title: Gene profiles of HUVECs in different phosphate concentration

status: Public on Aug 30 2014

first: Ling

last: Qin

address: No.301,Middle Yanchang Road

department: Nephrology

institute: Shanghai Tenth People's Hospital,Tongji University School of medicine

summary: Hyperphosphatemia is an independent risk factor for cardiovascular mortality in chronic kidney disease. High inorganic phosphorus can induce endothelial cell apoptosis, but the exact mechanism is not fully understood. This study addresses this knowledge gap.Microarray analysis was used to identify differentially expressed gene profiles in human umbilical vein endothelial cells (HUVECs) in high phosphate (3.0 mM)  normal phosphate (1.0 mM) medium and low phosphate( 0.5mM).

overall_design: Differential gene expression in HUVECs seeded in high phosphate (3.0 mM ) medium ,normal phosphate ( 1.0 mM ) medium and simulated hypophosphatemia (0.5mM) were identified using Affymetrix GeneChip Human Gene 1.0 ST arrays ( Affymetrix ). Three chips were used to minimize the random error in each group.

last: Tang

first: Bingqing

last: Deng

first: Chandra

last: Mohan

first: Tianfu

last: Wu

first: Ai

last: Peng


title: Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors (mRNA)

status: Public on Aug 24 2014

city: Basel

first: Jonathan

last: Moggs

address: Fabrikstrasse 2

country: Switzerland

institute: Novartis

summary: The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcino- genesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARKO -PXRKO ), double humanized CAR and PXR (CARh - PXRh), and wild-type C57BL/6 mice. Wild-type and CARh-PXRh mouse livers exhibited temporally and quantitatively similar tran- scriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were ob- served with peak expression occurring between 1 and 7 days PB ex- posure. All these transcriptional responses were absent in CARKO- PXRKO mouse livers and largely reversible in wild-type and CARh - PXRh mouse livers following 91 days of PB exposure and a subse- quent 4-week recovery period. Furthermore, PB-mediated upregu- lation of the noncoding RNA Meg3, which has recently been associ- ated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARh-PXRh mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.

overall_design: 13-week oral (drinking water) investigative phenobarbital study in male C57BL/6 wild type, CAR/PXR knockout and humanized CAR/PXR mice with a 4 week recovery period

first: Raphaelle

last: Luisier

first: Harri

last: Lempiäinen

first: Nina

last: Scherbichler

first: Albert

last: Braeuning

first: Miriam

last: Geissler

first: Valerie

last: Dubost

first: Arne

last: Müller

first: Nico

last: Scheer

first: Salah-Dine

last: Chibout

first: Hisanori

last: Hara

first: Frank

last: Picard

first: Diethilde

last: Theil

first: Philippe

last: Couttet

first: Antonio

last: Vitobello

first: Olivier

last: Grenet

first: Bettina

last: Grasl-Kraupp

first: Heidrun

last: Ellinger-Ziegelbauer

first: John

middle: P

last: Thomson

first: Richard

middle: R

last: Meehan

first: Clifford

last: Elcombe

first: Colin

middle: J

last: Henderson

first: C

last: Wolf

first: Michael

last: Schwarz

first: Pierre

last: Moulin

first: Rémi

last: Terranova

middle: G


title: miRNAs in Treg-derived Exosomes

status: Public on Aug 27 2014

city: London

first: Mark

middle: Stephen

last: Wilson

address: The Ridgeway

department: Molecular Immunology

country: United Kingdom

institute: MR, NIMR

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

summary: Foxp3+ regulatory T (Treg) cells prevent inflammatory disease but the mechanistic basis of suppression is not understood completely . Gene silencing by RNA interference can act in a cell-autonomous and non-cell-autonomous manner, providing mechanisms of inter-cellular regulation. Here, we demonstrate that non-cell-autonomous gene silencing, mediated by miRNA-containing exosomes, is a mechanism employed by Treg cells to suppress T cell-mediated disease. Treg cells transferred microRNAs (miRNA) to various immune cells, including T helper 1 (Th1) cells, suppressing Th1 cell proliferation and cytokine secretion. Use of Dicer-deficient or Rab27a and Rab27b double-deficient Treg cells to disrupt miRNA-biogenesis or the exosomal pathway, respectively, established a requirement for miRNAs and exosomes for Treg cell-mediated suppression. Transcriptional analysis and miRNA inhibitor studies showed that exosome-mediated transfer of Let-7d from Treg cell to Th1 cells contributed to suppression and prevention of systemic disease. These studies reveal a mechanism of Treg cell-mediated suppression mediated by miRNA-containing exosomes.

platform_organism:
Mus musculus
synthetic construct

overall_design: Regulatory T cells (CD4+CD25hiFoxp3rfp+, Treg) were isolated from naive mice. RNA as extracted form some Treg cells, while others were cultured in complete IMDM media for 3 days, stimulated with anti-CD3 anti-CD3 (1ug/ml) and anti-CD28 (10ug/ml). Exosomes were recovered from Treg cell supernatant, as described, and RNA was extracted form the purified exosomes. To identify which miRNAs were transferred to Dicer-deficient (KO) cells from Treg cells, we cultured Dicer KO cells alone, or co-cultured Dicer KO cells with Treg cells. RNA was extracted form Dicer KO cells cultured alone or from Dicer KO cells cultured in the presence of Treg cells. 3 x biological replicates were used. Each biological replicate was derived from a pool of 3-5 samples.

middle: S

first: Isobel

last: Okoye


title: Determination of prognosis in metastatic melanoma through integration of clinico-pathologic, mutation, mRNA, microRNA, and protein information

status: Public on Aug 18 2014

city: North Sydney

first: Graham

middle: J.

last: Mann

state: NSW

address: Poche Centre, 40 Rocklands Road

country: Australia

institute: Melanoma Institute Australia

summary: In patients with metastatic melanoma, the identification and validation of accurate prognostic biomarkers will assist rational treatment planning. Studies based on "-omics" technologies have focussed on a single high-throughput data type such as gene or microRNA transcripts. Occasionally, these features were evaluated in conjunction with limited clinico-pathologic data. With the increased availability of multiple data types, there is a pressing need to tease apart which of these sources contain the most valuable prognostic information. We evaluated and integrated several data types derived from the same tumor specimens in AJCC stage III melanoma patients - gene, protein, and microRNA expression as well as clinical, pathologic and mutation information - to determine their relative impact on prognosis. We used classification frameworks based on pre-validation and bootstrap multiple imputation classification to compare the prognostic power of each data source, both individually as well as integratively. We found that the prognostic utility of clinico-pathologic information was not out-performed by various "-omics" platforms. Rather, a combination of clinico-pathologic variables and mRNA expression data performed best. Furthermore, a patient-based classification analysis revealed that the prognostic accuracy of various data types was not the same for different patients, providing useful insights for ongoing developments in the individualized treatment of melanomas patients. SPECIAL NOTE: In this study, survival data were re-extracted from the MIA research database for all patients and brought up to date, revealing discrepancies affecting survival class in the case of four patients compared with the previous dataset (GSE53118: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53118). The current survival data are considered to be more accurate although the expression information has not changed. In addition, there were 5 samples (122, 144, 195, 264, and 358) for which gene expression information were not available at the time of analysis. However, the associated clinical information for these samples is provided since it was analysed elsewhere in the accompanying publication.

overall_design: Samples eligible for this study (n=84) were obtained from lymph node specimens (Melanoma Institute Australia (MIA) Biospecimen Bank) in which macroscopic tumor was observed, obtained from patients believed to be without distant metastases at the time of tumor banking based on clinical examination and computerised axial tomographic scanning of the brain, chest, abdomen and pelvis. Specimens were macro-dissected at time of banking and subsequently reviewed to meet minimum criteria for tumor cell content (>80%) and amount of necrosis (<30%). Linked clinical and pathologic data were obtained from the MIA research database. We previously analyzed the distribution of survival times in these samples and identified more favorable and less favorable groups as patients having time from surgery to death from melanoma greater than 4 years with no sign of relapse (n=25) or less than 1 year (n=22), respectively (Mann et al. 2013, PMID: 22931913). Since that publication, survival data have been re-extracted from the MIA research database for all patients and brought up to date, revealing discrepancies affecting survival class in the case of four patients compared with the previous dataset. The current survival data are considered to be more accurate. MRNA expression profiling and somatic mutation profiling, were performed as previously described in Mann et al. 2013 (PMID: 22931913).

first: Kaushala

last: Jayawardana

first: Sarah-Jane

last: Schramm

first: Lauren

last: Haydu

middle: F

last: Thompson

middle: A

last: Scolyer

first: Samuel

last: Müller

first: Yee

middle: H

last: Yang


title: Mouse Spontaneous C3H/HeJ AA Skin

status: Public on Aug 17 2014

city: Iowa City

first: Ali

last: Jabbari

state: IA

address: 200 Hawkins Dr, 40025 PFP

country: USA

institute: University of Iowa

summary: Our goal was to develop a transcriptomic description of affected alopecic skin from aged C3H/HeJ mice.  Affected skin from 3 mice was compared to skin from similarly aged but unaffected C3H/HeJ mice.

overall_design: 3 biological replicates from 3 separate affected mice compared with 3 biological replicate controls from 3 unaffected mice

first: Jane

middle: E

last: Cerise

first: Angela

middle: M

last: Christiano


title: Prevention of Mouse AA with IL-15 pathway inhibitors

summary:
Our goal was to identify gene expression patterns that correlated with prevention of autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
skin from 3-5 mice were taken at 5/6 weeks and 12/13 weeks of drug administration following grafting; mice were treated with ruxolitinib (jak12i) by oral gavage, tofacitinib (jak3i) by osmotic pump, antiIL15R-beta antibody by i.p. injection, or control pbs by either ip injection, oral gavage, or osmotic pump. sham indicates mice that received no graft.

overall_design: 3-5 biological replicates were taken at each time point for each treatment modality


title: Dissecting engineered cell types and enhancing cell fate conversion via CellNet

status: Public on Aug 14 2014

city: Rochester

first: Hu

last: Li

state: MN

address: 200 First Street, Gonda Building G19-408

department: Molecular Pharmacology & Experimental Therapeutics

institute: Mayo Clinic

summary: Engineering clinically relevant cells in vitro holds promise for regenerative medicine, but most protocols fail to faithfully recapitulate target cell properties. To address this, we developed CellNet, a network biology platform that determines whether engineered cells are equivalent to their target tissues, diagnoses aberrant gene regulatory networks, and prioritizes candidate transcriptional regulators to enhance engineered conversions. Using CellNet, we improved B cell to macrophage conversion, transcriptionally and functionally, by knocking down predicted B cell regulators. Analyzing conversion of fibroblasts to induced hepatocytes (iHeps), CellNet revealed an unexpected intestinal program regulated by the master regulator Cdx2. We observed functional engraftment of mouse colon by iHeps, thereby establishing their broader potential as endoderm progenitors and demonstrating direct conversion of fibroblasts into intestinal epithelium. Our studies illustrate how CellNet can be employed to improve direct conversion and to uncover unappreciated properties of engineered cells.

