title: Identification of a new pathway for Th1 cell development induced by cooperative stimulation with IL-4 and TGFbeta


title: Analysis of PGC-1alpha overexpression effects on the whole transcriptome in cultured skeletal muscle cells

status: Public on Mar 15 2012

city: Barcelona

first: Sergi

last: Beltran

address: Baldiri Reixac 10

department: Serveis Cientificotècnics

country: Spain

institute: Universitat de Barcelona

summary: The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) is a chief activator of the mitochondrial and metatolic program in skeletal muscle (skm) and prevents atrophy. Here we tested whether PGC-1α overexpression could restructure the transcriptome and metabolism of cultured human skeletal myotubes, which display an athropic phenotype. An oligonucleotide microarray analysis was used to reveal PGC-1α effects on the whole transcriptome, and the possible impact on fuel metabolism reprogramming was examined. Fifty-three different genes displayed changed expression levels in response to PGC-1α:  42 upregulated and 11 downregulated. Main associations of gene ontologies (GO) for the upregulated genes were mitochondrial components and processes and this correlated with an increase in COX activity, an indicator of mitochondrial content. Palmitate and lactate oxidation to CO2 was enhanced, but not glucose oxidation. The other most significant GO associations of upregulated genes were chemotaxis and cytokine activity, and accordingly, several cytokines, including IL8, CXCL6, CCL5 and CCL8, were within top induced genes. Among the most regulated genes were also potential metabolic regulators of fatty acid and glucose storage. FITM1/FIT1 induction was associated with an increased number of lipid droplets with smaller area, while  triglyceride levels were modestly increased in oleate-incubated cells. Downregulation of CALM1, the calcium-modulated δ subunit of phosphorylase kinase, was linked to inactivation of glycogen phosphorylase and greater accumulation of glycogen. The most upregulated gene was PVALB, which is also related to calcium signaling. In conclusion, only the deficient mitochondrial transcriptional program of cultured myotubes is rescued by PGC-1α. New PGC-1α gene targets and pathways arise, some of which may mediate its activating effects in processes such as lipid and carbohydrate storage and angiogenesis.

overall_design: 6 samples from 3 different skeletal muscle cell cultures were used: 3 were transfected with adenovirus containing PGC-1aplha and 3 with adenovirus containing GFP (control). The 3 PGC-1alpha samples were compared against the control samples.

first: Emma

last: Mormeneo

first: A

middle: M

last: Gomez-Foix


title: Gene Expression Analysis of mouse kidney at the developmental day 15 under iron deficient diet

city: New York

first: Max

last: Werth

state: NY

address: 630WEST 168th STREET P&S 10-501

country: USA

institute: Columbia University

summary:
While it is clear that iron deficiency affects both human and rodent development, and particularly kidney development, the precise pathological changes that occur with iron deficiency have not been distinguished. For example, it is not clear which compartment of the kidney is predominantly affected nor it is clear either which stage of development or which cell type require the most iron.
In this study, we used an in vivo mouse model of iron deficiency in order to better understand the targeting of iron in the developing kidney.

overall_design: Mouse kidneys at the embrionic stage E15 were used for the total RNA extraction

first: Melanie

last: Viltard

first: Jonathan

last: Barasch


title: Up-regulation of prolactin receptor in the proximal tubular cells in cardio-renal syndrome model mice

status: Public on Mar 19 2012

city: Niigata

first: yohei

last: Tsuchida

address: 1-757 Asahimachi-dori

country: Japan

institute: Niigata University Graduate School of Medical and Dental Sciences

summary:
The precise physiological mechanisms of cardio-renal syndrome are yet to be elucidated. In order to investigate the molecular basis of cardio-renal syndrome, we established a mouse model for cardio-renal syndrome by the combination of abdominal aortic banding and uninephrectomy.
Renal function of the cardio-renal syndrome mice was synergistically decreased compared with that of mice that underwent uninephrectomy alone. To investigate the molecules involved in the deterioration renal function in the AbNx mice, we conducted  comprehensive gene expression analysis using DNA array by comparing the molecules expressed in the remained kidney of AbNx mice with those of Nx mice.

overall_design: We conducted abdominal aorta banding or sham operation at 0 week, then We conducted uninephrectomy or sham operation at 2 week. We removed these kidney 6week after the uninephrectomy. These RNA samples were purified from the homogenized kidneys.

first: Yohei

first: Yoshikatsu

last: Kaneko

first: Tadashi

last: Otsuka

first: Akihiko

last: Saito

first: Keiko

last: Yamamoto

first: Ichiei

last: Narita


title: Identification of endoderm-specific genes in mouse embryos

status: Public on Mar 13 2012

city: Westmead

first: David

middle: A. F.

last: Loebel

state: NSW

address: 214 Hawkesbury Road

department: Embryology Unit

country: Australia

institute: Children's Medical Research Institute

summary: The foregut definitive endoderm is the precursor of many tissues including the liver, pancreas, thyroid, lungs, trachea and oesophagus. However, networks and pathways involved in the early development of the definitive endoderm of mammals are not well studied. To identify genes with potential roles in the early development of the foregut definitive endoderm in mouse embryos, we performed microarray analysis to compare the gene expression profile of foregut endoderm and non-endodermal tissues from early somite-stage mouse embryos.

overall_design: ARC/s embryos at 4- to 5-somite stages were collected and the anterior intestinal portal was isolated by digestion with trypsin and pancreatin and mechanical dissection. Ectoderm and mesoderm tissues were dissected from the head folds and the heart, and combined as the non-endoderm tissues for comparison of gene expression profiles. RNA was extracted from 15-20 pooled samples of endoderm or ectoderm plus mesoderm cells and subjected to two rounds of linear amplification and labelling according to standard methods (Affymetrix). The amplified products were hybridized to Affymetrix mouse MOE430 GeneChips. The experiment was performed twice. RNA amplification labelling, hybridization and scanning were performed by the Australian Genome Research Facility. GC-RMA data normalization and further analysis were performed using GenePattern software.

middle: A

first: Patrick

middle: P

last: Tam


title: Gene expression in mice with conditional over-activation of hedgehog signaling in the ovary

status: Public on Mar 14 2012

city: Ithaca

first: Susan

last: Quirk

address: 431 Morrison Hall

department: Animal Science

institute: Cornell University

summary:
The objective of the study was to determine the cause of anovulation in transgenic mice with conditional over-activation of the hedgehog signaling pathway in the ovary.  In Amhr2(cre/+)-SmoM2 transgenic mice, a constitutively active version of the hedgehog signal transducer, smoothened (SMO), known as SMOM2, is expressed in the ovary following cre-mediated recombination. The hypothesis tested is that changes in the neonatal ovary caused by over-activation of hedgehog signaling leads to the life-long anovulation phenotype in transgenic mice.
Microarrays were used to examine differences in gene expression in ovaries of two day old wild-type mice (Amhr2(+/+)-SmoM2) and transgenic mice (Amhr2(cre/+)-SmoM2) in which the hedgehog signaling pathway was conditionally over-activated in the ovary.

overall_design: Two microarrays were performed.  RNA samples were prepared from ovaries of 8 Amhr2(+/+)-SmoM2 control mice and 8 Amhr2(cre/+)-SmoM2 mutant mice on day two of age.  RNA quality was assessed by measurement of ribosomal RNA on an Agilent 2100 Bioanalyzer.

first: Robert

middle: G

last: Cowan

first: Yi

last: Ren


title: Expression variation in the mouse retina

city: Boston

first: Neena

middle: B

last: Haider

state: Massachusetts

address: 20 Staniford Steret

department: Ophthalmology

institute: Schepens Eye Research Institute/MEE/Harvard Medical School

summary: Expression analysis of multiple mouse strains across two developmental timepoints to determine both strain specific and temporal expression of genes in the mouse retina

overall_design: A total of 29 retinas were collected from 15 mice of each strain at similar time points during the day. Equimolar amounts of RNA isolated from ten retinas were pooled into three separate pools from each strain and time point, then hybridized to Affymetrix Mouse 420A 2.0 GeneChip arrays.

first: Austin

last: Jelcick

first: Yuan

last: Yang

first: Barrett

last: Leehy

first: Lakeisha

last: Cox

first: Alexandra

last: Silveira

first: Fang

last: Qiu

first: Sarah

last: Schenk

first: Andrew

last: Sachs

first: Margaux

last: Morrison

first: Arne

last: Nystuen

first: Margaret

last: DeAngelis


title: Dysregulation of c-terminal ezrin phosphorylation prevents tumor progression and metastasis and alters cellular metabolism in osteosarcoma

city: Bethesda

first: Chand

last: Khanna

state: MD

address: 37 Convent Drive, Suite 2144

department: Pediatric Oncology Branch

institute: NCI

summary: This dataset contains Affymetrix Mouse Genome 430 2.0 Array data obtained from K7M2 cells over-expressing ezrinT567A and the wild-type

overall_design: Gene expression analysis of K7M2 cells over-expressing ezrinT567A compared to the wild-type

first: Ling


title: Tg2576 and wild-type mice treated with PDE9A-inhibitor

status: Public on Mar 09 2012

city: Groton

first: Phillip

last: Yates

state: CT

address: 440 Eastern Point Rd

institute: Pfizer Inc.

summary: Many forms of synaptic plasticity are critically dependent upon production of cGMP to trigger activity-dependent increases in synaptic size and strength. Phosphodiesterase 9A (PDE9A) is a high affinity, cGMP-specific phosphodiesterase with widespread distribution in the central nervous system. Inhibition of PDE9A results in significant accumulation of cGMP in brain tissue and cerebrospinal fluid (CSF) of rodents, and increases CSF cGMP in human volunteers. We hypothesized that chronic exposure to a PDE9A inhibitor, and the associated elevations in brain cGMP could provide a therapeutic benefit to vulnerable synapses chronically exposed to Aβ in transgenic mice over-expressing human mutant amyloid precursor protein (Tg2576 mice).  A total of N=20 animals per group of 4 month old Tg2576 mice and non-transgenic littermates (WT) were  implanted with Alzet osmotic minipumps to deliver vehicle or the PDE9A inhibitor PF-04447943. Neurobehavioral outcomes were measured as conditioned fear response after 28 days of treatment and subsequently brains were harvested for measurement of Aβ, gene expression profiling or synaptic density as assessed by Golgi staining of dendrites.  Dendritic spine density on apical dendrites of CA1 neurons exhibited a small but significant deficit in the density of dendritic spines in vehicle treated Tg2576 mice as compared to WT mice. This deficit was ameliorated by 30 days of exposure to PF-04447943. No significant drug effect was observed in WT mice. No significant effects of drug treatment were observed on Aβ levels in Tg2576 mice.  Behavioral analysis of Tg2576 mice showed deficits in fear conditioning as early as 2 months old, and therefore were considered unlikely to be due to the accumulation of oligomeric Aβ. These deficits were not affected by drug treatment. Transcriptional profiles of Tg2576 mice treated with drug compared to vehicle showed evidence of regulation of pathways related to synaptic plasticity and remodeling of the dendritic cytoskeleton, consistent with stabilization of vulnerable spine structure. These data supports the hypothesis that PDE9A inhibition can stabilize vulnerable synapses early in the Alzheimer’s disease process.

