Va24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer, represent promising therapeutic target. However, reduced iNKT-cell numbers and function have been observed in many patients with cancer. To overcome this obstacle, we reprogramed human iNKT cells to pluripotency and then redifferentiated into regenerated iNKT cells in vitro through IL-7/IL-15-based optimized cytokine combination. They showed proliferation and IFN-? production in response to a-galactosylceramide, induced dendritic cell maturation and downstream activation of cancer antigen-specific cytotoxic T lymphocytes in vitro, and exhibited NKG2D- and DNAM-1-mediated natural killer celllike cytotoxicity against cancer cell lines. Their immunological features and availability in an unlimited supply from induced pluripotent stem cells offer the potential to develop effective immunotherapies against cancer. Overall design: Expression profile of the lymphocytes (n = 17) by highthrouput sequencing
Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells.
No sample metadata fields
View SamplesTo analyze roles of transcription factor Fezf2 in retinal development, knockout mouse of Fezf2 was generated, and gene expression pattern of Fezf2-KO retina and control retina was examined by RNA-seq. Overall design: To analyze roles of transcription factor Fezf2 in retinal development, knockout mouse of Fezf2 was generated, and gene expression pattern of Fezf2-KO retina and control retina was examined by RNA-seq.
Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in retina.
Specimen part, Subject
View SamplesMicroarray experiments were performed using Arabidopsis wild type plants (Col-0) and srk2cf double knockout mutants to investigate functions of two osmotic stress-activated protein kinases, SRK2C and SRK2F. Transcription profiles of wild type and mutants were compared under abscisic acid (ABA) treatment for 0, 1 and 4 h.
Two closely related subclass II SnRK2 protein kinases cooperatively regulate drought-inducible gene expression.
Age, Time
View SamplesMicroarray experiments were performed using Arabidopsis wild type plants (Col-0) and srk2cf double knockout mutants to investigate functions of two osmotic stress-activated protein kinases, SRK2C and SRK2F. Transcription profiles of wild type and mutants were compared under drought stress for 0, 1 and 4 h.
Two closely related subclass II SnRK2 protein kinases cooperatively regulate drought-inducible gene expression.
Age, Time
View SamplesIdentify transcriptional factors responsible for cytokine and chemokine production by fibroblasts
Autocrine Loop Involving IL-6 Family Member LIF, LIF Receptor, and STAT4 Drives Sustained Fibroblast Production of Inflammatory Mediators.
Specimen part, Disease, Disease stage
View SamplesCell cycle quiescence is a critical feature contributing to haematopoietic stem cell (HSC) maintenance. Although various candidate stromal cells have been identified as potential HSC niches, the spatial localization of quiescent HSC in the bone marrow (BM) remains unclear. Here, using a novel approach that combines whole-mount confocal immunofluorescence imaging technique and computational modelling to analyse significant tridimensional associations among vascular structures, stromal cells and HSCs, we show that quiescent HSCs associate specifically with small arterioles that are preferentially found in endosteal BM. These arterioles are ensheathed exclusively by rare Nestin-GFP-peri/NG2+ pericytes, distinct from sinusoid-associated Nestin-GFP-retic/LepR+ cells. The present RNA-seq study sought to obtain a comprehensive understanding of the differences between the two distinct HSC cellular niches. Overall design: mRNA profiles of sorted Nestin-GFP-peri and -GFP-retic bone marrow stromal cells were generated from pooled mice in triplicate by Illumina HiSeq 2000 sequencing.
Arteriolar niches maintain haematopoietic stem cell quiescence.
Specimen part, Subject
View SamplesRATIONALE: Human rhinovirus infections cause colds and trigger exacerbations of lower airway diseases. OBJECTIVES: To define changes in gene expression profiles during in vivo rhinovirus infections. METHODS: Nasal epithelial scrapings were obtained before and during experimental rhinovirus infection, and gene expression was evaluated by microarray. Naturally acquired rhinovirus infections, cultured human epithelial cells, and short interfering RNA knockdown were used to further evaluate the role of viperin in rhinovirus infections. MEASUREMENTS AND MAIN RESULTS: Symptom scores and viral titers were measured in subjects inoculated with rhinovirus or sham control, and changes in gene expression were assessed 8 and 48 hours after inoculation. Real-time reverse transcription-polymerase chain reaction for viperin and rhinoviruses was used in naturally acquired infections, and viperin mRNA levels and viral titers were measured in cultured cells. Rhinovirus-induced changes in gene expression were not observed 8 hours after viral infection, but 11,887 gene transcripts were significantly altered in scrapings obtained 2 days postinoculation. Major groups of up-regulated genes included chemokines, signaling molecules, interferon-responsive genes, and antivirals. Viperin expression was further examined and also was increased in naturally acquired rhinovirus infections, as well as in cultured human epithelial cells infected with intact, but not replication-deficient, rhinovirus. Knockdown of viperin with short interfering RNA increased rhinovirus replication in infected epithelial cells. CONCLUSIONS: Rhinovirus infection significantly alters the expression of many genes associated with the immune response, including chemokines and antivirals. The data obtained provide insights into the host response to rhinovirus infection and identify potential novel targets for further evaluation.
Gene expression profiles during in vivo human rhinovirus infection: insights into the host response.
No sample metadata fields
View SamplesLoss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling.
Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate.
Specimen part
View SamplesWe generated whole genome expression profiles from a homogeneous population of purified pacemaker neurons (ventral Lateral Neurons, LNvs) from wild type and clock mutant Drosophila. The study identifes a group of genes whose expression is highly enriched in LNvs compared to other neurons; and a second group of genes rhythmically expressed in LNvs in a clock-dependent manner.
A mechanism for circadian control of pacemaker neuron excitability.
Specimen part
View SamplesTo identify early processes in carcinogenesis, we used an in vitro model, based on the initiating event in cervical cancer, human papillomavirus (HPV) transformation of keratinocytes. We compared gene expression in primary keratinocytes (K) and HPV16-transformed keratinocytes from early (E) and late (L) passages, and from benzo[a]pyrene treated L cells (BP). The transformed cells exhibit similar transcriptional changes to clinical cervical carcinoma. We revealed a contraction in expression of the apoptotic network during HF1 cell transformation, which affected the ability of L and BP cells to execute apoptosis, but did not lead to resistance to apoptotic stimuli. The contraction in the apoptotic machinery during the process of transformation was accompanied by a switch from apoptosis to necrosis in response to CDDP. The shrinkage of the pro- and anti-apoptotic networks appears to be part of a general contraction in the number of genes transcribed in L and BP cells. We also identified a large group of genes with induced expression, which are involved in cell metabolism and cell cycle, suggesting increased investment of the transformed cell in cellular proliferation. We hypothesize that the decrease in expression of many diverse pathways, including the pro- and anti-apoptotic networks, cuts the energy requirements for cell maintenance, allowing energy to be diverted towards rapid cell proliferation. This study supports the hypothesis that the process of cancer transformation may be accompanied by a shift from apoptosis to necrosis.
Shift from apoptotic to necrotic cell death during human papillomavirus-induced transformation of keratinocytes.
Specimen part, Cell line
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