title: Altered gene expression in the lower expiratory tract of Car6-/- mice

status: Public on Oct 07 2015

city: Tampere

first: Maarit

middle: Susanna

last: Patrikainen

address: Medisiinarinkatu 3

department: School of Medicine/Anatomy

institute: University of Tampere

summary:
In order to explore the functions of carbonic anhydrase VI (CA VI) more fully, we examined the transcriptomic responses to CA VI deficiency in the trachea, and lung of Car6-/- mice by cDNA microarray. 44 and 2 genes were up- or down-regulated in the above-mentioned tissues of Car6-/- mice, respectively. The functional clustering of differentially expressed genes revealed a number of altered biological processes. In the trachea, the affected biological pathways included metabolic process, biological regulation, single-organism process, and immune response in mucosal-associated lymphoid tissue.
Trachea, and lung samples were collected from eight wild-type and six Car6-/- male mice, respectively, at the age of two months. Total RNAs were purified and used for cDNA microarray.

overall_design: 32 samples, including 4 replicates.

first: Pei-wen

last: Pan

first: Seppo

last: Parkkila


title: Sex hormones establish a reserve pool of adult muscle stem cells at puberty

status: Public on Sep 01 2015

city: Rockville

first: Daekwan

last: Seo

state: MARYLAND

address: 1330 Piccard Dr., Ste 103

department: Bioinformatics

country: USA

institute: Psomagen Inc

summary: Quiescent satellite cells, also known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle upon injury throughout life. Although they mainly originate from multipotent stem/progenitors of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb-1 (Mib1) expression in myofibers at puberty, which activates Notch signaling in cycling juvenile satellite cells and causes them to be converted into quiescent adult satellite cells. Myofibers lacking Mib1 failed to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Genetic and inhibitor studies revealed that the hypothalamic-pituitary-gonadal axis drives Mib1 expression in the myofiber niche. Our data show how sex hormones establish quiescent adult satellite cell populations by regulating the myofiber niche at puberty.

overall_design: Microarray analysis of Veh or DHT-injected 10-day-old mice s.c. injected with Veh or DHT. TA muscles were isolated 24 h after the injection.

first: Ji-hoon

last: Kim

first: Young-Yun

last: Kong


title: Transriptome analysis of Hi-Myc prostate tumors after castration and antiandrogen treatment

status: Public on Oct 01 2015

city: New York

first: Yu

last: Chen

state: NY

address: 1275 York Ave, Box 20

department: Human Oncology and Pathogenesis Program

institute: Memorial Sloan Kettering Cancer Center

summary: Transriptome analysis of prostate tumors from Hi-Myc mouse prostates 3 days after castration or treatment with bicalutamide or enzalutamide

overall_design: 12 month old Hi-Myc mice were surgically castrated or treated with vehicle or bicalutamide or enzalutamide for 3 days. Mice tissue was analyzed

first: Brett

middle: S

last: Carver

first: Charles

middle: L

last: Sawyers

first: Deyou

last: Zheng


title: The Ubiquitin Ligase Siah2 Regulates Obesity-induced Adipose Tissue Inflammation

status: Public on Sep 29 2015

city: Baton Rouge

first: Elizabeth

last: Floyd

state: Louisiana

address: 6400 Perkins Road

institute: Pennington Biomedical Research Center

summary: Chronic, low-grade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Although ubiquitin ligases are essential regulators of inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored.  In this study, we found that the ubiquitin ligase Siah2 is a central factor in obesity-related adipose tissue inflammation. When challenged with chronic excess energy intake, Siah2-null mice become obese with enlarged adipocytes, but do not develop obesity-induced insulin resistance.  Proinflammatory gene expression is substantially reduced in the Siah2-null epididymal adipose tissue of the obese Siah2KO mice.

