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SRP053235
Mus musculus
13 Downloadable Samples
Illumina HiSeq 2500
Description
Defective Hippo/YAP signaling in the liver results in tissue overgrowth and development of hepatocellular carcinoma (HCC). Here, we uncover mechanisms of YAP-mediated hepatocyte reprogramming and HCC pathogenesis. We show that YAP functions as a rheostat maintaining metabolic specialization, differentiation and quiescence within the hepatocyte compartment. Importantly, treatment with siRNA-lipid nanoparticles (siRNA-LNPs) targeting YAP restores hepatocyte differentiation and causes pronounced tumor regression in a genetically engineered mouse HCC model (mice with liver-specific Mst1/Mst2 double knockout). Furthermore, YAP targets are enriched in an aggressive human HCC subtype characterized by a proliferative signature and absence of CTNNB1 mutations. Thus, our work reveals Hippo signaling as a key regulator of positional identity of hepatocytes, supports targeting YAP using siRNA-LNPs as a paradigm of differentiation-based therapy, and identifies an HCC subtype potentially responsive to this approach. Overall design: Mice with liver-specific Mst1/Mst2 double-knockout (Adeno-Cre injected Mst1-/-; Mst2Flox/Flox mice) were monitored for the formation of HCC by ultrasound imaging. Animals were then randomized to be treated by intravenous injection of either siYap-LNPs or siLuciferase-LNPs for a period of 9 days.
Publication Title
YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 97 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The concept of tumor stem cells (TSCs) provides a new paradigm for understanding tumor biology, although it remains unclear whether TSCs will prove to be a more robust model than traditional cancer cell lines. We demonstrate marked phenotypic and genotypic differences between primary human tumor-derived TSCs and their matched glioma cell lines. TSCs derived directly from primary glioblastomas harbor extensive similarities to normal NSC and recapitulate the genotype, gene expression patterns and in vivo biology of human glioblastomas. By contrast, the matched, traditionally grown tumor cell lines do not secondary to in vitro genomic alterations. These findings suggest that TSCs may be a more reliable model than many commonly utilized cancer cell lines for understanding the biology of primary human tumors. Analysis of gene expression data is described in Lee et al., Cancer Cell, 2006.
Publication Title
Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion.
Publication Title
Identification of molecular pathways facilitating glioma cell invasion in situ.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We used laser capture microdissection to isolate both microvascular endothelial cells and neurons from post mortem brain tissue from patients with schizophrenia and bipolar disorder and healthy controls. RNA was isolated from these cell populations, amplified, and analysed using Affymetrix HG133plus2.0 GeneChips. In the first instance, we used the dataset to compare the neuronal and endothelial data, in order to demonstrate that the predicted differences between cell types could be detected using this methodology.
Publication Title
The cerebral microvasculature in schizophrenia: a laser capture microdissection study.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 577 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This is Rembrandt gene expression data (Affymetrix HG-U133Plus2).
Publication Title
Rembrandt: helping personalized medicine become a reality through integrative translational research.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
It has been postulated that during human fetal development all cells of the lung epithelium derive from an embryonic endodermal NKX2-1+ precursor, however, this hypothesis has not been formally tested due to an inability to purify or track this theorized cell for detailed characterization. Here we engineer and developmentally differentiate NKX2-1GFP reporter pluripotent stem cells (PSCs) in vitro to generate and isolate a human primordial lung progenitor that expresses NKX2-1 but is initially devoid of markers of differentiated lung lineages. As these progenitors move through the earliest moments of lung lineage specification from definitive endoderm they can be imaged in real time or isolated for time-series global transcriptomic profiling. We performed microarray analysis of 5 timepoints of human iPSC to lung directed differentiation compared to week 21 human fetal lung and Neural NKX2-1+ cell controls. These profiles indicate that evolutionarily conserved, stage-dependent developmental gene signatures are expressed in primordial human lung progenitors.
Publication Title
Efficient Derivation of Functional Human Airway Epithelium from Pluripotent Stem Cells via Temporal Regulation of Wnt Signaling.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Transcriptome analysis of growth hormone dependant genes in glomerular podocytes
Publication Title
Growth hormone (GH)-dependent expression of a natural antisense transcript induces zinc finger E-box-binding homeobox 2 (ZEB2) in the glomerular podocyte: a novel action of gh with implications for the pathogenesis of diabetic nephropathy.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 24 Downloadable Samples
Affymetrix Murine Genome U74B Version 2 Array (mgu74bv2), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Publication Title
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Publication Title
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74B Version 2 Array (mgu74bv2), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Analyses of six Ts1Cje (Down syndrome) and six normal littermate (2N) mouse brains at postnatal day 0.
Publication Title
Dosage-dependent over-expression of genes in the trisomic region of Ts1Cje mouse model for Down syndrome.
Sample Metadata Fields
No sample metadata fields
View Samples