title: Inhaled TLR9 Agonist Renders Lung Tumors Permissive to PD-1 Blockade Promoting Optimal CD4+ and CD8+ T cell Interplay

city: berkeley

first: Cristiana

last: Guiducci

state: California

address: 2929 seventh street suite 100

department: Discovery

institute: Dynavax

summary:
Currently approved inhibitors of the PD-1/PD-L1 pathway represent a major advance for the treatment of lung cancers, yet they are ineffective in a majority of patients due to lack of pre-existing T cell reactivity. Here we show that a TLR9 agonist delivered by inhalation is able to prime T cell responses against poorly immunogenic lung tumors and to complement the effects of PD-1 blockade. Treatment with inhaled TLR9 agonist causes profound remodeling in tumor-bearing lungs, leading to formation of tertiary lymphoid structures adjacent to the tumors, CD8+ T cell infiltration into the tumors, dendritic cell expansion and antibody production. Inhaled TLR9 agonist treatment increased the pool of functional PD-1lowT-bethigh effector CD8+ T in tumor-bearing lungs. We show by transcriptional profiling, that the effector CD8+ T cells generated by inhaled TLR9 agonist treatment are licensed by PD-1 blockade to become highly functional CTL, leading to a durable rejection of both lung tumors and tumor lesions outside the lungs. CD4+ T cells activated in response to inhaled TLR9 play a critical role in this process by controlling the proliferation, preventing exhaustion, and guiding the differentiation of optimally functional CTL. This study characterizes a strategy to apply localized TLR9 stimulation to a tumor type not accessible for direct injection, a strategy that may expand the therapeutic potential of PD-1 blockade in non-small cell lung cancer.
the scope of this experiment was to profile the gene expression of effector CD8 T cells from tumor bearing lungs treated by different drug regimen.

overall_design: Gene expression was performed on purified CD44+CD8+ effector T cells from 4T1 tumor-bearing lungs treated with the indicated treatment regimen (group names reflect treatment). Saline-CTRL (n=5), SD-101 (n=6), SD-101+anti-PD-1 (n=5), SD-101+anti-PD-1+a-CD4 (n=4)

first: Marilena

last: Gallotta


title: Identification of a novel LysR-type regulator involved in virulence and primary and secondary metabolism of Burkholderia pseudomallei.

status: Public on May 02 2018

city: Greifswald

first: Christian

last: Kohler

address: Ferdinand Sauerbruch Strasse 1

department: Friedrich Loeffler Institue of Medical Microbiology

country: Germany

institute: University Medicine Greifswald

summary: Burkholderia pseudomallei is a soil-dwelling bacterium which has to survive not only under harsh environmental conditions, but also within various hosts where it can cause the infectious disease melioidosis. The ability, to quickly adapt to these different conditions, is based on its huge genome which encodes for complex regulatory networks. Among them are more than 60 genes belonging to the group of LysR-type transcriptional regulators (LTTRs). Here we analyzed a B. pseudomallei mutant harboring a transposon in the gene BPSL0117 annotated as a LTTR, which we named gvmR (globally acting virulence and metabolism regulator). The gvmR mutant displayed a growth defect in minimal medium and macrophages in comparison with the wild type. Moreover, inactivation of GvmR rendered B. pseudomallei avirulent in mice indicating a critical role of GvmR in infection. These defects of the mutant were rescued by ectopic expression of gvmR. To identify genes whose expression is modulated by GvmR, global transcriptome analysis of the B. pseudomallei wild type and gvmR mutant was performed using whole genome tiling microarrays. Transcript levels of 190 and 142 genes were found to be up- and downregulated in the gvmR mutant relative to the wild type. Among the most downregulated genes in the gvmR mutant were important virulence factor genes (T3SS3, T6SS1 and T6SS2), which might provide an explanation for the virulence defect of the gvmR mutant. In addition, expression of genes related to amino acid synthesis, glyoxylate shunt, iron-sulfur cluster assambly and syrbactin metabolism (secondary metabolite) was decreased in the mutant. Furthermore, inactivation of GvmR increased expression of genes involved in pyruvate metabolism, ATP synthesis, malleobactin and porin genes. Quantitative RT-PCR verified the differential expression of 27 selected genes. In summary, our data show that GvmR acts as an activating and repressing global regulator that is required to coordinate expression of a diverse set of metabolic and virulence genes for survival in the animal host and under nutrient limitation.

overall_design: The transcriptome profiles of Burkholderia pseudomallei wild type strain E8 and corresponding transposon mutant strain (BPSL0117::Tn5) exposed to one growth condition (M9 minimal medium, exponential growth) were captured and compared using a custom-designed tiling microarray to elucidate the BPSL0117 dependent regulon. Three biological replicates per strain were used.


title: Genome-wide transcriptome analysis in PBMCs of HIES patient A.II.1 compared to healthy sibling A.II.5

status: Public on May 04 2018

city: Freiburg im Breisgau

first: Bodo

last: Grimbacher

address: Breisacher Str. 115

institute: Center for Chronic Immunodeficiency (CCI), Medical Center – University of Freiburg

summary: Signal-transducer-and-activator-of-transcription-3 (STAT3) is a central regulator of immune homeostasis. STAT3 levels are strictly controlled and STAT3 impairment contributes to several diseases including the monogenic autosomal-dominant hyper-IgE syndrome (AD-HIES). We investigated patients of four consanguineous families with an autosomal-recessive disorder resembling the phenotype of AD-HIES, with symptoms of immunodeficiency, recurrent infections, skeletal abnormalities, and elevated IgE. Patients presented with reduced STAT3 expression and diminished Th17 cell numbers, in absence of STAT3 mutations. We identified homozygous nonsense mutations in ZNF341, encoding a zinc-finger transcription factor. Wildtype-ZNF341 bound to and activated the STAT3 promoter, whereas the mutant variants showed impaired transcriptional activation, partly due to nuclear translocation failure. In summary, nonsense mutations in ZNF341 account for the STAT3-like phenotype in four autosomal-recessive kindreds. Thus, ZNF341 is a previously unrecognized regulator of immune homeostasis.

overall_design: Total RNA of PBMCs from patient A.II.1 was compared to healthy sibling A.II.5

first: Julia

last: Hartberger

first: Stefanie

last: Frey-Jakobs

first: Manfred

last: Fliegauf

first: Claudia

last: Bossen

first: Sandra

last: Winzer

first: Amos

last: Etzioni

first: Ben-Zion

last: Garty


title: Morphology and transcriptome of Atlantic salmon skin after seawater transfer, comparison of a semi-closed containment system and open net-pen

status: Public on May 05 2018

city: Aas

first: Aleksei

last: Krasnov

address: Osloveien 1

department: Fish Health

country: Norway

institute: Nofima AS

summary: Development of semi-closed containment systems is a promising strategy to further expand Atlantic salmon production. The technology operates with higher production intensities where skin integrity is recognized as a central factor for animal health and welfare. This study investigate the skin development and its immune status in healthy Atlantic salmon growers reared in a semi-closed containment system and a traditional open net-pen system (control).

platform_organism:
Oncorhynchus mykiss
Salmo salar

overall_design: Salmon smots (PLCS) were transferred to a control open cage (C) and a semi-closed containment system (Preline - PL). Skin samples were collected from smolts in freshwater and after one and four months in seawater

last: Karlsen


title: Genome-wide analysis of High glucose-induced gene expression by DKK2 protein

city: Shinheung- Dong, Jung-Gu Incheon

first: GUO NAN

last: YIN

address: 7-206, 3rd ST B dong, 3 floor room 307-2

department: Urology

country: South Korea

institute: Inha university hospital

summary: Transcriptional profiling of Mouse cavernous primary endothelial cells (MCECs) in comparing normal glucose condition with high glucose condition or DKK2 protein treatment condition. Objective was to determine the effect of DKK2 on high glucose conditioned cells on global gene expression.

overall_design: Total RNA obtained from MCECs, which were treated with High glucose (HG) condition or (HG+DKK2). Biological replicates: 1 control replicates, 1 HG replicates, 1 (HG+DKK2) replicates.

first: GuoNan

last: Yin

first: Ji-Kan

last: Ryu

first: Jun-Kyu

last: Suh


title: Genomic copy number variation induced by TAQing system in Arabidopsis thaliana.

city: Nagakute

first: Nobuhiko

last: Muramoto

state: Aichi

address: 41-1, Yokomichi

country: Japan

institute: TOYOTA Central R&D Labs., Inc.

type: Genome variation profiling by genome tiling array

summary:
We developed an artificial genome evolution system, which we termed ‘TAQing’, by introducing multiple genomic DNA double-strand breaks using a heat-activatable endonuclease in Arabidopsis plant. The heat-activated endonuclease, TaqI, induced random DSBs, which resulted in diverse types of chromosomal rearrangements including translocations.
To evaluate the potential of TAQing in multicellular organisms, we tested it in diploid and tetraploid Arabidopsis plants. In 9 out of 96 TQ4 plants, we detected 22 large copy number variations (CNVs) events compared witn wild type plant genome, whereas no CNV was found in the 16 control tetraploid plants, and 12 TQ2 plants. The combination of artificially introduced DSBs with whole-genome duplication (WGD) in plants enabled more complex genome reorganization.

overall_design: Array comparative genomic hybridization (aCGH) of 16 control tetraploid wild type strains (WT4), 80 TAQing tetraploid strain (TQ4), 1 control dioloid (1406), 12 TAQing diploid strain (TQ2) and 6 progenines of TQ4 strain.

first: Hidenori

last: Tanaka

first: Norihiro

last: Mitsukawa


title: Detection of genomic copy number variations induced by multiple DNA breaks

summary: This SuperSeries is composed of the SubSeries listed below.

sample_organism:
Arabidopsis thaliana
Saccharomyces cerevisiae

overall_design: Refer to individual Series


title: Comparative transcriptomic profiling of peripheral efferent and afferent nerve fibres at different developmental stages in mice

status: Public on May 01 2018

city: nantong

first: hongkui

last: wang

address: 19# qixiu road

country: China

institute: nantong university

summary:
In the present study, an unbiased cDNA microarray analysis was carried out to examine differential gene expression patterns in both efferent and afferent nerve fibres at different developmental stages in mice.
The aim of this study was to provide a framework for the integrated analysis of gene regulatory networks during peripheral motor and sensory neuron differentiation/maturation.

overall_design: Agilent SurePrint G3 Mouse GE V2.0 (8 × 60 K, Design ID: 074809) microarrays (Agilent Technologies) was performed on RNA samples extracted from efferent and afferent nerve fibres originating from the L4-L6 segments of the spinal cord at different developmental stages (P0, 1W, 3W, and 5W) in C57BL/6 mice. For each group, n = 9 for each developmental time point, and data from three independent experiments were assessed to ensure reproducibility.

