title: CLEFMA selectively induces necrotic cell death of H441 lung adenocarcinoma cells via oxidative stress

status: Public on Dec 18 2010

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary:
Despite the growing understanding about the molecular basis of oncogenesis, prevention and cure of cancer remains an unsurpassed challenge. Chemotherapeutic drugs are the mainstay in managing patients diagnosed with any form of cancer. The emergent chemo-resistance, morbid toxicities and overall inefficacy of current drug portfolios in many cancers necessitate the development of new drugs with novel mechanism of action and selective action on cancer cells.  We investigate the molecular action of new chemotherapeutic drug, CLEFMA, uponH441 lund adenocarcinoma cells. The drug was packaged into liposomes and ectopically applied to cells. A control condition comprised from vehicle treated cells. CLEFMA proved to be an effective means of eliminating lung cance rells via oxidative stress induced necrotic cell death.
Investigate the effect of new chemotherapeutic drug, CLEFMA.

overall_design: Two groups were compared, five replicates in each group. Control group comprised from cells treated with empty vehicle, test groups was treated with the drug.

first: Vibhudutta

last: Awasthi


title: Expression analysis of Wv/Wv fetal gonads

status: Public on Dec 20 2010

city: St Lucia

first: Antoine

middle: Dominique

last: ROLLAND

state: QLD, Brisbane

address: 306 Carmody Rd

department: Institute for Molecular Bioscience

country: Australia

institute: University of Queensland

summary: Following sex determination, XY and XX gonads develop into a testis and an ovary, respectively. Depending on the sex of the gonad, resident germ cells will subsequently be committed to either spermatogenesis or oogenesis. In this study we took advantage of the Wv/Wv mouse genetic model, in which gonads are almost devoided of germ cells, to uncover gene expression underlying fetal germ cell development.

overall_design: Male and Female gonads were collected at 12, 14 and 16 days post coitum (dpc) from wild-type and Wv/Wv mouse embryos. Total RNAs were extracted and hybridized on Affymetrix microarrays. Expression signals from male and female gonads or from wild-type and mutant gonads were compared to identify sexually dimorphic genes as well as genes expressed in germ cell during fetal gonad development.

middle: D

last: Rolland

first: Kim

middle: P

last: Lehmann

first: Kamin

middle: J

last: Johnson

first: Kevin

middle: W

last: Gaido

first: Peter

last: Koopman


title: Continuous expression of the transcription factor E2-2 maintains the cell fate of mature plasmacytoid dendritic cells

status: Public on Dec 21 2010

city: New York

first: Boris

last: Reizis

state: NY

department: Microbiology and Immunology

country: USA

institute: Columbia University Medical Center

type: Genome binding/occupancy profiling by array

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: A global expression switch marks pachytene initiation during mouse male meiosis

status: Public on Dec 16 2010

city: Jupiter

first: Philippe

middle: R

last: Bois

state: FL

address: 130 Scripps Way

department: Cancer Biology

institute: The Scripps Research Institute - Scripps Florida

summary: Male spermatogenesis is an essential and complex developmental process with the purpose to gain totipotency and allow a whole new organism to develop upon fertilization. While single-gene based studies have provided insights into the mechanisms at work, global profiling is clearly required to deconvolute these processes. Here, by isolating highly enriched mouse meiotic cell populations, we report a comprehensive gene expression map of mammalian meiosis. Our data reveal in unique details the dynamic of fundamental expression patterns such as the global chromosome X inactivation and reactivation allowing to precisely dissect this unique process. It also reveals a rapid global expression switch at the initiation of the long pachytene stage reminiscent and coincident with the commitment to meiosis observed in budding yeast. Overall, this meiotic atlas provides an exhaustive blueprint and resource for deconvoluting mammalian gametogenesis and meiosis.

overall_design: 10- to 16-week-old male C57BL/6 x DBA/2J F1 testis were used for sorting multiple meiotic fractions. These samples were used for subsequent RNA purification, labeling and hybridization to Affymetrix arrays. 1-4 biological replicates per fraction.

first: Mohammad

last: Fallahi

first: Irina

middle: V

last: Getun

first: Zhen

middle: K

last: Wu


title: Increased Expression of Angiogenic Genes in the Brains of Mouse Meg3-null Embryos

status: Public on Dec 17 2010

city: Boston

first: Xun

last: Zhang

state: MA

address: 55 Fruit St Rm Bull 450

department: Neuroendocrine Unit

institute: Massachusetts General Hospital

summary: MEG3 (Maternally Expressed Gene 3) is a non-coding RNA that is highly expressed in the normal human brain and pituitary.  Expression of MEG3 is lost in gonadotroph-derived clinically non-functioning pituitary adenomas.  Meg3 knock-out mice were generated to identify targets and potential functions of this gene in embryonic development and tumorigenesis.  Gene expression profiles were compared in the brains of Meg3-null embryos and wild-type litter-mate controls using microarray analysis.  Microarray data were analyzed with GeneSifter which uses Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) classifications to identify signaling cascades and functional categories of interest within the data set.  Differences were found in signaling pathways and ontologies related to angiogenesis between wild-type and knock-out embryos.  Quantitative RT-PCR and histological staining showed increased expression of some VEGF pathway genes and increased cortical microvessel density in the knock-out embryos.  These results are consistent with reported increases in VEGF signaling observed in human clinically non-functioning pituitary adenomas.  In conclusion, Meg3 may play an important role in control of vascularization in the brain and may function as a tumor suppressor by preventing angiogenesis.

first: Francesca

middle: E

last: Gordon

first: Catherine

middle: L

last: Nutt

first: Pornsuk

last: Cheunsuchon

first: Yuki

last: Nakayama

first: Yunli

last: Zhou

first: Anne

last: Klibanski


title: Developmental stages after fertilization in Salmo salar

status: Public on Dec 10 2010

city: Victoria

first: Ben

middle: F

last: Koop

state: BC

address: PO Box 3020 STN CSC

department: Biology

country: Canada

institute: The University of Victoria

summary: Atlantic salmon (Salmo salar L.) is an environmentally and economically important organism and its gene content is reasonably well characterized. From a transcriptional standpoint, it is important to characterize the normal changes in gene expression over the course of early development, from fertilization through to the parr stage.S. salar samples were taken at 17 time points from 2 to 89 days post fertilization. Total RNA was extracted and cRNA was synthesized and hybridized to a new 44K oligo salmonid microarray platform. Quantified results were subjected to preliminary data analysis and submitted to NCBI’s Gene Expression Omnibus. Throughout the entire period of development, several thousand genes were found to be differentially regulated. This work represents the trancriptional characterization of a very large geneset that will be extremely valuable in further examination of the transcriptional changes in Atlantic salmon during the first few months of development. The expression profiles can help to annotate salmon genes in addition to being used as references against any number of experimental variables that developing salmonids might be subjected to.

overall_design:
17 time points (2 - 89 dpf) with three samples for each time point
Equimolar amounts from all three individuals in each time point were pooled. Then reference pool was created by including equal quantities cRNA from each time point, except for the first time point which had less material included.

first: Stuart

middle: G

last: Jantzen

first: Dan

middle: S

last: Sanderson

first: Kris

last: von Schalburg

first: Motoshige

last: Yasuike


title: Gene expression analysis in the absence of Creb in Pomc-expressing neurons of the hypothalamus

status: Public on Dec 14 2010

city: NEW YORK

first: franck

last: oury

address: HHSC 701W 168th street

institute: Columbia University

summary: Brain-derived serotonin favors appetite in mice following its binding to the Htr1a and Htr2b receptors in arcuate neurons of the hypothalamus. In this study, we identified that CREB is the transcriptional effector of brain-derived serotonin control of appetite in arcuate nuclei.

overall_design:
In this dataset, we identified the downstream genes of CREB in arcuate neurons of the hypothalamus controling appetite.
We isolated hypothalami of wild type and Creb-pomcCre-/- (deleted for Creb selectively in arcuate neurons of the hypothalamus) mice and performed microarray experiments.

first: Vijay

last: Yadav

first: Franck

last: Oury

first: Kenji

last: Tanaka

first: Tiffany

last: Thomas

first: Ying

last: Wang

first: Serge

last: Cremers

first: Rene

last: Hen

first: Andree

last: Krust

first: Pierre

last: Chambon

first: Gerard

last: Karsenty


title: Differentially expressed genes of CD11b+Gr-1+ myeloid cells

status: Public on Dec 15 2010

first: XIANGDONG

last: YANG

address: 1130 St Nicholas Ave

department: Medicine

summary: Differentially expressed genes of CD11b+Gr-1+ immature myeloid cells (IMCs) in the bone marrow and colonic tumor setting of histidine decarboxylase (HDC)-KO mice were examined by microarray (Affymetrix Mouse 430.2 array). Myeloid differentiation-related candidate genes were sought to be isolated and functionally studied.

overall_design:
Total RNA of HDC-expressing CD11b+Gr-1+ IMCs of bone marrow were extracted from HDC-EGFP and HDC-EGFP/HDC-KO mice (3 mice in each group). CD11b+Gr-1+ myeloid-derived suppressor cells (MDSCs) of colon tumor were sorted from 10-12 colon tumors of WT and HDC-KO mice (5 mice in each group), and pooled to extract total RNA for microarray studies. Two technical replicates for each of the four groups.
Four sets of comparisons were performed to screen for upregulated or downregulated genes in the HDC-KO CD11b+Gr-1+ IMCs or MDSCs (experiment group) compared to the WT group: (1) HDC-expressing CD11b+Gr-1+ IMCs of bone marrow of HDC KO mice compared to bone marrow IMCs of WT mice; (2) CD11b+Gr-1+ MDSCs in tumors of HDC-KO mice compared to WT mice; (3) CD11b+Gr-1+ MDSCs of WT colon tumors compared to IMCs in the WT bone marrow; and (4) CD11b+Gr-1+ MDSCs of colon tumors of HDC-KO mice compared to IMCs in the bone marrow of HDC-KO mice.

first: Xiang-Dong

last: Yang

first: Walden

last: Ai

first: Samuel

last: Asfaha

first: Govind

last: Bhagat

first: Richard

middle: A

last: Friedman

first: Guangchun

last: Jin

first: Heuijoon

last: Park

first: Benjamin

last: Shykind

first: Thomas

last: Diacovo

first: Andras

last: Falus

first: Timothy

middle: C


title: Gene expression profile of the mammary stroma in Rarb -/- mice compared to their wild type littermates

city: Montréal

first: Xingxing

last: LIU

state: QC

address: 1160 Pine Ave

department: Biochemistry, GCC

institute: McGill University

summary:
Inactivation of RAR-b, which has been reported as a tumor suppressing gene by numerous studies, results in protective effect against the tumorigenesis induced by activated ErbB2. Moreover, tissue recombination indicates that the RAR-b deficient-microenvironment, rather than the RAR-b status of mammary epithelial cells, plays a key-determining role in the initiation and progression of the mammary carcinoma. Ablation of RAR-b extensively modulates the remodeling of stroma during tumor progression through suppressing the activation and transdifferetiation of myofibroblasts.
RNA microarray has been employed to identify the gene expression signature in the mammary stroma of our RAR-b null animals. We want to find out the underlining mechanism of the protective effects resulted from Rarb abliton.