overall_design: Twelve samples from four groups: WT low fat diet (LFD), WT high fat diet (LFD), Siah2KO LFD, Siah2KO HFD. There are three replicates for each group. For the replicates, equal amounts of RNA from each animal was combined into 3 pools/group for the four groups. The WT LFD, WT HFD and Siah2KO LFD groups each had 10 animals that were combined into 3, 3, or 4 animals/pool.  The Siah2KO HFD group had 8 animals that were combined into 3,3, and 2 animals/pool.

first: Gail

last: Kilroy

first: Lauren

middle: E

last: Carter

first: Susan

last: Newman

first: Sujoy

last: Ghosh


title: Gene expression pattern of pulmonary CD11c+ cells from middle-aged and young mice.

status: Public on Aug 11 2015

city: Iowa City

first: Thomas

middle: B

last: Bair

state: IA

address: 335 EMRB

institute: University of Iowa

summary: Analysis of function of CD11c+ cells from middle-aged and young mice at gene level. This experiment provided insight into the different genes that plays roles in inflammation, immune response and mainly arachidonic acid cascade that are differentiall expressed in CD11c+ cells from middle aged and young mice.

overall_design: Total RNA was isolated from pulmonary CD11c cells (separated using magnetic beads) from middle-aged and young mice

first: Rahul

last: Vijay

first: Stanley

last: Perlman


title: Expression analysis of KHR and KHR-NICD oral tumors

status: Public on Sep 09 2015

city: Chicago

first: Michael

last: Spiotto

state: IL

department: Radiation Oncology

institute: The University of Chicago

summary: KHR-NICD oral tumors grow faster than KHR oral tumors. The hypothesis was to test for differences in gene expression between KHR and KHR-NICD oral tumors.

overall_design: Total RNA was isolated for KHR (n=6) and KHR-NICD (n=6) oral tumors. Expression profiling was performed using the Illumina MouseRef-8 v2 (GPL6885) array. Studies were conducted using tumors from FVB x C57BL/6 F1 mice.

first: Rong

last: Zhong

first: Riyue

last: Bao

first: Pieter

last: Faber

first: Mark

last: Lingen


title: Expression analyses of E12.5 embryonic brains from Nestin Cre+, Rest GTi/GTi, p53 fl/fl vs Rest GTi/GTi, p53 fl/fl littermates

status: Public on Aug 01 2015

city: Portland

first: Tamilla

last: Nechiporuk

state: OR

address: 3181 Sam Jackson Park Road

department: Vollum

institute: OHSU

summary: We use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors.  We find catastrophic DNA damage that occurs during S-phase of the cell cycle, with consequences including abnormal chromosome separation, apoptosis, and smaller brains. Further support for persistent effects is the latent appearance of proneural glioblastomas in adult mice also lacking the tumor suppressor, p53.  A Rest deficient mouse line generated previously, using a conventional gene targeting approach, does not exhibit these phenotypes, likely due to a remaining C terminal peptide that still binds chromatin and recruits REST chromatin modifiers.Our results indicate that REST-mediated chromatin remodeling is required for proper S-phase dynamics, prior to its well-established role in relieving repression of neuronal genes at terminal differentiation.

overall_design: extract RNA from E12.5 brain in triplicates, compare gene expression profile between Gene Trap REST knockout mice and control littermates

first: James

last: McGann

first: Karin

last: Mullendorff

last: Floss

first: Wolfgang

last: Wurst

last: Mandel


title: microRNA expression signatures of imatinib-treated and non-treated gastrointestinal stromal tumors

city: Stockholm

first: Pinar

last: Akcakaya

address: CCK R8:04

department: Oncology-Pathology

country: Sweden

institute: Karolinska Institutet

summary: We performed microRNA expression profiling in  a series of fresh-frozen neoadjuvantly imatinib-treated and non-treated gastrointestinal stromal tumors (GIST), using a microarray approach. Significant differentially expressed microRNAs among imatinib-treated and non-treated groups were identified using SAM analysis.

overall_design: Agilent microarray platform with probes matching 903 human microRNAs was used to determine miRNA expression profiles in 34 GISTs (19 imatinib-treated and 15 non-treated). Re-analysis of GSE45901 for 17 imatinib-treated GISTs. To validate the microarray platform, the expression levels of selected microRNAs were evaluated using qRT-PCR.

