title: Expression data from mouse preimplantation cloned embryos

city: Tokyo

first: Feng

last: Cao

address: 1-1-1 Sakuraoka, Setagaya-ku

department: Bioscience

institute: Tokyo University of Agriculture

summary:
Transcriptiome analysis is an excellent approach to understand the mechanism underlying nuclear reprogramming in somatic-cell-cloned embryos. Analysis of the transcriptomic data from the oocyte to blastocyst stage revealed that specific genes were inappropriately reprogrammed at each stage. Sertoli cell-cloned embryos appear to develop normally because the progression of incorrect reprogramming is concealed throughout development.
The time-lapse gene expression profiles provide valuable information for understanding reprogramming in SCNT embryos.

overall_design: Single mouse oocyte (MII metaphase), in vitro fertilized embryo (replicates = 3 / each stage) and Sertoli cell cloned embryo (replicates = 5 / each stage) from 1-cell stage to blastocyst stage (16, 32, 48, 62, 72, 84 hours after sperm addition or activation) was used for total RNA extraction. Totally 51 Affymetrix microarrays were used in the experiment.

first: Hiroshi

last: Watanabe


title: Expression data from MLL-AF6 positive leukemia cells

status: Public on Apr 03 2013

city: Boston

first: Amit

last: Sinha

state: MA

address: 44 Binney St

department: Pediatric Oncology

country: USA

institute: Dana-Farber Cancer Institute

summary: The MLL gene on chromosome 11 fuses to the AF6 gene on chromosome 6 in a balanced chromosomal translocation that is characetristic of certain adult and pediatric human leukemias. We established a murine leukemia model of MLL-AF6 using the retroviral MLL-AF6 contruct in a bone marrow transplantation system.

overall_design: Leukemic bone marrow cells from a sacrificed moribund mouse were thawed and RNA was extracted using TRIZOL (Invitrogen) and purified further using the RNAeasy kit (Qiagen) under standard conditions and and hybridized onto Affymetrix arrays.

first: Aniruddha

last: Deshpande

first: Scott

last: Armstrong


title: The presence of the Y-chromosome, not the absence of the second X-chromosome, alters the mRNA levels stored in the fully grown XY mouse oocyte

status: Public on Apr 02 2013

address: Sakuragaoka 1-1-1, Setagaya-ku

country: Japan

summary: The oocytes of B6.Y(TIR) sex-reversed female mouse mature in culture but fail to develop after fertilization because of their cytoplasmic defects. To identify the defective components, we compared the gene expression profiles between the fully-grown oocytes of B6.Y(TIR) (XY) females and those of their XX littermates by cDNA microarray. 173 genes were found to be higher and 485 genes were lower in XY oocytes than in XX oocytes by at least 2-fold. We compared the transcript levels of selected genes by RT-PCR in XY and XX oocytes, as well as in XO oocytes missing paternal X-chromosomes. All genes tested showed comparable transcript levels between XX and XO oocytes, indicating that mRNA accumulation is well adjusted in XO oocytes. By contrast, in addition to Y-encoded genes, many genes showed significantly different transcript levels in XY oocytes. We speculate that the presence of the Y-chromosome, rather than the absence of the second X-chromosome, caused dramatic changes in the gene expression profile in the XY fully-grown oocyte.

overall_design:
We compared the gene expression profiles between the fully-grown oocytes of B6.Y(TIR) (XY) females and those of their XX littermates by cDNA microarray
Mouse GV oocytes of B6.Y(TIR) were collected for RNA extraction and hybridization to Affymetrix microarray. We sought to extract the differentially expressed genes in the XY oocytes.

first: Baozeng

last: Xu

first: Yayoi

last: Obata

first: Teruko

last: Taketo


title: Non-tumor/tumor intestinal tissue of control or intestine-specific HAI-1 deficient Apc(Min/+) mice

status: Public on Apr 01 2013

city: Miyazaki

first: Tsuyoshi

last: Fukushima

address: 5200 Kihara, Kiyotake

department: Pathology

institute: University of Miyazaki

summary:
To analyse roles of HAI-1/Spint1 in intestinal tumorigenesis, we examined the effect of intestine-specific deletion of Spint1 gene on Apc(Min/+) mice. The loss of Hai-1/Spint1 significantly accelerated tumor formation in ApcMin/+ mice and shortened their survival periods.
Mouse small intestine tumor tissue or background mucosa lacking macroscopically visible tumors were proceeded to RNA extraction and hybridization on microarrays (Affymetrix Mouse Genome 430 2.0 Array).

overall_design: Non-tumor or tumor intestinal mucosa tissues of Apc (Min/+)/Spint1 (flox/flox) mice and non-tumor or tumor intestinal mucosa tissues of  Apc (Min/+)/Spint1 (flox/flox)/Vil-Cre mice were analysed. The experiment was repeated respectively.

first: Hiroaki

last: Kataoka


title: Gene expression on CD11b+ IgA and CD11b- IgA cells in the small intestine #01

first: Jun

last: Kunisawa

address: 4-6-1 Shirokanedai, Minato-ku

institute: The University of Tokyo

summary: To compare gene expression between CD11b+ IgA and CD11b- IgA cells in the small intestine, each cell population was isolated from the murine small intestine.

overall_design: Similar experiment with different sample was performed as described in Gene expression on CD11b+ IgA and CD11b- IgA cells in the small intestine #02


title: IGROV1 miRNA expression analysis after in vivo locoregional treatment with CpG-ODN

status: Public on Mar 31 2013

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

country: Italy

institute: IRCSS Istituto Nazionale Tumori

summary: We reported that peri-tumoral CpG-ODN treatment, probably activating TLR9-expressing cells present in the tumor microenvironment, sensitized cancer cells to DNA-damaging chemotherapy (Cancer Res 2011 Oct 15;71(20):6382-90). Here, we investigated whether this treatment induces a modulation of miRNAs and their involvement in chemotherapy sensitivity. Twenty miRNAs were found differentially expressed in tumors from CpG-ODN-treated mice versus controls. Evaluation of the role of miR-424, miR-340 and miR-302b on cisplatin sensitivity revealed that ectopic expression of miR-302b (up-modulated in our array) in IGROV1 cells significantly improved cisplatin activity. The identification of miRNAs able to modify sensitivity to chemotherapy treatment will provide an experimental base for its future possible use as a target or tool of specific therapies.

overall_design: IGROV1 human ovarian carcinoma cells were adapted to growth intraperitoneally (i.p.) and maintained by serial i.p. passages of ascitic cells into healthy mice. Mice were injected i.p. with 2.5 x 10^6 ascitic cells in 0.2 ml of saline and treated starting 10-11 days later, when mice showed evident and established ascites, with CpG-ODN [phosphorothioated ODN1826 (5'-TCCATGACGTTCCTGACGTT-3')] delivered i.p. at a dose of 20 µg/mouse for 3 consecutive days, control mice received saline (4 mice/group). 24 hours after the last treatment, ascites-bearing mice were sacrificed. Tumor cells adherent to peritoneal wall were collected and immediately frozen in liquid nitrogen until RNA extraction.

first: L

first: A

last: Balsari

first: M

last: Berardi


title: Murine microenvironment metaprofiles associate with human cancer etiology and intrinsic subtypes

status: Public on Apr 04 2013

city: Berkeley

first: David

middle: H

last: Nguyen

state: CA

address: 1 Cyclotron Road, MS-977

department: Cancer & DNA Damage Response

institute: Lawrence Berkeley National Laboratory

summary:
We developed a mouse model that captures radiation effects on host biology by transplanting unirradiated Trp53 null mammary tissue to sham or irradiated hosts. Gene expression profiles of tumors that arose in irradiated mice are distinct from those that arose in naïve hosts.
Host irradiation induces a metaprofile consisting of gene modules representing stem cells, cell motility, macrophages and autophagy. Human orthologs of the host irradiation metaprofile discriminated between radiation-preceded and sporadic human thyroid cancers. An irradiated host centroid was strongly associated with estrogen receptor negative breast cancer. When applied to sporadic human breast cancers, the irradiated host metaprofile strongly associated with basal-like and claudin-low breast cancer intrinsic subtypes. Comparing host irradiation in the context of TGFβ levels showed that inflammation was robustly associated with claudin-low tumors.  The association of the irradiated host metaprofiles with estrogen receptor negative status and claudin-low subtype suggests that host processes similar to those induced by radiation underlie sporadic cancers.

overall_design: Total RNA was extracted from mammary tumors derived from transplantations of non-irradiated p53null mammary fragments into irradiated hosts.  We analyized a total of 32 p53null tumors from irradiated wild type mice: 9 from sham-irradiated hosts, and 23 from irradiated hosts.  We also analyzed 24 tumors from irradiated TGFb1 heterozygote hosts: 6 from sham-irradiated hosts, and 18 from irradiated hosts.

first: Erik

last: Fredlund

first: Wei

last: Zhao

first: Charles

middle: M

last: Perou

first: Allan

last: Balmain

first: Jian-Hua

last: Mao

first: Mary

last: Barcellos-Hoff


title: A transcriptomic analysis of a Caucasian family cohort of high risks for the metabolic syndrome

status: Public on Apr 12 2013

city: Milwaukee

first: Yi

last: Zhang

state: WI

address: 8701 W Watertown Plank Rd

department: Medicine

institute: Medical College of Wisconsin

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

overall_design: Refer to individual Series

first: Jack

middle: W

last: Kent Jr

first: Michael

last: Olivier

first: Diana

last: Cerjak

first: Joanne

middle: E

last: Curran

first: Melanie

middle: A

last: Carless

first: Harald

last: Göring

first: John

last: Blangero

first: Ahmed

last: Kissebah


title: elucidation a possible mechanism of kidney stone formation by using a MetS mouse model and to assess the effectiveness of adiponectin treatment in preventing kidney stones.

city: Nagoya

first: Yasuhiro

last: Fujii

department: Nephro-urology

institute: Nagoya City University

summary: we performed genome-wide expression analyses for investigating novel genetic environmental changes.

overall_design: 5 samples


title: MicroRNA-214 downregulation contributes to tumor angiogenesis via inducing secretion of hepatoma-derived growth factor in human hepatoma

city: TauYau

first: Yun-Shien

last: Lee

state: Taiwan

address: TauYau

department: Dept. Biotechnology

country: Taiwan

institute: Ming Chuan Univ

summary:
Abstract: Background & Aims: Unusual hypervascularity is a hallmark of human hepatocellular carcinoma (HCC). Although microRNA-214 (miR-214) is upregulated in other human cancers, it is downregulated in HCC. We elucidated the biological and clinical significance of miR-214
downregulation in HCC.
Methods: MicroRNAs deregulated in HCC were identified using array-based MicroRNA profiling. A luciferase reporter assay confirmed target association between miR-214 and hepatoma-derived growth factor (HDGF). Tube formation and in vivo angiogenesis assays validated the roles of miR-214/HDGF in angiogenesis.
Results: MiR-214 downregulation was associated with higher tumor recurrence and worse clinical outcomes. Ectopic expression of miR-214 suppressed xenograft tumor growth and microvascularity of the tumor and its surrounding tissues. The genes downregulated by ectopic expression of miR-214
were involved in the regulation of apoptosis, cell cycle, and angiogenesis. Integrated analysis disclosed HDGF as a downstream target of miR-214. Conditioned medium of HCC cells contained bioactivity to stimulate tube formation of human umbilical vein endothelial cells, which was abolished by pretreatment of the conditioned media with HDGF antibodies, silencing of HDGF expression or ectopic expression of miR-214 in the donor HCC cells. The angiogenic activity of the conditioned media lost by ectopic expression of miR-214 in the donor cells was restored by supplementation with recombinant HDGF. In vivo tumor angiogenesis assays showed significant suppression of tumor vascularity by ectopic expression of miR-214.
Conclusions: A novel role of microRNA in tumrigenesis is identified. Downregulation of miR-214 contributes to unusual hypervascularity of HCC via activation of the HDGF paracrine pathway for tumor angiogenesis.

