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Homo sapiens
24 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
Publication Title
A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MYB activation is proposed to underlie development of adenoid cystic cancer (ACC), an aggressive salivary gland tumor with no effective systemic treatments. To discover druggable targets for ACC, we performed global mRNA/miRNA analyses of 12 ACC with matched normal tissues, and compared these data with 14 mucoepidermoid carcinomas (MEC) and 11 salivary adenocarcinomas (ADC). We detected a unique ACC gene signature of 1160 mRNAs and 22 miRNAs. MYB was the top-scoring gene (18-fold induction), however we observed the same signature in ACC without detectable MYB gene rearrangements. We also found 4 ACC tumors (1 among our 12 cases and 3 from public databases) with negligible MYB expression that retained the same ACC mRNA signature including over-expression of extracellular matrix (ECM) genes. Integration of this signature with somatic mutational analyses suggests that NOTCH1 and RUNX1 participate with MYB to activate ECM elements including the VCAN/HAPLN1 complex. We observed that forced MYB-NFIB expression in human salivary gland cells alters cell morphology and cell adhesion in vitro and depletion of VCAN blocked tumor cell growth of a short-term ACC tumor culture. In summary, we identified a unique ACC signature with parallel MYB-dependent and independent biomarkers and identified VCAN/HAPLN1 complexes as a potential target.
Publication Title
A unifying gene signature for adenoid cystic cancer identifies parallel MYB-dependent and MYB-independent therapeutic targets.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 384 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Background: Tissue regeneration and recovery in the adult body depends on self-renewal and differentiation of stem and progenitor cells. Mesenchymal stem cells (MSCs) that have the ability to differentiate into various cell types, have been isolated from the stromal fraction of virtually all tissues. However, little is known about the true identity of MSCs. MSC populations exhibit great tissue-, location- and patient-specific variation in gene expression and are heterogeneous in cell composition. Methodology/Principal findings: Our aim was to analyze the dynamics of differentiation of two closely related stromal cell types, adipose tissue-derived MSCs and dermal fibroblasts (FBs) along adipogenic, osteogenic and chondrogenic lineages using multiplex RNA-seq technology. We found that undifferentiated donor-matched MSCs and FBs are distinct populations that stay different upon differentiation into adipocytes, osteoblasts and chondrocytes. The changes in lineage-specific gene expression occur early in differentiation and persist over time in both MSCs and FBs. Further, MSCs and FBs exhibit similar dynamics of adipogenic and osteogenic differentiation but different dynamics of chondrogenic differentiation. Conclusion: Our findings suggest that stromal stem cells including adipose-derived MSCs and dermal FBs exploit different molecular mechanisms of differentiation to reach a common cell fate. The early mechanisms of differentiation are lineage-specific and are similar for adipogenic and osteogenic differentiation but are distinct for chondrogenic differentiation between MSCs and FBs. Overall design: A total of 91 samples were analyzed by multiplex RNA-seq. Samples represented replicates from two patients, two cell types and three differentiation protocols, as indicated by the sample annotation. 5 barcodes were unused, but the corresponding FASTQ files are included for completeness.
Publication Title
RNA-seq analysis reveals different dynamics of differentiation of human dermis- and adipose-derived stromal stem cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
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SRP022764- Mus musculus
- 236 Downloadable Samples
- IlluminaHiSeq2000
Description
Purpose: We applied cDNA molecule counting using unique molecular identifiers combined with high-throughput sequencing to study the transcriptome of individual mouse embryonic stem cells, with spike-in controls to monitor technical performance. We further examined transcriptional noise in the embryonic stem cells. Overall design: One 96-well plate of single-stranded cDNA libraries generated from 96 single R1 mouse embryonic stem cells sequenced on two lanes, and one 96-well plate of the same libraries further amplified by 9 PCR cycles sequenced on one lane.
