Single cell transcripional analysis of murine adult hepatocytes following YAP induction [Liver_scRNAseq_perfused]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA575012 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10204571_1.fastq.gz | Fastqsanger.gz | |||
| SRR10204571_2.fastq.gz | Fastqsanger.gz | |||
| SRR10204572_1.fastq.gz | Fastqsanger.gz | |||
| SRR10204572_2.fastq.gz | Fastqsanger.gz |
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Project description:Single cell transcripional analysis of adult liver cells following YAP induction [Liver_scRNAseq_allTissue]
| PRJNA575013 | ENA
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.
2017-10-19 | GSE89284 | GEO
Project description:YAP1 is a transcriptional co-activator regulated by the Hippo pathway, mechano-transduction, G-protein coupled receptors and WNT signaling. YAP1 activity depends on its stabilization and its nuclear localization. Once in the nucleus, YAP1 can regulate gene expression by interacting with transcription factors with DNA binding capability. While YAP1 main transcriptional partners belong to the TEAD family, several reports indicate that YAP1 can also associate with SMADs, RUNX and other transcription factors. YAP1 acts as a broad regulator of cell growth and differentiation, thus playing a pivotal role in regeneration, re-programming and cancer. How YAP1 may control such a large number of cellular processes is still to be fully understood. To identify how YAP1 controls transcription and to define gene expression programs directly regulated by YAP1, we conducted a genome wide investigation in the mouse liver. Integrated analyses of ChIP-seq and RNA-seq data indicated that YAP1 can act both as an activator and as a repressor in a context dependent way, and allowed the dissection of transcriptional mechanisms. Longitudinal analysis by ChIP-seq and RNA-seq highlighted differences in genome binding and transcriptional control which allowed the identification of acute and tonic YAP1 dependent responses. While during acute activation YAP1 supported cell cycle and signal transduction programs, its prolonged activation sustained a feedforward loop that potentiated and expanded YAP1 dependent transcription thus leading to the direct engagement of cell identity programs. Overall this study provides a genome scale understanding of how YAP1 controls gene expression and reveals principles in gene regulation which account for YAP1 ability to orchestrate development, regeneration and cell reprogramming.
2022-07-25 | GSE138190 | GEO
Project description:Hepatocyte specific TBG promoter-driven Cre,GFP and YAP S127A expression was achieved by retro orbital injection of AAV. RNA-seq was performed for hepatocytes isolated by FACS.
2021-11-17 | GSE146589 | GEO
Project description:Objective: YAP impairs hepatocyte regeneration in alcohol-related hepatitis (AH) but its impact on fibrogenesis remains unknown. Our aim was to describe fibrogenesis during AH and the relationship between impaired hepatocyte regeneration and fibrogenesis. Design: Fibrosis distribution and colocalization of YAP and αSMA were assessed by immunostaining. Extracellular matrix (ECM) composition in patients with severe AH (n=22) or alcohol-related cirrhosis (Cirrh, n=24) and healthy livers (Ctrl, n=15) was assessed by bulk and spatial proteomics and PCR. We generated organoids from AH and Cirrh livers and evaluated their impact on myofibroblasts in a 3D coculture model. Cirrh organoids were transduced with an active YAP and cocultured with myofibroblasts. Myofibroblasts were also cultured with medium from transduced (YAP medium) or not-transduced hepatocytes (CTRL medium).
