title: cDNA microarray of hepatocellular carcinoma and nontumor liver tissues

status: Public on Dec 23 2011

city: Hangzhou

first: Meng

last: Xia

address: 866 Yuhangtang Road

country: China

institute: Institute of Immunology, Zhejiang University School of Medicine

summary: In order to identify the deregulated genes in hepatocellular carcinama, we applied the Agilent two-color chip cDNA microarray to explore the expression of genes in hepatocellular carcinoma and nontumor liver tissue samples. Hepatocellular carcinoma tissues and nontumor liver tissues were obtained from hepatocellular carcinoma patients during surgery. In these samples, RNA was extracted and cDNA microarray was performed to identify the differentially expressed genes in these samples.

overall_design: Hepatocellular carcinoma tissues and nontumor liver tissues were obtained from hepatocellular carcinoma patients during surgery. We included four hepatocellular carcinoma patients in this study, and there are four nontumor tissues and four hepatocellular carcinoma tissues.

last: Hou

first: Xuetao

last: Cao


title: Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways

status: Public on Dec 24 2011

city: Madrid

first: Beatriz

last: Martinez

address: Calle Melchor Fernandez Almagro 3

department: Human Cancer Genetics

country: Spain

institute: Spanish National Cancer Research Centre (CNIO)

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

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

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus
Human alphaherpesvirus 1
Human betaherpesvirus 5
Murid betaherpesvirus 1
human gammaherpesvirus 4
JC polyomavirus
Human immunodeficiency virus 1
Murid gammaherpesvirus 4
Human gammaherpesvirus 8
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: Refer to individual Series


title: A small molecule modulator of prion protein enhances proliferation and engraftment of mesenchymal stem cells and extends their lifespan upon serial passage in culture

status: Public on Jan 30 2012

city: Glasgow

first: Claire

middle: Judith

last: Cairney

address: Garscube Estate, Switchback Rd

department: College of Veterinary, Medical and Life Sciences

country: United Kingdom

institute: University of Glasgow

summary: Human mesenchymal stem cells (hMSC) play an important role in the maintenance of bone and blood. Most protocols rely on their in vitro expansion prior to clinical use. However, several groups including our own have shown that hMSC lose proliferation and differentiation ability with serial passage in culture, limiting their clinical applications. Here we show that targeting prion protein (PrP) by chemical intervention delays this process. When PrP expression was knocked down, cultures showed significant reduction in proliferation and differentiation capacity. In contrast hMSC expanded in the presence of small molecule modulator of PrP expression, 3/689, showed extended lifespan up to 10 population doublings. Upon re-plating cultures contained more than double the number of clonogenic progenitors and showed a 10 fold increase in engraftment levels in bone marrow 5 weeks post-transplant. Human MSC treated with 3/689 showed enhanced protection from DNA damage and enhanced cell cycle progression. Gene expression profiling revealed upregulation of superoxide dismutase 2 in cells treated with 3/689, dependent on PrP expression, and suggests increased scavenging of reactive oxygen species as mechanism of action. These data point to PrP as a good target to delay loss of proliferation and differentiation of hMSC with expansion in culture.

overall_design: Gene expression changes in hMSC expanded in the presence of 10uM small molecule modulator of prion protein 3/689 or DMSO were analysed at passage 2 and passage 8 from 3 separate donors.

first: Sindhu

middle: T

last: Mohanty

middle: J

first: W

middle: N

last: Keith

first: Ilaria

last: Bellantuono


title: Gene expression changes in primary mouse fibroblasts in the absence of ASCIZ

status: Public on Dec 21 2011

city: Fitzroy

first: Jörg

last: Heierhorst

state: Victoria

address: 9 Princes Street

country: Australia

institute: St. Vincent's Institute

summary: In order to identify potential transcriptional targets of ASCIZ, we performed a microarray analysis of three wildltype and ASCIZ(ATMIN/ZNF822)-deficient littermate single-passage MEF cultures.  Only 22 and 25 genes were found to be down- or upregulated in the KO, respectively, by >1.5-fold (p<0.05).  The most severely downregulated gene was Dynll1, which was confirmed by Norhtern and Western blot in mulitple embryonic tissues.

overall_design: Primary MEFs were isolated from embryonic day 12.5 embryos (3 wildtype, 3 knockouts), and passaged once before isolation of total RNA.


title: Gene expression changes in aortas of db/db versus control db/+ mice

city: New York

first: Nino

last: Mzhavia

state: NY

address: 630 West 168 Street PH 8-405

department: Medicine Cardiology

country: USA

institute: Columbia University Medical Centre

summary:
To determine effects of hyperglycemia and insulin resistance on arterial wall biology, aortic gene expression profiles were generated using aortas from Lepr^db/db and their respective nondiabetic Lepr^db/+ controls.

Keywords: Chip

overall_design: Experiment was done in triplicate with three independent pool of test Lepr^db/db and control Lepr^db/+ pooled samples. For RNA isolation aortas were striped of adventitia and periaortic fat. RNA from six aortas was pooled for the synthesis of probe for affymetrix array analysis.

first: Hayes

last: Dansky


title: Gene expression changes in aortas of mice on high fat versus regular chow diet.

summary:
To determine effects of hyperglycemia and insulin resistance on arterial wall biology, gene expression profiles were generated using aortas from mice on high fat (35% fat) diet and their respective non diabetic regular chow fed controls.
Keywords: Chip

overall_design: Experiment was done in triplicate with three independent pools from test mice on high fat diet and control mice on regular chow diet. For RNA isolation aortas were striped of adventitia and periaortic fat. RNA from three aortas was pooled for the synthesis of probe for affymetrix array analysis.


title: Effects of Mysm1 deficiency on gene expression across a range of mouse tissues and cell types

status: Public on Jan 01 2012

city: Montreal

first: Anastasia

last: Nijnik

state: Quebec

address: 3649 Promenade Sir William Osler

department: Physiology

country: Canada

institute: McGill University


title: Gene expression profiling of prostate cells with CHD1 knockdown

status: Public on Dec 19 2011

city: Stanford

first: Stephanie

last: Huang

state: CA

address: 269 Campus Drive, CCSR 3240

department: Pathology

institute: Stanford University

summary: Gene expression profiling of prostate tumor cells comparing cells that have CHD1 knockdown by shRNA (RWPE-1, OPCN2) or siRNA (LNCaP) with cells treated with non-targeted control.

overall_design: Prostate cell lines had CHD1 knockdown via shRNA or siRNA were hybridized against cells that were targeted with non-targeting control.  OPCN2 and RWPE-1 RNA were dye-swapped in replicate experiments.

first: Jonathan

middle: R

last: Pollack


title: The combination of valproic acid and lithium prevents hematopoietic stem/progenitor cell differentiation.

status: Public on Dec 15 2011

city: Groningen

first: Leonid

last: Bystrykh

state: Groningen

address: A. Deusinglaan 1

department: European Research Institute for the Biology of Ageing - ERIBA

country: Netherlands

institute: University Medical Center Groningen

first: Marta

middle: A

last: Walasek

first: Vincent

last: van den Boom

first: Sandra

last: Olthof

first: Albertina

last: Ausema

first: Martha

last: Ritsema

first: Gerwin

last: Huls

first: Gerald

last: de Haan

first: Ronald

last: van Os


title: siRNA knockdown of ribosomal protein gene RPL19 abrogates the aggressive phenotype of human prostate cancer

status: Public on Dec 08 2011

city: Sutton

first: Ian

last: Giddings

state: Surrey

address: 15 Cotswold Road

department: Section of Molecular Carcinogenesis

institute: Institute of Cancer Research

summary: Ribosomal protein RPL19 is an integral component of eukaryotic ribosomes and universally involved in protein synthesis. Although consistently stable  in normal cells, RPL19 transcription is relatively elevated in prostate cancer. Using siRNA, we inhibited RPL19 transcription and demonstrated the gene to be functionally involved in promoting the malignant phenotype. Reducing RPL19 modulates a subset of genes rather than globally down-regulating protein synthesis, as evidenced by Western blotting and maintenance of cell proliferation. Mechanistically, either all ribosomes are not structurally and functionally identical or absence of RPL19 is compensated by other ribosomal protein genes. Following RPL19 inhibition, gene expression analysis confirms induction of the non-malignant phenotype principally to involve perturbation of transcription factor networks and cellular adhesion genes.

overall_design: 10 microarray experiments were analysed using five different prostate cell types: PC3M, PNT2, PC3M with stable knockdown transfection, PC3M with a scrambled virus and various PC3M knockdowns pooled

first: Alix

last: Bee

first: Daniel

last: Brewer

first: Brian

last: Lane

first: Carol

last: Beesley

first: Andrew

last: Dodson

first: Shiva

last: Forootan

first: Timothy

last: Dickinson

first: Patricia

last: Gerald

first: Sheng

last: Yao

first: Colin

middle: S

last: Cooper

first: Christine

middle: M

last: Gosden

first: Youqiang

last: Ke

first: Mustafa

middle: B

last: Djamgoz

first: Christopher

last: Foster


city: Pittsburgh

first: Soonmuyung

last: Paik

state: PA

address: 1307 Federal Street, Suite 303

institute: NSABP Foundation

summary:
Gene expression profiling of invasive breast cancer events from the tamoxifen prevention trial validates low estrogen receptor mRNA level as the main determinant of tamoxifen resistance in estrogen receptor positive breast cancer.

In NSABP Breast Cancer Prevention Trial (BCPT), tamoxifen reduced the incidence of estrogen receptor (ER) positive tumors but not estrogen receptor negative breast cancer. More importantly, only 69% of estrogen receptor positive tumors were prevented by tamoxifen. The ER positive tumors arising in tamoxifen arm provides an ideal clinical model for acquired tamoxifen resistance. Based on data from NSABP trial B14 which showed linear prediction of the degree of benefit from adjuvant tamoxifen by the levels of ESR1 mRNA coding for ER-alpha, we hypothesized a priori that level of ESR1 mRNA would be lower in ER positive tumors arising in tamoxifen arm compared to those in placebo arm of BCPT.