overall_design: 15 samples

first: Patrick

last: Cahan

first: Samantha

last: Morris

first: George

middle: Q

last: Delay

first: James

last: Collins


title: Expression data from embryonic stem cells differentiation

city: Shanghai

first: Shiyue

last: Zhang

address: 225 South Chongqing Road

department: Institute of Health Sciences

country: China

institute: Shanghai Institutes for Biological Sciences, CAS

summary:
Pluripotency-associated transcription factor Foxd3 is required for maintaining pluripotent cells. However, the molecular mechanisms underlying its function are largely unknown. Here, we report that Foxd3 maintains the ESC identity through counteracting differentiation induction of Calcienurin-NFAT signaling.
We used microarrays to detail the global programme of gene expression underlying overexpression of Foxd3 and NFATc3 in ESCs or deletion of Foxd3 in ESCs

overall_design: Total RNA was extracted from the mESCs under the following conditions:1) a control group transfected with an empty vector; a Foxd3 overexpression group; a NFATc3 overexpression group and a combination group with Foxd3 and NFATc3 overexpression 2) Foxd3fl/fl:Cre-ERT cells treated with Tamoxifen for 0 day and 2 days.

first: Lili

last: Zhu

first: Ying

last: Jin


title: The HER2-encoded miR-4728-3p regulates ESR1 through a non-canonical internal seed interaction

status: Public on Aug 13 2014

city: Lund

first: Rolf

last: Søkilde

address: Scheelevägen 2

department: Department of Oncology

country: Sweden

institute: Lund University, Sweden

summary: Since the early 1980s remarkable progress has been made in understanding the role of the HER2 locus in carcinogenesis, but many details of its regulatory network are still elusive. We recently reported the finding of 367 new human microRNA (miRNA) genes of which one, mir-4728, is encoded in an intron of the HER2 gene. Here, we confirm that the HER2 oncogene is a bi-functional locus encoding the membrane receptor and a functional miRNA gene. We further show that miR-4728-3p has alternative functionalities depending on the region used for interaction with its target; the canonical seed between nucleotides 2-8 or a novel, more internal seed shifted to nucleotides 6-12. Analysis of public data shows that this internal seed region, although rare compared to the far more abundant canonical 2-8 seed interaction, can also direct targeted down-regulation by other miRNAs. Through the internal seed, miR-4728-3p regulates expression of estrogen receptor alpha, an interaction that would have remained undetected if classic rules for miRNA-target interaction had been applied. In summary, we present here an alternative mode of miRNA regulation and demonstrate this dual function of the HER2 locus, linking the two major biomarkers in breast cancer.

overall_design:
6 samples treated with hsa-miR-4728-3p mimic and 6 samples treated with non-targeting control
4 samples treated with hsa-miR-1-3p mimic and 4 samples treated with non-targeting control

last: Soekilde

first: Inga

last: Newie

first: Helena

last: Persson

first: Dorthe

last: Grabau

first: Natalia

last: Rego

first: Anders

last: Kvist

first: Kristoffer

last: von Stedingk

first: Håkan

last: Axelson

first: Åke

last: Borg

first: Johan

last: Vallon-Christersson

first: Carlos

last: Rovira


title: Treatment of established mouse AA with topical JAK inhibitors

first: Ali

last: Jabbari

summary:
Our goal was to identify gene expression patterns that correlated with treatment of established autoimmune alopecia in C3H/HeJ mice following alopecic graft transplantation
skin from 3 mice were taken at 6, 12 and, in some cases, 24 weeks of topical drug administration following grafting; mice were treated with ruxolitinib (jak1i), tofacitinib (jak3i), or control pbs

overall_design: 3 biological replicates were taken at each time point for each treatment modality

first: Jane

last: Cerise

first: Angela

last: Christiano


title: FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance

city: Uppsala

first: Maria

last: Pereira

address: Akademiska sjukhuset, Ing 70 3trp Lab 21

department: Department of Medical Sciences

institute: Uppsala University

summary: Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance.

overall_design: Paired human subcutaneous (sc) and omental (om) adipose tissue samples obtained from 4 non-diabetic adipose tissue donors (4 M; BMI: 20.8-27.5 Kg/m2)  were incubated without (Ctr) or with dexamethasone (Dex, 3 μM) for 24 h.

first: Jenny

last: Palming

middle: K

last: Svensson

first: Magnus

last: Rizell

first: Jan

last: Dalenbäck

first: Mårten

last: Hammar

first: Per-Arne

middle: W

last: Eriksson


title: Two Histone/Protein Acetyltransferases, CBP and p300, Are Indispensable for Foxp3+ T-regulatory Cell Development and Function

status: Public on Aug 12 2014

city: Philadelphia

first: Wayne

last: Hancock

state: PA

address: 916B ARC, 3615 Civic Ctr Blvd

institute: CHOP/UPenn

summary: T-regulatory (Treg) cells are important to immune homeostasis, and Treg cell deficiency or dysfunction leads to autoimmune disease. An histone/protein acetyltransferase (HAT), p300, was recently found important for Treg function and stability, but further insights into the mechanisms by which p300 or other HATs affect Treg biology are needed. Here we show that CBP, a p300 paralog, is also important in controlling Treg function and stability. Thus, while mice with Treg-specific deletion of CBP or p300 developed minimal autoimmune disease, the combined deletion of CBP and p300 led to fatal autoimmunity by 3-4 weeks of age. The effects of CBP and p300 deletion on Treg development are dose-dependent, and involve multiple mechanisms. CBP and p300 cooperate with several key Treg transcription factors that act on the Foxp3 promoter to promote Foxp3 production. CBP and p300 also act on the Foxp3 CNS2 region to maintain Treg stability in inflammatory environments by regulating pCREB function and GATA3 expression, respectively. Lastly, CBP and p300 regulate the epigenetic status and function of Foxp3. Our findings provide insights into how HATs orchestrate multiple aspects of Treg development and function, and identify overlapping but also discrete activities for p300 and CBP in control of Treg cells.

overall_design: RNA from three independent samples from magnetically separated CD4+CD25+ Treg of fl-p300/Foxp3cre mice and fl-CBP/Foxp3cre, compared to wild type (Foxp3cre) control (all C57Bl/6 background).

first: Yujie

last: Liu

first: Liqing

last: Wang

first: Rongxiang

last: Han

first: Ulf

last: Beier

first: Tatiana

last: Akimova

first: Tricia

last: Bhatti

first: Haiyan

last: Xiao

first: Philip

last: Cole

first: Paul

last: Brindle


title: Gene Expression Profile of Fibrovascular Membrane Associated with Proliferative Diabetic Retinopathy

status: Public on Aug 16 2014

city: Fukuoka

first: Keijiro

last: Ishikawa

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

department: Ophthalmology

country: Japan

institute: Kyushu University

summary:
Proliferative diabetic retinopathy (PDR) is a vision-threatening disorder characterized by the formation of cicatricial fibrovascular membranes leading to traction retinal detachment. Despite the recent advance in the treatment of PDR such as vitreoretinal surgery with use of anti-vascular endothelial growth factor (VEGF) drug as an adjunct, it still remains vision-threatening disease.
In order to identify genes associated with the pathogenesis of PDR, we performed gene expression analyses in fibrovascular membrane in patients with PDR using DNA microarray technology.

overall_design: This study was approved by the Ethics Committee of the Kyushu University Hospital and Fukuoka University Chikushi Hospital, and the surgical specimens were handled in accordance with the ethical standards of the 1989 Declaration of Helsinki. All patients gave informed consent before inclusion in the study. Fibrovascular membranes (FVMs) were surgically dissected from the retinal surface with horizontal scissors of patients with PDR undergoing pars plana vitrectomy. These specimens were classified into active and inactive according to the clinical findings of neovascularization (NV) in the FVMs.Total RNA were extracted from the FVMs. RNA from human retina was obtained from Clontech (Palo Alto, CA).

first: Shigeo

last: Yoshida


title: Effects of dPRP (PRL8a2) on gene expression of decidual-placental-embryonic tissue

status: Public on Aug 09 2014

city: Kansas City

first: Michael

last: Soares

state: KS

address: 3901 Rainbow Blvd

department: Department of Pathology and Laboratory Medicine

institute: University of Kansas Medical Center

summary: DPRP (PRL8a2) is critically involved in adaptations of the placentation site to physiological stressors.  DPRP (PRL8a2) restrains the expression of genes associated with ER stress.

overall_design: We used DNA microarrays to analyze the transcriptome of wild type and dPRP null mouse decidual-placental-embryonic tissues from gestation day 7.5.

first: Khoshed

last: Alam

first: Toshihiro

last: Konno


title: Misprocessing of APP and accumulation of β-Amyloid causes early alteration of pathways implicated in late-onset Alzheimer disease.

city: Toronto

first: Peter

last: St George-Hyslop

state: Ontario

address: 6 Queen’s Park Crescent West

country: Canada

institute: Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto

summary: Genome-wide association studies (GWAS) have identified genes in lipid metabolism,inflammation and vesicular trafficking pathways as risk factors for late onset Alzheimer disease (LOAD). The mechanism by which they cause AD and their relationship to the amyloid cascade affected by genes causing early onset familial AD is unknown. Unproven hypotheses are that these LOAD genes modulate the amyloid cascade itself or downstream targets affected by this cascade.If so, it is likely that these genes and/or other genes in the same pathways may show alterations in their expression as an early consequence of misprocessing of amyloid precursor protein (APP) and accumulation of amyloid β-peptides (Aβ). We report that in three independent APP transgenic mouse models of AD, multiple genes in lipid and inflammation pathways show very early changes in mRNA and protein expression. Many of these changes are reversed by treatment with LXR agonists, which regulate transcription of genes in lipid/inflammation pathways, and which we have previously shown can reverse the cognitive deficits and neuropathology in Tg2756 mice. These results suggest that changes in lipid and inflammation pathways are likely to be very early consequences of APP misprocessing and Aβ accumulation in AD. Moreover, genetic variants within these pathways might affect risk for AD by modulating this early response. These pathways are likely to contain biomarkers of early disease and targets for therapies.

overall_design: TgCRND8 mice and wild-type littermate controls at ages 70, 80, and 150 days (n = 4 mice per cohort) were used in the study.

