Memory B cells play essential roles in the maintenance of long-term immunity and may be important in the pathogenesis of autoimmune disease, but how these cells are distinguished from their nave precursors is poorly understood. To address this, it would be important to understand how gene expression differs between memory and naive B cells in order to elucidate memory-specific functions. Using model systems that help overcome the lack of murine memory-specific markers and the low frequency of antigen-specific memory and nave cells, we undertook a global comparison of gene expression between memory B cells and their naive precursors.
Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities.
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View SamplesNP-reactive murine splenic memory B cells were sorted based on the expression of the surface markers CD80 and PD-L2
CD80 and PD-L2 define functionally distinct memory B cell subsets that are independent of antibody isotype.
Specimen part
View SamplesPancreatic ductal adenocarcinoma (PDA) carries a dismal prognosis and current treatments are only modestly effective. We present evidence that this variation is caused in part by recurrent, pervasive molecular differences between tumors. mRNA expression profiles measured using microdissected PDA clinical samples reveal three dominant subtypes of disease; epithelial, mesenchymal and acinar-like. The classical and quasi-mesenchymal subtypes are observed in human and mouse PDA cell lines. Importantly, responses to cytotoxics and KRAS depletion in human PDA cell lines differ substantially between subtypes, and in opposing directions. Integrated genomics implicate and functional studies support overexpression of the trancription factor GATA6 as a driver of the epithelial subtype. These results provide a molecular framework for evaluating the prospects of personalized treatment in PDA.
Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy.
Specimen part, Cell line
View SamplesT84 cells were treated with DMSO, 30nM trametinib (MEKi), 1µM JQ1 (BRD4i) or the combination of trametinib and JQ1 (combo) for 24h. Overall design: 3 replicates per condition were analyzed by RNA-seq.
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
Cell line, Treatment, Subject
View SamplesHCT116 cells were treated with with increasing concentrations of trametinib over 2 months. Drug-resistant clones emerged and were cultured in the presence of 30 nmol/L trametinib. These cells exhibited a greater than 10-fold increase in the GI50 for trametinib compared to the parental cell line. RNA-seq of the resistant clone HCT116_R4 versus the parental cells identified differentially expressed genes potentially involved in resistance. Overall design: For the parental and resistant clone, 3 replicates each were analysed by RNA-seq.
Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer.
Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer.
Specimen part, Cell line, Treatment
View SamplesActivating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible KrasG12D-driven mouse model of PDAC has established a critical role for sustained KrasG12D expression in tumor maintenance, providing a model to determine the potential for, and underlying mechanisms of, KrasG12Dindependent PDAC recurrence. Here we show that some tumors undergo spontaneous relapse and are devoid of KrasG12D expression and downstream canonical MAPK signaling and instead acquired amplification and overexpression of the transcriptional co-activator Yap1. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving KrasG12Dindependent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models, portend a novel mechanism of escape from oncogenic Kras addiction in PDAC.
Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer.
Specimen part, Cell line, Treatment
View SamplesActivating mutations in KRAS are among the most frequent events in diverse human carcinomas and are particularly prominent in human pancreatic ductal adenocarcinoma (PDAC). An inducible KrasG12D-driven mouse model of PDAC has established a critical role for sustained KrasG12D expression in tumor maintenance, providing a model to determine the potential for, and underlying mechanisms of, KrasG12Dindependent PDAC recurrence. Here we show that some tumors undergo spontaneous relapse and are devoid of KrasG12D expression and downstream canonical MAPK signaling and instead acquired amplification and overexpression of the transcriptional co-activator Yap1. Functional studies established the role of Yap1 and the transcriptional factor Tead2 in driving KrasG12Dindependent tumor maintenance. The Yap1/Tead2 complex acts cooperatively with E2F transcription factors to activate a cell cycle and DNA replication program. Our studies, along with corroborating evidence from human PDAC models, portend a novel mechanism of escape from oncogenic Kras addiction in PDAC.
Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The MuvB complex sequentially recruits B-Myb and FoxM1 to promote mitotic gene expression.
Cell line
View SamplesWe report RNAseq data from subsequent passages of five organoid cultures. Overall design: RNA extracted from subsequent PDO passages was subjected to RNAseq.
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Disease, Subject
View Samples