Keywords: Gene expression profiling analysis

overall_design: Formalin fixed paraffin embedded tumor blocks with enough tumor tissue for RNA extraction were available from 108 cases (69 from placebo arm and 39 from tamoxifen arm) of the 264 that experienced invasive breast cancer (175 in placebo arm and 89 in tamoxifen arm) in BCPT before unblindings . Central ER immunohistochemistry identified 84 of them as ER positive (57 from placebo arm and 27 from tamoxifen arm). A novel protocol was developed and used to obtain microarray gene expression profiling from the degraded or fragmented RNA extracted from formalin fixed paraffin blocks.Hybridization intensity data were compiled using Partek Genomic Suite. After quantile normalization, genes with mean intensity below 500 were filtred out, which left 7743 probes with informative data. Data were log2 transformed for statistical analysis.

first: Katherine

last: Pogue-Geile

first: Joseph

middle: P

last: Costantino

first: Olga

last: Bohn

first: Debora

last: Fumagalli

first: Chungyeul

last: Kim

first: Yusuke

last: Taniyama

first: Ahwon

last: Lee

first: Megan

last: Reilly

first: Victor

middle: G

last: Vogel

first: Worta

last: McCaskil-Stevens

first: Leslie

last: Ford

first: Norman

last: Wolmark

first: D

middle: L

last: Wickerham

first: Soonmyung


title: Airway smooth muscle reponse to dexamathasone at 4 and 24 hours

status: Public on Dec 10 2011

city: Denver

first: Anthony

last: Gerber

state: CO

address: 1400 Jackson St

department: Medicine

institute: National Jewish Health

summary: Glucocorticoids, which activate glucocorticoid receptor signaling and thus modulate gene expression, are widely used to treat asthma. Glucocorticoids exert their therapeutic effects in part through modulating airway smooth muscle structure and function. However, the effects of genes that are regulated by GCs on airway function are not fully understood. Here, we used transcription profiling to characterize the effects of a potent glucocorticoid, dexamethasone, on cultured human airway smooth muscle gene expression at 4 and 24 hours.

overall_design: This study examined differential gene expression induced by treatment of cultured human airway smooth muscle cells with dexamethasone. There were 3 groups of samples and each group had 4 biological replicates.  Group 1 was no treatment, Group 2 was dexamethasone (dex) treatment for 4 hours, Group 3 was dex treatment for 24 hours. Cultures were synchronized so harvest occurred at the same time for all three groups. 2  samples are not included in this analysis (based on unsupervised clustering of samples and diagnostic plots).

first: Rebecca

last: Barbeau

first: David

last: Erle

first: Andrea

last: Barczak

first: Ritu

last: Roy


title: Identification of the tumor suppressor gene at chromosome 5q21

first: Stephanie

last: Huang

type: Genome variation profiling by genome tiling array


title: Expression profiles of HSPCs overexpressing microRNA cluster 99b/let-7e/125a, miR-125a, miR-155 and empty vector.

first: Leonid

last: Bystrykh

summary: Hematopoietic stem/progenitor cell (HSPC) traits differ between genetically distinct mouse strains. For example, DBA/2 mice have a higher HSPC frequency compared to C57BL/6 mice. We performed a genetic screen for microRNAs that are differentially expressed between LSK, LS−K+, erythroid and myeloid cells isolated from C57BL/6 and DBA/2 mice. This analysis identified 131 microRNAs that were differentially expressed between cell types and 15 that were differentially expressed between mouse strains. Of special interest was an evolutionary conserved miR-cluster located on chromosome 17 consisting of miR-99b, let-7e and miR-125a. All cluster members were most highly expressed in LSKs and down-regulated upon differentiation. In addition, these microRNAs were higher expressed in DBA/2 cells compared to C57BL/6 cells, and thus correlated with HSPC frequency. To functionally characterize these microRNAs, we overexpressed the entire miR-cluster 99b/let-7e/125a and miR-125a alone in BM cells from C57BL/6 mice. Overexpression of the miR-cluster or miR-125a dramatically increased day-35 CAFC activity and caused severe hematopoietic phenotypes upon transplantation. We showed that a single member of the miR-cluster, namely miR-125a, is responsible for the majority of the observed miR-cluster overexpression effects. Finally, we performed genome-wide gene expression arrays and identified candidate target genes through which miR-125a may modulate HSPC fate.

overall_design: These data consist of total mRNA obtained from 7-day cultured post 5-FU BM cells positively transduced with empty vector, miR-cluster 99b/let-7e/125a, miR-125a or miR-155 retroviral vector. Dataset (A) and dataset (B) were analyzed individualy. In each dataset, all samples were analyzed in independent biological triplicates.

first: Alice

last: Gerrits

first: Marta

last: Walasek

first: Sandra

last: Olthof

first: Ellen

last: Weersing

first: Martha

last: Ritsema

first: Erik

last: Zwart

first: Ronald

last: van Os

middle: V

first: Gerald

last: de Haan


title: Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

status: Public on Dec 07 2011

city: Buffalo

first: song

last: liu

address: Elm and Carlton Streets

institute: Roswell Park Cancer Institute

summary: Global gene expression studies were performed to determine whether the granulocytic-like MDSC populations from G-CSF treated mice resembled those of tumor-bearing (TB) mice more so than those of the non-tumor-bearing control (i.e., WT) at a molecular level.

overall_design: Splenic CD11b+Gr-1high cell populations from WT, G-CSF-treated or 4T1-TB mice  were purified in two independent experiments by flow cytometry (> 98% purity) and subjected to whole genome expression profiling using Illumina microarrays.

first: Jeremy

middle: D

last: Waight

first: Qiang

last: Hu

first: Song

last: Liu

first: Scott

middle: I

last: Abrams


title: Integration of BRCA1-mediated miRNA and mRNA signatures reveal miR-146a, miR-99b and miR-205 regulation of the TRAF2 and NFkB pathways (mRNA dataset)

first: Beatriz

last: Martinez

summary: BRCA1 deregulation is a frequent event in the pathogenesis of breast as well as other cancers. In addition to the DNA repair functions of BRCA1, it is involved in a wide range of cellular processes such as cell cycle, chromatin remodeling or transcription. However, the molecular events underlying BRCA1-associated tumorigenesis are still largely unknown. In order to deepen our understanding of BRCA1-associated tumorigenesis, we integrated data from mRNA and miRNA microarray experiments on the HCC1937 breast cancer cell line, and the isogenic HCC1937 stably expressing BRCA1, to obtain significant miRNA-mRNA relationships associated to the presence of the BRCA1 gene. Our results demonstrate that integration of mRNA and miRNA associated to BRCA1 expression was useful to discover new miRNA-gene interactions as molecular events underlying BRCA1-mediated tumorigenesis.

overall_design:
Transcriptional profiling of the BRCA1-null HCC1937 cell line and HCC1937 cells after stable transfection of BRCA1.
Two-condition experiment: Universal Human Reference RNA (Stratagene, catalog #740000) (Cy3) vs. cell line (Cy5). Biological replicates: 3 HCC1937, 3 BRCA1-transfected HCC1937 cells.

first: Miljana

last: Tanic

first: Magdalena

last: Zajac

first: Gonzalo

last: Gómez-López

first: Javier

last: Benítez

last: Martínez-Delgado


title: Expression data from mock treated/oxidized HF after 24h incubation with/without monocytes

status: Public on Dec 01 2011

city: Jerusalem

first: Jacob

last: Rachmilewitz

address: Ein Kerem

country: Israel

institute: Hadassah hospitals

summary: Cells are constantly exposed to stress. Most of those stresses do not necessarily cause cell death or visible damage. The present study explores the way the immune system responds to such sub lethal stressed cells.

overall_design: HF cells were exposed to sublethal oxidative stress or mock treated with PBS and after removal of the stressor, HF were incubated with/wthout monocytes for 24h and gene expression was evaluated.

first: Anat

last: Geiger-Maor


title: Gene expression analysis of Cbp deficient LSK cells

city: Cambridge

first: Wai-In

last: Chan

address: Wellcome Trust/MRC Building, Hills Road

department: Haematology

institute: Cambridge Institute for Medical Research

summary:
The transcriptional coactivator Cbp is critical for hematopoietic stem cell (HSC) development. However, its role in adult HSC and the mechanistic detail of Cbp control of HSC function remains unknown. Using conditional deletion of Cbp in the adult HSC compartment, we demonstrate an altered balance between differentiation and self-renewal with gradual loss of phenotypic HSC, differentiation defects in lower compartments and the development of myeloid malignancies. In addition, we demonstrate that Cbp -/- HSCs reconstitute hematopoiesis with lower efficiency than their wild type counterparts and readily exhaust over time when placed under the replicative stress of serial transplantation. Furthermore, we demonstrate abnormal cell cycle (re)entry and apoptosis in HSC which, with preferential differentiation, also contribute to stem cell exhaustion. Finally we demonstrate global transcriptional abnormalities predicted to alter cell cycle control, balanced differentiation and HSC function upon Cbp deletion and link Cbp to a critical HSC transcriptional regulatory network through genome-wide analysis of Cbp binding.
Genome-wide gene expression analysis of LSK population after Cbp deletion. The LSK population of bone marrow is enriched for hematopoietic stem cells.

overall_design: Total RNA was extracted from flow-sorted LSK population of bone marrow, 4 weeks after pIpC induced deletion of Cbp. 2 replicates for Cbp wt control, 2 replicates for Cbp Mx.

first: Rebecca

last: Hannah

first: Mark

last: Dawson

first: Clare

last: Pridans

first: Donna

last: Foster

first: Anagha

last: Joshi

first: Berthold

last: Göttgens

first: Jan

last: van Deursen


title: Molecular signature of CD8+ T cell exhaustion in metastases but not in peripheral blood from melanoma patients

status: Public on Nov 22 2011

city: Boston

first: Lukas

last: Baitsch

state: MA

address: 450 Brookline Avenue

department: Cancer Biology

institute: Dana Farber Cancer Institute

summary:
In chronic viral infections such as HIV-1, HBV and HCV, CD8+ T cells may become ”exhausted”, characterized by progressive functional deficiency. Recently, the underlying mechanisms have been characterized by molecular profiling of virus-specific CD8+ T cells. In contrast, only little is known of self/tumor-specific CD8+ T cells from cancer patients, likely because they are much more difficult to assess. For the first time, we determined the molecular profile of human tumor-specific CD8+ T cells, upon sorting of Melan-A/MART-1 specific T cells directly ex vivo from 19 melanoma patients after vaccination with peptide and CpG. For comparison, we sorted protective T cells specific for the two herpes viruses EBV and CMV.

In peripheral blood, we found multiple features of functional effector T cells, with only small but nevertheless significant differences between the three T cell populations, resulting in clean clustering according to antigen specificity. In contrast, Melan-A/MART-1 specific T cells obtained from tumor-infiltrated lymph nodes (TILNs) expressed multiple genes associated with T cell exhaustion, compatible with the known functional deficiencies of T cells in melanoma metastases. We show that individual T cells simultaneously expressed multiple inhibitory receptors implied in functional impairment. Together, the data indicate that in circulation, human tumor-specific T cells have the potential to become competent effector cells. In the tumor environment, however, T cells are exhausted and fail to control malignant disease. Our novel resource data identify mechanisms of functional T cell deficiency in melanoma patients, providing a rational basis for the improvement of immune therapy.

overall_design:
52 samples were measured in two sets of experiments. 4 self/tumor-specific samples from blood were replicated between the first and second sets.

Set 1 (32 samples, all from blood): 13 naive samples, 10 EBV-specific samples, 9 self/tumor-specific samples.

Set 2 (20 samples): 7 CMV-specific samples from blood, 7 self/tumor-specific samples from TILN, 6 self/tumor-specific samples from blood.

first: Daniel

middle: E

last: Speiser


title: Genetic Screen Identifies MicroRNA Cluster 99b/let-7e/125a as a Regulator of Primitive Hematopoietic Cells

first: Leonid

last: Bystrykh

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


title: Comparative analysis of gene expression in 9 BXH RI strains and progenitors (B6 and C3) and BXHF1.

status: Public on Nov 26 2011

city: Baltimore

first: vikas

last: misra

state: MD

address: 615 N. Wolfe street, E6609

department: Environmental health sciences

institute: Johns Hopkins University School of public health

summary:
We hypothesize that gene expression in the lungs of this RI panel are divergent thus contributing to the disparity in their phenotypes. More specifically, (1) B6 mice tend to have a much smaller lung volume than the C3 mice while the F1 appears to be like the B6 in lung structure and function. We postulate that their gene expression differences would reflect this. (2) The diversity in the phenotypes of this RI panel could be explained by a few genes whose expression spectrum across this panel could explain the physiological spectrum. In order to test these hypotheses at the gene expression level, we utilized microarray analysis to examine transcriptional differences among lungs of these strains of mice.

Keywords: comparative expression profiling

overall_design: This study utilizes microarray analysis to test these hypotheses. Two sets of lungs were harvested from each strain at 8 wks of age.  RNA was isolated and used for global gene expression profiling (Affymetrix Mouse 430A array).

first: Vikas

last: Misra

first: Benilton

last: Carvalho

first: Rafael

last: Irizarry

first: Clarke

last: Tankersley


title: Identification of SOX4 novel transcriptional targets.

status: Public on Nov 18 2011

city: L´Hospitalet de Llobregat

first: Sandra

last: Castillo

address: Avda. Gran Via 199-203

institute: IDIBELL-PEBC

summary: The SOX4 gene belongs to a family of transcription factors and we previously unveiled SOX4 gene amplification and over-expression in a subset of lung cancers, indicating it may constitute a driver oncogene. Here, we searched for SOX4 transcriptional targets and investigate their involvement in lung development and carcinogenesis. We abrogated SOX4 expression in the NIH-H522 lung cancer cell line, carrying SOX4 amplification and over-expression, using an inducible short-hairpin system. Global analysis of gene expression identified about 90 genes down-regulated after SOX4 abrogation many of them related to neural development. We also demonstrated recruitment of SOX4 to many of these promoters, evidencing their nature as direct transcriptional targets of SOX4. Most of these transcripts were significantly increased in lung cancer cells with ectopic SOX4 over-expression and in lung tumors with high levels of SOX4. Conversely, many of them exhibited significant low expression levels in embryonic fibroblasts from Sox4-/- mice.

overall_design: We generated H522-derived cells that down-regulate SOX4 in an inducible manner. The H522 cells were transfected with a tetracycline (tet) repressor expression construct and a tet-repressor-controlled expression vector (tet-on) containing a shSOX4. An stable clone, H522Tr-shSOX4-1, which down-regulate SOX4 expression by 90%, 48 hours after adding doxycycline, was chosen for further analysis. To determine the gene expression profile characteristic of SOX4 depleted expression we compared the global gene expression of the parental H522 cells to the H522Tr-shSOX4-1 cells at 0, 24 and 96 hrs after inducing the shSOX4 with doxycycline using the Whole Human Genome Microarray from Agilent.

first: Montse

last: Sanchez-Cespedes


title: Transcriptional targets of Trps1 in vibrissae

status: Public on Dec 22 2011

first: Katherine

last: Fantauzzo

address: 1150 St. Nicholas Avenue Room 307

institute: Columbia University

summary:
Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities.  Trps1 is a vertebrate transcription factor containing nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA.  Mice in which the GATA domain of Trps1 has been deleted (Trps1∆gt/∆gt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally.
To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis comparing expression patterns in the whisker pads of wild-type versus Trps1∆gt/∆gt embryos.  We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos, and several extracellular matrix proteins there were upregulated in the mutant samples.

overall_design: Whole whisker pads were dissected from E12.5 embryos and total RNA was isolated using the RNeasy Mini Kit (Qiagen). Triplicate RNA samples from three independent embryos of each genotype were amplified and labeled for hybridization to Affymetrix GeneChip MOE430A microarrays using Affymetrix reagents and protocols. The data output was analyzed using GeneSpring GX 10.0 commercial software (Agilent Technologies). P-values were calculated using an unpaired t-test. Expression values with a p-value less than or equal to 0.05 and a fold difference of at least 1.5 relative to wild-type baseline expression levels were considered significant.

first: Angela

last: Christiano


title: A genome wide RNAi screen in mouse embryonic stem cells identifies Mp1 as a key mediator of differentiation

status: Public on Nov 15 2011

city: Amsterdam

first: Bart A.

last: Westerman

address: De Boelelaan 1117

department: Cancer Center Amsterdam - Neurosurgery

institute: Cancer Center Amsterdam CCA

summary:
Despite intense investigation of intrinsic and extrinsic factors that regulate pluripotency, the process of initial fate commitment of embryonic stem (ES) cells is still poorly understood. Here, we used a genome wide shRNA screen in mouse ES cells to identify genes that are essential for initiation of differentiation. Knockdown of the scaffolding protein Mek binding protein 1 (Mp1, also known as Lamtor3, Map2k1ip1) stimulated self-renewal of ES cells, blocked differentiation and promoted proliferation. Fibroblast growth factor 4 (FGF4) signaling is required for initial fate commitment of ES cells. Knockdown of Mp1 inhibited FGF4-induced differentiation but did not alter FGF4 driven proliferation. This uncoupling of differentiation and proliferation was also observed when oncogenic Ras isoforms were over expressed in ES cells. Knockdown of Mp1 redirected FGF4 signaling from differentiation towards pluripotency and upregulated the pluripotency-related genes Esrrb, Rex1, Tcl1 and Sox2.
We also found that human germ cell tumors express low amounts of Mp1 in the invasive embryonic carcinoma and seminoma histologies and higher amounts of Mp1 in the non-invasive carcinoma in situ precursor and differentiated components. Knockdown of Mp1 in invasive germ cell tumor cells resulted in resistance to differentiation, thereby showing a functional role for Mp1 both in normal differentiation of ES cells as well as in germ cell cancer.

overall_design: 8 samples were analyzed, representing four different experimental conditions of which each condition was analyzed by two different shRNAs to prevent off target artifacts.

first: Bart

first: Maarten

last: van Lohuizen


title: human duodenum biopsy data

city: Bethesda

first: Natalia

last: Shulzhenko

address: 9000 Rockville Pike

department: Laboratory of Cellular and Molecular Immunology

institute: NIAID, USA

summary:
Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium, and the microbiota. We found that mice lacking B lymphocytes, or lacking IgA, have low intestinal expression of lipid metabolism genes regulated by the transcription factor GATA4, and a consequent decrease in fat absorption in the intestine. The defect disappeared in germ free mice, suggesting that it is dependent on the microbiota; and sequencing analysis of the bacteria showed subtle differences between normal and B-cell deficient mice. Analysis of gene expression of gut biopsies from patients with common variable immunodeficiency and intestinal dysfunction revealed a high similarity to mouse B-cell knockout profiles. These data provide an explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans.
this series represents the subsection of the study where we analize gene epxression in duodenum biopsies from CVID patients and contols with unrelated pathologies

overall_design: Reference sample is from normal duodenum (Clontech). Log2 ratio Cy5/Cy3 was used.

first: Andrey

last: Morgun


title: AIRE hypoexpression and transcriptome profiles correlate with thymic impairment in Down syndrome

status: Public on Nov 28 2011

city: Sao Paulo

first: Patricia

middle: Locosque

last: Ramos

state: SP

address: Av Dr Arnaldo 455

department: Pediatria

country: Brazil

institute: Universidade de Sao Paulo

summary: Down syndrome (DS) patients frequently develop organ-specific autoimmune disorders, particularly endocrinopathies and coeliac disease, as well as an increased susceptibility to mucosal candidiasis. These clinical features resemble APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy), a monogenic condition due to mutations in the AIRE gene, located on 21q22.3 and already described as down-regulated in 21 trisomy. Here we investigated AIRE expression and global gene expression profiles in surgically removed thymuses from 14 DS infants and children with congenital heart defects and from 42 age-matched individuals with cardiac defect as an isolated malformation. Immunohistochemistry revealed significantly reduced AIRE expression in DS thymuses (70.48±49.59 positive cells/mm2 in DS X 154.70±61.16 in controls, p<0.0001). qPCR confirmed the lower expression of AIRE in DS thymuses. Global thymic RNA profiles from DS patients and controls revealed 407 genes significantly hypoexpressed in DS. Network transcriptional analysis showed that hypoexpressed genes are related to biological processes such as antigen processing and presentation of endogenous antigen (ERAP2, CD1D), negative (PRDX2) and positive (CD3D, CD74) thymic T-cell selection and homeostasis of number of cells (PRDX2). Altogether these findings may explain the high prevalence of autoimmune phenomena in DS patients. Moreover, our data are in accordance with previous findings of thymic abnormal development in DS patients, characterized by lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation. Global gene profiles indicate that in DS patients, the trisomic imbalance probably leads to thymic hypofunction. In conclusion, lower AIRE expression and the impairment of other crucial pathways for central tolerance could well explain the high prevalence of organ-specific autoimmune disorders in DS.

overall_design: Among the 14 DS infants and 42 age-matched individuals with cardiac defect, only 4 from each group provided enough biological material (thymus fragments) for isolation of high-quality RNA to perform array analysis. Eight thymic samples were analyzed: C1, C2, C3 and C4 are controls, and D1, D2, D3 and D4 are from patients with Down syndrome.

first: Flavia

last: Lima

first: Carlos

last: Moreira-Filho

first: Helena

last: Brentani

first: Leandro

first: Magaly

last: Arrais

first: Luiz

last: Souza

first: Luciana

first: Maria

last: Duarte

first: Beatriz

last: Aguiar

first: Antonio

last: Coutinho

first: Magda

last: Carneiro-Sampaio


title: S100A8 treatment on gene expression of human umbilical vascular endothelial cells.

status: Public on Nov 20 2011

city: Suzhou

first: Yiqiang

last: Wang

state: Jiangsu

address: 111 Renai Road

institute: Xi'an Jiaotong-Liverpool University

summary: Previous studies showed that S100A8 and S100A9 are involved in neovascularization as well as in tumor development. At high concentrations, S100A8 and S100A9 cause inflammatory response or apoptosis mediated damage in vascular endothelial cells. But the effect of low concentrations of such proteins on endothelial cells remains unknown. This assay was performed to screen for genes that are involved in the response of Human Unbilican Vascular Endothelial Cells to low concentrations of S100A8.

overall_design:
Human Umblical Vascular Endothelial Cells (HUVEC) were cultuered and treated with 10ug/mL S100A8 proteins for 4 or 24 hours. Gene profiling was carried out using two-color microarray.
Two-condition experiment, S100A8 treatment vs. non-treatment. Two time points: 4 hours and 24 hours. Biological replicates at each time point: 3 control replicates, 3 treatment replicates.

first: Lingling

last: Yang

first: Changkai

last: Jia


title: Regulation of extraembryonic endoderm stem cell differentiation by Nodal and EGF-CFC signaling

status: Public on Nov 29 2011

city: New York

first: Mariano

middle: Javier

last: Alvarez

address: 1130 St. Nicholas ave.

department: Systems Biology

summary: The signaling pathway for Nodal, a ligand of the transforming growth factor-beta (TGF-beta) superfamily, plays a central role in regulating the maintenance and/or differentiation of stem cell types that can be derived from the peri-implantation mouse embryo. Extraembryonic endoderm stem (XEN) cells are derived from the primitive endoderm of the blastocyst, which normally gives rise to the parietal and the visceral endoderm in vivo, but XEN cells do not contribute efficiently to the visceral endoderm in chimeric embryos. We have found that treatment of XEN cells with Nodal and/or Cripto, an EGF-CFC co-receptor for Nodal, results in up-regulation of markers for visceral endoderm as well as anterior visceral endoderm (AVE). Re-introduction of treated XEN cells into chimeric embryos by blastocyst injection or morula aggregation results in contribution to visceral endoderm and AVE. In culture, XEN cells do not express Cripto, but do express the related EGF-CFC co-receptor Cryptic and require Cryptic for Nodal signaling. Notably, the response to Nodal can be blocked by treatment with the ALK4/ALK5/ALK7 inhibitor SB431542, but Cripto treatment is unaffected, suggesting that its activity is independent of type I activin receptors. Gene set enrichment analysis of genome-wide expression signatures generated from XEN cells under these treatment conditions confirms the differing responses of Nodal- and Cripto-treated XEN cells to SB431542. Our findings define distinct pathways for Nodal and Cripto in the differentiation of visceral endoderm and AVE from XEN cells, and provide new insights into the specification of these cell types in vivo.

overall_design: Murine Xen-eyfg cell line treated with Alk4 inhibitor SB431542, Nodal and Cripto recombinant proteins.

first: Marianna

last: Kruithof-de Julio

first: Sandy

last: Price

first: Andrea

last: Califano

first: Michael

last: Shen


title: OVCAR-3 Cells: Control vs. FBA-TPQ treated

status: Public on Nov 12 2011

city: Shanghai

first: hui

last: wang

address: Rm 429, No. 41 Building, 320 Yueyang Road, Shanghai

institute: Institute for Nutritional Sciences (INS), Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS).

summary: The study was designed to determine the biological effects of novel marine alkaloid analog, FBA-TPQ on human ovarian cancer cells for its anti-tumor potential and the underlying mechanisms as a novel chemotherapeutic agent. Transcriptional profiling of human ovarian cancer cells comparing control vehicle-treated OVCAR-3(a human ovarian cancer cell line) cells with OVCAR-3 cells treated with 1000nM FBA-TPQ for 24 hours. Goal was to determine the effects of FBA-TPQ on global OVCAR-3 cells gene expression.

overall_design: One-condition experiment, control vehicle-treated OVCAR-3  vs. FBA-TPQ treated-OVCAR-3 cells. Biological replicates: 2 replicates.

first: Tao

last: Chen

first: Yi

last: Xu


title: Gene expression profile of normoxic versus hypoxic HeLa cells

status: Public on Nov 08 2011

city: Madrid

first: eduardo

last: balsa

state: Madrid

address: Diego de león 62

department: Inmunologia

institute: Hospital de la Princesa

summary: To identify new primary HIF target genes we cultured HeLa cells under short period (6 hours) of mild hypoxia (1% oxygen)

overall_design: Hypoxia-induced gene expression in HeLa cells was measured after 6h exposure to 1% oxygen and compare to normoxic

first: Daniel

last: Tello

first: Eduardo

last: Balsa

first: Manuel

last: Ortiz-Landazuri


title: Gene expression change in Skov3 after EZH2 knockdown

status: Public on Dec 12 2011

city: Philadelphia

last: Slifker

address: 333 Cottman Ave.

institute: Fox Chase Cancer Center

summary: To identify genes whose expression was suppressed by EZH2, we performed gene expression microarray analysis in control and EZH2 knockdown human SKOV3 EOC cells. Two individual short hairpin RNAs to the human EZH2 gene (shEZH2) were used to limit potential off-target effects.

overall_design: Two individual short hairpin RNAs to the human EZH2 gene (shEZH2) were used to limit potential off-target effects. Three technical replicates per group were used.

first: Rugang

last: Zhang


title: Genome-wide analysis of exercise-responsive gene expression in murine hearts subjected to 7 days of voluntary wheel running

status: Public on Nov 01 2011

city: Gold Coast

first: Kevin

middle: John

last: Ashton

state: QLD

address: University Drive

department: Health Sciences & Medicine

institute: Bond University

summary: To undertake transcriptome-wide microarray analysis to develop a view of molecular adaptations that may underpin any benefit associated with the mild exercise regime of voluntary running

overall_design: Total RNA obtained from isolated whole hearts subjected to 7 days of voluntary exercise compared to sedentary control hearts (n=6/group).

first: Boris

last: Budiono

first: Louise

last: See-Hoe

first: Jason

last: Peart

first: Surendran

last: Sabapathy

first: Luke

last: Haseler

first: John

last: Headrick


title: Identification of the epithelial receptor for measles virus

status: Public on Nov 02 2011

city: Langen

last: Mühlebach

address: Paul-Ehrlich-Strasse 51-59

country: Germany

institute: Paul-Ehrlich-Institut

summary: Measles (MV) is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. While it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to initially infect macrophages and dendritic cells of the airways using the signaling lymphocytic activation molecule (SLAM, CD150) as receptor. These cells then cross the respiratory epithelium and ferry the infection to lymphatic organs where MV replicates vigorously. How and where the virus crosses back into the airways has remained unknown. However, certain carcinoma cell lines have been described to be either permissive for wt MV infection, or not (Leonard VHJ et al. 2008). Therefor, we decided to compare the expression pattern of permissive and non-permissive cell lines by micro array analysis. Based on functional analyses of surface proteins preferentially expressed on virus-permissive epithelial cell lines, we identified nectin-4 (poliovirus-receptor-like-4) as a candidate receptor.

overall_design: The dataset comprises 21 samples divided into seven sample groups each representing 3 biological replicates of one out of 7 cell lines.

first: Mathieu

last: Mateo

first: Patrick

last: Sinn

first: Steffen

last: Prüfer

first: Katharina

last: Uhlig

first: Vincent

middle: H

last: Leonard

first: Chanaka

middle: K

last: Navaratnarajah

first: Marie

last: Frenzke

first: Xiao

middle: X

last: Wong

first: Bevan

last: Sawatsky

first: Shyam

last: Ramachandran

first: Paul

last: McCray

first: Klaus

last: Cichutek

first: Veronika

last: von Messling

first: Marc

last: Lopez

first: Roberto

last: Cattaneo


title: Pre-miR-375_A549 vs. Pre-miR-NC#2 (Ambion) _A549

status: Public on Oct 31 2011

city: Nagoya

first: Osada

last: Hirotaka

state: Aichi

address: 1-1 Kanokoden, Chikusa-ku

country: Japan

institute: Aichi Cancer Center Research Institute

summary: We investigated the functional significance of ASH1-inducible miR-375 in terms of biologic phenotypes of ASH1-positive lung cancer cells. To this end, we conducted genome-wide expression profiling analysis of miR-375-transfected A549 cells.

overall_design: Microarray analysis using a Whole Human Genome 4 x 44K Microarray G4112F (Agilent) was conducted to examine changes in expression of potential target genes of miR-375 by transfection of Pre-miR-375 or Pre-miR-NC#2 (Ambion) in A549 cells, which were then harvested at 12, 24, 48, and 96 hours after transfection.

first: Eri

last: Nishikawa

first: Hirotaka

last: Osada

first: Yasumasa

last: Okazaki

first: Chinatsu

last: Arima

first: Shuta

last: Tomida

first: Yoshio

last: Tatematsu

first: Ayumu

last: Taguchi

first: Yukako

last: Shimada

first: Kiyoshi

last: Yanagisawa

first: Yasushi

last: Yatabe

first: Shinya

last: Toyokuni

first: Yoshitaka

last: Sekido

first: Takashi

last: Takahashi


title: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Illumina]

city: Houston

first: Paul

last: Webb

state: Texas

department: Diabetes Research Center

institute: Methodist Hospital Reseach Institute

summary: Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TRβ subtype versus TRα, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TRβ, HepG2.  We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TRβ to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare.

overall_design: We treated 9-week old euthyroid male C57/Bl6 mice with vehicle or ligand (T3 or GC-1) by a single oral gavage (n=5 per treatment) and also performed a similar study in which mice were first made hypothyroid by two week feeding on iodine deficient diet (n=3-4 per treatment), analyzing mRNA 24h post treatment [Illumina]. We also treated HepG2 with vehicle or 10nM ligand (T3 or GC1; n=3 / treatment), analyzing mRNA 24h post treatment [Affymetrix].

first: D

last: Sieglaff

first: P

last: WEbb


title: Identification of a neuronal gene expression signature:  Role of cell-cycle arrest in murine neuronal differentiation in vitro

city: La Jolla

first: Dan

last: Zhou

address: CMG 103, 9500 Gilman Drive, MC0735

department: Pediatrics

institute: University of California, San Diego, School of Medicine

summary: Stem cells are a potential key strategy for treating neurodegenerative diseases in which the generation of new neurons is critical. A better understanding of the characteristics and molecular properties of neural stem cells (NSC) and differentiated neurons can help in assessing neuronal maturity and possibly in devising better therapeutic strategies. We have therefore performed an in-depth gene expression profiling study of the C17.2 NSC line and primary neurons (PN) derived from embryonic mouse brains. Microarray analysis revealed a neuron-specific gene expression signature that distinguishes PN from NSCs, with elevated levels of transcripts involved in neuronal functions such as neurite development, axon guidance, in PN. The same comparison revealed decreased levels of multiple cytokine transcripts such as IFN, TNF, TGF, and IL. Among the differentially expressed genes, we found a statistically significant  enrichment of genes in the ephrin, neurotrophin, CDK5 and actin pathways which control multiple neuronal-specific functions. Furthermore, genes involved in cell cycle were among the most significantly changed in PN. In order to better understand the role of cell cycle arrest in mediating NSCs differentiation, we blocked the cell cycle of NSCs with Mitomycin C (MMC)  and examined cellular morphology and gene expression signatures. Although these MMC-treated NSCs displayed a neuronal morphology and expressed some neuronal differentiation marker genes, their gene expression patterns was very different from primary neurons. We  conclude that: 1) Fully differentiated primary neurons display a specific neuronal gene expression signature; 2) cell-cycle block in NSC does not induce the formation of fully differentiated neurons; 3) Cytokines such as IFN, TNF, TGF and IL are part of normal NSC function and/or physiology; 4) Signaling pathways of ephrin, neurotrophin, CDK5 and actin, related to major neuronal features, are dynamically enriched in genes showing changes in expression level.

overall_design: Gene expression profiles in neuronal stem cell, mitomycin-treated neuronal stem cells and primary neuronal cultures were compared to examine cellular morphology and gene expression signatures during neuronal differentiation.

first: Hady

last: Felfly

first: Jin

last: Xue

first: Gabriel

last: Haddad


title: Simultaneous analysis of tumor and stromal gene expression profiles from xenograft models

city: Miami

first: Jennifer

last: Clarke

state: FL

address: 1120 NW 14th Street

department: Epidemiology and Public Health

institute: University of Miami

summary:
Identifying the gene expression alterations that occur in both the tumor and stroma is essential to understanding tumor biology. We have developed a dual-species microarray analysis method that allows the dissection of both tumor and stromal gene expression profiles from xenograft models, based on limited interspecies cross-hybridization on Illumina gene expression beadchips. This methodology allows for simultaneous genome-wide analysis of gene expression profiles of both tumor cells and the associated stromal tissue.
Data is provided regarding the crosshybridization of mouse liver RNA on human microarray, and MDA-MB-231 breast cancer cell line RNA on mouse microarray. Data is also provided for comparisons of MDA-MB-231 gene expression in vitro vs. in vivo, and mouse liver gene expression in control mice vs. stroma from MDA-MB-231 xenograft liver metastasis in tumor bearing mice