overall_design: To identify miRNAs that are deregulated in human HCC, 68 HCC and 21 non-tumor liver tissues were subjected to profiling of miRNA expression using miRNA arrays containing 739 human miRNA probes. Differentially expressed microRNAs were identified.


title: Expression data from control and Pbx1-null CMPs and GMPs

city: Rozzano

first: Francesca

last: Ficara

state: MI

address: via Manzoni 56

institute: CNR/Istituto Clinico Humanitas

summary:
The capacity of the hematopoietic system to promptly respond to peripheral demands relies on adequate pools of progenitors able to transiently proliferate and differentiate in a regulated manner.  However, little is known about factors that may restrain progenitor maturation to maintain their reservoirs.  In addition to a profound defect in hematopoietic stem cell (HSC) self-renewal, conditional knockout mice for the Pbx1 proto-oncogene have a significant reduction in lineage-restricted progenitors, including common myeloid progenitors (CMPs) and, to a lesser extent, granulocyte-monocyte progenitors (GMPs).
Through analysis of purified progenitor proliferation, differentiation capacity and transcriptional profiling, we demonstrate that in the absence of Pbx1 the CMP pool is reduced due to aberrantly rapid myeloid maturation, associated with decreased expression of Meis1 and its targets including Flt3.

overall_design: BM cells were obtained from multiple bones of individual three to five week old Tie2Cre+.Pbx1-/f  or Tie2Cre+.Pbx1+/f control mice (4-5 biological replicates/group).  CMPs and GMPs were sorted by flow cytometry according to the following markers: Lin-/c-Kit+/Sca-/CD34+/CD16/32int, and Lin-/c-Kit+/Sca-/CD34+/CD16/32high, respectively, prior to RNA extraction.

first: Chenwei

last: Lin


title: Pneumonia infection, lung and liver inflammation

status: Public on Mar 29 2013

city: University Park

first: A.

middle: Catharine

last: Ross

state: PA

address: 110 Chandlee Laboratory

department: Nutritional Sciences

institute: Penn State

summary: Vaccination reduces morbidity and mortality from pneumonia but its effect on the tissue-level response to infection is still poorly understood. We evaluated pneumonia disease progression, acute phase response and lung gene expression profiles in mice inoculated intranasally with virulent gram-positive Streptococcus pneumoniae serotype (ST) 3, with and without prior immunization with pneumococcal polysaccharide ST 3 (PPS3), or co-immunization with PPS3 and with a low dose of lipopolysaccharide (LPS). Pneumonia severity was assessed in the acute phase, 5, 12, 24 and 48 h post-inoculation (p.i.) and the resolution phase of 7 days p.i. Primary PPS3 specific antibody production was upregulated and IgM binding to pneumococci increased in PPS3-immunized mice. Immunizations with PPS3 or PPS3 + LPS decreased bacterial recovery the lung and blood at 24 and 48 h and increased survival. Microarray analysis of whole lung RNA revealed significant changes in the acute phase protein serum amyloid A (SAA) between noninfected and infected mice, which were attenuated by immunization. SAA transcripts were higher in the liver and lungs of infected controls, and SAA protein was elevated in serum, but decreased in PPS3-immunized mice. Thus, during a virulent pneumonia infection, prior immunization with PPS3 in an IgM-dependent manner as well as co-immunization with PPS3 + LPS attenuated pneumonia severity and promoted resolution of infection, concomitant with significant regulation of cytokine gene expression in the lungs, and acute phase proteins in the lungs, liver and serum.

overall_design: Each lung RNA sample represented an individual mouse, creating biological repeats for each treatment. In-vivo treatments were as follows: non-infected lung (vehicle-immunized) control (n=5), infected lung (vehicle-immunized) control at 48 hr post-inoculation (n=5), PPS3 and LPS co-immunized lung at 48 hr post-inoculation (n=4) and PPS3 and LPS co-immunized lung at 7 days post-inoculation (n=4).

first: Katherine

last: Restori

first: Catharine


title: Expression data from mouse liver tumor-initiating cells

status: Public on Mar 30 2013

city: Los Angeles

first: Keigo

last: Machida

address: 2011 Zonal Ave., HMR503C

department: Molecular Microbiology and Immunology

institute: University of Southern California

summary: The Toll-like receptor 4 (TLR4) pathway is important for tumor-initiating cells. We used microarrays to obtain gene profiling data in order to increase understanding of the pathways.

overall_design: Liver tumor-initiating cells were used for RNA extraction and hybridization on Affymetrix microarrays.

first: Chia

middle: L

last: Chen


title: Expression data from J147-treated HT22 cells compared to untreated HT22 cells

status: Public on Mar 28 2013

city: La Jolla

first: Jennifer

middle: Lynn

last: Ehren

address: 10010 N Torrey Pines Road

department: Cellular Neurobiology

institute: Salk Institute

summary:
The Neurotrophic Compound J147 Reverses Cognitive Impairment In Aged Alzheimer's Disease
We used GeneChip® Mouse Genome 430 2.0 Arrays to probe global gene expression changes when adding J147 compound to HT22 cells and compared to untreated cells.
The hippocampal cell line HT22 were treated with the J147 compound for 1 hour and compared to HT22 treated only with vehicle (DMSO) for 1 hour.

overall_design: The gene expression profile from the J147-treated HT22 cells (1 hour exposure) was compared to HT22 cells treated with vehicle only (DMSO) for 1 hour.  The DMSO/vehicle treated cells serve as the control and are referred to as untreated with drug.

first: Marguerite

last: Prior

first: David

last: Schubert


title: A hypomorphic Lsd1 allele results in heart development defects in mice.

city: Cambridge

first: Joseph

last: Loureiro

address: 220 Massaxhusetts Ave.

institute: Novartis Institutes for Biomedical Research

summary:
Microarray characterization of Lsd1 knock-outs compared to littermate controls
Microarrays were employed to identify transcripts that were differentially modulated in the hearts of wild-type and Lsd1-hypomorphic late-stage embryos.

overall_design: Late-stage embryonic hearts were isolated from wild-type and Lsd1-hypomorphic hearts, in order to isolate RNA for hybridization on Affymetrix microarrays.  We sought to identify gene products that are differentially regulated between the two genotypes, in order to explain the observed ventricular septal defects in the hypomorphic animals.

first: Thomas

last: Nicholson


title: Expression analysis of GATA1s murine megakaryocyte progenitors from bone marrow and fetal Liver

city: Nedlands

first: Andrew

middle: Jonghan

last: Woo

state: WA

address: 6 Verdun Street

department: UWA Centre for Medical Research

country: Australia

institute: University of Western Australia

summary:
About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis.
kewywords: Mouse megakaryocyte progenitors

overall_design: Expression data of flow cytometrically isolated murine megakaryocyte progenitor cells (lin-, Sca-1-, c-kit+, CD150+, CD41+) from GATA1s fetal liver and bone marrow

middle: J

first: Karen

last: Wieland

first: Alan

middle: B

last: Cantor


title: Expression data from C57BL/6J and C57BL6/J Sarm-deficient mice uninfected or infected with vesicular stomatitis virus (VSV)

city: New York

first: Melissa

last: Uccellini

state: NY

address: 1468 Madison Ave

institute: Mt Sinai School of Medicine

summary: Sarm-deficient mice are protected from VSV encephalitis and death. Microarray was done to examine genes contributing to this phenotype

overall_design: WT and KO mice were infected with VSV and brains were harvested at day 5 post-infection for RNA extraction

first: Uccellini

last: Melissa


title: In TCR-stimulated T-cells, N-ras regulates specific genes and signal transduction pathways

first: stephen

last: Lynch

address: 550 First Ave

institute: NYU Langone School of Medicine

summary:
It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus.   The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome.
First, we showed via mRNA expression profiling that there were over four hundred genes that were uniquely differentially regulated either by N-ras or H-ras, which provided strong evidence in favor of the hypothesis that N-ras and H-ras have distinct functions in immune cells.  We next characterized the genes that were differentially regulated by N-ras in T cells following a low-level TCR stimulus.  Of the large pool of candidate genes that were differentially regulated by N-ras downstream of TCR ligation, four genes were verified in qRT-PCR-based validation experiments as being differentially regulated by N-ras (Dntt, Slc9a6, Chst1, and Lars2).  Finally, although there was little overlap between individual genes that were regulated by N-ras in unstimulated thymocytes and stimulated CD4+ T-cells, there was a nearly complete correspondence between the signaling pathways that were regulated by N-ras in these two immune cell types.
Since we were interested primarily in genes that were differentially regulated by N-ras following a low-level TCR stimulus, our microarray data comparison was between data from TCR-stimulated, WT CD4+ T-cells and from TCR-stimulated, N-ras KO CD4+ T-cells.  Genes that were differentially regulated in the comparison between stimulated N-ras KO CD4+ T-cells and unstimulated N-ras KO CD4+ T-cells, as well as those genes that were differentially regulated in the comparison between stimulated WT CD4+ T-cells and unstimulated WT CD4+ T-cells were excluded from this analysis.
To determine if N-ras and H-ras regulate different sets of genes in thymocytes, a comparison was made between the set of genes that were differentially regulated by N-ras in the [WT] vs. [N-ras KO] comparison and the set of genes that were differentially regulated by H-ras in the [WT] vs. [H-ras KO] comparison.

overall_design:
RNA was extracted from CD4+ T cell splenocytes isolated from 6-20 week old N-Ras KO and WT mice following growth in T cell growth media either with or without 1 microgram/milliliter ant-CD3 and anti-CD28 antibodies.
RNA was extracted from thymocytes isolated directly from 6-20 week old N-Ras KO, H-Ras KO and WT mice.

first: Stephen

first: Jiri

last: Zavadil

first: Angel

last: Pellicer


title: Expression analysis of nail matrix in mouse.

status: Public on Mar 27 2013

first: Makoto

last: Takeo

address: 522 First Ave.

institute: New York University School of Medicine

summary: Mammalian digit-tip can regenerate upon amputation1-3, like amphibians. It is unknown why this capacity is limited to the area associated with the nail3-5. Here, we show that nail stem cells (NSCs) reside in the Wnt-suppressed proximal nail matrix and that the mechanisms governing NSC differentiation are directly coupled with their ability of orchestrating digit regeneration. Early nail progenitors located distal to the NCS region undergo Wnt-dependent differentiation into nail. Upon amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to regeneration of the entire digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate nail/digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NCS differentiation and digit regeneration, suggesting a utility of the NSCs in developing novel treatments for amputees.