last: Akçakaya

first: Katarina

last: Zeljic

first: Jan

last: Åhlen

first: Anastasia

last: Gangaev

first: Mehran

last: Ghaderi

first: Stefano

last: Caramuta

first: Erik

last: Berglund

first: Robert

last: Bränström

first: Catharina

last: Larsson

first: Weng-Onn

last: Lui


title: Insights into ulcerative colitis and ileal pouchitis from a model of stasis-induced enteric dysbiosis and genetic susceptibility

status: Public on Sep 20 2015

city: Charlottesville

first: Yong

last: Huang

state: VA

address: 1340 Jefferson Park Ave

department: Medicine

institute: University of Viginia

summary: Gut dysbiosis and host genetics are implicated as causative factors in inflammatory bowel disease, yet mechanistic insights are lacking. Longitudinal analysis of ulcerative colitis patients following total colectomy with ileal anal anastomosis (IPAA) where >50% develop pouchitis, offers a unique setting to examine cause vs. effect. To recapitulate human IPAA, we employed a mouse model of surgically-created blind self-filling (SFL) and self-emptying (SEL) ileal loops. SFL exhibit fecal stasis due to directional peristalsis motility  oriented towards away from the loop end, whereas SEL remain empty.  In wild type mice, SFL, but not SEL, develop pouch-like microbial communities without accompanying active inflammation. However, in genetically susceptible IL-10-/- deficient mice, SFL, but not SEL, exhibit severe inflammation and mucosal transcriptomes resembling human pouchitis. Germ-free IL10-/- mice conventionalized with wild type SFL, but not SEL, microbiota, develop severe colitis. These data demonstrate an essential role for fecal stasis, gut dysbiosis, and genetic susceptibility and offer insights into human pouchitis and ulcerative colitis.

overall_design:
All animal protocols were approved by IACUC at the University of Chicago. All animals were C57Bl/6 mice that were bred and housed under standard 12:12 light/dark conditions at the University of Chicago. Female mice aged 6-8 weeks were fed ad libitum gel diet 76A (Cat# 72-07-5022, Clear H20, Portland, ME) for 5-days prior to surgery to prevent obstruction at the anastomosis. Animals were anesthetized with ketamine/xylazine. Aseptic surgery was performed to resect 2.5cm of ileum 3cm proximal to the ileal-cecal value with anastomosis to the ileum using 8-0 suture (Figure 1a). The abdominal wall was closed with interrupted 4-0 silk suture and skin was closed with staples. Analgesics (betanorphine mg/kg BW) were provided post-operatively. After 5 weeks, mice were humanely euthanized. Intestinal loops were collected for RNA, protein, and histology. Loop, sham ileum, and sham colon contents were collected and snap frozen at −80°C for microbiota analysis. Human biopsies and stool samples were obtained under IRB approval and privacy protocols were followed.
Our initial work demonstrated up regulation of TLR4 signaling in the mucosa of self-filling ileal loops. We hypothesized that TLR4 may be in-part responsible for mediating the metaplasia and inflammatory responses observed. Therefore, TLR4 KO mice were used to test this hypothesis and subsequently demonstrated attenuated responses in these parameters.

first: M

middle: A

last: Ward

first: J

middle: F

last: Pierre

first: R

last: Leal

first: Y

first: Benjamin

middle: D

last: Shogan

first: S

middle: R

last: Dalal

first: C

last: Weber

first: V

last: Leone

middle: W

last: Musch

middle: C

last: Rao

first: D

middle: T

last: Rubin

first: L

last: Raffals

first: G

last: An

last: Antonopoulos

last: Sogin

first: N

last: Hyman

last: Alverdy

first: E

last: Chang


title: Effect of muscle-specific ATF4 gene knockout (ATF4 mKO) on skeletal muscle mRNA levels in aged mice.