overall_design: A global gene expression profile of mouse mammary stroma was obtained on total RNA from the cleared mammary fat pads (stroma) of both RAR-b KO (n=3) and their wild type (n=3) littermates at the age of four weeks.

last: Liu

first: Vincent

last: Giguere


title: Expression time series during the differentiation of ventral motor neurons from embryonic stem cells

city: University Park

first: Shaun

last: Mahony

state: PA

address: 404 South Frear Bldg

department: Biochemistry & Molecular Biology

institute: Penn State University

summary: The aim of this study is to profile gene expression dynamics during the in vitro differentiation of embryonic stem cells into ventral motor neurons. Expression levels were profiled using Affymetrix microarrays at six timepoints during in vitro differentiation: ES cells (Day 0), embryoid bodies (Day 2), retinoid induction of neurogenesis (Day 2 +8hours of exposure to retinoic acid), neural precursors (Day 3), progenitor motor neurons (Day 4), postmitotic motor neurons (Day 7).

overall_design: The differentiation of ventral motor neurons is induced by treating embryonic stem cell cultures with retinoic acid and hedgehog agonist. Here, gene expression patterns are profiled at various defined stages during the differentiation process using Affymetrix expression arrays.

first: Esteban

middle: O

last: Mazzoni

first: Scott

last: McCuine

first: P

last: Rolfe

first: Robin

last: Dowell

first: Seraphim

last: Thornton

first: Laurie

last: Boyer

last: Young

first: David

last: Gifford

first: Hynek

last: Wichterle


title: Expression data from mouse Nuocytes

status: Public on Dec 09 2010

city: CAMBRIDGE

first: Andrew

last: MCKENZIE

address: HILLS ROAD

country: United Kingdom

institute: MRC-LMB

summary: Nuocytes are a recently described cell that responds to both IL-25 and IL-33 and produce high levels of IL-13 and IL-5

overall_design: Mice were administered with 3 daily doses of IL-25 (400 ng/dose).  Nuocytes were purified by flow cytometry. Spleen cells prepared from IL-25-treated mice were depleted of lineage+ cells before cell sorting by incubation with biotin-conjugated anti-CD3, anti-CD19, anti-CD11b and anti-FcεRI antibodies before removal of antibody-bound cells by magnetic separation using Dynabeads (Invitrogen). Lineage-depleted cells were stained with PE-conjugated antibodies against CD4, CD8, B220, TER-119 and CD11b, a FITC-conjugated antibody against CD45, and an APC-conjugated antibody against ICOS. PE−, FITC+, APC+ cells were collected using a Mo-flo cell sorter, and purity was checked by staining with lineage antibodies and antibodies against IL-17BR and T1/ST2.  Following purification nuocytes were prepared directly for microarray gene expression analysis or cultured with IL-33 and IL-7 (both at 10 nanograms/ml) for 9 days before being prepared for microarray gene expression analysis.

last: McKenzie


title: Gene expression change induced by bisphenol A in mouse urogenital sinus

status: Public on Dec 06 2010

city: Shinagawa-ku

first: KATSUHIDE

last: IGARASHI

state: Tokyo

department: Life Science Tokyo Advanced Research center (L-StaR)

country: Japan

institute: Hoshi University School of Pharmacy and Pharmaceutical Science

summary:
Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is a well-known, ubiquitous estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we first examined the alterations of in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS).
Next, to investigate the BPA-specific gene alterations related to increases of the E2 levels and aromatase activity, we performed comprehensive gene expression analysis using Affymetrix GeneChip in the BPA-treated or DES-treated male UGS at embryonic day 17th and postnatal day 1st.

overall_design: Pregnant female C57BL/6 mice were exposed to BPA (20 μg/kg/day) or synthetic estrogen Diethylstilbestrol (DES: 0.2 μg/kg/day), which were dissolved in tocopherol-stripped corn oil, on embryonic day 13 (E13) to E16. Between E17 and postnatal day 1 (P1), all animals were terminated by an overdose of isoflurane followed by cervical dislocation. Fetuses were collected at E17, E18, P0, and P1. The bladder and urethra were removed and dissected to isolate UGS and collected in RNA later. To isolate pure UGS, other tissues such as the bladder, urethra, Wolffian duct (WD), seminal vesicle (SV), and Mullerian duct (MD) were removed from both the male and female urogenital tracts. The histopathology of the mouse UGS was then examined by hematoxylin and eosin staining. Total RNA was extracted using the Qiagen mini RNA Easy kit. Each RNAs were linearly amplified and hybridized to Affymetrix GeneChip.

first: Kenichiro

last: Ishii

first: Katsuhide

last: Igarashi


title: Expression data from mouse collecting duct cell, mpkCCD, in response to a peptide hormone vasopressin analog, dDAVP

city: Taipei

first: Ming-Jiun

last: Yu

address: Rm 816, No. 1 Ren-Ai Road Section 1

department: Institute of Biochemistry and Molecular Biology

country: Taiwan

institute: National Taiwan University College of Medicine

summary: Vasopressin is the major hormone that regulates renal water excretion.  It does so by binding to a receptor in renal collecting duct cells, triggering signaling pathways that ultimately regulate the abundance, location, and activity of the water channel protein aquaporin 2.  We took an advantage of quantitative large scale proteomic technologies and oligonucleotide microarrays to quantify steady state changes in protein and transcript abundances in response to vasopressin in a collecting duct cell line, mpkCCD clone 11 (Yu et al. PNAS 2009, 106:2441-2446).  This cell line originally developed by Alan Vandewalle’s group recapitulates vasopressin-mediated AQP2 expression and phosphorylation as seen in native colleting duct cells.

overall_design: The mpkCCD cells were grown on membrane supports to permit polarization.  Once transepithelial resistance reached 5kohm per centimeter square and higher, the cells were exposed to the vasopressin V2 receptor analog, dDAVP, at a physiological concentration, 0.1nM, for 5 days.  Control experiments were done with cells exposed to vehicle alone.  Total RNA was harvested and processed for transcript expression analysis using Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.  Each experimental treatment, vehicle and dDAVP, was repeated 3 times.


title: Gene expression profile of mature plasmacytoid dendritic cells (PDC) after the deletion of transcription factor E2-2

first: Boris

last: Reizis

summary: The interferon-producing plasmacytoid dendritic cells (PDC) share common progenitors with antigen-presenting classical dendritic cells (cDC), yet they possess distinct morphology and molecular features resembling those of lymphocytes. It is unclear whether the unique cell fate of PDC is actively maintained in the steady state. We report that the deletion of transcription factor E2-2 from mature peripheral PDC caused their spontaneous differentiation into cells with cDC properties. This included the loss of PDC markers, increase in MHC class II expression and T cell priming capacity, acquisition of dendritic morphology and induction of cDC signature genes. Genome-wide chromatin immunoprecipitation revealed direct binding of E2-2 to key PDC-specific and lymphoid genes, as well as to certain genes enriched in cDC. Thus, E2-2 actively maintains the cell fate of mature PDC and opposes the “default” cDC fate, in part through direct regulation of lineage-specific gene expression programs.

overall_design: Inducible deletion of E2-2 (Tcf4) has been performed by administering tamoxifen to conditional E2-2flox/flox Rosa26-CreER+ mice or to E2-2flox/flox Rosa26-CreER- control littermates. Four or six days later total splenocytes were isolated, pooled from 2-3 mice and PDC (CD11b- B220+ CD11clow Bst2+) were isolated by sorting. Global gene expression profiles of E2-2-deficient (null) and control (Ctrl) PDC were compared using Affymetrix microarrays (GPL1261).

first: Anna

last: Bunin


title: Expression in wild type and TgDREAM mouse B cells unstimulated or 2 days after  LPS+IL4 stimulation

status: Public on Dec 07 2010

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

country: Spain

institute: CNB, CSIC

summary: DREAM/KChIP-3 is a calcium-dependent transcriptional repressor highly expressed in immune cells. Transgenic mice expressing a dominant active DREAM mutant show reduced serum immunoglobulin levels. In vitro assays show that reduced immunoglobulin secretion is an intrinsic defect of transgenic B cells that occurs without impairment in plasma cell differentiation but with an accelerated entry in cell division and an increase in class switch recombination. B cells from DREAM knockout mice did not show any phenotype, due to compensation by endogenous KChIP-2. Expression arrays revealed modified expression of Edem1 and Derlin3, two proteins related to the ER-associated degradation pathway and of Klf9, a cell-cycle regulator. Our results disclose a function of DREAM and KChIP-2 in Ig subclass production in B lymphocytes.

overall_design: We used Affymetrix microarrays (GeneChip Mouse Genome 430 2.0) to compare global gene expression in wild type (WT) versus transgenic B cells (Tg), unstimulated and 2 days after LPS + IL4 stimulation. For ech type of sample three hybridizations were carried-out (independent biological replicates).

first: Magali

last: Savignac

first: Britt

last: Mellström

first: Anne-Gaëlle

last: Bébin

first: Laurent

last: Delpy

first: Eric

last: Pinaud

first: Jose

last: Naranjo


title: Genome-wide microarray analysis of normal human fibroblasts in response to γ-radiation and the radiation induced bystander effect

status: Public on Dec 03 2010

city: Oslo

first: Erta

last: kalanxhi

address: Montebello 0310

country: Norway

institute: Oslo University Hospital

summary: The bystander effect from ionizing radiation consists of cellular responses generated from non-irradiated cells to the irradiation of their neighbors. The bystander effect can lead to DNA damage and genomic instability in the affected cells. This non-targeted effect of radiation has received attention due to its potential implications for cancer therapy and radiation protection. Although studied extensively, a complete understanding of its molecular mechanism is the subject of ongoing research. While many studies have targeted specific factors which are suggested to be involved in the bystander effect, few have looked at whole genome gene expression in bystander cells. Furthermore, even fewer studies have looked at the expression in normal human cell lines. In this study, we have monitored transcriptional responses to γ-radiation in irradiated and bystander normal fibroblasts simultaneously using a genome-wide microarray approach. In this study we have investigated the transcriptional response in F11hTERT fibroblasts irradiated with 2 Gy, 2 hours after irradiation.

overall_design:
GSM634191-226: Total RNA was isolated from normal human fibroblasts irradiated with 2.0 Gy and fibroblasts incubated with medium from sham irradiated and irradiated cells 2 h after irradiation. RNA was isolated 4, 8 and 26 h after irradiation and there are 4 replicates for each sample for a total of 36 samples.
GSM795448-455: Total RNA was isolated from immortalized human fibroblasts F11hTERT irradiated with 0 and 2 Gy g-radiation, 2 h following irradiation. There are 4 replicates for each sample for a total of 8 samples.

