Neutrophils are one of key innate immune cells which play an important role in pathogen clearance. Neutrophils can also exert immunoregulatory functions via direct or indirect means, particularly on T cell responeses. However, there is little study for its role on T cell differentiation, especially whether neutrophils regulate human neonatal T cell differentiation is not clear. In the current study, we have demonstrated that human neonatal neutrophils can initiate the de novo Th2 cell differentiation. Besides, neonatal neutrophils showed an immature and less differentiated phenotype compared to adult neutrophils. RNAseq results indicated that the gene expression profiles of neonatal neutrophils were quite different from those of adult neutrophils. Specifically, the gene pathways related to eliminating microbes were impared in neonatal neutrophils, which could be another reason contributing to the high susceptibility to pathogens at neonatal stage.
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Sex, Age, Specimen part, Disease, Treatment, Race
View SamplesObjective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.
Ductular Reaction Cells Display an Inflammatory Profile and Recruit Neutrophils in Alcoholic Hepatitis.
Sex, Age, Specimen part, Disease, Disease stage, Cell line, Treatment, Race
View SamplesTo gain a deep understanding of mRNA turnover dynamics in mammalian cells, we pulse labeled newly synthesized RNA in 3t3 cells for 2 h with 4sU. RNA samples were fractionated into the newly synthesized and pre-existing fractions. Both fractions and the total RNA sample were analyzed by mRNA sequencing. We estimated mRNA half-lives based on the ratios of newly synthesized RNA/total RNA ratio and the preexisting RNA/total RNA.
Global quantification of mammalian gene expression control.
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View SamplesRecent studies suggest vitamin D deficiency is associated with chronic lung diseases such as asthma and chronic obstructive pulmonary disease. Each of these are characterised by airway hyperresponsiveness (AHR) and airway remodeling, the latter characterized by increased airway smooth muscle (ASM) mass. In this study we investigated the biological mechanisms underlying increased ASM mass and AHR due to vitamin D deficiency via RNA-seq transcriptome analysis of female BALB/c mice at 8 weeks of age.
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View SamplesRNA expression in adipose and skin from women with polycystic ovary syndrome (PCOS) was examined using RNA sequencing (Illumina HiSeq 50 cycle single-read sequencing) as a function of the genotype at 16 PCOS genetic risk variants. We hypothesized that the tissue expression pattern in adipose and skin would help identify candidate genes and pathways that could provide insight into the underlying mechanism for risk at these loci.
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Sex, Age, Specimen part
View SamplesHigh-throughput sequencing of RNA (RNA-Seq) in human cancer shows remarkable potential to simultaneously identify expression levels of protein-coding genes and long non-coding RNAs (lncRNAs). We performed RNA-Seq to investigate expression level of lncRNAs and protein-coding genes in 30 esophageal samples, including 15 esophageal squamous cell carcinoma (ESCC) tissue samples and 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE (for unsupervised random walk with each dysregulated lncRNA/PCG), to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. By this method, multiple known cancer and novel potentially functional lncRNAs were effectively identified. Quantitative reverse-transcription PCR was performed to confirm the lncRNA expression level of eight novel functional lncRNAs in an additional 120 paired ESCC patient samples. Finally, we characterized lncRNA625 as a novel ESCC regulator of cell proliferation, invasion and migration. Moreover, we identified E1A-binding protein p300 (EP300) as playing a key role in executing lncRNA625-induced transcriptional responses. These findings establish the utility of integrative bioinformatics analyses of RNA-Seq to identify cancer-associated functional lncRNAs.
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View SamplesWe report a comprehensive large-scale expression profiling analysis of mammalian male germ cells undergoing mitotic growth, meiosis and gametogenesis using High Density Oligonucleotide Microarrays and highly enriched cell populations. Among 11955 rat loci investigated, 1268 were identified as differentially transcribed in germ cells at subsequent developmental stages as compared to total testis, somatic Sertoli cells as well as brain and skeletal muscle controls. The loci were organized into four expression clusters that correspond to somatic, mitotic, meiotic and post-meiotic cell types. This work provides information about expression patterns of approximately 200 genes known to be important during male germ cell development. Approximately 40 of those are included in a group of 121 transcripts for which we report germ cell expression and lack of transcription in three somatic control cell types. Moreover, we demonstrate the testicular expression and transcriptional induction in mitotic, meiotic and/or post-meiotic germ cells of 293 as yet uncharacterized transcripts some of which are likely to encode factors involved in spermatogenesis and fertility. This group also contains numerous potential germ cell specific targets for innovative contraceptives. A graphical display of the data is conveniently accessible through the GermOnline database at <a href="http://www.germonline.org" target="_blank">http://www.germonline.org</a>.
Expression profiling of mammalian male meiosis and gametogenesis identifies novel candidate genes for roles in the regulation of fertility.
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View SamplesCH causes perivascular inflammation, enhanced pulmonary arterial constriction and remodeling leading to the development of pulmonary hypertension. Pulmonary hypertension is a debilitating disease with a high mortality rate. CH develops in patients with chronic obstructive pulmonary disease (COPD), sleep apnea or people living at high altitude. Both COPD and sleep apnea are very prevalent and pulmonary hypertension develops in a large % of COPD and sleep apnea patients. The molecular mechanisms that underlie the development of CH-induced pulmonary hypertension are far from clear. We have previously demonstrated that CH activates the Ca2+/calcineurin-regulated transcription factor NFATc3 in PASMC and that NFATc3 is required for CH-induced pulmonary hypertension in mice. Although this work was the first to identify a role for this transcription factor in an experimental model of pulmonary hypertension, since a conventional whole animal KO was used it is unknown if PASMC NFATc3 contributes to CH-induced PH. Furthermore, the genes regulated by NFATc3 in PASMC under control and CH conditions are largely unknown.
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View SamplesThe transcriptome of the three atino80 allelic mutants was compared to that of wild-type and 50B Arabidopsis plants (see Fritsch et al. 2004). Since the transcriptomes of 50B and wild-type plants were found to be identical, we compared expression in the mutant with 50B and with wild-type without distinction. Therefore, we had four replicates of the wild type condition (50B line, wild-type) and two replicates for each of the mutant alleles (atino80-1, atino80-2 and atino80-3), all ecotype Columbia. All lines were profiled in duplicate (grown independently at 2-week-intervals).
The INO80 protein controls homologous recombination in Arabidopsis thaliana.
Age, Specimen part
View SamplesAnalysis of nuclear atrial gene expression in purified atrial cardiac myocyte nuclei isolated from right atrial appendages from adult patients undergoing open-heart surgery for coronary bypass or valve correction.
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