first: Yosuke

last: Wakutani

first: Mahdi

last: Ghani

first: Shinya

last: Tokuhiro

first: Christopher

last: Bohm

first: Fusheng

last: Chen

first: Christine

last: Sato

first: Erik

middle: D

last: Roberson

first: William

last: Meilandt

first: Jochen

last: Walter

first: Badri

last: Vadarajan

first: Naomi

last: Visanji

first: Janice

last: Wong

first: Ekaterina

last: Rogaeva

first: Richard

last: Mayeux

first: Lindsay

last: Farrer

first: Helen

last: Warwick

first: Suzan

last: Aschmies

first: Max

last: Follettie

first: David

last: von Schack

first: Tarek

last: Samad

last: Riddell

first: Lennart

last: Mucke

first: Lili-Naz

last: Hazrati


title: Genome-wide analysis of monocyte derived macrophages from Crohn's Disease patients and controls

status: Public on Aug 06 2014

first: Tony

last: Segal

address: 5 University Street

department: Medicine

institute: UCL

summary: Crohn's disease (CD) is a complex and highly heterogeneous chronic inflammatory disorder, primarily affecting the gastrointestinal tract. Genetic and functional studies have highlighted a key role for innate immunity in its pathogenesis. Profound systemic defects in innate immunity and acute inflammation are understood to result in markedly delayed clearance of bacteria from the tissues, leading to local chronic granulomatous inflammation and compensatory adaptive immunological changes. Macrophages, key orchestrators of acute inflammation, are likely to play an important role in the initial impaired innate immune response. Monocyte-derived macrophages from CD patients stimulated with E. coli were shown to release attenuated levels of TNF and IFNγ with normal secretion of IL8, IL10 and IL6. In controls, the secretion of these cytokines was strongly positively correlated, which was not seen with CD macrophages. The transcriptomes of CD and control macrophages were examined in an attempt to understand the molecular basis of this defect. There were no differentially expressed genes identified between the two groups, consistent with genetic heterogeneity; however, a number of molecules were found to be under-expressed in subgroups of CD patients. The most common of these was optineurin (OPTN) which was under-expressed in approximately 10% of the CD patients. Reduced OPTN expression coincided with lower intracellular protein levels and diminished cytokine secretion after bacterial stimulation both in the patients and with siRNA knockdown in THP-1 cells. Identifying and studying subgroups of patients with shared defective gene expression could aid our understanding of the mechanisms underlying highly heterogeneous diseases such as CD.

overall_design: Total RNA obtained from monocyte derived macrophages from Crohn's disease patients (n=58) or healthy volenteers (n=42) were cultured for six days before being stimulated with heat killed E. coli for four hours or left unstimulated.

first: Andrew

last: Smith

first: Gavin

last: Sewell

first: Adam

last: Levine

first: Anthony


title: Gene Profiling in Mouse Fetal Ductus Arteriosus

status: Public on Aug 05 2014

city: Nashville

first: John

middle: Jeffrey

last: Reese

state: TN

address: 2200 Children's Way

department: Division of Neonatology

institute: Vanderbilt

summary:
The ductus arteriosus (DA) is a fetal vascular shunt that is located between the main pulmonary artery and the aorta. Oxygenated fetal blood from the placenta is shunted past the uninflated fetal lungs, crosses the DA, and is then available to the peripheral organs. In utero closure of the DA is deleterious, but postnatal closure of the DA is necessary for establishment of pulmonary circulation and the transition to newborn life.
We used microarrays to compare ductus arteriosis (DA) and aortic gene expression at a single time point (day 19 of gestation, which is the day of expected delivery).

overall_design: DA and corresponding aortic vascular segments from fetal mice on day 19 of gestation  were collected from every pup in a litter (up to the first 10 pups). These samples were pooled and considered representative of the DA's or aortas from one pregnant female. Tissues were homogenized via 27g needle, per GentraSystems Versagene kit

first: Jeff

first: Cristi

middle: L

last: Galindo


title: Tfap2a dependnt cha

city: Calgary

first: Benedikt

last: Hallgrimsson

state: AB

address: 3330 Hospital Dr NW

department: Cell Bio and Anatomy

institute: University of Calgary

summary: Neo/null loss of Tfap2a in E10.5 mouse facial prominences

overall_design: triplicate run comparing tissue dissected from the nasal, maxillary and mandibular comparing AP-2 mutant and control embryos

first: Weiguo

last: Feng

first: Trevor

last: Williams


title: Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors

first: Jonathan

last: Moggs

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

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

overall_design: Refer to individual Series


title: Expression profiling of prostate cancer biopsies.

city: Porto

first: Manuel

middle: R.

last: Teixeira

address: Rua Dr. António Bernardino de Almeida

department: Department of Genetics

country: Portugal

institute: Portuguese Oncology Institute-Porto

summary: This work was conducted to identify shared and specific target genes of different ETS transcription factor rearrangements in prostate cancer. Potential target genes were identified by differential gene expression analysis of primary tumor samples with ETS rearrangements, and validated by ETS silencing in prostate cancer cell lines.

overall_design: The series consists of 50 primary tumor samples from a consecutive series of 200 clinically localized cancers treated with radical prostatectomy at the Portuguese Oncology Institute, Porto, Portugal. The series is enriched in tumors with ETS transcription factor rearrangments.

middle: R

first: Paula

last: Paulo

first: Anita

last: Sveen

first: Rolf

middle: I

last: Skotheim


title: Modeling the clinical phenotype of BTK inhibition in the mature murine immune system

status: Public on Aug 01 2014

city: Cambridge

last: Hill

state: MA

address: 300 Technology Square

department: Research Business Technology

institute: Pfizer

summary:
Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice autoimmune indications. However, our current knowledge of the role of BTK in immune competence has been gathered in the context of genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice. We implicate BTK in tonic BCR signaling, demonstrate dependence of the T3 B cell subset and IgM surface expression on BTK activity, and find that B1 cells survive and function independently of BTK. While BTK inhibition does not impact humoral memory survival, antigen-driven clonal expansion of memory B cells and antibody secreting cell generation are inhibited. These data define the role of BTK in the mature immune system and mechanistically predict the clinical phenotype of BTK inhibition.
We used Affymetrix genechips to profile the transcriptional changes downstream of BTK inhibition after in vivo B-cell activation by anti-IgD

overall_design: Mice were injected with the novel BTK inhibitor PF-303 2 hours prior to anti-IgD mediated in vivo B-cell activation; B-cells where harvested 2 hours after anti-IgD activation and RNA isolated.

first: Micah

middle: J

last: Benson

first: Varenka

last: Rodriguez

first: Sean

last: Keegan

first: Tim

last: Cook

first: Stephen

last: Benoit

first: Nilufer

last: Seth

first: Cheryl

last: Nickerson-Nutter

first: Kyri

last: Dunussi-Joannopoulos

last: Rankin

first: Melanie

last: Ruzek

first: Dean

last: Messing

first: Jason

last: Edmonds

first: Sarah

last: Du

first: Mark

last: Schnute

last: Douhan

first: David

last: von Schack


title: Expression data from mouse luminal mammary epithelial cells

status: Public on Aug 20 2014

city: Singapore

first: Alexandra

last: Pietersen

address: 11 Hospital Drive

country: Singapore

institute: National Cancer Centre Singapore

summary:
We used a mouse strain in which one Tbx3 gene was replaced with the yellow fluorescent protein variant Venus. Luminal cells had either very high Tbx3 promoter activity or not at all.
We performed an expression analysis on luminal mammary epithelial cells sorted based on their Venus expression (reporting Tbx3 promoter activity) to investigate the difference between these two cell populations.

overall_design: Mammary epithelial cells from 3 Tbx3-Venus-KI adult virgin female mice (FVB background) were pooled and luminal cells were sorted into a Venus-hi and a Venus-neg sample. There were no repeats for this study.


title: Gene expression microarray of HT1080 cell line

status: Public on Jul 31 2014

city: Seattle

middle: W.

last: Russell

state: WA

address: 1959 NE Pacific St

institute: University of Washington

summary: Analysis of the effects of genomic elements, gene transcritpion, and DNA replication on gene targeting.  The hypothesis tested was that genomic elements and processes either positively or megatively influence AAV-mediated gene targeting.  Results show that homologous recombination increases when the target site is transcribed in the opposite orientation of an incoming replication or transcription fork.

overall_design: Total RNA obtained from cultured HT1080 cell lines

last: Deyle


title: GeneChip expression profiling of Glud1 (glutamate dehydrogenase 1) transgenic mice across age

city: Lawrence

first: Xinkun

last: Wang

address: 2099 Constant Ave

department: Genomics Facility

institute: The University of Kansas

summary:
Glud1 (Glutamate dehydrogenase 1) transgenic mice release more excitatory neurotransmitter glutamate to synaptic cleft throughout lifespan.
Here we compared transcriptomic profiles of these animals to their wild-type counterparts across 5 ages. The hippocampus was used for the analysis.

overall_design: Longitudinal studies of Glud1 transgenic and wide-type mice across 5 age points: 10 days post birth,  4.5 mo, 9 mo, 14.5 mo, and 20 mo.

first: Elias

last: Michaelis


title: Gene expression data from mouse HDAC4 KO pups, postnatal day 3

status: Public on Jul 30 2014

city: Lausanne

first: Tamara

last: Seredenin

address: AI2135 Station 15 EPFL

institute: EPFL

summary:
Reversible protein acetylation provides a central mechanism for controlling gene expression and cellular signaling events. It is governed by the antagonistic commitment of two enzymes families: the histone acetyltransferases (HATs) and the histone deacetylases (HDACs). HDAC4, like its class IIa counterparts, is a potent transcriptional repressor through interactions with tissue-specific transcription factors via its N-terminal domain. Whilst the lysine deacetylase activity of the class IIa HDACs is much less potent than that of the class I enzymes, HDAC4 has been reported to influence protein deacetylation through its interaction with HDAC3.
To investigate the influence of HDAC4 on protein acetylation, we employed the unbiased AcetylScan proteomic screen. We identified many proteins known to be modified by acetylation, but found that the absence of HDAC4 had no effect on the acetylation profile of the murine neonate brain. This is consistent with the biochemical data suggesting that HDAC4 may not function as a lysine deacetylase, but these in vivo data do not support the previous report showing that the enzymatic activity of HDAC3 might be modified by its interaction with HDAC4. To complement this work, we used Affymetrix arrays to investigate the effect of HDAC4 knock-out on the transcriptional profile of the postnatal murine brain. There was no effect on global transcription, consistent with the absence of a differential histone acetylation profile. Validation of the array data by Taq-man qPCR indicated that only protamine 1 and Igfbp6 mRNA levels were increased by more than one-fold and only CamK4 was decreased. The lack of a major effect on the transcriptional profile is consistent with the cytoplasmic location of HDAC4 in the P3 murine brain.

