsic and intrinsic mechanisms determine the developmental potential of neural progenitors and that epigenetic, or chromatin structural, changes regulate and coordinate hierarchical changes in fate-determining gene expression. Here, we review the temporal changes in developmental plasticity of neural progenitor cells and discuss the epigenetic mechanisms that underpin these changes. We propose that understanding the processes of epigenetic programming within the neural lineage is likely to lead to the development of more rationale strategies for cell reprogramming that may be used to expand the developmental potential of otherwise restricted progenitor populations.