overall_design: 4-month old Tg2576 mice and non-transgenic (WT) littermates were implanted with minipumps to deliver vehicle or the PDE9A-inhibitor, PF-04447943, for 28 days.  At the end of the study, hippocampus and frontal cortex were dissected from n=8 mice per group, RNA was isolated, and hybridized to Affymetrix 430 2.0 mouse whole genome microarray.

first: Thomas

last: Lanz

middle: D


title: Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes

first: WeiPing

last: Chen

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

department: GCL

institute: NIDDK/NIH

summary: Stat5+/- mice were bred into the C57BL/6 background. Stat5+/- mice were intercrossed and mouse embryonic fibroblasts (MEFs) were isolated from 12.5-13.5-day WT or Stat5-/- fetuses. The retroviral-expression vector carrying a wild-type Stat5A gene based on an MSCV-IRES-GFP backbone (gift from Richard Moriggl, Ludwig-Boltzmann Institute, Vienna, Austria) was infected into Stat5-/- MEFs. FACS was used to select GFP+ cells. After 5 hours starvation in serum free medium with 0.1% of BSA, MEFs were treated with growth hormone for 2 hours. Total cellular RNA from each group of the MEFs was extracted with TRIzol reagent (Invitrogen) according to the manufacturer's instructions. Microarray analyses were performed using Affymetrix Mouse Genome 430 2.0 GeneChips (Affymetrix, Santa Clara, CA) (six groups, biological replicates for each group). Expression values were determined with GeneChip Operating Software (GCOS) v1.1.1 software. RMA signals were summarized using GeneSpring GX 10.0.1 (Agilent) and normalized by quantile normalization. All data analysis was performed with GeneSpring software GX 10.01.

overall_design: Total 6 groups (S5, S5-GH, WT, WT_GH, KO, KO_GH), biological duplicate replication for each group

first: BingMei

last: Zhu

first: Keunsoo

last: Kang

first: Ji

middle: H

last: Yu

first: Weiping

first: Harold

middle: E

last: Smith

first: Daeyup

last: Lee

first: Hong

middle: W

last: Sun

first: Lai

last: Wei

first: Lothar

last: Hennighausen


title: Gene Expression profiling in DBA/2J glaucoma

status: Public on Mar 28 2012

city: Mount Desert

first: Gareth

middle: Rhys

last: Howell

address: 600 Main Street

institute: The Jackson Laboratory

type:
Expression profiling by array
Third-party reanalysis

summary: Glaucoma is a common ocular disorder that is a leading cause of blindness worldwide. It is characterized by the dysfunction and loss of retinal ganglion cells (RGCs). Although many studies have implicated various molecules in glaucoma, no mechanism has been shown to be responsible for the earliest detectable damage to RGCs and their axons in the optic nerve. Here, we show that the leukocyte transendothelial migration pathway is activated in the optic nerve head at the earliest stages of disease in an inherited mouse model of glaucoma. This resulted in proinflammatory monocytes entering the optic nerve prior to detectable neuronal damage. A 1-time x-ray treatment prevented monocyte entry and subsequent glaucomatous damage. A single x-ray treatment of an individual eye in young mice provided that eye with long-term protection from glaucoma but had no effect on the contralateral eye. Localized radiation treatment prevented detectable neuronal damage and dysfunction in treated eyes, despite the continued presence of other glaucomatous stresses and signaling pathways. Injection of endothelin-2, a damaging mediator produced by the monocytes, into irradiated eyes, combined with the other glaucomatous stresses, restored neural damage with a topography characteristic of glaucoma. Together, these data support a model of glaucomatous damage involving monocyte entry into the optic nerve. Genome-wide assessment of gene expression changes was performed in DBA/2J-Gpnmb+, DBA/2J mice and irradiated DBA/2J mice at 8.5 and 10.5 months of age.

overall_design: In this study (Howell et al, JCI, 2012), 50 samples (10 D2-Gpnmb+ control at 8.5 mos, 20 NOE DBA/2J at 8.5 mos, 10 radiation-treated DBA2J at 8.5 mos and 10 radiation-treated DBA/2J at 10.5 mos) were combined with 30 of ONH samples from the GSE26299 study (10 D2-Gpnmb+ and 20 NOE DBA/2J all at 10.5 mos). One D2-Gpnmb+ 8.5mo sample failed QC and was not included in the analysis. Quantile normalization was performed for all optic nerve head samples reported in the study. The complete dataset is linked below as a supplementary file.

first: G

middle: R

first: S

last: John


title: Expression data from pulmonary Type 2 Myeloid (T2M) cells, Eosinophils, Neutrophils, and Macrophages, from IL-25 treated 4get mice

status: Public on Mar 10 2012

city: Ann Arbor

first: Bryan

middle: C

last: Petersen

state: MI

address: 109 Zina Pitcher, 4620 BSRB

department: Pathology

institute: University of Michigan

summary:
Many symptoms associated with allergic asthma result from the sequelae of type 2 inflammation.  Interleukin (IL)-25 promotes type 2 inflammatory responses, and T2M cells represent an IL-4 and IL-13 producing granulocytic IL-25 responsive population.
We used microarrays to characterize the gene expression profile of T2M cells, and compared T2M cells to other inflammatory subsets (eosinophils, neutrophils, and macrophages) in the lungs of mice with IL-25-induced pulmonary inflammation.

overall_design:
Inflammatory subsets were isolated from the lungs of IL-25 treated 4get mice for RNA extraction and hybridization on Affymetrix microarrays. We pooled cells from 4 donor mice for each replicate, and used FACS to isolate pure populations of each inflammatory subset in parallel.
We analyzed 3 T2M replicates and 2 replicates each of the other inflammatory subsets.

first: Nicholas

last: Lukacs


title: microRNA alterations associated to clinical response in advanced stage ovarian cancer patients (test set)

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

country: Italy

institute: IRCSS Istituto Nazionale Tumori

summary: In order to investigate miRNA alterations associated to early relapse in ovarian cancer patietns, we analyzed miRNA expression profile in a test set of 30 surgical specimens including 13 early and 17 late relapsing patients. Samples included in test set were obtained from formalin-fixed paraffin-embedded (FFPE) specimens.

overall_design:
Patients were selected on the basis of residual disease after primary surgery and time to relapse (TTR) after front-line chemotherapy. For the test set, a selection of the outliers concerning TTR was made: 12 months from the end of therapy was the TTR selected to define early (<12 months) or late (>12 months) relapsing patients.

Clinical codes:

Histotype: according to International Federation of Gynecological and Obstetrics guidelines

Stage: according to International Federation of Gynecological and Obstetrics guidelines

Grading: according to WHO guidelines

Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease

Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel

End Point: Early: relapse whithin 12 and 6 months from the end of therapy for optimally (NED+ mRD) and sub-optimally (GRD) debulked patients respectively. Late: median time to relapse 48 and 34 months from the end of therapy for optimally and sub-optimally debulked patients respectively.

Time to relapse (TTR) code: 0=no relapse; 1=relapse

Overall survival (OS) code: 0=alive; 1=dead


title: Comparison of exercise and pregnancy-induced cardiac hypertrophy

status: Public on Mar 08 2012

city: Boulder

first: Joseph

middle: K

last: Heimiller

state: CO

address: 347 UCB

department: MCDB

institute: Univ of Colorado Boulder

summary: Comparative analysis of mouse cardiac left ventricle gene expression: voluntary wheel exercise and pregnancy-induced cardiac hypertrophy

overall_design: We performed microarray analysis on RNA from left ventricles of mice in non-pregnant diestrus cycle, mid-pregnancy (MP), late-pregnancy (LP), and immediate post-partum (0PP). These were compared to 7days (7EX) and 21 days (21EX) of voluntary wheel running exercise.

first: Eunhee

last: Chung

first: Leslie

last: Leinwand


title: Expression and ChIP-seq analysis LPS stimulated THP-1 cells

status: Public on Mar 07 2012

city: Copenhagen

first: Lasse

last: Folkersen

address: Artellerivej

department: Bioinformatics

country: Denmark

institute: National Genome Center

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Expression data for OVE26 diabetic mouse podocyte

status: Public on Mar 02 2012

city: Louisville

first: Jianxiang

last: Xu

state: KY

address: 570 S. Preston ST Suite 304

department: Pediatrics

institute: University of Louisville

summary:
Podocytes form filtration barrier through foot process around glomerualar basement membrane and selectively permit permeability of molecular smaller than albumin. Diabetes  can cause podocyte pathological changes leading to high urine albumin level. Diabetic mouse model OVE26 has extremly high urine albumin and previously studies indicated its podocyte damaged.
Here we try to find the key genes change in OVE26 diabetic mouse model podocyte by microarray assay while normal FVB mouse podocyte set as control.

overall_design: Podocyte eGFP transgenic mice were made on FVB background and crossbred to OVE26 diabetic model. Glomeruli isolated from OVE-GFP mice were digested by trypsin into signal cell. Podocytes with GFP were sorting out by FACS.

first: Paul

middle: N

last: Epstein


title: Human CD4+ T-cell transcriptome in early arthritis

status: Public on Mar 03 2012

city: Newcastle

first: Simon

last: Cockell

address: Framlington Place

country: United Kingdom

institute: Newcastle University

summary: An exploration of the peripheral blood CD4+ T-cell transcriptome of early arthritis clinic attendees, seeking novel diagnostic tools and pathophysiological insights.

overall_design:
Ex-vivo CD4+ T-cell RNA was obtained following first early arthritis clinic attendance from 173 patients.  Four diagnostic categories were confirmed at median 28 months follow-up. Outcome categories are ACPA- RA (A; n=31), ACPA+ RA (B; n=41), Non-RA Inflammatory arthritis (C; n=56), and Non-RA/Non-Inflammatory arthritis (D; n=45).
In order to derive and validate a diagnostic gene signature, samples were split into Training set (where patients could be diagnosed at presentation; n=111) and validation set of undifferentiated arthritis (UA; n=62) patients, in whom diagnosis could only be confirmed after the follow-up period.
Arrays were processed in two phases (phases 1 and 2). Phase 1 was split into 4 labelling batches, Phase 2 was split into 2 labelling batches. Batch effects were controlled for using this information using the empirical Bayes approach of Johnson et al. (2007).

