Project description:We exploited label-free quantitative mass spectrometry to compare primary human blood Dendritic cells (DCs) subsets protein expression to identify new markers. Subsets distinguished are: Plasmacytoid DCs (pDC) and BDCA3+ and CD1c+ myeloid DCs and CD16+ monocytes. The dendritic cells were analyzed by LC-MS/MS and processed by MaxQuant for identification and LFQ quantification.
Project description:This SuperSeries is composed of the following subset Series: GSE24726: Gene expression profile of mature plasmacytoid dendritic cells (PDC) after the deletion of transcription factor E2-2 GSE24740: Binding targets of transcription factor E2-2 in human plasmacytoid dendritic cells Refer to individual Series
Project description:<p>Plasmacytoid dendritic cells (pDC) are a subset of dendritic cells with unique immunophenotypic properties and functions. While their role in antiviral immunity through production of type I interferons is well-established, their contributions to anti-tumor immunity are less clear. While some evidence demonstrates that pDC in the tumor microenvironment (TME) may drive CD4+ T cell to become <a href="https://www.ncbi.nlm.nih.gov/gene/50943">Foxp3</a>+ T regulatory cells, little is understood about the relationship of pDC with cytotoxic CD8+ T cell, the key player in antitumor immune responses.</p> <p>In this study, we perform comprehensive immunophenotyping and functional analysis of pDC from the TME and draining lymph nodes of patients with head and neck squamous cell carcinoma (HNSCC) and identify a novel pDC subset characterized by expression of the TNF receptor superfamily member <a href="https://www.ncbi.nlm.nih.gov/gene/?term=7293">CD134 (OX40)</a>. We show that OX40 expression is expressed on intratumoral pDC in both humans and mice in a tumor-model specific fashion and that this subset of pDC enhances tumor associated-antigen (TAA)-specific CD8+ T cell responses. Through transcriptomic profiling of OX40-expressing pDC from the TME, we further characterize gene signatures unique to this pDC subset that support its role as an important immunostimulatory immune population in the TME.</p>
Project description:Langerhans cell histiocytosis (LCH) is a disease characterized by the accumulation of eponymous CD1a+ Langerin+ Langerhans-cell (LC)-like dendritic cells (DC) of largely unknown origin. Here we have performed comparative transcriptome analysis of highly purified CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations and disease courses and three major human dendritic cell lineages: epidermal Langerhans cells, myeloid dendritic cells (mDC1) and plasmacytoid dendritic cells (pDC) in order to investigate the relationship between LCH cells and naturally occurring dendritic cells. Data obtained indicate that LCH cells form a distinct DC entity. Furthermore, we have identified transcripts that are uniquely expressed by LCH cells in comparison to LC, mDC1, and pDC, and induce LCH-specific features in human DC. Primary cells were isolated from peripheral blood (mDC1 and pDC), skin (epidermal Langerhans cells) and CD207+/CD1a+ Langerhans cell histiocytosis (LCH) cells derived from different locations. RNA was isolated from these cells ex vivo.
Project description:To identify microRNA changes during plasmacytoid dendritic cell (PDC) activation, we stimulated human primary PDCs with 10ug/ml R837 (Invivogen, San Diego, CA, USA) for 4 hours.
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
Project description:The interferon-producing plasmacytoid dendritic cells (PDC) share common progenitors with antigen-presenting classical dendritic cells (cDC), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of PDC is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral PDC caused their spontaneous differentiation into cells with cDC properties. This included the loss of PDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key PDC-specific and lymphoid genes, as well as to certain genes enriched in cDC. Thus, E2-2 actively maintains the cell fate of mature PDC and opposes the “default” cDC fate, in part through direct regulation of lineage-specific gene expression programs. Cells of the human PDC lymphoma line CAL-1 (Maeda et al., Int J Hematol 2005) were crosslinked with formaldehyde, sonicated, and subjected to immunoprecipitation with anti-E2-2 mAb (Bain et al., Mol Cell Biol 1993) or mouse IgG control as described (Cisse et al., Cell 2008). After crosslink reversal, the isolated chromatin was amplified, labeled and hybridized to Human Promoter ChIP-on-chip Microarray Set (Agilent Technologies). Hybridized microarrays were scanned and analyzed using DNA Analytics software (Agilent Technologies).
Project description:Plasmacytoid dendritic cells [pDCs] represent a rare innate immune subset uniquely endowed with the capacity to produce substantial amounts of type-I interferons [IFN-I]. This function of pDCs is critical for effective antiviral defenses and has been implicated in autoimmunity. While IFN-I and select cytokines have been recognized as pDC secreted products, a comprehensive agnostic profiling of the pDC secretome in response to a physiologic stimulus has not been reported. We applied LC-MS/MS to catalogue the repertoire of proteins secreted by pDCs in response to challenge with live influenza H1N1. Additionally, using single-cell RNA-seq [scRNA-seq], we perform multidimensional analyses of pDC transcriptional diversification following stimulation. Our data reveal an abundance of protein species released by pDCs in addition to IFN-I, and evidence highly specialized roles within the pDC population ranging from dedicated cytokine super-producers to cells with APC-like functions. Moreover, dynamic expression of transcription factors and surface markers characterize activated pDC fates.