overall_design: mRNA expression analysis was performed by microarray in 3-day-old HDAC4 KO pups and WT littermates. Ten samples were analysed for each genotype. Microarray quality control was performed using the software package provided on RACE (http://race.unil.ch).

first: Michal

last: Mielcarek

last: Seredenina

first: Georgina

last: Osborne

first: Christian

last: Landles

first: Linda

last: Inubasi

first: Sophie

last: Franklin

first: Jeffrey

last: Silva

first: Ruth

last: Luthi-Carter

first: Vahri

last: Beaumont

first: Gillian

middle: P

last: Bates


title: Association of prognosis of acute myeloid leukemia patients with leukemia stem cell gene signature based on nucleostemin promoter activity

city: Kanazawa

first: Atsushi

last: Hirao

address: kakuma

department: Division of Molecular Genetics

institute: kanazawa university

summary: Acute myeloid leukemia (AML) is a heterogeneous neoplastic disorder, in which only a subset of cells have function as leukemia-initiating cells (LICs). In this study, we prospectively evaluated leukemia-initiating capacity of fractionated subpopulations of AML cells depending on expression of a nucleolar GTP binding protein, Nucleostemin (NS). To monitor NS expression in living AML cells, we generated a mouse AML model using a transgenic mouse, in which green florescence protein (GFP) is expressed under the control of particular region of NS promoter (NS-GFP). In AML cells, NS-GFP levels were correlated with endogenous NS mRNA. AML cells with the highest expression of NS-GFP were very immature blast-like cells, efficiently formed leukemia colonies in vitro, and exhibited high leukemia-initiating capacity in vivo. Gene expression profiling analysis revealed that cell cycle regulators and nucleotide metabolism-related genes were highly enriched in a gene set associated with leukemia-initiating capacity, i.e., leukemia stem cell gene signature. Furthermore, we found that the leukemia stem cell gene signature stratified human AML patients into two distinct clusters, reflecting prognosis. These data demonstrate that the mouse leukemia stem cell gene signature is significantly associated with malignant properties of human AML patients. Further analyses of gene regulation related with leukemia stem cells would provide novel insights for the progress in diagnostic and therapeutic approach of AML patients.

overall_design: A mouse acute myeloid leukemia model was generated by introduction of HoxA9/Meis1 to bone marrow cells from a transgenic mouse, in which green florescence protein (GFP) is expressed under the control of particular region of NS promoter (NS-GFP).The leukemia cells were fractionated into 4 subpopulations based on NS-GFP level and c-Kit expression,  (a) c-Kit-NS-GFPlow, (b) c-Kit-NS-GFPmiddle, (c) c-Kit+NS-GFPmiddle and (d) c-Kit+NS-GFPhigh cells.


title: Comparison of pDCs isolated from recipients of STAT1+/+ vs. STAT1-/- bone marrow

status: Public on Jul 25 2014

city: Madison

last: Capitini

state: WI

address: 1111 Highland Ave, WIMR 4137

institute: University of Wisconsin

summary: The goal of this study is to determine if pDCs reconstituted from T cell depleted allogeneic STAT1-/- bone marrow express genes that contribute to Graft versus host disease (GVHD) resistance as compared to STAT1+/+ bone marrow

overall_design: Lethally irradiated B6 x C3H.SW mice were transplanted with T cell depleted 129 or 129 STAT1-/- bone marrow. 14 days later, pDCs were isolated from spleens by magnetic cell selection, and pooled from 12 mice/group. cDNA was generated and hybridized to an Affymetrix genechip mouse genome 430 2.0 array. Samples were normalized by RMA algorithm to a log2 intensity value and analyzed by Ingenuity Pathway Analysis v8.5 software.

first: Nicole

last: Nasholm

first: Christopher

last: Chien

first: Shannon

last: Larabee

first: Haiying

last: Qin

first: Young

last: Song

first: Peter

last: Klover

first: Lothar

last: Hennighausen

first: Javed

last: Khan

first: Terry

last: Fry


title: Identification of hormone-correlated genes as biomarkers for menstrual cycle phases and menopausal status

city: Chicago

first: Jun

last: Wang

state: IL

address: 303 E Superior Street

department: Department of Surgery

institute: Northwestern University

summary: Gene and protein expression in the breast varies relative to menopausal status (MS) and menstrual phase (MP), but cancer risk biomarker research using archived benign breast samples is usually uninformed by MS-MP data. We hypothesized that gene expression variation relative to ambient hormones can be exploited to develop markers of MS-MP that can be measured directly in breast tissue.

overall_design: Random fine needle aspiration samples from the unaffected breasts of 18 women were utilized for Illumina microarray analysis. Gene expression was correlated with simultaneous serum levels of estradiol, progesterone, and follicle stimulating hormone (FSH). True MS-MP states were defined by age and serum hormones. Genes highly correlated to serum hormones were used to classify samples into 2 MS groups: premenopause or postmenopause. The premenopausal samples were further classified into 3 MP groups: early follicular, late follicular or luteal.

first: Denise

last: Scholtens

first: Seema


title: Exon-level expression profiling of normal colonic mucosa samples.

city: Oslo

first: Anita

last: Sveen

address: P.O.Box 4953, Nydalen

department: Department of Molecular Oncology

country: Norway

institute: Institute for Cancer Research, Oslo University Hospital

summary: These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers.

overall_design: This Series consists of 19 normal colonic mucosa samples from colorectal cancer patients,  and is an amendment to a larger series of colorectal cancer and adjacent normal colonic mucosa samples analyzed for gene expression at the exon-level (GSE24550).

first: Trude

last: Ågesen

first: Arild

last: Nesbakken

first: Ragnhild

last: Lothe

first: Rolf

last: Skotheim


title: Calcineurin-dependent transcriptome in ICN1 (activated NOTCH1)-induced T cell acute lymphoblastic leukemia (T-ALL)

city: Orsay

first: Jacques

last: GHYSDAEL

address: Centre Universitaire, Bat 110

country: France

institute: Institut Curie

summary:
Activated NOTCH1 induces T-ALL in mice when transduced in bone marrow (BM) cells. T-ALL cells activate the calcineurin/NFAT pathway in vivo (Medyouf H. et al. Nat Med 2007 [PMID 17515895]).
Through appropriate crosses, mouse ICN1-induced T-ALL were generated that include a ROSCreERT2 transgene and 2 copies of a CnB1 floxed alleles.

overall_design: Cohorts of secondary recipient mice were injected with these T-ALL cells, and when becoming leukemic, divided into 2 subgroups. Group 1 was treated with Tamoxifen (TAM), resulting in CnB1 gene deletion and inactivation of calcineurin. Group 2 was treated with carrier solvent (corn OIL), thus maintaining CnB1 and calcineurin activity. RNAs were extracted from flow cytometry-sorted leukemic cells. Details in Gachet S. et al. Leukemia 2013 (PMID 23689515).

first: J

last: Ghysdael


title: Gene expression differences between prion-resistant and prion-susceptible cells

city: London

middle: Christian

last: Kloehn

state: Greater London

address: Queen Square

department: MRC Prion Unit

institute: UCL Institute of Neurology

summary: Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin α8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.

overall_design: For each of the  three biological repeats cell clones (samples) were harvested at a subclonfluent state and total RNA isolated using Rneasy (Qiagen) according to the specification of the manufacturer. Retinoic acid treatment of revertant cell clones (R2, R5, R7) increased prion replication by up to fourty-fold. To test differential gene expression under these conditions R7 cells were treated with retinoic acid (0.5 microM) and vehicle for six hours, before isolation of total RNA as described previously (PK 11.1 210307, PK 11.3 210307,PK 13.1 210307,PK 13.2 210307,PK 13.3 210307)

first: Masue

last: Marbiah

first: Anna

last: Harvey

first: Billy

last: West

first: Anais

last: Louzolo

first: Priya

last: Banerjee

first: Jack

last: Alden

last: Grigoriadis

first: Parmjit

last: Jat

first: Holger

last: Hummerich

first: Ho-Man

last: Kan

first: Ying

last: Cai

first: George

middle: S

last: Bloom

first: John

last: Collinge

first: Peter-Christian

last: Klöhn


title: In vitro selection for chitosan-resistant Staphylococcus aureus - phenotypic and molecular characterisation of resistance development

status: Public on Jul 15 2014

city: Geneva

first: FRANCOIS

last: Patrice

state: Ge 4

address: Rue Gabrielle-Perret-Gentil, 4

department: Service of Infectious Diseases

institute: Genomic Research Laboratory

summary: A mutant of SG511 (wild type isolate), resistant to the presence of chitosan (polycationic molecule) was obtained following serial passage experiments resistance to chitosan exposition. Transcriptomic experiments showed alteration in the expression of genes involved in the cell wall regulon resulting in the modification of susceptibility phenotype against cell wall active antibiotics

platform_organism: Staphylococcus aureus subsp. aureus NCTC 8325

platform_organism: Staphylococcus aureus subsp. aureus Mu50

platform_organism: Staphylococcus aureus subsp. aureus N315

platform_organism: Staphylococcus aureus subsp. aureus MRSA252

platform_organism: Staphylococcus aureus subsp. aureus MSSA476

platform_organism: Staphylococcus aureus subsp. aureus USA300

overall_design: Microarray was used to evaluate alteration in the transcriptome between wild tpye strain SG511 and its spontaneous chitosan resistant variant (CRV)

first: Dina

last: Raafat

first: Nicole

last: Leib

first: Miriam

last: Wilme

first: Patrice

last: Francois

last: Schrenzel

first: Hans-Georg

last: Sahl


title: Expression data from murine eGFP+ relfl/flCg1-Cre and eGFP-Cg1-Cre splenic germinal center B cells purified by fluorescent activated cell sorting.

city: New York

first: Ulf

last: Klein

state: NY

address: 1130 St. Nicholas Avenue

department: Herbert Irving Comprehensive Cancer Center

institute: Columbia University

summary: Gene expression profiling of murine eGFP+ relfl/flCg1-Cre and eGFP− Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factor c-REL in germinal center B cells.

overall_design: Germinal center B cells from 12-week old relfl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated. Following a cDNA amplification step, labeled cRNA was hybridized to microarrays and genes specifically expressed in eGFP+ relfl/flCg1-Cre and eGFP− Cg1-Cre samples were identified by supervised analysis.

last: Heise


title: Gene Expression Profiling of Peri-implant Healing of PLGA-Li+ Implants Suggests an Activated Wnt Signaling Pathway in vivo

status: Public on Jul 21 2014

city: Gothenburg

first: Anna

last: Thorfve

address: Arvid Wallgrens backe 20

department: Biomaterials

institute: University of Gothenburg

summary: Bone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of β-catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors’ knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.