The supplementary file 'GSE20098_non-normalized.txt' contains non-normalized data for Samples GSM502124-GSM502280 and GSM506251-GSM506266.

first: Arthur

last: Pratt

first: Daniel

last: Swan


title: Expression analysis LPS stimulated THP-1 cells in four paired samples

summary: Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS).  To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.

overall_design:
4 pairs of THP-1 cells either stimulated with LPS or not

This submission represents transcriptome component of study.

first: Maria

middle: J

last: Iglesias

first: Sarah-Jayne

last: Reilly

first: Olof

last: Emanuelsson

first: Per

last: Eriksson

first: Anders

last: Hamsten

first: Jens

last: Lagergren

last: Mälarstig

first: Mohammad

last: Najafabadi

first: Bengt

last: Sennblad

first: Jacob

last: Odeberg


title: miR-18a regulates the miRNAs by target  Dicer in Nasopharyngeal carcinoma HK-1 cell.

status: Public on Mar 01 2012

city: Changsha

first: luo

last: zhaohui

state: Hunan

address: 110 Xiangya Road

country: China

institute: Cancer  Research  Institute

summary: As the biogenesis of miRNAs depends on the cleavage by the RNase III enzyme Dicer, miR-18a may change the miRNA expression profiles by targeting dicer. We then performed the miRNA array assay to investigate the miRNA profiles change caused by miR-18a.

overall_design: Total RNA obtained from two pairs,one is the miR-18a overexpression cell line compared to the miRNAs (control), the other is the over-expression miR-18a cell line transfected Dicer plasmid.

first: Luo

last: Zhaohui

first: Xiang

last: Juanjuan


title: Comparison between mouse ES/iPS derived neurosphere and mouse primary culture of neurospheres obtained from fetal mouse ganglionic eminence

city: Kobe

first: Kenji

last: Yoshida

address: 2-2-2, Minatojima Minamimachim Chuo-ku

department: Regenerative & Cellular Medicine

institute: Sumitomo Dainippon Pharma Co.,Ltd.

summary:
Recent reports have emphasized the pitfalls of iPSC technology including the potential for immunogenicity of transplanted cells. It is serious safety-related concern for iPSC-based cell therapy. However, preclinical data supporting the safety and efficacy of iPSCs are also accumulating. To address the concern of immunogenicity of ESCs/iPSCs or ESCs/iPSCs-derived neurospheres, global gene expression profiles were compared between undifferentiated mouse ESCs (EB3 line), mouse iPSCs (38C2 line), and ESC/iPSC-derived neurosphere and mouse primary culture of neurosphere obtained from fetal mouse ganglionic eminence. Mouse adult sklin fibroblast was used as a control.
We used affymetrix microarrays to compare the global gene expression of neurospheres prepared several origins.

Keywords: Expression profiling by array

overall_design: RNA extracted from neurospheres was hybridized to Affymetrix microarrays.

first: Takeshi

last: Matsui

first: Wado

last: Akamatsu

first: Hideyuki

last: Okano


title: White adipose tissue from aP2-Pex5 knockout and control mice

city: Cologne

first: Emiel

last: Ver Loren van Themaat

address: Carl von linneweg

country: Germany

institute: Max Planck Institute

summary: These arrays contain data from gonodal adipose tissue of aP2-Pex5 -/- male mice

overall_design: 4 arrays from gonadal adipose tissue from control mice (Swiss background) are compared with 4 arrays from gonadal adipose tissue of aP2-Pex5 knockout mice. The latter lack functional peroxisomes in adipose tissue.

first: Myriam

last: Baes


title: Pten loss and RAS/MAPK activation cooperate to promote EMT and prostate cancer metastasis initiated from stem/progenitor cells

status: Public on Feb 28 2012

city: Los Angeles

first: Linh

middle: My

last: Tran

state: California

department: Medicine - Pulmonary & Critical Care

institute: University of Los Angeles

summary: PTEN loss or PI3K/AKT signaling pathway activation correlates with human prostate cancer progression and metastasis. However, in preclinical murine models, deletion of Pten alone fails to mimic the significant metastatic burden that frequently accompanies the end stage of human disease.  To identify additional pathway alterations that cooperate with PTEN loss in prostate cancer progression, we surveyed human prostate cancer tissue microarrays and found that the RAS/MAPK pathway is significantly elevated both in primary and metastatic lesions.  In an attempt to model this event, we crossed conditional activatable K-rasG12D/WT mice with the prostate conditional Pten deletion model we previously generated. Although RAS activation alone cannot initiate prostate cancer development, it significantly accelerated progression caused by PTEN loss, accompanied by epithelial-to-mesenchymal transition (EMT) and macrometastasis with 100% penitence. A novel stem/progenitor subpopulation with mesenchymal characteristics was isolated from the compound mutant prostates, which was highly metastatic upon orthotopic transplantation.  Importantly, inhibition of RAS/MAPK signaling by PD325901, a MEK inhibitor, significantly reduced the metastatic progression initiated from transplanted stem/progenitor cells.  Collectively, these data indicate that activation of RAS/MAPK signaling serves as a potentiating second hit to alteration of the PTEN/PI3K/AKT axis and co-targeting both pathways is highly effective in preventing the development of metastatic prostate cancers.

overall_design: Murine mutants with prostate specific loss of Pten and K-ras activation (K-rasG12D) under regulation of the probasin promoter developed high grade, invasive prostate cancer.  RNA was extracted from dissected prostate lobes from individual mutants with pathology thought to closely mimic human disease.  Prostate tissue was subject to RNA extraction and hybridization on Affymetrix cDNA microarrays.

first: David

last: Mulholland

first: Kobayashi

last: Naoko

first: Ruscetti

last: Marcus

first: Zhi

last: Allen

first: Tran

last: Linh

first: Huang

last: Jiaoti

first: Gleave

last: Martin

first: Wu

last: Hong


title: Prostatic Stromal Cell Gene Expression

status: Public on Feb 27 2012

city: Cleveland

first: Gurkan

last: Bebek

state: OH

address: 10900 Euclid Ave

institute: Case Western Reserve Univ.

summary: We generated prostatic stromal microarray expression data for functional validation of our LOH/AI hot-/cold-spots in stroma. Stromal cells from normal peripheral zone tissue and from tumors are grown in culture, and were analyed on gene expression platform.

overall_design: Stromal cells cultured from normal peripheral zone tissues (F-PZ-64, F-PZ-79, F-PZ-82, F-PZ-102, F-PZ-105) and from tumors (F-CA-31, F-CA-39, F-CA-52, F-CA-67, F-CA-93) were established and grown as previously described in Peehl et al. (2000). Total RNAs were extracted from semi-confluent cells (passages 4-5) one day after feeding fresh medium using RNeasy Mini Kit (Qiagen) according to the manufacturer’s instructions and treated with TURBO DNA-free kit (Ambion).  Hybridizations were performed according to Illumina protocols by the Genomic Core, Lerner Research Institute, Cleveland Clinic.  All samples were hybridized to the Illumina Sentrix Human-6_v3 Expression BeadChip (GPL6884) which contains 48,000 distinct oligonucleotide probes.  Normalization is done using average normalization algorithm of BeadStudio Gene Expression Module v3.4 (Illumina).

first: Shingo

last: Ashida

first: Mohammed

middle: S

last: Orloff

first: Li

last: Zhang

first: Pan

last: Zheng

first: Donna

middle: M

last: Peehl

first: Charis

last: Eng


title: microRNA alterations associated to clinical response in advanced stage ovarian cancer patients (training set)

first: Loris

last: De Cecco

summary: In order to investigate miRNA alterations associated to early relapse in ovarian cancer patients, we analyzed miRNA expression profile in a training set of 55 surgical specimens including 30 early relapsing and 25 late relapsing patients.

overall_design:
Patients were selected on the basis of residual disease after primary surgery and time to relapse (TTR) after front-line chemotherapy. For training set, a selection of the outliers concerning TTR was made: as early relapsing were defined optimally debulked (OD) patients with a TTR< 12 months and sub-optimally debulked (SOD) patients with TTR< 6 months; late relapsing were defined OD patients with TTR> 36 months and SOD patients with TTR> 12 months.

Clinical codes:

Histotype: according to International Federation of Gynecological and Obstetrics guidelines

Stage: according to International Federation of Gynecological and Obstetrics guidelines

Grading: according to WHO guidelines

Debulking: NED: not evident disease; mRD: minimal residual disease; GRD: gross residual disease

Therapy code: P: Platinum without taxanes; PT: Platinum/paclitaxel

End Point: Early: relapse whithin 12 and 6 months from the end of therapy for optimally (NED+ mRD) and sub-optimally (GRD) debulked patients respectively. Late: median time to relapse 48 and 34 months from the end of therapy for optimally and sub-optimally debulked patients respectively.

Time to relapse (TTR) code: 0=no relapse; 1=relapse

Overall survival (OS) code: 0=alive; 1=dead


title: Gene Expression profiles of colon from VhlF/F, VhlΔIE, VhlF/F/Apcmin/+, VhlΔIE/Apcmin/+

first: XIANG

last: XUE

state: Michigan

address: 1301 E. Catherine Street

institute: Umich

summary:
To identify the precise molecular mechanisms that could contribute to the increase in colon carcinogenesis, microarray gene expression analysis was performed on colon RNA isolated from 5-week-old VhlF/F and VhlΔIE, VhlΔIE/Apcmin/+ and VhlF/F/Apcmin/+ mice.
Hypoxia-inducible factor (HIF) is a key modulator of the transcriptional response to hypoxia and is increased in colon cancer. However, the role of HIF in colon carcinogenesis in vivo remains unclear. Intestinal epithelium-specific disruption of the von Hippel-Lindau tumor suppressor protein (VHL) resulted in constitutive HIF signaling, and increased HIF expression augmented colon tumorigenesis in the Apcmin/+ intestinal tumor model. Intestine-specific disruption of Vhl increased colon tumor multiplicity and progression from adenomas to carcinomas. These effects were ameliorated in mice with double disruption of Vhl and Hif-2α. Activation of HIF signaling resulted in increased cell survival in normal colon tissue, however tumor apoptosis was not affected. Interestingly, a robust activation of cyclin D1 was observed in tumors of Apcmin/+ mice in which HIF-2α was activated in the intestine. Consistent with this result, BrdU incorporation indicated that cellular proliferation was increased in colon tumors following HIF activation. Further analysis demonstrated that dysregulation of the intestinal iron absorption transporter divalent metal transporter-1 (DMT-1) was a critical event in HIF-2α-mediated colon carcinogenesis. These data provide a mechanistic basis for the widely reported link between iron accumulation and colon cancer risk. Together, our findings demonstrate that a chronic increase in HIF-2α in the colon initiates pro-tumorigenic signaling which may have important implications in developing preventive and therapeutic strategies for colon cancer.

overall_design: Global gene expression profiling in colon RNAs isolated from 5-week-old VhlF/F (n=4, Shah 001), VhlF/F/Apcmin/+(n=3, Shah 003), VhlΔIE (n=3, Shah 002) and VhlΔIE/Apcmin/+ mice (n=5, Shah 004).