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: A total of 18 samples were analyzed. Samples consist of 6 different types with each type in triplicate. Types are (1) MDA-MB-231 cell line grown in vitro and arrayed on mouse chips, (2) mouse liver from NOD/SCID mice arrayed on human chips, (3) MDA-MB-231 cell line grown in vitro arrayed on human chips, (4) MDA-MB-231 xenograft liver metastasis arrayed on human chips, (5) mouse liver from NOD/SCID mice arrayed on mouse chips, and (6) MDA-MB-231 xenograft liver metastasis arrayed on mouse chips. The overall design had three objectives: (1) to determine crosshybridizing probes based on sample types 1, 2, 3, and 5, (2) detect stromal and tumor expression using sample types 4 and 6, and (3) determine genes differentially expressed in tumor or metastasis compared to normal by comparing sample types 3 and 4 and comparing sample types 1 and 5.

first: Elizabeth

last: Iorns


title: Global gene expression analysis in murine iPS cells derived with mouse and human Nanog orthologs

status: Public on Oct 24 2011

city: Cambridge

first: Jose

last: Silva

state: Cambridgeshire

address: Tennis Court Road

department: Biochemistry

institute: Wellcome Trust Centre for Stem Cell Research

summary: Nanog null neural stem (NS) cells were reprogrammed to naive pluripotency in 2i/LIF conditions with mouse (m) Nanog and human (h) Nanog. Global gene expression in resulting iPS cells was compared to embryonic stem (ES) cells and nanog null NS cells.

overall_design: Murine iPS cells derived with mouse nanog iPS and human nanog iPS and then compared to embryonic stem cells and nanog null neural stem cells (3 replicates each).

first: Thorold

middle: W

last: Theunissen

middle: C


title: Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

first: Natalia

last: Shulzhenko

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

overall_design: Refer to individual Series


title: Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes

status: Public on Oct 23 2011

city: Salt Lake City

first: Alana

last: Welm

state: UT

address: 2000 Circle of Hope

department: Oncological Sciences

institute: Huntsman Cancer Institute / University of Utah

type:
Expression profiling by array
Genome variation profiling by SNP array


title: The role of HIF in FH-associated renal neoplasia

city: Oxford

first: Natasha

last: Sahgal

address: Old Road Campus

department: Ludwig Institute of Cancer Research

institute: University of Oxford

summary: Fumarate hydratase (FH) mutations predispose to renal cysts cancer. These cancers overexpress hypoxia-inducible factor-alpha (Hif-1a). We have generated a conditional Fh1 (mouse FH) knockout mice that develop renal cysts and overexpress Hif-1a. In order to identify the contribution of Hif-1a to cyst formation we have intercrossed our mice with conditional HIf-1a KO mice.

overall_design: We intercrossed Fh1/Hif1a mice with kidney specific cre recombinase (Ksp-Cre) and analysed kidney cyst formation. RNA was extracted from cysts from 4xFh1 KO, 4xFh1/Hif-1a KO and 4 control mice. For each comparison littermates were used and the animals were aged 15 weeks i.e. early cystic disease.

first: Julie

last: Adam

first: Emine

last: Hatipoglu

first: Linda

last: O'Flaherty

first: Nicola

last: Ternette

first: Helen

last: Lockstone

first: Dilair

last: Baban

first: Emma

last: Nye

first: Gordon

last: Stamp

first: Benedikt

last: Kessler

first: Norma

last: Frizzell

first: Chris

last: Pugh

first: Mona

last: El-Bahrawy

first: Peter

last: Ratcliffe

first: Patrick

last: Pollard


title: Molecular markers of predictive value associated with low birth weight

status: Public on Oct 21 2011

city: Singapore

first: Emilia

last: Tng

address: 30 Medical Drive

country: Singapore

institute: Singapore Institute for Clinical Sciences

summary: Sub-optimal fetal development is associated with an increased risk of developing cardiovascular disease, type 2 diabetes (T2D) and adiposity later in life. However, definitions of intrauterine growth restriction (IUGR) and small for gestational age (SGA) are based on simple statistical approaches that may misclassify infants with a normal developmental profile and vice versa. We used an unbiased global profiling approach to identify gene expression patterns in umbilical cord tissue from 38 infants and identified a set of 466 genes which separated the subjects into 2 distinct groups – one biased towards lower birth weight and one biased towards normal birth weight. The data suggest that approximately 30% of children of normal size have a molecular profile more typical of impaired fetal development and who may be on a programmed trajectory. Differences in expression between the two groups encompassed 384 upregulated and 82 downregulated genes. Molecular profiling at birth may have utility in identifying markers that potentially reflect antenatal developmental and may be predictive of future phenotypic development after birth. Importantly, it may provide an alternative to the current classification of infants using birth weights.

overall_design: RNA from umbilical cord tissue from full term neonates was extracted and hybridized. Separation into 2 distinct groups, independent of birth weight, but based solely on gene expression levels was analysed by Genespring. After appropriate statistical analysis, one group was keenly associated with a higher birth weight (22 samples) while the other was associated with a lower birth-weight (18 samples). Technical replicates were included for all 40 samples.

last: Gluckman

first: Siew

last: Goh

first: Yiong

last: Chan

first: Kenneth

last: Kwek

first: Yap

middle: S

last: Chong

first: Allan

middle: M

last: Sheppard


title: Gene Expression Profile of Cisplatin Resistance in Ovarian Cancer Cell Lines

status: Public on Nov 05 2011

city: Kingston

first: Alexandria

last: Haslehurst

state: ON

address: Richardson Laboratory 88 Stuart St

institute: Queen's University

summary: To determine the signaling networks that are dysregulated in platinum-resistant ovarian cancer, gene expression data were obtained from, and compared between, the ovarian cancer cell line, A2780, and its cisplatin-resistant derivative, A2780cis.

overall_design: Gene expression data from a cisplatin-sensitive ovarian cancer cell line (A2780) were collected and compared to gene expression data from a cisplatin-resistant cell line (A2780cis). 6 independent experiments were completed for both the sensitive and resistant cell lines.

first: Harriet

last: Feilotter

first: Jeremy

last: Squire

first: Paul

last: Park

first: Madhuri

last: Koti


title: Global gene expression analysis in murine iPS cells derived with mouse, chick and zebrafish Nanog orthologs

first: Jose

last: Silva

summary: Nanog null  neural stem (NS) cells were reprogrammed to naive pluripotency in 2i/LIF conditions with chick (c) and zebrafish (z) Nanog orthologs. Global gene expression was compared to iPS cells derived with mouse (m) Nanog.

overall_design: Murine iPS cells derived with zebrafish nanog, chick nanog, and mouse nanog orthologs (2 replicates each).

first: Thorold

last: Theunissen


title: Gene expression profiles due to common seed sequence of members of miR-302/372/373/520 family miRNAs and dsEcad640 in human PC-3 cells

status: Public on Oct 14 2011

city: Tokyo

first: Kumiko

last: Ui-Tei

address: 2-11-16 Yayoi Bunkyo-ku

department: Biophysics and Biochemistry, Graduate School of Science

institute: The University of Tokyo

summary: To examine the genome-wide gene regulation due to the common seed sequence of the members of miR-302/3272/3273/520 family miRNAs and dsEcad640, we performed microarray profiling of gene expression by the transfection of chemically synthesized dsEcad640, miR-302a,miR-372, miR-373, miR-520c,and miR-520f duplexes into PC-3 cells.

overall_design: Chemically synthesized dsEcad640, miR-302a, miR-372, miR-373, miR-520c,and miR-520f duplexes were transfected into PC-3 cells. At 24 hours after  transfection,the total RNA was extracted using the RNeasy Mini Kit (Qiagen). As a control, mock transfected cells treated with transfection reagent  without siRNA and miRNA were used.Transfection was carried out four times independently, and the RNA quality was examined using Bioanalyzer (Agilent).  Mixed RNA samples (150 ng total) of four experiments were used for the microarray analysis. After cDNA was synthesized with the Agilent One Color  Spike Mix Kit, cRNA was prepared using the Quick Amp Labeling Kit (Agilent), labeled with Cy-3, and purified with the RNeasy Mini Kit (Qiagen).The cRNA  was hybridized against the Agilent Whole Human Genome Microarray (4 × 44 K multipack format) at 65°C for 17 hours, then washed with Gene Expression Wash Buffer 1 and Wash Buffer 2 (Agilent) in 0.005% Triton X-102. The microarray slide was scanned using the DNA Microarray Scanner (Agilent) and quantified using Feature Extraction Software (Agilent).

first: M

last: Mazda

first: K

last: Nishi

first: Y

last: Naito


title: Effect of heme on macrophage gene expression

status: Public on Oct 19 2011

city: London

first: Joseph

middle: J

last: Boyle

address: Du Cane Rd

department: NHLI

institute: Imperial College London

summary: Heme generates an atheroprotective macrophage phenotype in humans, in coronary atherosclerotic intraplaque hemorrhage. We carried out microarray analysis to define this phenotype and assess its likely mechanism.

overall_design: Paired samples, at 2 time points, on monocytes from n=4 human donors

first: J


title: Id1 maintains embryonic stem cell self-renewal by upregulation of Nanog and repression of Brachyury expression

city: New York

first: Jeffrey

last: Zhao

state: NY

address: 1275 York Avenue

department: Genomics Core

institute: Memorial Sloan Kettering Cancer Center

summary: Understanding the mechanism by which embryonic stem (ES) cells self-renew is critical for the realization of their therapeutic potential.  Previously it had been shown that in combination with LIF, Id proteins were sufficient to maintain mouse ES cells in a self-renewing state.  Here we investigate the requirement for Id1 in maintaing ES cell self-renewal and blocking differentiation.  We find that Id1-/- ES cells have a propensity to differentiate and a decreased capacity to self-renew.  Chronic or acute loss of Id1 leads to a down-regulation of Nanog, a critical regulator of self-renewal.  In addition, in the absence of Id1, ES cells express elevated levels of Brachyury, a marker of mesendoderm differentiation.  We find that loss of both Nanog and Id1 is required for the up-regulation of Brachyury, and Id1 maintains Nanog expression by blocking the expression of Zeb1, a repressor of Nanog transcription.  These results identify Id1 as an important factor in the maintenance of ES cell self-renewal and suggest a plausible mechanism for its control of lineage commitment.

overall_design: Wild type and Id1-/- ES cells were grown on gelatin under normal self-renewing conditions (in the presence of serum and LIF).

