title: Comparison of the expression profiles of the 630E strain and a sigE mutant after 14h of growth

first: Marc

last: Monot

summary:
Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG.

Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigE mutant after 14h of growth in MS is performed.

overall_design: Two-condition experiment: 630E strain 14h vs. sigE mutant 14h. 4 biological replicates for each condition, including dye-swaps.

first: Laure

last: Saujet


title: Comparison of the expression profiles of the 630E strain and a sigG mutant after 19h of growth

status: Public on Feb 20 2014

city: Paris

address: 28 rue du docteur roux

country: France

institute: Institut Pasteur

summary:
Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG.

Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigG mutant after 19h of growth in MS is performed.

overall_design: Two-condition experiment: 630E strain 19h vs. sigG mutant 19h. 4 biological replicates for each condition, including dye-swaps.


title: Comparison of the expression profiles of the 630E JIR8094 strain and sporulation sigma factor mutants (sigE, sigF, sigG, sigK, spoIIID) in MS

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

overall_design: Refer to individual Series


title: Comparison of the expression profiles of the 630E strain and a sigK mutant after 24h of growth

summary:
Compartment-specific control of gene expression during Bacillus subtilis sporulation is governed by a cascade of four sigma factors, sigmaF and sigmaG in the forespore and sigmaE and sigmaK in the mother cell. In this work, we combined transcriptional analyses and transcriptional start site mapping to define the sigmaF, sigmaE, sigmaG and sigmaK regulons in Clostridium difficile. A total of about 225 genes were under the control of these sigma factors: 25 in the sigmaF regulon, 97 sigmaE-dependent genes, 50 sigmaG-governed genes and 56 genes specifically controlled by sigmaK. A significant fraction of genes in each regulon are of unknown function and we can propose new candidates for spore coat proteins synthesized under the control of sigmaE and sigmaK among proteins previously detected in the spore proteome (Lawley et al., 2009 (PMID 19542279)). Global analysis of developmental gene expression under the control of these sigma factors indicate deviations from the B. subtilis model regarding the communication between mother cell and forespore in C. difficile. We show that the expression of the sigmaE regulon in the mother cell is not strictly under the control of sigmaF despite the fact that the forespore product SpoIIR is required for the processing of pro-sigmaE. In addition, the sigmaK regulon is not controlled by sigmaG in C. difficile in connection with the lack of pro-sigmaK processing in this bacterium. However, a control of the forespore on sigmaK targets is maintained through a sigmaF-dependent regulation of sigmaK-controlled genes, a process that bypasses sigmaG.

Here, transcriptional profiling of the Clostridium difficile 630E strain vs. a sigE mutant after 24h of growth in MS is performed.

overall_design: Two-conditions experiments, 630E strain 24h vs sigK mutant 24h, 4 biological replicates for each condition


title: Comparison of the expression profiles of R20291 strain : a wild type strain, a fliC mutant and a fliC mutant complemented after 14h of growth in PY and a wild type strain and a fliC mutant after 14h of mouse infection in vivo

status: Public on Dec 31 2013

summary: Transcriptionnal profiling of C. difficile R20291 strain : a wild type strain, a fliC mutant and a fliC mutant complemented after 14h of growth in PY and a wild type strain and a fliC mutant after 14h of mouse infection in Vivo

overall_design: two-conditions experiments, R20291 strain : a wild type strain, a fliC mutant and a fliC mutant complemented in Vitro and a wild type strain and a fliC mutant in Vivo, 4 biological replicates for each condition, in an direct design.

first: Amira

last: Barketi


title: Comparison of the expression profiles of the 630E strain and a sigF mutant after 14h of growth

overall_design: Two-condition experiment: 630E strain 14h vs. sigF mutant 14h. 4 biological replicates for each condition, including dye-swaps.


title: Comparison of the expression profiles of the 630E strain after 8h, 14h and 38h of infection in mouse

status: Public on Nov 04 2013

summary: The virulence factors of Clostridium difficile have been studied for many years, but the main in vivo pathogenesis processes of this bacterium has to be investigated. Especially, data on the early mechanisms of C. difficile adaptation to the host is not yet available. The objective of our study was to improve the understanding of the pathogenesis of C. difficile by the analysis of the genome-wide temporal expression of C. difficile genes during the first hours of infection. Three groups of 4 axenic mice each were challenged by vegetative cells of the 630 C. difficile strain, and sacrified at 8, 14, and 38 hours post-infection. Pure prokaryotic RNA was obtained from caecal bacteria. Comparative hybridizations on strain 630 microarrays were done using cDNA issued from an 8-hours in vitro culture as control, with a dye-swap protocol for each sample. Normalisation and statistical analysis of all data were done with different functions of the limma package. The pathogenesis of C. difficile could be seen as a result of the successful metabolic adaptation of the bacteria to its host, contributing to its persistence and multiplication, and the coordinate expression of virulence factors. Analysis of our data enlightened some of these aspects. The results support strongly a two-step infection model, since there is, during the course of infection, a significant increase in the toxins expression contrasting with a decreased expression of most of the putative colonization factors. Several paralogs of the HMW S-layer protein are also down-regulated, some of them could be strong candidates as colonisation factors. Bacterial adaptation to the microenvironment of the host is assessed by the regulation of numerous metabolic pathways, i.e., the upregulation of the ethanolamine catabolic operon or the modulation of several PTS systems. Inactivation of some putative virulence factors identified by this methodology will complete this analysis.

overall_design:
Transcriptional profiling of the C. difficile 630E strain after 8h, 14h or 38h of infection in mouse.
Three-condition experiments: 630E strain 8h, 14h or 38h of infection in mouse vs. 630E strain 8h in culture. 4 biological replicates for each condition in dye swap.

first: Cecile

last: Deneve

first: Laxmee

last: Caleechurn


title: Comparison of the expression profiles of the 630E strain after 8h, 14h and 38h in TY

overall_design:
Transcriptional profiling of the C. difficile 630E strain after 8h, 14h or 38h in TY.
Two-condition experiments: 630E strain 14h or 38h in TY vs. 630E strain 8h in TY. 2 biological replicates for each condition in dye swap.


