Hematopoietic stem cells(HSCs)are a population of multipotent cells that can self-renew and differentiate into all blood *** development must be tightly controlled from cell fate determination to self-maintenance duri...
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Hematopoietic stem cells(HSCs)are a population of multipotent cells that can self-renew and differentiate into all blood *** development must be tightly controlled from cell fate determination to self-maintenance during *** involves a panel of important developmental signaling pathways and other factors which act synergistically within the HSC population and/or in the HSC *** conserved processes of HSC development plus many other developmental advantages make the zebrafish an ideal model organism to elucidate the regulatory mechanisms underlying HSC programming in vertebrates.I will talk about our recent progress on zebrafish HSCs using functional genomics approaches,with particular focus on how developmental signaling controls hemogenic endothelium-derived HSC *** hematopoietic stem cell system is a paradigm for stem cell *** of the zebrafish model to study signaling regulation of HSCs in vivo has resulted in a great deal of information concerning HSC biology in *** new findings facilitate a better understanding of molecular mechanisms of HSC programming,and will provide possible new strategies for generation and/or expansion of transplantable and functional HSCs in vitro.
抗心律失常药物的主要作用靶点是对心肌动作电位的形成有重要贡献的离子通道。心肌内向整流钾通道(IK1通道)是维持和稳定心肌静息电位的最重要的离子通道,也参与动作电位的形成。因此干预IK1通道对心肌的兴奋性和心律失常的发生将产生重要的作用。但是目前还没有用于临床的主要以IK1通道为靶点的药物。我们课题组前期的研究发现zacopride可以选择性激动IK1通道电流,并观察了激动IK1通道的抗心律失常和抗心室重构的作用,得到了非常令人兴奋的结果。***通过选择性激动IK1电流起到抗心律失常的作用:1)Zacopride可特异性激动大鼠心肌细胞IK1电流,对INa、ICa-L、Ito、IKsus、IKr、和INa/Ca无显著作用,对Ipump也无显著作用。2)Zacopride通过特异性激动大鼠心肌细胞IK1电流抑制aconitine诱发的DADs(delayed after depolarization),TA和心室的心动过速。3)Zacopride可以抗室性心律失常,对心房的节律无影响。4)体外表达IK1通道的三种亚单位Kir2.1、Kir2.2和Kir2.3发现,zacopride只激动Kir2.1同源聚合体,对Kir2.2和Kir2.3的同源体和这三种亚单位任意组合的异聚体都无效。而心室肌IK1的构成是以Kir2.1为主的。***通过激动大鼠心肌细胞IK1通道发挥抗心室重构的作用:1)Zacopride对大鼠心室肥厚具有抗重构作用。2)Zacopride可以抑制ISO引发的延迟后除极和乌头碱引起的触发性心律失常。3)Zacopride减轻心肌肥厚大鼠心肌细胞Ca2+超载,抑制了促进心肌肥大基因表达的钙调蛋白激酶Ⅱ表达。这些研究为IK1激动剂的作用找到了分子靶点,理论上排除了激动心房肌IK1诱发房颤的可能。且Zacoprid还可以通过激动IK1发挥抗心室重构作用.
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