In the normal prostate, most basal and some luminal cells are castration-resistant (CR). The identity of these CR cells and their relation to CR prostate cancer are unresolved. We compared single-cell expression profiles of prostate cells sorted from hormonally nave (HN) and castrated mice. We found both basal and luminal-localized cells, particularly the latter, were molecularly heterogeneous. CR luminal cells and a subset of HN luminal cells exhibited a similar intermediate expression pattern, including high-level expression of multiple prostate stem/progenitor marker genes and androgen receptor gene. We validated LY6D as a marker linking CR luminal cells to luminal progenitors. LY6D+ prostate cells, including LY6D+ luminal cells, were enriched for organoid-forming potential regardless of the presence or absence of androgen. Krt8-based lineage-tracing revealed that LY6D+ CR luminal cells produced LY6D- normal luminal cells upon regeneration, but LY6D+ luminal cancer cells under PTEN-deficiency. Furthermore, prostate cancers originating from CR luminal cells (LY6D+) exhibited a more advanced phenotype than those from HN luminal cells (LY6D+ or LY6D-). Lastly, LY6D amplification/upregulation appear associated with advanced prostate cancer in patient samples. Together, our studies demonstrate LY6D as a novel progenitor marker predictive of lethal CR disease.
Single-Cell Analysis Identifies LY6D as a Marker Linking Castration-Resistant Prostate Luminal Cells to Prostate Progenitors and Cancer.
Sex, Specimen part
View SamplesThe goal of this study was to determine developmental differences in gene expression between left and right ventricle, and to assess the differential effect of altered hemodynamic loading on left and right ventricle. Chick ventricles from different developmental stages were isolated for assessment of normal developmental profiles. Conotruncal banding or partial ligation of the left atrial appendage was performed in ovo at embryonic day 4 and ventricles were isolated at embryonic day 5 (banding) or 8 (ligation) for assessment of altered loading effects.
Microarray analysis of normal and abnormal chick ventricular myocardial development.
Specimen part
View SamplesChanges in Treg function are difficult to quantify due to the lack of Treg-exclusive markers in humans and the complexity of functional experiments. We sorted naive and memory human Tregs and conventional T cells, and identified genes that identify human Tregs regardless of their state of activation. We developed this Treg signature using Affymetrix human genome U133A 2.0 microarrays.
A Regulatory T-Cell Gene Signature Is a Specific and Sensitive Biomarker to Identify Children With New-Onset Type 1 Diabetes.
Treatment, Subject
View SamplesBecause of the extensive data in mice supporting the concept that ST2+ Tregs might have desirable therapeutic properties, including tissue repair function, high suppressive capacity, and enhanced stability, we engineered human blood Tregs to constitutively express ST2 (IL-33R). Here we used RNA sequencing to explore the effects of short-term culture with IL-33 on human ST2-transduced Tregs. Overall design: Human naive Tregs flow-sorted from 4 independent donors were lentivirally transduced with ST2, expanded for 13 days, then stimulated with IL-2 and TCR (16 h) or IL-2, TCR, and IL-33 (16 h).
Innate Control of Tissue-Reparative Human Regulatory T Cells.