title: Comparison of the expression profiles of 630E strain and an Hfq antisense after 7.5h of growth in Tyt

status: Public on Jul 15 2014

summary: Transcriptional profiling of C. difficile 630E strain vs. an Hfq antisense after 7.5h of growth inTYt.

overall_design: Two-conditions experiments, 630E strain vs. Hfq antisense grown in TYt, 4 biological replicates for each condition.

first: Pierre

last: Boudry


title: Clostridium difficile CD630E: growth with 10 mM cysteine in PY vs growth in PY

summary:
Comparison of Clostridium difficile transcriptome of strain CD630E grown for 10 hours in PY (supplemented with mild concentration of cysteine) versus PYC (PY supplemented with 10 mM of cysteine).
Experimental procedure was designed to investigate the influence of cysteine on toxins production and the regulatory network involved.

overall_design:
two-conditions experiments, excess of cysteine vs mild concentration of cysteine, 4 biological replicates for each condition

Description of the supplementary files:
Main - Short description of the experiment
Result_all - All significative genes
Result_Gold* - High quality significative gene
Result_Silver** - Medium quality significative gene
All_Raw_data - All genes results significative and non significative
Design_Genes-OUT - Genes not present in the platform
Design_Genes-Oligos - Number of oligos design per gene

* Gold : Nbr significative oligos = Nbr oligos designed for this gene
** Silver : Nbr significative oligos = Nbr oligos designed for this gene -1

first: Marie

middle: B

last: Dancer-Thibonnier


title: Comparison of the expression profiles of 630E strain and a sigD mutant after 6h of growth.

status: Public on Aug 31 2013

summary: Transcriptionnal profiling of C. difficile 630E strain vs a sigD mutant after 6h of growth in BHI

overall_design: Two-conditions experiments, 630E strain 6h vs sigD mutant 6h, 4 biological replicates for each condition

first: Imane

last: El Meouche


title: CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AHR signaling

status: Public on Dec 21 2012

city: San Diego

first: John

last: Walker

state: CA

address: 10675 John Jay Hopkins Dr

country: USA

institute: NIBR

summary: Targeting the estrogen signaling pathway has proved to be of great value in the treatment of human breast cancer. Tamoxifen, a selective estrogen receptor modulator (SERM), is the most widely used antiestrogen. However, only 40-50% of patients with estrogen receptor (ER) positive breast cancer benefit from tamoxifen treatment and 30-50% acquire resistance and the disease progresses. Continuous treatment with conventional therapy may contribute to cancer progression in recurring cancers through the accumulation of drug resistant cancer progenitors. We found that MCF7 tamoxifen-resistant (TAM-R) cells possess a significantly higher proportion of cancer progenitor cells than tamoxifen-sensitive MCF7 cells. Our results indicate that the chemokine receptor CXCR4 plays an important role in the maintenance of cancer progenitors in a tamoxifen-resistant cell line and downregulation of CXCR4 signaling by small molecule antagonists specifically inhibits growth of a stem-like cell population in tamoxifen-resistant tumors both in vitro and in vivo. Whole genome gene expression analysis revealed aryl hydrocarbon receptor (AhR) signaling as one of the top networks that is differentially regulated in MCF7(TAM-R) xenograft tumors treated with the CXCR4 antagonist AMD3100 as compared to MCF7 tumors. Further, small molecule antagonists of AhR signaling specifically inhibit the progenitor population in MCF7(TAM-R) cells suggesting that the aryl hydrocarbon receptor could be a putative target for the treatment of tamoxifen-resistant breast cancers. Introduction transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy.

overall_design: Tamoxifen resistant or sensitive xenografts; mice treated with estrogen and/or CXCR4 modulators

first: A

last: Dubrovska

last: Hartung

first: L

middle: C

last: Bouchez

first: J

middle: R

first: C

middle: Y

last: Cho

first: P

middle: G

last: Schultz


title: Comparison of the expression profiles of 630E JIR8094 strain and a ccpA mutant after 10h of growth in TY with 0.5% glucose.

status: Public on Oct 02 2012

summary: Transcriptionnal profiling of C. difficile 630E JIR8094 strain vs a ccpA mutant after 10h of growth in TY with 0.5% glucose

overall_design: two-conditions experiments, WT strain vs ccpA mutant strain, 4 biological replicates for each condition, in an indirect design using a 8h TY RNA preparation as Reference

first: Frederic

last: Barbut

first: Ana

last: Antunes


title: Comparison of the expression profiles of 630E JIR8094 strain and a ccpA mutant


title: ccpA Chromatin immunoprecipitation on chip of JIR8094 (CD630E) WT strain and a ccpA mutant after 6h of growth in TY

status: Public on Nov 13 2012

type: Genome binding/occupancy profiling by array

summary: Comparison of ccpA Chromatine immunoprecipitation on chip using 2 strains : JIR8094 (CD630E) wild type strain and a ccpA mutant after 6h of growth in TYG. This experimental procedure was designed to investigate the consensus binding site, CRE, of pleiotropic regulator ccpA.

overall_design: Two-conditions experiments, JIR8094 (CD630E) strain 6h vs ccpA mutant 6h, 3 biological replicates for each condition

first: Emmanuelle

last: Courtois


title: Comparison of the expression profiles of 630E JIR8094 strain and a ccpA mutant after 10h of growth in TY.

first: Marc

last: Monot

summary: Transcriptionnal profiling of C. difficile 630E JIR8094 strain vs a ccpA mutant after 10h of growth in TY


title: A Chondrogenic Molecule that Repairs Cartilage by Transcriptional Regulation of CBF-beta

status: Public on May 02 2012

summary: Osteoarthritis (OA) is a degenerative joint disease that involves destruction of articular cartilage and eventually leads to disability. Mesenchymal stem cells (MSCs) reside in healthy and diseased cartilage, and through their chondrogenic potential may provide a strategy for cartilage repair. To this end, we performed an image-based, high throughput screen and identified the small molecule, kartogenin, that promotes selective MSC differentiation into chondrocytes (EC50=100nM), shows chondroprotective effects in vitro, and is efficacious in two OA animal models. Kartogenin binds filamin A and induces chondrogenesis by regulating the CBFbeta-RUNX1 transcriptional program. This work provides new insights into the control of chondrogenesis that may ultimately lead to an effective stem-cell based therapy for osteoarthritis.