last: Kalanxhi

first: Jostein

last: Dahle


title: A mouse Embryonic Stem Cell Bank for inducible overexpression of human chromosome 21 genes

city: Napoli

first: Mario

last: Lauria

address: via P. Castellino 111

country: Italy

institute: TIGEM

summary:
The HSA21-mES Cell Bank includes, in triplicate clones, thirty-two murine orthologs of HSA21 genes, which can be overexpressed in an inducible manner using the Tet-off system integrated in the Rosa26 locus.
The following subset of twenty clones were characterized by microarray analysis: Bach1, Erg, Ets2, Gabpa, ZFP295, Nrip1, Olig1, Olig2, Pknox1, 1810007M14Rik, Runx1, Aire, Sim2, Dscr1, DYRK1A, SNF1LK, Ripk4 , Hunk,  Pdxk, Pfkl.

overall_design: Each triplicate clone was transcriptionally profiled by microarray analysis using Affymetrix Mouse 430_2 arrays before and after induction (Affymetrix 430A_2 in case of Runx1), yielding six arrays for each overexpression experiment.

first: R

last: De Cegli

first: A

last: Romito

first: S

last: Iacobacci

first: L

last: Mao

first: M

last: Fedele

first: J

last: Klose

first: C

last: Borel

first: P

last: Descombes

last: Antonarakis

first: D

last: di Bernardo

last: Banfi

last: Ballabio

first: G

last: Cobellis


title: Expression data from MxCre;E2F1-/-2-/-3f/f Cd11B myeloid cells

city: Columbus

first: Prashant

last: Trikha

state: OH

address: 460 W 12 Avenue

department: HCG

institute: Ohio State University

summary: To understand the underlying cause for the observed apoptosis in E2f1-3 deficient myeloid cells. We compared gene expression profiles of Cd11b+ sorted myeloid cells isolated from bone marrow of control (E2F1-/- ) and experimental (Mxcre;E2F1-/-2-/-3f/f ) mice.

overall_design: RNA was extracted from Cd11b cells from bone marrow of eight-week-old mice after FACS sorting with FITC- cojugated Cd11b antibody.


title: Activation and Function of Alternatively and Classically Activated MH-S Alveolar Macrophages

city: Baltimore

first: Joshua

last: Reece

state: MD

address: 615 N. Wolfe Street

department: MMI

institute: Johns Hopkins University BSPH

summary:
Alveolar macrophages (AMs), the tissue dwelling monocytes of the lungs, are the first to encounter the menagerie of items that pass the mechanical barriers of the nose and throat. AMs must be able to mount an effective immune response against invading pathogens as well as maintain homeostasis in the lungs to avoid excessive inflammatory responses.  In vivo data suggests that AMs can take on different phenotypes depending on the conditions of simulation.  Limited progress has been made in defining the mechanisms responsible for these phenotypic issues largely due to logistical difficulties in isolating a sufficient number of cells from the lungs that have not been activated by the isolation protocol.  To circumvent these logistical issues, an in vitro cell culture model was developed to study AM biology with specific emphasis on the generation of alternatively activated alveolar macrophages (AAAMs).  Utilizing the BALB/c AM cell line MH-S it was determined that LPS could be used to generate classically activated AMs (CAAMs) and that IL-4 was effective in producing AAAMs.  We examined the full transcriptome of AAAMs and CAAMs using microarray technology in an attempt to confirm previously described AAAM expression patterns and to identify new molecules associated with AM phenotypic change.  AAAMs up-regulated an entirely distinct group of transcripts including genes encoding Arg1, Ym1 and a number of repair and remodeling genes whereas CAAMs up-regulated proinflammatory cytokines such as IL-1, IL-6 and IL-12. Additional novel markers are identified in this study to better characterize CAAMs and AAAMs in the lung.
Keywords: Characterization of Cell Type Based on Activation Stimulus

overall_design: MH-S Cells (ATCC CRL-2019) were stimulated with either 50 ng/ml IL-4 or 1µg/ml LPS and analyzed 12 hours later by whole genome DNA microarray analysis.

first: Mark

last: Siracusa

first: Alan

last: Scott


title: Genome profiling of mouse pulmonary epithelial type II cells

city: Rochester

first: Stephen

last: Welle

address: 601 Elmwood Avenue

institute: University of Rochester

summary: Pulmonary alveoli contain two distinct populations of epithelial cells.  Type II cells produce pulmonary surfactant lipids and surfactant-associated proteins (SP) required for maintaining alveolar surface tension at the air-liquid interface and host defense against respiratory pathogens.  Type II cells are also progenitors for epithelial type I cells, a terminally differentiated elongated cell that covers microvascular endothelial cells and participates in gas exchange.   Despite some indirect evidence, it is unknown whether subpopulations of type II cells exist.   We created a line of transgenic mice expressing enhanced green fluorescent protein (EGFP) under control of the human SP-C promoter.  Expression of EGFP may define a subpopulation of type II cells because it is 1) expressed in approximately 10% of type II cells, 2) appears much later in embryonic development than SP-C, and 3) selectively proliferates in mice infected with influenza A virus.  To determine whether EGFP defines a unique subpopulation of type II cells, RNA was isolated from EGFP-positive and negative type II cells and hybridized to affymetrix arrays.  Of the genes detected in EGFP-positive cells, most were equally detected in EGFP-negative cells.  However, approximately 350 genes were selectively elevated ≥5-fold in EGFP-positive cells and 1500 genes selectively expressed by EGFP-negative cells.  These findings suggest EGFP defines a subpopulation of type II epithelial cells in this line of transgenic mice.

overall_design: Type II cells were harvested from approximately 10 young adult (8-week) mice and sorted into EGFP-positive (sample EGFP-1) and EGFP-negative (sample nonEGFP-1) populations using a B-D FACSVantage SE cell sorter.  RNA was prepared from approximately two million cells and hybridized to Affymetrix M430 2.0 array as a one by one comparison.  The isolation and gene expression analysis of EGFP-positive and EGFP-negative type II cells was repeated a second (using EGFP-2 and nonEGFP-2 samples) and third (using EGFP-3 and nonEGFP-3 samples) time.

first: Michael

last: O'Reilly


title: Genome-wide expression analysis of the mouse pars tuberalis (PT) under chronic short-day and long-day conditions

status: Public on Dec 02 2010

city: Kobe, Hyogo

first: Hiroki

last: Ueda

address: 2-2-3, Minatojima-minamimachi, Chuo-ku

department: Center for Developmental Biology

institute: RIKEN

summary: Living organisms detect seasonal changes in day length (photoperiod), and alter their physiological functions accordingly, to fit seasonal environmental changes. This photoperiodic system is implicated in seasonal affective disorders and the season-associated symptoms observed in bipolar disease and schizophrenia. Thyroid-stimulating hormone beta subunit (Tshb), induced in the pars tuberalis (PT), plays a key role in the pathway that regulates animal photoperiodism. However, the upstream inducers of Tshb expression remain unknown. Here we show that late-night light stimulation acutely triggers the Eya3-Six1 pathway, which directly induces Tshb expression. Using melatonin-proficient CBA/N mice, which preserve the photoperiodic Tshb-expression response, we performed a genome-wide expression analysis of the PT under chronic short-day and long-day conditions. These data comprehensively identified long-day and short-day genes, and indicated that late-night light stimulation induces long-day genes. We verified this by advancing and extending the light period by 8 hours, which acutely induced Tshb expression, within one day. In a genome-wide expression analysis under this condition, we searched for candidate upstream genes by looking for expression that preceded Tshb’s, and identified Eya3 gene. These results elucidate the comprehensive transcriptional photoperiodic response in the PT, revealing the complex regulation of Tshb expression and unexpectedly rapid response to light changes in the mammalian photoperiodic system.

overall_design: Mice were separated into 2 groups. One group was maintained under the short-day conditions (light: dark = 8 h:16 h, ZT0 = lights on, ZT8 = lights off, 400 lux) and the other was housed under long-day conditions (light:dark = 16 h:8 h, ZT0 = lights on, ZT16 = lights off, 400 lux) for 2 weeks. The PTs of both groups were retrieved every 4 h for 1 day (6 time points for each group), starting at ZT0. For the experiments performed during the first day of the long-day conditions, we applied two different conditions, following 3 weeks under short-day conditions. In one, the light-onset was advanced by 8 hours (advance condition), and in the other, the dark period was delayed by 8 hours (delay condition). PTs from both groups were obtained every 4 h for 1 day, starting at the lights-on time. (Lights on for the advance condition was ZT16 as defined by the short-day condition. Lights on for the delay condition was ZT0).  We sampled 25 mice at each time point. This whole procedure was repeated twice (n = 2) to obtain experimental replicates.

first: Koh-hei

last: Masumoto

first: Maki

last: Ukai-Tadenuma

first: Takeya

last: Kasukawa

first: Mamoru

last: Nagano

first: Kenichiro

last: Uno

first: Kaori

last: Tsujino

first: Kazumasa

last: Horikawa

first: Yasufumi

last: Shigeyoshi


title: WIN 18,446 2dpp testis culture

status: Public on Nov 25 2010

city: Pullman

first: Ryan

last: Evanoff

state: WA

department: School of Molecular Biosciences

institute: Washington State University

summary: Analysis of 2dpp whole testes cultured for 24h in the presence of WIN 18,446, a BDAD compound.  BDADs (Bis-(dichloroacetyl)-diamines) have been shown previously to inhibit spermatogenesis and function as male contraceptives in many species; however, their mechanism of action has yet to be fully described.  Results provide insight into the ability of WIN 18,446 to inhibit retinoic acid synthesis in the murine testis.

overall_design: Testes were removed from 2dpp 129 mice and cultured for 24h in an organ culture mold in the presence of WIN 18,446.  Total RNA was extracted and hybridized to Affymetrix Mouse Genome 430 2.0 arrays.

first: C

last: Hogarth

first: M

last: Griswold


title: Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using TALLYHO x C57BL6 F2 mice

status: Public on Dec 01 2010

city: Knoxville

first: Arnold

last: Saxton

state: TN

address: Dept. of Animal Science

institute: University of Tennessee

summary: Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The TALLYHO/JngJ (TH) mouse is a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia. To determine the genetic factors that contribute to these T2D related characteristics in TH mice, we interbred TH mice with C57BL/6J (B6) mice. The parental, F1, and F2 mice were phenotyped at 8, 12, 16, 20, and 24 weeks of age for 4-hour fasting plasma triglyceride, cholesterol, insulin, and glucose levels, as well as body weights. Fat pad and carcass weights were measured at 24 weeks after sacrificing the mice. The F2 mice were genotyped genome-wide for 68 markers. Of 393 genotyped F2 mice, 16 were chosen from the extremes of the triglyceride distribution (8 high and 8 low), and liver, pancreas, muscle and adipose tissue were measured for gene expression. Gene expression quantitative trait locus (eQTL) analysis aided in selection of candidates underlying hyperlipidemia, diabetes and obesity QTLs. We identified several genetic loci that affected quantitative variation in plasma lipid and glucose levels and obesity traits.

overall_design: 16 (8 high and 8 low) out of 393 F2 mice were chosen from the extremes of the triglyceride distribution, excluding overtly diabetic mice, and liver, pancreas, muscle and adipose tissue were measured for gene expression. In addition to data from the 64 microarrays on the 16 mice, a supplemental file with phenotypes and marker genotypes is provided for all mice as a supplementary file on the Series record (below). Mouse identification numbers are included to connect the data files.