overall_design: Nail matrix cells were harvested from proximal and distal matrix region by microdissection and processed to RNA extraction and hybridization on Affymetrix microarrays. We analyzed two proximal and two distal matrix cells.

first: Mayumi

last: Ito


title: Identification of genes responsive to low-intensity pulsed ultrasound (LIPUS) in MC3T3-E1 preosteoblast cells

status: Public on Mar 26 2013

city: Toyama

first: Yoshiaki

last: Tabuchi

state: Toyama

address: 2630 Sugitani

department: Life Science Research Center

institute: University of Toyama

summary: Although LIPUS has been shown to enhance fracture healing, the underlying mechanism of LIPUS remains to be fully elucidated. Here, to understand the molecular mechanism underlying cellular responses to LIPUS, we investigated gene expression profiles in mouse MC3T3-E1 preosteoblast cells using a GeneChip® system.

overall_design: The mouse preosteoblast MC3T3-E1cells were treated with LIPUS (30 mW/cm2) for 20 min followed by culturing for 6 and 24 h at 37C. Mock-treated cells were served as control. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was monitored by an Affymetrix GeneChip system with a Mouse Genome 430 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturer's instructions.

first: Yuuki

last: Sugahara


title: Exon-array profiling of peripheral blood cells in the first hours of acute coronary syndrome patients

city: Valencia

first: Francisco

middle: García

last: García

address: Eduardo Primo Yúfera, 3

department: Bionformatics & Biostatistics Unit

country: Spain

institute: CIPF

summary: Identifying novel candidate biomarker gene differentially expressed in the peripheral blood cells of patients with early stage acute myocardial infarction  using  microarray as a high throughput screening technology.

overall_design: In this study, we used exon array profiling to investigate biomarker gene analyzing  49 patients samples  (six time points)  and 6 control samples. Whole-blood cell drawn from an antecubital vein at six time points following STEMI diagnosis. The first time (T0) was on patient admission to the Emergency Unit prior to receiving any medication. The second time (T2) blood collection occurred after successful mechanical reperfusion and stenting of the infarct artery within 2 h after T0.  Collections for the subsequent four time points were at 12 h (T12), 24 h (T24), 36 h (T36) and 48 h (T48). For the control group, peripheral blood was collected at one time point.

first: Vivian

middle: N

last: Silbiger

first: Andre

middle: D

last: Luchessi

first: R

last: Hirata

first: L

middle: G

last: Neto

first: Débora

last: Decavi

last: Carracedo

first: María

last: Brión

first: Joaquín

last: Dopazo

last: García-García

first: Elizabete

middle: S

last: dos Santos

first: Marcos

middle: P

last: Pereira

first: Rui

middle: F

last: Ramos

first: Marcelo

last: Sampaio

first: Dikran

last: Armaganijan

first: Amanda

last: Sousa

first: Mario


title: Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis:  A model for “active” disease.

status: Public on Apr 10 2013

city: Gaithersburg

first: Sriram

last: Sridhar

state: MD

address: 1 MedImmune Way

department: Translational Medicine

institute: MedImmune

summary: Genomic profiling of bleomycin- and saline-treated mice across 7 timepoints (1, 2, 7, 14, 21, 28, 35 days post treatment) was carried out in C57BL6/J mice to determine the phases of response to bleomycin treatment which correspond to onset of active pulmonary fibrosis.

overall_design: Temporal genomic characterization of lung homogenate from male C57BL6/J mice treated intratracheally with bleomycin or saline was carried out at 7 timepoints post treatment (1, 2, 7, 14, 21, 28, 35 days). Bleomycin (2U/kg) in 50 μl was intratracheally sprayed once into mice lightly anaesthetized with isoflurane (5% in 100% O2). Control animals received 50 μl of saline. Total RNA was isolated from the mouse lung tissue of bleomycin- and saline-treated mice across the 7 time points (n=8 per group) and homogenized in QIAzol reagent. Purified total RNA was amplified and labeled using NuGen Ovation kits (NuGEN Technologies, Inc., San Carlos, CA), and RNA from samples was hybridized to Affymetrix Mouse 430 2.0 arrays. One sample (saline treated, d14) was flagged as an outlier in principal component analysis and removed from subsequent analysis.

first: Christopher

last: Stevenson


title: Expression profiling in palatal mesenchymal cells stimulated with TGF-beta2 in the presence and absence of TGFbRI and Tak1 kinase inhibitors

city: Ann Arbor

first: Vesa

middle: Matti

last: Kaartinen

address: 1011 N. University

department: BMS

institute: University of Michigan

summary:
TGF-beta signaling in neural crest cells is required for normal craniofacial development. This signaling can be transduced via TGF-beta type I receptors (TGFbRI) using Smad-dependent or Smad independent signaling pathways.
We used microarrays to identify TGF-beta-responsive genes that are dependent either on TGFbRI kinase, Tak1 kinase or both.

overall_design: Primary palatal mesenchymal cell cultures were established. Cultured cells were stimulated with TGF-beta2 in the presence or absence of TGFbRI kinase and Tak1 kinase inhibitors. Unstimulated cells were used as controls. Total RNAs were isolated and hybridized on Affymetrix microarrays.

first: Kenji

last: Yumote

first: Penny

last: Thomas


title: Comparative Effects of Statins on Murine Cardiac Gene Expression Profiles in Normal Mice

city: Shimotsuke

first: Masafumi

last: Kumazaki

state: Tochigi

address: 3311-1 Yakushiji

department: Pharmacology

institute: Jichi Medical University

summary:
Recent clinical data suggest that the efficacy of statin treatment in patients with heart failure varies depending on the drugs administered. Therefore, the present study was undertaken to compare murine cardiac gene expression following treatment with four different statins.
Statins directly regulated cardiac gene expression in a drug-specific manner in mice. The influence of each statin on the cardiac mRNA expression of various genes, including several genes that might be involved in the development of cardiac disease, was not a general effect of this class of drugs.

overall_design: Male C57BL/6J mice (n = 20) were treated with or without a statin (pitavastatin calcium, pravastatin sodium, rosuvastatin calcium, or atorvastatin calcium hydrate) (n = 4 in each group) for four weeks. Total RNA was isolated from the left ventricle of each animal. The fragmented and labeled amplified cDNA was hybridized to a GeneChip Mouse Genome 430 2.0 Array (Affymetrix). Data and statistical analysis were performed with GeneSpring GX version 11.0 software (Agilent Technologies).

first: Hitoshi

last: Ando

first: Kentarou

last: Ushijima

first: Akio

last: Fujimura


title: Genome-wide expression study of the early/innate responses of murine B and T cells to MCMV infection

city: marseille

first: Thien-Phong

last: Vu Manh

address: 163 avenue de Luminy

country: France

institute: CIML

summary:
Murine Cytomegalovirus (MCMV) infection leads to early activation of various immune cells, including B and T lymphocytes, before the actual initiation of antigen-specific adaptive immunity. This activation is partly driven by innate cytokines, including type I interferon (IFN), which are induced early after infection. The objective of this study was to address the role of type I IFN in shaping early/innate B and T cell responses to a primary acute viral infection.
In order to decipher the specific impact of IFN-I on cell subsets, we performed a genome-wide expression analysis on WT splenic B and CD8 T lymphocytes isolated from C57BL/6 [CD45.1 WT / CD45.2 IFNAR-KO] mixed bone marrow chimera mice. This study complements series GSE39555, which focused on early responses of NK cells and of the two subsets of conventional dendritic cells.

overall_design: This study includes data from B and CD8 T lymphocytes purified by flow cytometry sorting from the spleen of bone marrow chimera (BMC) mice, under steady-state or MCMV conditions. Two independent replicates were made for each cell type, from two independent pools of spleens from uninfected or d1.5 MCMV-infected BMC 5-8 mice, and were hybridized on 3 separate batches of GeneChips.

first: T

last: Baranek

first: M

last: Dalod


title: Expression data from splenic B-cells isolated from DmU50(HG-b) mice or wild-type C57BL/6J

city: Tokyo

first: Yuuichi

last: Soeno

address: 1-9-20 Fujimi, Chiyoda-ku

institute: The Nippon Dental University

summary: Box C/D-type small nucleolar RNAs (snoRNAs) are functional RNAs responsible for mediating 2’-O-ribose methylation of ribosomal RNAs (rRNAs) within the nucleolus. Previously, in relation to a novel chromosomal translocation in a human B-cell lymphoma, we identified U50HG, a non-protein-coding gene that hosted a box C/D-type U50 snoRNA within its intron. To investigate the physiological importance of the U50 snoRNA and its involvement in tumorigenesis, we generated a mouse model deficient in mouse U50 (mU50) snoRNA expression without altering the expression of mouse mU50 host-gene, mU50HG-b. The established mU50 snoRNA-deficient mice showed a significant reduction of mU50 snoRNA expression and the corresponding target rRNA methylation in various organs. Lifelong phenotypic monitoring showed that the mU50-deficient mice looked almost normal without accelerated tumorigenicity; however, a notable difference was the propensity for anomalies in the lymphoid organs.

overall_design: B-cells were isolated from spleens of DmU50(HG-b) mice or wild-type C57BL/6J with antibody-conjugated magnetic beads system (Myltenyi Biotec). Total RNA was purified with QIAGEN RNeasy Micro kit. Affymetrix GeneChip® Microarrays (Mouse Expression 430 2.0 Array) were used.

last: SOENO

first: Kazuya

last: FUJITA

first: Yuji

last: TAYA

first: Takaaki

last: AOBA


title: Lipid metabolism genes in contralateral unaffected breast and estrogen receptor status of breast cancer

city: Chicago

first: Jun

last: Wang

state: IL

address: 303 E Superior Street

department: Department of Surgery

institute: Northwestern University

summary: The contralateral unaffected breast of women with unilateral breast cancer (cases) is a good model for defining subtype-specific risk since women with ER-negative index primaries are at high risk for subsequent ER-negative primary cancers. We performed random fine needle aspiration (rFNA) of the unaffected breasts of cases; samples from 30 subjects (15 ER-positive and 15 ER-negative cases matched for age, race and menopausal status), were used for Illumina expression array analysis.

overall_design: In this study, we have examined gene expression profiles in random fine needle aspirate (rFNA) samples from the contralateral breasts of women with new unilateral breast cancer (cases) to seek candidate panels of ER-specific risk biomarkers.  On a discovery set of 30 women, we have identified gene expression differences in the contralateral breast that associate with ER+ or ER- index primary tumors.

first: Denise

last: Scholtens

first: Seema

last: Khan


title: Mouse lung transcriptional response to flagellin stimulation

status: Public on Mar 22 2013

city: Lille

first: Jean-Claude

last: SIRARD

address: 1 rue du Pr Calmette

department: Centre d'Infection et d'Immunité de Lille

institute: Institut Pasteur de Lille

summary: Vaccine adjuvants enhance adaptive immunity to co-administered antigens. Whereas the modes of action are multiple, the activation of antigen-presenting cells (APC) like dendritic cells by adjuvants is a prerequisite. Detection of microbial signals by innate sensors like Toll-like receptors (TLR) is a major mechanism of APC activation. Most candidate or licensed vaccines assume that adjuvant activity of TLR agonists depends on direct effect on APCs. This study addressed whether TLR stimulation of non-hematopoietic cells could contribute to the adjuvant effect. Nasal administration of flagellin enhanced T cell- and antibody-mediated immunity to co-administered antigens in a TLR5-dependent but inflammasome-independent manner. We found that lung radioresistant cells were sufficient to promote immunity, thereby suggesting that direct TLR5-mediated APC stimulation is dispensable to adjuvant activity. Consistent with this, radioresistant compartment is essential to stimulate the swift TLR5-dependent transcription. The transcriptional response was restricted to the epithelial compartment and was associated to the production of a narrow set of mediators including the chemokine CCL20, known to promote APC recruitment in mucosal tissues. Besides, flagellin was rapidly degraded in lower airways and was not transported into lung parenchyma or peripheral tissues. This study therefore suggests an unexpected mechanism for how TLR agonists act as adjuvant and how epithelium is instrumental to sense and integrate microbial signals to promote adaptive immunity. In conclusion, the immune-enhancing effect of adjuvants on epithelial cells can be harnessed for improving vaccines.

overall_design: 1 µg of flagellin was instillated intranasally to LPS-unresponsive C3H/HeJ mice. Total lung RNA was extracted 1h later and prepare for hybridization on Affymetrix microarrays.

last: Sirard


title: Translational profiling of hypocretin neurons identifies Lhx9 as necessary for normal development of the hypocretinergic system.

city: St Louis

first: Joseph

last: Dougherty

state: Missouri

address: 4566 Scott Ave, box 8232

department: Genetics and Psychiatry

institute: Washington University

summary: The immense molecular diversity of neurons challenges our ability to deconvolve the relationship between the genetic and the cellular underpinnings of neuropsychiatric disorders. Hypocretin (orexin) containing neurons of the lateral hypothalamus are clearly essential for the normal regulation of sleep and wake behaviors, and have been implicated in feeding, anxiety, depression and reward. However, little is known about the molecular phenotypes of these cells, or the mechanism of their specification. We have generated a Hcrt bacTRAP line for comprehensive translational profiling of these neurons in vivo. From this profile, we have identified 188 transcripts, as enriched in these neurons, in additions to thousands more moderately enriched or nominally expressed. We validated many of these at the RNA and protein level, including the transcription factor Lhx9. Lhx9 protein is found in a subset of these neurons, and ablation of these gene results in a 30% loss of Hcrt neuron number, and a profound hypersomnolence in mice. This data suggests that Lhx9 may be important for specification of some Hcrt neurons, and the subsets of these neurons may contribute to discrete sleep phenotypes.

overall_design: Four independent TRAP replicates were collected, and total RNA from both the immunoprecipitate(IP) and unbound(total) fractions were seperately amplified and hybridized. Unbound fractions are provided to serve as total RNA controls for the tissue.  Biological replicates are GCRMA normalized within groups. Following averaging of replicates, we recommend further global normalization between groups, using affymetrix biotinylated controls, to correct for any broad biases in scanning and hybridization. Finally for many analyses, we also recommend filtering to remove those probesets with low IP/Total fold change values from each cell type(see PMID:20962086). Researchers can contact us for spreadsheets where these additional steps have been completed.

first: Jasbir

last: Dalal

first: Jee

middle: H

last: Roh

first: Samir

last: Shah

first: Han

last: Yuan

first: Afua

last: Akuffo

first: Brie

last: Wamsley

first: David

last: Holtzman

first: Nathaniel

last: Heintz


title: High-fat diet induced changes to mouse liver mRNA

status: Public on Mar 21 2013

city: Nashville

first: Kasey

middle: C

last: Vickers

state: TN

address: 2220 Pierce Ave   358 PRB

institute: Vanderbilt Univ. School of Medicine

summary: Wild-type c57Bl/6 mice were placed on high-fat diet (21% fat) for 3 weeks, and total RNA from liver was used for affymetrix microarray analysis. Data were analyzed using GeneSpring GX12.0.

overall_design: Briefly, raw data was normalized using RMA (summarization algorithm) and quantile normalized, data was baseline transformed to median of all samples.

first: Alan

middle: T

last: Remaley


title: Prox1 determines hepatocyte versus cholangiocyte cell fate in liver progenitors

status: Public on Mar 15 2013

city: Memphis

first: Geoffrey

last: Neale

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary: The mammalian liver, the largest solid organ in the body, accomplishes multiple critical roles necessary to preserve homeostasis. Human liver diseases are debilitating, costly and very often result in death. Uncovering developmental mechanisms that establish the complex architecture of the liver or generate the cellular diversity of this organ is necessary to develop more adequate methods to prevent, diagnose and cure liver diseases. This study investigated the role of the homeobox gene Prox1 during mouse hepatogenesis.

overall_design: We used microarrays to detail the global program of gene expression in liver samples from wildtype mice and  Prox1 f/f;Foxa3Cre (conditional knockout) mice.

first: Asha

last: Seth

middle: A

first: Beatriz

last: Sosa-Pineda


title: Expression data for program activation by IR-induced DNA breaks in G1 phase Murine PreB cells

status: Public on Mar 13 2013

city: RTP

first: NIEHS

last: Microarray Core

state: NC

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: The objective of this set of samples is to identify genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by ionizing radiation in wild-type murine pre-B cells.  The data generated in this project will be compared to the data generated in GSE9024, in which genes that are differentially expressed following the introduction of DNA double strand breaks (DSBs) by the Rag proteins in murine pre-B cells were examined.  In order to understand the differences between the physiologic and genotoxic responses to DSB DNA damage, we need to compare cells that are all in the same compartment of the cell cycle.  We are therefore examining the response to IR-induced damage in cells that are arrested in G1, which would correspond to our previous study of G1 arrested cells with Rag-induced breaks.  This will illuminate the difference directly, allowing us to better understand the signaling responses to the different types of DNA damage.

overall_design: Murine v-abl-transformed pre-B cells were treated with 3 uM STI571 for 48 hours. The cell type is Wild type (3 biological replicates).  For each wild type cell line, cells were treated with 1 Gy ionizing radiation or no ionizing radiation.  Each sample was hybridized once using Affymetrix Mouse Genome 2.0 GeneChip arrays (Mouse 430 v2, Affymetrix, Santa Clara, CA). Data were analyzed using the unirradiated samples as the controls.

first: Cynthia

middle: L

last: Innes

first: Jill

middle: E

last: Hesse

first: Palii

last: Stela

first: Beth

last: Helmink

first: Abigail

last: Holub

first: Barry

last: Sleckman

first: Richard

last: Paules


title: Gene activation by Rag-mediated DNA double-strand breaks in G1-phase murine pre-B cells

summary: The objective is to identify genes that are differentially expressed following the introduction of DNA double-strand breaks (DSBs) by the Rag proteins in murine pre-B cells. Cells lacking Artemis are used since the Rag-induced DSBs will not be repaired, and thus, will provide a continuous stimulus to the cell.

overall_design: Murine v-abl-transformed pre-B cells were treated with 3 uM STI571 for 48 hours. Cell types included RAG-2-deficient (3 biological replicates) and Artemis-deficient (3 biological replicates) G1-phase pre-B cells. Each sample was hybridized once using Affymetrix Mouse Genome 2.0 GeneChip arrays (Mouse 430 v2, Affymetrix, Santa Clara, CA). Data were analyzed using the RAG-2-deficient samples as the controls.

first: Stela

last: Palii


title: Expression data from miR-203 induction in mouse skin

status: Public on Mar 14 2013

city: Boulder

first: Zhaojie

last: Zhang

state: CO

address: 2300 Arapahoe Ave

institute: University of Colorado at Boulder

summary:
We identify numerous miR-203 in vivo targets that are highly enriched for the promotion of cell cycle and cell division. Importantly, individual targets including p63, Skp2 and Msi2 play distinct roles downstream of miR-203 to regulate the cell cycle and long-term proliferation. Together, our findings reveal rapid and widespread impact of miR-203 on the self-renewal program during the epidermal differentiation and provide mechanistic insights for the potent role of miR-203 where coordinated repression of multiple targets is required for the function of this miRNA.
We used microarrays to measure transcriptome changes upon miR-203's induction in mouse skin and identified new targets of miR-203.

overall_design: We use two pairs of biological duplicates to perform the microarray analysis from the epidermal samples harvested from K14-rtTA/TRE-miR-203/K14-H2BGFP (DP) and TRE-miR-203/K14-H2BGFP (SP) littermates at P4, 24h after the Dox injection.

first: Zhang

last: Zhaojie

first: Feng

last: Dejiang

first: Yi

last: Rui


title: Functional dissection of the Paired domain of Pax6 – distinct roles of subdomains in neurogenesis and proliferation

status: Public on Mar 19 2013

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary:
The transcription factor Pax6 acts as a key developmental regulator in various organs. In the developing brain Pax6 regulates patterning, neurogenesis and proliferation, but how these diverse effects are mediated at the molecular level is not well understood. As Pax6 regulates forebrain development including neurogenesis, proliferation and patterning, almost exclusively by one of its DNA-binding domains, the bipartite paired domain, we examined the role of its respective DNA-binding subdomains (PAI and RED). Using mice with point mutations in the PAI (Pax6Leca4, N50K) and RED (Pax6Leca2, R128C) subdomains we unravelled opposing roles of mutations in these subdomains in regulating genes that control proliferation in the developing cerebral cortex.
Mutation of the PAI domain reduced proliferation of both apical and basal progenitors, while the RED domain mutation significantly increased proliferation. Conversely, neurogenesis was affected only by the PAI domain mutation phenocopying the neurogenic defects observed in full Pax6 mutants. Genome-wide expression analysis supported the molecularly distinct signature upon mutation of these subdomains unravelling the key neurogenic signature mediated by the PAI domain. The altered expression of genes identified as direct Pax6 targets by chromatin immunoprecipitation allowed to further identify regulatory elements whose function was impaired by each individual Pax6 mutated protein. Thus, Pax6 achieves its key roles in the developing forebrain by utilizing distinct subdomains to regulate neurogenesis and exert opposing effects on proliferation, while Pax6-target genes involved in patterning tolerate either subdomain mutation.