overall_design: one compound, three doses, two time points, a vehicle control

first: Shoutian

last: Zhu

first: Matthew

middle: S

last: Tremblay

first: Joshua

middle: N

last: Payette

first: Jianing

last: Wang

first: Laure

first: Shelly

last: Meeusen

first: Alana

last: Althage

first: Charles

first: Xu

last: Wu

first: Peter

first: Kristen

middle: A

last: Johnson


title: Gene Expression Profiles of MYC+ and MYC- mouse Germinal Center B cells

status: Public on Sep 24 2012

city: New York

first: David

last: Dominguez-Sola

state: NY

address: One Gustave L. Levy Place, Box 1044A

department: Oncological Sciences

institute: Icahn School of Medicine at Mount Sinai

summary:
Germinal centers (GC) arise within B cell follicles upon antigenic challenge. In the dark zones (DZ) of GCs, B cells proliferate and hypermutate their immunoglobulin genes, and mutants with increased affinity are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells, or re-enter the DZ for further refinement. However, the molecular circuits governing GC positive selection are not known. Here, we show that the GC reaction requires the biphasic regulation of c-MYC expression, involving its transient induction during early GC commitment, its repression by BCL6 in DZ B cells, and its re-induction in a subpopulation of positively selected LZ B cells destined to DZ re-entry. Accordingly, acute disruption of MYC function in vivo leads to GC collapse, indicating an essential role in GC physiology. These results have implications for our understanding of GC selection and the role of MYC deregulation in B cell lymphomas.
We used microarrays to determine the global gene expression programs that distinguish MYC+ GC B cells from their MYC- negative counterparts.

overall_design: GFPMYC+ and GFPMYC- GC B cell subpopulations were collected by Fluorescence Activated Cell Sorting (FACS) from B cell enriched fractions of splenic mononuclear cell pools of GFPMYC knock-in mice (12 days after SRBC immunization).  5-20ng of total RNA (RIN>9) for each sample was used as a template for linear cDNA amplification (Ovation RNA amplification Kit, NuGen). cDNA was labeled using the Encore Biotin Labeling Kit (NuGen) and hybridized to Affymetrix Mouse 430.2 gene expression arrays.

first: Riccardo

last: Dalla-Favera


title: Comparison of the expression profiles of the Clostridium difficile 630E strain after 8h, 14h and 38h of infection in mouse and after 8h, 14h and 38h growth in vitro


title: Clostridium difficile CD630E JIR8094: growth 10h with 0.5% glucose in TY vs growth 10h in TY

summary: transcriptionnal profiling of a C. difficile strain JIR8094 comparing growth 10h in 0.5% TY medium with growth 10h in TY medium

overall_design: two-conditions experiments, 0.5% glucose TY for 10h vs TY for 10h, 4 biological replicates for each condition, in an indirect design using a 8h TY RNA preparation as Reference

first: Frederic


title: An RNAi Screen Identifies TRRAP as a Regulator of Brain Tumor-Initiating Cell Differentiation

status: Public on Mar 14 2011

first: John

last: Walker

summary:
Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor. The brain-infiltrative character of glioblastoma makes complete surgical removal of the tumor impossible and neither radiation nor current chemotherapy provide cure. Recent evidence shows that glioblastoma multiforme consists of heterogeneous cell populations which differ in tumor-forming potential. Enriched tumor-initiating capacity has been linked to poorly differentiated glioblastoma cells sharing features with neural stem cells. Thus, these cells are important targets for new therapeutic strategies.
We aim to identify novel targets controlling maintenance and differentiation in glioblastoma-initiating cells through high throughput screening. To this end, we utilized libraries of small chemical compounds and small interference RNAs in combination with automated imaging and data analysis. Patient-derived glioblastoma cells were expanded and characterized using neural stem cell conditions. In culture, the cells showed low differentiation but expression of neural stem cell markers such as Nestin and Sox2. Upon intracranial injection into SCID mice these cells gave rise to tumors displaying the hallmarks of the human disease.
Differentiation of glioblastoma-initiating cells (for example elicited through bone morphogenetic protein, BMP) was associated with strong morphological changes. Hence, cellular morphology, as well as markers specific for differentiation or death were used as screen readout. Lentiviral RNA interference-based screening yielded several gene knockdowns leading to ‘forced’ differentiation of glioblastoma-initiating cells. For example, knockdown of TRRAP (transformation/transcription domain associated protein) led to strongly increased differentiation and loss of proliferative and self-renewing capacity in these cells. TRRAP is an adapter protein implicated in oncogenic transformation through c-MYC transcription activation, also participating in chromatin remodeling and DNA repair. Glioblastoma-initiating cells with reduced TRRAP displayed increased apoptosis upon treatment with the genotoxic agent temozolomide. In vivo, Trapp knockdown cells were not able to give rise to glioblastoma upon transplantation into the brain of SCID mice. Together, these findings support a crucial role for TRRAP in maintenance and tumorigenicity of glioblastoma-initiating cells and might offer future therapeutic options.

overall_design: Two treatments compared to control: two different shRNA sequences for TRRAP were compared to a control shRNA sequence in their effects on global transcription in brain tumor initiating cells

first: Heiko

last: Wurdak

first: Angelica

last: Romero

first: Mihaela

last: Lorger

first: James

last: Watson

first: Chih-yuan

last: Chiang

first: Jay

last: Zhang

first: Vanita

last: Natu

first: Buu

middle: P

last: Tu

first: Griffith

last: Harsh

first: Hannes

last: Vogel

first: Brunhilde

last: Felding-Habermann

first: Anthony

last: Orth

first: Loren

middle: J

last: Miraglia

first: Daniel

last: Rines

first: Stephen

middle: L

last: Skirboll


title: A Regenerative Trait in Mice with a Point Mutation in TGFBR1

status: Public on Jul 11 2011

summary:
Regeneration of differentiated tissue in mammals is rare.  In an effort to identify genes that affect the healing process, we screened G3 mice containing germline point mutations for closure of an ear punch wound.  One particular line was identified with a heritable hole closure phenotype containing differentiated tissue. Mapping and sequencing efforts revealed that the mutant mice harbor a R244Q point mutation coded by the TGFBR1 gene which leads to enhanced signaling activity in a reporter gene assay.  Although there was no obvious effect on the immune system, bone marrow stromal cells from the mutant mice revealed accelerated chondrogenesis, mimicking the in vivo development of cartilage islands in the regenerated ears. This genetically well-defined mouse model should help to further dissect the role of TGF-beta signaling in vertebrate healing and regeneration.

Keywords: treatment and time course in wt and mutant samples

overall_design: TGFb or vehicle treatment at different time points in mouse embryonic fibroblasts from wildtype and TGFb1 mutant (heterozygous and homozygous) mice.  Mutant is constitutively active.

first: Jun

last: Liu

first: Kristen

last: Johnson

first: Jie

last: Li

first: Victoria

last: Piamonte

first: Brian

middle: M

last: Steffy

first: Mindy

last: Hsieh

first: Xu

last: Wu

first: Sheng

last: Ding

first: Richard

last: Glynne

first: Peter

last: Schultz


title: Comparison of the expression profiles of 630E strain and a sigH mutant after 10h of growth

status: Public on Aug 22 2011

first: Marc

last: Monot

summary: Transcriptionnal profiling of C. difficile 630E strain vs a sigH mutant after 10h of growth in TY

overall_design: Two-conditions experiments, 630E strain 10h vs sigH mutant 10h, 4 biological replicates for each condition

first: Laure

last: Saujet


title: Comparison of the expression profiles of 630E strain after 4h and 10h of growth

summary: Transcriptional profiling of C. difficile 630E strain after 4h vs 10h of growth

overall_design: Two-conditions experiments, 630E strain 4h vs 630E strain 10h, 4 biological replicates for each condition


title: Effect of sigH in the growth phase transition of Clostridium difficile

summary:
This study is based on two microarray datasets, in one hand a phase transition comparison using the expression profiles of 630E strain after 4h and 10h of growth. In other hand a comparison at 10h of growth between a mutant of the sigH gene and the WT strains. This experimental procedure was designed to investigate the effect of sigH in the growth phase transition of Clostridium difficile.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series


title: Aryl hydrocarbon receptor antagonists promote the expansion of human hematopoietic stem cells

status: Public on Apr 04 2011

first: John

last: Walker

summary:
Although practiced clinically for more than 40 years, the use of hematopoietic stem cell (HSC) transplants remains limited by the ability to expand these cells ex vivo. An unbiased screen with primary human HSCs identified a purine derivative, StemRegenin 1 (SR1), that promotes the ex vivo expansion of CD34+ cells. Culture of HSCs with SR1 led to a 50-fold increase in cells expressing CD34 and a 17-fold increase in cells that retain the ability to engraft immunodeficient mice. Mechanistic studies show that SR1 acts by antagonizing the aryl hydrocarbon receptor (AHR). The identification of SR1 and AHR modulation as a means to induce ex vivo HSC expansion should facilitate the clinical use of HSC therapy.
LGC006, a less potent SR1 analog, was also examined.

KEYWORDS: two compounds, multiple doses, one time point

middle: E

last: Boitano

first: Jian

last: Wang

first: Russell

last: Romeo

last: Bouchez

first: Albert

last: Parker

first: Sue

last: Sutton

first: Colin

last: Flaveny

first: Gary

middle: H

last: Perdew

first: Michael

last: Denison

last: Cooke


title: Clostridium difficile mutant ccpA CD630E JIR8094: growth 10h with 0.5% glucose in TY vs growth 10h in TY

summary: transcriptionnal profiling of a ccpA mutant of C. difficile strain JIR8094 comparing growth 10h in 0.5% TY medium with growth 10h in TY medium

first: Frederic

last: Barbut

first: Ana

last: Antunes


title: A small molecule accelerates neuronal differentiation in the adult rat

status: Public on Aug 18 2010

summary: Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain.However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a unique small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brainandresulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention.directed at endogenous NPCs.

overall_design: Compare expression profile of KHS101-treated hippocampal progenitor cells (2 concentrations) vs. DMSO (negative control), retinoic acid (positive control)

first: Heiko

last: Wurdak

first: Shoutian

last: Zhu

first: Kyung

last: Min

first: Lindsey

last: Aimone

first: Luke

last: Lairson

first: James

last: Watson

first: Gregory

last: Chopiuk

last: Demas

first: Bradley

last: Charette

first: Eranthie

last: Weerapana

first: Benjamin

middle: F

last: Cravatt

first: Hollis

middle: T

last: Cline

first: Eric

last: Peters

first: Jay

last: Zhang

first: Chunlei

last: Wu

first: Jonathan

last: Chang

first: Tove

last: Tuntland

first: Charles

last: Cho


title: C. perfringens 13 strain vs 13∆cpe1786 erm strain

status: Public on Oct 01 2010

first: Marc

last: Monot

summary: Transcriptional profiling of C. perfringens 13 strain compared with strain 13∆cpe1786 erm after growth in minimal medium with 0.5 mM cystine.

overall_design: two-condition experiment, 13 vs 13∆cpe1786 erm, 4 biological replicates for each condition

first: Gaëlle

last: André


title: C. perfringens 13 strain: growth with 1 mM homocysteine vs growth with 0.5 mM cystine

status: Public on Jun 01 2010

summary: Transcriptionnal profiling of C. perfringens 13 strain comparing growth in minimal medium with 1 mM homocysteine with growth in minimal medium with 0.5 mM cystine.

overall_design: two-condition experiment, homocysteine vs cystine, 4 biological replicates for each condition


title: Letrozole (Femara) early and late responses to treatment

status: Public on Jul 28 2010

first: John

last: Walker

summary:
In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days or 90 days treatment with letrozole.  RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation.

