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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
- 4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Trans-splicing is a post-transcriptional event that joins exons from separate pre-mRNAs. Detection of trans-splicing is usually severely hampered by experimental artifacts and genetic rearrangements. Here, we develop a new computational pipeline, TSscan, which integrates different types of high-throughput long-/short-read transcriptome sequencing of different human embryonic stem cell (hESC) lines to effectively minimize false positives while detecting trans-splicing. Combining TSscan screening with multiple experimental validation steps revealed that most chimeric RNA products were platform-dependent experimental artifacts of RNA sequencing. We successfully identified and confirmed four trans-spliced RNAs, including the first reported trans-spliced large intergenic noncoding RNA ("tsRMST"). We showed that these trans-spliced RNAs were all highly expressed in human pluripotent stem cells and differentially expressed during hESC differentiation. Our results further indicated that tsRMST can contribute to pluripotency maintenance of hESCs by suppressing lineage-specific gene expression through the recruitment of NANOG and the PRC2 complex factor, SUZ12. Taken together, our findings provide important insights into the role of trans-splicing in pluripotency maintenance of hESCs and help to facilitate future studies into trans-splicing, opening up this important but understudied class of post-transcriptional events for comprehensive characterization
Publication Title
Integrative transcriptome sequencing identifies trans-splicing events with important roles in human embryonic stem cell pluripotency.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Gene expression profiling of primary mouse articular chondrocyte infected with recombinant adenovirus expressing the zinc transporter ZIP8 (SLC39A8) protein.
Publication Title
Pleiotropic roles of metallothioneins as regulators of chondrocyte apoptosis and catabolic and anabolic pathways during osteoarthritis pathogenesis.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 53 Downloadable Samples
- Illumina HiSeq 2000
Description
We report global gene expression profilies of Brassinosteroid related Arabidopsis mutants in response to dehydration and fixed-carbon starvation stresses by RNA-seq Overall design: Arabidopsis plants of listed genotypes were grown for 4 weeks under long day (16 hour light) conditions before being subjected to control, 4 hour dehydration, or 5 day fixed carbon starvation treatments.
Publication Title
Arabidopsis WRKY46, WRKY54, and WRKY70 Transcription Factors Are Involved in Brassinosteroid-Regulated Plant Growth and Drought Responses.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The underlying change of gene network expression of Guillain-Barre syndrome (GBS) remains elusive. We sought to identify GBS-associated gene networks and signalling pathways by analyzing the transcriptional profile of leukocytes in the patients with GBS.
Publication Title
Identification of gene networks and pathways associated with Guillain-Barré syndrome.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We performed knockdown of circARID1A, overexpression of circARID1A and overexpression of miR-204-3p in ReNcell, independently. The 22,480 gene expression changes were examined by microarray analysis.
Publication Title
Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Research in human immunobiology is mainly based on working with peripheral blood mononuclear cells (PBMC). However, recent investigations have shown that circulating CD4+ T cells are less sensitive to several T-cell activating monoclonal antibodies (mAb) and to recall antigens as compared to tissue-resident cells or cells that were in-vitro cultured at a high cell density of 10^7 cells/mL for 2 days at 37C and 5% CO2 (RESTORE protocol, Rmer et al., Blood 2011, PMID: 21931118). To explain the increase in sensitivity of CD4+ T-cells to mAbs and recall antigens on a molecular level, we performed microarray hybridizations of total RNA from T-cells isolated from PBMC that were cultured at a low or high cell density. To avoid the detection of genes that are up- or down-regulated by the culture process itself, we used low cell density cultured PBMC, instead of freshly prepared PBMC.
Publication Title
High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The feather follicle is a “professional” regenerative organ that undergoes natural cycling and, regeneration after wound plucking. Similar to mammalian hair follicle, dermal papilla (DP) controls feather regeneration, shape, size, and axis. Here we report gene expression profiling for feather DP at different growth stages. For growth phase, we compared gene expression of DP, the ramogenic zone of feather branching epithelium (Erz) and the mesenchymal pulp (Pp). We also compared gene expression of DP at resting phase. To characterize the feather regeneration process, we further profiled gene expression at Day-2 and Day-4 post wound. Our results provide a resource for investigating feather growth and regeneration. Overall design: Examination of gene expression in dermal papilla (DP) at growth phase and resting phase feather follicle, and during feather regeneration.
Publication Title
Dkk2/Frzb in the dermal papillae regulates feather regeneration.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The gene expression of bone marrow Hdc-/- and WT (LSK, Lin-c-kit+Sca-1+) hematopoetic stem and progenitor cells were isolated from Hdc-/- or WT mice. Cells were sorted by the cell surface markers of LSK total RNA was isolated from sorted 2,000 HSPCs using the ARCTURUS PicoPure RNA isolation kit (Life Technologies). cDNA was amplified and libraries were constructed by using the SMARTer Ultra Low Input RNA kit (Clontech Laboratories) and the Nextera XT DNA Library Preparation kit (Illumina) according to the respective manufacturer's instructions. Sequencing was performed on the Illumina HiSeq2500 platform. Overall design: a. Hdc-/- bone marrow HSPC (n=4) b. WT bone marrow HSPC (n=4)
Publication Title
Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3<sup>+</sup> regulatory T cells in murine colon cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Bone marrow Hdc-GFP+/hi and Hdc-GFP-/loCD11b+Gr1+ cells were isolated from bones from histidine decarboxylase (Hdc) green fluorescent protein (Hdc-GFP) mice Hdc-GFP+/hiCD11b+Gr1+ cells and Hdc-GFP-/loCD11b+Gr1+ cells were sorted by combinations of GFP and myeloid cell surface markers CD11b and Gr1 and their differential mRNA expression compared with Affymetrix microarrays.
Publication Title
Histidine decarboxylase (HDC)-expressing granulocytic myeloid cells induce and recruit Foxp3<sup>+</sup> regulatory T cells in murine colon cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples