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GSE9715
Homo sapiens
11 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Patients with tuberous sclerosis complex (TSC) develop hamartomas containing biallelic inactivating mutations in either TSC1 or TSC2, resulting in mammalian target of rapamycin (mTOR) activation. Hamartomas overgrow epithelial and mesenchymal cells in TSC skin. The pathogenetic mechanisms for these changes had not been investigated, and the existence or location of cells with biallelic mutations (two-hit cells) that resulted in mTOR activation was unclear. We compared TSC skin hamartomas (facial angiofibromas and periungual fibromas) to normal-appearing skin of the same patient, and observed more proliferation and mTOR activation in hamartoma epidermis. Two-hit cells were not detected in the epidermis. Fibroblast-like cells in the dermis, however, exhibited allelic deletion of TSC2, in both touch preparations of fresh tumor samples and cells grown from TSC skin tumors, suggesting that increased epidermal proliferation and mTOR activation were not caused by second-hit mutations in the keratinocytes but by mesenchymal-epithelial interactions. Gene expression arrays, used to identify potential paracrine factors released by mesenchymal cells, revealed more epiregulin mRNA in fibroblast-like angiofibroma and periungual fibroma cells than in fibroblasts from normal-appearing skin of the same patient. Elevation of epiregulin mRNA was confirmed using real-time PCR, and increased amounts of epiregulin protein were demonstrated using immunoprecipitation and ELISA. Epiregulin stimulated keratinocyte proliferation and phosphorylation of ribosomal protein S6 in vitro. These results suggest that hamartomatous TSC skin tumors are induced by paracrine factors released by two-hit cells in the dermis, and that proliferation with mTOR activation of the overlying epidermis is an effect of epiregulin.
Publication Title
Mesenchymal-epithelial interactions involving epiregulin in tuberous sclerosis complex hamartomas.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Osteosarcoma (OS) is the malignant bone tumor with a high tendency to metastasize to the lung, where the molecular mechanisms are unclear. The mouse OS cell line LM8 has been isolated originally from the Dunn OS cell line by in vivo selection as a subline with a high metastatic potential to the lung.
Publication Title
Stable knockdown of S100A4 suppresses cell migration and metastasis of osteosarcoma.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
EWS-FLI1, a multi-functional fusion oncogene, is exclusively detectable in Ewing sarcomas. However, previous studies reported that a subset of osteosarcomas also harbor EWS-ETS family fusion, suggesting that the fusion gene may be involved in the development of a particular type of osteosarcomas. Here using the doxycycline inducible EWS-FLI1 system, we established an EWS-FLI1-dependent osteosarcoma model from murine bone marrow stromal cells. We revealed that the withdrawal of EWS-FLI1 expression enhances the osteogenic differentiation of sarcoma cells, leading to mature bone formation. Taking advantage of induced pluripotent stem cell (iPSC) technology, we also showed that the sarcoma-derived iPSCs with cancer-related genetic abnormalities exhibited the impaired differentiation program of osteogenic lineage irrespective of the EWS-FLI1 expression. Finally, we demonstrated that EWS-FLI1 contributed to in vitro sarcoma development from the sarcoma-iPSCs after osteogenic differentiation. These findings demonstrated that modulating cellular differentiation is fundamental principle of the EWS-FLI1-induced osteosarcoma development. Furthermore, the in vitro cancer model using sarcoma-iPSCs should provide a novel platform for dissecting relationship between cancer genome and cellular differentiation.
Publication Title
An EWS-FLI1-Induced Osteosarcoma Model Unveiled a Crucial Role of Impaired Osteogenic Differentiation on Osteosarcoma Development.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
RNA sequencing was performed to examine differential gene expression profiles in the ring gland of PG-specific Séance RNAi animals versus control. Overall design: Drosophila larvae with PG-specific knockdown of Séance and control animals were carefully staged at the larval L2/L3 molt. Ring glands were dissected at 44 hours L3. RNA isolated from ring glands were subject to RNA sequencing. Differential gene expression profiles were compared between control and RNAi animals.
Publication Title
Cooperative Control of Ecdysone Biosynthesis in <i>Drosophila</i> by Transcription Factors Séance, Ouija Board, and Molting Defective.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Global gene expression profiling of FOP-iMSCs after chondrogenic differentiation with ERBB2 inhibitors
Publication Title
An mTOR Signaling Modulator Suppressed Heterotopic Ossification of Fibrodysplasia Ossificans Progressiva.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Comparison of gene expressions among FOP- or resFOP-iMSCs after chondrogenic differentiation with Activin-A, BMP-7 or TGF-B3
Publication Title
Activin-A enhances mTOR signaling to promote aberrant chondrogenesis in fibrodysplasia ossificans progressiva.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
In vivo reprogramming drives Kras-induced cancer development.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Accumulation of genetic mutations is thought to be a primary cause of cancer. However, a set of genetic mutations sufficient for cancer development remains unclear in most cancers, including pancreatic cancer. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We first demonstrate that Kras and p53 mutations are insufficient to induce activation of ERK signaling and cancer development in the pancreas. We next show that short transient expression of reprogramming factors (1-3 days) in pancreatic acinar cells results in repression of acinar cell enhancers and reversible loss of acinar cell properties. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma (PDAC). In contrast, forced expression of acinar cell-related transcription factors inhibits pancreatitis-induced activation of ERK signaling and development of precancerous lesions in Kras-mutated acinar cells.
Publication Title
In vivo reprogramming drives Kras-induced cancer development.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 26 Downloadable Samples
- NextSeq 500
Description
Experience-dependent plasticity (EDP) is essential for anatomical and functional maturation of sensory circuits during development and can be readily studied is the rodent barrel cortex. Using this model we aimed to uncover changes on the transcriptome level and applied RNA sequencing upon altered sensory experience in juvenile mice in a cortical column and layer specific manner. From column- and layer-specific barrel cortical tissue, high quality RNA was purified and sequenced. The current dataset entails an average of 50 million paired-end reads per sample, 75 base pairs in length. Overall design: Wild type mice were deprived of their C-row whiskers from P12 until P23-P24, after which acute brain slices were prepared and tissues were excised from L2/3 and L4 from specific barrel columns. RNA isolated from these tissue sections was then subjected to RNA-sequencing.
Publication Title
Transcriptional mapping of the primary somatosensory cortex upon sensory deprivation.
Sample Metadata Fields
Cell line, Subject
View Samples