Keywords: Timecourse between subjects

overall_design: Biopsies were taken from the same subjects at three timepoints: pretreatment, after 10-14 days Letrozol (2.5 mg/day, oral), and after 90 days Letrozol (2.5 mg/day, oral).

first: William

last: Miller

first: Alexey

last: Larionov

first: Lorna

last: Renshaw

first: Thomas

last: Anderson

first: Sharon

last: White

first: Garret

last: Hampton

first: Steven

last: Ho

first: Andreas

last: Krause

first: Dean

last: Evans

first: J

last: Dixon


title: GNF mouse atlas_macrophages

status: Public on May 05 2008

summary:
Monocytes and macrophages express an extensive repertoire of G Protein-Coupled Receptors (GPCRs) that regulate inflammation and immunity. In this study we performed a systematic microarray analysis of GPCR expression in primary mouse tissues to identify family members that are either enriched in macrophages compared to a panel of other cell types, or are regulated by an inflammatory stimulus, the bacterial product lipopolysaccharide (LPS).
Keywords: macrophage

overall_design: Macrophage, osteoblast, osteoclast, and mast cell samples were profiled on our GNF1M array.

first: Kate

last: Schroder

first: Allison

last: Pettit

first: Liza

last: Raggatt


title: Mouse Exon Atlas

status: Public on May 08 2009

summary:
The purpose of the study was to compare exon expression across a diverse collection of mouse tissues

Keywords: between tissue comparison

overall_design: between tissue comparison

first: Andrew

last: Su

first: Jay

last: Zhang


title: Small molecule inducers of pancreatic beta-cell expansion

status: Public on Jan 19 2009

summary:
New insulin-producing pancreatic beta-cells are formed primarily by self-replication during adult life. To identify small molecules that can induce beta cell replication, a large chemical library was screened for proliferation of growth-arrested, reversibly immortalized mouse beta-cells using an automated high-throughput screening platform. A number of structurally diverse, active compounds were identified including phorbol esters, which likely act through protein kinase C, and a group of thiophene-pyrimidines that stimulate beta-cell proliferation by activating the Wnt signaling pathway. A group of dihydropyridine (DHP) derivatives was also shown to reversibly induce beta-cell replication in vitro by activating L-type calcium channels (LTCCs). Our data indicate that the LTCC agonist 2a affects the expression of genes involved in cell cycle progression and cellular proliferation. Furthermore, treatment of beta-cells with both LTCC agonist 2a and the Glp-1 receptor agonist Ex-4 showed an additive effect on beta-cell replication. The identification of small molecules that induce beta-cell proliferation suggests that it may be possible to reversibly expand other quiescent cells to overcome deficits associated with degenerative and/or autoimmune diseases.

Keywords: treatment and time course

overall_design: compound treatment and time course

first: Weidong

last: Wang

first: Xia

first: Matthew

last: Tremblay

first: Jae

middle: W

last: Lee

first: Xu

last: Wu

first: Peter

last: Schultz


title: Pathway analysis of expression QTL data in fat identifies a role for cyclin H in oxidative phosphorylation

status: Public on May 01 2008

first: John

last: Walker

summary:
Genome-wide gene expression profiling has been extensively used to generate biological hypotheses based on differential expression.  Recently, many studies have used microarrays to measure gene expression levels across genetic mapping populations.  These gene expression phenotypes have been used for genome-wide association analyses, an analysis referred to as expression QTL (eQTL) mapping.   Here, eQTL analysis was performed in fat issue from 28 inbred strains of mice.  We focused our analysis on “trans-eQTL bands”, defined as instances in which the expression patterns of many genes were all associated to a common genetic locus.  Genes comprising trans-eQTL bands were screened for enrichments in functional gene sets representing known biological pathways, while genes located at associated trans-eQTL band loci were considered candidate transcriptional modulators.  We demonstrate that these patterns reflect previously characterized relationships between known upstream transcriptional regulators and their downstream target genes.   Moreover, we used this strategy to identify both novel regulators and novel members of known pathways.  Finally, based on putative regulatory relationship identified in our analysis, we validated in vitro a previously uncharacterized role for cyclin H in the regulation of oxidative phosphorylation.
Keywords: strain comparison

overall_design: tissues were taken from different mouse strains under identical baseline conditions

first: Chunlei

first: David

last: Delano

first: Nico

last: Mitro

first: Stephen

middle: V

first: Jeff

last: Janes

first: Phillip

last: McClurg

first: Serge

last: Batalov

first: Genevieve

last: Welch

first: Jie

first: Anthony

last: Orth

first: Richard

last: Glynne

first: Michael

last: Cooke

first: Joseph

last: Takahashi

first: Kazu

last: Shimomura

first: Akira

last: Kohsaka

last: Bass

first: Enrique

last: Saez

first: Tim

last: Wiltshire

middle: I


title: Plasmodium Circumsporozoite Protein Promotes the Development of the Liver Stages of the Parasite

status: Public on Oct 30 2007

first: John

summary:
The liver stages of malaria sporozoites develop in the hepatocyte cytoplasm inside a parasitophorous vacuole (PV). The circumsporozoite (CS) protein, the major surface protein of sporozoites, traverses the PV membrane and enters the cytoplasm and nucleus of hepatocytes. CS export into the cytoplasm requires the presence of pexel/VTS motifs. The transport of CS into the host nucleus is then mediated by importin (Imp) alpha3/beta1 that binds to the nuclear localization signal of CS localized in the conserved region II-plus. The NLSs of CS and of NFkB p50 share the same Imp. The entry of NFkB p50 into the nucleus is strongly inhibited in cell lines expressing CS, and in infected hepatocytes.  Micro-array data from CS expressing cell line shows that 40 NFkB targets were significantly down regulated. Among them inflammation related MIP3a and PTGS transcripts were 65 and 22 fold down regulated, thus explaining the notable absence of inflammatory cells surrounding exo-erythrocytic forms (EEFs). The presence of CS in the cytoplasm of hepatocytes enhances EEF growth both in vitro and in vivo. Therefore Plasmodium blood stages and EEFs use the same strategy to secrete proteins into the cytoplasm of host cells and remodel it to the parasite’s advantage.
Keywords: treatment and construct

overall_design: cells were isolated after inducing CSP and stimulating with TNF

first: Agam

last: Singh

first: Carlos

last: Buscaglia

first: Qian

last: Wang

first: Agata

last: Levay

first: Daniel

middle: R

last: Nussenzweig

first: Elizabeth

last: Winzeler

first: Hodaka

last: Fujii

first: Beatriz

last: Fontoura

first: Victor


title: GNF Mouse GeneAtlas V3

status: Public on Apr 29 2008

last: Walker

summary: High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we profiled gene expression from  a diverse array of normal tissues, organs, and cell lines in mice.  Keywords: multiple tissues

