Human Yes Associated Protein (hYAP) expressing mouse liver (set 1)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE98228 | GEO | 2017/05/01
SECONDARY ACCESSION(S): PRJNA384357
REPOSITORIES: GEO
Similar Datasets
Project description:To check the gene expression profiles on hYAP Wild-type (WT) or active-form (1SA) and (2SA) expressing mouse liver
2017-05-01 | GSE98229 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-05-01 | GSE98231 | GEO
Project description:Human Yes Associated Protein (hYAP) expressing mouse liver
| PRJNA384350 | ENA
Project description:Adult radial glia-like cells (RGLs) residing in the subgranular zone (SGZ) of the dentate gyrus (DG) are finely regulated to control the generation of new neurons. Quiescence is essential for the long-term maintenance of the RGL pool. Intrinsic factors as well as extrinsic niche signals orchestrate the balance between RGL quiescence and activation, but the mechanisms are still not completely understood. Yap1, a core factor of Hippo signaling, is very important for the proliferation of stem cells of various organs and species, such as intestinal stem cells of the mouse and neural stem cells in Drosophila brain. Here I addressed the role of Yap1 in adult hippocampal neurogenesis by gain- and loss-of-function studies. I found that the expression of Yap1 was enriched in adult RGLs, but was undetectable in other cell types such as neurons and cells of the oligodendroglial lineage. Through the analysis of conditional knock-out of Yap1 in adult RGLs and their lineage, I found that fewer RGLs became activated while a significantly higher proportion of RGLs remained in the quiescent state. Conversely, overexpression of constitutively active mutant variant of Yap1 (Yap1 5SA) induced the proliferation of quiescent RGLs in vitro and in vivo. This effect was dependent on functional interaction with the TEA Domain Transcription Factor (TEAD). Pharmacological blocking the interaction between endogenous Yap1 and TEAD by verteporfin reduced the rate of proliferation of neural progenitors in vitro, which indicates a physiological role of Yap1-TEAD interaction in regulating the transition between quiescence and activation. Interestingly, constitutive expression of Yap1 5SA in RGLs blocked adult neurogenesis and retained the cells in a progenitor-like (Sox2+) state. To further explore the molecular mechanisms of Yap1 in regulating the activation of quiescent RGLs, single-cell RNA sequencing analysis was performed at 3 and 7 days following Yap1 5SA overexpression. Yap1 5SA overexpressing cells exhibited increased signature of active NSCs but also displayed distinct features such as epithelial-to-mesenchymal transition (EMT). Importantly, we found that Catenin Beta 1 (CTNNB1) was upregulated suggesting a potential involvement of Wnt signaling in the proliferative effect of Yap1 5SA overexpression in adult NSCs. In sum, this work provides compelling evidence for regulation of the balance between activation and quiescence of adult hippocampal RGLs by Yap1.
2023-01-16 | GSE144967 | GEO
Project description:UnlabelledAdult liver regeneration requires induction and suppression of proliferative activity in multiple types of liver cells. The mechanisms that orchestrate the global changes in gene expression that are required for proliferative activity to change within individual liver cells, and that coordinate proliferative activity among different types of liver cells, are not well understood. Morphogenic signaling pathways that are active during fetal development, including Hedgehog and Hippo/Yes-associated protein 1 (Yap1), regulate liver regeneration in adulthood. Cirrhosis and liver cancer result when these pathways become dysregulated, but relatively little is known about the mechanisms that coordinate and control morphogenic signaling during effective liver regeneration. We evaluated the hypothesis that the Hedgehog pathway controls Yap1 activation during liver regeneration by studying intact mice and cultured liver cells. In cultured hepatic stellate cells (HSCs), disrupting Hedgehog signaling blocked activation of Yap1, and knocking down Yap1 inhibited induction of both Yap1- and Hedgehog-regulated genes that enable HSC to become myofibroblasts (MFs). In mice, disrupting Hedgehog signaling in MFs inhibited liver regeneration after partial hepactectomy (PH). Reduced proliferative activity in the liver epithelial compartment resulted from loss of stroma-derived paracrine signals that activate Yap1 and the Hedgehog pathway in hepatocytes. This prevented hepatocytes from up-regulating Yap1- and Hedgehog-regulated transcription factors that normally promote their proliferation.ConclusionsMorphogenic signaling in HSCs is necessary to reprogram hepatocytes to regenerate the liver epithelial compartment post-PH. This discovery identifies novel molecules that might be targeted to correct defective repair during cirrhosis and liver cancer. (Hepatology 2016;64:232-244).