overall_design: PLGA implants with +/- incorporated Li were inserted in rat tibia for 7 or 28 days, peri-implant bone was harvested and RNA extracted using Qiazol lysis reagent and TissueLyser followed by Qiagen's Rneasy Micro Kit. The microarray experiment was conducted at SCIBLU Genomics (www.lu.se/sciblu) according to Affymetrix guidelines (n=6).

first: Pentti

last: Tengvall


title: Gene expression profiling of uterine epithelial cells isolated from Msx1Msx2 floxed and Msx1Msx2 ablated mice on day 4 of pregnancy

status: Public on Jul 20 2014

city: Urbana

first: Shanmugasundaram

last: Nallasamy

address: 2001 S Lincoln Ave

department: Comparative Biosciences

institute: University of illinois at Urbana-Champaign

summary:
Our preliminary study revealed that the homeobox transcription factors, Msx1 and Msx2, are expressed in the mouse uterus during early pregnancy. Further, conditional deletion of Msx1 and Msx2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity.
To identify the downstream targets of Msx1Msx2 in the uterus, we performed gene expression profling of uterine epithelial cells isolated from Msx1Msx2-null mice and the corresponding controls on day4 of pregnancy (the time of implantation). The microarray results revealed elevated expression of mRNAs corresponding to several Wnts in uterine epithelium of Msx1Msx2-ablated mice.

overall_design: We performed conditional ablation of Msx1Msx2 in the mouse uterus using the PRcre mouse model. we isolated uterine epithelial cells from day4 pregnant mice (n=5 for each genotype). Total RNA was purified from these cells to hybridize to high density affymetrix microarrays.

first: Quanxi

last: Li

first: Indrani

middle: C

last: Bagchi

first: Milan


title: NKT-10 cells represent a novel invariant NKT cell subset with regulatory characteristics

city: La Jolla

first: Gerhard

last: Wingender

state: CA

address: 9420 Athena Circle

department: Developmental Immunology

institute: La Jolla Institute for Allergy and Immunology

summary: We compared splenic Va14i NKT cells from C57BL/6 control mice and from mice injected 4 weeks earlier intravenously with 4ug/mouse of the iNKT cell antigen alpha-galactosylceramide (aGalCer). These mice were either left unstimulated or were stimulated with 1ug/mouse aGalCer i.v.. All mice were female and 8 weeks of age at the beginning of the experiment. Va14i NKT cells were enriched via magnetic selection and cell sorted for TCRb+ CD1d/aGalCer-tetramer+. Total RNA were prepared using a Qiagen RNeasy mini kit. IVT probe generation and hybridization to Affymetrix Mouse Genome 430 2.0 arrays was carried out by the Veterans Medical Research Foundation GeneChipTM Microarray located at UCSD.

overall_design: Group 1 (Ctr_unstim) = iNKT cells from C57BL/6 control mice and left unstimulated / Group 2 (Ctr_stim) = iNKT cells from C57BL/6 control mice and injected 1h before purification with 1ug aGalCer i.v. / Group 3 (Pre_unstim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and left unstimulated / Group 4 (Pre_stim) = iNKT cells from C57BL/6 mice injected 4weeks earlier with 4ug aGalCer i.v. and injected 1h before purification with 1ug aGalCer i.v. / Sample were prepared in duplicates in two independent experiments.

first: Mitchell

last: Kronenberg


title: Gene expression profiling of uterine stromal and epithelial cells isolated from Msx1Msx2 floxed and Msx1Msx2 ablated mice on day 4 of pregnancy

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

overall_design: Refer to individual Series


title: Mice Lacking the β2 Adrenergic Receptor Have a Unique Genetic Profile Before and After Focal Brain Ischemia

status: Public on Jul 14 2014

city: Stanford

first: Robin

last: White

address: Grant Building S272, 300 Pasteur Drive

department: Anesthesia

institute: Stanford University

summary: The role of the beta2 adrenergic receptor (β2AR) after stroke is unclear as pharmacological manipulations of the β2AR have produced contradictory results. We previously showed that mice deficient in the β2AR (β2KO) had smaller infarcts compared to wild-type mice (FVB) after middle cerebral artery occlusion (MCAO), a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell death were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischemia (Ccl9, Gem, and Prg4). In addition to networks that were similar between genotypes, one network with a central node of G protein-coupled receptor and including biological functions carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in β2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype in all conditions. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in β2KO mice. As both genes are implicated in NFκB signaling, we measured p65 activity and tumor necrosis factor alpha (TNFα) levels 24h after MCAO. MCAO-induced p65 activation and post-ischemic TNFα production were both greater in FVB compared to β2KO mice. These results suggest that loss of β2AR signaling results in a neuroprotective phenotype in part due to decreased NFκB signaling, decreased inflammation, and decreased apoptotic signaling in the brain.

overall_design:
MCAO and sham surgery samples:
A total of 20 samples were analyzed, with 10 of each genotype, wildtype (FVB) and beta2 adrenergic receptor deficient (B2) mice.  Of the 10 in each group, 7 received middle cerebral artery occlusion (MCAO) and 3 received a sham surgery.  The sham samples serve as the controls for the MCAO samples in each genotype.  All samples were taken from the ischemic or control hemisphere 24 hours after surgery.

Naive samples:
A total of 15 naïve samples were analyzed, with 7-8 of each genotype, wild-type (FVB) and beta2 adrenergic receptor deficient (B2) mice. The naive samples were normalized independently of the MCAO and sham surgery samples.

middle: E

first: Curtis

last: Palm

first: Lijun

last: Xu

first: Evelyn

last: Ling

last: Ginsburg

first: Bernie

last: Daigle

first: Ruquan

last: Han

first: Andrew

last: Patterson

first: Russ

middle: B

last: Altman

first: Rona

middle: G

last: Giffard


title: NF-kB in Tumor Initiation

city: Columbus

first: David

middle: Jingxin

last: Wang

state: Ohio

department: Comprehensive Cancer Center

institute: The Ohio State University

summary: p65-/-Ras cells show delayed tumor formation in SCID mice. However, after prolonged latency, tumor formation was observed from these mice. To understand the changes of NF-kB regulated genes before and after tumor formation, RNA from p65+/+Ras, p65+/+RasTumor, p65-/-Ras, p65-/-RasTumor cells were isolated and microarray were performed.

overall_design: p65+/+Ras and p65-/-Ras cells were injected into SCID mice. Tumors were removed and put back into tissue culture. RNA was isolated from these cells and microarrays were performed.

first: Nivedita

last: Ratnam

first: Denis

last: Guttridge

first: John

last: Byrd


title: Loss of lamin B1 results in prolongation of S-phase and decondensation of chromosome territories in the interphase nucleus of mammalian cells

status: Public on Jul 16 2014

city: Barcelona

first: Jordi

last: Camps

state: Catalonia

address: c/Rosselló 149-153 4th floor, Center Esther Koplowitz

department: Gastroenterology

country: Spain

institute: IDIBAPS / Hospital Clinic

summary:
Nuclear lamin B1 constitutes one of the major structural proteins in the lamina mesh. We silenced the expression of lamin B1 by RNA interference in the colon cancer cell line DLD-1 and showed a dramatic redistribution of H3K27me3 from the periphery to a more homogeneous nuclear dispersion; in addition we observed an increased frequency of micronuclei and nuclear blebs. By 3D-FISH analyses, we demonstrate that the volume and surface of chromosome territories were significantly larger in LMNB1-depleted cells, suggesting that lamin B1 is required to maintain chromatin condensation in interphase nuclei. These changes led to a prolonged S-phase due to activation of Chk1 and telomere attrition. Finally, silencing of LMNB1 resulted in extensive changes in alternative splicing of multiple genes and in a higher number of enlarged nuclear speckles. Taken together, our results suggest a mechanistic role of the nuclear lamina in the organization of chromosome territories, maintenance of genome integrity and proper gene splicing.
This dataset includes the comparison of gene  transcripts between cells with silenced lamin B1 and empty vector negative control transfected cells.

overall_design: Single cell clones were generated after transfection of DLD-1 cells with shRNA against LMNB1. Two different constructs were used. For clone number 2, three replicates of the the same clone were included in the analysis. The rest of the clones correspond to biological replicates. As control, we used three different cones transfected with an empty vector control as well as wild type cells.

first: Darawalee

last: Wangsa

first: Martin

last: Falke

first: Markus

last: Brown

first: Chanelle

middle: M

last: Case

first: Mike

last: Erdos

first: Thomas

last: Ried


title: Fezf2 overexpression in murine cortical progenitors in vivo

status: Public on Jul 06 2014

city: Cambridge

first: Paola

last: Arlotta

state: Massachusetts

address: 7 Divinity Ave SF301-7

department: Stem Cell and Regenerative Biology

institute: Harvard University

summary:
Corticospinal motor neurons (CSMN) are one specialized class of cortical excitatory neurons, which connect layer Vb of the cortex to the spinal cord. a master transcription factor –Forebrain expressed zinc finger 2 (Fezf2) – has been identified that is necessary for the fate specification of CSMN. Fezf2 alone can cell-autonomously instruct the acquisition of CSMN-specific features when expressed in diverse, permissive cellular contexts, in vivo.
In order to understand the molecular logic underlying the acquisition of CSMN traits upon Fezf2 expression, we compared the in vivo gene expression of FACS-purified cortical progenitors that ectopically expressed Fezf2 to control progenitors.

overall_design: We used in utero electroporation to deliver Fezf2GFP or CtrlGFP expression vectors to neocortical progenitors at E14.5, when they primarily generate CPN of the upper layers. Overexpression of Fezf2 in these progenitors is sufficient to instruct a fate-switch resulting in the generation of CSMN and other subtypes of corticofugal projection neurons. Fezf2GFP- and CtrlGFP -electroporated progenitors were FACS-purified at 24 and 48 hours after surgery and acutely profiled by microarrays.

first: Simona

last: Lodato

first: Bradley

last: Molyneaux

first: Emanuela

last: Zuccaro

first: Loyal

middle: A

last: Goff

first: Hsu-Hsin

last: Chen

first: Wen

last: Yuan

first: Alyssa

last: Meleski

first: Emi

last: Takahashi

first: Shaun

last: Mahony

last: Rinn

middle: K

last: Gifford


title: Glomerular transcriptomic analysis of the influence of Genetic background effect during anti-GBM glomerulonephritis in mice

city: PARIS

first: Laurent

last: MESNARD

state: idf

address: 4 rue de la chine, Hôpital Tenon

institute: INSERM

summary:
We analyzed the impact of the genetic background during experimental passive non-accelerated anti-glomerular basement membrane glomerulonephritis (anti-GBM-GN) (an equivalent to nephrotoxic nephritis) in two different mouse genetic backgrounds (C57BL6/J vs 129S2svPAS/crl).
Glomerular extracts have been made at an early time point (e.g day 4 of the induction of the glomerulonephritis). RNA have been extracted following standard procedures.