overall_design: Multiple tissues were taken from naïve male C57BL6 mice for hybridization to MOE430_2 arrays

first: Jane

last: Lattin

first: Kate

last: Schroder

first: Andrew

last: Su

first: Jie

last: Zhang

first: Kaoru

last: Saijo

first: Christopher

middle: K

last: Glass

first: David

last: Hume

first: Stuart

last: Kellie

first: Matthew

last: Sweet


title: Letrozole (Femara) early response to treatment

status: Public on Dec 10 2007

first: John

summary:
In the present investigation, we have exploited the opportunity provided by neoadjuvant treatment of a group of postmenopausal women with large operable or locally advanced breast cancer (in which therapy is given with the primary tumour remaining within the breast) to take sequential biopsies of the same cancers before and after 10-14 days treatment with letrozole.  RNA extracted from the biopsies has been subjected to Affymetrix microarray analysis and the data from paired biopsies interrogated to discover genes whose expression is most influenced by oestrogen deprivation.
Keywords: time course

overall_design: biopsies were taken from the same subjects both pretreatment and after 10-14 days Letrozol, 2.5 mg/day, oral

first: William

last: Miller

first: Alexey

last: Larionov

first: Lorna

last: Renshaw

first: Thomas

last: Anderson

first: Sharon

last: White

first: Garret

last: Hampton

first: Steven

last: Ho

first: Andreas

last: Krause

first: Dean

middle: B

last: Evans

first: J

last: Dixon


title: IMI MARCAR Project: towards novel biomarkers for cancer risk assessment

status: Public on Apr 29 2015

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

country: Switzerland

institute: Novartis

type: Methylation profiling by genome tiling array

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

platform_organism:
Homo sapiens
Mus musculus
Rattus norvegicus
synthetic construct


title: The role of PTEN/Akt1/PI3K signaling on the maintenance and viability of prostate cancer stem-like cell populations

status: Public on Dec 09 2008

last: Walker

summary:
Self-renewing tumor initiating cells that are capable of differentiation and responsible for tumor growth have been isolated from cancers and cell lines. If such minor populations are associated with tumor progression, understanding molecular pathways that are required for viability and maintenance of these populations will allow to target these pathways to eradicate tumors that are resistant to existing therapies. In this study we enriched for prostate cancer progenitors (Pr. CP’s) expressing cell surface markers CD44/CD133/alpha 2 beta 1 integrin in non-adherent serum-free growth conditions maintained as spheres. Cells grown in these conditions have increased in vivo clonogenic and in vivo tumorigenic potential. microarray analysis of cells grown in sphere conditions compared with long term monolayer culture conditions revealed preferential activation of PI3K/AKT pathway in prostate cancer progenitors. PI3K p110 alpha and beta protein levels were high in sphere condition cultured cells, and PTEN knockdown lead to an increase in Pr.CP’s, and to increased clonogenic and tumorigenic potential. Inhibition of Akt1 phosphorylation target FoxO3a lead to inhibition of tumorigenic capacity in vivo for prostate cancer cells.  Inhibition of PI3K activity by PI3K inhibitor NVP-BEZ235 lead to a selective inhibition of Pr.CP’s, nuclear localization of FoxO3a and increase in GADD45a in prostate cancer cells. Taken together our data strongly suggest that PTEN and PI3K/Akt pathways are critical for prostate cancer stem-like cell maintenance and targeting the PI3K signaling by selective inhibitors may give an incredible advancement in prostate cancer treatment.
Keywords: multiple tissues

overall_design: sphere and monolayer cultures from two different prostate cancer cell lines

first: Anna

last: Dubrovska

first: Richard

last: Salamone

first: Peter

middle: G

last: Schultz

first: Venkateshwar

last: Reddy


title: Identification and characterization of small molecule inducers of epidermal keratinocyte differentiation

status: Public on Feb 07 2007

summary:
An essential function of the human epidermis is the maintenance of a protective barrier against the environment. As a consequence, keratinocytes, which make up this layer of the skin, undergo an elaborate process of self-renewal, terminal differentiation and cell death. Misregulation of these processes can lead to several human diseases including psoriasis and basal cell and squamous cell carcinomas. To identify novel regulators of keratinocyte differentiation, a cell-based screen of small molecule libraries was carried out for molecules that induce terminal differentiation of normal human epidermal keratinocytes (NHEKs). One class of molecules was identified, the 2-(3,4,5-trimethoxy-phenylamino)-pyrrolo[2,3-d]pyrimidines, which were shown to induce differentiation of epidermal progenitor cells to terminally differentiated keratinocytes. These molecules serve as useful mechanistic probes of the cellular differentiation programs that regulate the formation and homeostasis of the epidermis, and may lead to novel therapeutic approaches for the treatment of skin hyperproliferative disorders.
Keywords: time course of compound treatment

overall_design: samples were taken from duplicate treatments of cells with DMSO or PP-2 (compound 9) at various time points

first: Jiyong

last: Hong

first: Jongkook

last: Lee

first: Kyung

last: Min

first: Nathanael

middle: S

last: Gray

first: Charles

middle: Y

last: Cho

first: Eric

middle: C

last: Peters


title: A genomic screen for activators of the antioxidant response element

status: Public on Feb 22 2007

first: John

summary:
The antioxidant response element (ARE) is a cis-acting regulatory enhancer element found in the 5’ flanking region of many phase II detoxification enzymes.  Upregulation of ARE-dependent target genes is known to have neuroprotective effects; yet, the mechanism of activation is largely unknown.  By screening an arrayed collection of approximately 15,000 full-length expression cDNAs in the human neuroblastoma cell line IMR-32 with an ARE-luciferase reporter, we have identified several cDNAs not previously associated with ARE activation.  A subset of cDNAs, including sequestosome 1 (SQSTM1) and dipeptidylpeptidase III (DPP3), activated the ARE in primary mouse-derived cortical neurons.  Overexpression of SQSTM1 and DPP3 in IMR-32 cells stimulated NRF2 nuclear translocation and led to increased levels of NAD(P)H:quinone oxidoreductase 1 (NQO1), a protein which is transcriptionally regulated by the ARE.  When transfected into IMR-32 neuroblastoma cells that were depleted of transcription factor NRF2 by RNA interference, SQSTM1 and DPP3 were unable to activate the ARE or induce NQO1 expression, indicating that the ARE activation upon ectopic expression of these cDNAs is mediated by NRF2.  Studies with pharmacological inhibitors indicated that 1-phosphatidylinositol 3-kinase (PI3K) and protein kinase C (PKC) signaling are also essential for activity.  Lastly, overexpression of these cDNAs conferred partial resistance to hydrogen peroxide induced toxicity, consistent with the induction of antioxidant and phase II detoxification enzymes which can protect from oxidative stress.  This work and other such studies may provide mechanisms for activating the ARE in the absence of general oxidative stress, and a novel therapeutic approach to degenerative diseases and aging.
Keywords: overexpression of different antioxidant response element activators

