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GSE24553
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We developed a novel culture system to obtain multilineage undifferentiated stem/progenitor cells from normal human thyroid tissues. This seems to be achieved by direct reprogramming of thyroid follicular cells. The objective of the study was to reveal gene expression profile of the obtained cells compared to primary thyrocytes. After enzymatic digestion, primary thyrocytes, expressing thyroglobulin and cytokeratin-18, were cultured in a serum-free medium called SAGM containing insulin and EGF. Although the vast majority of cells died, a small proportion (~0.5%) survived and proliferated. During initial cell expansion, thyroglobulin/cytokeratin-18 expression was gradually declined, suggesting that those cells are derived from thyroid follicular cells or at least thyroid-committed cells. The SAGM-grown cells did not express any thyroid-specific genes. However, after four-week incubation with FBS and TSH, cytokeratin-18, thyroglobulin, TSH receptor, PAX8 and TTF1 expressions re-emerged. Moreover, surprisingly, the cells were capable of differentiating into neuronal or adipogenic lineage depending on differentiating conditions.
Publication Title
Dedifferentiation of human primary thyrocytes into multilineage progenitor cells without gene introduction.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Primary T cells were isolated from spleen of Parp-1-/- and wild-type mice by magnetic depletion of non-T cells using a MACS Pan-T Cell isolation kit, according to the manufacturer´s instruction (Mintenyi Biotec, Bergisch Gladbach, Germany). Purity was assessed by flow cytometry analysis using antibodies against CD3, CD4 and CD8 and all preparations were more than 98% pure of T cells. The cells were activated with plate-bound anti-mouse CD3 (clone 145-2C11) (5 microg/ml) in the absence or the presence of anti-mouse CD28 (clone 37.51) (5microg/ml) both from BD PharMingen (San Diego, CA) and culture for 3.5 h in RPMI 1640 medium (BioWhittaker) supplemented with 10% FCS, 2mM L-glutamine, 5x10-5 M 2-mercaptoethanol (Sigma), 2.5 microg/ml fungizone, 100 IU/ml penicillin, and 10 microg/ml streptomycin.
Publication Title
Transcriptional regulation by poly(ADP-ribose) polymerase-1 during T cell activation.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Gamma tocotrienol induces apoptosis in breast cancer cells however, the molecular mechanisms are not completely understood.
Publication Title
Gamma-tocotrienol induced apoptosis is associated with unfolded protein response in human breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 36 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tissue-resident macrophages can derive from yolk sac macrophages, fetal liver monocytes or adult bone marrow monocytes. Whether these precursors can give rise to transcriptionally identical alveolar macrophages is unknown. Here, we transferred traceable yolk sac macrophages, fetal liver monocytes, adult bone marrow monocytes or adult alveolar macrophages as a control, into the empty alveolar macrophage niche of neonatal Csf2rb-/- mice. All precursors efficiently colonized the alveolar niche and generated alveolar macrophages that were transcriptionally almost identical, with only 22 genes that could be linked to their origin. Underlining the physiological relevance of our findings, all transfer-derived alveolar macrophages self-maintained within the lungs for up to 1 year and durably prevented alveolar proteinosis. Thus, precursor origin does not affect the development of functional self-maintaining tissue-resident macrophages.
Publication Title
Yolk Sac Macrophages, Fetal Liver, and Adult Monocytes Can Colonize an Empty Niche and Develop into Functional Tissue-Resident Macrophages.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To determine the global transcriptome changes in mantle cell lymphoma cells following treatment with the BET bromodomain antagonist, JQ1
Publication Title
Synergistic activity of BET protein antagonist-based combinations in mantle cell lymphoma cells sensitive or resistant to ibrutinib.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Extramedullary hematopoiesis (EMH) refers to the differentiation of hematopoietic stem cells (HSCs) into effector cells that occurs in compartments outside of the bone marrow. Previous studies linked pattern recognition receptor (PRR)-expressing HSCs, EMH and immune responses to microbial stimuli. However, the factors that regulate EMH and whether EMH operates in broader immune contexts remain unknown. Here, we demonstrate a previously unrecognized role for thymic stromal lymphopoietin (TSLP) in promoting the population expansion of progenitor cells in the periphery and identify that TSLP-elicited progenitors differentiate into effector cells including macrophages, dendritic cells and granulocytes that contribute to TH2 cytokine responses. The frequency of circulating progenitor cells was also increased in allergic patients with a gain-of-function polymorphism in TSLP, suggesting the TSLP-EMH pathway may operate in human disease. These data identify that TSLP-induced EMH contributes to the development of allergic inflammation and indicate that EMH is a conserved mechanism of innate immunity.