overall_design: We performed gene expression microarray analysis of Pax6 mutant mice (Leca2, Leca4, Sey) and control mice

first: Tessa

last: Walcher

first: Qing

last: Xie

first: Dierk

last: Nissing

first: Martin

last: Irmler

first: Anastassia

last: Stoykova

first: Ales

last: Cvekl

first: Jovica

last: Ninkovic

first: Magdalena

last: Götz


title: Expression analysis of BL6 murine megakaryocyte progenitors from bone marrow and fetal Liver

city: Nedlands

first: Andrew

middle: Jonghan

last: Woo

address: 6 Verdun Street

institute: University of Western Australia

summary:
About 10% of Down syndrome (DS) infants are born with a myeloproliferative disorder (DS-TMD) that spontaneously resolves within the first few months of life. About 20-30% of these infants subsequently develop acute megakaryoblastic leukemia (DS-AMKL). In order to understand differences that may exist between fetal and bone marrow megakaryocyte progenitor cell populations we flow sorted megakaryocyte progenitor cells and performed microarray expression analysis.
kewywords: Mouse megakaryocyte progenitors

overall_design: Expression data of flow cytometrically isolated murine megakaryocyte progenitor cells (lin-, Sca-1-, c-kit+, CD150+, CD41+) from C57/BL6 murine fetal liver and bone marrow

first: Karen

last: Wieland

first: Alan

last: Cantor


title: Induction of pathogenic Th17 cells by salt inducible kinase SGK-1 (NaCl)

status: Public on Mar 07 2013

city: Berkeley

first: Nir

last: Yosef

address: Berkeley

department: EECS

institute: UC Berkeley

summary: Th17 cells are highly proinflammatory cells that are critical for clearing extracellular pathogens like fungal infections and for induction of multiple autoimmune diseases1. IL-23 plays a critical role in stabilizing and endowing Th17 cells with pathogenic effector functions2. Previous studies have shown that IL-23 signaling reinforces the Th17 phenotype by increasing expression of IL-23 receptor (IL-23R)3. However, the precise molecular mechanism by which IL-23 sustains the Th17 response and induces pathogenic effector functions has not been elucidated. Here, we used unbiased transcriptional profiling of developing Th17 cells to construct a model of their signaling network and identify major nodes that regulate Th17 development. We identified serum glucocorticoid kinase-1 (SGK1), as an essential node downstream of IL-23 signaling, critical for regulating IL-23R expression and for stabilizing the Th17 cell phenotype by deactivation of Foxo1, a direct repressor of IL-23R expression. A serine-threonine kinase homologous to AKT4, SGK1 has been associated with cell cycle and apoptosis, and has been shown to govern Na+ transport and homeostasis5, 6 7, 8. We here show that a modest increase in salt (NaCl) concentration induces SGK1 expression, promotes IL-23R expression and enhances Th17 cell differentiation in vitro and in vivo, ultimately accelerating the development of autoimmunity. The loss of SGK1 resulted in abrogation of Na+-mediated Th17 differentiation in an IL-23-dependent manner. These data indicate that SGK1 is a critical regulator for the induction of pathogenic Th17 cells and provides a molecular insight by which an environmental factor such as a high salt diet could trigger Th17 development and promote tissue inflammation.

overall_design: Effects of NaCl on Th17 differentiation

first: Chuan

last: Wu

first: Vijay

middle: K

last: Kuchroo


title: Influence of developmental stage and genotype on liver mRNA levels among wild, domesticated, and hybrid rainbow trout (Oncorhynchus mykiss)

status: Public on Mar 18 2013

city: West Vancouver

first: Samantha

middle: Louise

last: White

state: BC

address: 4160 Marine Drive

department: CAER

country: Canada

institute: Fisheries and Oceans Canada

summary: A 44K salmonid oligoarray was used to examine the influence of genotype and developmental stage on mRNA expression in wild-type (age matched and size matched to domesticated), domesticated and wild-domesticated hybrid populations. Significant differences were found in mRNA expression between genotypes. The largest proportion of differentially expressed mRNAs were found in comparisons of domesticated and wild-type groups. Significant differences were also noted in pairings of wild-domesticated hybrid progeny to both parental strains. Differences in gene expression were found in comparison of both wild-type age and size matched to each other and in combination with genotype analysis, showing a strong effect of fish developmental stage on differential gene expression. Domestication was found to modify biological pathways associated with transport, metabolism, cell tissue structure and development, stress and immune response and protein synthesis. Genotype analysis of hybrid progeny inheritance patterns showed similar levels of recessive, dominant and additive effects.

overall_design: Microarray analysis was performed on liver RNA from 6 individual fish per group of age-matched wild, size-matched wild, domesticated and wild-domesticated hybrids. Samples were hybridized against a common wild-type reference pool (n=6 wild size-matched fish). One individual from each of the groups was hybridized to one array on each of the individual slides (n=6) in the order of domestic, hybrid, age-matched wild and size-matched wild. In total, 6 4x44K oligoarray slides were used to complete the study.

first: Dionne

last: Sakhrani

first: Roy

last: Danzman

first: Robert

last: Devlin


title: Induction of pathogenic Th17 cells by salt inducible kinase SGK-1 (SGK-1 KO)

overall_design: Th17 cells; comparing Sgk1-/- to WT


title: Gene expression changes induced in the stromal cell line EL08-1D2 by co-culture with leukemic B cells (CLL)

status: Public on Mar 08 2013

city: Essen

first: Ludger

last: Klein-Hitpass

address: Virchowstr. 173

department: Universitaetsklinikum

institute: Institut fuer Zellbiologie

summary:
Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients.  The expression of PKC-βII and the subsequent activation of NF-κB in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC-β knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-βII- NF-κB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-βII in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
We used microarrays to determine gene expression changes induced by co-culturing with leukemic B-cells (CLL) in EL08-1D2 cells.

overall_design: We compared  EL08-1D2 cells co-cultured for 5 days with leukemic B-cells to EL08-1D2 mono-cultured cells by microarray analysis on Affymetrix MG-430_2.0 arrays.

first: L

first: I

last: Ringshausen


title: Gene expression profiles of CD4SP Foxp3GFP-CD25+ Treg precursors and Foxp3GFP-CD25- thymocytes

city: Braunschweig

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

institute: HCI - Helmholtz Centre for Infection Research

summary: We  investigated at which stage of maturation commitment to a stable Foxp3-expressing phenotype takes place. We assessed stability of Foxp3 expression in thymic Foxp3+ Treg subsets of different maturity, defined by CD24 expression. Next we compared gene expression profiles of Foxp3+ Treg subsets (+) of different maturity (24lo, 24int, 24hi) and could identify a set of genes that were specifically up or downregulated in Foxp3+ Tregs, but not in Foxp3- conventional T cells, in a maturation-dependent manner.

overall_design: Gene expression of Foxp3+ Treg subsets (+) of different maturity (24lo, 24int, 24hi) compared to their  Foxp3- conventional Tcell subsets (-) counterpart.

first: A

last: Toker

first: R

first: J

last: Huehn


title: Effect of NF-kappaB activation in bone marrow stromal cells co-cultured with CLL cells

summary:
Tumor cell survival critically depends on heterotypic communication with benign cells in the microenvironment. Here we describe a novel survival signaling pathway activated in stromal cells by contact to B-cells from chronic lymphocytic leukemia (CLL) patients.  The expression of PKC-βII and the subsequent activation of NF-κB in bone marrow stromal cells is a prerequisite to support the survival of malignant B-cells. PKC-β knockout mice are insusceptible to CLL-transplantations, underscoring the in vivo significance of the PKC-βII- NF-κB signaling pathway in the tumor microenvironment. Upregulated stromal PKC-βII in biopsies from CLL, breast- and pancreatic- cancer patients suggest that this pathway may commonly be activated in a variety of malignancies.
We used microarrays to determine Nemo/ IKK-gamma dependent gene expression changes in bone marrow stromal cells (BMSCs) induced by co-culturing with leukemic B-cells (CLL)

overall_design: We compared mouse BMSC cells from Nemo knockout cells (Nemo+CRE)  and Nemo wild type cells (Nemo-CRE) co-cultured for 5 days with leukemic B-cells microarray analysis on Affymetrix MG-430_2.0 arrays..


title: Protein kinase C-beta dependent activation of NF-kB in stromal cells is indispensable for the survival of chronic lymphocytic leukemia in B-cells in vivo.

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

overall_design: Refer to individual Series


title: Hlxb9 regulated genes in pancreatic beta cells

city: Bethesda

first: WeiPing

last: Chen

address: Bldg 8, Room 1A11, NIDDK/NIH

department: GCL

institute: NIDDK/NIH

summary: Hlxb9 is a differentiation factor important for neuronal, and pancreatic beta cell differentiation. It is a transcription factor that represses transcription. It's target genes are unknown. The mouse pancreatic beta cell line MIN6 was used to assess the expression of genes de-repressed upon Hlxb9 knockdown.

overall_design: Several independent transfections of MIN6 cells were performed with scrambled negative control siRNA (Qiagen) or with mouse Hlxb9 siRNA (Dharmacon). The cells were processed for RNA isolation and whole cell protein extracts, 72 hours post-transfection.  The level of Hlxb9 knockdown was assessed by western blot analysis. RNA preps from those samples that showed more than 75% knockdown were used for microarray analysis.

first: Kerong

last: Shi

first: Sunita

last: Agarwal


title: Genome wide expression in ADAMTS13-deficient thrombotic thrombocytopenic purpura TTP

city: Oklahoma City

first: Bart

last: Frank

state: OK

institute: OMRF

summary: This study sought correlates of relapse tendency in TTP by examining gene expression profiles in peripheral blood leukocytes from patients with acquired ADAMTS13-deficient TTP in remission and matched healthy controls for global gene expression and autoantibodies.

overall_design: Total RNA was isolated from PAXgene RNA tubes from 39 patients with with acquired ADAMTS13-deficient TTP (all patients had relapsed) and 39 healthy controls.

first: Mark

middle: B

first: Contessa

last: Edgar

last: Farris


title: Sox4 is a key oncogenic target in C/EBPα mutant Acute Myeloid Leukemia

status: Public on Mar 23 2013

city: Singapore

first: Henry

last: Yang

address: 28 Medical Drive

country: Singapore

institute: Cancer Science Institute of Singapore

summary: Mutation or epigenetic silencing of the transcription factor C/EBPα is observed in ~10% of patients with acute myeloid leukemia (AML). In both cases, a common global gene expression profile is observed, but down-stream targets relevant for leukemogenesis are not known. Here we identify Sox4 as a direct target of C/EBPα whereby its expression is inversely correlated with C/EBPα activity. Downregulation of Sox4 abrogated increased self-renewal of leukemic cells and restored their differentiation. Gene expression profiles of leukemia initiating cells (LICs) from both Sox4 overexpression and murine mutant C/EBPα AML models clustered together, but differed from other types of AML. Our data demonstrate that Sox4 overexpression resulting from C/EBPα inactivation contributes to the development of leukemias with a distinct LIC phenotype.

overall_design: K/L (bi-allelic Cebpa mutations) leukemic mice and Sox4 overexprssing leukemic mice were used for RNA extraction and hybridization on Affymetrix microarrays. We compared these microarray samples with the C57/BL6 wild type mice.

first: Hong

last: Zhang

first: Min

last: Ye

first: Meritxell

last: Alberich-Jordà

first: Giovanni

last: Amabile

first: Philipp

last: Staber

first: Rob

last: Welner

first: Junyan

first: Véronique

last: Lefebvre

first: Peter

middle: J

last: Valk

first: Ruud

last: Delwel

first: Maarten

last: Hoogenkamp

first: Borja

last: Saez

first: David

last: Scadden

first: Constanze

last: Bonifer

first: Daniel

last: Tenen


title: Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice

status: Public on Mar 04 2013

city: Nara

first: Kazuki

last: Kurimoto

address: 840 Shijo-Cho, Kashihara

department: School of medicine

institute: Nara Medical University

summary: Genome-wide DNA demethylation, including the erasure of genome imprints, in primordial germ cells (PGCs), is critical as a first step for creating the totipotent epigenome in the germ line. Here, we provide evidence that contrary to the prevailing model involving active DNA demethylation, imprint erasure in mouse PGCs occurs in a manner consistent with replication-coupled passive DNA demethylation: PGCs erase imprints during their rapid proliferation with little de novo as well as maintenance DNA methylation potential and no major chromatin alterations. Our findings necessitate the re-evaluation of and provide novel insights into the mechanism of genome-wide DNA demethylation in PGCs.