overall_design: 3 mice per group have been compared. 3 Control mice from each background. And 3 anti-GBM-GN challenged mice from each Genetic background, corresponding to 12 samples in total.

last: Mesnard

first: Sophie

last: Vandermeersch


title: Expression data of LPS-stimulated macrophages in wild-type and LysM-Cre+;Akirin2fl/fl mice

status: Public on Jul 11 2014

city: Kyoto

first: Osamu

last: Takeuchi

state: Kyoto

address: Yoshida-konoe-cho, Sakyo-ku,

department: Grad School of Medicine

institute: Kyoto University

summary:
Akirin2 is an evolutionally conserved nuclear protein involved in the regulation of a set of inflammatory gene expression in various cell types.
We used microarrays to examine the effect of Akirin2 deficiency in LPS-inducible gene expression in macrophages

overall_design: Peritoneal macrophages from wild-type and LysM-Cre+;Akirin2fl/fl mice were stimulated with LPS for 0, 2 and 4 hours, followed by RNA extraction and microarray analysis.

first: Sarang

last: Tartey


title: KrasG12D partially compensates for the loss of beta-catenin in MLL-AF9 AML

status: Public on Jul 02 2014

first: Amit

last: Sinha

address: 1275 York Avenue

institute: Memorial Sloan-Kettering Cancer Center

summary:
The Wnt/beta-catenin pathway is required for the development of leukemia stem cells in MLL-AF9 AML.
We evaluated the dependance on beta-catenin for KrasG12DMLL-AF9 leukemia.

overall_design: Lin-Kit+ bone marrow cells obtained from mice transplanted with primary MLL-AF9 leukemia cells and KRasG12DMLL-AF9 leukemia cells were assessed for gene expression in the presence or absence of beta-catenin

first: Cherry

last: Ng

first: Demetrios

last: Kalaitzidis

first: Scott

last: Armstrong


title: Fluorochrome-based definition of naturally occurring Foxp3+ regulatory T cells of intra- and extrathymic origin

status: Public on Jul 09 2014

city: Dresden

first: Sonja

last: Schallenberg

state: Saxony

address: Fetscherstrasse 105

department: Research Group Molecular and Cellular Immunology/Immune Regulation

country: Germany

institute: Technische Universität Dresden; DFG-Center for Regenerative Therapies Dresden

summary:
Here, we report on experiments in double-transgenic mice, in which RFP is expressed in all Foxp3+ Treg cells, whereas Foxp3-dependent GFP expression is exclusively confined to intrathymically induced Foxp3+ Treg cells. This novel molecular genetic tool enabled us to faithfully track and characterize naturally induced Treg cells of intrathymic (RFP+GFP+) and extrathymic (RFP+GFP−) origin in otherwise unmanipulated mice.
These experiments directly demonstrate that extrathymically induced Treg cells substantially contribute to the overall pool of mature Foxp3+ Treg cells residing in peripheral lymphoid tissues of steady-state mice. Furthermore, we provide evidence that intra- and extrathymically induced Foxp3+ Treg cells represent distinct phenotypic and functional sublineages.

overall_design: CD4+CD25+ RFP+GFP- and CD4+CD25+ RFP+GFP+ T cells from pooled lymph nodes and pooled spleens of 20 mice were FACS sorted for RNA extraction and hybridization on Affymetrix microarrays in duplicates.

first: Cathleen

last: Petzold

first: Robert

last: Geffers

first: Karsten

last: Kretschmer


title: Gene expression accompanying the promotion of hepatocellular carcinoma by intestinal microbiota and Tlr4 in mice.

status: Public on Jul 04 2014

last: Schwabe

address: 1150 St. Nicholas Ave

summary: The effect of Tlr4P712H mutation (rendering TLR4 non-functional), or gut-sterilization by antibiotics, on the induction of tumorgenesis by CCl4 and diethylnitrosamine (DEN) was characterized. Affymetrix Mouse 430 2.0 gene expression measurements were used to characterize the transcriptomic basis of the effects of the above treatments and genotypes on tumorgenesis.

overall_design: Gene expression of mouse livers of A. WT C3H/HeOuJ mice, B. WT C3H/HeOuJ mice treated with CCl4 and DEN, C. TLR4-mutant C3H/HeJ mice (Tlr4P712H) treated with CCl4 and DEN and D. WT C3H/HeOuJ mice treated with antibiotics (a combination of ampicillin (1 g/l), neomycin [1 g/l], metronidazole[1 g/l]  and vancomycin [500 mg/l] in drinking water) and CCl4 and DEN were characterized.

first: Dianne

middle: H

last: Dapito

first: Ali

last: Mencin

first: Geum-Youn

last: Gwak

first: Jean-Philippe

last: Pradere

first: Myoung-Kuk

last: Jang

first: Adebowale

last: Adeyemi

first: Ingmar

last: Mederacke

first: Ramon

last: Bataller

first: Richard

last: Friedman

middle: F


title: Noncoding RNA expression in myocardium from infants with tetralogy of Fallot [mRNA profiling]

status: Public on Jul 12 2014

city: Kansas City

first: Douglas

last: Bittel

state: MO

address: 2401 Gillham Rd

department: Genetics research

institute: Childrens Mercy Hospital

summary:
This is the first report characterizing noncoding RNA expression in a congenital heart defect. The striking shift in expression of noncoding RNAs reflects a fundamental change in cell biology, likely impacting expression, transcript splicing and translation of developmentally important genes and possibly contributing to the cardiac defect. The importance of noncoding RNAs (ncRNA), especially microRNAs, for maintaining stability in the developing vertebrate heart has recently become apparent. However, there is little known about the expression pattern of ncRNA in the human heart with developmental anomalies.
We examined the expression of microRNAs and small nucleolar RNAs (snoRNAs) in right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart samples and eight normally developing infants. We found 61 microRNAs and 135 snoRNAs to be significantly changed in expression in myocardium from children with TOF compared to normally developing comparison subjects. The pattern of ncRNA expression in TOF myocardium had a remarkable resemblance to expression patterns in fetal myocardium, especially for the snoRNAs. Potential targets of microRNAs with altered expression were enriched for gene networks of importance to cardiac development. We derived a list of 229 genes known to be critical to heart development and found 44 had significantly changed expression in TOF myocardium relative to normally developing myocardium. These 44 genes had significant negative correlation with 33 microRNAs, each of which also had significantly changed expression. The primary function of snoRNAs is targeting specific nucleotides of ribosomal RNAs and spliceosomal RNAs for biochemical modification. The targeted nucleotides of the differentially expressed snoRNAs were concentrated in the 28S and 18S ribosomal RNAs and two spliceosomal RNAs, U2 and U6. In addition, in myocardium from children with TOF, we observed splicing variants in 51% of the critical cardiac developmental genes. Taken together, these observations suggest a link between snoRNA level in the myocardium, spliceosomal function and heart development.

overall_design: mRNA profiling: Right ventricular myocardium from 16 infants with nonsyndromic tetralogy of Fallot (TOF) without a 22q11.2 deletion, three fetal heart and eight normally developing infants

first: James

last: O’Brien Jr

first: Nataliya

last: Kibiryeva

first: Xin-Gang

last: Zhou

first: Jennifer

last: Marshall

first: Gary

last: Lofland

first: Michael

last: Artman

first: Jie

last: Chen


title: p38a-dependent gene expression in the colonic mucosa

status: Public on Jul 01 2014

city: Charlestown

first: Jin Mo

last: Park

address: 149 Thirteenth Street

department: Cutaneous Biology Research Center

institute: Massachusetts General Hospital

summary:
Gene expression in the colonic mucosa of wild-type and p38a-knockout intestinal epithelial cells (IECs) were compared.
C57BL/6 wild-type mice, and intestinal epithelial cell-specific p38a-knockout mice on a C57BL/6 background were used for isolation of colonic mucosa

overall_design: Gene expression in each genotype was analyzed in triplicate.

first: Celia

last: Caballero-Franco

first: Jin


title: Expression data from postnatal mouse brain regions of Ts1Cje and disomic C57BL/6 mice.

status: Public on Jul 23 2014

city: UPM Serdang

first: King Hwa

last: Ling

state: Selangor

address: Faculty of Medicine and Health Sciences

department: Department of Biomedical Science

country: Malaysia

institute: Universiti Putra Malaysia

summary: The Ts1Cje mouse model of Down syndrome (DS) has partial triplication of mouse chromosome 16 (MMU16), which is partially homologous to human chromosome 21. The mouse model develops various neuropathological features identified in DS individuals. We analysed the effect of partial triplication of the MMU16 segment on global gene expression in the cerebral cortex, cerebellum and hippocampus of Ts1Cje mice at 4 time-points; postnatal day (P)1, P15, P30 and P84.

overall_design: RNA was extracted from thre brain regions (Cerebral cortex, hippocampus and cerebellum) for hybridization to arrays from 3 pairs of Ts1Cje and disomic C57BL/6 littermate control for each timepoints at postnatal (P) day 1, P15, P30 and P84.

first: King-Hwa

first: Chelsee

last: Hewitt

first: Kai-Leng

last: Tan

first: Pike-See

last: Cheah

first: Ken

last: Simpson

first: Lavinia

last: Hyde

first: Gordon

last: Smyth

first: Tim

last: Thomas

first: Hamish

last: Scott


title: Expression Data comparing Gene Expression in 27-day old testes of wild-type and Brwd1-/- mice

city: ITHACA

first: John

last: Schimenti

state: New York

department: Biomedical Sciences

institute: Cornell University

summary:
Brwd1-/- mice are infertile with post-meiotic defects in the male. BRWD1 contains bromodomains and may function as a transcriptional regulator important for post-meiotic development in the male germline.
This microarray compares post-meiotic gene expression between WT and mutant mice.

overall_design: We collected total RNA from testes of 27-day old WT and Brwd1-/- (MT) mice. At this age, germ cells have completed meiosis and are mid-way in post-meiotic development. Any gene expression changes in spermatids would be apparent at this time-point. We decided to do this with 4 WT and 4 Brwd1-/- mice.

first: Shrivatsav

last: Pattabiraman


title: DNA methylation data from Reduced Representation Bisulphite sequencing in the Dutch Hunger Winter Families Study

city: Leiden

first: Elmar

middle: Wouter

last: Tobi

address: Einthovenweg 20

department: Medical Statistics and Bioinformatics

country: Netherlands

institute: Leiden University Medical Center

type: Methylation profiling by high throughput sequencing

summary: We report on genome-wide DNA methylation differences associated with early gestational famine exposure. We find that open chromatin regions and enhancers are especially sensitive to prenatal famine exposure.