first: Taryn

last: Stewart

first: Hyoung

middle: Y

last: Kim

middle: M

first: Jung

middle: H


title: Expression data from wild type or FIZZ2 knockout murine lungs

status: Public on Nov 29 2010

city: Ann Arbor

first: Tianju

last: Liu

state: Michigan

address: 109 Zina pitcher pl

department: Pathology

institute: University of Michigan

summary:
To study the possible fibrotic role of FIZZ2, bleomycin was used to induce pulmonary fibrosis in wild type and FIZZZ2 knockout mice, lungs were then harvested and processed for RNA isolation.
We used microarrays to detail the global gene expression regulated by FIZZ2 during fibrotic process.

overall_design: Bleomycin/saline treated wild type or FIZZ2 knockout lungs at day 21 post injection were harvested for RNA isolation and hybridization on Affymetrix microarrays

first: Sem

last: Phan


title: mRNA expression data from primary untreated neuroblastoma tumour samples

city: Gent

first: Pieter

last: mestdagh

address: De Pintelaan 185

country: Belgium

institute: Center for Medical Genetics

summary:
The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains largely elusive. Here we examined the effects of activation of the entire miR-17-92 cluster on global protein expression in neuroblastoma cells.
In this dataset we deposit global mRNA expression data obtained form primary neuroblastoma tumour cells. This data was used to demonstrate negative correlation between TGFB target gene expression and expression of the miR-17-92 cluster.

overall_design: Expression of different TGFB target genes was correlated to miR-17-92 expression using Spearman's Rank statistics in 40 tumours. A correlation heatmap was calculated to visualize the inverse relation between miR-17-92 expression and TGFB target gene expression.

last: Mestdagh

first: Anna-Karin

last: Boström

first: Francis

last: Impens

first: Erik

last: Fredlund

first: Gert

last: Van Peer

first: Pasqualino

last: De Antonellis

first: Kristoffer

last: von Stedingk

first: Bart

last: Ghesquière

first: Stefanie

last: Schlierf

first: Johannes

last: Schulte

first: Massimo

last: Zollo

first: Alexander

last: Schramm

first: Kris

last: Gevaert

first: Håkan

last: Axelson

first: Frank

last: Speleman

first: Jo

last: Vandesompele


title: KKTa_isolated glomeruli

city: Tokyo

first: Maki

last: Murakoshi

address: 2-1-1, Hongo, Bunkyo-ku

department: Division of Nephrology, Department of Internal Medicine

institute: Juntendo University School of Medicine

summary: High dietary fat intake is a major risk factor for the development of obesity, which is frequently associated with diabetes. To identify genes involved in diabetic nephropathy, GeneChip Expression Analysis was employed to survey the glomerular gene expression profile in diabetic KK/Ta mice fed with a high-fat diet (HFD).

overall_design: Isolated glomeruli from three 20-week-old KK/Ta mice fed with HFD (HFD group) or a normal fat diet (Chow group) were dissected. Total RNA was extracted and labeled for hybridization using the Affymetrix GeneChip Mouse Genome 430 2.0 Array. The gene expression profile was compared between the HFD and Chow groups using GeneSpring 7.3.1 software.

first: Mitsuo

last: Tanimoto

first: Tomohito

last: Gohda

first: Yasuhiko

last: Tomino


title: Subcellular expression profiling of the growth cones of retinal ganglion cells (RGC)

status: Public on Nov 23 2010

city: Cambridge

first: Brian

middle: Yee Hong

last: Lam

address: Box 289 Addenbookes Hospital, Hills Road

department: Metabolic Research Laboratories

institute: University of Cambridge

summary:
Cue-directed axon guidance depends partly on local translation in growth cones. Many mRNA transcripts are known to reside in developing axons yet little is known about their subcellular distribution or, specifically, which transcripts are in growth cones.
Laser capture microdissection (LCM) was used to isolate the growth cones of retinal ganglion cell (RGC) axons of two vertebrate species, mouse and Xenopus, coupled with unbiased genome-wide microarray profiling.

sample_organism:
Xenopus laevis
Mus musculus

platform_organism:
Xenopus laevis
Mus musculus

overall_design: Localized mRNA from the isolated growth cones of  Xenopus laevis and Mus musculus retinal ganglion cells were subjected to microarray analysis

first: Krishna

last: Zivraj

first: Yi

last: Tung

first: Michael

last: Piper

first: Laura

last: Gumy

first: James

last: Fawcett

first: Giles

last: Yeo

first: Christine

last: Holt


title: Exon-level expression profiles of GBM brain tumors

status: Public on Nov 21 2010

city: new york

first: Viviane

last: Tabar

address: 411 east 67th street

department: neurosurgery

institute: MSKCC

summary:
Transcriptome analysis of RNAs from brain tumor
Investigate potential of true exon level expression profiling .

overall_design: We analyzed brain tumor from 16 patients (9 males, 7 females) using the Affymetrix Human Exon 1.0 ST V2 platform. Array data was processed by Affymetrix Exon Array Computational Tool.

first: Cameron

last: Brennan


title: Knockout of the Acyl CoA binding protein (ACBP) in mice - expression profile from the liver of 21 days old ACBP-/- and +/+ mice.

status: Public on Nov 26 2010

city: Odense M

first: Susanne

last: Mandrup

address: Campusvej 55

department: Biochemistry and Molecular Biology

country: Denmark

institute: University of Southern Denmark

summary: The ACBP knockout were created by targeted disruption of the gene in mice. The expression profiling was performed on liver tissue from ACBP-/- (KO) and +/+ (WT) mice at the age of 21 days, which in our study is the time immediately before weaning. The mice used for this experiment were taken directly away from their mother. Thus, having free access to chow and breast milk until sacrificed at 8-11am

overall_design: 15 ACBP-/- and 15 +/+ control mice divided into 6 groups (KO1, KO2, KO3, WT1, WT2 and WT3) with 5 individuals in each group were used for this study.

first: Ditte

last: Neess

first: Maria

last: Bloksgaard

first: Signe

last: Bek

first: Ann-Britt

last: Marcher

first: Ida

last: Elle

first: Torben

last: Helledie

first: Marianne

last: Due

first: Vasileios

last: Pagmantidis

first: Bente

last: Finsen

first: Johannes

last: Wilbertz

first: Mogens

last: Kruhøffer

first: Nils

last: Færgeman


title: The transcriptome of prospectively isolated adult neural stem cells

status: Public on Nov 19 2010

city: Neuherberg

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary:
Since the discovery of adult neural stem cells, their exact identity is still under discussion. Moreover, the lack of a reproducible procedure to purify neural stem cells prospectively rather than by growing them in vitro has so far precluded their study at the transcriptome level. Here we demonstrate a novel procedure to prospectively isolate neural stem cells from the adult mouse subependymal zone on the basis of their GFAP- and prominin1-expression by fluorescence-activated cell sorting. All self-renewing, multipotent stem cells are contained in this fraction at 70% purity. The stem cell identity of these double-positive cells is further demonstrated in vivo, by using a novel split-Cre-technology for fate mapping.
Comparison of the transcriptome of these prospectively isolated neural stem cells to the transcriptomes of other astrocytes or ependymal cells revealed a distinct clustering of the stem cells, highlighting their unique features, as well as profound similarities to the astrocyte as well as ependyma transcriptome.

overall_design: FACS-sorting was used to isolate prospective neural stem, astrocytes and ependymal cells from brain regions of hGFAP eGFP expressing mice. Total RNA from these cells was hybridised on Affymetrix MOE430 2.0 arrays and expression patterns were analysed.

first: Pratibha

last: Tripathi

first: Ruth

last: Beckervordersandforth-Bonk

first: Jovica

last: Ninkovic

first: Efil

last: Bayam

first: Frank

last: Kirchoff

last: Hirrlinger

first: Martin

last: Irmler

first: Magdalena

last: Götz


title: Expression data from SSEA1+ c-kit+  differentiated murine embryonic stem cells

city: Los Angeles

first: Anne

last: Lindgren

state: CA

address: 621 Charles E Young Dr S

department: MCDB

institute: UCLA

summary:
SSEA1+ c-kit+cells sorted from mouse embryonic stem cells differentiated for 4 days in 10uM Retinoic acid do not form teratomas when transplated into SCID mice while Pten-/- cells do.
We used microarrays to identify genes and pathways besides Pten that could explain this difference in tumorigenicity.

overall_design:
Wild type and Pten mutant SSEA1 c-kit positive differentiated cells were compared as the wild type cells were non-tumorigenic upon transplant to SCID mice and the Pten-/- cells were tumorigenic.
wild type vs Pten-/-

first: Amander

middle: T

last: Clark


title: Myocardial expression data from wild-type and akt2-/- mice

city: St. Louis

first: Anthony

middle: J

last: Muslin

state: MO

address: 660 s. Euclid ave

institute: Washington University

summary:
Wild-type (WT) C57Bl/6 and akt2-/- male mice.

Keywords: RNA Expression Array

overall_design: Left ventricles (LV) from 12-16 week-old male wild type mice and age-matched akt2-/- mice


title: GBM brain tumors

first: Viviane

last: Tabar

type: Genome variation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Hypothalamic transcriptome plasticity in two rodent species reveals divergent differential gene expression but conserved pathways

city: Bristol

first: DAVID

last: MURPHY

state: AVON

address: Whitson Street

department: Medicine and Dentistry

institute: University of Bristol

summary: We have addressed the question of how different rodent species cope with the life-threatening homeostatic challenge of dehydration at the level of transcriptome modulation in the supraoptic nucleus (SON), a specialised hypothalamic neurosecretory apparatus responsible for the production of the antidiuretic peptide hormone arginine vasopressin (AVP). AVP maintains water balance by promoting water conservation at the level of the kidney. Dehydration evokes a massive increase in the regulated release of AVP from SON axon terminals located in the posterior pituitary, and this is accompanied by a plethora of changes in the morphology, electrophysiological properties, biosynthetic and secretory activity of this structure. Microarray analysis was used to generate a definitive catalogue of the genes expressed in the mouse SON, and to describe how the gene expression profile changes in response to dehydration. Comparison of the genes differentially expressed in the mouse SON as a consequence of dehydration with those of the rat has revealed many similarities, pointing to common processes underlying the function-related plasticity in this nucleus. In addition we have identified many genes that are differentially expressed in a species-specific manner. However, in many cases, we have found that the hyperosmotic cue can induce species-specific alterations in the expression of different genes in the same pathway. The same functional end can be served by different means, via differential modulation, in different species, of different molecules in the same pathway. We suggest that pathways, rather than specific genes, should be the focus of integrative physiological studies based on transcriptome data.

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus

overall_design:
Animals. Adult male C57BL/6 mice (Harlan Sera-Lab, Loughborough, UK) were group housed (4 per cage) under controlled temperature (21+ 2ºC) and diurnal light conditions (14-h light, 10-h dark, lights on at 05.00). Food and water were available ad libitum until the experiment commenced. Complete fluid deprivation was imposed for 48 hours starting at 11.00 a.m. Control animals maintained free access to drinking water, and both groups had access to standard laboratory rodent chow. Experiments on adult male rats described previously (27). All procedures were conducted in strict accordance with the Animal Scientific Procedures Act (1986), UK, and were approved by the local University of Bristol Ethical Review Process.