overall_design: We performed expression analysis of primordial germ cells (PGCs) at embryonic days 10.5-13.5. Because the number of PGCs available at these stages were low, cDNAs were amplified by the method that we previously published (Kurimoto et al. 2006, NAR 34: e42 (PMID 16547197)). To include analysis of PGC gene expression at E9.5, we re-normalized the data from our E9.5 PGC samples (GSM744103, GSM744104) from our previous publication (Hayashi et al., 2011, Cell 146: 519-32 (PMD 21820164)) together with the data from this submission.

first: Saya

last: Kagiwada

first: Takayuki

last: Hirota

first: Masashi

last: Yamaji

first: Mitinori

last: Saitou


title: Diffusible factors released from human prostate carcinoma cells restrained cancer stem cells from contributing to tumor progression

status: Public on Mar 01 2013

city: Torino

first: Raffaele

last: Calogero

state: To

address: Via Nizza 52

department: Molecular Biotechnology Center

institute: University of Torino

summary: The growth and progression of many cancers is thought to be driven by small subpopulations of cancer stem cells (CSC). Long-term cultures of CSC have been established to develop therapeutic strategies aimed at eradicating these tumorigenic cells. To evaluate the contribution of CSC to the progression of prostate cancer we isolated a CD44+CD24- tumor cell population from the DU145 cell line, derived from a brain metastasis of human prostate carcinoma, and established their CSC properties. The behaviour of selected CSC was then investigated with respect to the bulk DU145 cells. Interestingly, CSC were able to generate very aggressive tumors in immunodeficient mice, but this capacity was interfered by the presence of differentiated DU145 cells, resulting in the growth of scarcely aggressive tumors. To understand the influence of DU145 cells on CSC we performed co-culture experiments, demonstrating that signals released from differentiated tumor cells interfered with CSC acquisition of an aggressive phenotype. Our findings highlight that the fate of prostate CSC can be controlled by microenvironmental signals that restrain CSC from contributing to prostate cancer progression. Finally, we identified several molecules possibly involved in this cell-to-cell signaling, hypothesizing their potential value as novel prognostic markers or therapeutic targets.

overall_design: To investigate the cellular response involved in tumorigenesis both at the level of gene expression and at the pre-mRNA splicing level we performed a whole genome microarray analysis of two paradigmatic experimental conditions, DU145 cells and their selected CSC.

first: Luisa

last: Salvatori

first: Francesca

last: Caporuscio

first: Alessandra

last: Verdina

first: Stefania

last: Crispi

first: Andrea

last: Russo

first: Giuseppe

last: Starace

first: MariaRita

last: Nicotra

first: Emanuela

last: Morgante

first: PierGiorgio

last: Natali

first: Matteo

first: Elisa

last: Petrangeli


title: Expression profiling of mouse primary prostate luminal cells from WT and T-ETV1 mice, which contains human ETV1 cDNA under the endogenous Tmprss2 promoter.

city: Boston

first: Esther

last: Baena

state: MA

address: 300 Longwood Avenue

department: Hematology/Oncology

institute: Childrens Hospital Boston

summary: Chromosomal rearrangements involving ETS factors, ERG and ETV1, occur frequently in prostate cancer. We here examine mouse prostate cells from WT mice with s with T-ETV1 mice, which contains express the truncated human ETV1 under the endogenous Tmprss2 promoter. ETV1 expression can be tracked by GFP expression.

overall_design: Primary prostate cells were isolated and luminal prostate cells were FACS-sorted by CD49F+ Sca1- from the lineage (CD31, CD45, Ter119) negative fraction.  Total RNA was extracted from three biological replicates, and amplified using NuGEN V2cDNA amplification kit. This was used to hybridize to Affymetrix expression arrays using the Mouse Genome 430 2.0 platform.

first: Zhen

last: Shao

first: Zhe

last: Li

first: Stuart

last: Orkin


title: Expression data of hepatic iNKT cells from pLck-hCD1d transgenic mice

city: Milan

first: Giulia

last: Casorati

state: Milan

address: Via Olgettina 58

department: Division of Immunology, Transplantation and Infectious Diseases

institute: San Raffaele Scientific Institute

summary: CD1d expression by thymocytes is required to select iNKT cells. When CD1d is expressed only on thymocytes (pLck-CD1d tg mice), iNKT cells are hyperresponsive to antigen stimulation suggesting that, in physiological conditions, these cells undergo functional education mediated by additional CD1d-expressing cells. Here, we investigated the mechanisms of this functional education. We find that peripheral iNKT cells from pLck-CD1d tg mice express significantly less SHP-1, a tyrosine phosphatase negatively regulating TCR signaling, than WT cells. iNKT cells from heterozygous SHP-1-mutated motheaten mice, displaying similar SHP-1 reduction as pLck-CD1d tg iNKT cells, are antigen-hyperresponsive. Restoring normal CD1d expression in pLck-CD1d tg mice normalizes SHP-1 expression and responsiveness of iNKT cells. In WT mice, iNKT cells upregulate SHP-1 and decrease responsiveness upon emigration from thymus to periphery. This depends on contacts with CD1d-expressing DCs. iNKT cell functional education is therefore controlled by DCs via tuning SHP-1 expression level in the periphery.

overall_design: Hepatic iNKT cells from wild-type and transgenic mice (expressing hCD1d molecule under the pLck promoter)

first: Paola

last: Pittoni

first: Anna

last: Napolitano


title: Murine germinal center and naive B cells

status: Public on Mar 06 2013

city: New Haven

first: Hailong

last: Meng

state: CT

address: 300 George Str

institute: Yale University

summary: Gene expressions of murine germinal center and naive B cells on Affymetrix platform

overall_design: The experiment include 3 d14 GC B1-8, 3 d14 GC V23 and 4 Naïve samples

first: Jamie

last: Duke

first: Ashraf

middle: M

last: Khalil

first: Mary

last: Tomayko

first: Mark

last: Shlomchik

first: Steven

last: Kleinstein


title: Atxn1L is a novel regulator of Hematopoietic Stem Cell Quiescence

status: Public on Feb 28 2013

city: Houston

first: Chad

middle: A.

last: Shaw

state: TX

address: 1 Baylor Plaza

department: Molecular and Human Genetics

institute: BCM

summary:
We compared gene expression differences in Atxn1L knockout vs wildtype HSCs
KO allele described in Pub Med ID: 22014525

overall_design: HSCs were purified as Lineage-negative, Sca-1+ c-Kit+ (LSK), CD150+ and Side population from both Atxn1L-null and WT mice on C57Bl/6 background

first: Juliette

last: Kahle

first: George

last: Souroullas

first: Margaret

last: Goodell


title: Gene Expression profiles of colon from Hif-2αF/F, Hif-2αlΔIE treated with DSS

city: Ann Arbor

first: XIANG

last: XUE

state: Michigan

address: 1301 E. Catherine Street

institute: Umich

summary:
To investigate the detailed molecular mechanisms for the regulatory role of HIF-2α in experimental colitis, microarray gene expression analysis was performed on colon RNA isolated from 6- to 8-week-old Hif-2αF/F, Hif-2αlΔIE mice treated with 3%DSS for 3 days.
Background & Aims: Hypoxic inflammation is characterized by decreased oxygen tension in inflammatory foci, and is a notable feature in inflammatory bowel disease (IBD). Hypoxic response is mediated by transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α, both of which are highly induced in IBD. HIF-1α is a protective factor that limits intestinal barrier dysfunction during inflammation. However, the role of HIF-2α has not been assessed in hypoxic inflammation and IBD.   Methods: A hypoxia reporter mouse model was used to test the presence of hypoxia and HIF-2α in dextran sulfate sodium (DSS) and Citrobacter rodentium (C.rod)-induced colitis. The role of HIF-2α in these mouse models of colitis was further assessed in mice with an intestinal epithelium-specific gain- and loss-of-function of HIF-2α.   Results: Induction of hypoxia and HIF-2α was confirmed in both murine experimental colitis models and human IBD samples. Disruption of HIF-2α attenuated colonic inflammation whereas stabilization of HIF-2α potentiated inflammation in mouse models of colitis. Interestingly, intestine specific overexpression of HIF-2α but not HIF-1α leads to spontaneous colitis and premature death in mice. Further mechanistic analysis showed that HIF-2α is a driver for pro-inflammatory response and is critical regulator of intestinal epithelial-derived tumor necrosis factor (TNF)-α. Blocking TNF-α completely ameliorated HIF-2α potentiated intestinal inflammation.   Conclusions: These data demonstrate that HIF-2α is a critical transcription factor essential in intestinal epithelium elicited inflammatory response.

overall_design: Global gene expression profiling in colon RNAs isolated from 7-week-old Hif-2αF/F (n=6, Shah 007) and Hif-2αΔIE (n=5, Shah 008).

first: Xiang

last: Xue

first: Yatrik

last: Shah


title: Transcriptomal profiling of C57BL/6 wild type and ER-alpha KO mice fetal mammary gland after fetal exposure to Bisphenol A (BPA) and 17alpha-ethynylestradiol (EE2)

city: Charlestown

first: Toshihiro

last: Shioda

address: Building 149 - 7th Floor, 13th Street

department: Center for Cancer Research

institute: MGH Cancer Center

summary: To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice.

overall_design: Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E) 8 were harvested at E19. Total RNA was subjected to transcriptomal profiling using Affymetrix mouse genome 430 2.0 microarray.

first: Perinaaz

middle: R

last: Wadia

first: Nicolas

last: Cabaton

first: Michael

middle: D

last: Borrero

first: Beverly

middle: S

last: Rubin

first: Carlos

last: Sonnenschein

first: Toshi

first: Ana

last: Soto


title: Gene expression profiling: human CD8+CD45RO+ memory T cells in IL23 responsive and nonresponsive individuals

first: Wei

last: Zhang

state: Connecticut

institute: Yale School of Medicine

summary: The interleukin-23 (IL-23) pathway plays a critical role in the pathogenesis of multiple chronic inflammatory disorders, however, inter-individual variability in IL-23-induced signal transduction in circulating human lymphocytes has not been well-defined. In this study, we observed marked, reproducible inter-individual differences in IL-23 responsiveness (measured by STAT3 phosphorylation) in peripheral blood CD8+CD45RO+ memory T and CD3+CD56+ NKT cells. To define mechanisms that might be contributing to the differential IL-23-induced STAT3 activation between individuals, we examined mRNA expression differences in CD8+CD45RO+ memory T cells between IL-23 responsive and non-responsive individuals.

overall_design: We analyzed unstimulated and IL-23 stimulated FACS sorted CD8+CD45RO+ memory T cells from two individuals demonstrating robust IL-23 responsiveness, and two individuals demonstrating low IL-23 responsiveness, using the Affymetrix Human Exon 1.0 ST platform. Array data was processed by Affymetrix Expression Console software. No techinical replicates were performed.