overall_design: Samples were taken from duplicate transfections of different antioxidant response element activators

first: Yanxia

last: Liu

last: Kern

first: Jeffrey

middle: A

last: Johnson

first: Hendrik

last: Luesch


title: Circadian skeletal muscle_wt and Clock mutants

status: Public on Feb 08 2007

summary:
One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), the left leg muscle from 5 wildtype mice, and the right leg muscle from the same wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints.  Total RNA from each side (left or right) were separately pooled to make a single sample for amplification and hybridization.  Therefore, duplicate arrays (from left and right side) were performed at each time point. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected. As for the wildtype mice, right and left sides were collected, prepared, amplified, and hybridized in separate pools. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ?l RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at –80?C until use.
Keywords: time course

overall_design: duplicates consisted of pools from independent mice

first: Brooke

last: Miller

first: Erin

middle: L

last: McDearmon

first: Satchidananda

last: Panda

first: Jessica

last: Andrews

first: Martin

last: Straume

first: Karyn

last: Esser

last: Hogenesch

first: Joseph

last: Takahashi


title: Circadian liver_wt and Clock mutants

last: Walker

summary:
One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ?l RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at –80?C until use.
Keywords: time course


title: Comparison between naïve, tolerant and memory CD8+ T cells

status: Public on Jan 01 2006

summary:
To elucidate transcriptional differences between naïve, tolerant and memory CD8+ T cells, genome-wide gene expression profiling was performed.  The indicated cell populations were purified from immunized or naïve Rag-/- TCR mice by cell sorting and RNA was extracted labeled and hybridized to an Affymetrix custom mouse array GNF1M GeneChip.  RNA from sorted samples was prepared, split into two aliquots prior to making labeled cDNA, so that two arrays were used for each cell population.Alterations in transcript levels were determined through pair wise comparisons of naïve cells to either memory or tolerant CD8+ T cells.
Keywords: cell type

overall_design: duplicates consisted of replicate aliquots of the same total RNA

first: Ryan

middle: M

last: Teague

first: Blythe

middle: D

last: Sather

first: Jilian

last: Sacks

first: Maria

middle: Z

last: Huang

first: Michelle

last: Dossett

first: Junko

last: Morimoto

first: Susan

last: Sutton

first: Michael

middle: P

last: Cooke

first: Xiaoxio

last: Tan

first: Claes

last: Öhlén

first: Philip

last: Greenberg


title: Transcriptome analysis in rat

status: Public on Jan 27 2004

first: John

summary:
Large scale transcriptome analysis of Wistar and Sprague Dawley rat tissues.
Keywords: other

first: Andrew

last: Su

first: David

last: Self

first: Hilmar

last: Lapp

first: Rainer

last: Maier

first: Daniel

last: Hoyer

first: Graeme

last: Bilbe


title: Genomic Strategies Identify the Antitumor Agent Apratoxin A as a Potent Antagonist of FGF Signaling and STAT3 Activation

status: Public on Feb 08 2006

last: Walker

summary:
Total RNA was extracted from apratoxin A or vehicle treated HT29 cells using the RNeasy Mini Kit (Qiagen).  Probe values from CEL files were condensed to probe sets using Rosetta Resolver software.  Resolver ANOVA analysis was then performed between groups.
Keywords: time course and dose

overall_design: 2 doses were compared to vehicle at 3 time points.  Each time point had its own vehicle control

first: Hendrik

last: Luesch

first: Sumit

last: Chanda

first: R

last: Raya

first: Anthony

last: Orth

first: J

last: Belmonte

first: Peter

last: Schultz


title: TFIIH mutants treated with methyl methanesulfonate

status: Public on Apr 20 2005

summary:
Purpose of profiling experiment was to examine effects of a mutation of a subunit of TFIIH, ssl1p, which has ubiquitin ligase activity.
The whole complex has previously been shown to have both kinase and helicase activities.  We wanted to see if 1) there were
general transcriptional defects with these mutations, as there are with other mutations to kinase activity, and 2) if there
were transcriptional effects on DNA repair machinery when the mutants were treated with MMS, which is an alkylating agent.
Keywords: other

first: Claudio

last: Masuda

last: Joazeiro

first: Yuichiro

last: Takagi

first: Wei-Hau

last: Chang

first: Hirofumi

last: Komori

first: Dong

last: Wang

first: Tony

last: Hunter

first: Roger

last: Kornberg


title: Circadian rhythm in clock mutants

first: John

summary:
One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at –80 degrees C until use.