first: Elizabeth

last: Romero-Lanman

first: Yvette

last: Chin

first: Svetlana

last: Pavlovic

first: Robert

last: Benezra


title: Gene expression analysis of T cell subsets from MS patients undergoing autologous hematopoietic stem cell transplantation reveals significant changes in immune function

status: Public on Nov 03 2011

first: Alessandra

middle: De Paula Alves

last: Sousa

address: Du Cane Road

department: Medicine

summary: Multiple sclerosis is an immune mediated disease of the central nervous system. High-dose immunosuppression therapy followed by autologous hematopoietic stem cell transplantation (HDI/AHSCT) has emerged in the past few years as a new treatment strategy in patients with severe MS and refractory to conventional treatment. We characterized the molecular profile of T cells  during immune reconstitution of these patients. Total RNA of CD4+ and CD8+ T cells from eight MS patients before transplantation and four patients at 6 months, 1 and 2 years after transplantation was processed for DNA microarray analysis. We investigated the molecular and biological function of DEG using bioinformatics tools and selected genes involved with immune response to measure quantitative gene expression by Real-time PCR.  In CD8+ T cells, we measured the levels of expression of 23 genes modulated after transplantation:  nine transcriptional factors (LEF1, FOXD1, CEBPD, JUN, JUNB, RELB, IFI16, AEBP1) including the translational factor PDCD4, the chemokine CCR7 and adhesion molecule L Selectin, three TNF superfamily members (TNFRSF4, TNFRSF19L, LTβ), seven genes involved with molecular signaling (SOCS1, SOCS3, DGKH, CSNK1L1, IKBα, IKBβ, IKBε), and the immune cell receptors CD47 and SIRPG. In CD4+ T cells, we evaluated the relative level of expression of STAT3, FcRL3, PDCD1, DGKH, CSNK1L1, L Selectin, CCR7 and PIAS3 that were all modulated after transplantation. We found significantly transcriptional changes in both T cells subsets during the first 2 years post-transplantation, but the analysis of CD8+ T cells revealed more extensive changes of genes involved in effector immune responses.

overall_design: In order to study the transcriptional changes in T cell subsets from MS patients submitted HID/HSCT, immunomagnetically purified CD4+ and CD8+ T-cells from the peripheral blood of 8 patients before transplantation and 4 patients 6 months, 1 year and 2 years after tranplantation, as well as from 4 healthy controls were isolated and processed the microarray assay according Agilent's protocol. The differential expressed genes, molecular characterization and networks analysis were evaluated using robust bioinformatic tools, then  the real time PCR was done to validate the 27 immune related-genes.

middle: P

first: Kelen

last: Malmegrim de Farias

first: Rodrigo

middle: A

last: Panepucci

first: Doralina

last: Brum

first: Antonio

last: Santos

first: Amilton

last: Barreira

first: Amélia

middle: G

last: Araujo

first: Dimas

middle: T

last: Covas

first: Maria

last: Oliveira

first: Daniela

last: Moraes

first: Fabiano

last: Pieroni

first: Paolo

last: Muraro

first: Júlio

last: Voltarelli


title: Gene expression profiles of DLD1 cells in which GATA6 or LGR5 expression was suppressed.

status: Public on Oct 18 2011

first: Tetsu

last: Akiyama

address: 1-1-1, Yayoi, Bunkyo-ku

department: Institute of Molecular and Cellular Biosciences

institute: Tokyo University

summary: Mutations in APC or β-catenin that cause aberrant activation of Wnt signaling are responsible for the initiation of colorectal tumor development. LGR5 is specifically expressed in stem cells of the intestine, stomach and hair follicle, and plays essential roles in maintaining tissue homeostasis. LGR5-positive stem cells have been shown to be responsible for the intestinal adenoma initiated by some mutations in APC . Furthermore, it has recently been reported that Lgr5, which is associated with the Frizzled/Lrp Wnt receptor complex, interacts with R-spondins and thereby activates Wnt signaling. However, the function of LGR5 in colorectal tumorigenesis has been unclear. Here we show that LGR5 is required for the tumorigenicity of colorectal cancer cells. We also show that the transcription factor GATA6 directly enhances the expression of LGR5.

overall_design: DLD1 cells were infected with a lentivirus expressing an shRNA targeting GATA6 or LGR5.

first: Kenzui

last: Taniue

first: Tomoatsu

last: Hayashi

first: Shinnosuke

last: Tsuji

first: Yoshihiro

last: Kawasaki


title: Gene expression profiles of T cell fraction enriched for donor antigen-reactive T cells in skin allografted recipient mice (II)

status: Public on Oct 13 2011

city: Seoul

first: Dong-Gyun

last: Lim

address: 245 Eulji-ro, Jung-gu

country: South Korea

institute: National Medical Center, Research Institute

summary: Measurement of specific gene expression in clinical samples is a promising approach for monitoring the recipient immune status to the graft in organ transplantation. Identification of biomarker genes closely associated with tolerance or rejection is critical for this monitoring protocol. Unlike previous studies, our microarray analysis focused on donor antigen-reactive T cells, which were prepared by collecting CD69+ T cells from cocultures of recipient peripheral T cells and donor antigen-presenting cells. A comparison of different recipient groups enabled us to identify several tolerance- and rejection-correlated biomarker genes, including previously unknown genes. By measuring biomarker gene expression in the CD69+ T cell fraction using quantitative reverse-transcription polymerase chain reaction, we were able to precisely detect the immune status of recipients relative to their graft.

overall_design: Full-thickness donor (BDF1; C57BL/6 x DBA/2) tail skin was grafted onto recipient (C57BL/6) mice. Tolerance to the graft was induced by donor specific transfusion combined with administration of anti-CD40L Ab (MR-1). Total T lymphocytes were prepared from spleen and lymph nodes of tolerant recipient mice on day 100 after skin transplantation, untreated recipient mice on day 7, and ungrafted, healthy C57BL/6 mice and used as tolerant, rejecting and naïve T lymphocyte samples, respectively. In order to isolate alloantigen-reactive cells, T lymphocytes were cocultured with donor T cell-depleted splenocytes for 20-21 hours and then separated into two subpopulations based on CD69 expression using fluorescence cell sorter. Total RNA was extracted from these CD69+ and CD69- T cells and subjected to microarray using Illunima MouseWG-6 Expression BeadChip. All data analysis and visualization of differentially expressed genes was conducted using Illumina GenomeStudio v2009.2 (Gene Expression Module v1.5.4) and R statistical language v2.6.1.  Candidate tolerance genes were defined as the common genes satisfying the following criteria; 1) 1.5 fold or higher expression in CD69+ T cells isolated from tolerant recipients than those from naïve mice, 2) 1.5 fold or higher expression in CD69+ T cells than CD69- T cells from tolerant mice, 3) 500 or higher average signal measured in CD69+ T cells from tolerant mice. The criteria for candidate rejection genes were 1) 1.5 fold or higher expression in CD69+ T cells isolated from rejecting recipients than those from tolerant mice, 2) 1.5 fold or higher expression in CD69+ T cells than CD69- T cells from rejecting mice, 3) 500 or higher average signal measured in CD69+ T cells from rejecting mice.

first: Youn-Hee

last: Park

first: Sung-Eun

last: Kim

first: Eun-Jung

last: Jung

first: Seong-Hee

last: Jeong

first: Su-Jin

last: Shin

first: Chan-Sik

first: Duck-Jong

last: Han

first: Song-Cheol


title: Gene expression profiles of T cell fraction enriched for donor antigen-reactive T cells in skin allografted recipient mice


title: MicroRNA-145 Regulates Human Corneal Epithelial Differentiation [Agilent-014850 array data]

status: Public on Oct 10 2011

city: Hong Kong

first: Gary

last: Yam

address: 147K Argyle St, Mongkok

institute: Chinese University of Hong Kong

summary:
To investigate the gene expression in human corneal epithelial overexpressing hsa-miR-145 by transfection , we have employed Whole Human Genome Oligo Microarray (Agilent) as a screening platform to identify gene regulation.
We discovered a differential gene expression in HCE cells transfected with hsa-mIR-145 against cells with scrambled sequences. Among them, genes related with corneal development, integrity, differentiation and inflammatory responses were found and this was validated by real-time PCR.

overall_design: HCE cells transfected with hsa-miR-145 or scrambled sequences were collected at 24 hours after transfection.  Total RNA was extracted by Trizol/chloroform and purified with RNeasy mini spin column. RNA samples with 28S/18S ratios in the range of 1.4 to 1.8 were used for expression RNA profiling using Whole Human Genome Oligo Microarray (Agilent).

first: Chi-Pui

last: Pang


title: Gene Expression profiling of Myc-induced lymphomagenesis

city: Tampa

first: John

middle: Lamoine

last: Cleveland

address: 12902 USF Magnolia Drive

institute: H. Lee Moffitt Cancer Center

summary: The ability of oncogenes to provoke cancer is harnessed by regulators that control cell proliferation or induce apoptosis, and bypass of these checkpoints is a hallmark of malignancies. Myc oncoproteins are overexpressed in ~70% of all cancers and induce numerous transcription targets that regulate cell growth, metabolism, and the ribosome machinery. We used the Eμ-Myc mouse model from which one can directly compare expression profiles of wild type versus Myc-expressing B220+ pre-malignant lymphocytes and also queried differences in gene expression that ensue following the neoplastic switch to lymphoma (Nilsson et al., 2005 - PMID:15894264 and Keller et al. 2010 - PMID:20598117).

overall_design: Wild type and precancerous Eμ-Myc transgenic B cells (from 4-6 week old littermates), and lymphomas from 13 independent  Eμ-Myc mice  were investigated.  These samples were used for subsequent RNA purification, labeling and hybridization to MOE430A Affymetrix arrays.

middle: L

first: Mohammad

last: Fallahi

first: Jonas

last: Nilsson

first: Mark

last: Hall

first: Robert

last: Rounbehler


title: Global gene expression analysis in murine iPS cells derived with Nanog orthologs

first: Jose

last: Silva


title: Human keratinocytes stimulated with IL-17C

status: Public on Oct 12 2011

city: South San Francisco

first: Alex

last: Abbas

state: CA

address: 1 DNA Way

department: Bioinformatics

institute: Genentech, Inc.

summary:
IL-17C is important for the pathogenesis of inflammatory diseases such as IBD and psoriasis. We found that IL-17C is highly induced in a murine model of psoriasis. Recent results suggest that IL-17C can target epithelial cells that express both IL-17RA and IL-17RE receptor chains.
Here we identify genes induced in response to IL-17C treatment of human keratinocytes to provide the tools for dissection of the IL-17C signaling pathway.

overall_design: Human keratinocytes, HEKn, were incubated in the absence (n = 3) and presence (n = 5) of 500 ng/ml recombinant human IL-17C for 3 and 24 hours. Whole RNA was isolated via RNeasy kit (Qiagen).