overall_design: We compared 24 individuals conceived during the Dutch Famine, a brief 6 month famine at the end of WWII, with a same sex sibling.

middle: W


title: Spontaneous Elimination of Intraocular Tumors is Associated with IFNγ- and Fas/FasL-Dependent Activation of Macrophages

city: Pittsburgh

first: Stephen

middle: Alan Kenneth

last: Harvey

state: PA

address: 203 Lothrop St

department: Ophthalmology

institute: University of Pittsburgh School of Medicine

summary: Ocular immune privilege (IP) limits immune surveillance of intraocular tumors as certain immunogenic tumor cell lines (P815, E.G7-OVA) that are rejected when transplanted in the skin grow progressively when placed in the anterior chamber (a.c.) of the eye. As splenectomy (SPLNX) is known to terminate ocular IP, we characterized immune mechanisms responsible for spontaneous rejection of intraocular tumors in SPLNX mice as a first step toward identifying how to restore tumoricidal activity within the eye. Microarray data showed a 3-fold increase in interferon (IFN)-γ and a 2.7-fold increase in Fas ligand (FasL). There was a robust increase in transcripts (127 of 408 surveyed) from interferon (IFN)-stimulated genes and a marked decrease (in 40 of 192 surveyed) in the expression of cell-cycle-associated genes. Non-microarray data confirmed that IFNγ, FasL and CD8+ T cells but not perforin or TNFα were required for elimination of intraocular E.G7-OVA tumors that culminated in destruction of the eye (ocular phthsis). IFNγ and FasL did not target tumor cells directly as the majority of SPLNX IFNγR1-/- mice and Fas-defective lpr mice failed to eliminate ocular E.G7-OVA tumors that expressed Fas and IFNγR1. Bone marrow chimeras showed that immune cell expression of IFNγR1 and Fas was critical and that SPLNX increased the frequency of activated macrophages within ocular tumors in an IFNγ- and Fas/FasL-dependent manner. Rejection of intraocular tumors was associated with increased ocular mRNA expression of several inflammatory genes including FasL, NOS2, CXCL2 and T-bet. Our data support a model in which IFNγ- and Fas/FasL-dependent activation of intratumoral macrophage by CD8+ T cells promotes severe intraocular inflammation that indirectly eliminates intraocular tumors by inducing phthisis. The immunosuppressive mechanisms which maintain ocular IP likely interfere with the interaction between CD8+ T cells and macrophage to limit immunosurveillance of intraocular tumors.

overall_design: C57BL/6 mice that were splenectomized (Tumor_splnx) or were not surgically manipulated (Tumor_intact) were challenged with 10^4 luciferase-expressing E.G7-OVA cells injected into the anterior chamber of the eye. Fifteen days later, the animals were euthanized and tumor-bearing eyes were removed.

first: Maxine

middle: R

last: Miller

first: Jonathan

last: Mandell

first: Kelly

last: Beatty

first: Michael

middle: J

last: Rizzo

first: Dana

last: Previte

last: Thorne

first: Kyle

last: McKenna


title: Up-regulation of IFN-related genes in BRCA2-/- cells

city: Vancouver

first: Steven

last: McKinney

state: BC

address: 675 West 10th Ave

department: Molecular Oncology

institute: British Columbia Cancer Agency

summary: Microarray-based expression profiling of BRCA2 knockout and isogenic wild type HCT116 human colorectal cancer cells

overall_design: One way ANOVA, single factor comparison of wild type and BRCA2 knockout cells, three CEL files for wild type, three CEL files for BRCA2 knockout

first: Hong

last: Xu

first: Jian

last: Xian

first: Emmanuelle

last: Vire

first: Jason

last: Wong

first: Vivien

last: Wei

first: Rebecca

last: Tong

first: Tony

last: Kouzarides

first: Carlos

last: Caldas

first: Samuel

last: Aparicio


title: Gene expression profiling of uterine stromal cells isolated from Msx1Msx2 floxed and Msx1Msx2 ablated mice on day 4 of pregnancy

first: Shanmugasundaram

last: Nallasamy

institute: University of illinois at Urbana-Champaign

summary:
Our preliminary study revealed that the homeobox transcription factors, Msx1 and Msx2, are expressed in the mouse uterus during early pregnancy. Further, conditional deletion of Msx1 and Msx2 in mouse uterus leads to implantation failure due to impaired uterine epithelial receptivity.
To identify the downstream targets of Msx1Msx2 in the uterus, we performed gene expression profling of uterine stromal cells isolated from Msx1Msx2-null mice and the corresponding controls on day4 of pregnancy (the time of implantation). The microarray results revealed elevated expression of mRNAs corresponding to several members of the fibroblast growth factor family and Wnts in uterine stroma of Msx1Msx2-ablated mice.

overall_design: We performed conditional ablation of Msx1Msx2 in the mouse uterus using the PRcre mouse model. we isolated uterine stromal cells from day4 pregnant mice (n=5 for each genotype), purified total RNA from these cells, pooled these samples and then hybridized to high density affymetrix microarrays.

first: Quanxi

last: Li

first: Indrani

last: Bagchi

first: Milan


title: GEMM CRC collection analysis

city: San Diego

first: Peter

last: Belmont

address: 10724 Science Center Drive

institute: Pfizer

summary:
A collection of genetically engineered mouse models (GEMM) of colorectal cancer (CRC) were created, and primary tumors from these GEMMs were analyzed.
Primary CRC tumors from these GEMMs were genotyped to confirm that they contain the core genetic lesions of interest, including APC, P53, KRAS, and BRAF. Primary tumors from GEMMs with combinations of lesions of interest were analyzed by whole genome expression, and their expression profiles were compared to determine how they segregate. Signatures were then generated from GEMM tumors of interest and compared to human clinical datasets with expression and outcome data.

overall_design: Primary tumors from CRC GEMMs with different combinations of mutant alleles of interested were generated and analyzed. Alleles include mutant forms of APC (A), P53 (P), KRAS (K) and BRAF (B).

first: Eva

last: Budinska


title: Role of Notch signaling pathway in urothelial cancer

city: New York

first: Prokopios Alexandros

last: Polyzos

address: 413 E 69th St

institute: Weill Cornell Medicine

summary: The Notch signaling pathway controls cell fates through interactions between neighboring cells by positively or negatively affecting, in a context-dependent manner, processes of proliferation, differentiation, and apoptosis1. It has been implicated in human cancer both as an oncogene and a tumor suppressor2. Here we report, for the first time, novel inactivating mutations in the Notch pathway components in over forty percent of the human bladder cancers examined. Bladder cancer is the fourth most commonly diagnosed malignancy in the US male population3. Thus far, driver mutations in the FGFR3 and less commonly RAS proteins have been identified4,5. We show that Notch activation in bladder cancer cells suppresses proliferation both in vitro and in vivo by directly upregulating dual specificity phosphatases (DUSPs), thus reducing ERK1/2 phosphorylation. In mouse models, genetic inactivation of Notch signaling leads to ERK1/2 phosphorylation resulting in tumorigenesis in the urinary tract. In recent years, the tumor suppressor role of Notch has been recognized by loss-of-function mutations identified in myeloid cancers6 as well as squamous cell carcinomas of the skin, lung7, and the head and neck8,9. Of the 4 Notch receptors (N1-4), only N1 and 2 have been implicated in human cancer.

overall_design: two biological replicates from normal and tumor urothelial tissue were hybridized on Affymetrix mm 430 2.0 chips

first: Klinakis

last: Apostolos

first: Rampias

last: Theodoros


title: Expression data from NOD and C57BL/6 mouse pancreas CD8α- Dendritic Cells (DCs) under steady-state and after in-vitro LPS stimulation

city: Rotterdam

first: Wouter

last: Beumer

address: Dr. Molenwaterplein 50

department: Immunology

institute: Erasmus MC

summary:
Abstract  Two major dendritic cell (DC) subsets have been described in the islets of mice: The immunogenic CD8α-CD11b+ DCs and the tolerogenic CD8α+CD103+ DCs. We have recently reported on reduced numbers of the minor population of tolerogenic CD8α+CD103+ DCs in the pancreas of 5 week old pre-diabetic non-obese diabetic (NOD) mice.   Aim: To analyze also the larger subset of CD11c+CD8α- DCs isolated from the pancreas of pre-diabetic NOD mice 1) for maturation and tolerance inducing molecules found abnormally expressed on CD8α+CD103+ DCs, and 2) for genome-wide gene expression to further elucidate abnormalities in underlying gene expression networks.  Methods: CD11c+CD8α- DCs were isolated from 5 week old C57BL/6 and NOD pancreas. Expression of cell surface markers including CD86, CCR5, CD11b, CD103, Clec9a, CD24 and CD200R3 were measured by FACS. Genome-wide gene expression by microarray was assessed during the steady state and after in vitro LPS stimulation.   Results: The steady state pancreatic CD11c+ CD8α- DCs during the pre-diabetic stage showed:   1) A reduced expression of several gene networks important for the prime functions of the cell, such as for cell renewal, immune stimulation and immune tolerance induction, for migration and for the provision of growth factors for beta cell regeneration. This general deficiency state was corroborated by a reduced in vivo proliferation (BrdU incorporation) of the cells and the reduced expression in FACS analysis of CD86, CCR5, CD103, Clec9a, CD24 and CD200R3 on the cells.  2) A hyper reactivity of these cells to LPS correlated with an enhanced pro-inflammatory state characterized by altered expression of a number of classical pro-inflammatory factors and cytokines.  Conclusion: The NOD CD11c+CD8α- DCs seem to be Janus-faced depending on the conditions: Deficient in steady state with reduced immune stimulation capabilities also for tolerance induction; over-inflammatory with a molecular profile suggesting a preferential stimulatory capacity for Th1 cells when encountering a Pathogen-Associated Molecular Pattern (PAMP) in the form of LPS.
We used microarray gene expression analysis to explain the abnormal expression of several cell surface markers involved in tolerace, migration and maturation in the steady-state and to measure the effect of a PAMP such as LPS

overall_design: We isolated RNA from FACS sorted CD11c+CD8α- DCs  in 10 pooled pancreases from pre-diabetic NOD and non-diabetic C57BL/6 mice at 5 weeks. In addition, we treated in another experiment the isolated pancreas DCs with LPS (and PBS), incubated for 18h and measured gene expression. We compared gene expression between strains NOD vs C57BL/6  under steady-state and after in-vitro LPS/PBS stimulation.

