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The Analysis Of The Expression Of YAP1in The Mouse Pancreatic Progenitor Cells And Investigations Over The Regulation Of The Pancreatic Progenitor Cells Proliferation By YAP1

Posted on:2015-02-13Degree:MasterType:Thesis
Country:ChinaCandidate:T MenFull Text:PDF
GTID:2180330434451049Subject:Developmental Biology
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In mammals, the Hippo pathway coordinates cell growth, proliferation, differentiation and apoptosis signals to regulate organ development. Central to this pathway is the transcriptional regulators YAP in mammals. The Hippo pathway has been involved in cell fate determination and organ development by phosphorylating and inhibiting YAP. Some evidences indicate that the Hippo pathway also has a crtical role for the self-renewal, expansion and differentiation of stem cells and tissue-specific progenitor cells through control of YAP. Although emerging research results show that the Hippo pathway transcriptional effector YAP promotes many tissue-specific stem/progenitor cells proliferation, such as intestinal stem cells, epidermal stem cells and liver bi-potential cells, the functions of YAP in pancreatic stem/progenitor cells is unclear. Here, firstly, We tetected the spatio-temporal expression pattern of yap1in mouse developing pancreata by in situ hybridization.The study results showed yapl mRNA was expressed highly in pancreatic epithelial cells at E12.5, subsequently, yapl expression was gradually decreased during the secondary transition (from E13.5toE15.5) Along with the pancreas development, the mRNA expression of yap1was almost undetectable at E17.5. Moreover, we found that YAP1was also highly expressed in adult pancreatic progenitor cells. Secondly, we performed si-YAP1knockdown of YAP1in pancreatic stem/progenitor cells. Knocking down YAP1by siRNA inhibited the proliferation of pancreatic progenitor cells. Finally, we preliminarily investigated the mechanism by which YAP1maintain the proliferative activity of pancreatic progenitor cells through using semi-RT-PCR. Our results revealed that si-YAP1knockdown of YAP1results in the decreased expression level of CyclinE1, which is known to promote the cell proliferation. Given the fact that the role of Yki for acceleration of cell proliferation is mostly mediated by CycE in Drosophila, our studies may suggest a potential evolutionary conservation from Drosophila to mammals.
Keywords/Search Tags:YAP1, pancreas development, pancreatic progenitor cells, the Hippo pathway, cell proliferation, differentiation, self-renewal
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