Roles of EpCAM and CLDN-7 in reprogramming mouse fibroblast into induced pluripotent stem cells

Autor: Yao-De Huang, 黃耀德
Rok vydání: 2010
Druh dokumentu: 學位論文 ; thesis
Popis: 98
Epithelial cell adhesion molecule (EpCAM) is a cell adhesion molecule and a potential target for therapeutic antibodies. Recently, EpCAM has been shown to regulate tumor cell proliferation by its nucleocytoplasmic intracellular domain fragment (ICD). EpCAM intracellular domain (EpICD) activates C terminal myelocytomatosis oncogene (c-Myc) in nucleus by Wnt signal pathway. On the other hand, the complex of EpCAM and the tight junction protein claudin-7 (CLDN-7) would promote tumorigenicity and accelerates tumor growth. We observed that EpCAM and CLDN-7 express in both mouse embryonic stem cells and induced poluripotent stem cells. In this study we first discovered that the expressions of EpCAM and CLDN-7 would be activated when reprogramming mouse embryonic fibroblast cells into induced pluripotent stem cells. The efficiency of iPS reprogramming was enhanced by overexpressing EpCAM, CLDN-7 or both. Furthermore, silence of endogenous EpCAM or CLDN-7 resulted in the reduction of iPS reprogramming. However, ectopic expression of EpCAM and CLDN-7 in differential somatic cells such as mouse fibroblast cells had no effect on the activation of pluripotency-associated gene Nanog, Oct4, Sox2, c-Myc and KLF4. Our data show that EpCAM positively regulates iPS reprogramming, yet the detail mechanism remains unclear.
Databáze: Networked Digital Library of Theses & Dissertations