first: Xin

last: Tang


title: Transcriptional profiling to compare genes induced by CYTL1 to genes triggered by VEGF-A under normoxic and hypoxic conditions

city: Vienna

first: Markus

last: Jeitler

address: Lazarettgasse 14

country: Austria

institute: Medical University Vienna

summary:
CYTL1 is a bona fide pro-angiogenic factor produced by endothelial colony forming cells (ECFCs), which mediates high angiogenic sprouting of ECFCs and vessel wall endothelial cells by autocrine and paracrine stimulation, respectively.
To evaluate whether the signaling response to CYTL1 mimics the response to VEGF-A or induces unique signaling pathways in endothelial cells, we performed transcriptional profiling to compare the gene repertoire induced by CYTL1 to the repertoire triggered by VEGF-A in HUVEC under standard normoxic conditions or angiogensis stimulating hypoxic conditions.

overall_design: Each experimental treatment condition was conducted in triplicates. After RNA isolation triplicates were pooled and subjected to cRNA synthesis. Untreated HUVECs were used as reference.

first: Doris

last: Schneller

first: Erhard

last: Hofer

first: Martin

last: Bilban


title: MicroRNA-590-3p promotes ovarian cancer growth and metastasis via a novel FOXA2-Versican pathway

status: Public on Apr 21 2018

city: Toronto

first: Chun

last: Peng

state: Ontario

address: 4700 Keele Street, North York, ON, Canada

department: Biology

country: Canada

institute: York University

summary: Epithelial ovarian cancer (EOC) is the deadliest gynecological cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play important roles in gene regulation and their dysregulation is associated with many diseases. In this study, we determined the expression and function of miR-590-3p in EOC. We found that miR-590-3p levels were higher in high-grade carcinoma when compared to low-grade or tumours with low malignant potential. Interestingly, plasma levels of miR-590-3p were significantly higher in EOC patients than in subjects with benign gynaecological disorders. Transient transfection of miR-590-3p mimics, or stable transfection of mir-590, increased cell growth, migration, and invasion. In vivo studies revealed that mir-590 accelerated tumour growth and metastasis. Using a cDNA microarray, we identified Forkhead box A2 (FOXA2) and Versican (VCAN) as a top downregulated and a top upregulated gene, respectively, by mir-590. We showed that miR-590-3p targeted FOXA2 3’ UTR to suppress its expression. In addition, knockdown of FOXA2 by siRNAs or knockout of FOXA2 by CRISPR/Cas9 enhanced cell proliferation, migration, and invasion. Overexpression of FOXA2 decreased, while knockout of FOXA2 increased, VCAN mRNA and protein levels and ChIP-qPCR revealed that FOXA2 binds to VCAN promoter. Interrogation of the TCGA ovarian cancer database revealed a negative relationship between FOXA2 and VCAN mRNA levels in EOC tumours and that high FOXA2/low VCAN mRNA levels in tumours were positively correlated with patient survival. Finally, overexpression of FOXA2 or silencing of VCAN reversed the effects of mir-590. These findings demonstrate that miR-590-3p promotes EOC development via a novel FOXA2-VCAN pathway.

overall_design: A total of 6 samples were analyzed. Three control (EV) and three mir-590 overexpressing samples

first: Mohamed

last: Salem


title: Genomic copy number variation induced by TAQing system in Saccharomyces cerevisiae.

summary:
We developed an artificial genome evolution system, which we termed ‘TAQing’, by introducing multiple genomic DNA double-strand breaks using a heat-activatable endonuclease in mitotic yeast. The heat-activated endonuclease, TaqI, induced random DSBs, which resulted in diverse types of chromosomal rearrangements including translocations.
Array comparative genomic hybridization (aCGH)  analysis was performed with cell-fused Saccharomyces cerevisiae strains induced genome evolution by TAQing system. Some of copy number variations (CNVs) induced by massive genome rearrangements were detected in the TAQed yeast strains.

overall_design: We generated 13 mutrant strains with CNVs using TAQing system in yeast. We analyze contorol strain (WT14) and 13 mutants genome using aCGH, and detected CNVs in these mutants genome as compared to WT14 genome.

first: Muramoto

last: Nobuhiko

first: Akinori

last: Ikeuchi

first: Takahiro

last: Nakamura


title: Identification of gene expression biomarkers in urine for the non-invasive detection of bladder cancer

status: Public on Apr 17 2018

city: Alameda

first: Karen

middle: B.

last: Chapman

state: CA

address: 1301 Harbor Bay Parkway

country: USA

institute: OncoCyte Inc.

summary: Fifty patient urine samples diagnosed as high-grade urothelial carcinoma (HGUC) or benign were evaluated for bladder cancer via urine cytology.  RNA was isolated and analyzed by microarray to identify a panel of biomarkers differentially expressed in HGUC and benign.

overall_design: Total RNA obtained from urine sediments from patients diagnosed with HGUC (n=30) compared with benign (n=20).

middle: B


title: The Suppression of Medium Acidosis Improves the Maintenance and Differentiation of Human Pluripotent Stem Cells at High Density in Defined Cell Culture Medium

status: Public on Apr 12 2018

city: Taipa

first: Guokai

last: Chen

address: University of Macau E12-3060

department: Faculty of Health Sciences

country: Macau

institute: University of Macau

summary: We use a chemically defined medium to systemically examine cellular activities and the impact of medium components in high-density culture. We show that medium acidosis is the main factor that alters cell cycle, gene expression and cellular metabolism at high cell density. The low medium pH leads to inhibition of glucose consumption, cell cycle arrest, and subsequent cell death. At high cell density, the suppression of medium acidosis with sodium bicarbonate (NaHCO3) significantly increases culture capacity for stem cell survival, derivation, maintenance and differentiation.

overall_design: Total RNA obtained from high density (HD) and low density (LD) embryonic stem cell culture subjected to no treatment (ctrl) or treatment with sodium bicarbonate (bicarb). Samples were collected on day 2 (D2).


title: TSA-Seq Mapping of Nuclear Genome Organization [array]

status: Public on Apr 25 2018

city: Urbana

first: Andrew

middle: S

last: Belmont

state: IL

address: 601 S Goodwin Ave, CLSL B509

institute: University of Illinois at Urbana-Champaign

type: Genome binding/occupancy profiling by genome tiling array

summary: We describe TSA-Seq, a new mapping method able to estimate mean chromosomal distances from nuclear speckles genome-wide and predict several Mbp chromosome trajectories between nuclear compartments without sophisticated computational modeling. Ensemble-averaged results reveal a clear nuclear lamina to speckle axis correlated with a striking spatial gradient in genome activity. This gradient represents a convolution of multiple, spatially separated nuclear domains, including two types of transcription "hot-zones". Transcription hot-zones protruding furthest into the nuclear interior and positioning deterministically very close to nuclear speckles have higher numbers of total genes, the most highly expressed genes, housekeeping genes, genes with low transcriptional pausing, and super-enhancers.

overall_design: LaminB1-chromatin interactions were assayed in human K562 cells. There were 2 biological replicates, that were hybridized in a dye-swap design.

first: Eva

middle: K

last: Brinkman

first: Bas

last: van Steensel


title: Expression data from murine mice microglia treated with Glioma Conditioned Medium for 6h

status: Public on Apr 20 2018

city: Warsaw

first: Kacper

middle: Adam

last: Walentynowicz

address: Pastuera 3

department: Neurobiology Centre

country: Poland

institute: Nencki Institute of Experimental Biology PAS

summary: Immune cells accumulating in the microenvironment of malignant tumors are tumor-educated, and contribute to its growth, progression and evasion of antitumor immune responses. Glioblastoma (GBM), the common and most malignant primary brain tumor in adults, shows considerable accumulation of resident microglia and peripheral macrophages, and their polarization into tumor-supporting cells. There are controversies regarding a functional phenotype of glioma-associated microglia/macrophages (GAMs) due to a lack of consistent markers. Previous categorization of GAM polarization towards the M2 phenotype has been found inaccurate because of oversimplification of highly complex and heterogeneous responses. In this study we characterized functional responses and gene expression in mouse and human microglial cultures exposed to fresh conditioned media (GCM) from human U87 and LN18 glioma cells. Functional analyses revealed mutual communication reflected by strong stimulation of glioma invasion by microglial cells and increased microglial phagocytosis after GCM treatment. To define transcriptomic markers of GCM-activated microglia, we performed selected and global gene expression analyses of stimulated microglial cells. We found activated pathways associated with immune-evasion and TGF signaling. We performed computational comparison of the expression patterns of GAMs from human GBMs and rodent experimental gliomas to select genes consistently changed in different datasets. The analyses of marker genes in GAMs from different experimental models and clinical samples revealed only a small set of common genes, which reflects variegated responses in clinical and experimental settings. We discuss potential sources of the observed differences and stress a great need for definitive elucidation of a functional state of GAMs.

overall_design: Primary mouse microglia was obtained from the neonatal cortical primary cultures (P0-P2). Microglia cells were seeded and stimulated with fresh Glioma Conditioned Medium (GCM) for 6h and RNA was collected. The study includes three biological replicates derived from seperate cortical cultures.

middle: A

first: Karolina

last: Stepniak


title: Agonistic Activation of LRH-1/NR5A2 To Treat Type 1 Diabetes Mellitus

city: Seville

first: Benoit

middle: Raymond

last: Gauthier

state: Seville

address: Americo Vespucio Avenue

department: Stem Cells

country: Spain

institute: Andalusian Center for Molecular Biology and Regenerative Medicine (CABIMER)

summary: Strategy to repress autoimmunity and promote islet beta cell regeneration

overall_design: 4 groups of 3 samples. Isolated mouse pancreatic islets were cultured in the presence of increasing concentrations of the LRH1 agonist BL001.

first: Nadia

last: Cobo-Vuilleumier


title: Differentially expressed genes in human IL-7Ra high and low EM CD8+ T cells

status: Public on Apr 09 2018

city: LA

first: Sungyong

last: You

address: Beverly Blvd 8400

department: Surgery

institute: Cedars-Sinai Medical Center

summary: It is known that human IL-7R low and high EM CD8+ T cells have a difference in the expression of some co-stimulatory, effector and cytotoxic molecules. However, their global gene expression profiles have not been characterized.  We thus analyzed global gene expression by IL-7R low and high EM CD8+ T cells in healthy human peripheral blood.

overall_design: Total RNA from the 6 samples were hybridized to the Illumina HumanHT-12 V4.0 expression beadchip

first: Insoo

last: Kang


title: KDM4 inhibition targets breast cancer stem cells

status: Public on Apr 10 2018

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

institute: University of Lübeck

summary: Cancer progression is associated with alterations of epigenetic regulators such as histone-lysine demethylases 4 (KDM4)2-5. During breast cancer therapy, classical treatments fail to address resistant cancer stem cell populations6-10. Here, we identified a novel KDM4 inhibitor (KDM4(i)) with unique preclinical characteristics. KDM4(i) is a highly potent pan KDM4 inhibitor that specifically blocks the demethylase activity of KDM4A, B, C, and D but not that of the other members of the KDM family. We validated the KDM4(i) anti-tumoral properties under conditions recapitulating patient tumors. Therefore, we established a method to isolate and grow triple-negative breast cancer stem cells (BCSCs) from individual patient tumors after neoadjuvant chemotherapy. Limiting dilution orthotopic xenografts of these BCSCs faithfully regenerate original patient tumor histology and gene expression. KDM4(i) blocks proliferation, sphere formation and xenograft tumor growth of BCSCs. Importantly, KDM4(i) abrogates expression of EGFR, a driver of therapy-resistant triple-negative breast tumor cells11, via inhibition of the KDM4A demethylase activity. Taken together, we present a unique BCSC culture system as a basis for therapeutic compound identification and demonstrate that KDM4 inhibition is a new therapeutic strategy for the treatment of triple-negative breast cancer.