Publication Title
Thymic stromal lymphopoietin-mediated extramedullary hematopoiesis promotes allergic inflammation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
Illumina Genome Analyzer II
Description
Bromodomain extraterminal protein (BETP) inhibitors transcriptionally repress oncoproteins and NFkB target genes, which undermines the growth and survival of MCL cells. However, BETi treatment causes accumulation of BETPs, associated with reversible binding and incomplete inhibition of BRD4, which potentially compromises the activity of BETi in MCL cells. Unlike BETi, BET-PROTACs (proteolysis-targeting chimera) ARV-825 and ARV-771 (Arvinas, Inc.) recruit and utilize an E3-ubiquitin ligase to effectively degrade BETPs in MCL cells. BET-PROTACs induce more apoptosis than BETi of MCL cells, including those resistant to ibrutinib. BET-PROTAC treatment induced more perturbations in the mRNA and protein expressions than BETi, with depletion of c-Myc, CDK4, cyclin D1, and the NFkB transcriptional targets Bcl-xL, XIAP and BTK, while inducing the level of HEXIM1, NOXA and CDKN1A/p21. Treatment with ARV-771, which possesses superior pharmacological properties compared to ARV-825, inhibited the in vivo growth and induced greater survival improvement than the BETi OTX015 of immune-depleted mice engrafted with MCL cells. Co-treatment of ARV-771 with ibrutinib or the BCL2-antagonist venetoclax or CDK4/6 inhibitor palbociclib synergistically induced apoptosis of MCL cells. These studies highlight promising and superior pre-clinical activity of BET-PROTAC than BETi, requiring further in vivo evaluation of BET-PROTAC as a therapy for ibrutinib-sensitive or resistant MCL. Overall design: Twelve samples in biologic triplicates
Publication Title
BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mantle cell lymphoma cells.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The two most common melanoma histopathologic subtypes, superficial spreading (SSM) and nodular melanoma (NM), are believed to represent sequential phases of linear progression from radial to vertical growth. Studies suggest, however, that SSM and NM are biologically distinct. We utilized an integrative genomic approach to examine the possibility that SSM and NM are the result of independent pathways characterized by unique molecular alterations. Cell lines including SSM, NM, metastatic melanoma, and melanocyte controls were evaluated for copy number changes and differential mRNA expression using single nucleotide polymorphism array (SNP 6.0, Affymetrix) and gene array (U133A 2.0, Affymetrix). Data sets were integrated to identify copy number alterations that correlated with gene expression, and array results were validated using immunohistochemistry on human tissue microarrays (TMAs) and an external data set. The functional effect of genomic deletion was assessed by lentiviral overexpression. Integrative genomics revealed 8 genes in which NM/SSM-specific copy number alterations were correlated with NM/SSM differential gene expression (P<0.05, Spearmans rank). Pathways analysis of differentially expressed genes (N=114) showed enrichment for metabolic-related processes. SSM-specific genomic deletions (DIS3, MTAP, G3BP2, SEC23IP, USO1) were verified in an expanded panel of cell lines, and forced overexpression of MTAP in SSM resulted in reduced cell growth. Metabolism-related gene ALDH7A1 was verified as overexpressed in NM using human TMAs.The identification of recurrent genomic deletions in SSM not present in NM challenges the linear model of melanoma progression and supports the unique molecular classification of SSM and NM.
Publication Title
Integrative genomics identifies molecular alterations that challenge the linear model of melanoma progression.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Toxoplasma strains are known to inhibit the expression of several interferon-gamma induced genes, and a type II strain was shown to dysregulate genome-wide responses to interferon-gamma in human fibroblasts (Kim et al., 2007, J Immunol.). In this study we aimed to determine the effect of infection with three clonal lineages of Toxoplasma, type I, II, and III strains on genome-wide interferon-gamma induced transcription in murine macrophages. We also assessed the effect of the two main Toxoplasma modulators of mouse macrophage transcription, ROP16 and GRA15 (Jensen et al., 2011, Cell Host Microbe).
Publication Title
Toxoplasma gondii clonal strains all inhibit STAT1 transcriptional activity but polymorphic effectors differentially modulate IFNγ induced gene expression and STAT1 phosphorylation.
Sample Metadata Fields
Specimen part
View Samples