first: Xiang

last: Xue

first: Yatrik

last: Shah


title: Effect of GRHL2 in HMLE+Twist-ER+4-OHT cells

status: Public on Feb 25 2012

city: Huntington

first: James

last: Denvir

state: WV

address: One John Marshall Drive

department: Biochemistry and Microbiology

institute: Marshall University School of Medicine

summary: Grainyhead genes are involved in wound healing and developmental neural tube closure. In light of the high degree of similarity between the epithelial-mesenchymal transitions (EMTs) occurring in wound healing processes and the cancer stem cell-like compartment of tumors, including TGF-β-dependence, we investigated the role of a Grainyhead gene (GRHL2) in oncogenic EMT.  Grainyhead was specifically down-regulated in the claudin-low subclass of mammary tumors and in the basal-B subclass of breast cancer cell lines.  Functionally, GRHL2 suppressed TGF-β-induced, Twist-induced or spontaneous EMT, enhanced anoikis-sensitivity, and suppressed mammosphere generation in mammary epithelial cells.   These effects were mediated, in part, by its suppression of ZEB1 expression, through direct repression of the ZEB1 promoter.  GRHL2 also inhibited Smad-mediated transcription, and up-regulated mir200b/c as well as the TGF-β receptor antagonist, BMP2.  The expression of GRHL2 in the breast cancer cell line MDA-MB-231 triggered a mesenchymal-to-epithelial transition and sensitized the cells to anoikis.  These results indicate that GRHL2 is a suppressor of the oncogenic EMT.

overall_design: 3 biologic replicates for each cell line. Comparison of HMLE+Twist-ER cells expressing GRHL2/pMIG vs. HMLE+Twist-ER cells expressing empty pMIG.

first: Benjamin

last: Cieply

first: Philip

last: Riley

first: Phillip

last: Pifer

first: Joseph

last: Widmeyer

last: Addison

first: Alexey

middle: V

last: Ivanov

first: Steven

last: Frisch


title: A mouse model of the most aggressive subgroup of human medulloblastoma [Mouse430_2]

status: Public on Feb 29 2012

city: Memphis

first: David

last: Finkelstein

state: TN

address: 332 N. Lauderdale St.

department: Computational Biology

institute: St Jude Children's Research Hospital

summary: Mouse models of medulloblastoma are compared to human subgroups through microarray expression and other measures

overall_design: This study contrasts mouse medullablastomas from a range of mouse genetic  models. For Shh-type medulloblastoma [dka001-005, 009, 033 and 034] and [dka050-057], spontaneous medulloblastomas from [Cdkn2c-/-; Trp53Fl/Fl; Nestin-Cre] and [Cdkn2c-/-; Ptch1+/-] (Uziel et al.,2005 Genes Dev) were used, respectively.  For Myc [dka010-022, 037, 046, 049 and 058-71] and Mycn [dka023-032, 036 and 047] were generated by orthotopic injection of either Myc or Mycn overexpression in Cdkn2c-/-, Trp53-/- cerebellar cells into immunocompromised nude mice.  For Wnt-type medulloblastomas [pgr003, 016 and 066], spontaneously developed tumors from CTNNB1+/lox (ex3); BLBP-Cre; Trp53Fl/Fl (Gibson et al., Nature, 2010) were removed for RNA extraction.

first: Daisuke

last: Kawauchi

first: Giles

last: Robinson

first: Tamar

last: Uziel

first: Paul

last: Gibson

first: Jerold

last: Rehg

first: Cuilan

last: Gao

first: Chunxu

last: Qu

first: Stanley

last: Pounds

last: Ellison

first: Richard

last: Gilbertson

first: Martine

middle: F

last: Roussel


title: microRNA alterations associated to clinical response in advanced stage ovarian cancer patients

first: Loris

last: De Cecco


title: Expression data from mouse embryo during neural tube closure

city: Edmonton

first: Heather

last: McDermid

state: Alberta

address: University of Alberta

department: Biological Sciences

country: Canada

institute: University of Alberta

summary:
This data series was used for two separate studies. The initial study was aimed to idenify expression changes brought about by the Cecr2Gt45Bic mutation during neural closure. The study included two different strains, BALB/cCrl in which Cecr2GT45Bic shows a neural tube defect phenotype and FVB/N in which Cecr2Gt45Bic does not manifest neural closure defects. The second was to idenify strain specific expression differences present during neural closure of the mouse embryo between BALB/cCrl and FVB/N in order to identify candidate modifiers of the Cecr2Gt45Bic neural tube defect. Relevant abstracts are included below.

The initial study ;
BACKGROUND: Over 200 mouse genes are associated with neural tube defects (NTDs), including Cecr2, the bromodomain-containing subunit of the CERF chromatin remodeling complex.
METHODS: Gene-trap mutation Cecr2Gt45Bic results in 74% exencephaly (equivalent of human anencephaly) on the BALB/c strain. Gene expression altered during cranial neural tube closure by the Cecr2 mutation was identified through microarray analysis of 11–14 somites stage Cecr2Gt45Bicembryos.
RESULTS: Analysis of Affymetrix Mouse 430 2.0 chips detected 60 transcripts up-regulated and 54 transcripts down-regulated in the Cecr2Gt45Bic embryos (fold > 1.5, p < 0.05). The Cecr2 transcript was reduced only ∼7- to 14-fold from normal levels, suggesting the Cecr2Gt45Bic is a hypomorphic mutation. We therefore generated a novel Cecr2 null allele (Cecr2tm1.1Hemc). Resulting mutants displayed a stronger penetrance of exencephaly than Cecr2Gt45Bic in both BALB/c and FVB/N strains, in addition to midline facial clefts and forebrain encephalocele in the FVB/N strain. The Cecr2 transcript is reduced 260-fold in the Cecr2tm1.1Hemc line. Subsequent qRT-PCR using Cecr2tm1.1Hemc mutant heads confirmed downregulation of transcription factors Alx1/Cart1,Dlx5, Eya1, and Six1.
CONCLUSIONS: As both Alx1/Cart1 and Dlx5 mouse mutations result in exencephaly, we hypothesize that changes in expression of these mesenchymal/ectodermal transcription factors may contribute to NTDs associated with Cecr2. Birth Defects Research (Part A), 2010. 010 Wiley-Liss, Inc.

The second study:
ABSTRACT:Although neural tube defects (NTDs) are common in humans, little is known about their multifactorial genetic causes. While most mouse models involve NTDs caused by a single mutated gene, we have previously described a multigenic system involving susceptibility to NTDs. In mice with a mutation in Cecr2, the cranial NTD exencephaly shows strain specific differences in penetrance, with 74% penetrance in BALB/cCrl and 0% penetrance in FVB/N. Whole genome linkage analysis showed that a region of chromosome 19 was partially responsible for this difference in penetrance. We now reveal by genetic analysis of three subinterval congenic lines that the chromosome 19 region contains more than one modifier gene. Analysis of embryos showed that although a Cecr2 mutation causes wider neural tubes in both strains, FVB/N embryos overcome this abnormality and close. A microarray analysis comparing neurulating female embryos from both strains identified differentially expressed genes within the chromosome 19 region, including Arhgap19, which is expressed at a lower level in BALB/cCrl due to a stop codon specific to that substrain. Modifier genes in this region are of particular interest because it is syntenic to human chromosome 10q25, the site of a human susceptibility locus. (MANUSCRIPT PENDING SUBMISSION)

overall_design: Thieler STAGE 13-14 (11-14 somite) female embryos where disected away from extraembryonic membranes for RNA extraction and hybridization on Affymetrix microarrays. A single embryo was processed per array, with four biological replicates per genotype BALB/cCrl, Cecr2GT45Bic BALB/cCrl, FVB/N, and Cecr2Gt45Bic FVB/N.

first: Nicholas

middle: A

last: Fairbridge

first: Megan

last: Kooistra

first: Christine

last: Dawe

first: Kirst

last: King-Jones


title: Gene expression profiles of subepithelial myofibroblasts from mouse ileum or colon, implanted together with human cancer cells in mouse xenografts

status: Public on Feb 24 2012

city: Boston

first: Janghee

last: Woo

address: 44 Binney st.

institute: Dana-Farber Cancer Institute

summary:
We isolated myofibroblasts from C57BL6/J mouse ileum or colon and analyzed gene expression profiles from the cultured cells. We also isolated human colon cancer cells from xenografts interacting with mouse intestinal subepithelial myofibroblasts (ISEMFs) and analyzed gene expression in sorted human cancer cells.
We used Affymetrix microarrays to detail the global gene expression prolfiles in mouse fibroblasts and human colon cancer cells  and identified distinct biological processes of differentially expressed genes in mouse fibroblasts and interacting human colon cancer cells

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: For mouse SEMFs, we isolated fresh fibroblasts from mouse ileum and colon, confirmed their predicted immunophenotype (alpha SMA positive, vimentin positive, desmin negative), and expanded cells in culture before expression array analysis. We examined gene expression in human cancer cells following their interaction with murine ileal or colonic SEMFs, using flow cytometry to isolate DsRed-expressing Caco2 or T84 cells after 5 weeks of growth in NOD/SCID mice in the presence of GFP-expressing ileal or colonic SEMFs.

first: D

middle: G

last: Gilliland

first: Ramesh

last: Shivdasani


title: Expression profiling of secondary wild type (WT) and Ezh2-null murine MLL-AF9 AML

status: Public on Feb 22 2012

first: Amit

last: Sinha

state: MA

address: 44 Binney St

department: Pediatric Oncology

summary: We evaluated gene expression changes in secondary recipient murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of a homozygous conditional allele for Ezh2, a component of the Polycomb Repressive Complex2.

overall_design: For WT cells, 4 biological replicates were hybridized. For Ezh2-null cells, 5 biological replicates were hybridized.

first: Tobias

last: Neff

middle: U

first: Scott

last: Armstrong


title: A mouse model of the most aggressive subgroup of human medulloblastoma

first: David

last: Finkelstein


title: Gene expression data from IL13-induced allergic airway inflammation of mice lungs

status: Public on Feb 23 2012

first: Aik

middle: T

last: Ooi

address: 650 Charles E Young Dr S, Factor 9-240

institute: UCLA

summary:
Asthma is a common chronic inflammatory airway condition with a strong genetic and inheritability component, as siblings and first-degree relatives of those with the disease are often affected.
For our studies, we used a well-characterized transgenic mouse model of allergic airway inflammation induced by IL13. In this model, IL13 is conditionally overexpressed in the mouse lung when treated with doxycycline. Upon IL13 induction, these mice showed inflammatory cell infiltration, pronounced emphysema, increased pulmonary compliance, lung volume enlargement, mucus metaplasia, and increased expression of matrix metalloproteinases and cathepsins in the lung. We performed gene expression microarray to examine the changes in gene expression during IL13-induced allergic airway inflammation.