overall_design: Collection of primary breast cancer tumor cells as well as the corresponding tumor derived cancer stem cells and mouse xenografts from four patients.

first: Melanie

last: Boerries

first: Jochen

last: Maurer

first: Elmar

last: Stickeler

first: Stella

last: Stepputtis

first: Juliane

last: Strietz

first: Bogdan-Tiberius

last: Preca


title: Nano-targeted double-edged induction of ferroptosis eradicates high-risk neuroblastoma

city: Antwerp (Wilrijk)

first: Ken

last: Declerck

address: Universiteitsplein 1

country: Belgium

institute: University of Antwerp

summary:
High-risk neuroblastoma is a devastating malignancy with few therapeutic options. We identify withaferin A (WA) as a natural ferroptosis inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA targets and inactivates glutathione peroxidase 4, as well as increases intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which both independently result in ferroptosis. This double-edged mechanism results in a high efficacy of WA compared to etoposide in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing neuroblastoma xenografts growth and relapse rate. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced targeting to the tumor site. Collectively, our data propose a novel therapeutic strategy to kill cancer cells by ferroptosis.
High-risk neuroblastoma is a devastating malignancy with few therapeutic options. We identify withaferin A (WA) as a natural ferroptosis inducing agent in neuroblastoma, which acts through a novel double-edged mechanism. WA targets and inactivates glutathione peroxidase 4, as well as increases intracellular labile Fe(II) upon excessive activation of heme oxygenase-1, which both independently result in ferroptosis. This double-edged mechanism results in a high efficacy of WA compared to etoposide in killing a heterogeneous panel of high-risk neuroblastoma cells, and in suppressing neuroblastoma xenografts growth and relapse rate. Nano-targeting of WA allows systemic application and suppressed tumor growth due to an enhanced targeting to the tumor site. Collectively, our data propose a novel therapeutic strategy to kill cancer cells by ferroptosis.

overall_design: Gene expression profiles from IMR-32 and SK-N-SH cell lines treated with either 1 µM withaferin A (WA), 1 µM withanone (WN) or DMSO (control) were measured using the Illumina HumanHT-12 v4.0 expression beadchip. Three biological replicates of each treatment condition were measured

first: Behrouz

last: Hassannia

first: Bartosz

last: Wiernicki

first: Irina

last: Ingold

first: Feng

last: Qu

first: Simon

last: Van Herck

first: Yulia

middle: Y

last: Tyurina

first: Hülya

last: Bayir

first: Behnaz

last: Abhari

first: Jose

last: Pedro Friedmann Angeli

first: Sze

last: Men Choi

first: Eline

last: Meul

first: Karen

last: Heyninck

first: Chandra

last: Sekhar Chirumamilla

first: Maija

last: Lahtela-Kakkonen

first: Guy

last: Van Camp

first: Dmitri

middle: V

last: Krysko

first: Paul

middle: G

last: Ekert

first: Simone

last: Fulda

first: Bruno

last: De Geest

first: Marcus

last: Conrad

first: Valerian

middle: E

last: Kagan

first: Wim

last: Vanden Berghe

first: Peter

last: Vandenabeele

first: Tom


title: Acute v. baseline PBMC gene expression in patients with Systemic Capillary Leak Syndrome

status: Public on Mar 31 2018

city: Bethesda

first: Timothy

last: Myers

state: MD

address: 50 South Drive, Room 5509

department: Research Technologies Branch

institute: National Institute of Allergy and Infectious Diseases

summary: The Systemic Capillary Leak Syndrome (SCLS) is an extremely rare and potentially life-treating vascular disorder of unknown etiology. SCLS is characterized by dramatic and transient episodes of hypotensive shock and edema due to plasma leakage into peripheral tissues. The disorder has garnered increased attention during the last several years because of the resemblance of its initial presentation to more common disorders such as systemic anaphylaxis, sepsis, and acute infections with the Ebola/Marburg family of filoviruses. Although approximately 70-80% of patients with SCLS have a concurrent monoclonal gammopathy of unknown significance (MGUS), any contribution of the paraprotein to acute flares is unknown. To identify circulating factors that contribute to the onset of acute SCLS crises, we performed transcriptomic profiling of paired peripheral blood mononuclear cell fractions obtained from patients during acute attacks and convalescent intervals using microarray. 61 genes were significantly up- or downregulated more than 2.5 fold in acute samples relative to baseline. One of the most upregulated genes was ADM, which encodes the vasoactive peptide adrenomedullin. The ADM surrogate pro-ADM was markedly elevated in SCLS acute sera compared to remission samples or sera from healthy controls. Monocytes and endothelial cells (ECs) from SCLS subjects expressed significantly more ADM in response to proinflammatory stimuli compared to healthy control cells. Application of ADM to ECs exerted protective effects on vascular barrier function. These results suggest a pathogenic contribution of ADM to the profound pressor-resistant hypotension that characterizes the initial stages of SCLS.

overall_design: Peripheral blood mononuclear cells (PBMC) were collected from Systemic Capillary Leak Syndrome patients during a SCLS crisis or convalescent interval. Samples for both intervals, crisis (epi) and convalescent (bas), were successfully hybridized for 7 patients. An additional 5 patients are represented by a single disease interval, for a total of 19 samples.

first: Zhihui

last: Xie

first: Francisco

last: Otaizo-Carrasquero

first: Kirk

middle: M

last: Druey


title: Expression data from Ulcerative Colitis subjects

status: Public on Apr 01 2018

city: Cambridge

first: William

last: Gordon

address: 1 Portland Street

institute: Pfizer Inc

summary: We used microarrays to detail the global gene expression of inflamed vs non-inflamed colon tissue from UC subjects

overall_design: Multiple biopsies were taken from UC subjects to better understand the variability of gene expression withiin and between individuals for use in clinical planning for future studies


title: Dual inhibition of Src and MEK decreases the growth of human ovarian cancer cells

status: Public on Mar 28 2018

city: Philadelphia

first: Gao

last: Zhang

state: PA

address: 3601 Spruce Street

institute: The Wistar Institute

summary: Treatment of established lines and primary ovarian cancer cultures with Src and MEK inhibitors, saracatinib and selumetinib, respectively, showed target kinase inhibition and synergistic induction of apoptosis and cell cycle arrest in vitro and tumor inhibition in xenografts.

overall_design: There are three biological replicates per experimental sample.


title: Alteration of TAC1 expression in Prunus species leads to pleiotropic shoot phenotypes

status: Public on Apr 04 2018

city: East Lansing

first: Courtney

last: Hollender

state: MI

address: 1066 Bogue St

department: Dept. of Horticulture

institute: Michigan State University

type: Expression profiling by high throughput sequencing

summary: Prunus persica (peach) trees carrying the ‘Pillar’ or ‘Broomy’ trait (br) have vertically oriented branches caused by loss of function mutations in a gene called TILLER ANGLE CONTROL 1 (TAC1). TAC1 encodes a protein in the IGT gene family that includes LAZY1 and DEEPER ROOTING 1 (DRO1), which regulat lateral branch and root orientations, respectively. Here, we found that some of the native TAC1 alleles in the hexaploid plum species Prunus domestica, which has a naturally more upright stature, contained a variable length trinucleotide repeat within the same exon 3 region previously found to be disrupted in pillar peach trees. RNAi silencing of TAC1 in plum resulted in trees with severely vertical branch orientations similar to those in pillar peaches but with an even narrower profile. In contrast, PpeTAC1 over-expression in plum led to trees with wider branch angles and more horizontal branch orientations. Pillar peach trees and transgenic plum lines exhibited pleiotropic phenotypes including differences in trunk and branch diameter, stem growth, and twisting branch phenotypes. Expression profiling of pillar peach trees revealed differential expression of numerous genes associated with biotic and abiotic stress, hormone responses, plastids, reactive oxygen, and secondary and cell wall metabolism. Collectively, the data provide important clues for understanding TAC1 function and show that alteration of TAC1 expression may have broad applicability to agricultural and ornamental tree industries.

overall_design: mRNA was isolated from four shoot tips (approximately 4cm long) from standard and pillar peach trees. Four biological replicates for each type of tree were sequenced using illumina Hiseq2000

first: Chris

last: Dardick


title: Depletion of DNMT1 in differentiated human cells highlights key classes of sensitive genes and an interplay with polycomb repression [expression]

city: Coleraine

first: Colum

middle: Patrick

last: Walsh

state: County Londonderry

address: Cromore Road

department: Life and Health Sciences

country: United Kingdom

institute: Ulster University

summary: DNA methylation plays a vital role in the cell, but loss-of-function mutations of the maintenance methyltransferase DNMT1 in normal human cells are lethal, precluding target identification, and existing hypomorphic lines are tumour cells. We generated instead a hypomorphic series in normal hTERT-immortalised fibroblasts using stably integrated short hairpin RNA. Approx 2/3 of sites showed demethylation as expected, with 1/3 showing hypermethylation, and targets were shared between the three independently-derived lines. Enrichment analysis indicated significant losses at promoters and gene bodies with four gene classes most affected: 1)protocadherins, which are key to neural cell identity; 2)genes involved in fat homeostasis/body mass determination; 3)olfactory receptors and 4) cancer/testis antigen (CTA) genes. Overall effects on transcription were relatively small in these fibroblasts, but CTA genes showed robust derepression. Comparison with siRNA-treated cells indicated that shRNA lines show substantial remethylation over time. Regions showing persistent hypomethylation in the shRNA lines were associated with polycomb repression, and were derepressed on addition of an EZH2 inhibitor. Persistent hypermethylation in shRNA lines was in contrast associated with poised promoters. Our results suggest polycomb marking blocks remethylation and indicate the sensitivity of key neural, adipose, and cancer-associated genes to chronic depletion of maintenance methylation activity.

overall_design: Stable knockdowns of the maintenance methyltransferase DNMT1 were generated in hTERT-immortalised adult fibroblasts using shRNA. WThTERT-1604 cells were used in triplicate as a control . Genome wide methylation and transriptional levels were assayed using the Illumina 450k BeadChip and HT12 arrays respectively and subsequently analysed using bioinformatic approaches. Genes targets of relevant interest identified through bioinformatic mining were validated using wet lab approaches.

