In this study Panc-1 cells and BxPC-3 cells were cultured. The cells were harvested (untreated control 'cont') for RNA extraction, or treated for 3 hours with various exosomes preparations. The exosomes were collected from BJ human foreskin fibroblast culture supernatant without further processing (control exosomes or 'CE'), or engineered to contain scrambled siRNA ('scr') or KRASG12D siRNA ('iExo). Two or three distinct wells of cells were evaluated per treatment condition and assigned a well number (well -1, -2 or 3).
Generation and testing of clinical-grade exosomes for pancreatic cancer.
Cell line, Treatment
View SamplesThe aim of this experiment was to investigate differential gene expression in splenocytes stimulated with BCG from nave and BCG vaccinated mice. The differences between nave and BCG vaccinated mice might indicate the mechanisms by which BCG vaccination confers an enhanced ability of splenocytes from BCG vaccinated mice to inhibit growth of BCG in splenocyte cultures as compared with splenocytes from naive animals.
Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb).
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer.
Specimen part, Cell line
View SamplesLung cancer is a devastating disease that remains the top cause of cancer mortality. While targeted therapies against EGFR and EML4-ALK fusion and recent advances in immunotherapy have shown substantial clinical benefit for some patients, the vast majority of patients with lung cancer still lack effective therapies underscoring the dire need for more context-specific therapeutics. Cancer genomic studies have identified frequent genetic alterations in chromatin and epigenetic regulators including inactivating mutations in components of the SWI/SNF chromatin remodeling complex. In lung adenocarcinoma, about 20% of tumors have inactivating mutations in components of the SWI/SNF chromatin remodeling complex including SMARCA4 and ARID1A. With the aim of understanding the mechanism of tumor development driven by mutations in this complex, we developed a genetically engineered mouse (GEM) model of lung adenocarcinoma by selectively ablating Smarca4 in the lung epithelium. We demonstrate that Smarca4 acts as a bona fide tumor suppressor and cooperates with p53 loss and Kras activation. Cross species integrative gene expression analyses revealed signature of enhanced oxidative phosphorylation (OXPHOS) in SMARCA4 mutant murine as well as human lung adenocarcinomas. We further show that SMARCA4 mutant cells have increased oxygen consumption and increased respiratory capacity primarily driven by increased expression of the mitochondrial master regulator, PGC1-. Importantly, we show that SMARCA4 and other SWI/SNF mutant lung cancer cell lines and xenograft tumors have exquisite sensitivity to inhibition of OXPHOS by a novel small molecule, IACS-010759, that is under clinical development. Mechanistically, we show that SMARCA4 deficient cells have a blunted transcriptional response to energy stress creating a therapeutically attractive collateral vulnerability. These findings provide the mechanistic basis for further development of OXPHOS inhibitors as therapeutics against SWI/SNF mutant tumors.
Mutations in the SWI/SNF complex induce a targetable dependence on oxidative phosphorylation in lung cancer.
Specimen part, Cell line
View SamplesTransient expression of two factors, or from Oct4 alone, resulted in efficient generation of human iPSCs. The reprogramming strategy described revealed a potential transcriptional signature for human iPSCs yet retaining the gene expression of donor cells in human reprogrammed cells free of viral and transgene interference.
Transcriptional signature and memory retention of human-induced pluripotent stem cells.
Sex, Specimen part
View SamplesHuman medulloblastoma (MB) can be segregated into four major categories based on gene expression patterns: Hedgehog (HH) subtype, Wnt subtype, Group 3, and Group 4. However, they all exhibit strikingly different gene expression profiles from Atypical Teratoid/Rhabdoid Tumor (AT/RT). We re-analyzed published gene expression microarray dataset of pediatric brain tumors to identify a gene expression profile that clearly distinguished human AT/RT from human MB. We used this profile, choosing only genes that have clear murine orthologs, to compare tumors from Snf5F/Fp53L/LGFAP-Cre mice (in C57Bl/6 strain background) with MB from Ptc1+/- mice (in mixed C57Bl/6 and 129Sv strain background). Snf5F/Fp53L/LGFAP-Cre tumors are clearly very different from mouse MB and the markers that distinguish human AT/RT from human MB also distinguish the mouse tumors.
Generation of a mouse model of atypical teratoid/rhabdoid tumor of the central nervous system through combined deletion of Snf5 and p53.
No sample metadata fields
View SamplesSMARCA2 and SMARCA4 are two mutually exclusive ATPase subunits of SWI/SNF complex. SMARCA4 deficient lung cancer population selectively depend on SMARCA2 for cancer growth phenotype. Rescue experiments with ectopic expression of wild-type, bromodomain mutant and ATPase dead SMARCA2 and SMARCA4 highlight that ATPase domain is the drug target.
The SMARCA2/4 ATPase Domain Surpasses the Bromodomain as a Drug Target in SWI/SNF-Mutant Cancers: Insights from cDNA Rescue and PFI-3 Inhibitor Studies.
Specimen part, Cell line
View SamplesFour vehicle-treated and four HhAntag-treated pancreatic xenograft tumors were profiled for gene expression changes using Affymetrix U133 Plus 2.0 and Affymetrix Mouse Genome 430 2.0 arrays.
A paracrine requirement for hedgehog signalling in cancer.
No sample metadata fields
View SamplesAbout 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI.
Rapidly acquired resistance to EGFR tyrosine kinase inhibitors in NSCLC cell lines through de-repression of FGFR2 and FGFR3 expression.
Cell line, Treatment
View SamplesPeripherally derived macrophages infiltrate the brain after bone marrow transplantation and during central nervous system (CNS) inflammation. It was initially suggested that these engrafting cells were newly derived microglia and that irradiation was essential for engraftment to occur. However, it remains unclear whether brain-engrafting macrophages (beMfs) acquire a unique phenotype in the brain, whether long-term engraftment may occur without irradiation, and whether brain function is affected by the engrafted cells. In this study, we demonstrate that chronic, partial microglia depletion is sufficient for beMfs to populate the niche and that the presence of beMfs does not alter behavior. Furthermore, beMfs maintain a unique functional and transcriptional identity as compared with microglia. Overall, this study establishes beMfs as a unique CNS cell type and demonstrates that therapeutic engraftment of beMfs may be possible with irradiation-free conditioning regimens. Overall design: Microglia were isolated from the brains of adult male c57BL/6 mice given bone marrow tranplants (BMT) with or without head shield. All mice received PLX5622 for 2 weeks, then placed and normal chow to recoever. Some mice were then challenged with LPS. Cells were isolated by MACS using CD11b magnetic beads.
Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia.
Age, Specimen part, Cell line, Treatment, Subject
View Samples