Tissue collection. Mice were killed using cervical dislocation and the brain was carefully removed from the cranium and snap frozen using powdered dry ice and stored at -80oC for no more than 14 days. Sections of brain (14μm) were cut using an RNase free cryostat and mounted onto RNase free membrane coated glass slides (P.A.L.M. Membrane slides; P.A.L.M. Microlaser Technologies). Immediately after sectioning, frozen sections were thawed and fixed (30s; in 95% [v/v] EtOH), rehydrated (30s in each of 75% [v/v] and 50% [v/v] EtOH) before being stained (60s 1% [v/v] cresyl violet). Sections were then dehydrated in a graded EtOH series (30s in each of 50% [v/v], 75% [v/v] and 95% [v/v]. then 2x 30s in 100% [v/v]). Laser microdissection was performed using a P.A.L.M. MicrolaserSystem (P.A.L.M. Microlaser Technologies). The SON was identified with reference to Franklin and Paxinos (28) and the tissue from each animal was independently pooled into collection vials containing RNAlater® (Ambion, Huntingdon, UK). A single operative carried out all dissections. Total RNA was isolated without delay (within 24h) according to standard procedures that accompany the Ambion RNAqueous MicroKit (Ambion).

Microarray analysis. Separate microarrays (n=4) were probed using independently generated target. For each completely independent replicate, tissue from 1 mouse was used for RNA extraction.

first: Charles

last: Hindmarch

first: Lesley

middle: Q

last: Stewart

first: David

last: Murphy

first: Yi-Chun-Loraine

last: Tung

first: Giles

last: Yeo


title: Differential gene expression in mouse skNAC knockout heart at E11.5

city: San Francisco

first: Chong

middle: Yon

last: Park

address: 1650 Owens St.

department: Cardiovascular Diseases

institute: Gladstone Institute

summary:
Targeted deletion of skNAC in mice resulted in early embryonic lethality with cardiac defects.  In order to investigate the molecular mechanism of the cardiac defect, we designed the microarray comparing gene expression of the mutant E11.5 heart to wild type E11.5 heart.
Keywords: genetic modification in mouse

overall_design: 3 for each genotypes,  comparing Littermates of E11.5, total RNA (500ng) from ventricles,  Affymetrix GeneChip Mouse Genome 430 2.0 Array

first: Stephanie

last: Pierce

first: Deepak

last: Srivastava


title: Critical Role of Sphingolipid Pathway Components in Murine Radiation-Induced Lung Injury: Protection by Sphingosine-1-Phosphate Analogues

status: Public on Nov 17 2010

city: Reno

first: Tong

last: Zhou

state: NV

address: 1664 N Virginia St

institute: University of Nevada School of Medicine

summary: Clinically significant radiation-induced lung injury (RILI) is associated with significant morbidity and mortality and a common toxicity in patients administered thoracic radiotherapy. While the molecular etiology of RILI is poorly understood, we previously characterized a murine model of RILI in which alterations in lung endothelial barrier integrity surfaced as a potentially important pathobiologic event. In these studies, inhibition of HMG-CoA reductase activity (simvastatin) reduced murine RILI-associated lung inflammation and vascular leak and attenuated radiation-induced dysregulation of sphingolipid metabolic pathway genes identified by genome-wide lung gene expression profiling. In the present study, we test the hypothesis that sphingolipid signaling components serve as important modulators of RILI pathobiology and novel therapeutic targets. Sphingolipid involvement in murine RILI was confirmed by radiation-induced increases in lung expression of sphingosine kinase (SphK) isoforms 1 and 2 and increases in the ratio of ceramide to cumulative sphingosine-1-phosphate (S1P) and dihydro-S1P (DHS1P) levels in plasma, bronchoalveolar lavage (BAL) fluid and lung tissue following 25 Gy exposure (6 weeks).  Moreover, genetically-engineered mice with either targeted deletion of SphK1 (SphK1-/-), or with reduced expression of selective members of the S1P receptor family (S1PR1+/-, S1PR2-/-, S1PR3-/-,), exhibited marked susceptibility to RILI-mediated lung inflammation. Finally, we assessed the efficacy of three potent vascular barrier-protective S1P analogues FTY720 (FTY), fTysiponate (fTyS) and SEW-2871 (SEW) in attenuating indices of RILI.  The phosphonate analogue, fTyS, and to a lesser degree SEW, exhibited significant attenuation of RILI and RILI-induced gene dysregulation compared to control RILI-challenged mice (6 weeks).  In contrast, FTY failed to significantly alter physiologic or genomic changes compared to RILI-challenged controls. Together, these results support the targeting of sphingolipid components as a novel and effective therapeutic strategy in RILI.

overall_design: Four mice were treated with PBS as a control. Three mice were treated with (S)-FTY-phosphonate (0.1mg/kg) as a drug control. Three mice were treated with SEW-2871 (0.1mg/kg) as a drug control. Three mice were treated with FTY720 (0.1mg/kg) as a drug control. Three mice were treated with administered radiation (25 Gy) alone. Three mice were treated with both administered radiation (25 Gy) and (S)-FTY-phosphonate (0.1mg/kg). Three mice were treated with both administered radiation (25 Gy) and SEW-2871 (0.1mg/kg). Three mice were treated with both administered radiation (25 Gy) and FTY720 (0.1mg/kg).

first: Biji

last: Mathew

first: Jeffrey

middle: R

last: Jacobson

first: Evegeny

last: Berdyshev

first: Yong

last: Huang

first: Xiaoguang

last: Sun

first: Yutong

last: Zhao

first: Lynnette

last: Gerhold

first: Jessica

last: Siegler

first: Carrie

last: Evanovski

first: Ting

last: Wang

first: Rafe

last: Zaidi

first: Liliana

last: Moreno-Vinasco

first: Robert

last: Bittman

first: Chin-Tu

last: Chen

first: Patrick

last: LaRiviere

first: Saad

last: Sammani

first: Yves

last: Lussier

first: Steven

last: Dudek

first: Viswanathan

last: Natarajan

first: Ralph

last: Weichselbaum

first: Joe

last: Garcia


title: Gene expression data in murine nasal mucosa following nanoemulsion adjuvant exposure

status: Public on Nov 18 2010

first: Paul

middle: Edward

last: Makidon

state: MI

address: 9340 MSRB III, 1150 W. Medical Center Dr.

department: Internal Medicine

summary:
Antigen uptake, processing, trafficking and presentation in nasal mucosal tissues are regulated by complex intra- and inter-cellular signalling events.  Typical vaccine adjuvants lead to the transcription of pro-inflammatory cytokines and chemokines which relate to immune induction.
We used microarrays to detail the global expression of genes in murine nasal mucosa underlying immune induction with a non-inflammatory nanoemulsion nasal adjuvant.

overall_design: 8 week old female CD-1 mice were nasally treated with 5 microliters/nare of either  20% (v/v) naomeulsion (W805EC) or PBS.  Nasal epithelium was harvested immediately post-mortem at either 6 (6 hr) or 24 hours (24 hr) following treatment.  The tissue was placed in OTC and frozen by immersion in liquid nitrogen.  Total RNA was extracted per sample using RNA easy (Qiagen).

first: Ania

last: Bielinska


title: Nanoemulsion-Specific Gene Expression Data in Bone Marrow Derived Dendritic Cells and in Murine Nasal Epithelium


title: PPARg and IL-4-induced gene expression data from PPARg +/- LysCre and PPARg fl/- LysCre mouse bone marrow-derived macrophages

city: Boston

first: Attila

last: Szanto

address: 185 Cambridge St.

department: Molecular Biology

institute: Massachusetts General Hospital

summary: Conditional macrophage-specific PPARg knockout mice were generated on C57Bl/6 background by breeding PPARg fl/- (one allele is floxed, the other is null) and lysozyme Cre transgenic mice. PPARg and IL-4 signaling was analyzed on bone marrow-derived macrophages. Bone marrow of 3 mice per group was isolated and differentiated to macrophages with M-CSF (20 ng/ml). 20 ng/ml IL-4 was used to induce alternative macrophage activation and 1 uM Rosiglitazone (RSG) was used to activate PPARg. From each mouse 4 samples were generated: 1. M-CSF, 2. M-CSF+RSG, 3. IL-4 and 4. IL-4+RSG. All compounds were added throughout the whole differentiation process, and fresh media was added every other day. Control cells were treated with vehicle (DMSO:ethanol). After 10 days, RNA was isolated and gene expression profiles were analyzed using Mouse Genome 430 2.0 microarrays from Affymetrix.

overall_design: 3 PPARg +/- LysCre and 3 PPARg fl/- LysCre mice were used to isolate bone marrow and from each macrophages were differentiated with or without IL-4 and simultaneously treated with vehicle or RSG. Altogether we analyzed 24 samples with 3 biological replicates as below.

first: Laszlo

last: Nagy


title: Gene expression data in Bone Marrow Derived Dendritic Cells (BMDC) following nanoemulsion adjuvant exposure

summary:
Antigen uptake, processing and presentation by dendritic cells are regulated by complex intra- and inter-cellular signalling events.  Typical vaccine adjuvants lead to the transcription of pro-inflammatory cytokines and chemokines which relate to immune induction.
We used microarrays to detail the global expression of genes in BMDC underlying emulsion internalization and DC activation with a non-inflammatory nanoemulsion adjuvant.

overall_design: BMDC were incubated with 0.001% v/v  naomeulsion (W805EC) or media alone for  6 hours.  Total RNA was extracted per sample using RNA easy (Qiagen).


title: The transcription factors STAT5a/b negatively regulate cell proliferation through the activation of cdkn2b and cdkn1a expression

status: Public on Nov 15 2010

city: Bethesda

first: WeiPing

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

department: GCL

institute: NIDDK/NIH

summary: Although the cytokine-inducible transcription factors STAT5a/b promote proliferation of a wide range of cell types, there are cell- and context specific cases in which loss of STAT5a/b results in enhanced cell proliferation. Here we report that loss of STAT5a/b from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitor p15INK4B and p21CIP1. We further demonstrate that growth hormone through the transcription factor STAT5a/b enhances expression of the cdkn2B gene and that STAT5a binds to GAS sites within the promoter. We have recently demonstrated that ablation of STAT5a/b from liver results in hepatocellular carcinoma upon a CCl4 insult. We also established that in liver tissue, like in MEFs, STAT5a/b activates expression of the cdkn2B gene. Loss of STAT5a/b led to diminished p15INK4B and increased hepatocyte proliferation. This study for the first time demonstrates that cytokines through STAT5a/b can induce the expression of a key cell cycle inhibitor. These experiments therefore shed a light on the context-specific role of STAT5a/b as tumor suppressors.