first: Karla

last: O’Neill

first: Rachelle

last: Irwin

first: Sarah-Jayne

last: Mackin

first: Sara-Jayne

last: Thursby

first: Avinash

last: Thakur

first: Ciske

last: Bertens

first: Laura

last: Masala

first: Jayne

last: Loughery

first: Darragh

last: McArt

middle: P


title: Genome-wide expression profiling after TRRAP silencing in Burkitt's lymphoma

city: Heidelberg

first: Alexander

last: Jethwa

address: Im Neuenheimer Feld 460

department: Translational Oncology

institute: German Cancer Research Center (DKFZ) / National Center for Tumor Diseases (NCT)

summary: Silencing of the histone acetyltransferase (HAT) complex member TRRAP in Burkitt’s lymphoma results in a significant deregulation of histone deacetylase (HDAC)-related gene sets.

overall_design: Total RNA obtained from Burkitt's lymphoma cells harboring TRRAP or control knock-down.

first: Mikolaj

last: Slabicki

first: Jennifer

last: Hüllein

first: Marius

last: Jentzsch

first: Vineet

last: Dalal

first: Sophie

last: Rabe

first: Lena

last: Wagner

first: Tatjana

last: Walther

first: Wolfram

last: Klapper

first: Hanibal

last: Bohnenberger

first: Mandy

last: Rettel

first: Junyan

last: Lu

first: Arne

middle: H

last: Smits

first: Frank

last: Stein

first: Mikhail

last: Savitski

first: Wolfgang

last: Huber

first: Yael

last: Aylon

first: Moshe

last: Oren

first: Thorsten

last: Zenz


title: Transcriptome analysis of CHARGE patients iPSC-derived neural stem/progenitor cells

city: Shinjuku-ku

first: Tsukasa

last: Sanosaka

state: Tokyo

address: 35 Shinanomachi

department: Department of Physiology

institute: Keio University School of Medicine

summary: We performed a microarray experiment to analyze the transcriptional profile of CHARGE patient iPSC-derived neural stem/progenitor cells to identify CHD7 target genes.

overall_design: 12 samples.


title: Genome-wide analysis of high glucose regulated genes expression in fully differentiated and polarized CaCo-2 Cells

status: Public on Apr 14 2018

city: Urla

first: sukru

last: gulec

state: İzmir

address: Gülbahçe Mah., İzmir Yüksek Teknoloji Enstitüsü,

department: Food Engneering

country: Turkey

institute: Izmir Institute of Technology

summary:
Cells were grown on collagen coated insert for 21 days under 25mM (high glucose) or 5mM (control) glucose conditions. We investigated relevant target genes that could be regulated by high glucose levels in CaCo-2 cells. We intended to find candidate genes that may play a role for intestinal glucose absorption.

Fund Source: The Scientific and Technological Research Council of Turkey Project ID: 214Z217 (T B TAK/ PN:214Z217)

overall_design: Samples were collected from 3 independent experiments and each samples from individual experiments were performed as a triplicate.

first: Tugce

last: Boztepe


title: Molecular profiling of SV-BR-1-GM, a clinically effective GM-CSF-secreting human breast cancer cell line

status: Public on Mar 23 2018

first: Markus

middle: Daniel

last: Lacher

address: 2929 Arch Street, 4th floor

department: R&D

institute: BriaCell Therapeutics Corp.

summary: The SV-BR-1 cell line was derived from a chest wall lesion of a breast cancer patient. SV-BR-1 cells were stably transfected with CSF2 (encoding GM-CSF), resulting in the SV-BR-1-GM cell line. Following irradiation to prevent cell replication, both SV-BR-1 (Wiseman and Kharazi, The Open Breast Cancer Journal, 2010, 2, 4-11) and SV-BR-1-GM (Wiseman and Kharazi, Breast J. 2006 Sep-Oct;12(5):475-80) cells have been applied as whole-cell therapeutics in clinical trial settings for advanced breast cancer. Molecular profiles of non-irradiated SV-BR-1-GM cells have been established from various manufacturing lots via Illumina HumanHT-12 V4.0 expression beadchip arrays (GPL10558). A key finding from the study is the identification of an immune signature expressed in SV-BR-1-GM cells which includes the MHC class II factors HLA-DMA, HLA-DMB, HLA-DRA, and HLA-DRB3. Since tumor regressions were  apparent in clinical trial subjects matching at an HLA-DRB3 allele with SV-BR-1-GM we hypothesize that (partial) HLA matching is needed for maximal tumor-directed clinical responses to occur.

overall_design: Total RNA was extracted via RNeasy Mini kit (Qiagen) from cultured SV-BR-1-GM cells or from cryopreserved SV-BR-1-GM cells obtained directly from cryovials. RNA was amplified as antisense RNA and biotinylated using the Illumina™ TotalPrep™-96 RNA Amplification Kit (Thermo Fisher Scientific). The biotinylated antisense RNA was then hybridized onto HumanHT-12 v4 Expression BeadChip arrays (Illumina, San Diego, CA) and thereafter stained with Cy3-streptavidin. Fluorescent signal intensities were acquired on an iScan array scanner (Illumina). Average signal intensities and detection p-values were calculated using GenomeStudio (Illumina).

middle: D


title: Analysis of altered miRNA, lncRNA and mRNA expression profiles in the streptozotocin-induced diabetic rats compared to normal SD rats

city: Wuhan

first: Guojun

last: Guo

state: Hubei

address: 1277# Jiefang Avenue

department: Hand Surgery

institute: Union Hospital of Tongji medical college, Huazhong University of Science & Technology

type:
Non-coding RNA profiling by array
Expression profiling by array

summary: This SuperSeries is composed of the SubSeries listed below.

platform_organism:
Rattus norvegicus
synthetic construct

overall_design: Refer to individual Series


title: RNAseq for peach weeping and standard lateral shoot (branch) tips

status: Public on Mar 21 2018

first: Courtney

last: Hollender

summary: Plant shoots typically grow upward in opposition to the pull of  gravity. However, exceptions exist throughout the plant kingdom.  Most conspicuous are trees with weeping or pendulous branches.  While such trees have long been cultivated and appreciated for  their ornamental value, the molecular basis behind the weeping  habit is not known. Here, we characterized a weeping tree  phenotype in Prunus persica (peach) and identified the underlying  genetic mutation using a genomic sequencing approach. Weeping  peach tree shoots exhibited a downward elliptical growth pattern  and did not exhibit an upward bending in response to 90° reorientation.  The causative allele was found to be an uncharacterized  gene, Ppa013325, having a 1.8-Kb deletion spanning the 5′ end.  This gene, dubbed WEEP, was predominantly expressed in phloem  tissues and encodes a highly conserved 129-amino acid protein  containing a sterile alpha motif (SAM) domain. Silencing WEEP in  the related tree species Prunus domestica (plum) resulted in more  outward, downward, and wandering shoot orientations compared  to standard trees, supporting a role for WEEP in directing lateral  shoot growth in trees. This previously unknown regulator of  branch orientation, which may also be a regulator of gravity per-  ception or response, provides insights into our understanding of  how tree branches grow in opposition to gravity and could serve  as a critical target for manipulating tree architecture for improved  tree shape in agricultural and horticulture applications.

overall_design: mRNA was isolated from four shoot tips (approximately 4cm long) from standard and weeping peach trees. Four biological replicates for each type of tree were sequenced using illumina Hiseq2000

first: Chris

last: Dardick


title: Emory University African American Microbiome in Pregnancy Cohort [expression]

status: Public on Mar 19 2018

city: Atlanta

first: Anna

last: Knight

state: Georgia

address: 101 Woodruff Circle NE

institute: Emory University

summary: All subjects were enrolled from Grady Memorial and Emory Midtown Hospitals. Subjects provided blood samples at two timepoints during pregnancy. Medical record abstraction was used to determine the presence of fetal intolerance of labor.

overall_design: Subjects provided blood samples at two timepoints during pregnancy, which were processed into peripheral blood mononuclear cells (PBMC). RNA was extracted usingthe AllPrep RNA/DNA Mini Kit (Qiagen).RNA expression was assessed on the Human HT-12v4 Expression Array

first: Alicia

last: Smith

first: Anne

middle: L

last: Dunlop


title: Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC

city: Martinsried

first: Jürg

last: Müller

state: Bavaria

address: Am Klopferspitz 18

institute: Max Planck Institute of Biochemistry

summary: The goal of this study was to identify genes that are differentially expressed in animals that lack the histone methyltransferase Ash1 that generates H3K36 di-methylation

overall_design: Comparison of the transcriptome in 3rd leg and haltere imaginal discs (T3 discs) and in wing imaginal discs (T2 discs) between wild-type animals and in animals that were homozgyous for the ash1[22] null mutation

first: Sigrun

last: Schmähling

first: Arno

last: Meiler


title: Altered Cell-Cycle Control, Inflammation and Adhesion in High-Risk Persistent Bronchial Dysplasia

status: Public on May 16 2018

city: Salt Lake City

first: Aik Choon

last: Tan

state: UT

address: 2000 Circle of Hope

department: Oncological Sciences

institute: Huntsman Cancer Institute

summary: Persistent bronchial dysplasia (BD) is associated with increased risk of developing invasive squamous cell carcinoma (SCC) of the lung.  We hypothesized that differences in gene expression profiles between persistent and regressive BD would identify cellular processes that underlie progression to SCC.  RNA expression arrays (Affymetrix Hu 1.0) comparing baseline biopsies from 32 bronchial sites that persisted/progressed to 31 regressive sites showed 395 differentially expressed genes (ANOVA, FDR</=0.05).  Thirty-one pathways showed statistically significant evidence of altered activity between the two groups.  Multiple pathways were associated with cell cycle control/proliferation, inflammation, or epithelial differentiation/cell-cell adhesion.  Polo-like kinase 1 (PLK1) was associated with multiple cell cycle pathways.  Cultured persistent BD cells showed increased PLK1 expression, and following treatment with PLK1 inhibitor, showed induction of apoptosis, G2/M phase arrest and decreased proliferation compared to untreated cells.  These effects were not seen in normal or regressive BD cultures.  Inflammatory pathway activity was decreased in persistent BD and the presence of an inflammatory infiltrate was more common in regressive BD.  Regressive BDs were also associated with trends toward overall increases in macrophages and T-lymphocytes and altered polarization of these inflammatory cell subsets.  Increased desmoglein 3 and plakoglobin expression was associated with higher grade and persistence of BD.  The results identify alterations in cell cycle control, inflammatory activity, and epithelial differentiation/cell-cell adhesion in the persistent subset of BDs that are associated with high risk for progression to invasive SCC.  These pathways may provide strong markers of risk and effective targets for lung cancer prevention.

overall_design:
Lung biopsy gene expression profiles.

We performed two primary analyses.  The first compared persistent/progresive sites defined as those with follow-up (F/U) scores of 4 (mild bronchial dysplasia) or greater to regressive sites with F/U scores of 1 or 2 (normal or reserve cell hyperplasia).  The second analysis looked for genes whose expression was correlated with change in baseline (BL) diagnosis.  This was based on the BL Frozen Dx.  The diagnosis scores are: 1=normal, 2=reserve cellhyperplasia, 3=squamous metaplasia without atypia, 4=mild dysplasia, 5=moderate dysplassia, 6=severe dysplasia and 7=carcinoma-in-situ.  X.1 indicates the biopsy showed features of angiogenic squamous dysplasia.

