Project description:Hippo signaling is highly associated with activity in the stem cell compartment of many epithelial tissues. In this study, we examined if Hippo signaling inhibition (by inducing Yap expression) could convert differentiated cells into a progenitor like phenotype. Organoid cells derived from mouse livers under various conditions, wild-type, Yap ON (Plus Dox), and Yap ON then OFF (Minus Dox) was examined. Comparison between freshly isolated hepatocytes; Uninduced_YPF-#.cel against Organoids grown in wild-type conditions (WT), Yap On (in vivo) off (in vitro) - YapOrganoidDoxMinus , and Yap On continuously - YapOrganoidDoxPlus.
Project description:Hippo signaling is highly associated with activity in the stem cell compartment of many epithelial tissues. In this study, we examined if Hippo signaling inhibition (by inducing Yap expression) could convert differentiated cells into a progenitor like phenotype. Organoid cells derived from mouse livers under various conditions, wild-type, Yap ON (Plus Dox), and Yap ON then OFF (Minus Dox) was examined. Comparison between freshly isolated hepatocytes; Uninduced_YPF-#.cel against Organoids grown in wild-type conditions (WT), Yap On (in vivo) off (in vitro) - YapOrganoidDoxMinus , and Yap On continuously - YapOrganoidDoxPlus. Organoids grown in culture or YFP+ sorted liver cells after the indicated time of Yap expression were collected. These were amplified using Nugene technology and hybridized to Affymetrix MoGene1.0 st arrays.
Project description:Primary isolated hepatocytes derived from wildtype mice are compared with hepatocytes isolated from YAP(S127A) transgenic mice (Tschaharganeh at al., 2013 Gastroenterology, PMID 23419361). YAP induction was done for 8 weeks and livers showed hyperplasia without signs of malignant transformation.
Project description:Comparison of gene expression in adult male mouse livers between wildtype mice and Transgenic mice expressing human Small Heterodimer Partner in hepatocytes.
Project description:The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signaling provides the cellular building blocks required for rapid growth. Here, we report that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 develop enlarged livers and are prone to liver tumor formation. Transcriptomic profiling reveals that Yap1 reprograms genes involved in glutamine metabolism. Analysis of gene expression in WT and lf:Yap transgenic zebrafish livers.
Project description:To investigate how tumour cell-derived YAP is changing the paracrine communication network between tumour cells and non-tumorous cells in hepatocarcinogenesis, the expression and secretion of cytokines, growth factors and chemokines were analysed in transgenic mice with liver-specific and inducible expression of constitutively active human YAP (YAPS127A). Transcriptome analysis of primary isolated hepatocytes revealed that YAP overexpression induced the expression and secretion of many paracrine-acting factors with potential impact on other tumorous or non-tumorous cells (e.g. plasminogen activator inhibitor-1 (PAI-1), C-X-C motif chemokine ligand 13 (CXCL13), CXCL16).
Project description:We generated chimeric mice with livers that were predominantly repopulated with human hepatocytes. Hepatocytes were isolated from the chimeric mouse livers and their gene expressions were compared with hepatocytes isolated from normal human livers . Cluster and principal components analyses showed that gene expression profiles of hepatocytes from the chimeric mice and those from normal human livers were extremely closed. Additionally, we performed microarray experiments to examine gene expression in human tissues. This data was used for comparison with hepatocytes. A total of 22 tissues (bone marrow, cerebellum, colon, cortex, fetal brain, heart, kidney, liver, lung, pancreas, prostate, salivary gland, skeletal muscle, small intestine, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea and uterus) were examined.