overall_design: Control and Stat5a/b-null embryonic fibroblasts (MEFs) cells were stimulated w/o a GH including two biological replications per group (Total four groups)

first: Ji

last: Yu

first: Bingmei

last: Zhu

first: Weiping

first: Atsushi

last: Hosui

first: Gertraud

middle: W

last: Robinson

first: Lothar


title: Effects of chlorella in OVA-sensitized BALB/c mice

status: Public on Nov 16 2010

city: Kyoto

first: Masaki

last: Fujishima

state: Kyoto

address: 369, Karasuma-dori, Gojo, Shimogyo-ku

department: Research and Development Department

institute: Sun Chlorella Corp.

summary: Chlorella has been reported to have various physiological activities, including antiarteriosclerotic, cholesterol-lowering, anti-inflammatory, and immunoregulatory effects. However, there has been no report on the long-term effects of chlorella ingestion on immunity. In the present study, 4- to 10-week-old (young) and 4- to 50-week-old (old) female BALB/c mice were sensitized or not with ovalbumin (OVA), and given basic diet containing chlorella powder at 2% or basic diet alone. The effects of chlorella ingestion on immunity were investigated by measurement of splenic cytokines and immunoglobulin (Ig), analysis of T- and B-cells in the spleen and small intestine by flow cytometry, and analysis of the liver by DNA microarray. Results were compared between the young and old, OVA-sensitized and -nonsensitized, and chlorella and non-chlorella ingestion groups. Production of interferon-γ (IFN-γ) was maintained in the nonsensitized old groups, and ratios of T-helper type 1 (Th1) to T-helper type 2 (Th2) cells were similar in the young and old groups. In addition, overproduction of OVA-specific Igs due to OVA sensitization was strongly suppressed, and significant immunotolerance was exhibited irrespective of age. In addition, suppression of T-cell decreases in the spleen due to aging and suppression of changes in T- and B-cells due to OVA sensitization in the small intestinal lymph were demonstrated on flow cytometric analyses. On DNA microarray analysis, immune-related terms including IL11 and major histocompatibility complex (MHC) class 1 were detected, and expression of genes was shown, which were related to IL1-linked genes and complex involving macrophages from the pathways of cytokines and inflammatory response. In addition, suppressions of declined lipid metabolism and energy production were also suggested. Although how the ingredients in chlorella were involved in these changes is unclear, our findings suggest that prevention of decrease in acquired immunity by aging and induction of strong immunotolerance occurred following chlorella ingestion.

overall_design:
The Young Control group and Old Control group were fed normal food, and the Old Chlorella intake group was fed food including 2.0% Chlorella powder. The total RNA was isolated from liver and samples was pooled for each group (n = 6 for each group).

A table of normalized log2 ratios (where numerator is sample expression data, and denominator is all sample median data) is linked below as a supplementary file.

last: Fujisima

first: Yukari

last: Arakawa

first: Masakatsu

last: Shibata

first: Noriyuki

last: Yamazaki

first: Michie

last: Kobayashi

first: Toru

last: Mizoguchi


title: Long-range expression effects of CNV:  insights from Smith-Magenis and Potocki-Lupski syndrome mouse model

status: Public on Nov 10 2010

city: Lausanne

first: Sylvain

last: Pradervand

address: Genopode

department: CIG

country: Switzerland

institute: UNI Lausanne

summary:
To study the effect of structural changes on expression, we assessed gene expression in genomic disorder mouse models. Both a microdeletion and its reciprocal microduplication mapping to mouse chromosome 11 (MMU11), which model the rearrangements present in Smith-Magenis (SMS) and Potocki-Lupski (PTLS) syndromes patients, respectively, have been engineered. We profiled the transcriptome of five different tissues affected in human patients in mice with 1n (Deletion/+), 2n (+/+), 3n  (Duplication/+) and uniallelic 2n (Deletion/Duplication) copies of the same region in an identical genetic background. The most differentially expressed transcripts between the four studied genotypes were ranked. A highly significant propensity, are mapping to the engineered SMS/PTLS interval in the different tissues. A statistically significant overrepresentation of the genes mapping to the flanks of the engineered interval was also found in the top-ranked differentially expressed genes. A phenomenon efficient across multiple cell lineages and that extends along the entire length of the chromosome, tens of megabases from the breakpoints. These long-range effects are unidirectional and uncoupled from the number of copies of the copy number variation (CNV) genes. Thus, our results suggest that the assortment of genes mapping to a chromosome is not random. They also indicate that a structural change at a given position of the human genome may cause the same perturbation in particular pathways regardless of gene dosage. An issue that should be considered in appreciating the contribution of this class of variation to phenotypic features.

Keywords: Genetic modification

overall_design: Comparisons of heterozygous mice carrying a duplication, Dp(11)17/+, a deletion, Df(11)17)/+, or both rearrangements, Df(11)17/Dp(11)17, with wild-type mice. Gene expression of at least two male individuals of each of the four genotypes were measured in hippocampus, cerebellum, testis, kidney and heart.

first: Guénola

last: Ricard

first: Alexandre

last: Reymond

first: Nele

last: Gheldof

first: Jacqueline

last: Chrast

first: Jessica

last: Molina

first: Frédéric

last: Schütz

first: Katherina

last: Walz

first: James

last: Lupski


title: Prostate specific Pten deletion, Pten-Smad4 deletion, and Pten-p53 deletion

status: Public on Nov 05 2010

first: Zhihu

last: Ding

state: MA

address: 44 Binney Street

department: Medical Oncology

institute: Dana-Farber Cancer Institute

summary: We used microarrays to detail the global gene expression and identified differentially expressed gene list between wild-type anterior prostates and Ptenpc-/- anterior prostates, Ptenpc-/-Smad4pc-/- and Ptenpc-/- anterior prostates, Ptenpc-/-p53pc-/- and Ptenpc-/- anterior prostates at 15 weeks of age.

overall_design: Prostate-specific Pten deletion (Ptenpc-/-) results in prostate intraepithelial neoplasia (PIN) which, following a long latency, can progress to high-grade adenocarcinoma, albeit with minimally invasive and metastatic features.  To understand this feeble progression phenotype, we conducted transcriptome comparison of five Ptenpc-/- PIN relative to three wild-type anterior prostate.  Moreover,  Ptenpc-/-Smad4pc-/- progress to metastasis, while Ptenpc-/-p53pc-/- not progress to metastasis.   To understand this phenotype difference, we conducted transcriptome comparison of five Ptenpc-/-Smad4pc-/-to five Ptenpc-/- prostate tumor, and three Ptenpc-/-p53pc-/- to five Ptenpc-/- tumor.

first: Yonghong

last: Xiao


title: The influence of segmental copy number variation on tissue transcriptomes through development

summary:
A preliminary understanding of the phenotypic effect of copy number variation (CNV) of DNA segments is emerging. These rearrangements were demonstrated to influence, in a somewhat dose-dependent manner, the expression of genes mapping within. They were shown to also affect the expression of genes located on their flanks, sometimes at great distance. Here, we show by monitoring these effects at multiple life stages, that these controls over expression are effective throughout mouse development. Similarly, we observe that the more specific spatial expression patterns of CNV genes are maintained throughout life. However, we find that some brain-expressed genes appear to be under compensatory loops only at specific time-points, indicating that the influence of CNVs on these genes is modulated through development. We also observe that CNV genes are significantly enriched upon transcripts that show variable time-course of expression in different strains. Thus modifying the number of copy of a gene not only potentially alters its expression level, but possibly also its time of expression.

Keywords: comparative genomic

overall_design: Expression from brain and liver tissues from C57BL/6J, DBA2/J and 129S2 mouse strains at different developmental time points.

first: Evelyne

last: Chaignat

first: Emilie

last: Aït Yahya-Graison

first: Charlotte

middle: N

last: Henrichsen


title: Expression data from wild-type and Zmpste24-/- mouse embryonic fibroblasts (MEFs) at an early passage (passage 3, P3)

status: Public on Nov 11 2010

city: Hong Kong

first: William

last: Niu

address: #21, Rd. Sassoon

department: Dept. Biochemistry

country: Hong Kong

institute: The University of Hong Kong

summary:
Zmpste24 is a metalloproteinase processing prelamin A into mature lamin A, a nuclear structure protein. Zmpste24-/- mice which accumulate prelamin A in cells recapitulate accelerated aging phenotypes observed in human premature aging disorder, Hutchinson Gilford progeria sydrome (HGPS). Zmpste24-/- mouse embryonic fibroblasts (MEFs) exhibited genomic instabiliy and accelerated aging at cellular level, which is premature senescence.
We performed microarray analysis on Zmpste24-/- MEFs, compared to wild-type littermates' MEFs, at an early passage (P3), which is a pre-symptom stage before cellular senescence occurs in the mutant MEFs, in order to examine gene expression profile and figure out the underneath mechanism triggering the premature aging process.

overall_design: Early passage wild-type and Zmpste24-/- MEFs were collected for RNA extraction, the quality of RNAs were determinded by Electrophoresis Assay (2100 Bioanalyzer, Agilent) and RNA extractions were used for hybridization on Affymetrix microarrays.

first: Le

last: Zhang

first: Gang

first: Zhongjun

last: Zhou


title: A comprehensive and universal method for assessing the performance of differential gene expression analyses

status: Public on Nov 09 2010

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: The number of methods for pre-processing and analysis of gene expression data continues to increase, often making it difficult to select the most appropriate approach. We present a simple procedure for the comparative estimation of a variety of methods for microarray data pre-processing and analysis. Our approach is based on the use of real microarray data in which controlled fold changes are introduced into 20% of the data to provide a metric for comparison with the unmodified data. The data modification can be easily applied to raw data measured with any technological platform and retains all the complex structures and statistical characteristics of the real-world data. The power of the method is illustrated by its application to a comparative analysis of the significance analysis of microarray (SAM), Limma, and associative analysis tuned to the exact structure of the experimental data. We present a novel finding that SAM and Limma analyses fail to detect the most interesting differentially expressed genes at high expression level, while the associative analysis does recognize them. Our results demonstrate that the method of controlled modifications of real experimental data provides a simple tool for assessing the performance of data preprocessing and analysis methods.

overall_design: 20 samples of Epstein-Barr Virus-transformed B cells collected from normal healthy donors. All samples were biological. No treatment were introduced, and the whole group of 20 samples is presumably homogeneous

middle: G

first: Joel

last: Guthridge

first: Robert

middle: E

last: Hurst

first: Igor


title: Helicobacter pylori colonization ameliorates glucose homeostasis in mice

status: Public on Nov 13 2010

city: blacksburg

first: Saroj

middle: K

last: Mohapatra

address: washington Street

department: VBI

institute: Virginia Tech

summary:
Background: Helicobacter pylori has been shown to alter the secretion of gastric hormones that modulate body fat deposition. Since cag-positive H. pylori strains interact intimately with the host gastric epithelial cells and trigger higher inflammation than cag-negative strains, we hypothesized that gastric colonization with H. pylori strains without functional cagA ameliorates obesity and its complications by modulating gastric gene expression and inflammation.   Methodology/Principal Findings: To test this hypothesis we examined the effects of gastric colonization on metabolic and inflammatory markers in mice infected with two isogenic strains of H. pylori: 26695 strain 98-325 (cagA+ wild-type) and its cag pathogenicity island (cagPAI) mutant strain 99-305, a knockout made by inserting a chloramphenicol resistance cassette. Only the cagPAI mutant decreased fasting blood glucose levels, improved glucose tolerance and suppressed weight gain in db/db mice and mice with diet-induced obesity. These effects were associated with increased gastric leptin levels, suppressed infiltration of macrophages, enhanced influx of regulatory T cells (Treg) in adipose tissue and suppressed gastric inflammation. Gene set enrichment analyses of gastric mucosal samples identified six differentially modulated pathways, including the Hedgehog signaling pathway that is associated with control of cellular proliferation and gastric carcinogenesis as well as the insulin signaling pathway.
Conclusions/Significance: Gastric colonization with cagPAI-negative strains of H. pylori ameliorate obesity and inflammation by modulating gastric gene expression, suggesting that cag-negative H. pylori strains might be beneficial in ameliorating obesity and its co-morbidities.