first: Jojanneke

last: Welzen-Coppens

first: Marjan

last: Versnel

first: Hemmo

last: Drexhage


title: Translation control of TAK1 mRNA by hnRNP K modulates LPS-induced macrophage activation

city: Aachen

first: Bernd

last: Denecke

state: NRW

address: Pauwelsstrasse 30

department: IZKF Aachen

institute: RWTH Aachen University

summary:
Macrophage activation by bacterial lipopolysaccharides (LPS) is induced through Toll-like receptor 4 (TLR4). The synthesis and activity of TLR4 downstream signalling molecules modulates the expression of pro- and anti-inflammatory cytokines. To address the impact of post-transcriptional regulation on that process, we performed RIP-Chip analysis. Differential association of mRNAs with heterogeneous ribonucleoprotein K (hnRNP K), an mRNA-specific translational regulator in differentiating haematopoietic cells, was studied in non-induced and LPS-activated macrophages. Analysis of interactions affected by LPS revealed an enrichment of mRNAs encoding TLR4 downstream kinases and their modulators. We focused on transforming growth factor β activated kinase-1 (TAK1), a central player in TLR4 signalling. HnRNP K interacts specifically with a sequence in the TAK1 mRNA 3' UTR in vitro. Silencing of hnRNP K does not affect TAK1 mRNA synthesis and stability, but enhances TAK1 mRNA translation, resulting in elevated TNF-alpha, IL-1beta and IL-10 mRNA expression. Our data suggest that the hnRNP K-3' UTR complex inhibits TAK1 mRNA translation in non-induced macrophages. LPS-dependent TLR4 activation abrogates translational repression and newly synthesised TAK1 initiates the inflammatory response of macrophages.
In this dataset, we include expression data of RAW 264.7 cells comparing untreated cells and 6h Lipopolysaccharide treatment, and analyse RNAs co-precipitating with hnRNP K dependent on LPS treatment.

overall_design: 12 total samples were analyzed, 6 samples of 2 biological replicates.

first: Anke

last: Liepelt

first: Jana

last: Mossanen

first: Felix

last: Heymann

first: Frank

last: Tacke

first: Gernot

last: Marx

first: Dirk

last: Ostareck

first: Antje

last: Ostareck-Lederer


title: A pivotal role of SRC-2 in Metastatic and Castration Resistant Prostate Cancer

status: Public on Jun 30 2014

city: Houston

first: Hui-Ju

last: Lee

state: Texas

address: One Baylor Plaza

department: Molecular & Cellular Biology

institute: Baylor College of Medicine

summary:
SRC-2 is frequently amplified or overexpressed in metastatic prostate cancer patients. In this study, we used genetically engineered mice, overexpressing SRC-2 specifically in the prostate epithelium as a mouse model to examine the role of SRC-2 in prostate tumorigenesis. Over-expression of SRC-2 in PTEN heterozygous mice accelerates PTEN mutation induced tumor progression and develops a metastasis-prone cancer.
We used microarrays to examine the molecular profile of prostate-specific SRC-2 overexpression adult dorsal-lateral prostate in comparison with that of control PTENF/+ heterozygous deletion  mice.

overall_design: total RNA was extracted from dorsal-lateral prostate of 7 months old-PTEN flox/+ control and PTEN flox/+; Rosa26-SRC-2 OE/+ adult mice, followed by gene expression profiling using Affymetrix microarrays. Each sample contains pooled prostate RNA from 3 mice.

first: Sophia

middle: Y

last: Tsai

first: Ming-Jer


title: Expression data from maternally inflamed and Dap12-mutant microglia at E17.5.

summary:
Microglia colonize the brain parenchyma at early stages of development and accumulate in specific regions where they actively participate in cell death, angiogenesis, neurogenesis and synapse elimination. A recurring feature of embryonic microglial distribution is their association with developing axon tracts which, together with in vitro data, supports the idea of a physiological role for microglia in neurite development. Yet the demonstration of this role of microglia is still lacking. Here, we have studied the consequences of microglial dysfunction on the formation of the corpus callosum, the largest connective structure in the mammalian brain, which shows consistent microglial accumulation during development. We studied two models of microglial dysfunction: the loss-of-function of DAP12, a key microglial-specific signaling molecule, and a model of maternal inflammation by peritoneal injection of LPS at E15.5. We performed transcriptional profiling of maternally inflamed and Dap12-mutant microglia at E17.5. We found that both treatments principally down-regulated genes involved in nervous system development and function, particularly in neurite formation. We then analyzed the functional consequences of these microglial dysfunctions on the formation of the corpus callosum. We also took advantage of the Pu.1-/- mouse line, which is devoid of microglia. We now show that all three models of altered microglial activity resulted in the same defasciculation phenotype. Our study demonstrates that microglia are actively involved in the fasciculation of corpus callosum axons.
To investigate possible roles for microglial during brain development, we challenged microglial function by two complementary approaches. First, we induced maternal inflammation by peritoneal injection of LPS into pregnant dams. Next, we analyzed the consequences of a loss of function of DAP12, a signaling molecule specifically expressed in microglia that is crucial for several aspects of microglia biology (references in Wakselman et al., 2008). We compared the gene expression profiles of microglia from control, maternally-inflamed by LPS (MI), and Dap12-mutated embryos.

overall_design: We isolated RNA from FACS sorted maternally inflamed (by LPS) and Dap12-mutant microglia at E17.5 pooled per pregnant dam; as a control we included PBS treated and untreated (UT) microglia. We compared gene expression between maternally inflamed microlgia (PBSvsLPS) and DAP12-mutant microglia (UTvsDAP12KO).

first: Lorena

last: Pont-Lezica

first: Alain

last: Bessis


title: c-Jun promotes cell migration and drives expression of the motility factor ENPP2 in soft tissue sarcomas [array]

city: Boston

first: Stefano

last: Sioletic

state: Ma

address: 450 Brookline Ave, Boston,

department: Medical Oncology

institute: Dana Farber Cancer Institute

summary: Affymetrix exon arrays to identify genes that were differentially expressed after c-Jun inhibition in LPS cell line with and with no Jun amplification.

overall_design: We compared the consequences of c-Jun inhibition in LP6 (genomically c-Jun amplified) and LPS141 (non-amplified) DDLPS cells after Lentivrus modulation. We used lentivirus to deliver 2 control (shGFP, shNT) and 2 Jun (shJun1, shJun3) shRNAs and harvested total RNA on days 4 and 7 after infection, timepoints at which we observed maximum c-Jun inhibition by qRT-PCR and immunoblotting

first: Lan

last: Hu

first: Eric

last: Snyder


title: Gene expression profiling in subarachnoid haemorrhage

city: Glostrup

first: Ajoy

middle: Kumar

last: Samraj

address: NDR Ringvej 69

department: Department of clinical experimental medicine

country: Denmark

institute: Glostrup Hospital

summary: We used microarrays to profile the changes in gene signatures after 6 hours of subarachnoid haemorrhage in the rat cerebral arteries .

overall_design: Cerebral arteris of rats subjected to SAH or SHAM operated animals were isolated after 6 hours of SAH and total RNA was extracted for the array

first: A

first: L

last: Edvinsson


title: Differential effects of maternal high protein diets on liver transcriptomes

city: Dummerstorf

first: Jens

last: Vanselow

address: Wilhelm-Stahl-Allee 2

department: Reproductive Biology

institute: Leibniz Institute for Farm Animal Biology

summary: The objective of this study was to test if maternal high protein diet during pregnancy or lactation, imposes different transient or persistently imprinted effects on the liver transcriptome of offspring

overall_design: Livers from 4 to 5 animals (one animal per litter) at days 21 and 150 of of each dietary group were combined to 3 pools each, and processed for microarray analysis.

first: Cornelia

middle: C

last: Metges


title: microRNA expression profiling in TPC1 cell line treated with the RTK inhibitor RPI-1

city: Milan

first: Matteo

last: Dugo

address: via Olgettina 60

department: Department of Medical Oncology

country: Italy

institute: IRCCS Ospedale San Raffaele

summary: We treated the papillary thyroid carcinoma-derived cell line TPC1 with the RTK inhibitor RPI-1 to obtain a thyroid carcinoma cell model. The RET tyrosine kinase is a target of the inhibitor. microRNA expression changes were evaluated comparing cells treated with the inhibitor fo 24 hours versus cells treated with DMSO for 24 hours.

overall_design: Biological triplicates for RPI-1 and DMSO treated cells were generated by independent treatments and total RNA extractions. One sample from each class did not pass quality control, and thus was discarded. The final dataset comprises two samples for each class.

first: Maria

last: Borrello

first: Emanuela

last: Minna

first: Paola

last: Romeo

first: Giuliana

last: Cassinelli

first: Cinzia

last: Lanzi

first: Debora

last: Degl'Innocenti

first: Loris

last: De Cecco


title: miRNA profile induced by RET/PTC1 oncogene in human thyrocytes

summary: To obtain a PTC cell model, primary human thyrocytes have been infected with a retrovirus expressing RET/PTC1 oncogene, using parental thyrocytes as control. The obtained RET/PTC-dependent differential miRNA expression profile, representing the effects of RET/PTC1 oncogene present in about one third of papillary thyroid carcinoma (PTC), models the early event of thyrocytes transformation ending to PTC.

overall_design: miRNA expression profiles of thyrocytes expressing RET/PTC1 oncogene and parental thyrocytes were compared. Biological replicates could not be generated.


title: hsa-miR-199a-3p is an oncosuppressor microRNA in papillary thyroid carcinoma

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

overall_design: Refer to individual Series


title: Suppressed cytokine and chemokine transcriptional signatures in mammary stem/progenitor cells are associated with dietary protection against Wnt1-driven mammary tumorigenesis

city: Little Rock

first: Rosalia

middle: CM

last: Simmen

state: Arkansas

address: 15 Children's Way Slot 512-20B

department: Physiology and Biophysics

institute: University of Arkansas for Medical Sciences

summary: Maintenance and propagation of breast cancer stem cells (BCSCs) is mediated via cytokine and growth factor networks. Direct in vivo linkage between dietary regulation of mammary stem (MaSC)/progenitor cell numbers and protection from breast cancer has not been reported. Here, we investigated the effect of post-weaning intake of soy protein isolate (SPI) relative to the control casein (CAS) diet on the stem/progenitor population and tumor formation in MMTV-Wnt1-Transgenic (Wnt1-Tg) female mice. Gene expression profile of the basal (MaSC-enriched) sub-population in preneoplastic Wnt1-Tg mice demonstrated a stem cell-like expression pattern and markedly suppressed expression of inflammatory cytokines, C-X-C family chemokines, and metastasis-associated genes with dietary SPI exposure.

overall_design: four Samples: two CAS diet, two SPI diet

first: Omar

last: Rahal

first: Heather

middle: L

last: Machado

first: MariaTheresa

middle: E

last: Montales

first: JohnMark

middle: P

last: Pabona

first: Melissa

last: Heard

first: Shanmugam

last: Nagarajan