Microarrays were used to detail the global program of gene expression underlying differences in the organisation of inflammatory cells classified by the expression of the CD21L and IL-17A genes. Synovia were defined by the expression of the CD21L and IL-17A genes as determined by semi-quantitative PCR.
Co-expression of CD21L and IL17A defines a subset of rheumatoid synovia, characterised by large lymphoid aggregates and high inflammation.
Specimen part, Disease, Disease stage, Subject
View SamplesTo identify genes expressed during initiation of lung organogenesis, we generated transcriptional profiles of the prospective lung region of the mouse foregut (mid-foregut) microdissected from embryos at three developmental stages between embryonic day 8.5 (E8.5) and E9.5. This period spans from lung specification of foregut cells to the emergence of the primary lung buds. We identified a number of known and novel genes that are temporally regulated as the lung bud forms. Genes that regulate transcription, including DNA binding factors, co-factors, and chromatin remodeling genes, are the main functional groups that change during lung bud formation. Members of key developmental transcription and growth factor families, not previously described to participate in lung organogenesis, are expressed in the mid-foregut during lung bud induction. These studies also show early expression in the mid-foregut of genes that participate in later stages of lung development. This characterization of the mid-foregut transcriptome provides new insights into molecular events leading to lung organogenesis.
Characterization of the mid-foregut transcriptome identifies genes regulated during lung bud induction.
No sample metadata fields
View SamplesThe long noncoding RNA NKX2-1-AS1 is highly expressed in primary lung adenocarcinomas compared to squamous carcinomas, similar to its adjacent protein-coding gene NKX2-1, but its contribution to lung tumorigenesis is not well understood. In this study we knockdown NKX2-1-AS1 by siRNA transfection and analyze the effect on gene expression in the lung carcinoma H441 cell line.
NKX2-1-AS1 negatively regulates CD274/PD-L1, cell-cell interaction genes, and limits human lung carcinoma cell migration.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer.
Specimen part, Cell line, Treatment
View SamplesA significant fraction of breast cancers exhibit de novo or acquired resistance to estrogen deprivation. To model resistance to aromatase inhibitor (AI) therapy, long-term estrogen-deprived (LTED) derivatives of MCF-7 and HCC-1428 cells were generated through culture for 3 and 7 months under hormone-depleted conditions, respectively. These LTED cells showed sensitivity to the ER downregulator fulvestrant under hormone-depleted conditions, suggesting continued dependence upon ER signaling for hormone-independent growth. To evaluate the role of ER in hormone-independent growth, LTED cells were treated +/- 1 uM fulvestrant x 48 h before RNA was harvested for gene expression analysis.
ERα-dependent E2F transcription can mediate resistance to estrogen deprivation in human breast cancer.
Specimen part, Cell line, Treatment
View SamplesRNA from circulating blood reticulocytes was utilized to provide a robust description of genes transcribed at the final stages of erythroblast maturation. After depletion of leukocytes and platelets, Affymetrix HG-U133Plus 2.0 arrays were hybridized with probe from total RNA isolated from blood sampled from 6 umbilical cords and 6 healthy adult humans.
Let-7 microRNAs are developmentally regulated in circulating human erythroid cells.
Specimen part
View SamplesHyperactivation of phosphatidylinositol-3 kinase (PI3K) promotes escape from hormone dependence in estrogen receptor-positive breast cancer.
Hyperactivation of phosphatidylinositol-3 kinase promotes escape from hormone dependence in estrogen receptor-positive human breast cancer.
Specimen part, Cell line
View SamplesMultiple sclerosis involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system. Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells are stem cells in the central nervous system and the principal source of myelinating oligodendrocytes. These cells are abundant in demyelinated regions of patients with multiple sclerosis, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention. To discover therapeutic compounds for enhancing myelination from endogenous oligodendrocyte progenitor cells, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem-cell-derived oligodendrocyte progenitor cells. Here we show seven drugs function at nanomolar doses selectively to enhance the generation of mature oligodendrocytes from progenitor cells in vitro. Two drugs, miconazole and clobetasol, are effective in promoting precocious myelination in organotypic cerebellar slice cultures, and in vivo in early postnatal mouse pups. Systemic delivery of each of the two drugs significantly increases the number of new oligodendrocytes and enhances remyelination in a lysolecithin-induced mouse model of focal demyelination. Administering each of the two drugs at the peak of disease in an experimental autoimmune encephalomyelitis mouse model of chronic progressive multiple sclerosis results in striking reversal of disease severity. Immune response assays show that miconazole functions directly as a remyelinating drug with no effect on the immune system, whereas clobetasol is a potent immunosuppressant as well as a remyelinating agent. Mechanistic studies show that miconazole and clobetasol function in oligodendrocyte progenitor cells through mitogen-activated protein kinase and glucocorticoid receptor signalling, respectively. Furthermore, both drugs enhance the generation of human oligodendrocytes from human oligodendrocyte progenitor cells in vitro. Collectively, our results provide a rationale for testing miconazole and clobetasol, or structurally modified derivatives, to enhance remyelination in patients. Overall design: RNA sequencing of oligodendrocyte progenitor cells treated with vehicle, miconazole or clobetasol for 0, 2, 6, or 12 hours. Cells were plated 1.5 hours prior to addition of drug.
Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo.
No sample metadata fields
View SamplesWe report the RNA profiles of both control and Kif3a f/f; Wnt1-Cre mandibular prominences of the murine face at embryonic day E11.5. We sought to determine the gene expression changes which occurr in the mandibular prominence when primary cilia are lost on neural crest cells. Overall design: The mandibular prominence from 10 control e11.5 embryos were collected and pooled, and 10 mutant e11.5 embryos were collected and pooled. RNA-seq was performed on these samples.
Cilia-dependent GLI processing in neural crest cells is required for tongue development.
Specimen part, Subject
View SamplesmRNA microarray analysis of bone marrow derived macrophages treated under four conditions, including Nave (N). Bone marrow derived macrophages (BMDM) were derived from the bone marrow of mice and cultured in the presence of PAO, IFN-gamma, or lipopolysaccharide (LPS). Profiled groups include Naive, LPS, IFN, PAO.
Cleavage of fibrinogen by proteinases elicits allergic responses through Toll-like receptor 4.
Sex, Specimen part
View Samples