overall_design: The CC10-rtTA-IL13 transgenic (TG) and wildtype (WT) mice were treated with doxycycline for seven days. Mice were euthanized and the left upper lobes from all mice were removed for RNA extraction using the TRIzol method.

first: Sonal

last: Ram

first: Alan

last: Kuo

first: Derek

last: Nickerson

first: Jennifer

middle: L

last: Gilbert

first: Weihong

last: Yan

first: Matteo

last: Pellegrini

first: Talal

last: Chatila

first: Brigitte

last: Gomperts


title: Expression profiling of primary wild type (WT), Ezh2-null and Eed-null murine MLL-AF9 AML

summary: We evaluated gene expression changes in murine leukemia caused by retroviral overexpression of MLL-AF9. We compared wild-type (WT) leukemia cells with mutant leukemia cells after cre-mediated inactivation of homozygous conditional alleles for Ezh2 or Eed, both of which are components of the Polycomb Repressive Complex2.

overall_design: For WT cells, 3 biological replicates were hybridized. For Ezh2-null cells, 4 biological replicates were hybridized. For Eed-cells, 3 biological replicates were hybridized.


title: Hypothalamus

first: Emiel

last: Ver Loren van Themaat

summary: These arrays contain data from hypthalamus tissue of nestin-Pex5 -/- male mice

overall_design: Gene expression in biological replicates from hypothalamus of 4 wild type mice was compared with 4 NestinPex5-/- mice. In the latter, functional peroxisomes were deleted from all neural cells.

first: Myriam

last: Baes


title: GPR120 mediates high-fat diet induced obesity

city: Kyoto

first: Akira

last: Hirasawa

state: Kyoto

address: 46-29 Yoshida Shimoadachi-cho, Sakyo-ku

department: Genomic Drug Discovery Science

institute: Kyoto University Graduate School of Pharmaceutical Sciences

summary: Analysis of GPR120 which play roles for the fatty acid sensor in adipose tissue. Results provide insight into the transcriptional effects caused by the loss of the GPR120 proteins and provide further insight into their functions.

overall_design: GPR120 KO mice and the corresponding wild-type with normal diet(ND) or high fat diet(HFD), were subjected to Affymetrix Mus musculus microarrays. Epididymal adipose tissue and liver were analyzed in triplicates.

first: Atsuhiko

last: Ichimura

first: Gozoh

last: Tsujimoto


title: Expression data from antigen-presenting cells (APCs)

city: Toyama City

first: Ai

last: Kariyone

address: 2630 Sugitani

institute: University of Toyama

summary: P25 is the major T cell epitope for Ag85B and enables them to induce P25-specific CD4+ Th1 cells. We used microarrays to examine the gene expression of antigen-presenting cells (APCs) stimulated with P25 and P25-specific CD4+ T cells.

overall_design: Splenic APCs from WT mice were cultured with P25 or medium in the presence of P25 TCR CD4+ T cells. After overnight culture, these APCs were enriched and total RNA was prepared using RNeasy (QIAGEN) according to the manufacturer's instructions. Mixed total RNA from three independent experiments was used for microarray analysis.

first: Masashi

last: Ikutani

first: Yoshinori

last: Nagai

first: Kiyoshi

last: Takatsu


title: ChIP-seq analysis LPS stimulated THP-1 cells

first: Lasse

last: Folkersen

summary: Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS).  To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of up-regulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.

overall_design: 2 pairs of THP-1 cells either stimulated with LPS or not. ChIP using either H3K9/K14Ac, RNA Pol II (phospho S5) or SP1 antibody. This submission represents chip-seq component of study.

first: Maria

last: Iglesias

first: Sarah-Jayne

last: Reilly

first: Olof

last: Emanuelsson

first: Per

last: Eriksson

first: Anders

last: Hamsten

first: Jens

last: Lagergren

last: MÃ¤larstig

first: Mohammad

middle: P

last: Najafabadi

first: Bengt

last: Sennblad

first: Jacob

last: Odeberg


title: Expression data from mouse liver treated with metformin

status: Public on Feb 21 2012

city: Kanazawa

first: Hirofumi

last: Misu

address: 13-1 Takaramachi

institute: Kanazawa University

summary:
Optimal treatment for nonalcoholic steatohepatitis (NASH) has not yet been established, particularly for individuals without diabetes.
We examined the effects of metformin, commonly used to treat patients with type 2 diabetes, on liver pathology in a non-diabetic NASH mouse model.

overall_design: Eight-week-old C57BL/6 mice were fed a methionine- and choline-deficient (MCD) + high fat (HF) diet with or without 0.1% metformin for 8 weeks.

first: Toshinari

last: Takamura


title: Renormalization of GSE32442 and GSE33128

city: St Louis

first: Tiandao

last: Li

state: MO

address: 4444 Forest Park Ave

institute: Washington University

summary: Raw data from GSE32442 and GSE33128 and the input dataset for GSE32442 were renormalized by using reads per million.

overall_design: 11 samples from GSE32442 and GSE33128

first: David

middle: H

last: Price


title: Developmental timecourse of mouse ocular lens and whole embryo control

status: Public on Feb 16 2012

first: Joshua

middle: WK

last: Ho

address: 41 Avenue Louis Pasteur

department: Department of Medicine

institute: Brigham and Women's Hospital

summary: Identification of genes involved in ocular birth defects remains a challenge. To facilitate the identification of genes associated with cataract, we developed iSyTE (integrated Systems Tool for Eye gene discovery; http://bioinformatics.udel.edu/Research/iSyTE). iSyTE contains microarray gene expression profiles of the mouse embryonic lens as it transitions from the stage of placode invagination to that of vesicle formation. We identified differentially regulated genes by comparing lens microarray profiles to those representing whole embryonic body (WB) without ocular tissue. These were then utilized to generate a ranked list of lens-genes enrichment, which can be viewed as iSyTE tracks in the UCSC Genome browser to aid identification of genes with lens function.

overall_design: We microdissected embryonic lens from mice at E10.5, E11.5, and E12.5 (triplicate at each time point). To have a proper control, we also generated gene expression profiles of whole embryonic body (WB) at these time points. For comparative analysis, we also generated gene expression profiles of E13.5 tooth germs tissues, and matched WB. These profiles are used to identify lens and tooth specific gene expression enrichment at these embryonic time points. This dataset is then used to prioritize analysis of candidate cataract associated genes.

first: Salil

last: Lachke

middle: W

first: Gregory

last: Kryukov

first: Daniel

last: O'Connell

first: Richard

last: Maas


title: Role of PKD2 in TCR-induced transcriptional reprogramming of naïve T cells

city: DUNDEE

first: Maria

last: Navarro

address: Dow Street

department: Cell Signallig and Immunology

institute: University of Dundee

summary: Comparison of transcriptional profile of TCR stimulated P14-TCR wild-type and P14-PKD2 null murine lymph node cells

overall_design: Lymph node cells from 3 biological replicates (3 wild-type and 3 PKD2 null mice) were isolated and left unstimulated or stimulated for 4 hours with antigenic peptide (gp33-41) prior to RNA extraction and hybridization to Affymetrix microarray.

first: M

first: D

last: Cantrell


title: Detailed transcriptomics analysis of the effect of dietary fatty acids on gene regulation in the murine heart [superseries]

city: Wageningen

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

department: Div. Human Nutrition & Health

country: Netherlands

institute: Wageningen University

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

overall_design: Refer to individual Series


title: Gene expression analysis of human serious ovarian tumors and fimbria control

city: Houston

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: The cell of origin of serious ovarian cancer is unknown. To create a mouse model for this lethal cancer and identify early cancer biomarkers, we conditionally deleted both Dicer (essential for microRNA biosynthesis) and Pten (a negative regulator of the PI3K pathway) in the female reproductive tract. Beginning at ~3-5 months, these Dicer/Pten mutant mice develop high-grade serious carcinomas that initiate in the stroma of the fallopian tube through a mesenchymal-to-epithelial transition (MET), subsequently envelop the ovary, and then metastasize throughout the peritoneum, resulting in ascites and 100% lethality by 13 months. The fallopian tube cancers demonstrate upregulation of genes encoding known and novel secreted proteins that are potential biomarkers. This study uncovers a new paradigm for the initiation of high-grade serous ovarian cancer.

overall_design: We generated gene expression profiles of 8 human primary serious tumors, and 2 independent samples of human normal fimbria.  We defined genes that were high or low in tumors relative to fimbria, and compared these results with those of the correponding mouse model.

first: Marty

last: Matzuk

first: Jaeyeon

last: Kim

first: Shannon

last: Hawkins


title: Stem Cell Antigen-1 (Sca-1) Regulates Mammary Tumor Development and Cell Migration

summary: Stem cell antigen-1 (Sca-1 or Ly6A) is a member of the Ly6 family of glycosyl phostidylinositol (GPI)-anchored cell surface proteins. To determine the potential mechanisms by which Sca-1 regulates cell migration, adhesion, and tumor development; we performed an Affymetrix mouse genome 430A 2.0 array on cDNA comparing shLuc and shSca-1 from cells grown in vitro.

overall_design: We performed an Affymetrix mouse genome 430A 2.0 array on cDNA comparing shLuc and shSca-1 from cells grown in vitro.  Experimental groups were profiled in biological triplicate.

first: Torey

last: Batts

first: Jeff

last: Rosen


title: Expression data from adult mice breast cancer cell 4T1

status: Public on Feb 15 2012

city: Tokyo

first: Osamu

last: Nagano

state: DDS PhD

address: ３５　Shinanomachi

department: Institute for Advanced Medical Research

institute: Keio University School of Medicine

summary:
Microaaray data for CD44v8-10-positive / CD44v8-10-negative 4T1 cancer cells (mouse breast cancer cells)
We used microarrays to detail the global programming of gene expression of 4T1 cells depending on whether CD44v is present or not.

overall_design: 4T1 cells, one of the mouse breast cancer cells, were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the data about to which extent gene expression profile is different between CD44v-positive and CD44v-negative 4T1 cancer cells.

first: Toshifumi

last: Yae


title: Identification of hypoxia regulated HIF-1A and HIF-2A specific target genes in Glioblastoma

first: Mei Yee

last: Koh

address: 1515 Holcombe Blvd

department: Experimental Therapeutics

institute: U.T. M.D. Anderson Cancer Center

summary:
HIF-1A and HIF-2A regulate both overlapping and unique target genes in response to hypoxia.
In this dataset, we identify specific HIF-1A and HIF-2A target genes in glioblastoma cells.

overall_design: 12 samples were analysed comprising 4 experimental conditions (normoxia scr, hypoxia scr, hypoxia siHIF1, hypoxia siHIF2) in triplicate. We made pairwise comparisons between the averages of each triplicate set to normoxia scr using the Partek suite.

first: MY

first: Robert

last: Lemos Jr.

