Klf4在维持胚胎干细胞干性方面的分解.ppt

Klf4在维持胚胎干细胞干性方面的研究;;Epiblast; The newly formed epiblast is a cluster of 10–20 unspecialized cells sandwiched between the trophoblast and the hypoblast.;The Limitation of Totipotency ; The ICM produces a second extraembryonic lineage, the hypoblast, and around the same time, the remaining cells develop into pluripotent epiblast.The epiblast is functionally and molecularly distinct from blastomeres and early inner cell mass (Gardner, 1998;Kaji et al., 2007; Kurimoto et al., 2006). Thus, rather than representing a diminution in potency from the egg,we suggest that the epiblast constitutes the ground state, meaning a fully unrestricted population that harbors the requisite developmental potency and ?exibility to produce all embryonic lineages. ; Nichols and Smith have suggested that the two types of ESC differ fundamentally in the gene networks that maintain their pluripotency and named the LIF-dependent ESC “naive”and the FGF2-dependent type “primed.”;The Ground State and True Embryonic Stem Cells ; Embryonic stem cells (ESCs) can be derived at this point(Evans and Kaufman, 1981; Martin, 1981). ESCs represent immortalization of the naive epiblast. Under appropriate conditions, they exhibit unlimited selfrenewal capacity while retaining the attributes of preimplantation epiblast identity and potency. ; ESCs also share an epigenetic feature with preimplantation epiblast. This trait is the presence of two active X chromosomes in female cells. In female embryos, the paternally inherited X chromosome is silenced during cleavage and remains silent in extraembryonic lineages. Reactivation occurs transiently in the pluripotent lineage prior to implantation (Heard,2004). ; ; In XX embryos, one of the X chromosomes undergoes random inactivation in early egg cylinder epiblast cells (Heard, 2004). The epiblast is then subject to a systematic topological bomb