Human mononuclear phagocytes comprise phenotypically and functionally overlapping subsets of dendritic cells (DC) and monocytes, but their identification remains elusive. By integrating high-dimensional single-cell protein and RNA expression data, we clearly delineated monocytes from conventional DC2 (cDC2), identifying new markers including CD88/CD89 for monocytes and HLA-DQ/Fc?RI? for cDC2, allowing their unambiguous characterization in blood and tissues. We also show that cDC2 can be subdivided into phenotypically and functionally distinct subsets based on CD5, CD163 and CD14 expression, including a unique subset of circulating inflammatory CD5-CD163+CD14+ cells related to previously defined DC3. These inflammatory DC3 were expanded in systemic lupus erythematosus patients, correlating with disease activity. Unravelling the heterogeneity of DC sub-populations in health and disease paves the way for specific DC subset-targeting therapies. Overall design: Indexed single cell RNAseq (scRNAseq) of human peripheral blood dendritic cells and monocytes
Single-Cell Analysis of Human Mononuclear Phagocytes Reveals Subset-Defining Markers and Identifies Circulating Inflammatory Dendritic Cells.
Specimen part, Subject
View SamplesWe used microarrays to detail the global programme of gene expression in lung SCC cells treated with belinostat, a pan-HDAC inhibitor. The primary focus of this work is to investigate the efficacy of belinostat on lung SCC cells. Our phosphoproteomic profiling analyses revealed the downregulation of MAPK signaling pathway upon drug treatment, together with the induction of apoptosis. While HDAC inhibition generally affects transcription, the mechanism of SOS/MAPK downregulation was therefore proposed to be affected at the transcriptomic level. However, genes related to MAPK pathway were not significantly regulated upon belinostat treatment, whereas ubiquitin-proteasome gene signature was affected. This supports an indirect mechanism of epigenetic regulation on MAPK signaling that should be explored further.
Belinostat exerts antitumor cytotoxicity through the ubiquitin-proteasome pathway in lung squamous cell carcinoma.
Cell line, Treatment
View SamplesWe show that aneuploidy is common in wild isolates of yeast, which are inherently tolerant to chromosome amplification and down-regulate expression at 40% of amplified genes. To dissect the mechanism of this dosage response, we generated isogenic strain panels in which diploid cells carried either two, three, or four copies of the affected chromosomes. Using a mixture of linear regression (MLR) model to classify genes, we find that expression is actively down regulated in proportion to increased gene copy at up to 30% of genes. Genes subject to dosage control are under higher expression constraint – but show elevated rates of gene amplification – in wild populations, suggesting that dosage compensation buffers copy number variation (CNV) at toxic genes Overall design: RNA-seq and transcriptome analysis of S. cerevisiae natural isolates having aneuploidy. Technical triplicate was performed for isogenic diploid strains having 2, 3 and 4 copies of a given chromosome (strain panels), while technical duplicate or singulate was performed on all other aneuploids.
Dosage compensation can buffer copy-number variation in wild yeast.
Subject
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Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesArs2 is a component of the nuclear cap-binding complex that is required for cellular proliferation and contributes to microRNA biogenesis. Arrays were performed to determine the repertoire of genes that change following knock-down of Ars2. Knock-down of DGCR8 was also performed to determine which changes in Ars2 knock-down cells resulted from defects in microRNA expression.
Ars2 promotes proper replication-dependent histone mRNA 3' end formation.
Specimen part, Cell line, Treatment
View SamplesPseudomonas aeruginosa undergoes cell elongation and forms robust biofilms during anaerobic respiratory growth using nitrate (NO3-) as an alternative electron acceptor. Understanding the mechanism of cell shape change induced upon anaerobiosis is crucial to the development of effective treatments against P. aeruginosa biofilm infection. Anaerobic growth of PAO1 reached higher cell density in the presence of vitamin B12, an essential coenzyme of class II ribonucleotide reductase. In addition, cell morphology returned to a normal rod shape. These results suggest that vitamin B12, the production of which was suppressed during anaerobic growth, can restore cellular machineries for DNA replication and therefore facilitate better anaerobic growth of P. aeruginosa with normal cell division.
Vitamin B12-mediated restoration of defective anaerobic growth leads to reduced biofilm formation in Pseudomonas aeruginosa.
No sample metadata fields
View SamplesWe have determined that tenascin C (TNC) regulates the growth of human brain tumor initiating cells (BTICs). We have identified novel mechanisms by which TNC regulates BTIC growth. Analysis of the array data identified a number of genes that were altered with TNC treatment that could potentially regulate BTIC growth. The study provides the mechanistic basis for the regulation of BTIC growth with TNC.
Activation of NOTCH Signaling by Tenascin-C Promotes Growth of Human Brain Tumor-Initiating Cells.
Specimen part, Cell line, Treatment
View SamplesGenome-wide analysis of decidual transcriptome in pre-eclampsia compared with normotensive controls to find differentially expressed genes/pathways.
Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.
Specimen part, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
Cell line
View SamplesEstrogen receptor (ER) is key player in the progression of breast cancer. ER binds to DNA and mediates long-range chromatin interactions throughout the genome, but the underlying mechanism in this process is unclear. Here, we show that AP-2 motifs are highly enriched in the ER binding sites (ERBS) identified from the recent ChIA-PET of ER. More importantly, we demonstrate that AP-2 (also known as TFAP2C), a member of the AP-2 family which has been implicated in breast cancer oncogenesis, is recruited to chromatin in a ligand-independent manner and co-localized with ER binding events. Furthermore, pertubation of AP-2 expression disrupts ER DNA binding, long-range chromatin interactions, and gene transcription. Using ChIP-seq, we show that AP-2 and ER binding occurs in close proximity on a genome-wide scale. The majority of these shared genomic regions are also occupied by the pioneer factor, FoxA1. AP-2 is required for efficient FoxA1 binding and vice versa. Finally, we show that most ERBS associated with long-range chromatin interactions are co-localized with both AP-2 and FoxA1. Together, our results suggest AP-2 is an essential factor in ER-mediated transcription, primarily working together with FoxA1 to facilitate ER binding and long-range chromatin interactions.
AP-2γ regulates oestrogen receptor-mediated long-range chromatin interaction and gene transcription.
Cell line
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