first: Xiuping

last: Liu

first: Garth

last: Powis


title: Gene expression profiles of serous ovarian cancer in human and mouse


title: A combined RNAi and localization approach for dissecting long noncoding RNAs reveals a function of Panct1 in ES cells

city: Dresden

first: Maciej

last: Paszkowski-Rogacz

address: Tatzberg 47/49

department: UCC / Medical Faculty and University Hospital Carl Gustav Carus

institute: Technische Universität Dresden

summary: Long non-coding RNAs (lncRNAs) regulate diverse biological pathways. Unlike protein coding genes, where methods to comprehensibly study their functional roles in cellular systems are available, techniques to systematically investigate lncRNAs have largely remained unexplored. Here, we report a technology for combined Knockdown and Localization Analysis of Non-coding RNAs (c-KLAN) that merges phenotypic characterization and localization approaches to study lncRNAs. Using a library of endoribonuclease prepared short interfering RNAs (esiRNAs) coupled with a pipeline for synthesizing labeled riboprobes for RNA fluorescence in situ hybridization (FISH), we demonstrate the utility of c-KLAN by identifying a novel transcript Panct1 (Pluripotency associated non-coding transcript 1) that regulates embryonic stem cell identity. We postulate that c-KLAN should be generally useful in the discovery of lncRNAs implicated in various biological processes.

overall_design: In this experiment, the levels of Panct1(AK156552) have been depleted by RNAi and the expression levels of all genes have been monitored 72 hours post transfection with esiRNAs against Panct1. An esiRNA against non-targeting Luciferase was used as a negative control.

first: Debojyoti

last: Chakraborty

first: Herbert

last: Schulz

first: Kathrin

last: Saar

first: Norbert

last: Huebner


title: DNA methylation profiling of embryonic stem cell differentiation into the three germ layers [Expression analysis]

first: Takayuki

last: Isagawa

address: 4-6-1 Komaba, Meguro-ku

department: RCAST

institute: The University of Tokyo

summary: Embryogenesis is tightly regulated by multiple levels of epigenetic systems such as DNA methylation, histone modification, and chromatin remodeling.  DNA methylation patterns are erased in primordial germ cells and in the interval immediately following fertilization.  Subsequent reprogramming occurs by de novo methylation and demethylation.  Variance of DNA methylation patterns between different cell types is not well understood.  Here, using methylated DNA immunoprecipitation and tiling array technology, we have comprehensively analysed DNA methylation patterns at proximal promoter regions in mouse embryonic stem (ES) cells, ES cell-derived early germ layers (ectoderm, endoderm and mesoderm) and four adult tissues (brain, liver, skeletal muscle and sperm).  Most of the methylated regions in the three germ layers and in the three adult somatic tissues are shared in common.  This commonly methylated gene set is enriched in germ cell associated genes that are generally transcriptionally inactive in somatic cells.  We also compared DNA methylation patterns with global mapping of histone H3 lysine 4/27 trimethylation, and found that gain of DNA methylation correlates with loss of histone H3 lysine 4 trimethylation.  Taken together, our findings indicate that differentiation from ES cells to the three germ layers is accompanied by an increase in the number of commonly methylated DNA regions and that these tissue-specific alterations are present for only a small number of genes.  Our findings indicate that DNA methylation at the proximal promoter regions of commonly methylated genes act as an irreversible mark which fixes somatic lineage by repressing transcription of germ cell specific genes.

overall_design: Expression profiling of SK7 ES cells, SK7 derived-Ectoderm, - Endoderm, and -Paraxial mesoderm, and brain, liver, skeletal muscle tissues from ICR mouse.

first: Genta

last: Nagae

first: Nobuaki

last: Shiraki

first: Takanori

last: Fujita

first: Noriko

last: Sato

first: Shumpei

last: Ishikawa

first: Shoen

last: Kume

first: Hiroyuki

last: Aburatani


title: DNA methylation profiling of embryonic stem cell differentiation into the three germ layers

type: Methylation profiling by genome tiling array


title: gene expression profile after GGPPS deletion in sertoli cell

status: Public on Feb 13 2012

city: Nanjing

first: Xiu-Xing

last: Wang

state: Jiangsu

address: #22 Hankou Road

department: MOE Key Laboratory of Model Animals for Disease Study, Model Animal Research Center and the School of Medicine

institute: Nanjing University

summary:
GGPPS was the key enzyme of mevalonate metabolic pathway which was used to  synthesize the geranylgeranyl pyrophosphate (GGPP). When we deletion the GGPPS in the sertoli cell and  the germ cell loss were found .
We used microarrays to detail the global programme of gene expression after GGPPS deletion in sertoli cell and identified 1623 gene expression level change more than 2 times.

overall_design: Primary sertoli cells from 3 days old of control and KO mice for RNA extraction and hybridization on Affymetrix microarrays, every group primare sertoli cell were from  more than 30 mice.

first: Chao-Jun

last: Li


title: Detailed transcriptomics analysis of the effect of dietary fatty acids on gene regulation in the murine heart.

first: Guido

last: Hooiveld

summary: Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid.  Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPARα−/− mice to allow exploration of the specific contribution of PPARα. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPARα agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPARα-dependent manner, emphasizing the importance of PPARα in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPARα had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPARα.

overall_design: To study the transcriptional effects of specific fatty acids in the intact heart, wild type and PPARα−/− mice were given a single oral dose of 4 synthetic triglycerides composed of one single fatty acid, as well as of the synthetic PPARα agonist Wy14,643. Hearts were collected 6h after gavag and used for whole genome gene expression profiling.

first: Anastasia

last: Georgiadi

first: Mark

last: Boekschoten

first: Michael

last: Muller

first: Sander

last: Kersten


title: Expression data from ZMYM2-FGFR1-induced T-cell lymphomas in a mouse model

status: Public on Feb 14 2012

city: Augusta

first: Mingqiang

last: Ren

state: GA

address: 1120 15th Street

department: Cancer Center

institute: Georgia Regents University

summary:
The ZMYM2-FGFR1 (formerly known as ZNF198-FGFR1) fusion kinase induces stem cell leukemia-lymphoma syndrome (SCLL), a hematological malignancy characterized by rapid transformation to acute myeloid leukemia and T-lymphoblastic lymphoma.
We previously developed a mouse model of ZMYM2-FGFR1 (Ren et al. 2009, Blood). To further investigate mechanisms of oncogenesis and progression, we undertook a global gene expression analysis of leukemic T-cells from the animal model compared with Thy1+DP+ (CD4+CD8+) cells isolated from normal Balb/c thymuses, as well as lukemic stem cells (LSK, GFP+Lin-Sca-1+c-kit+ cells) sorted from the leukemic mice versus hematopoietic stem cells (HSC, Lin-Sca-1+c-kit+ cells) sorted from normal BALB/c bone marrow cells. We found high expressions of Notch1 and its downstream target genes in T-cell lymphomas that arise in a murine model of ZMYM2-FGFR1 SCLL. Our functional studies demonstrate the importance of Notch signaling in the etiology of SCLL and suggest that targeting this pathway could provide a novel strategy for molecular therapies to treat SCLL patients.

overall_design: RNA was isolated from HSC (Lin-Sca-1+c-kit+) sorted from normal BALB/c bone marrow cells and lukemic stem cells  (LSK, GFP+ Lin-Sca-1+c-kit+ cells) sorted from the leukemic mice bone marrow or spleen cells. To minimize biological variability, each HSC sorting experiment used BM cells from 5 normal female Balb/c. LSC were obtained from BM or spleen cells from 2-3 leukemic mice. Gene expression profiles of T-lymphoma and Thy1+DP+ (CD4+CD8+) cells were obtained from three independently sorted Thy1+DP+ cell samples (each sample was derived from thymuses from 3 normal Balb/c mice). The T-lymphoma samples were derived from third serial transplanted disease mice, where >90% of cells were GFP+Thy1+DP+. To investigate whether the sorting process influenced gene expression, one T-lymphoma sample was sorted for GFP+Thy1+DP+ cells. RNA was amplified using a GeneChip Two-Cycle Target Labeling and Control Reagents kit (Affymetrix), and cRNA was hybridized to the Affymetrix Mouse430 2.0 arrays.

first: Ming

middle: Q

first: John

middle: K

last: Cowell


title: miRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes

status: Public on Feb 10 2012

city: Basel

first: Morgane

last: RAVON

address: Grenzacherstrasse 124

country: Switzerland

institute: Hoffmann-La Roche

summary: To gain insight into the molecular regulation of human heart development, a detailed comparison of the mRNA and miRNA transcriptomes across differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes and biopsies from fetal, adult, and hypertensive human hearts was performed. Gene ontology analysis of the mRNA expression levels of the hiPSCs differentiating into cardiomyocytes revealed 3 distinct groups of genes: pluripotent specific, transitional cardiac specification, and mature cardiomyocyte specific. Hierarchical clustering of the mRNA data revealed that the transcriptome of hiPSC cardiomyocytes largely stabilizes 20 days after initiation of differentiation. Nevertheless, analysis of cells continuously cultured for 120 days indicated that the cardiomyocytes continued to mature toward a more adult-like gene expression pattern. Analysis of cardiomyocyte-specific miRNAs (miR-1, miR-133a/b, and miR-208a/b) revealed a miRNA pattern indicative of stem cell to cardiomyocyte specification. A biostatistitical approach integrated the miRNA and mRNA expression profiles revealing a cardiomyocyte differentiation miRNA network and identified putative mRNAs targeted by multiple miRNAs. Together, these data reveal the miRNA network in human heart development and support the notion that overlapping miRNA networks re-enforce transcriptional control during developmental specification.

overall_design: miRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes (days 0-120)


title: Comparison of mRNA expression profiling of differentiating human-induced pluripotent stem cell (hiPSC)–derived cardiomyocytes, biopsies from fetal, adult and hypertensive human hearts and primary cardiomyocytes


title: Characterisation of early thymic progenitors and thymus seeding progenitors

status: Public on Feb 19 2012

city: Oxford

first: Sten Eirik

last: Jacobsen

address: Headington

department: Weatherall Institute

institute: University of Oxford

summary: Gene expression analysis of early thymic progenitors and thymus seeding progenitors

overall_design: Eight distinct populations were analysed, each with between 2 and 6 biological replicates.

first: Sten

middle: E

first: Sidinh

last: Luc

first: Iain

middle: C

last: Macaulay


title: Correlation between gene expression responses to FUS, EWS, and TAF15 reduction and the stress granule sequestering capacity

status: Public on Feb 07 2012

city: aarhus

first: Yonglun

last: Luo

address: Wilhelm Meyers Allé 4

institute: Aarhus University

summary: Analysis of differentially expressed genes after siRNA mediated knock-down of the FET-family of proteins; the FUS, EWS, and TAF15 proteins. The FET-proteins are thought to function as transcription factors, and this hypothesis is tested in the present study. Results provide important information of the genes which expression are controlled by the FET-family of proteins.