status: Public on Sep 03 2015

first: Scott

middle: M

last: Ebert

address: 500 Newton Rd

department: Int Med

summary: For additional details see Ebert et al, Identification and Small Molecule Inhibition of an ATF4-dependent Pathway to Age-related Skeletal Muscle Weakness and Atrophy.

overall_design: Quadriceps femoris muscles were harvested from 22-month-old muscle-specfic ATF4 knockout (ATF4 mKO) mice and littermate controls.  mRNA levels in ATF4 mKO muscles were normalized to levels in littermate control muscles.

first: Christopher

last: Adams


title: Genome wide expression in liver of young adult (D90) and aged (D456) female C57/BL6 mice in F1 and F3 generations.

status: Public on Jul 24 2015

city: Southampton

first: Samuel

middle: Peter

last: Hoile

state: Hampshire

address: IDS Building, SGH

department: Human Development and Health

country: United Kingdom

institute: University of Southampton

summary: Analysis of the effect of diet and ageing in the liver at gene expression level. The hypothesis tested in the present study was that dietary energy would be associated positively with the magnitude of age-related changes in the expression of the liver transcriptome and that such effects would accumulate between generations. Results provide insight into the realtionship between diet across generations and ageing.

overall_design: Total RNA obtained from livers of D90 or D456 females in the F1 and F3 generation, following a 6 hour fast.

middle: P

first: Leonie

last: Grenfell

first: Mark

last: Hanson

first: Karen

last: Lillycrop

first: Graham

last: Burdge


title: Genomic profile of foamy and non-foamy granuloma macrophages from fat-fed ApoE null mice or control mice fed a normal diet

status: Public on Jul 23 2015

city: Bristol

first: Anita

last: Thomas

state: Bristol

address: 7th Floor, Queens Building, Bristol Royal Infirmary

department: Bristol Heart Institute

institute: University of Bristol

summary: Formation of foam cell macrophages (FCMs), which sequester extracellular modified lipids, is a key event in atherosclerosis. How lipid loading affects macrophage phenotype is controversial, with evidence suggesting either pro- or anti-inflammatory consequences. To investigate this further, we compared the transcriptomes of foamy and non-foamy macrophages (NFMs) that accumulate in the subcutaneous granulomas of fed-fat ApoE null mice and normal chow fed wild-type mice in vivo. Consistent with previous studies, LXR/RXR pathway genes were significantly over-represented among the genes up-regulated in foam cell macrophages. Unexpectedly, the hepatic fibrosis pathway, associated with platelet derived growth factor and transforming growth factor-β action, was also over-represented. Several collagen polypeptides and proteoglycan core proteins as well as connective tissue growth factor and fibrosis-related FOS and JUN transcription factors were up-regulated in foam cell macrophages. Increased expression of several of these genes was confirmed at the protein level in foam cell macrophages from subcutaneous granulomas and in atherosclerotic plaques. Moreover, phosphorylation and nuclear translocation of SMAD2, which is downstream of several transforming growth factor-β family members, was also detected in foam cell macrophages. We conclude that foam cell formation in vivo leads to a pro-fibrotic macrophage phenotype, which could contribute to plaque stability, especially in early lesions that have few vascular smooth muscle cells.

overall_design: Samples (n=4/group): Foam cell macrophages (FCM) isolated from inflammatory sponges placed in ApoE null mice fed a high-fat diet (n=4), non-foamy macrophages (NFM) isolated from inflammatory sponges placed in control mice fed a normal diet (n=4).

first: Wouter

middle: J

last: Eijgelaar

first: Mat

last: Daemen

first: Andrew

last: Newby


title: Synergism of calcium sensing receptor and vitamin D receptor mediated signaling in epidermal differentiation

status: Public on Jul 31 2015

city: San Francisco

first: Yuko

last: Oda

state: CA

address: 111N-MB 360 1700 Owens St, Suite 360

department: Endocrine Research

institute: VA Medical Center UCSF

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

overall_design: Refer to individual Series


title: Synergism of calcium sensing receptor and vitamin D receptor mediated signaling in epidermal differentiation [VDR KO]