overall_design: Gastric mucosa from three groups of mice: uninfected, infected with H. pylori 26695 strain 98-325 (cagA+ wild-type) or infected with H. pylori mutant strain 99-305 (lacking cag pathogenicity island; cagA-)

first: Raquel

last: Hontecillas

first: Josep

last: Bassaganya-Riera


title: Phosphatidylinositol 3-Kinase (PI3K) Signaling via Glycogen Synthase Kinase-3 (Gsk-3) Regulates DNA Methylation of Imprinted Loci.

city: Columbus

first: Christopher

last: Phiel

address: 700 Children's Drive W432

institute: The Research Institute at Nationwide Children's Hospital

summary:
The two vertebrate Gsk-3 isoforms, Gsk-3a and Gsk-3b, are encoded by distinct genetic loci and exhibit mostly redundant function in murine embryonic stem cells (ESCs). Here we report that deletion of both Gsk-3a and Gsk-3b in mouse ESCs results in misregulated expression of imprinted genes and hypomethylation of corresponding imprinted loci. Treatment of wild-type ESCs with small molecule inhibitors of Gsk-3 phenocopies the DNA hypomethylation of imprinted loci observed in Gsk-3 null ESCs. We provide evidence that DNA hypomethylation in Gsk-3 null ESCs is due to a reduction in the levels of the de novo DNA methyltransferase, Dnmt3a2.
Gsk-3 activity serves as a node for several signal transduction pathways, and its regulation of Dnmt3a2 expression raises the possibility that DNA methylation could be transiently affected by different types of environmental stimuli. Our data suggest that modulating Gsk-3 activity could have further reaching effects in the regulation of the epigenome.

Keywords: Gene expression array-based

overall_design: The study was designed to examine the changes in gene expression between wild-type and Gsk-3a-/-;Gsk-3b-/- mouse embryonic stem cells.

first: Anthony

middle: P

last: Popkie

first: Leigh

middle: C

last: Zeidner

first: Ashley

last: Albrecht

first: Sigrid

last: Eckardt

first: David

last: Newsom

first: Bruce

last: Aronow

first: Joanna

last: Groden

first: K.

last: McLaughlin

first: Peter

last: White


status: Public on Nov 20 2010

city: Baltimore

first: Kim

last: Walter

address: 1550 Orleans St.

institute: Johns Hopkins University

summary:
Gene expression analysis of 5-aza-dC treated pancreatic cancer associated fibroblasts
To identify genes silenced by methylation in pancreatic CAFs, we performed gene expression profiling on 5-aza-dC treated pancreatic cancer associated fibroblast cultures using Affymetrix Exon arrays.

overall_design: We analyzed 5 untreated and 5-aza-dC-treated pancreatic cancer associated fibroblast cultures using the Affymetrix Human Exon 1.0 ST platform. Gene expression levels were compared using Partek (version 6.3beta).

first: Kimberly

first: Noriyuki

last: Omuri

first: Michael

last: Goggins


title: Subtypes of medulloblastoma have distinct developmental origins

status: Public on Nov 01 2010

city: Memphis

last: Finkelstein

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Medulloblastoma encompasses a collection of clinically and molecularly diverse tumor subtypes that together comprise the most common malignant childhood brain tumor.  These tumors are thought to arise within the cerebellum, with approximately 25% originating from granule neuron precursor cells (GNPCs) following aberrant activation of the Sonic Hedgehog pathway (hereafter, SHH-subtype).  The pathological processes that drive heterogeneity among the other medulloblastoma subtypes are not known, hindering the development of much needed new therapies.  Here, we provide evidence that a discrete subtype of medulloblastoma that contains activating mutations in the WNT pathway effector CTNNB1 (hereafter, WNT-subtype), arises outside the cerebellum from cells of the dorsal brainstem. We found that genes marking human WNT-subtype medulloblastomas are more frequently expressed in the lower rhombic lip (LRL) and embryonic dorsal brainstem than in the upper rhombic lip (URL) and developing cerebellum.  Magnetic resonance imaging (MRI) and intra-operative reports showed that human WNT-subtype tumors infiltrate the dorsal brainstem, while SHH-subtype tumors are located within the cerebellar hemispheres.  Activating mutations in Ctnnb1 had little impact on progenitor cell populations in the cerebellum, but caused the abnormal accumulation of cells on the embryonic dorsal brainstem that included aberrantly proliferating Zic1+ precursor cells.  These lesions persisted in all mutant adult mice and in 15% of cases in which Tp53 was concurrently deleted, progressed to form medulloblastomas that recapitulated the anatomy and gene expression profiles of human WNT-subtype medulloblastoma.  We provide the first evidence that subtypes of medulloblastoma have distinct cellular origins.  Our data provide an explanation for the marked molecular and clinical differences between SHH and WNT-subtype medulloblastomas and have profound implications for future research and treatment of this important childhood cancer.

overall_design: A total of 16 samples are analyzed, repsresenting 4 experimental groups: Ctnnb1 medulloblastoma (3 samples); Ptch1 medulloblastoma (6 samples); embryonic dorsal brainstem (4 samples); and postnatal granule neuron precursor cells (3 samples). Every sample was prepared from a different mouse.

first: Richard

last: Gilbertson


title: Expression data from CD19-positive splenic B cells isolated from 1-month old ID4+/-TCL1-tg and ID4+/+TCL1-tg mice

status: Public on Nov 04 2010

first: Lianbo

last: Yu

address: 1800 Cannon Drive

department: Center for Biostatistics

institute: The Ohio State University

summary:
The function of ID4 in CLL development was studied in vivo using TCL1 transgenic mouse model that develop leukemia similar to human CLL. TCL1 mice with ID4 single knockout gene have accelerated CLL progression.
Results from the animal study suggest ID4 as a tumor suppressor gene that might regulate cell proliferation and apoptosis in B lymphocytes.

overall_design: Gene expression in CD19-positive splenic B cells collected from 1-month old ID4+/-TCL1-tg and ID4+/+TCL1-tg mice was compared by microarray, the goal is to find ID4-regulated genes involved in CLL development.

first: Shih-Shih

last: Chen


title: Comparison of hepatic gene change after partial hepatectomy

city: New York

first: Bisen

last: Ding

state: NY

address: 1300 York Avenue

institute: Cornell Medical College

summary: Partial hepatectomy, resection of a portion of liver mass, indues significant liver regenerative responses that consist of numerous genetic changes. To identify specific genetic changes, we compare the liver of mice underwent either hepatectomy or sham operation.

overall_design: The experiment compared 2 sets of biological duplicates which included hepatectomized liver and sham-operated liver

first: Bi-Sen

first: Koji

last: Shido

first: Daniel

last: Nolan

first: Alex

last: Babazadeh

first: Jason

last: Butler

last: Lyden

first: Daylon

last: James

first: Thomas

last: Sato

first: Zev

last: Rosenwaks

first: Sina

middle: Y

last: Rabbany

first: Vivek

last: Mittal

first: Shahin

last: Rafii

first: Hideki

last: Kobayashi


title: Her2/Neu breast cancer mouse model whole tissue transcriptome

status: Public on Oct 22 2010

city: Seattle

first: Regine

middle: M

last: Schoenherr

address: 1100 Fairview Ave N, LE-360

institute: Fred Hutchinson Cancer Research Center

summary:
Purpose:  We generated extensive transcriptional and proteomic profiles from a Her2-driven mouse model of breast cancer that closely recapitulates human breast cancer.  This report makes these data publicly available in raw and processed forms, as a resource to the community.  Importantly, we previously made biospecimens from this same mouse model freely available through a sample repository, so researchers can obtain samples to test biological hypotheses without the need of breeding animals and collecting biospecimens.
Experimental design:  Twelve datasets are available, encompassing 841 LC-MS/MS experiments (plasma and tissues) and 255 microarray analyses of multiple tissues (thymus, spleen, liver, blood cells, and breast).  Cases and controls were rigorously paired to avoid bias.
Results:  In total, 18,880 unique peptides were identified (PeptideProphet peptide error rate ≤1%), with 3884 and 1659 non-redundant protein groups identified in plasma and tissue datasets, respectively.  Sixty-one of these protein groups overlapped between cancer plasma and cancer tissue.
Conclusions and clinical relevance:  These data are of use for advancing our understanding of cancer biology, for software and quality control tool development, investigations of analytical variation in MS/MS data, and selection of proteotypic peptides for MRM-MS.  The availability of these datasets will contribute positively to clinical proteomics.

overall_design: Affymetrix GeneChip Mouse Genome 430 2.0 microarrays were used to profile whole tissues from 5 different tissue types of 25 tumor-bearing and 25 control mice of the Her2/Neu breast cancer mouse model.  The 5 tissues tested were from breast, liver, spleen, blood cell, and thymus.  The tumor-bearing mice were bitransgenic for MMTV-rtTA/TetO-NeuNT, and the control mice were transgenic for TetO-NeuNT only.  The control mice were age- and cage-matched to the tumor-bearing mice.  All samples were lysed and total RNA isolated and amplified prior to hybridization.

first: Karen

middle: S

last: Kelly-Spratt

first: ChenWei

last: Lin

first: Jeffrey

last: Whiteaker

first: Tao

last: Liu

first: Ted

last: Holzman

first: Ilsa

last: Coleman

first: Li-Chia

last: Feng

first: Travis

middle: D

last: Lorentzen

first: Alexei

middle: L

last: Krasnoselsky

first: Pei

last: Wang

first: Yan

first: Kay

last: Gurley

first: Lynn

last: Amon

first: Athena

middle: A

last: Schepmoes

first: Ronald

last: Moore

first: David

last: Camp II

first: Lewis

last: Chodosh

last: Smith

first: Peter

last: Nelson

first: Martin

last: McIntosh

first: Christopher

last: Kemp

first: Amanda

last: Paulovich


title: Time Course Gene Expression Microarray Analysis of a Mouse B-cell Line (CH12.LX) Activated with Lipopolysaccharide and Treated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin

status: Public on Oct 21 2010

city: Research Triangle Park

first: Russell

middle: Scott

last: Thomas

state: NC

address: 6 Davis Drive

institute: The Hamner Institutes for Health Sciences

summary: The objective of the study was to characterize gene expression cascade involved in the suppression of B-cell activation and differentiation by 2,3,7,8-tetrachlorodibenzo-p-dixoxin (TCDD). The underlying hypothesis was that multiple nodes in the B-cell differentiation network are directly or indirectly regulated by TCDD through its receptor, the AHR.