2025-09-09 | PXD044031 | Pride
Project description:Role of Sox9 in Yap activated hepatocytes
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Project description:Assessment of Hepatocytes in response to Yap/Taz knockout and also CCl4 injury
2019-09-01 | GSE113756 | GEO
Project description:siRNA-mediated inhibition compared to untreated cells and cells transfected with nonsense siRNA. Loss of contact inhibition and anchorage-independent growth are hallmarks of cancer cells. In this context, frequent inactivation of the Hippo pathway and subsequent nuclear enrichment of the transcriptional coactivator yes-associated protein (YAP) uncouple cell proliferation and anti-apoptosis from contact inhibition, associated with uncontrolled tumor growth and tumor cell dissemination. However, general molecular mechanisms of tumor-supporting YAP activity remain unclear. In this study, we show that overexpression and nuclear accumulation of YAP in hepatocytes and hepatocellular carcinoma (HCC) cells leads to an induction of the Notch pathways through transcriptional activation of the Notch ligand jagged-1 (Jag-1). This induction of Jag-1 strictly depends on binding of YAP to TEAD4 and does not rely on WNT/β-catenin pathway activity. Co-activation of YAP, TEAD4, Jag-1, and the Notch target gene Hes-1 was significantly higher in HCC from patients with poor prognosis. High-level expression and nuclear accumulation of YAP correlates with Jag-1/Notch activation not only in human HCC tissues, but also in colon and pancreatic cancer tissues. Thus, our data demonstrate that YAP-driven co-activation of the Jag-1/Notch pathway in part facilitates oncogenic properties of the oncogene YAP not only in HCC but also in different gastrointestinal malignancies. Expression profiling of untreated HCC cell lines (control 1), cells transfected with scrambled/nonsense siRNA (control 2), and after siRNA-mediated YAP inhibition.
2012-11-01 | E-GEOD-35004 | biostudies-arrayexpress
Project description:Constitutive androstane receptor (CAR) agonists, such as TCPOBOP, are known to cause robust hepatocyte proliferation and hepatomegaly in mice along with induction of drug metabolism genes, without any associated liver injury. Yes-associated protein (YAP) is a key transcription regulator that tightly controls organ size including that of liver. Ours and other previous studies suggested increased nuclear localization and activation of YAP after TCPOBOP treatment in mice and potential role of YAP in CAR-driven proliferative response. Here, we investigated a direct role of YAP in CAR-driven hepatomegaly and hepatocyte proliferation using hepatocyte-specific YAP-KO mice. AAV8-TBG-CRE vector was injected to YAP-floxed mice for achieving hepatocyte-specific YAP deletion followed by TCPOBOP treatment. YAP deletion did not alter protein expression of CAR or CAR-driven induction of drug metabolism genes (including Cyp2b10, Cyp2c55 and UGT1a1). However, YAP deletion substantially reduced TCPOBOP-induced hepatocyte proliferation. TCPOBOP-driven cell cycle activation was disrupted in YAP-KO mice due to delayed (and decreased) induction of cyclin D1 and higher expression of p21, resulting in decreased phosphorylation of retinoblastoma (Rb) protein. Further, induction of other cyclins, which are sequentially involved in progression through cell cycle (including cyclin E1, A2 and B1) and important mitotic regulators (such as aurora B kinase and polo-like kinase 1) was remarkably reduced in YAP-KO mice. Microarray analysis revealed that 26% of TCPOBOP‐responsive genes mainly related to proliferation, but not to drug metabolism, were altered by YAP deletion. YAP regulated these proliferation genes via alerting expression of cMyc and FOXM1, two critical transcriptional regulators of CAR-mediated hepatocyte proliferation. Conclusion: Our study revealed an important role of YAP signaling in CAR-driven hepatocyte proliferation; however, CAR-driven induction of drug metabolism genes was independent of YAP. We used microarrays to detail the global programme of gene expression in livers of hepatocyte-specific YAP KO mice following TCPOBOP treatment
2021-09-09 | GSE148607 | GEO
Project description:The transcriptional coactivator Yap promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. Here we present evidence that Yap activation is insufficient to promote growth in the otherwise normal tissue. Using a mosaic mouse model, we demonstrate that Yap overexpression in a fraction of hepatocytes does not lead to their clonal expansion, as proliferation is counterbalanced by increased apoptosis. To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required. In response to liver injury, Yap drives clonal expansion, suppresses hepatocyte differentiation and promotes a progenitor phenotype. These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair. Totally sixteen samples
2015-02-07 | E-GEOD-65207 | biostudies-arrayexpress