This SuperSeries is composed of the SubSeries listed below.

overall_design:
This reference Series links data in the following related Series:
GSE3746 Circadian skeletal muscle_wt and Clock mutants
GSE3748 Circadian liver_wt and Clock mutants

first: Erin

last: McDearmon

first: Satchidananda

last: Panda

first: Jessica

last: Andrews

first: Martin

last: Straume

first: Karyn

last: Esser

last: Hogenesch

first: Joseph

last: Takahashi


title: Large-scale analysis of the human transcriptome

status: Public on Dec 06 2002

last: Walker

summary:
High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://expression.gnf.org) that integrates data visualization and curation of current gene annotations.
Keywords: other

first: A

last: Su

first: M

last: Cooke

first: K

last: Ching

first: Y

last: Hakak

first: T

last: Wiltshire

last: Orth

first: R

last: Vega

first: L

last: Sapinoso

last: Moqrich

last: Patapoutian

first: G

last: Hampton

first: P


status: Public on Mar 19 2004

summary:
The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.
Keywords: different tissues

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: baseline gene expression was taken from various human and mouse tissues

first: Andrew

first: Tim

first: Serge

last: Batalov

first: Hilmar

last: Lapp

first: Keith

first: David

last: Block

first: Jie

last: Zhang

first: Richard

last: Soden

first: Mimi

last: Hayakawa

first: Gabriel

last: Kreiman

first: Michael


title: Hypothalamus response to LPS and restraint stress

status: Public on Apr 17 2003

first: John

last: Walker

summary:
The paraventricular hypothalamic nucleus (PVH) is a key site for integrating neuroendocrine, autonomic, and behavioral adjustments to diverse homeostatic challenges, including "physiological" (e.g., infection or hemorrhage) and "emotional" [e.g., restraint (RST) or footshock] stresses. Both types of challenges ultimately converge to activate common response systems represented in PVH, including the hypothalamo-pituitary-adrenal axis and the sympathoadrenal system. Oligonucleotide microarrays (U74A; Affymetrix, Santa Clara, CA) were used to compare and contrast gene expression profiles in the PVH elicited at 1 and 3 hr after acute exposure to representative physiological [intraperitoneal injection of 10 microg lipopolysaccharide (LPS)] and emotional (30 min RST) stressors. In general, the two challenges recruited relatively few genes in common, with the degree of overlap varying across functional classes of genes. The greatest degree of commonality was seen among signaling molecules and neuropeptides, whereas transcription factors upregulated by RST and LPS were largely distinct. Unexpectedly, RST induced a number of immune-related molecules, which were not regulated by LPS. Hybridization histochemical analyses localized a subset of responsive transcripts to the PVH and/or immediately adjoining regions. Immunerelated molecules in particular distributed broadly to vascular and other barrier-associated cell types. These global transcriptional profiles inform the search for early (transcription factors) and late (target genes) mechanisms in the modulation of PVH, and generalized CNS, responses to categorically distinct stressors.
Keywords: other

last: Reyes

middle: E

last: Sawchenko


title: Large-scale analysis of the mouse transcriptome

summary:
High-throughput gene expression profiling has become an important tool for investigating transcriptional activity in a variety of biological samples. To date, the vast majority of these experiments have focused on specific biological processes and perturbations. Here, we have generated and analyzed gene expression from a set of samples spanning a broad range of biological conditions. Specifically, we profiled gene expression from 91 human and mouse samples across a diverse array of tissues, organs, and cell lines. Because these samples predominantly come from the normal physiological state in the human and mouse, this dataset represents a preliminary, but substantial, description of the normal mammalian transcriptome. We have used this dataset to illustrate methods of mining these data, and to reveal insights into molecular and physiological gene function, mechanisms of transcriptional regulation, disease etiology, and comparative genomics. Finally, to allow the scientific community to use this resource, we have built a free and publicly accessible website (http://biogps.gnf.org) that integrates data visualization and curation of current gene annotations.
Keywords: other

first: A

last: Su

first: M

last: Cooke

first: K

last: Ching

first: Y

last: Hakak

first: J

first: T

last: Wiltshire

last: Schultz

last: Hogenesch


title: Genome-wide association analysis in diverse inbred mice: power and population structure

status: Public on Apr 18 2007

summary:
The discovery of quantitative trait loci (QTL) in model organisms has relied heavily on the ability to perform controlled breeding to generate genotypic and phenotypic diversity.  Recently, we and others have demonstrated the use of a set of diverse inbred mice as a QTL mapping population.  The use of this population has many advantages, including increased phenotypic diversity, a higher recombination frequency and the ability to collect genotype data in community databases.  However, these methods are complicated by inherent population structure and the inability to accurately assess statistical power.  To address these issues, we measured gene expression levels in hypothalamus across the diverse inbred mapping population.  We then mapped these phenotypes as quantitative traits with our association algorithm, resulting in a large set of expression QTLs.  We utilized these eQTLs (and specifically the cis-eQTLs) to devise a relative measure of statistical power which does not rely on parametrically simulated data.  Finally, we utilized this approach to develop and optimize a novel method of accounting for population structure in the Mouse Diversity Panel.
Keywords: strain and gender

overall_design: samples were taken from naïve mice of different strains and both genders

first: Phillip

last: McClurg

first: Jeff

last: Janes

first: Chunlei

last: Wu

last: Delano

first: Joseph

last: Takahashi

first: Kazu

last: Shimomura

first: Akira

last: Kohsaka

last: Bass

first: Tim

first: Andrew


title: Identification of genes and quantitative trait loci (QTL) that control hematopoietic stem cell functioning

status: Public on Dec 02 2004

last: Walker

summary:
We have combined large-scale mRNA expression and gene mapping methods to identify genes and loci that control hematopoietic stem cell (HSC) functioning. mRNA expression levels were measured in purified HSC isolated from a panel of densely genotyped recombinant inbred mouse strains. Quantitative trait loci (QTLs) associated with variation in expression of thousands of transcripts were mapped. Comparison of the physical transcript position with the location of the controlling QTL identified polymorphic cis-acting stem cell genes. In addition, multiple trans-acting control loci were highlighted that modify expression of large numbers of genes. These groups of co-regulated transcripts identify pathways that specify variation in stem cells. We illustrate this concept with the identification of strong candidate genes involved with HSC turnover.  We compared expression QTLs in HSC and brain from the same animals, and document both shared and tissue-specific QTLs. Our data are accessible through WebQTL, a web-based interface that allows custom genetic linkage analysis and identification of co-regulated transcripts.
Keywords: other

first: Leonid

last: Bystrykh

first: Ellen

last: Weersing

first: Bert

last: Dontje

first: Sue

last: Sutton

first: Mathew

middle: T

last: Pletcher

first: Edo

last: Vellenga

first: Jintao

last: Wang

first: Kenneth

middle: F

last: Manly

first: Lu

last: Lu

first: Elissa

last: Chesler

first: Rudi

last: Alberts

first: Ritsert

last: Jansen

first: Robert

middle: W

last: Williams

first: Gerald

last: de Haan