overall_design: The mouse B-cell line (CH12.LX) was plated at 1X10^5 cells/ml at time 0 and activated with lipopolysaccharide (LPS, Salmonella typhosa).  The cells were then treated with either dimethyl sulfoxide (DMSO, 0.01%) or 10 nM 2,3,7,8-tetrachlorodibenzo-p-dixoxin (TCDD). The cells were harvested at 0, 8, 12, 24, 36, and 48 hrs post-treatment. At the 0 hr time point, cells were untreated. A total of 4 experimental replicates per time point per treatment group were included with the cells for each replicate treated and harvested on separate days.  Single color Affymetrix Mouse 430 2.0 arrays were used.

first: Nadira

last: De Abrew


title: Microarray data from control and pericyte-deficient mouse brain microvascular transcriptomes

city: Stockholm

first: Elisabet

last: Wallgard

address: Nobels väg 12A, PO Box 281

department: Dept. of Medical Epidemiology and Biostatistics

country: Sweden

institute: Karolinska Institutet

summary: The blood-brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS). The main physical barrier is found in the CNS endothelial cell, and depends on continuous complexes of tight junctions combined with reduced vesicular transport. Other possible constituents of the BBB include extracellular matrix, astrocytes and pericytes, but the relative contribution of these different components to the BBB remains largely unknown. Here we demonstrate a direct role of pericytes at the BBB in vivo. Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers. The increased permeability occurs by endothelial transcytosis, a process that is rapidly arrested by the drug imatinib. Furthermore, we show that pericytes function at the BBB in at least two ways: by regulating BBB-specific gene expression patterns in endothelial cells, and by inducing polarization of astrocyte end-feet surrounding CNS blood vessels. Our results indicate a novel and critical role for pericytes in the integration of endothelial and astrocyte functions at the neurovascular unit, and in the regulation of the BBB.

overall_design: The brain microvascular fragments were isolated from mice with different genotypes, each represented by 3-4 biological replicates. Genotypes 1-2: Platelet derived growth factor-B (PDGF-B) retention-motif knockout (pdgfbret/ret) represent the pericyte-deficient situation, and the heterozygous mice (pdgfbret/+)  are used as controls. Genotypes 3-4: Hypomorphic PDGF-B mutants that rescue pdgfb-/- null mice, in which a one copy of a conditionally silent human PDGF-B transgene targeted to the Rosa 26 locus (R26P) is turned on by endothelial-specific expression of Cre recombinase. In this data set these mice are named as Tie2Cre, R26P+/0, pdgfb-/- (representing the pericyte-deficient situation). Mice wt for  pdgfb (pdgfb+/+) and carrying one silent copy of R26P (R26P+/0), are used as controls. Genotype 5: Adult Notch3+/+ wildtype (WT).

first: Annika

last: Armulik

first: Guillem

last: Genové

first: Maarja

last: Mäe

first: Maya

middle: H

last: Nisancioglu

first: Colin

last: Niaudet

first: Liqun

last: He

first: Jenny

last: Norlin

first: Per

last: Lindblom

first: Karin

last: Strittmatter

first: Bengt

last: Johansson

first: Christer

last: Betsholtz


title: Effects of MMSET on gene expression in multiple myeloma

status: Public on Oct 20 2010

city: Chicago

first: Eva

last: Martinez-Garcia

state: IL

address: 303 E. Superior St.

institute: Northwestern University

summary: The MMSET (Multiple Myeloma SET domain) protein is overexpressed in multiple myeloma patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/WHSC1 in development, its mode of action in the pathogenesis of multiple myeloma (MM) is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase (HMT) activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM.

overall_design: Total RNA was isolated from two different systems: an inducible knock down designed in the 5' region of MMSET. Upon addition of doxycycline we block MMSET expression. The second system we used was a repletion system. By retroviral infection of knock out cells for MMSET we restored the expression of MMSET wild type and two mutants of the protein: one active and one catalytically inactive. Triplicates of each sample were analyzed.


title: Transcription Factor Redundancy Ensures Induction of the Antiviral State

status: Public on Oct 15 2010

first: Benjamin

last: tenOever

address: 430 East 29th Street, Room 540

department: Microbiology

institute: New York University

summary:
Transcriptional response to virus infection in mice lacking type I and type III signaling
The transcriptional response to virus infection is thought to be predominantly induced by interferon (IFN) signaling. Here we demonstrate that, in the absence of IFN signaling, an IFN-like transcriptome is still maintained. This transcriptional activity is mediated from IFN-stimulated response elements (ISREs) that bind to both the IFN stimulated gene factor 3 (ISGF3) as well as to IFN response factor 7 (IRF7). Through a combination of both in vitro biochemistry and in vivo transcriptional profiling, we have dissected what constitutes IRF-specific, ISGF3-specific, or universal ISREs. Taken together, the data presented here suggests that IRF7 can induce an IFN-like transcriptome in the absence of type-I or -III signaling and therefore provides a level of redundancy to cells to ensure the induction of the antiviral state.

overall_design:
Mouse: Infections were performed in triplicate and lungs from each condition were pooled for total RNA isolation.
Human: Analysis of IRF7 transcriptome in U3A cell line was performed in duplicates.

first: Sonja

last: Schmid

middle: R


title: Oligoarray analysis of mRNA species from DCs treated with C. parvum for 24 h.

city: North Grafton

first: Hanping

last: Feng

address: 200 Westboro Rd.

institute: Tufts University

summary: To investigate whether C. parvum treatment of DCs regulates other inflammatory genes, mouse BMDCs (CD11c and CD11b positive) were treated with C. parvum for 24 hr. Control groups included untreated BMDCs and DCs treated with E. cuniculi.  We noticed that a significant upregulation of the expression of interferon-related genes, which may correlation the critical role of interferon in host defense against C. parvum infection.

overall_design: DCs were treated with C. parvum for 24 hr. Control groups included untreated BMDCs and DCs treated with E. cuniculi. Group comparison was performed using the data of 3 replicate arrays from each time point.

first: Saul

last: Tzipori

first: Louis

last: Weiss


title: Comparison of adult intact naive C57Bl/6 Nogo-A KO versus WT spinal cord

city: Zurich

first: Laura

last: Montani

address: Winterthurerstrasse 190

department: Neuromorphology

institute: Brain Research Institute - UZH/ETHZ - Zurich

summary:
Nogo-A localized on myelin adaxonal membrane in the adult CNS is well known for its role as neurite outgrowth inhibitor following a lesion. Nogo-A KO mice show enhanced regenerative/compensatory fiber growth following CNS lesion. However, changes undergoing in their intact CNS have not been studied. Moreover, Nogo-A in the intact adult CNS in also expressed in some neuronal subpopulations, e.g. in the hippocampus, olfactory bulbs and dorsal root ganglia.
We compared the intact adult CNS (spinal cord) of Nogo-A KO mice in order to identify: potential compensating molecules which could be interesting new inhibitory neurite outgrowth candidates, possible molecules involved in the up to now not yet clarified downstream signalling pathway of Nogo-A, additional new functions for myelin or neuronal Nogo-A in the intact adult CNS.
Keywords: gene expression, Nogo-A KO, spinal cord, adult, naive, unlesioned

overall_design: Spinal cords from 3 adult C57Bl/6 wild type and Nogo-A KO mice have been explanted. Total RNA has been extracted and processed for hybridization on Mouse 430 2.0 Affymetrix GeneChips. Following scanning and first analysis with MAS 5.0, further analysis was performed by GeneSpring 7.2 (Silicon Genetics, Redwood City, CA). A present call filter (2 out of 3 present calls in at least one out of the different studied conditions) was applied. Normalization was run per chip as well as per gene to the median of the control replicates. Data were statistical restricted through a 1-way Anova (p=0.05). A final threshold of =1.2 folds of increase or decrease in the expression level of each single transcript was applied. Regulated transcripts have been assigned to functional categories according to GeneOntology as well as literature and database mining (Pubmed and Bioinformatics Harvester EMBL Heidelberg).

first: Leda

last: Dimou

first: Martin

last: Schwab


title: Gene Expression profiling of human PBMCs with different ANA titer

city: Dallas

first: yun

last: lian

state: TX

address: 5323 Harry Hines Blvd.

institute: UT Southwestern Medical Center

summary: Total 48 samples with different ANA titer were analyzed for their gene expression profiles with Illumina HumanWG-6 V3 chips

overall_design: 10 healthy control (HC) samples with high ANA, 7 first degree relative of SLE patientw (FDR) with high ANA, 10 HCs with low ANA, 6 FDR with low ANA, 15 SLE patients (SLE) with high ANA were used for the microarray analysis.

first: Quan-Zhen

last: Li

first: Shengxi

last: Liu

first: Jinchun

last: Zhou

first: Yun

last: Lian

first: Nancy

last: Olsen


title: Expression data from mouse colon tissue response to DSS induction at day 0, 2, 4 and 6

status: Public on Oct 13 2010

city: Shreveport

first: Kevil

last: Christopher

state: LA

address: 1501 Kings Highway

department: Pathology

institute: Louisiana State University Health Science Center, Shreveport

summary:
Temporal genome profiling of DSS colitis
The DSS induced mouse colitis model is often used to emulate Ulcerative Colitis (UC) in order understand pathophysiological mechanism of inflammatory bowel disease (IBD). Given the progressive nature of IBD, colon tissue gene expression changes during the evolution of disease, and knowing the changes in gene expression profiles could indentify potential diagnostic markers or additional therapeutic targets for colitis. Therefore, we performed temporal genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with the development of colitis.

Keywords: Expression time course of mouse colon tissue induced by 3% DSS.

overall_design: C57BL/6J mice were given 3% DSS in the drinking water and tissues from individual cohorts were collected at days 0, 2, 4 and 6. Total RNA were extracted from the colon tissue and detected by Affymerix GeneChip Mouse Genome 430 2.0 Array.

first: Christopher

last: Kevil

first: Kai

last: Fang


title: Microarray analysis of defective cartilage in Hoxc8- and Hoxd4-transgenic mice

city: Baton Rouge

first: Claudia

last: Kappen

address: 6400 Perkins Road

department: Developmental Biology

institute: Pennington Biomedical Research Center

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

overall_design: Refer to individual Series


title: Overexpression of Hoxc8 transcription factor alters transcriptional profiles in mouse chondrocytes at E18.5

summary: Homeobox genes of the Hox class are required for proper patterning of skeletal elements and play a role in cartilage differentiation. In transgenic mice with overexpression of Hoxc8 during cartilage development, we observed severe defects, namely physical instability of cartilage, accumulation of immature chondrocytes, and decreased maturation to hypertrophy. To define the molecular basis underlying these defects, we performed gene expression profiling using the Affymetrix microarray platform.

overall_design: Embryos were dissected from four different mouse litters at E18.5. Embryos from each litter were grouped according their genotype: TA=control; TR=transgenic.

last: Kruger