将iPS细胞定向分化为胰岛β细胞-北京生命科学研究所.docVIP

iPS细胞定向分化为胰岛β细胞 研究小组成员：刘楠，李辉莹，吴德伟，窦坤，蒋韬，周溦，陈珺，曾扬，杨杨，李磊，吴尚宜，朱翔龙 指导教师：高绍荣博士 Abstract: iPS cells are somatic cell derived pluripotent cells induced by four factors. These cells can give rise to derivatives of all three germ layers. iPS cells have the potential to be differentiated into cell types such as neurons and blood precursors, which has broad implications for the use of stem cells for potential use in therapy. In this project we want to induce iPS cells instead of ES cells to induce pancreatic β cells for transplantation therapy of type I diabetes mellitus which is caused by an autoimmune destruction of the insulin-producingβ cells. A. Introduction to iPS cells and Pancreatic β cells What are iPS cells? iPS细胞（induced pluripotent stem cells）这一名词由Yamanaka在2006年提出。他的小组通过对胚胎干细胞的研究发现，胚胎干细胞中存在一系列特异性表达的蛋白质，而当胚胎干细胞分化时，这些蛋白表达减少。那么如果在小鼠体细胞内表达这些蛋白，能否使体细胞转变为具有干细胞全能性质的细胞呢？经过对这些因子的组合和筛选，他们确定了Oct4，Sox2，c-Myc和Klf4这四种转录因子。他们使用慢病毒载体将这四种因子（及其各自的启动子）导入到小鼠皮肤成纤维细胞中，并经过筛选，发现了具有干细胞形态的细胞群落。这些细胞群落具有胚胎干细胞特异的表面抗原（Stage specific embryonic antigen ，SSEA），也通过Teratoma formation、Chimera formation和Tetraploid complementation检测（参考method），充分证明了它们具有多能性（pluripotent），因此命名为induced Pluripotent Stem cells。 ADDIN REFMGR.CITE RefmanCiteAuthorTakahashi K ./AuthorYear2006/YearRecNum4/RecNumIDTextInduction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors/IDTextMDL Ref_Type=GenericRef_TypeGeneric/Ref_TypeRef_ID4/Ref_IDTitle_PrimaryInduction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors/Title_PrimaryAuthors_PrimaryTakahashi K ./Authors_PrimaryAuthors_PrimaryYamanaka S/Authors_PrimaryDate_Primary2006/Date_PrimaryReprintNot in File/ReprintStart_Page663/Start_PageVolume126/VolumeIssue4/IssuePub_PlaceCell/Pub_PlaceZZ_WorkformID33/ZZ_WorkformID/MDL/Cite/Refman1 2007年12月，日本的Yamanaka和美国威斯康辛大学的Thomson小组分别在cell和science上同时发表自己的研究成果 ADDIN REFMGR.CITE RefmanCiteAuthorTakahashi K ./AuthorYear2006/YearRecNum4/RecNumIDTextInductio