summary: Calcium and 1,25-dihydroxyvitamin D3 (1,25D3), through the actions of their respective receptors, the Ca2+-sensing receptor (CaSR) and the vitamin D receptor (VDR), potentiate keratinocyte differentiation. VDR regulates epidermal keratinocyte proliferation and differentiation by modulating gene transcription, whereas the CaSR, a member of the family C G-protein coupled receptor, calcium mobilizes intracellular calcium and induces the formation of cell-cell junctions. 1,25D3 augments the sensitivity of the prodifferentiating actions of calcium by increasing the expression of CaSR. CaSR- and VDR-deficient keratinocytes share common characteristics such as abnormal intercellular adhesion and sphigolipid metabolism. Both CaSR and VDR are abundantly expressed in epidermal stem cell populations including CD34 expressing bulge keratinocytes in hair follicles and basal cells in interfollicular epidermis. To delineate the role of CaSR- and VDR-dependent pathways in regulating epidermal development and functions in physiological state, we generated conditional CaSR-null and VDR-null mice, where Casr and VDR gene was removed from keratinocytes. Keratinocyte-specific CaSR-null and VDR-null mice manifest distinct phenotypes. CaSR-null mice display defective epidermal permeability barrier function due to aberrant keratinocyte differentiation. VDR-null mice develop alopecia after completing the first hair follicle cycling. Concurrent ablation of CaSR and VDR genes in keratinocytes delays rate of wound repair and increases incidence of skin tumor formation to a greater extent than deletion of the CaSR or VDR alone, indicative of synergistic effects of calcium and 1,25D3 signaling. Gene expression profiles and subsequent pathway analysis on the epidermis derived from 5-day-old neonates revealed that ablation of CaSR or VDR increased expression of genes associated with cancer progression and metastasis. Deletion of VDR markedly inhibited signaling pathways that regulate hair development. Furthermore, concurrent ablation of CaSR and VDR significantly suppressed calcium, VDR, Wnt/b-catenin signaling, as well as epithelial adherence junction signaling to maintain appropriate keratinocyte adhesion. These results indicated the interplay of calcium/CaSR and 1,25D3/VDR signaling in keratinocyte proliferation and differentiation, and their importance in maintaining normal epidermal adhesion and functions.

overall_design: n=3 CON and KO (each sample contain RNA isolated from neonatal epidermis separated from 3 mice)

first: Chialing

last: Tu

first: Thai

last: Nguyen

first: Daniel

last: Bikle


title: Eosinophil-derived IL-4 promotes nematode growth in an innate context

status: Public on Jul 10 2015

city: Philadelphia

first: daniel

last: beiting

state: PA

address: 380 S. University Ave

department: Pathobiology

institute: University of Pennsylvania

summary: It has become increasingly clear in recent years that the function for eosinophils in health and disease is highly varied. Recent studies have revealed novel functions for eosinophils in metabolism and tissue regeneration. Such mechanisms have strong potential to be relevant in worm infections in which parasites rely on host metabolism for nutrients that support worm growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that normal larval growth requires IL-4 and STAT6 signaling that are intrinsic to eosinophils.  Support of growth by eosinophil-derived IL-4 occurs independently of adaptive immunity. Host gene expression in skeletal muscle was compatible with a regenerative response to invasion by newborn larvae and a shift in the source of energy in infected tissue. Furthermore, the presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, compatible with enhancement of glucose uptake and storage of glycogen by larvae that is known to occur. The results suggest that eosinophil-derived IL-4 may promote larval growth by altering nutrient metabolism in infected muscle. Our findings document a novel interaction between worms and host, in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth.

overall_design: Whole diaphragms from WT, Rag1-/-  and PHIL mice were harvested at 0, 2 and 7 days post-infection of mice with 25,000 Trichinella spiralis newborn larvae (administered retro-orbitally) and preserved in RNAlater (Qiagen). Two to three replicate mice were used for each condition.

