RNAseq characterization of gene expression changes 72 hours after genomic excision of Cebpa in murine hematopoietic progenitors from Cebpaf/f;CreER mice transformed by Hoxa9/Meis1. In the presence of tamoxifen (4OHT), Cre-ER localizes to the nucleus of cells allowing for excision of Cebpa and loss of C/EBPa protein levels. Loss of C/EBPa leads to a decrease in cellular proliferation. Overall design: Examination of gene expression by RNAseq in two conditions in biological replicates.
C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis.
No sample metadata fields
View SamplesCharacterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage. Overall design: Examination of gene expression by RNAseq in two conditions in biological replicates.
C/EBPα is an essential collaborator in Hoxa9/Meis1-mediated leukemogenesis.
No sample metadata fields
View SamplesImportantly increasing evidence shows that Hox genes such as Hoxa9 are key regulators of stem cell self-renewal and hematopoiesis. Hoxa9 is expressed in early hematopoietic progenitor cells and promotes stem cell expansion. In contrast Hoxa9 down regulation is associated with hematopoietic differentiation. In addition to its role in development, HOXA9 has been intensively studied because of its central role in human acute leukemias. Despite their obvious biomedical importance, the mechanisms through which Hoxa9 and its partner proteins exert their downstream functions are poorly understood.
The PAF complex synergizes with MLL fusion proteins at HOX loci to promote leukemogenesis.
Sex, Specimen part, Cell line, Time
View SamplesACTH-dependent hypercortisolism caused by a pituitary adenoma [Cushings disease (CD)] is the most common cause of endogenous Cushings syndrome. CD is often associated with several morbidities, including hypertension, diabetes, osteoporosis/bone fractures, secondary infections, and increased cardiovascular mortality. While the majority (80%) of the corticotrophinomas visible on pituitary magnetic resonance imaging are microadenomas (MICs, <10 mm of diameter), some tumors are macroadenomas (MACs, 10 mm) with increased growth potential and invasiveness, exceptionally exhibiting malignant demeanor. In addition, larger and invasive MACs are associated with a significant increased risk of local complications, such as hypopituitarism and visual defects. Given the clinical and molecular heterogeneity of corticotrophinomas, the aim of this study was to investigate the pattern of genetic differential expression between MIC and MAC, including the invasiveness grade as a criterion for categorizing these tumors. In this study, were included tumor samples from patients with clinical, laboratorial, radiological, and histopathological diagnosis of hypercortisolism due to an ACTH-producing pituitary adenoma. Differential gene expression was studied using an Affymetrix microarray platform in 12 corticotrophinomas, classified as non-invasive MIC (n = 4) and MAC (n = 5), and invasive MAC (n = 3), according to modified Hardy criteria. Somatic mutations in USP8 were also investigated, but none of the patients exhibited USP8 variants. Differential expression analysis demonstrated that non-invasive MIC and MAC have a similar genetic signature, while invasive MACs exhibited a differential expression profile. Among the genes differentially expressed, we highlighted CCND2, ZNF676, DAPK1, and TIMP2, and their differential expression was validated through quantitative real-time PCR in another cohort of 15 non-invasive and 3 invasive cortocotrophinomas. We also identified potential biological pathways associated with growth and invasiveness, TGF- and G protein signaling pathways, DNA damage response pathway, and pathways associated with focal adhesion. Our study revealed a differential pattern of genetic signature in a subgroup of MAC, supporting a genetic influence on corticotrophinomas in patients with CD.
Transcriptome Analysis Showed a Differential Signature between Invasive and Non-invasive Corticotrophinomas.
Sex, Specimen part, Disease
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Identification and characterization of Hoxa9 binding sites in hematopoietic cells.
Sex, Specimen part, Cell line, Time
View SamplesWe report the application of RNA sequencing for transcriptome analysis of virus infected tissues, enabling the study of tissue responses to infection Overall design: Transcriptome analysis of 2 different tissues infected with two different viruses
Correction for Weisblum et al., "Zika Virus Infects Early- and Midgestation Human Maternal Decidual Tissues, Inducing Distinct Innate Tissue Responses in the Maternal-Fetal Interface".
Specimen part, Subject, Time
View SamplesAnalysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Induced p53 loss in mouse luminal cells causes clonal expansion and development of mammary tumours.
Sex, Specimen part
View SamplesMany components of Wnt/-catenin signaling pathway also play critical roles in mammary tumor development. To study the role of Apc in mammary tumorigensis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-Cre (progenitor) and WAP-cre (lactaing luminal) transgenic mice. Only the K14-cre mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological and molecular heterogeneity, suggesting the progenitor cell origin of these tumors. These tumors harbored truncation mutation in a very defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of -catenin signaling. Our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of -catenin signaling optimal for mammary tumor development.
Genetic mechanisms in Apc-mediated mammary tumorigenesis.
No sample metadata fields
View SamplesGlioblastoma multiforme (GBM) is an aggressive primary brain cancer that includes focal amplification of PDGFR and for which there are no effective therapies. Herein, we report the development of a genetically engineered mouse model of GBM based on autocrine, chronic stimulation of PDGFR and the analysis of GBM signaling pathways using proteomics. We discovered the tubulin-binding protein Stathmin1 (STMN1) as a PDGFR phospho-regulated target and that this mis-regulation conferred selective sensitivity to vinblastine (VB) cytotoxicity. Treatment of PDGFR GBMs with VB in mice drastically prolonged survival and was dependent on STMN1. Our work provides a rationale for evaluating genotype-specific anti-microtubule drugs as cancer treatment in select GBM patient populations.
A PDGFRα-driven mouse model of glioblastoma reveals a stathmin1-mediated mechanism of sensitivity to vinblastine.
Specimen part, Treatment
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