Sex, Specimen part, Subject
View SamplesDifferences in the inherent properties of undifferentiated fat cell progenitors may contribute to the biological specificity of the abdominal subcutaneous (Sc) and visceral omental (V) fat depots. In this study, the biological characteristics of three distinct subpopulations of adipose tissue-derived stem cells (ASC), i.e. ASCSVF, ASCBottom and ASCCeiling isolated from Sc and V adipose tissue biopsies of non-obese subjects, were investigated. Genome-wide differential gene expression analysis followed by quantitative RT-PCR and analysis of cytokines in the ASC-derived conditioned medium were performed. By analysis of 28,869 annotated genes, 1,019 genes resulted differentially expressed between Sc-ASC and V-ASC. Within the Sc-ASC and V-ASC populations, 546 and 1,222, respectively, were the genes differentially expressed among ASCSVF, ASCBottom and ASCCeiling. A far more striking difference was found when the hierarchical clusters analysis was performed comparing each Sc-ASC with its own homologous V-ASC subset. mRNA levels of HoxA5, Tbx15, PI16, PITPNC1, FABP5, IL-6, IL-8, MCP-1, VEGF, MMP3, TFPI2, and ANXA10 were significantly different between Sc-ASC and V-ASC. Of the 27 cytokines measured, 14 (IL-2, IL-4, IL-5 IL-7, IL-9, IL-10, IL12, IL13, MIP1-, MIP1-, PDGF-, FGFbasic, GM-CSF, IP-10) were not released, whereas 13 were expressed (IL-1beta, IL-1ra, IL-15, IL-17, G-CSF, IFN, RANTES, TNF-, Eotaxin, IL-8, MCP-1, VEGF, IL-6), and of these, MCP-1, Eotaxin, IL-1ra, FGFbasic, IL-6, IL-8, G-CSF, and VEGF were significantly different among ASCSVF, ASCCeiling and ASCBottom of the two adipose tissue depots. These results demonstrate the existence of genetically and functionally heterogeneous fat-derived ASC populations, which may add to the complexity and specificity of Sc and V adipose tissue in humans.
Differences in gene expression and cytokine release profiles highlight the heterogeneity of distinct subsets of adipose tissue-derived stem cells in the subcutaneous and visceral adipose tissue in humans.
Specimen part
View SamplesSugars modulate expression of hundreds of genes in plants. Previous studies on sugar signaling, using intact plants or plant tissues, were hampered by tissue heterogeneity, uneven sugar transport and/or inter-conversions of the applied sugars. This, in turn, could obscure the identity of a specific sugar that acts as a signal affecting expression of given gene in a given tissue or cell-type. To bypass those biases, we have developed a novel biological system, based on stem-cell-like Arabidopsis suspension culture. The cells were grown in a hormone-free medium and were sustained on xylose as the only carbon source. The functional genomics approach was used to identify sugar responsive genes, which rapidly (within 1 h) respond specifically to low concentration (1 mM) of glucose, fructose and/or sucrose.
Functional dissection of sugar signals affecting gene expression in Arabidopsis thaliana.
No sample metadata fields
View SamplesWe report differences in mRNA gene expression in rectal biopsies from MSM compared to controls and for MSM timed with episodes of CRAI. Overall design: Rectal biopsies were obtained from MSM at two study timepoints: 1. after who abstaining from CRAI for >72 hours and 2.after engaing in CRAI within the last 24 hours. Rectal biopsies were also obtained from men who never engaged in AI.
Short Communication: Anatomic Site of Sampling and the Rectal Mucosal Microbiota in HIV Negative Men Who Have Sex with Men Engaging in Condomless Receptive Anal Intercourse.
Specimen part, Subject
View SamplesAnalysis of T-cells lacking the proprotein convertase furin. Proprotein convertases promote the proteolytic maturation of proproteins. Furin is induced in activated T-cells. Results provide insight into the function of furin in T-cells.
Proprotein convertase FURIN regulates T cell receptor-induced transactivation.
Age, Treatment
View SamplesTranscriptomic analysis of gene expression during the differentiation of cell suspension cultures into tracheary elements using the biological system published by Pesquet et al., Current Biology (2010): tracheary element differentiation was triggered by externally supplying hormone-free habituated cell suspension cultures of Arabidopsis thaliana Col-0 with auxin, cytokinin and epibrassinolides; RNA samples extracted from 3 independent time-courses every 12h from 0h to 4 days were analyzed using ATH1 Arabidopsis Affymetrix micro-array
Proteomic Analysis of Microtubule Interacting Proteins over the Course of Xylem Tracheary Element Formation in Arabidopsis.
Specimen part, Time
View SamplesThe basic defect of IgA nephropathy (IgAN) lies within peripheral blood mononuclear cells rather than local kidney abnormalities. Previously we showed an altered gene expression in monocytes compared to B and T cells isolated from IgAN patients (Kidney Int, 2010), thus our aim here was to study this subset more closely at genome-wide level.
Altered monocyte expression and expansion of non-classical monocyte subset in IgA nephropathy patients.
Specimen part, Disease
View Samples