overall_design: Total RNA obtained HEK293-cells transfected with siRNA targeted against the FUS, EWS, or TAF15 mRNA, or a combination of all three of them. Control cells are transfected with an equal amount of unspecific siRNA without known targets.

first: Jenny

last: Blechingberg

first: Anders

last: Nielsen


title: Expression data from Bmi1-null common myeloid progenitor (CMP)

status: Public on Feb 08 2012

city: Chiba

first: ATSUSHI

last: IWAMA

address: 1-8-1 Inohana, Chuo-ku

department: Department of Cellular and Molecular Medicine

institute: Graduate School of Medicine, Chiba University

summary: Bmi1 is a component of polycomb repressive complex 1 and its role in the inheritance of the stemness of adult somatic stem cells has been well characterized.  Bmi1 maintains the self-renewal capacity of adult stem cells, at least partially, by repressing the Ink4a/Arf locus that encodes a cyclin-dependent kinase inhibitor, p16Ink4a, and a tumor suppressor, p19Arf 14.  Deletion of both Ink4a and Arf in Bmi1-deficient mice substantially restored the defective self-renewal capacity of HSCs and neural stem cells.

overall_design: Purified CMP from BM of recipient mice repopulated with wild-type, Ink4a-/-Arf-/-, and  Bmi1-/- Ink4a-/-Arf-/- BM cells were subjected to RNA extraction and hybridization on Affymetrix microarrays.

first: Atsushi

last: Iwama

first: Hideyuki

last: Oguro

first: Hitoshi

last: Ichikawa


title: CDDP treatment of U2OS cells with NCOR and SMRT knock-down

status: Public on Feb 06 2012

city: La Jolla

first: Claudio

last: Scafoglio

state: CA

address: 9500 Gilman drive, CMM-W room 345, MC0648

institute: University of California san Diego

summary: We detected an interaction between checkpoint kinase Chk2 and some members of the NCOR/SMRT co-repressor complex. In order to study the role of gene repression in the checkpoint response to DNA damage, we performed RNA profiling in NCOR or SMRT knockdown cells after treztment with cisplatin.

overall_design: U2OS cells were transfected with siRNAs for NCOR or SMRT, grown for 2 days in complete medium, and then treated with 100 microM cisplatin (CDDP) for 6h. Biological duplicates were used for RNa profiling

first: Anna

last: Krones

first: Kenneth

last: Ohgi

first: Marcus

last: Smolka

first: Huilin

last: Zhou

first: Michael

last: Rosenfeld


title: Search for a gene-expression signature of breast cancer local recurrence in young women

status: Public on Feb 04 2012

city: Paris Cedex 05

first: Nicolas

last: Servant

address: 26 rue d'ulm

country: France

institute: Institut Curie

summary:
Kreike et al, have constructed a gene-expression (GE) profile predictive for local recurrence (LR) after breast-conserving treatment (BCT) from a series of 165 patients .
This study aimed to test this signature both internally (cross-platform) and externally on a independent series and to further explore the search for a GE signature of breast cancer LR in young women.

overall_design: The transcriptome of 343 primary breast cancer carcinoma were analyzed using Illumina HumanWG-6_v3 Arrays.

first: Marc

last: Bollet

first: Hans

last: Halfwerk

first: Kevin

last: Bleakley

first: Bas

last: Kreike

first: Laurent

last: Jacob

first: Daoud

last: Sie

first: Ron

last: Kerkhoven

first: Philippe

last: Hupé

first: Rim

last: Hadhri

first: Alain

last: Fourquet

first: Harry

last: Bartelink

first: Emmanuel

last: Barillot

first: Brigitte

last: Sigal-Zafrani

middle: J

last: van de Vijver


title: Genome-wide expression analysis in Down syndrome: insight into immunodeficiency

city: Shanghai

first: Chong

last: Li

address: Bldg.1,No.250 Bi Bo Rd.,Shanghai

institute: Chineses National Human Genome Center at Shanghai

summary: Down syndrome (DS) is caused by triplication of Human chromosome 21 (Hsa21) and associated with an array of deleterious phenotypes, including mental retardation, heart defects and immunodeficiency. Genome-wide expression patterns of uncultured peripheral blood cells are useful to understanding of DS-associated immune dysfunction. We used a Human Exon microarray to characterize gene expression in uncultured peripheral blood cells derived from DS individuals and age-matched controls from two age groups: neonate (N) and child (C). A total of 174 transcript clusters (gene-level) with eight located on Hsa21 in N group and 383 transcript clusters including 56 on Hsa21 in C group were significantly dysregulated in DS individuals. Microarray data were validated by quantitative polymerase chain reaction. Functional analysis revealed that the dysregulated genes in DS were significantly enriched in two and six KEGG pathways in N and C group, respectively. These pathways included leukocyte trans-endothelial migration, B cell receptor signaling pathway and primary immunodeficiency, etc., which causally implicated dysfunctional immunity in DS. Our results provided a comprehensive picture of gene expression patterns in DS at the two developmental stages and pointed towards candidate genes and molecular pathways potentially associated with the immune dysfunction in DS.

overall_design: All 37 samples, including 15 DS patients and 22 control individuals were analysized and divided into two age-matched groups: N group (5 DS versus 7 control individuals, age: 3 days to 38 days) and C group (10 DS versus 15 control individuals, age: 1 year to 13 years). N group includes DS (D11-D15) and Control (C16-C22), and C group includes DS (D1-D10) and Control (C1-C15).

first: Lei

last: Jin

first: Yun

last: Bai

first: Qimin

last: Chen

first: Lijun

last: Fu

first: Minjun

last: Yang

first: Huasheng

last: Xiao

first: Guoping

last: Zhao

first: Shengyue

last: Wang


title: Skeletal muscle PGC-1a mediates mitochondrial, but not metabolic, changes during calorie restriction.

city: Boston

first: Marcia

last: Haigis

address: 77 Ave Louis Pasteur

institute: Harvard Medical School

summary: Calorie restriction (CR) is a dietary intervention that extends lifespan and healthspan in a variety of organisms. CR improves mitochondrial energy production, fuel oxidation and reactive oxygen species scavenging in skeletal muscle and other tissues, and these processes are thought to be critical to the benefits of CR. PGC-1a is a transcriptional coactivator that regulates mitochondrial function and is induced by CR. Consequently, many of the mitochondrial and metabolic benefits of CR are attributed to increased PGC-1a activity. To test this model for the first time, we examined the metabolic and mitochondrial response to CR in mice lacking skeletal muscle PGC-1a (MKO). Surprisingly, MKO mice demonstrated a normal improvement in glucose homeostasis in response to CR, indicating that skeletal muscle PGC-1a is dispensable for the whole-body benefits of CR. In contrast, gene expression profiling and electron microscopy demonstrated that PGC-1a is required for the full CR-induced increases in mitochondrial gene expression and mitochondrial density in skeletal muscle. These results demonstrate that PGC-1a is a major regulator of the mitochondrial response to CR in skeletal muscle, but surprisingly show that neither PGC-1a nor mitochondrial biogenesis in skeletal muscle are required for the metabolic benefits of CR.

overall_design: Control (FLOX) and PGC-1a skeletal muscle specific knock out (MKO) mice were placed on a control diet [C] or a calorie restriction diet [CR] for 12 weeks. RNA was isolated from TA/EDL muscles for microarray analysis. The following numbers of mice were analyzed from each group: C FLOX: n = 6; C MKO: n = 7; CR FLOX: n = 6; CR MKO: n = 7. Mice were mixed C57/BL6 and 129 background.


title: Gene expression profiling of Myf5-Cre;Smad4flox/flox mouse models of tongue development

status: Public on Feb 03 2012

city: Los Angeles

first: Joseph

middle: Gerard

last: Hacia

address: 2250 Alcazar Street, IGM 261

department: Biochemistry and Molecular Biology

institute: University of Southern California

summary: We investigated Smad4-mediated TGF-beta signaling in the development of occipital somite-derived myogenic progenitors during tongue morphogenesis by comparing the transcriptomes of tongue derived from Myf5-Cre;Smad4flox/flox mutant and Myf5-Cre;Smad4flox/+ control mice at day E13.5. Based on gene expression profiles and functional studies, we elucidated the influences Smad4 activity and TGF-beta signaling have on the gene expression profiles underlying tongue development. The data are consistent with the hypothesis that TGF-beta-Smad4-FGF6 signaling cascade plays a crucial role in myogenic cell fate determination and lineage progression during tongue myogenesis.

overall_design: We obtained RNA samples from tongue tissues of mutant and control mouse embryos (C57BL/6J) at day E13.5 RNA and subjected them to analysis on Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.

first: D

last: Han

first: Y

last: Chai

first: J


title: Systems approach identifies HIPK2 as a critical regulator of kidney tubulointerstitial fibrosis

status: Public on Feb 01 2012

city: New York

first: Avi

last: Ma'ayan

state: NY

address: One Gustave L. Levy Place Box 1215

department: Pharmacology and Systems Therapeutics

institute: Mount Sinai School of Medicine

summary:
We used an integrated computational/experimental systems biology approach to identify upstream protein kinases that regulate gene expression changes in kidneys of HIV-1 transgenic mice (Tg26), which have significant tubulo-interstitial fibrosis (TIF) and glomerulosclerosis (GS). We identified the homeo-domain interacting protein kinase 2 (HIPK2) as a key regulator of TIF and GS. HIPK2 was upregulated in kidneys of Tg26 and patients with various kidney diseases. HIV infection increased the protein level of HIPK2 by promoting oxidative stress, which inhibited Siah1-mediated proteasomal degradation of HIPK2.
The data contain two sets: kidney corticies from WT and Tg26 mice and HEK293 transfected with HIPK2, HIPK2-DN and wild type.

overall_design: Gene expression comparison between kidney cortecies of Tg26 HIV mouse model and wild type. Gene expression comparison between 293 HEK cells with HIPK-DN, HIPK-KO and normal.

first: John

last: He


title: All-iPS cell mice generated from terminally differentiated B cells

city: Charlestown

first: Toshihiro

last: Shioda

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

department: Center for Cancer Research

institute: MGH Cancer Center

summary: The generation of induced pluripotent stem cells (iPSCs) often results in aberrant silencing of the imprinted Dlk1-Dio3 gene cluster, which compromises their ability to generate entirely iPSC-derived mice (“all-iPSC mice”). Here, we show that reprogramming in the presence of ascorbic acid attenuates hypermethylation of Dlk1-Dio3 by enabling a chromatin configuration at its imprint control region that interferes with abnormal binding of the DNA methyltransferase Dnmt3a. This approach allowed us to generate adult all-iPSC mice from mature B cells, which have thus far failed to support the development of exclusively iPSC-derived postnatal mice. Our data demonstrate that factor-mediated reprogramming can endow a defined, terminally differentiated cell type with a developmental potential equivalent to that of embryonic stem cells. More generally, these findings indicate that the choice of culture conditions used for transcription factor-mediated reprogramming can strongly influence the epigenetic and biological properties of resultant iPSCs.