Publication Title
Quantitative single-cell RNA-seq with unique molecular identifiers.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
- IlluminaHiSeq2000
Description
Cancer tissue-like structures were developed by using established human tumor cell lines in perfusion-based bioreactor systems. In colorectal cancer (CRC) cell lines, perfusion allowed more homogeneous scaffold seeding than tri-dimensional (3D) static cultures and significantly (13.7 fold, p<0.0001) higher proliferation. Resulting tissues exhibited morphology and phenotypes similar to xenografts generated in immunodeficient mice. Whole transcriptome analysis of 2D, 3D static and 3D perfusion cultures revealed the highest correlation between xenografts and 3D perfusion cultures (r=0.985). Clinically relevant concentrations of 5-FU, used in neo- and adjuvant CRC treatment, had no effect on numbers of HT-29 CRC cells cultured in 3D perfusion or xenografts, as compared with a 55.8% reduction in 2D cultures. Treatment induced apoptosis in 2D cultures, but only “nucleolar stress” in perfused cells and xenografts, consistent with partial responsiveness. In 3D perfusion cultures BCL-2, TRAF1, and FLIP gene expression was marginally affected, as compared with significant down-regulation in 2D cell cultures. Accordingly, ABT-199 BCL-2 inhibitor, induced cytostatic effects in 3D perfusion but not in 2D cell cultures (p=0.003). Tumor cells from partially responsive (Dworak 2) patients undergoing neo-adjuvant treatment, typically (10/11) expressed BCL-2, as compared with 0/3 highly (Dworak 3-4) responsive and 4/15 fully resistant CRC (Dworak 0/1, p=0.03), closely matching 3D perfusion cultures data. These results indicate that 3D perfusion cultures efficiently mimic phenotypic and functional features observed in xenografts and clinical specimens. These models may be of critical translational relevance to address fundamental human tumor cell biology issues and to develop predictive pre-clinical tests of novel compounds. Overall design: Expression profiles of colorectal cancer cell lines cultured in 2D, 3D static, 3D perfusion or growing as xenografts were generated by deep sequencing, in triplicates, using Illumina HiSeq2000.
Publication Title
Bioreactor-engineered cancer tissue-like structures mimic phenotypes, gene expression profiles and drug resistance patterns observed "in vivo".
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To determine how mutation of BRAF affected the response to RAF265, we utilized a tumor orthotopic implant model of early passage melanoma tumors in nude mice from a series of 17 patients with advanced metastatic Tumor growth was compared between RAF265 treatment (40 mg/kg, QD) and diluent control groups. The melanoma associated gene mutation profile and global gene expression profile were determined on these human melanoma samples by SNaPshot and Affymetrix Human Gene ST 1.0 Array, respectively. Tumors were evaluated for growth response to RAF265 in an orthotopic implant model using nude mice. Comparisons were made between gene expression profiles of responders and non-responders, BRAF mutant and BRAF wild type tumors. Analysis of the microarray data revealed responders exhibited enriched expression of genes involved in cell cycle, apoptosis, cell-cell adhesion and initiation of epithelial/mesenchymal transition. It is concluded that RAF265 significantly inhibits the growth of a sub-population of V600E mutant and wild type BRAF human melanoma tumors in vivo and the gene expression profile of this subset of tumors that may predict response to RAF265.
Publication Title
RAF265 inhibits the growth of advanced human melanoma tumors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Zea mays
- 12 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
The hemibiotrophic fungal pathogen Colletotrichum graminicola is the causal agent of anthracnose disease on maize stalks and leaves. After the formation of appressoria the host cell wall is penetrated by the conversion of appressorial turgor pressure into forceful ejection of a penetration peg. Subsequently, C. graminicola establishes biotrophic hyphae in the penetrated epidermis cell at around 36 hours post inoculation (hpi) until a switch of hyphal morphology and lifestyle takes place during the colonization of neighboring host cells at around 72 hpi. During the ensuing necrotrophic growth, dark necrotic lesions are formed that are visible as anthracnose symptoms. We used microarrays to detail the global programme of gene expression during the infection process of Colletotrichum graminicola in its host plant to get insight into the defense response of this compatible interaction and into the metabolic reprogramming needed to supply the fungus with nutrients.
Publication Title
Common Motifs in the Response of Cereal Primary Metabolism to Fungal Pathogens are not Based on Similar Transcriptional Reprogramming.
Sample Metadata Fields
Time
View Samples