first: Alexander

middle: R

first: Rajita

last: Pappu

first: Vladimir

last: Ramirez-Carrozzi

first: Jason

last: Hackney


title: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1

first: Paul

last: Webb

first: D

last: Sieglaff

first: P

last: WEbb


title: Genome-wide analysis of gene expression of Th1 and Tfh LCMV-specific Smarta  CD4 T cell populations

status: Public on Oct 05 2011

city: New Haven

first: Hailong

last: Meng

state: CT

address: 300 George Str

institute: Yale University

summary: In this study, we sought to distinguish phenotypically and functionally distinct virus-specific effector CD4 T cell subsets that form during acute lymphocytic choriomeningitis virus (LCMV) infection and to examine their ability to develop into memory T cells.  To further characterize the effector subsets and identify genetic pathways and transcription factors involved in their differentiation, we performed genome-wide gene expression profiling of the three day 8 effector cell populations: (1) PSGL1hi Ly6Chi, (2) PSGL1hi Ly6Clo and (3) PSGL1lo Ly6Clo Smarta CD4 T cells along with (4) day 60 memory PSGL1hi and (5) naïve Smarta CD4 T cells using Illumina BeadChips. Results of this microarray confirmed the validity of our phenotyping by flow cytometry in many ways and showed distinct gene signatures for the three effector subsets.

overall_design: DNA microarray analysis was performed on two or three independent samples of five different Smarta CD4 T cell populations: (1) naïSGL1lo, (3) day 8 PSGL1hi Ly6Clo, (4) day 8 PSGL1hi Ly6Clo and (5) day 60 PSGL1hi memory cells.

first: H

last: Marshall

first: S

last: Kaech

last: Kleinstein


title: Expression profile of carcinosarcoma (CS), endometrioid adenocarcinoma (EC) and sarcoma (US) of uterine corpus

status: Public on Oct 01 2011

first: Tatsuyuki

last: Chiyoda

address: 35 Shinanomachi Shinjuku-ku

department: Obstetrics and Gynecology

institute: Keio University School of Medicine

summary: To examine the simlarity of CS, EC and US, we performed microarray analysis of frozen tissues of 46 patients (14 CS, 24 EC and 8 US).

overall_design: Frozen tissues of 46 patients (14CS, 24EC and 8US) were subjected to cDNA microarray analysis.

first: T

last: Tsuda

last: Aoki


title: Human glioma cells treated with irradiation and/or CCI-779

status: Public on Sep 20 2011

city: Heidelberg

first: Jan

last: Gronych

address: Im Neuenheimer Feld 280

department: Molecular Genetics

institute: German Cancer Research Center

summary: Gene expression profiling of human glioma cell line LN-308. Cells were treated with the mTOR inhibitor CCI-779 or irradiated with a single dose of 4 Gy or a combination of both. The objective of this studywas to evaluate CCI-779 as a radio-sensitizing agent and to elucidate the underlying mechanisms.

overall_design: Irradiated, CCI-779-, DMSO- (vehicle control) or combination treated LN-308 samples were hybridized against pooled untreated LN-308 samples as reference (CCI+Irradiation vs. Ref; CCI vs. Ref; DMSO+Irradiation vs Ref; DMSO vs. Ref).Three independent replicates were generated for each treatment and control, respectively.

first: Markus

last: Weiler


title: Gene-expression profile in a series of  non-Hodgkin lymphoma (NHL) patients

status: Public on Oct 17 2011

city: Madrid

first: Cristina

last: Gomez-Abad

address: Melchor Fernández Almagro, 3

department: Molecular Pathology Program

institute: CNIO

summary: PIM serine/threonine kinases are overexpressed, translocated or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types, and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBLC), follicular lymphoma (FL), marginal zone lymphoma-MALT type (MZL-MALT), chronic lymphocytic leukemia (CLL) and nodal marginal zone lymphoma (NMZL) cases. Increased PIM2 protein expression was associated with an aggressive clinical course in ABC-DLBCL patients. Pharmacological and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity, and indicated the involvement of PIM2 kinase in regulating mTORC1. The simultaneous genetic inhibition of all three PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.

overall_design: Gene-expression profiling was conducted in a series of 114 B-cell non-Hodgkin lymphoma patients (DLBCL, FL, MALT, MCL, CLL and NMZL).  Seven freshly frozen lymph nodes and six freshly frozen reactive tonsils were used as controls.

last: Gómez-Abad

first: María

middle: E

last: Rodríguez

first: Miguel

last: Piris


title: Transcriptional profiling and functional characterization of Schistosoma japonicum-stimulated Alternatively Activated Macrophages

city: Herston

first: Melissa

middle: Louise

last: Burke

address: 300 Herston Road

department: Division of Infectious Diseases and Immunology

institute: Queensland Institute of Medical Research

summary: Alternatively activated macrophages (AAMφs) play important roles in a number of Th2 driven pathologies including asthma and allergy, and a number of parasitic infections. Our  studies, and those of others, investigating the pathologies associated with infection with the helminth Schistosoma japonicum implicate a role for AAMφs in fibrosis and immunomodulation.. In the present study we show  that S. japonicum-secreted egg antigens are able to induce the alternative activation of macrophages as characterised by the induction of Chi3l3 and Arg1 expression. Retnla, another common marker of AAMφs, was not consistently induced in these macrophages suggesting that the specific function of these cells may differ to those induced by S. mansoni and other parasites. Closer examination of the gene expression profile and functionality of these cells identified pathways independent of Retnla expression that could  be important for their immunomodulatory activity such as modulating expression of T-cell co-stimulatory molecules and chemokines. In vivo generated S. japonicum soluble egg antigen stimulated AAMφs also exhibited a reduction in their phagocytic ability likely related to the induction of IL4 and decreased expression of cell surface receptors. Additionally these macrophages exhibited reduced  expression of Toll-like receptors (TLRs) and an associated reduction in responsiveness to stimulation with TLR ligands. We did not observe pathways that would suggest that  AAMφs have a direct profibrotic activity. Taken together, these data describe a mechanism by which alternative activation of macrophages may be induced during S. japonicum infection and highlight the importance of the context of activation in directing AAMφ phenotype and function.

overall_design:
The gene expression profile of Schistosoma japonicum soluble egg antigen (SEA)-stimulated macrophages was compared with that of PBS stimulated controls. Macrophages were isolated from the peritoneal cavity of BALB/c mice (n=6 per group) stimulated by intraperitoneal injection with SEA or PBS. The macrophages were pooled and RNA was extracted from these cells. Microarray analysis was performed on cRNA synthesised from total RNA derived from these macrophages. The experiment was performed twice creating two biological replicates.

Fold-change (relative to the respective PBS control) reported in supplementary file linked below.

first: Sheila

last: Donnelly

first: Donald

last: McManus

first: John

last: Dalton

first: Geoffrey

middle: N

last: Gobert


title: Genome-wide analysis of induced expression of TBX3 in the atrial appendage of the heart and controls.

city: amsterdam

first: Martijn

last: Bakker

state: NH

address: meibergdreef 15

department: heart failure research center

institute: academic medical center

summary:
to study the effect of induced expression of TBX3 within the atrium of the heart
Background: Treatment of congenital or acquired disorders of the sinus node or atrioventricular node requires insight into the molecular mechanisms for the development and homeostasis of these pacemaker tissues. In the developing heart, transcription factor TBX3 is required for pacemaker and conduction system development. Here, we explore the role of TBX3 in the adult heart and investigate whether TBX3 is able to reprogram terminally differentiated working cardiomyocytes into pacemaker cells. This would be an attractive approach in biological pacemaker formation.     Methods and results: TBX3 expression was ectopically induced in cardiomyocytes of adult transgenic mice. Expression analysis revealed an efficient switch from the working myocardial expression profile to that of the pacemaker myocardium. This included suppression of genes encoding gap junction subunits (Cx40, Cx43), the cardiac Na+ channel (NaV1.5; INa) and inwardly rectifying K+ ion channels (Kir-genes; IK1). Concordantly, we observed conduction slowing in these hearts, and reductions in INa and IK1 in cardiomyocytes isolated from these hearts. The reduction in IK1 resulted in a more depolarized maximum diastolic potential, thus enabling spontaneous diastolic depolarization. Neither ectopic pacemaker activity nor pacemaker current, If, were observed. Lentiviral expression of TBX3 in ventricular cardiomyocytes resulted in conduction slowing and development of heterogeneous phenotypes, including depolarized and spontaneously active cardiomyocytes.     Conclusions: TBX3 partially reprograms terminally differentiated working cardiomyocytes into pacemaker-like cells and induces important pacemaker properties. The ability of TBX3 to reduce intercellular coupling to overcome current-to-load mismatch and the ability to reduce IK1 density to enable diastolic depolarization, are very promising TBX3 characteristics for biological pacemaker formation strategies.

overall_design: 5 TBX3 expressing left atrial appendage samples (Tamoxifen-treated Myh6MCM;CTBX3 adult male mice) and 6 controls ((Tamoxifen-treated Myh6MCM adult male mice)

first: Vincent

last: Christoffels

first: Henk

last: Buermans

first: Peter

last: 't Hoen


title: Patient-derived tumor grafts authentically reflect tumor pathology, growth, metastasis, and disease outcomes (expression)

first: Alana

last: Welm

address: 2000 Circle of Hope

institute: Huntsman Cancer Institute / University of Utah

summary:
Development and pre-clinical testing of new cancer therapies is limited by the scarcity of in vivo models that authentically
reproduce tumor growth and metastatic progression. We report new models for breast tumor growth and metastasis, in the form
of transplantable tumors derived directly from individuals undergoing treatment for breast cancer. These tumor grafts represent
the diversity of human breast cancer and maintain essential features of the original tumors, including metastasis to specific
sites.  Co-engraftment of primary human mesenchymal stem cells maintains phenotypic stability of the grafts and increases tumor
growth by promoting angiogenesis. We also report that tumor engraftment is a prognostic indicator of disease outcome for newly
diagnosed women; orthotopic breast tumor grafting marks a step toward individualized models for tumor growth, metastasis,
and prognosis. This bank of tumor grafts also serves as a publicly available resource for new models in which to study the biology of
breast cancer.

overall_design: Single replicates of total RNA from 12 human breast cancer tumors and xenografts of those tumors in immunodeficient mice were hybridized to Agilent Whole Human Genome expression arrays.

first: Yoko

last: DeRose

first: Guoying

last: Wang

first: Yi-Chun

last: Lin

first: Philip

last: Bernard

first: Saundra

last: Buys

first: Mark

last: Ebbert

first: Rachel

last: Factor

first: Cindy

last: Matsen

first: Brett

last: Milash

first: Edward

last: Nelson

first: Leigh

last: Neumayer

first: Lor

last: Randall

first: Inge

last: Stijleman

first: Bryan


title: BMP4 signalling directs primitive endoderm-derived XEN cells to an extraembryonic visceral endoderm identity

status: Public on Sep 14 2011

first: Yupu

last: Liang

address: 1230 York Avenue

institute: The Rockefeller University

summary: The visceral endoderm (VE) is an epithelial tissue in the early postimplantation mouse embryo that encapsulates the pluripotent epiblast distally and the extraembryonic ectoderm proximally. In addition to facilitating nutrient exchange before the establishment of a circulation, the VE is critical for patterning the epiblast. Since VE is derived from the primitive endoderm (PrE) of the blastocyst, and PrE-derived eXtraembryonic ENdoderm (XEN) cells can be propagated in vitro, XEN cells should provide an important tool for identifying factors that direct VE differentiation. In this study, we demonstrated that BMP4 signalling induces the formation of a polarized epithelium in XEN cells. This morphological transition was reversible, and was associated with the acquisition of a molecular signature comparable to extraembryonic (ex) VE. Resembling exVE which will form the endoderm of the visceral yolk sac, BMP4-treated XEN cells regulated hematopoiesis by stimulating the expansion of primitive erythroid progenitors. We also observed that LIF exerted an antagonistic effect on BMP4-induced XEN cell differentiation, thereby impacting the extrinsic conditions used for the isolation and maintenance of XEN cells in an undifferentiated state. Taken together, our data suggest that XEN cells can be differentiated towards an exVE identity upon BMP4 stimulation, and therefore represent a valuable tool for investigating PrE lineage differentiation.