Group 1 = Persistent bronchial dysplasia (BL >/= histology score 4, FU >/= histology score 4)
Group 2 = Regressive bronchial dysplasia (BL >/= histology score 4, FU </= histology score 2)
Group 3 = Progressive non-dysplasia (BL </= histology score 2, FU >/= histology score 4)
Group 4 = Stable non-dysplasia (BL </= histology score 2, FU </= histology score 2)

first: Dan

last: Merrick


title: Expression data from HCCC-9810 cells with MBD5 or BAP1 knockdown

status: Public on Mar 15 2018

city: Beijing

first: Yuanfeng

last: Li

address: No.38 shengmingyuan Road

institute: Beijing Institute of Radiation Medicine

summary:
MBD5 can physically interact with BAP1. Some genes may be regulated by both MBD5 and BAP1.
We used microarrays to check whether the overlaps of differentially expressed genes when knockdown MBD5 or BAP1 were more than that would be expected by chance. Thus, we could suggest that BAP1 was required for the regulatory effect of MBD5

overall_design: The human cholangiocarcinoma cell lines HCCC-9810 were transfected with BAP1 siRNAs or MBD5 siRNAs or control shRNA. Three biological replicates each.

first: Gangqiao

last: Zhou

first: Yahui

last: Wang


title: Expression data of intact and ventilated wildtype and Zmpste24-deficient mice

status: Public on Mar 20 2018

city: Oviedo

first: Guillermo

last: Albaiceta

address: Avenida de Roma s/n

institute: Instituto de Investigación Sanitaria del Principado de Asturias

summary: To study how changes in the nuclear mechanical properties may modify the development of Ventilator-induced lung injury, mice of both genotypes were studied at baseline or after 2.5 hours of mechanical ventilation (PIP 15cmH2O, ZEEP, 100 breaths/min, inspiratory:expiratory ratio 1:1, inpired oxygen fraction 0.21).After that, mice were sacrificed, the lungs estracted and gene expression measured in order to identify the differential gene expression depending on the different nuclear stifness.

overall_design: 12 samples were analyzed. 6 from Zmpste24-deficient mice where 3 were baseline and 3 were submitted to mechanical ventilation and 6 wiltype where 3 were baseline and 3 were submitted to mechanical ventilation.

first: Inés

last: Alonso

first: Jorge

middle: B

last: Prieto

first: Laura

last: Rodríguez


title: Gene expression analyses of  CWR22Res Nsi (non-silencing) control and with stable knockdown of Sprouty2 (SPRY2)

status: Public on Mar 13 2018

city: Glasgow

first: Rachana

middle: Ravindra

last: Patel

state: Outside the United States or Canada

address: Bearsden, Switchback Road

department: Prostate Cancer

institute: Cancer Research UK Beatson Institute

summary: Effects of SPRY2 deficiency in gene expression of CWR22Res prostate cancer cells.

overall_design: Stable SPRY2 knockdown was established in CWR22Res cells. RNA was extracted from biological triplicates of the Nsi control and stable SPRY2 knockdown clone (Pool) CWR22Res cells.

first: Hing

last: Leung


title: Comparison of ITGA2+ trophoblast progenitors to VCT and EVT

status: Public on Mar 18 2018

city: Singapore

first: Cheryl

last: Lee

address: 8 College Road

country: Singapore

institute: Duke-NUS Medical School

summary: During pregnancy, trophoblast cells in the placenta are the only fetal cells in direct contact with the maternal blood and decidua. They have many functions, including transport of nutrients and oxygen, remodelling the uterine arteries, and communicating with maternal cells. Despite their importance in development and in the success of pregnancy, little is known about human trophoblast progenitors and their differentiation. We identify a proliferative trophoblast niche at the base of cytotrophoblast cell columns in first trimester placentas that is characterised by integrin α2 (ITGA2) expression. Pulse-chase experiments with 5-Iodo-2′-deoxyuridine (IdU) imply that these cells can contribute to both villous and extravillous lineages. Importantly, these cells can be isolated by ITGA2 using flow cytometry and express genes from both VCT and EVT. Microarray shows that they display a unique gene signature including NOTCH signalling and mesenchymal characteristics. ITGA2 allows for the first time the study of a pure population of trophoblast progenitor cells.

overall_design: Overall 12 samples: 3 cell types from 4 donors

middle: Q

first: Myriam

last: Hemberger

first: Ashley

last: Moffett


title: Transcriptional profile of differentially matured human monocyte-derived DCs

status: Public on Mar 14 2018

city: Würzburg

first: Florian

last: Erhard

address: Versbacher Str. 7

department: Institut für Virologie und Immunbiologie

institute: Julius-Maximilians-Universität Würzburg

summary: Human MoDCs were stimulated with TNF, Cholera Toxin or LPS to identify candidates for common genes expression.

overall_design: single replicate samples of each condition were used

first: Manfred

last: Lutz


title: Expression data from renal collecting duct epithelial cell line

status: Public on Mar 08 2018

city: Hefei

first: Guanqing

last: Wu

state: Anhui

address: 218 Jixi Road

institute: Anhui Province PKD Center, Institute/Department of Urology, The First Affiliated Hospital of Anhui Medical University

summary:
Morphogenesis of epithelial tissues relies on the precise developmental control of cell polarity and architecture. In the early Drosophila embryo, the primary epithelium forms during cellularisation, following a tightly controlled genetic programme where specific sets of genes are up-regulated. Some of them, for instance, control membrane invagination between the nuclei anchored at the apical surface of the syncytium.
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.

overall_design: renal collecting duct epitheliao cell line of different genotypes were selected  for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain different expression profiles between WT Pkd2 knockout cells.

first: Ao


title: Soft Hydrogels Support Differentiation of Induced Pluripotent Stem Cells toward Mesenchymal Stromal Cells [expression]

city: Aachen

first: Wolfgang

last: Wagner

address: Pauwelsstrasse 20

department: Helmholtz Institute for Biomedical Engineering

institute: RWTH Aachen University

summary: Induced pluripotent stem cells (iPSCs) can be differentiated toward mesenchymal stromal cells (MSCs), but at least on epigenetic level this transition remains incomplete with the current culture conditions. Hydrogels provide a more physiologic three-dimensional environment for in vitro cell culture than conventional tissue culture plastic (TCP). In this study, we followed the hypothesis that growth and differentiation of primary MSCs and of iPSC-derived MSCs (iMSCs) can be enhanced on hydrogels. To this end, we used a hydrogel made of human platelet lysate (hPL). MSCs were effectively cultured on and inside hPL-gel and demonstrated more structured deposition of extracellular matrix (ECM) components than TCP. Furthermore, hPL-gel supported differentiation of iPSCs toward MSCs. Unexpectedly, the differentiation process seemed to be hardly affected by the substrate: iMSCs generated either on TCP or hPL-gel did not reveal differences in morphology, immunophenotype, or differentiation potential. Moreover, global gene expression and DNA-methylation profiles were almost identical in iMSCs generated on TCP or hPL-gel. Our results indicate that matrix elasticity is less crucial for directed lineage-specific differentiation toward MSCs than expected.

overall_design: MSCs and iMSCs were either cultured with human platelet lysate (hPL) gel or tissue culture plastic (TCP) as substrate to compare impact on gene expression profiles with Illumina HT-12 v4 Expression BeadChip.

first: Roman

last: Goetzke

first: Julia

last: Franzen

first: Alina

last: Ostrowska

first: Michael

last: Vogt

first: Gerd

last: Klein

first: Björn

last: Rath

first: Martin

last: Zenke


title: Gene expression profile of colorectal cancer cell Caco-2 after OCC-1 knockdown

status: Public on Mar 11 2018

city: Chengdu

first: Yang

last: Lan

address: No. 29 Wangjiang Road

department: Center for Functional Genomics and Bioinformatics

institute: Sichuan University

summary:
OCC-1 is one of the earliest annotated long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). In our study, we found that knockdown of OCC-1 by shRNAs promotes CRC cell growth both in vitro and in vivo.
To gain insight into the molecular function of OCC-1, we profiled the gene expression of Caco-2 cells after OCC-1 knockdown by microarray.

overall_design: OCC-1 was knockdown by two independent shRNAs, shOCC-1-1 and -2, in Caco-2 cells. The change of gene expression was determined relative to a non-target shRNA control, shCTRL. Overlapped differentially expressed genes in shOCC-1-1 and -2 cells were considered as OCC-1 regulated genes.

first: Xu

last: Song


title: No-glucose, hypoxic or ischemic (ODG) treatment of pericytes

city: Lund

first: Robert

last: Carlsson

address: Sölvegatan 17

department: IKVL

country: Sweden

institute: Lund University

summary: Brain pericytes are important to maintain vascular integrity of the neurovascular unit under both, physiological and ischemic conditions. Ischemic stroke is known to induce an inflammatory and hypoxic response due to the lack of oxygen and glucose in the brain tissue. How this early response to ischemia is molecularly regulated in pericytes is largely unknown but may be of importance for future therapeutic targets .Here we evaluate the transcriptional responses in in vitro cultured human brain pericytes after oxygen and/or glucose deprivation. Hypoxia has been widely known to stabilise the transcription factor hypoxia inducible factor 1-alpha (HIF1alpha) and mediate the induction of hypoxic transcriptional programs after ischemia.  However, we find that the transcription factors Jun Proto-Oncogene (c-JUN), Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells (NFkappaB) and signal transducer and activator of transcription 3 (STAT3) bind genes regulated after 2 hours of omitted glucose and oxygen before HIF1alpha. Potent HIF1alpha responses require 6 hours of hypoxia to substantiate transcriptional regulation comparable to either c-JUN or STAT3. We show that STAT3 and c-JUN are regulating their bound genes before HIF1alpha after 2 hours of hypoxia or omitted glucose and oxygen, suggesting that HIF1alpha is not the initiating trans-acting factor in the response of pericytes to ischemia.

overall_design: No-glucose, hypoxic or ischemic (ODG) treatment of human adult pericyte cell cultures. Sub-vetricular zone (SVZ) pericytes from a temporal lobe epilepsy (TLE) patient material was subjected to normal cell culture, lack of glucose, lack of oxygen (hypoxia), or lack of oxygen and glucose (ischemic condition). Cell cultures were exposed to lack of oxygen in a hypoxic chamber at 0.5-0.7% oxygen. Total RNA was extracted after 2 and 6 hours of treatment. The total RNA was hybridized to an Illumina bead array.

first: Ilknur

last: Özen

first: Marco

last: Barbariga

first: Gesine

last: Paul-Visse


title: Effect of transgenic RNAi on wandering third instar larval fat body gene expression in Drosophila melanogaster

city: Binghamton

first: Laura

middle: Palanker

last: Musselman

state: New York

address: 4400 Vestal Parkway East

department: Biological Sciences

institute: Binghamton University

summary: We compared four transcription factor knockdowns using transgenic RNAi expressed in the larval fat body. FOXO, Tfb1, p53, and Stat92E-dependent gene expression in the Drosophila fat body was quantified on control and high-sugar diets in order to generate expression profiles via RNA-seq. These expression data were used to build a gene regulatory network to predict novel roles for these and other genes during caloric overload.