| S-EPMC4917408 | biostudies-literature
Project description:It is known that the liver undergoes size increase and differentiation simultaneously during the postnatal period. Cells in the liver undergo a period of well-controlled proliferation to achieve the adult liver-to-body weight ratio. The postnatal liver growth is also accompanied by simultaneous hepatic differentiation. However, the mechanisms of liver size regulation and differentiation are not completely clear. Herein we report that yes-associated protein (Yap), the downstream effector of the Hippo Kinase signaling pathway, plays a role in liver size regulation and differentiation during the postnatal liver growth period. Postnatal liver growth was studied in C57BL/6 mice over a time course of postnatal days (PND) 0-30. Analysis of nuclear Yap by Western blot indicated peak Yap activation between PND15-20, which coincided with increased cyclin D1 expression and liver cell proliferation. Analysis of postnatal liver development in Yap(+/-) mice revealed a significant decrease in the liver-to-body weight ratio compared with Yap(+/+) mice at PND15 and -30. Yap(+/-) mice exhibited a significant decrease in postnatal liver cell proliferation, but no change in apoptosis was observed. Furthermore, global gene expression analysis of Yap(+/-) livers revealed a role of Yap in regulation of genes involved in bile acid metabolism, retinoic acid metabolism, ion transport, and extracellular matrix proteins. Taken together, these data indicate that Yap plays a role in both cell proliferation and possibly in hepatic differentiation during postnatal liver development.
| S-EPMC3311431 | biostudies-literature
Project description:The activation of CD81 [the portal of entry of hepatitis C virus (HCV)] by agonistic antibody results in phosphorylation of Ezrin via Syk kinase and is associated with inactivation of the Hippo pathway and increase in yes-associated protein (Yap1). The opposite occurs when glypican-3 or E2 protein of HCV binds to CD81. Hepatocyte-specific glypican-3 transgenic mice have decreased levels of phosphorylated (p)-Ezrin (Thr567) and Yap, increased Hippo activity, and suppressed liver regeneration. The role of Ezrin in these processes has been speculated, but not proved. We show that Ezrin has a direct role in the regulation of Hippo pathway and Yap. Forced expression of plasmids expressing mutant Ezrin (T567D) that mimics p-Ezrin (Thr567) suppressed Hippo activity and activated Yap signaling in hepatocytes in vivo and enhanced activation of pathways of β-catenin and leucine rich repeat containing G protein-coupled receptor 4 (LGR4) and LGR5 receptors. Hepatoma cell lines JM1 and JM2 have decreased CD81 expression and Hippo activity and up-regulated p-Ezrin (T567). NSC668394, a p-Ezrin (Thr567) antagonist, significantly decreased hepatoma cell proliferation. We additionally show that p-Ezrin (T567) is controlled by epidermal growth factor receptor and MET. Ezrin phosphorylation, mediated by CD81-associated Syk kinase, is directly involved in regulation of Hippo pathway, Yap levels, and growth of normal and neoplastic hepatocytes. The finding has mechanistic and potentially therapeutic applications in hepatocyte growth biology, hepatocellular carcinoma, and HCV pathogenesis.
| S-EPMC10069283 | biostudies-literature
Project description:Activation of pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, is known to induce liver enlargement, but the molecular signals and cell types responding to PXR-induced hepatomegaly remain unknown. In this study, the effect of PXR activation on liver enlargement and cell change was evaluated in several strains of genetically modified mice and animal models. Lineage labeling using AAV-Tbg-Cre-treated Rosa26EYFP mice or Sox9-CreERT , Rosa26EYFP mice was performed and Pxr-null mice or AAV Yap short hairpin RNA (shRNA)-treated mice were used to confirm the role of PXR or yes-associated protein (YAP). Treatment with selective PXR activators induced liver enlargement and accelerated regeneration in wild-type (WT) and PXR-humanized mice, but not in Pxr-null mice, by increase of cell size, induction of a regenerative hybrid hepatocyte (HybHP) reprogramming, and promotion of hepatocyte and HybHP proliferation. Mechanistically, PXR interacted with YAP and PXR activation induced nuclear translocation of YAP. Blockade of YAP abolished PXR-induced liver enlargement in mice. Conclusion: These findings revealed a function of PXR in enlarging liver size and changing liver cell fate by activation of the YAP signaling pathway. These results have implications for understanding the physiological functions of PXR and suggest the potential for manipulation of liver size and liver cell fate.
| S-EPMC6324985 | biostudies-literature
Project description:Aim of the study was to elucidate YAP-regulated trophoblast-specific genes by analyzing differentially-expressed gene signatures between first trimester human cytotrophoblasts (vCTBs) transfected with a YAP-5SA mutant or a control plasmid.
2020-05-19 | GSE143858 | GEO
Project description:Cell competition is a cell-cell interaction by which a cell compares its fitness to that of neighboring cells. The cell with the relatively lower fitness level is the "loser" and actively eliminated, while the cell with the relatively higher fitness level is the "winner" and survives. Recent studies have shown that cells with high Yes-associated protein (YAP) activity win cell competitions but the mechanism is unknown. Here, we report the unexpected finding that cells overexpressing constitutively active YAP undergo apical extrusion and are losers, rather than winners, in competitions with normal mammalian epithelial cells. Inhibitors of metabolism-related proteins such as phosphoinositide-3-kinase (PI3K), mammalian target of rapamycin (mTOR), or p70S6 kinase (p70S6K) suppressed this apical extrusion, as did knockdown of vimentin or filamin in neighboring cells. Interestingly, YAP-overexpressing cells switched from losers to winners when co-cultured with cells expressing K-Ras (G12V) or v-Src. Thus, the role of YAP in deciding cell competitions depends on metabolic factors and the status of neighboring cells.
| S-EPMC4914932 | biostudies-literature