Mammalian microRNAs (miRNAs) are emerging as key regulators of the development and function of the immune system. Here, we report a strong but transient induction of miR-155 in mouse bone marrow after injection of bacterial lipopolysaccharide (LPS) correlated with granulocyte/monocyte (GM) expansion. Demonstrating the sufficiency of miR-155 to drive GM expansion, enforced expression in mouse bone marrow cells caused GM proliferation in a manner reminiscent of LPS treatment. However, the mir-155-induced GM populations displayed pathological features characteristic of myeloid neoplasia. Extending possible relevance to human disease, miR-155 was overexpressed in the bone marrow of patients with acute myeloid leukemia (AML). Furthermore, miR-155 repressed a subset of genes implicated in hematopoietic development and disease. These data implicate miR-155 as a contributor to physiological GM expansion during inflammation and to certain pathological features associated with AML, emphasizing the importance of proper miR-155 regulation in developing myeloid cells during times of inflammatory stress.
Sustained expression of microRNA-155 in hematopoietic stem cells causes a myeloproliferative disorder.
No sample metadata fields
View SamplesThe main goal of our study is to identify the molecular events that determine the gonadal identity in mammals. Although testis and ovary arise from a common embryonic primordium, they represent outcomes of opposing fate determination. This decision to differentiate into a testis or an ovary hinges upon the balance between two antagonizing factors, pro-testis SOX9 and pro-ovary -catenin.
Gonadal Identity in the Absence of Pro-Testis Factor SOX9 and Pro-Ovary Factor Beta-Catenin in Mice.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.
Cell line, Treatment
View SamplesIn this work we investigated the combined effects of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Mouse BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.
VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.
Cell line, Treatment
View SamplesIn this work we investigated the combined effects of the BRAF inhibition and of the VEGF blockade in a preclinical model of melanoma. The purpose of this dataset was to examine the transcriptional responses of a A375 xenograft model to PLX472 and bevacizumab, either as single agents or as combination therapy. We performed species-specific analysis of gene expression to discriminate the effects of the different therapeutic regimens on tumor cells (human) and stromal microenvironment (mouse). Here, Illumina Human BeadChips were used to profile the transcriptome after 12 days treatment. We reported that dispensing the dual treatment is more efficient than the single compounds and the occurrence of resistance by modifying the tumor genetic programs regulating myeloid cells recruitment and extracellular matrix remodeling.
VEGF blockade enhances the antitumor effect of BRAFV600E inhibition.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An FGFR3/MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers.
Cell line
View SamplesTo better understand the molecular mechanisms underlying altered-FGFR3 oncogenic activity in bladder carcinomas, we made use of RT112 cell lines, which were derived from a human bladder tumor and endogenously expressed the FGFR3-TACC3 fusion protein, the growth and transformation of these cell lines being dependent on activated-FGFR3 activity. We conducted a gene expression analysis using Affymetrix DNA arrays in this cell line treated or not with FGFR3 siRNAs.
An FGFR3/MYC positive feedback loop provides new opportunities for targeted therapies in bladder cancers.
Cell line
View SamplesWe generated genome-wide RNASeq data from freshly isolated airway epithelial cells of asthmatics and non-asthmatics. This data was paired with genome-wide genetic and methylation data from the same individuals allowing for an integrated analysis of genetic, transcriptional, and epigenetic signatures in asthma. Overall design: examination of genome-wide genome-wide gene expression levels and comparison to phenotypes
DNA methylation in lung cells is associated with asthma endotypes and genetic risk.
Specimen part, Disease, Subject
View SamplesIdentifying the Mechanism of Action (MoA) of drugs is critical for the development of new drugs, understanding their side effects, and drug repositioning. However, identifying drug MoA has been challenging and has been traditionally attempted only though large experimental setups with little success. While advances in computational power offers the opportunity to achieve this in-silico, methods to exploit existing computational resources are still in their infancy. To overcome this, we developed a novel method to identify Drug Mechanism of Action using Network Dysregulation (DeMAND).
Elucidating Compound Mechanism of Action by Network Perturbation Analysis.
Cell line, Time
View SamplesThird instar larval eye discs provide an in vivo model for cell cycle exit studies. Posterior to the Second Mitotic Wave proliferation is absent in a wild type eye disc. Inactivating mutations in tumor suppressor-like genes can lead to genome wide changes in gene expression that allow for inappropriate bypass of cell cycle exit signals posterior to the Second Mitotic Wave.
Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit.
Specimen part
View Samples