overall_design: Total RNA isolated in triplicate from XEN stem cell cultures that were untreated (samples 1-3) or treated with BMP4 growth factor (samples 4-6). Total RNA isolated in triplicate from XEN stem cells that were treated with BMP4 and were flow sorted as Afp::GFP-positive (samples 7-9) or Afp::GFP-negative (samples 10-12).

first: Jerome

last: Artus

first: Anna-Katerina

last: Hadjantonakis


title: Gene expression profiling of colorectal carcinoma

status: Public on Sep 10 2011

city: Berlin

first: Qing

state: Berlin

address: Robert Rössle Str. 10

department: Surgical Oncology

institute: Charite-Berlin

summary: To identify the prognostic gene expression markers in early primary colorectal carcinomas, we analyzed genome-wide gene expression profiles using Agilent 4x44K oligonucleotide microarrays. By SVM we selected a gene signature which discriminated patients which later developed metastasis from patients with a good prognosis. Most of the genes that were found to be informative for patients’ distant recurrence were related to the patient’s immune response. Furthermore, our microarray data confirmed the specificity and sensitivity of the angiogenesis-related genes signature.

overall_design: Gene expression profiling of 67 specimens of 55 colorectal carcinomas, 7 normal and 5 adenomas  was studied.

first: Marion

last: Fehlker


title: Deep subcutaneous adipose tissue (dSAT) vs. superficial subcutaneous adipose (sSAT)

status: Public on Sep 01 2011

city: Paris

first: Edi

last: Prifti

state: IDF

address: 15, rue de l'école de Médecine

country: France

institute: INSERM UMRS-U872

summary: In addition to total body fat, the regional distribution and inflammatory status of enlarged adipose tissue are strongly linked to metabolic and cardiovascular complications of obesity. We recently showed that the severity of liver non-alcoholic histopathology in obese subjects increased with the amounts of macrophages in visceral adipose tissue (VAT), while no relation was found with the subcutaneous adipose tissue (SAT). In the abdominal region, SAT is anatomically divided into superficial (sSAT) and deep (dSAT) layers. The aim of the present study was to test the hypothesis that these distinct compartments differentially contribute to hepatic alteration in obesity.

overall_design: Total RNA was isolated from two different strata of human adipose tissue of 8 subjects.

first: Veronique

last: Pelloux


title: Genome-wide analysis of gene expression regulated by nucleolin in mouse embryonic stem cells

status: Public on Oct 20 2011

city: Shanghai

first: Ying

last: Jin

address: 225 South Chongqing Road

department: Shanghai Stem Cell Institute

institute: Shanghai Jiao Tong University School of Medicine

summary: To further explore the function and underlying mechanism of nucleolin in embryonic stem cells (ESCs), we compared the transcription profile of tetracycline (Tc)-inducible EGFP (as a control) or nucleolin siRNA expression-stable ESCs cultured with or without Tc for 3 days, and identified distinct classes of up- and down-regulated genes by nucleolin in mouse ESCs.

overall_design: Total RNA obtained from CGR8 ES cells stably integrated with Tc-inducible siRNA EGFP, nucleoin-1 or nucleolin-2 cultured with or without Tc for 3 days, and then hybridized to Illumina Sentrix Mouse-6 v2.0 BeadChips. Three replicates each condition.

first: Acong

last: Yang

first: Yin


title: Six-week-old R6/2 HD mouse striatum

city: Lausanne

first: Darlene

last: Goldstein

department: IMA

country: Switzerland

institute: EPFL

summary:
Wild-type CBAxC57BL/6 (6 weeks of age) and HD Exon 1 R6/2 CBAxC57BL/6 (6 weeks of age).  Control groups for two drug studies. All animals injected with normal saline 30-60 minutes prior to sacrifice.
Keywords: parallel sample

first: Ruth

last: Luthi-Carter

first: Thierry

last: Sengstag

first: Mauro

last: Delorenzi

first: Robert

last: Ferrante


title: Gene expression profiles in 132 laser microdissected colorectal cancer tissues

city: Beppu

first: Koshi

last: Mimori

state: Oita

address: 4546 Tsurumihara

department: Department of Surgery

institute: Kyushu university

summary: Tissues from another series of 132 patients with colorectal cancer were collected by laser micro-dissection with the Leica Laser Microdissection System (Leica Microsystems).

overall_design: Gene expression levels obtained from 132 microdissected colorectal tumors were compared with microdissected normal colon epitheliums. we used the commercially available Human Whole Genome Oligo DNA Microarray Kit (Agilent Technologies). Labeled cRNAs were fragmented and hybridized to an oligonucleotide microarray (Whole Human Genome 4×44K Agilent G4112F). Fluorescence intensities were determined with an Agilent DNA Microarray Scanner and were analyzed using G2567AA Feature Extraction Software Version A.7.5.1 (Agilent Technologies).

first: Masaki

last: Mori

first: Takehiko

last: Yokobori


title: MicroRNA-145 Regulates Human Corneal Epithelial Differentiation

first: Gary

last: Yam

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

overall_design: Refer to individual Series


title: The addition of chromosome 8 leads to characteristic dysregulation of gene expression on all chromosome and transformed-associated phenotypes

status: Public on Oct 08 2011

city: osaka

first: Hisakatsu

last: Nawata

institute: Kyoto University

summary: To examain effects of trisomy 8 on gene expression in normal human cells, we have employed whole genome microarray expression profiling. To study the effects of aneuploidy in normal human cells, we generated cells which are artificially trisomic chromosome 8 (trisomy 8) using human primary fibroblast cells by microcell-mediated chromosome transfer (HE35tri8 clones).

overall_design: Gene expression in trisomy 8 clones (HE35tri8-1, 2 and3) and euploid clones (HE35-1, 2 and 4). Three independent experiments were performed at each clone.

first: Kazuhiro

last: Daino

first: Genro

last: Kashino

first: Hiroyuki

last: Kugoh

first: Mitsuo

last: Oshimura

first: Yoshiya

last: Shimada

first: Keizo

last: Tano

first: Masami

last: Watanabe


title: Bystander response to 0.5 Gy of alpha-particles in a human 3-dimensional skin model in 16h after exposure to ionizing radiation

status: Public on Aug 31 2011

first: Alexandre

last: Mezentsev

address: 630 west 168th Street, VC 15-204

department: Dermatology

institute: Columbia University

summary: Ionizing radiation (IR) not only affects cells that are directly irradiated but also their non-irradiated neighbors, which show responses known as bystander effects. While bystander and direct responses have several common end points including apoptosis and micronucleation, chromatin remodeling and altered levels or activities of regulatory proteins, they can be quantitatively and qualitatively different. The majority of studies of radiation bystander effects have utilized 2-dimensional in vitro systems, but we have recently demonstrated such effects in EPI-200 (Mat-Tek, Ashland, MA), a 3-dimensional tissue model that precisely imitates the structure and function of human epidermis. Global gene expression is a powerful tool for uncovering both fundamental signaling processes and the mechanistic basis of cellular or physiological effects. By exposing only a thin strip across the center of the EPI-200 tissue, we have been able to measure global gene expression responses in bystander cells located at 0.125 and 0.625 um from the irradiation line, in 16h after irradiation. The data were analyzed using BRB-Array Tools (NIH), and further network analysis was performed with IPA (Ingenuity). Significantly responding genes were identified at the both distances. For instance, all sets demonstrated upregulation of two key enzymes of the lipid biosynthesis, UGT1 and PITPNB, and downregulation of proapoptotic proteins: BAX and ARHGEF5. In contrast, several proteins involved in transcriptional repression (CHD6, CHD8 andWRNIP1) were strongly upregulated suggesting a rearrangement in the gene transcription. These changes suggest an activation of bystander mechanisms different from those observed in 2-dimensional cell cultures.

overall_design: Radiation induced gene expression in 3-dimensional tissue model, Epi-200, was measured in 16 hours after exposure to  0.5 Gy of alpha-particles. Three independent experiments were performed for the samples collected at different distances from the irradiation line (125-625 and 625-1125 um) using three tissue fragments per a data point.

first: Sally

last: Amundson

middle: V


title: Comprehensive transcriptome and immunophenotype analysis of renal and cardiac MSC-like populations supports strong congruence with bone marrow MSC despite maintenance of distinct identities.

city: St Lucia

first: Darrin

middle: F

last: Taylor

state: Qld

address: Research Rd

department: Genomics and Bioinformatics

institute: Institute for Molecular Bioscience, Uni of Qld

summary:
Cells resembling bone marrow mesenchymal stem cells (MSC) have been isolated from many organs but their functional relationships have not been thoroughly examined. Here we compared the immunophenotype, gene expression, multipotency and immunosuppressive potential of MSC-like colony-forming cells from adult murine bone marrow (bmMSC), kidney (kCFU-F) and heart (cCFU-F), cultured under uniform conditions. All populations showed classic MSC morphology and in vitro mesodermal multipotency. Of the two solid organ-specific CFU-F, only kCFU-F displayed suppression of T-cell alloreactivity in vitro, albeit to a lesser extent than bmMSC. Quantitative immunophenotyping using 81 phycoerythrin-conjugated CD antibodies demonstrated that all populations contained high percentages of cells expressing diagnostic MSC surface markers (Sca1, CD90.2, CD29, CD44), as well as others noted previously on murine MSC (CD24, CD49e, CD51, CD80, CD81, CD105).
Illumina microarray expression profiling and bioinformatic analysis indicated a correlation of gene expression of 0.88-0.92 between pairwise comparisons. All populations expressed approximately 66% of genes in the pluripotency network (Plurinet), presumably reflecting their stem-like character. Furthermore, all populations expressed genes involved in immunomodulation, homing and tissue repair, suggesting these as conserved functions for MSC-like cells in solid organs. Despite this molecular congruence, strong biases in gene and protein expression and pathway activity were seen, suggesting organ-specific functions. Hence, tissue-derived MSC may also retain unique properties potentially rendering them more appropriate as cellular therapeutic agents for their organ of origin.

overall_design: 3 way comparison of MSC derived from Bone marrow, heart and kidney cells. Four biological replicates from each cell type were grown and total RNA extracted and compared.

first: Rebecca

last: Pelekanos

first: Joan

last: Li

first: Milena

last: Gongora

first: Vashe

last: Chandrakanthan

first: Janelle

last: Scown

first: Norseha

last: Suhaimi

last: Brooke

first: Melinda

last: Christensen

first: Tram

last: Doan

first: Alison

last: Rice

first: Geoffrey

middle: W

last: Osborne

first: Sean

last: Grimmond

first: Richard

last: Harvey

first: Kerry

last: Atkinson

first: Melissa

middle: H

last: Little