overall_design: Control and fat body-expressed transcription factor RNAi Drosophila were reared on control (0.15M sucrose) and high-sugar (0.7M or 1M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.

first: Thomas

last: Baranski

first: Ezekiel

last: Maier

last: Brent


title: Effects of a mixture of amino acids and other small molecules on the gene expression profile of HeLa cells

status: Public on Mar 07 2018

city: Pécs

first: Tamás

last: Czömpöly

address: Finn 1/1

department: Cancer research and drug development

country: Hungary

institute: Culevit Ltd.

summary: Hela cells were treated with a mixture of amino acids and other small molecules, called active mixture for various time periods. The aim was to identify the differentially expressed genes that are upregulated or downregulated upon treatment at different time points.

overall_design: Hela cells were treated with the active mixture for various time periods (3h, 6h, 24h). Total RNA was isolated and global gene expression profiling was performed using Illumina’s HumanHT-12 v4 Expression BeadChip Array. Gene expression of treated samples was compared to untreated control samples.12 samples were analysed, 3 replicates in 4 sample groups. Sample groups: control (no treatment), 3 hours of treatment, 6 hours of treatment, 24 hours of treatment.


title: Genome-wide study of transcriptional profile of human cytotoxic CD4 T cells

status: Public on Mar 06 2018

city: Gosselies

last: Bizet

address: Rue Adrienne Bolland, 8

institute: Université Libre de Bruxelles

summary: The transcriptional profile of human cytotoxic CD4 T cells was compared to their naive counterpart, to central memory Th1 cells,  and to naive and cytotoxic CD8 T cells in order to elucidate the epigenetic basis of cytotoxic differentiation in CD4 T cells.

overall_design: Total RNA obtained from ex-vivo isolated blood lymphocytes of 5 CMV-seropositive healthy adults. For each subject, five populations were sorted: naive CD4, naive CD8, central memory CD4 Th1 cells, cytotoxic CD28- CD4 T cells and cytotoxic CD27- CD8 T cells.


title: Gene expression data in U87MG cell line transfected with NeuroD2-overexpression and control vector

status: Public on Mar 01 2018

city: New Delhi

first: Dr. Ritu

last: Kulshreshtha

state: New Delhi

address: Room 134, Block I

department: Dept of Biochemical Engineering and Biotechnology

country: India

institute: Indian Institute of Technology

summary:
NeuroD2 is downregulated in glioblastoma (GBM) tumor samples. The study identifies the genes regulated by NeuroD2 in GBM cell lines grown under hypoxia
We used human primeview gene expression microarray chips to assess the mRNA expression profile in response to NeuroD2 overexpression in U87MG cells under hypoxic microenvironment.

overall_design: U87MG cells were transfected with control and NeuroD2-overexpression vector and allowed to grow in hypoxic microenvironment (0.2% oxygen in in vivo200 hypoxia workstation from Ruskinn, UK). The total RNA from cells was harvested 48 hours post transfection and mRNA profiling was done using human primeview gene chips.

first: Rahul

last: Agrawal

first: Ritu


title: Integrated Molecular Analysis of Tamoxifen-Resistant Invasive Lobular Breast Cancer Cells

status: Public on Mar 05 2018

city: Washington

first: Rebecca

middle: B.

last: Riggins

state: DC

address: E412 Research Building, 3970 Reservoir Rd. NW

department: Oncology, and Lombardi Comprehensive Cancer Center

institute: Georgetown University

summary:
Invasive lobular breast cancer (ILC) is an understudied malignancy with distinct clinical, pathological, and molecular features that distinguish it from the more common invasive ductal carcinoma (IDC). Mounting evidence suggests that estrogen receptor-alpha positive (ER+) ILC has a poor response to Tamoxifen (TAM), but the mechanistic drivers of this are undefined. In the current work, we comprehensively characterize the SUM44/LCCTam ILC model system through integrated analysis of gene expression, copy number, and mutation, with the goal of identifying actionable alterations relevant to clinical ILC that can be co-targeted along with ER to improve treatment outcomes. We show that TAM has several distinct effects on the transcriptome of LCCTam cells, that this resistant cell model has acquired copy number alterations and mutations that impinge on MAPK and metabotropic glutamate receptor (GRM/mGluR) signaling networks, and that pharmacological inhibition of either improves or restores the growth-inhibitory actions of endocrine therapy.
These samples form a SuperSeries with GSE12708.

overall_design: Total RNA was extracted from sub-confluent T-25 cm^2 tissue culture flasks of SUM44 and LCCTam cells, then processed and arrayed. Microarray data quality was then assessed using several tools, including those recommended by Affymetrix and a series of additional QC measures. The Robust Multiple-Array Average (RMA) method was used to preprocess the raw gene expression data, as implemented in the Bioconductor project (http://bioconductor.org).


title: Progression of whole blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in patients with severe influenza

status: Public on Mar 03 2018

city: London

first: Long

last: Hoang

address: Dovehouse Street

department: Genomic Medicine

institute: Imperial College London

summary: Transcriptional profiles are increasingly used to investigate the severity, subtype and pathogenesis of disease. We now describe whole blood RNA signatures and local and systemic immune mediator levels in a large cohort of adults hospitalised with influenza from which extensive clinical and investigational data was obtained. Signatures reflecting interferon-related antiviral pathways were common up to day 4 of symptoms in cases not requiring mechanical ventilatory support; in those needing mechanical ventilation, an inflammatory, activated neutrophil and cell stress/death (‘bacterial’) pattern was seen, even early after disease onset. Identifiable bacterial co-infection was not necessary for this ‘bacterial’ signature but could enhance its development while attenuating the early ‘viral’ signature. Our findings emphasise the importance of timing and severity in the interpretation of transcriptomic profiles and soluble mediator levels, and identify specific patterns of immune activation that may enable the development of novel diagnostics and therapeutics

overall_design:
At each time point, 3 ml of whole blood were collected into each of two Tempus tubes (Applied  Biosystems/Ambion) by trained research staff following a standard phlebotomy protocol. Blood was vigorously mixed immediately following collection and stored at -80°C before RNA extraction. For each patient, the contents of one tube were used for analysis and the other tube was retained in case of assay failure. RNA was isolated using 1.5 ml whole blood and the MagMAX-96 Blood RNA Isolation Kit (Applied Biosystems/Ambion), as per the manufacturer’s instructions. 250 ug of isolated total RNA was globin-reduced using the GLOBINclear 96-well format kit (Applied Biosystems/Ambion) according to the manufacturer’s instructions. Total and globin-reduced RNA integrity was assessed using an Agilent 2100 Bioanalyzer (Agilent Technologies). RNA yield was assessed using a NanoDrop8000 spectrophotometer (NanoDrop Products, Thermo Fisher Scientific). High-quality (>6.5 RIN) whole blood RNA was successfully obtained and processed by microarray in all cases. Biotinylated, amplified antisense complementary RNA (cRNA) targets were prepared from 200-250 ng of globin-reduced RNA using the Illumina CustomPrep RNA amplification kit (Applied Biosystems/Ambion). For each sample, seven hundred and fifty nanograms of labelled cRNA were hybridised overnight to Illumina Human HT12 V4 BeadChip arrays (Illumina), which contained greater than 47,000 probes. The arrays were washed, blocked, stained and scanned on an Illumina iScan, as per the manufacturer’s instructions. GenomeStudio (Illumina) was used to perform quality control and generate signal intensity values.

Contributor: the MOSAIC Investigators

first: Jake

last: Dunning

first: Simon

last: Blankley

middle: T

first: Mike

last: Cox

first: Christine

last: Graham

first: Philip

last: James

first: Chloe

middle: I

last: Bloom

first: Damien

last: Chaussabel

first: Jacques

last: Banchereau

first: Stephen

middle: J

last: Brett

first: Miriam

middle: F

last: Moffatt

first: Anne

last: O’Garra

first: Peter

last: Openshaw


title: A kinome-wide RNAi screen identifies ALK as a target to sensitize neuroblastoma cells for HDAC8-inhibitor treatment

status: Public on Feb 21 2018

city: Heidelberg

first: Emily

last: Koeneke

address: Im Neuenheimer Feld 280

country: Germany

institute: German Cancer Research Center (DKFZ)

summary: The prognosis of advanced stage neuroblastoma patients remains poor and, despite intensive  therapy, the 5-year survival rate remains less than 50%. We previously identified histone deacetylase  (HDAC) 8 as an indicator of poor clinical outcome and a selective drug target for differentiation  therapy in vitro and in vivo. Here we performed kinome-wide RNAi screening to identify genes that  are synthetically lethal with HDAC8 inhibitors. These experiments identified the neuroblastoma  predisposition gene ALK as a candidate gene. Accordingly, the combination of the ALK/MET inhibitor  crizotinib and selective HDAC8 inhibitors (3-6μM PCI-34051 or 10μM 20a) efficiently killed  neuroblastoma cell lines carrying wildtype ALK (SK-N-BE(2)-C, IMR5/75), amplified ALK (NB-1), and  those carrying the activating ALK F1174L mutation (Kelly), and, in cells carrying the activating R1275Q  mutation (LAN-5), combination treatment decreased viable cell count. The effective dose of crizotinib  in neuroblastoma cell lines ranged from 0.05μM (ALK-amplified) to 0.8μM (wildtype ALK). The  combinatorial inhibition of ALK and HDAC8 also decreased tumor growth in an in vivo zebrafish  xenograft model. Bioinformatic analyses revealed that the mRNA expression level of HDAC8 was  significantly correlated with that of ALK in two independent patient cohorts, the Academic Medical  Center cohort (n=88) and the German Neuroblastoma Trial cohort (n=649), and co-expression of  both target genes identified patients with very poor outcome. Mechanistically, HDAC8 and ALK  converge at the level of receptor tyrosine kinase (RTK) signaling and their downstream survival  pathways, such as ERK signaling. Combination treatment of HDAC8 inhibitor with crizotinib efficiently  blocked the activation of growth receptor survival signaling and shifted the cell cycle arrest and  differentiation phenotype toward effective cell death of neuroblastoma cell lines, including  sensitization of resistant models, but not of normal cells. These findings reveal combined targeting of  ALK and HDAC8 as a novel strategy for the treatment of neuroblastoma.

overall_design: Total RNA was isolated from neuroblastoma cells (SK-N-BE(2)-C) treated for six days with solvent control (DMSO) or an HDAC8 inhibitor (PCI-34051; 4µM).