first: Hui

last: Shen

first: Clara

last: Abraham

first: Judy

last: Cho


title: Expression data from neurotrophin transgenic mice

city: Louisville

first: Tao

last: Huang

state: KY

address: 500 S Preston St, Rm1004

department: Anatomical Sciences and Neurobiology

institute: University of Louisville

summary:
A limited number of growth factors are capable of regulating numerous developmental processes, but how they accomplish this is unclear. In the gustatory system, brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT4) have different developmental roles but exert their effects through the same receptors (TrkB and p75).
Using genome wide expression analysis, we determined that BDNF and NT4 also regulate the expression of different sets of genes downstream of receptor signaling in geniculate ganglion. These differences in gene expression likely determine their different roles. BDNF and NT4 could function differently because of temporal or spatial differences of expression or the activation of different signaling pathways.

overall_design: BDNF and NT4 regulate cell death, axonal growth and axonal guidance by altering gene expression. Because many of these functions of the two neurotrophins differ in taste development, each likely alters gene expression in a unique way. To determine if removal of BDNF and NT4 alters gene expression in different ways, I will compare microarray gene expression profiles in the geniculate ganglion among BDNF knockout, Nt4 knockout, and wild type mice during development.

first: Robin

middle: F

last: Krimm


title: Double-stranded RNA induces molecular and inflammatory signatures that are directly relevant to COPD

status: Public on Feb 27 2013

city: Gaithersburg

first: Sriram

last: Sridhar

state: MD

address: 1 MedImmune Way

department: Translational Medicine

institute: MedImmune

summary: Polyinosinic:polycytidylic acid (poly I:C) is a synthetic analogue of double-stranded (ds)RNA, a molecular pattern associated with viral infections, that is  used to exacerbate inflammation in lung injury models.  Despite its frequent use, there are no detailed studies of the responses elicited by a single topical administration of poly I:C to the lungs of mice.  Our data provides the first demonstration that the molecular responses in the airways induced by poly I:C correlate to those observed in the lungs of COPD patients.  These expression data also revealed three distinct phases of response to poly I:C, consistent with the changing inflammatory cell infiltrate in the airways.  Poly I:C induced increased numbers of neutrophils and NK cells in the airways, which were blocked by CXCR2 and CCR5 antagonists, respectively.  Using gene set variation analysis on representative data sets, gene sets defined by poly I:C-induced DEGs were enriched in the molecular profiles of chronic obstructive pulmonary disease (COPD), but not idiopathic pulmonary fibrosis patients.  Collectively, these data represent a new approach for validating the clinical relevance of preclinical animal models and demonstrate that a dual CXCR2/CCR5 antagonist may be an effective treatment for COPD patients.

overall_design: Temporal genomic characterization of lung homogenate from male BALB/cJ mice treated intranasally with poly I:C or saline was carried out at 7 timepoints post poly I:C/saline adiministration (2, 6, 24, 48, 72, 96, 168 hours). Mice were anesthetized with isoflurane and intranasally (i.n.) administered saline or poly I:C (InvivoGen, San Diego, CA) at a sub-maximal dose of 30 µg in 50 µl sterile saline.  For time course studies, the 30 µg was administered i.n. once and assessed from 2 – 168 hours. Total RNA was isolated from the mouse lung tissue of poly I:C and saline treated mice across 7 time points (2, 6, 24, 48, 72, 96, and 168 hours, n=6 per group) and homogenized in QIAzol reagent. Purified total RNA was amplified and labeled using NuGen Ovation kits (NuGEN Technologies, Inc., San Carlos, CA) and RNA from samples was hybridized to Affymetrix Mouse 430 2.0 arrays.

first: Christopher

last: Stevenson


title: MicroRNA-34a regulates cardiac ageing and function

status: Public on Feb 20 2013

city: Amsterdam

first: Reinier

last: Boon

address: De Boelelaan 1117

country: Netherlands

institute: Amsterdam UMC

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

summary: We compared the heart of 6-weeks-old mice (young) with 18-months-old mice (old)

overall_design: hearts of 6 week old and 18 month old mice

first: Stefanie

last: Dimmeler


title: Gene expression by Retinoic Acid in mouse Dendritic Cells

status: Public on Feb 26 2013

city: West Lafayette

first: Chang

last: Kim

state: IN

address: 725 Harrison St

department: Comparative Pathobiology

institute: Purdue

summary: The purpose of this study was to determine and clarify the retinoic effect on the gene expression profile for mouse dendritic cells.

overall_design: Dendritic cells were prepared from marrow cells by culturing them for 10 days with GM-CSF (20 ng/ml). These cells were cultured with the following reagents from the beginning of the culture: Two groups of dendritic cell conditions (Control, all-trans-retinoic acid (10 nmol) and Ro41-5253 (100 nmol)) with and without LPS(1 ug/ml).  The above conditions were done in BALB/c and BL6 mouse strains and compared for reproducible gene expression.

middle: H

first: JinSam

last: Chang

first: Benjamin

last: Ulrich

first: Ann

last: Feil


title: The C-terminus of CBFß-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis.

status: Public on Feb 19 2013

first: R. Katherine

last: Hyde

address: 49 Convent Dr

institute: NHGRI/NIH

summary:
The C-terminus of CBFß-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-mulimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFß-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFß-SMMHC (CBFß-SMMHCΔC95). Embryos with a single copy of CBFß-SMMHCDC95 were viable and showed no defects in hematopoiesis, while embryos homozygous for the CBFß-SMMHCΔC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFß-SMMHCΔC95.
To identify gene expression changes induced by CBFß-SMMHCDC95, we compared the gene expression profile in the blood cells of Cbfb+/+, Cbfb+/ΔC95, and CbfbΔC95/ΔC95 embryonic day 12.5 (E12.5) mice.

overall_design: Cbfb+/ΔC95 were mated together to generate Cbfb+/+, Cbfb+/ΔC95, and CbfbΔC95/ΔC95 embryos. Blood from 8-10 E12.5 embryos of the same genotype was pooled, and RNA was isolated, labeled, and hybridized to Affymetrix Genechip mouse microarray (430 2.0) chips. 3 chips were used for each genotype.

first: Yasuhiko

last: Kamikubo

first: R

first: Ling

last: Zhao

first: Lemlem

last: Alemu

first: Cecillia

last: Rivas

first: Lisa

last: Garrett

first: P

middle: P

last: Liu


title: Expression data from adult mouse mesenteric arteries

city: Los Angeles

first: Kirsten

middle: Ann

last: Turlo

state: CA

address: 621 Charles E Young Dr

department: Molecular Cell and Developmental Biology

institute: UCLA

summary: Vascular smooth muscle cells require beta1 integrin for survival. Following the induced deletion of smooth muscle beta1 integrin, smooth muscle cells undergo apoptosis and arteries become fibrotic. This microarray study on mesenteric arteries 2 weeks after the initiation of beta1 integrin deletion specifically in smooth muscle cells of the adult mouse aimed to examine early changes in expression following deletion.

overall_design: Mesenteric arteries from three wild type mixed background and three beta1 integrin smooth muscle knockout mixed background mice are examined.

first: M

last: Iruela-Arispe


title: Distinguishing innate memory CD8+ T from homeostatically expanded CD8+ T cells

city: Ithaca

first: Weishan

last: Huang

state: New York

address: C5 121, Cornell U.

department: Microbiology & Immunology

institute: Cornell University

summary:
Innate memory phenotype (IMP) CD8+ T cells are non-conventional αβ T cells exhibiting features of innate immune cells, and are significantly increased in the absence of non-receptor tyrosine kinase ITK. Their developmental path and function are not clear, particularly whether they can contribute to antigen specific responses. We found that WT bone marrow gives rise to IMP CD8+ T cells in irradiated MHCI-/- recipients, resembling those in Itk-/- mice determined by expression of surface markers. However, CD8+ T cells share similar expression of memory markers.
We used microarrays to compare the global programme of gene expression to determine whether the CD8+ T cells selected by hematopoietic MHCI are IMP CD8+ T cells as observed in the absence of ITK, or the result of homeostatic expansion of T cell contamination in the donor bone marrow. Through analysis of global gene expression correlation and differential expression, we determined that hematopoietic MHCI dependent IMP CD8+ T cells generated in irradiated MHCI-/- recipients, resemble those in Itk-/- mice, but distinct from CD8+ T cells derived via homeostatic proliferation.

overall_design: Cell sorting was performed using a FACSAria Cell Sorter (BD Biosciences, San Diego, CA). IMP CD8+ T cells (TCRβ+CD8α+CD44hi) were sorted from splenocytes of WT→MHCI-/- chimeras 8 weeks post transplantation and 8-week old Itk-/- mice. To generate HP cells, naïve CD8+ T cells (TCRβ+CD8α+CD44lo) were sorted and injected into Rag1-/- recipients (0.5 million /mouse, retro-orbital injection), followed by sorting of TCRβ+CD8α+ splenocytes 8 weeks post adoptive transfer. We sought to compare cells with the same gender and age, thus all donors were female, and ages (absolute age for Itk null and age post transfer for chimeras and HP model) were 8 weeks.

first: Avery

last: August


title: Long noncoding RNA as regulatory switch of protein turnover

status: Public on Feb 18 2013

city: Stanford

first: Kun

last: Qu

address: 269 Campus Dr. CCSR 2150

department: Dermatology

institute: Stanford University

summary: Long intervening noncoding RNAs (lincRNAs) are prevalent genes with poorly understood functions. Here we discover a pathway of lincRNA-regulated proteolysis. The enhancer-like lincRNA HOTTIP extends the half-life of its binding protein WDR5, a subunit of the MLL H3K4 methylase complex, resulting in increased chromatin occupancy and gene activation. LincRNA-mediated stabilization requires direct RNA-protein interaction in a long RNA context, and blocks turnover at a step after target protein poly-ubiquitination. We elucidate the lincRNA binding interface on WDR5. A WDR5 mutant that selectively abrogates lincRNA binding becomes unstable, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and embryonic stem cell self renewal. The ability to modulate protein turnover may allow lincRNAs to control the lifespan of molecular interactions at chromatin and elsewhere, broadening their scope in epigenetics and cell fate control.

overall_design: Gene expression analysis: To establish a differentiation signature for mouse V6.5 ES cells infected with anti mouse WDR5 shRNA, rescued with doxycycline inducible WDR5 WT or WDR5 F266A, total RNA was isolated in biologic duplicate from cells in different conditions and hybridized to Affymetrix Mouse 430 2.0 arrays.

first: Yul

middle: W

last: Yang

first: Yong

last: Chen

first: Bingbing

last: Wan

first: Ming

last: Lei

first: Howard

middle: Y


title: Effect of sleep restriction on the human transcriptome during extended wakefulness

city: Guildford

first: Emma

last: Laing

address: Stag Hill

country: United Kingdom

institute: University of Surrey

summary: In a cross balanced design human subjects were given one week of sufficient sleep and insufficient sleep (6 h per day). Following each of these conditions they were then kept awake for a day, a night and the subsequent day. During each of these periods of extended wakefulness 10 blood samples were taken, RNA was extracted from leukocytes, labelled and hybridised to human whole-genome microarrays

overall_design: A total of 438 samples comprising 26 human subjects, for which 20 samples across multiple time-points/sleep condition were collected.