overall_design:
This series consists of quadruplicated mRNA expression microarray data (Affymetrix mouse 430_2 3'-IVT array) for iPS cells derived from MEF cells under cell culture conditions with or without ascorbic acid supplementation.

iPS cells were generated from MEFs of the Col-OKSM reprogrammable mice. In the presence of doxycycline, the reprogramming transcription factors Oct4, Sox2, Klf4, and cMyc were induced in MEFs to derivate iPS cells. Total RNA was isolated from iPS cells derivated in the presence or absence of ascorbic acid in culture medium.

first: Matthias

last: Stadtfeld

first: Effie

last: Apostolou

first: Francesco

last: Ferrari

first: Jiho

last: Choi

first: Ryan

middle: M

last: Walsh

first: Taiping

first: Sang

middle: Y

last: Kim

first: Tim

last: Bestor

first: Toshi

first: Peter

last: Park

first: Konrad

last: Hochedlinger


title: Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects

status: Public on Jan 26 2012

city: San Diego

first: Tiziano

last: Pramparo

address: 3611 Valley Centre Drive

department: R&D

institute: Travere

summary:
Proper cortical development relies on the balance of neuronal migration and proliferation. We investigated the gene expression differences of mouse knock-outs for Lissencephaly in humans.
Our analysis suggests that gene expression and pathway analysis in mouse models of a similar disorder or within a common pathway can be used to define novel candidates for related human diseases.

overall_design: We investigated the developing brain of four mutants and wild-type mice using expression microarrays, bioinformatic analyses, and in vivo/in vitro experiments to address whether mutations in different members of the LIS1 neuronal migration complex lead to similar and/or distinct global gene expression alterations.

first: Anthony

last: Wynsha-Boris


title: mRNA expression profiling in mouse bronchoalveolar stem cells (BASC)

city: Rochester

first: Jie

last: Dong

state: MN

address: 200 1st SW

department: Thoracic Surgery

institute: Mayo Clinic

summary: We performed miRNA and mRNA profiling in BASC cells and c-Myc depleted BASC cells. We built potential miRNA-mRNA interaction networks specific to c-Myc regulation in BASCs

overall_design: Replicated profilling for both BASC cells and c-Myc depleted BASC cells.

first: Dennis

middle: A

last: Wigle


title: mRNA and miRNA expression profiling in mouse bronchoalveolar stem cells (BASC)

type:
Expression profiling by array
Other

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

overall_design: Refer to individual Series


title: Regulatory T cells

status: Public on Jan 18 2012

first: Piotr

last: Kraj

department: Centr. for Biotech. and Gen. Medicine

institute: Medical College of Georgia

summary: Induced and activated regulatory CD4+ Foxp3+ cells compared

overall_design: Conventional naive CD4+ T cells were sorted and converted in vitro into adaptive Treg cells, activated Treg cells were generated in vitro from sorted Foxp3GFP+ cells


title: The eIF2 kinase PERK and the integrated stress response facilitate activation of ATF6 during endoplasmic reticulum stress

status: Public on Jan 20 2012

city: Indianapolis

first: Ron

last: Wek

state: IN

address: 635 Barnhill Dr. MS4065

department: Biochemistry & Molecular Biology

institute: Indiana University School of Medicine

summary: Disruptions of the endoplasmic reticulum (ER) that perturb protein folding cause ER stress and elicit an unfolded protein response (UPR) that involves translational and transcriptional changes in gene expression aimed at expanding the ER processing capacity and alleviating cellular injury. Three ER stress sensors PERK, ATF6, and IRE1 implement the UPR.  PERK phosphorylation of eIF2 during ER stress represses protein synthesis, which prevents further influx of ER client proteins, along with preferential translation of ATF4, a transcription activator of the integrated stress response.  In this study we show that the PERK/eIF2α~P/ATF4 pathway is required not only for translational control, but also activation of ATF6 and its target genes. The PERK pathway facilitates both the synthesis of ATF6 and trafficking of ATF6 from the ER to the Golgi for intramembrane proteolysis and activation of ATF6.  As a consequence, liver-specific depletion of PERK significantly reduces both the translational and transcriptional phases of the UPR, leading to reduced protein chaperone expression, disruptions of lipid metabolism, and enhanced apoptosis.  These findings show that the regulatory networks of the UPR are fully integrated, and helps explain the diverse pathologies associated with loss of PERK.

overall_design:
14 gene expression arrays, 3 WT control arrays; 3 lsPERK control arrays; 4 WT Treated arrays; 4 lsPERK treated arrays.
Comparison of gene expression profiles for treated vs control in wildtype and knock-out.

first: Brian

middle: F

last: Teske

first: Sheree

first: Jeanette

middle: N

last: McClintick

first: Tracy

middle: G

last: Anthony

first: Ronald


title: Genome unstable murine prostate cancers acquire genomic aberrations and bone metastatic features of the human disease

status: Public on Jan 21 2012

first: Zhihu

last: Ding

address: 44 Binney Street

department: Medical Oncology

institute: Dana-Farber Cancer Institute

type: Genome variation profiling by genome tiling array

summary: Gene copy numbers of prostate tumors of G3 and G4 generations of LSL-mTert PB-Pten/p53 mouse model

overall_design: Prostate tumors were developed in G3 and G4 generations of LSL-mTert PB-Pten/p53 mice. These tumors were profiled with affy and aCGH. We used affy gene expression to correlate with the copy number alterations in the mouse prostate tumors.

first: Chang-Jiun

last: Wu


title: Expression profiling analysis of differentiating human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes

first: Morgane

last: RAVON

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


title: Analysis of cellular responsive nuclear/cytoplasmic mRNA distribution to viral virulence factor and dihydroorotate dehydrogenase (DHODH) inhibition

status: Public on Jan 17 2012

city: Dallas

first: liang

last: zhang

state: Texas

address: 5323 harry hines blvd k2.202

institute: utsw

first: Liang

last: Zhang

first: Beatriz

last: Fontoura


title: Genome-wide analysis of gene expression by compound 1 treatment [HBEC_3h]

summary:
Analysis of cellular response to DHODH inhibition at gene expression level.
The NS1 protein of influenza virus is a major virulence factor essential for virus replication as it re-directs the host cell to promote viral protein expression. NS1 inhibits cellular mRNA processing and export, down-regulating host gene expression and enhancing viral gene expression. We report here the identification of a non-toxic quinoline carboxylic acid that reverts the inhibition of mRNA nuclear export by NS1, in the absence or presence of virus. This quinoline carboxylic acid directly inhibited dihydroorotate dehydrogenase (DHODH), a host enzyme required for *de novo* pyrimidine biosynthesis, and partially reduced pyrimidine levels. This effect induced NXF1 expression, which promoted mRNA nuclear export in the presence of NS1. The release of NS1-mediated mRNA export block by DHODH inhibition also occurred in the presence of VSV M protein, another viral inhibitor of mRNA export. This reversal of mRNA export block allowed expression of antiviral factors. Thus, pyrimidines play a necessary role in the inhibition of mRNA nuclear export by virulence factors.

overall_design: Total RNA obtained from HBEC cells subjected to 3 hours compound 1 treatment compared to DMSO treatment.


title: Expression data from collecting lymphatic vessels

status: Public on Jan 15 2012

city: Melbourne

first: tara

last: karnezis

address: St.Andrews place

institute: Peter macallum cancer center

summary:
Lymphogenous metastasis is an important event in the progression of many human cancers, and is associated with expression of vascular endothelial growth factor-D (VEGF-D). Changes to the lymphatic vasculature can occur during metastasis, and may aid metastatic spread. We investigated the effect of tumour derived VEGFD on the endothelium of the collecting lymphatic vessels draining primary tumors.
We used microarrays to detail the changes in gene expression in the collecting lymphatic endothelium of mice with 293EBNA xenografts compared to 293EBNA xenografts overexpressing VEGFD.

overall_design: Mice were injected with 293EBNA cells (transfected with either empty APEX vector, or vector containing VEGFD) and tumours were allowed to grow to size. Mice were sacrificed and collecting lymphatic vessels were dissected. The endothelial cell population was isolated and RNA was extracted and hybridized on Affymetrix microarrays.

first: Tara

last: Karnezis

first: Steven

last: Stacker


title: Direct Recruitment of Polycomb Repressive Complex 1 (PRC1) to Chromatin by Core Binding Transcription Factors (microarray)

city: Cambridge

first: Tali

last: Mazor

address: 77 Massachusetts Ave

institute: MIT

summary: Polycomb repressive complexes (PRCs) play key roles in developmental epigenetic regulation. Yet the mechanisms that target PRCs to specific loci in mammalian cells remain incompletely understood. In this study, we show that Bmi1, a core component of Polycomb Repressive Complex 1 (PRC1), binds directly to the Runx1/CBFbeta transcription factor complex. Genome-wide studies in megakaryocytic cells demonstrate considerable chromatin occupancy overlap between the PRC1 core component Ring1b and Runx1/CBFbeta and functional regulation of a significant fraction of commonly bound genes. Bmi1/Ring1b and Runx1/CBFbeta deficiency generate partial phenocopies of one another in vivo. We also show that Ring1b occupies key Runx1 binding sites in primary murine thymocytes and that this occurs via Polycomb Repressive Complex 2 (PRC2) independent mechanisms. Genetic depletion of Runx1 results in reduced Ring1b binding at these sites in vivo. These findings provide evidence for site-specific PRC1 chromatin recruitment by core binding transcription factors in mammalian cells.

overall_design: shRNA mediated knockdown of CBFb, Ring1b and control in biological triplicate

first: Ming

last: Yu

first: Hui

last: Huang

first: Hsuan-Ting

first: Katie

middle: L

last: Kathrein

first: Andrew

last: Woo

first: Candace

middle: R

last: Chouinard

first: Adam

last: Labadorf

first: Thomas

last: Akie

first: Tyler

middle: B

last: Moran

first: Huafeng

last: Xie

first: Sima

last: Zacharek

first: Ichiro

last: Taniuchi

first: Robert

last: Roeder

first: Carla

last: Kim

first: Leonard

middle: I

last: Zon

first: Ernest

last: Fraenkel

first: Alan

last: Cantor


title: EVI1 and AP1 Interact to Transcriptionally Regulate a Feed-Forward Loop Important for Cancer Cell Proliferation and Adhesion

city: Singapore

first: Justin

middle: Jeyakani

last: Joseph Gnanakkan

state: Singapore

address: 60, Biopolis street

department: Computational and Systems Biology

country: Singapore

institute: Genome Institute of Singapore