first: Ina

last: Oehme

first: Olaf

last: Witt


title: Human NPY/AgRP hypothalamic cell lines for study of obesity susceptibility

status: Public on Feb 22 2018

city: San Antonio

first: Yidong

last: Chen

state: Texas

address: 8403 Floyd Curl Drive, MSC 7784

department: Population Health Sciences

institute: UT Health Science Center at San Antonio

summary: Recent data suggests that common genetic risk for metabolic disorders such as obesity may be human-specific and exert effects through the central nervous system.  To overcome the limitation of human tissue access for study, we have generated induced human pluripotent stem cell (hiPSC)- derived neuronal cultures which recapture many features of hypothalamic neurons within the arcuate nucleus.  Here we have comprehensively characterized this model across development and benchmarked these neurons to in vivo events.  We also demonstrate their utility in study of obesity risk variants. The dynamic transcriptome across neuronal maturation was examined using microarray and RNAseq methods at 9 time points.  K-means clustering of the longitudinal data was conducted to identify co-regulation and miRNA control of biological processes.  The transcriptomes were compared to those of 103 samples from 13 brain regions reported in the Genotype-Tissue Expression database (GTEx) using principal components analysis.  Genes with proximity to body mass index (BMI)-associated genetic variants were mapped to the developmentally expressed genesets, and enrichment significance was assessed with Fisher’s exact test. The human neuronal cultures have a transcriptional and physiological profile of NPY/AgRP hypothalamic neurons.  The neuronal transcriptomes were highly correlated with adult hypothalamus as compared to any other brain region from the GTEx. Also, roughly 25% of the transcripts showed changes in expression across maturation stages and potential co-regulation of biological processes that mirror neuronal development in vivo. These developmentally expressed genes were significantly enriched for genes in proximity to BMI-associated variants.

overall_design: We collected total RNA of two samples at each of the 9 time points, day 0, 10, 25, 35, 45, 55, 75, 95, 115 , from day 0 to 115 during the differentiation and maturation process.  Total RNA was isolated using Qiagen RNeasy kit according to the manufacturer’s protocol.

first: Li

last: Yao

first: Yuanhang

last: Liu

first: Iriscilla

last: Ayala

first: Zhifang

last: Qiu

first: Sateesh

last: Kumar

first: Joanne

middle: E

last: Curran

first: Donna

last: Lehman


title: Transcriptomic response of Drosophila melanogaster whole bodies or dissected brains to Entomophthora muscae 'Berkeley'

status: Public on Feb 23 2018

city: Cambridge

first: Carolyn

last: Elya

state: MA

address: 52 Oxford Street

department: Organismic and Evolutionary Biology

institute: Harvard University

summary: We report the transcriptional profiles from individual Drosophila melanogaster (whole bodies or dissected brains) to Entomophthora muscae at 24 time points following fungal exposure. In whole fruit fly bodies, a significant immune response is observed following exposure to the fungus. In brains, few differences are consistently observed between infected and uninfected animals.

overall_design: Three mock vials and three exposure vials were started with 25 CantonS Wolbachia-free flies 0-1 days old (RT-PCR, whole flies) or 1-2 days old (dissected brains) with either zero (mock) or six (exposure) Entomophthora muscae-killed D. melanogaster cadavers. For whole bodies, three uninfected females were individually collected at 24, 48, 72, 96 and 120 hours following mock exposure. Six exposed female flies were individually collected at each 24, 48 and 72 hours; three exposed females were collected at 96 hours and three fresh female cadavers were collected at each 96 and 120 hours. For dissected brains, three uninfected and three exposed female brains were individually collected at 24, 48 and 72 hours following mock exposure or exposure, respectively.

first: Michael

last: Eisen


title: Gene expression profiles of human memory B cells stimulated with BCR/CD40L/IFN-γ/IL21

city: Fukuoka

first: Kohta

last: Miyawaki

address: 3-1-1, Maidashi, Higashi-ku

institute: Kyushu University

summary: Analysis of the effect of BCR/CD40/IFN-γ/IL21 on human B cells at gene expression level.

overall_design: Total RNA samples were obtained from human memory B cells subjected to 24 hours of in vitro culture with or without BCR, CD40, IFN-γ, IL21.

first: Tsuyoshi

last: Nakayama


title: Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development [Primary CTB]

status: Public on Feb 15 2018

city: La Jolla

first: Mana

last: Parast

state: California

address: 9500 Gilman drive #0695

department: Pathology

institute: University of California San Diego

summary: In this study, we compared the genome-wide transcriptome of mouse and human placentas across gestation to identify species-specific signatures of early development. We also compared human placental signatures to purified primary cytotrophoblasts (CTB) isolated from placentae at different gestational age.

overall_design: We isolated primary CTB from placentae at different gestational age and subjected them to RNA microarray profiling on the Illumina platform. CTB signature was compared to signature from whole placentae.

first: Francesca

last: Soncin

first: Marwa

last: Kather

first: Cuong

last: To

first: Donald

last: Pizzo

first: Omar

last: Farah

first: Anna

last: Wakeland

first: Kanaga

last: Arul Nambi Rajan

first: Katharine

middle: K

last: Nelson

first: Ching-Wen

last: Chang

first: Matteo

last: Moretto Zita

first: David

middle: R

last: Natale

first: Louise

last: Laurent

middle: M


title: Molecular changes in premenopausal estrogen receptor-positive primary breast cancer after oophorectomy

status: Public on Feb 14 2018

first: Alice

last: Gao

state: London

address: 237 Fulham Road

department: Breast Cancer Now

institute: The Institute of Cancer Research

summary: For premenopausal women with primary ER+ breast cancer, oophorectomy (OvX) is an evidence-based cost-effective option and is standard treatment in many countries. However, there is virtually no data describing the effects of OvX on breast tumour biology. We therefore characterized the endocrine and genome-wide transcriptional impact of OvX in 56 premenopausal women with ER+ breast cancer for two weeks prior to mastectomy. Plasma estradiol concentrations decreased from 421±305 to 24.1±24.5 pmol/l (mean±sd) 24 hours after OvX and to 8.8±7.3pmol/l two weeks later at mastectomy. Ki67 decreased in 33/36 (91.7%) tumours. The expression of 655 genes changed significantly (FDR<1%) with an absolute mean fold-change (FC) ≥1.25 (257 up, 398 down). Archetypal oestrogen-regulated genes, proliferation-associated genes and putative progesterone-regulated genes were strongly down-regulated. The gene expression changes did not differ according to HER2 status and correlated strongly with those after aromatase inhibitor (AI) treatment in 81 postmenopausal women. However, after OvX the mean FC was significantly higher compared to AI. In conclusion, changes in tumoural gene expression after OvX were largely similar but of a greater magnitude to those observed after AI in postmenopausal patients but OvX appeared to have a greater effect on progesterone-regulated genes than AI.

overall_design:
A non-randomized phase II trial of neoadjuvant OvX was conducted in 56 premenopausal women with ER+ breast cancer in Vietnam in order to identify the most important genes and pathways associated with the response to OvX as well as determinants of that response. In addition, the degree to which the relationships differed from those observed after an AI in postmenopausal women (i.e. comparing withdrawal of oestrogen and progesterone vs. withdrawal of oestrogen alone) was assessed. Global gene expression profiles from ERα-positive breast carcinomas before and after OvX treatment were compared. Transcripts responding differently to OvX and estrogen deprivation were identified and integrated using Gene Ontology and pathway analyses. This represents the data for OvX only.

Please note that 88 paired frozen samples from 32 patients (out of 56 in the trial; 24 with A, B & C samples; 5 with A & C and 3 with B & C) were used for Illumina whole genome expression BeadChips analysis.

first: Qiong

first: Ben

last: Haynes


title: Expression data from TCF19 knockdown in HepG2 cells maintained under high glucose (40mM) condition

status: Public on Feb 13 2018

city: Bangalore

first: madavan

last: vasudevan

state: Karnataka

address: Kasturi Nagar

institute: Theomics International Private Limited

summary:
Changes in concentration of glucose in the cellular environment results in a variety of changes in the transcription program. Liver is the primary organ for metabolic regulation in the body, and hence, any surge in circulating blood glucose leads to changes in transcriptional states of important enzymes tasked to maintain metabolic homeostasis. Chromatin modification reader proteins play an important role in maintaining metabolic homeostasis by identification of the histone modification, and facilitating recruitment of chromatin remodelling enzymes.
We knocked down an important reader domain containing protein, TCF19, in human hepatocellular carcinoma cells ( HepG2) maintained under high glucose condition and used microarray to investigate the changes in gene expression profile.

overall_design: Gene expression profile was compared between two experimental sets : Control ( HepG2 cells treated with non-targeting siRNA and maintained in 40mM glucose for 48 hours) vs. TCF19 siRNA treated ( HepG2 cells treated with TCF19 siRNA, and maintained in 40mM glucose for the same time period as Control set)

first: Sabyasachi

last: Sen

first: Sulagna

last: Sanyal

first: Dushyant

last: Srivastava

first: Dipak

last: Dasgupta

first: Siddhartha

last: Roy

first: Chandrima

last: Das


title: Genome-wide analysis of gene expression by SGC7901 subjected to recombinant human STIP1 (rhSTIP1)

city: Guangzhou

first: Lin

middle: Lin

last: Huang

address: 58 Zhongshan 2nd Road

department: Department of Gastroenterology

institute: the First Affiliated Hospital of Sun Yat-sen University

summary: Analysis of SGC7901 in proliferation, apoptosis, metastasis, and metabolism at gene expression level. The hypothesis tested in the present study was that rhSTIP1 influences the epithelial-to-mesenchymal transition of SGC7901. Results provide important information of the epithelial-to-mesenchymal transition, such as Wnt signaling pathway genes, up- or down-regulated specific metastasis cellular functions.

overall_design: Total RNA obtained from SGC7901 subjected to rhSTIP1 in vitro compared to IgG-SGC7901.

first: Sui

last: Peng


title: Effect of EcR RNAi on wandering third instar larval fat body gene expression in Drosophila melanogaster

status: Public on Feb 10 2018

first: Laura

last: Musselman

summary: We compared ecdysone receptor (EcR)-dependent gene expression in the Drosophila fat body on 0.15 M sucrose and 0.5 M sucrose high-sugar diets in order to gain insight into the role of this gene during caloric overload. Phenotypic analyses showed an increased severity of EcR RNAi phenotypes with increasing dietary sugar concentration. Because EcR is a transcription factor, we performed RNA-seq studies to identify transcriptional targets that might underlie insulin resistance downstream of EcR RNAi.

overall_design: Control and fat body-expressed EcR RNAi Drosophila were reared on control (0.15 M sucrose) and high-sugar (0.5 M sucrose) diets until the wandering stage. Fat bodies were isolated and RNA extracted to determine the effects of diet on gene expression using Illumina RNA-seq.

first: Thomas

last: Baranski


title: PHLDA1 mediates drug resistance in receptor tyrosine kinase driven cancer

status: Public on Feb 19 2018

first: Jun

last: Wang

address: Charterhouse Square

institute: Barts Cancer Institute, Queen Mary, London

summary:
Mutations or amplifications of receptor tyrosine kinases (RTKs) are common in many cancers. Given the emergence of small molecule inhibitors specific to RTKs, these signalling cascades are attractive therapeutic targets. However, compensatory and adaptation mechanisms limit the clinical utility of compounds that target nodes in RTK networks.
Here we show that PHLDA1 down-regulation is critical to acquisition and maintenance of drug resistance in RTK-driven cancer.

overall_design: Total RNA obtained from cell lines resistant to small molecule FGFR inhibitors AZD4547 or PD173074 were profiled together with RNA from the parental cell line (MFE-296).