first: Carla

last: Moller-Levet

first: Simon

last: Archer

first: Giselda

last: Bucca

first: Ana

last: Slak

first: Renata

last: Kabiljo

first: June

last: Lo

first: Nayantara

last: Santhi

first: Malcolm

last: von Schantz

first: Colin

last: Smith

first: D

last: Dijk


title: Genome wide gene expression in a patient with 15q13.3 homozygous microdeletion syndrome

status: Public on Feb 17 2013

city: Kansas City

first: Douglas

middle: C

last: Bittel

state: MO

address: 2401 Gillham Rd

department: Genetics research

institute: Childrens Mercy Hospital

summary: We identified a novel homozygous 15q13.3 microdeletion in a young boy with a complex neurodevelopmental disorder characterized by severe cerebral visual impairment with additional signs of congenital stationary night blindness (CSNB), congenital hypotonia with areflexia, profound intellectual disability, and refractory epilepsy. The mechanisms by which the genes in the deleted region exert their effect are unclear. In this paper we probed the role of downstream effects of the deletions as a contributing mechanism to the molecular basis of the observed phenotype.  We analyzed gene expression of lymphoblastoid cells derived from peripheral blood of the proband and his relatives to ascertain the relative effects of the homozygous and heterozygous deletions.

overall_design: The proband with 15q13.3 homozygous deletion and his parents with 15q13.3 heterozygous deletions described in our previous report 15 were evaluated using Affymetrix aCGH-244K arrays (build hg18).  The aCGH data were validated by qPCR using primers specific to CHRNA7 as previously described. 15   The extended family and comparison subjects were also screened using the CHRNA7 primers. Immortalized lymphoblastoid lines were created from the proband, his mother, father, a paternal half sister, a paternal half brother, a paternal grandmother and two paternal great uncles.   Three lymphoblastoid lines from age- and sex- matched normally developing comparison subjects with normal chromosomes were obtained from the Coriell cell repository [(AG14724 (8 yo),  AG14948 (10 yo),  AG14980 (9 yo)] were used for gene expression comparison with the proband.  The samples from the father, mother and paternal grandmother with heterozygous 15q13.3 deletions were compared to samples from lymphoblastoid cells from adult male and female subjects respectively (normal copy number for 15q13.3 determined by qPCR).

first: Jean-Baptiste

last: Le Pichon

first: Shihui

last: Yu

first: Nataliya

last: Kibiryeva

first: William

last: Graf


title: Parthenogenetic stem cells for tissue-engineered heart repair

status: Public on Feb 23 2013

city: Aachen

first: Martin

last: Zenke

state: NRW

address: Universitatsklinikum Aachen, RWTH

department: Cell Biology

institute: Institute for Biomedical Engineering

summary: Uniparental parthenotes are considered an unwanted byproduct of in vitro fertilization. In utero parthenote development is severely compromised by defective organogenesis and in particular by defective cardiogenesis. Although developmentally compromised, apparently pluripotent stem cells can be derived from parthenogenetic blastocysts. Here we hypothesized that nonembryonic parthenogenetic stem cells (PSCs) can be directed toward the cardiac lineage and applied to tissue-engineered heart repair. We first confirmed similar fundamental properties in murine PSCs and embryonic stem cells (ESCs), despite notable differences in genetic (allelic variability) and epigenetic (differential imprinting) characteristics. Haploidentity of major histocompatibility complexes (MHCs) in PSCs is particularly attractive for allogeneic cell-based therapies. Accordingly, we confirmed acceptance of PSCs in MHC-matched allotransplantation. Cardiomyocyte derivation from PSCs and ESCs was equally effective. The use of cardiomyocyte-restricted GFP enabled cell sorting and documentation of advanced structural and functional maturation in vitro and in vivo. This included seamless electrical integration of PSC-derived cardiomyocytes into recipient myocardium. Finally, we enriched cardiomyocytes to facilitate engineering of force-generating myocardium and demonstrated the utility of this technique in enhancing regional myocardial function after myocardial infarction. Collectively, our data demonstrate pluripotency, with unrestricted cardiogenicity in PSCs, and introduce this unique cell type as an attractive source for tissue-engineered heart repair.

overall_design:
8 samples in total.
Parthenogenetic stem cells (PSC):
- PSC_1
- PSC_2
- PSC_3
Embryoid body (EB) assays of parthenogenetic stem cells:
- EB_PSC_1
- EB_PSC_2
Embryonic stem cells (ESC):
- ESC_1
- ESC_2
- ESC_3

first: Michael

last: Didié

first: Peter

last: Christalla

last: Rubart

first: Vijayakumar

last: Muppala

first: Stephan

last: Döker

first: Bernhard

last: Unsöld

first: Ali

last: El-Armouche

first: Thomas

last: Rau

last: Eschenhagen

first: Alexander

last: Schwoerer

first: Heimo

last: Ehmke

first: Udo

last: Schumacher

first: Sigrid

last: Fuchs

first: Claudia

last: Lange

last: Becker

first: Tao

last: Wen

first: John

last: Scherschel

first: Mark

last: Soonpaa

last: Yang

first: Qiong

last: Lin

first: Dong-Wook

last: Han

first: Hans

last: Schöler

first: Cornelia

last: Rudolph

first: Doris

last: Steinemann

first: Brigitte

last: Schlegelberger

first: Steve

last: Kattman

first: Alec

last: Witty

first: Gordon

last: Keller

first: Loren

last: Field

first: Wolfram

last: Zimmermann


title: Expression data from human lung cancer cell lines with NEDD9 overexpression or NEDD9 knockdown

status: Public on Feb 21 2013

city: Shanghai

first: Hongbin

last: Ji

address: 320 Yue Yang Road

country: China

institute: Shanghai Institutes for Biological Sciences

summary:
NEDD9 is important for lung cancer metastasis. However, the detailed mechanism remains elusive. Using the microarray data generated with human lung cancer cell lines with either NEDD9 overexpression or NEDD9 knockdown, we  plan to idnetify important signal pathways regulated by NEDD9. This may explain how NEDD9 excutes its function in lung cancer.
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.

overall_design: Human lung cancer cell line A549, which has LKB1 loss-of-function mutation and increased expression of NEDD9, was used for two individual NEDD9 knockdown. Human lung cancer cell line CRL-5907, which has wild-type LKB1 and low NEDD9 expression level, was used for NEDD9 overexpression. The microarray was done in A549 cells, A549 cells with two different NEDD9 knockdown; CRL-5907 cells and CRL-5907 cells with NEDD9 overexpression.

first: Yan

last: Feng

first: Zhaoyuan

last: Fang


title: Foxo1/3 depletion in granulosa cells reveals novel mechanisms controlling follicle growth and death and endocrine regulation of pituitary FSH.

status: Public on Feb 16 2013

first: JoAnne

last: Richards

address: One Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: The Foxo transcription factors regulate multiple cellular functions. Foxo1 and Foxo3 are highly expressed in granulosa cells of ovarian follicles. Selective depletion of the Foxo1 and Foxo3 genes in granulosa cells revealed a novel ovarian-pituitary endocrine feedback loop characterized by: 1) undetectable levels of serum FSH but not LH, 2) reduced expression of the pituitary Fshb gene and its transcriptional regulators and 3) ovarian production of a factor(s) that suppresses pituitary cell Fshb. Equally notable and independent of FSH, depletion of Foxo1/3 altered the expression of specific genes associated with follicle growth versus apoptosis by disrupting critical regulatory interactions of Foxo1/3 with the activin and BMP2 pathways, respectively.  As a consequence, granulosa cell proliferation and apoptosis were decreased.  These data provide the first evidence that Foxo1/3 divergently regulate follicle growth or death by interacting with the activin and BMP pathways in granulosa cells and by modulating pituitary FSH production.

overall_design: A direct comparison of ovarian granulosa cells from wild type d25, Foxo1/3 dKO d25 and Foxo1/3 dKO 2 month mice.

first: Zhilin

last: Liu

first: Diego

last: Castrillon

first: Wei

last: Zhou


title: Gene expression data from mouse CD8 T cells

status: Public on Feb 13 2013

first: Yoko

last: Kidani

address: 650 Charles E Young Drive

summary: Determing the influence of lipid metabolism on murine T cell blastogenesis. Gene expression studies from purified  spleen and lymph node T cells with conditional deletion of the SREBP Cleavage Activating Protein (SCAP) ex vivo or activated with plate-bound anti-CD3 and CD28 antibodies for 6 h.

overall_design: CD8 T cells were purified from T cell specific Scap deficient mouse spleens (KO, n=3) and control littermate (WT, n=3). The cells from each mouse were used for RNA extraction at either quiescent (T0) or 6 h activation (T6).

first: Steven

last: Bensinger


title: Expression profile of telomerase deficient iPSC

status: Public on Feb 11 2013

city: Bethesda

first: Yanqin

last: Yang

state: Maryland

address: 10 Center Dr.

institute: NIH

summary:
Critically short telomeres activate p53-mediated apoptosis, resulting in organ failure and causing malignant transformation. Mutations in genes responsible for telomere maintenance are linked to a number of specific human diseases. We derived induced pluripotent stem cells (iPSCs) from patients with mutations in the TERT and TERC telomerase genes. Telomerase-mutant iPSCs elongated telomeres, but at a lower rate than healthy iPSCs, and the magnitude of the elongation deficit correlated with the specific mutation’s impact on telomerase activity. However, elongation significantly varied among iPSC clones harboring the same mutation, and was affected by genetic and environmental factors. iPSCs cultured in hypoxia showed increased telomere length. Potential influence of residual expression of reprogramming factors on telomerase regulation and telomere length was ruled out by excising the transgenes after successful reprogramming. Evidence for telomerase-independent telomere elongation was not observed in these cells. We demonstrate that telomerase is required for telomere elongation in iPSCs and uncover heterogeneity in telomere maintenance even between clones derived from individual patients or siblings with the same mutation, indicating that telomere phenotype may be influenced by acquired and environmental agents. Our data underscore the necessity of studying multiple clones when using iPSCs to model disease.   The exon array were done to validate the pluripotent phenotype of the derived normal and telomerase mutant iPSC and to potentially identify differentially expressed genes in mutant iPSC.
Objective: confirming pluripotency by comparing telomerase mutated-, control-iPSC to  human ESC and to their parental somatic cells (fibroblast used for iPSC derivation)

overall_design: 20 samples total, 5 different fibroblast cells, 13 iPSC lines, 1 ES line (H1) from different passages

first: Thomas

last: Winkler


title: Expression data from FDC-induced myeloid cells (FDMCs)

status: Public on Jun 23 2013

city: Okayama-shi

first: Masaki

last: Magari

address: 3-1-1, Tsushima-naka, Kita-ku

institute: Okayama University

type:
Expression profiling by array
Third-party reanalysis

summary:
We observed that follicular dendritic cell line induced a new type of CD11b+ myeloid cells (FDMCs) when cultured with a lineage-negative c-kit+ population from mouse spleen cells.
Thus, we used microarrays to characterize gene expression of FDMCs.

overall_design:
FDMCs were induced on FDC line for RNA extraction and hybridization on Affymetrix microarrays.
Microarray data of "FDC-induced myeloid cells (FDMCs)" sample were combined with a large collection of other cell- and tissue-specific gene expression data sets (total: 205 individual data sets).  Raw data (.cel) files were normalized using Robust Multichip Analysis (RMA Express; http://rmaexpress.bmbolstad.com/), annotated using the latest libraries available from Affymetrix, and arranged according to cell-type grouping.

first: Neil

middle: A

last: Mabbott

first: Hitoshi

last: Ohmori