first: A

last: Fearon

first: R

middle: P

last: Grose


title: 61 lymphoma cell lines gene expression profiles

status: Public on Feb 09 2018

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: assess the gene expression profiling of 61 cell lines

overall_design: GEP analysis of 61 lymphoma cell lines

first: Andrea

last: Rinaldi

first: Ivo

last: Kwee

first: Eugenio

last: Gaudio


title: Unexpected growth-promoting effect of oxaliplatin in ERCC1-transfected human colon cancer cells

city: Lyon

first: abdelakamel

last: chettab

address: 8 avenue Rockeffeler

department: centre de recherche en cancérologie de lyon

country: France

institute: université claude bernard lyon1

summary: The nucleotide excision repair protein ERCC1 has been repeatedly shown to be involved in the sensitivity of cancer cells to platinum derivatives. In order to better understand this process, we transfected HCT-116 cells with a plasmid encoding ERCC1 and studied their in vitro and in vivo behaviour. The Trop2 protein was identified as being potentially involved in the underlying mechanism for these observations. Our results suggest complex regulation of signalling in cancer cells exposed to cancer drugs.

overall_design: Analysis of gene expression of Hcont cells (Stable HCT-116 cells transfected with control plasmid) and Hercc1 cells (Stable HCT-116 cells transfected with ERCC1-coding plasmid) in cells from tumors grown in mice treated or not with oxaliplatin (2 mg/kg) two hours before the recovery of tumors. The experiment was performed in triplicate

first: Lars

last: Jordheim

first: Kamel

last: Chettab

first: Emeline

last: Cros-Perrial

first: Eva-Laure

last: Matera

first: Charles

last: dumontet


title: Transcriptome profiles of MDA-MB-231 breast cancer cells cultured with interstitial fluids from post-mastectomy breast cancer patients

status: Public on Feb 01 2018

city: Dallas

first: Yujin

last: Hoshida

state: TX

address: 5323 Harry Hines Blvd

institute: University of Texas Southwestern Medical Center

summary:
Background: While body fluids are widely used in medicine, despite the fact that interstitial fluid (IF) represents a third of our body fluid, it is the most poorly understood and under-studied. In cancer, IF pressure is elevated due to increased extracellular matrix deposition in the desmoplastic stroma surrounding tumors. However, whether IF affects cancer behavior remains unclear.

Methods: We collected 180 IF using drains from patients that underwent bilateral mastectomy for unilateral breast cancer with or without immediate reconstruction. The IF were classified based on their ability to promote invasion of breast cancer cells and tested in vivo. A retrospective study linking IF-invasion score to clinical parameters was performed.

Results: We observed a wide range of invasion score among IF between patients, and analysis of different IF from the same patient suggests that IF are organ-specific. Patients with high-grade tumors at diagnosis have high score IF. In mice, injections of high-score IF in a normal mammary gland promoted ductal hyperplasia, increased collagen deposition and local invasion. In a mouse model of residual disease, high-score IF increased local recurrence and promoted aggressive visceral metastases.

Discussion: Exposure of normal breasts to high-score IF predisposes to the development of aggressive breast cancer long before surgery. Further, such exposure following surgery increases the risk of recurrence. Therefore, our study raises the provocative possibility that intrinsic difference in IF between individuals play an active role in the predisposition, development and clinical course of sporadic breast cancers.

overall_design: Post-mastectomy fluids were collected from breast cancer patients 24h after surgery from drain. MDA-MB-231 breast cancer cells were cultured with serum-free DMEM with 1% post-mastectomy fluid for 24h, and transwell invasiveness was assessed for each patient's fluid. Cells were harvested, and total RNA was extracted and subjected to gene-expression profiling by Illumina BeadArray.

first: Timothy

last: Kenny

first: Doris

last: Germain


title: Expression data from patients with HCC receiving Nivolumab

status: Public on Jan 31 2018

city: New York

first: Daniela

last: Sia

address: 1425 Madison Avenue

department: Liver Diseases

institute: Icahn school of Medicine at Mount Sinai

summary:
We have generated an immune classifier able to identify patients belonging to the immune subclass of HCC. Characteristics of the immune subclass resemble those of patients  who most respond to immunotherapy.
We performed microarray expression of the tumors of two patients before starting treatment with nivolumab to verify if the immune classifier generated was able to predict response to immunotherapy.

overall_design: Upon patients’ consent, RNA extraction and RNA profiling were performed on tumoral sections derived from available archived tissues collected any time before treatment.


title: BV6 induces an early wave of gene expression via NF-κB and AP-1 and a second wave via TNFα/TNFR1 signaling

status: Public on Feb 05 2018

city: Lübeck

first: Hauke

last: Busch

state: Schleswig-Holstein

address: Ratzeburger Allee 160

department: Lübeck Institute of Experimental Dermatology

institute: University of Lübeck

summary: Smac mimetics are considered as promising cancer therapeutics, but little is yet known about how they alter gene expression. In this study we used an unbiased genome-wide expression array to investigate Smac mimetic BV6-induced gene regulation in breast cancer cell lines. Kinetic analysis revealed that BV6 alters gene expression in two waves. The first wave primarily involves NF-κB- and AP-1 families of transcription factors, while the second wave largely depends on tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, disrupting auto-/paracrine tumor necrosis factor-α (TNFα)/ (TNFR1) signaling by knockdown of TNFR1 strongly attenuates the BV6-induced second wave of gene expression and upregulation of many pathways including NF-κB signaling, apoptosis and immune signalling, but not MAPK signaling pathways. Consistently, BV6 stimulates phosphorylation of cJun, a marker of MAPK cascade activation, irrespective of the presence or absence of the TNFα blocking antibody Enbrel.  We show here in a comprehensive overview that BV6-induced gene expression in breast cancer cells takes place in a time- as well as TNFR1-dependent manner.

overall_design: A total of 48 samples was analyzed. EVSA-T cells and MDA-MB-231 cells were transfected with control siRNA or siRNA directed at TNFR1 and then each of these conditions were treated with BV6 or left untreated. Samples were provided in duplicates for EVSA-T cells and triplicates for MDA-MB-231.  Untransfected MDA-MB-231 were treated with BV6 for 3, 6, 9, 12, 15 hours in duplicates. Untreated controls were collected at 0, 9 and 15 hours in duplicates.

first: Melanie

last: Boerries

first: Simone

last: Fulda

first: Nadine

last: Schmidt


title: Gene expression profiling of idiopathic pulmonary fibrosis and non-specific interstitial pneumonia

status: Public on Feb 06 2018

first: Marco

last: Mura

state: Ontario

address: 800 Commissioners Road East E6-203

department: Medicine

institute: Western University

summary:
Idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP
We used microarray to identifiy the gene expression profiles in patients with IPF and NSIP, mixed IPF/NSIP histologic pattern and normal controls.

overall_design: Fresh frozen lung samples were obtained from the recipients organs of 22 patients with IPF, 10 with NSIP and 5 with mixed IPF-NSIP undergoing lung transplantation. Normal lung tissue (n=11) was obtained from tissue flanking lung cancer resections. RNA was extracted and hybridized on Affymetrix microarrays.


title: Gene expression data of organoids derived from human pancreatic tumor and normal pancrea samples.

status: Public on Feb 08 2018

city: Tokyo

first: Mariko

last: Shimokawa

address: 35, Shinanomachi, Shinjuku-Ku

country: Japan

institute: Keio University

summary: We analyzed gene expression of 39 patient-derived pancreatic tumor, 6 normal-like, 2 normal and 10 engineered organoids.

overall_design: mRNA from organoids were extracted and hybridized to GeneChip PrimeView Human Gene Expression Array, and scanned using GeneChip Scanner 3000 7G.

first: Takashi

last: Seino


title: Gene expression data from tumor-bearing mice, either left untreated, treated with MUC1 peptide vaccine, indomethacin, or MUC1 peptide vaccine + indomethacin

status: Public on Jan 26 2018

city: Charlotte

last: Erick

state: North Carolina

address: 9201 University City Blvd, Woodward Hall 461

institute: University of North Carolina at Charlotte

summary: RNA was isolated from the tumors of untreated mice, mice treated with MUC1 vaccine alone, indomethacin alone, or MUC1 vaccine + indomethacin. We used microarrays to identify changes in gene expression between these treatment groups.

overall_design: RNA samples from the tumors of untreated mice, indomethacin only mice, vaccine only mice, and vaccine + indomethacin mice were reverse transcribed, amplified and labeled using 3’ IVT Express Kit (Affymetrix Inc.). The resultant labeled complementary RNA (cRNA) was purified and fragmented as per vendor’s instructions. The cRNA samples together with probe array controls were hybridized onto Affymetrix® HT MG-430 PM array strips which cover over 39,000 mouse transcripts and variants selected from GenBank®, dbEST, and RefSeq. Hybridization controls were spiked into the cRNA samples in order to monitor and troubleshoot the hybridization process. Probes for housekeeping genes were used to assess sample integrity. Hybridization, washing, staining and scanning were performed using Affymetrix GeneAtlas® personal microarray system instruments. Affymetrix GeneAtlas® instrument control software version 1.0.5.267 was used to analyze microarray image data and to compute intensity values. Affymetrix.CEL files containing raw, probe-level signal intensities were analyzed using Partek Genomics Suite version 6.6.12.0713 (Partek). Robust multichip averaging (RMA) was used for background correction, quantile normalization and probe set summarization with median polish (1). Statistical difference was calculated by two-way ANOVA analysis with false discovery rate (FDR). Pathway analysis was performed using Ingenuity Pathway Analysis software (Ingenuity Systems, Inc.). (1) Bolstad, B. M., R. A. Irizarry, M. Astrand, and T. P. Speed. 2003. A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics 19: 185-193.

first: Jennifer

last: Curry

first: Dahlia

last: Besmer

first: Nury

last: Steuerwald

first: Lopamudra

last: Das Roy

first: Priyanka

last: Grover

first: Shanti

last: Rao

first: Sritama

last: Nath

first: Pinku

last: Mukherjee


title: Transcriptomic analysis of the peripheral nervous system of Schwann cell-conditional FASN knockout mice

status: Public on Feb 02 2018

city: Zürich

first: Laura

last: Montani

state: ZH

address: Otto Stern Weg 7

institute: IMHS - ETH Zürich

summary: Myelination calls for a tremendous surge in cell metabolism towards lipids and membrane production. However, functional relevance of de novo fatty acid synthesis in myelinating cells remains unclear. We generated mutant mice in which the enzyme fatty acid synthase (FASN) was depleted conditionally in Schwann cells, the myelinating glial cells of the peripheral nervous system. To address how lack of FASN was affecting the development of the peripheral nervous system, we screened with an Affymetrix Transcriptomic approach the transcriptome of sciatic nerves and roots of P60 FASN mutant mice, comparing to control mice.

overall_design: N = 3 sample per condition, 2 tissues analyzed: sciatic nerve and roots, 2 genotypes: DhhCre+ Fasn lox/lox (mutant) and DhhCre- Fasn lox/lox (control)

first: Ueli

last: Suter