last: Beiting

first: Judith

last: Appleton

first: Lu

last: Huang


title: Gene expression profile in Liver, skeletal muscle, brown and white adipose tissues in mice after different interventions

status: Public on Jul 14 2015

city: Lausanne

first: Marie

last: Boutant

address: EPFL Innovation Park, Bâtiment G

country: Switzerland

institute: Nestle Institute of Health Sciences

summary: SIRT1 is a NAD+-dependent protein deacetylase. SIRT1 plays key roles in metabolic regulation and adaptation. In this study, we wanted to compare gene expression profile in SIRT1 overexpressing mice to WT mice submitted to different intervention (caloric restriction and exercise training) in different tissues (liver, skeletal muscle, brown and white adipose tissues).

overall_design:
SIRT1 transgenic model has already been described (Pfluger et al., 2008). Here we used homozygote transgenic mice which had been backcrossed to C57Bl/6N background. 3 months old WT and SIRT1tg mice were fed with a low fat diet. After sacrifice, total mRNA obtained from brown adipose were used for microarray.
Caloric restriction (CR) : everyother day feeding during 3 months
Exercise training (EX) : mice were housed in running wheel cages during 10 weeks

first: Carles

last: Cantó

first: Frederic

last: Raymond

first: Sylviane

last: Metairon


title: Skin Resident Memory CD4+ T Cells Enhance Protection Against Leishmania Major Infection

status: Public on Jun 19 2015

summary: Leishmaniasis causes a significant disease burden worldwide.  Although Leishmania-infected patients become refractory to reinfection following disease resolution, effective immune protection has not yet been achieved by human vaccines.  While circulating Leishmania-specific T cells are known to play a critical role in immunity, the role of memory T cells present in peripheral tissues has not been explored. Here, we identify a population of skin-resident Leishmania-specific memory CD4+ T cells. These cells produce IFNγ, and remain resident in the skin when transplanted by skin graft onto naïve mice. They function to recruit circulating T cells to the skin in a CXCR3 dependent manner, resulting in better control of the parasites. Our findings are the first to demonstrate that CD4+ TRM cells form in response to a parasitic infection, and indicate that optimal protective immunity to Leishmania, and thus the success of a vaccine, may depend on generating both circulating and skin-resident memory T cells.

overall_design: Two conditions were analyzed.  For each condition, four mice were used, resulting in eight samples in total.

first: Phillip

last: Scott

first: Nelson

last: Glennie


title: DNA damage responses activate a multi-functional genetic program in murine bone marrow-derived macrophages

status: Public on Jul 03 2015

city: Saint Louis

first: Barry

last: Sleckman

state: MO

address: 4940 Parkview Place

department: Pathology and Immunology

institute: Washington University in St Louis

summary: DNA damage response kinase ATM regulates the genetic program of lymphocytes with phsiologically induced DNA DSBs.  In bone marrow-derived macrophages, related kinase DNAPKcs is also responsible for activating DNA damage responses after infection with Listeria monocytogenes.  Here we show that both ATM and DNA-PKcs regulate the genetic program of Listeria monocytogenes-infected macrophages.

overall_design: Two independent bone marrow-derived macrophage cultures for each genotype (LysMcre/+ and Scid: Atmc/c: LysMcre/+) were infected with Listeria monocytogenes for 24 hrs at an MOI of 5.  RNA was isolated using RNeasy (Qiagen).  Gene expression profiling was performed using Illumina MouseRef-8 expression microarrays.

first: Abigail

last: Morales


title: Transcriptome analysis of Prdm11 knockout mice after OVA challenge

status: Public on Jul 15 2015

city: Neuherberg

first: Martin

last: Irmler

state: Bayern

address: Ingolstaedter Landstrasse 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum München GmbH

summary: PRDM family members encode for progeins functionally associated with the control of cell proliferation, differentiation as well as apoptosis action in cell and tissue-specific menner. As important factors in maintenance and differentiation of human and mouse ES cells several PRDM family members were identified. Prdm11 has and outsider position within the PRDM family due to the lack of zinc-finger domains. However, a zic-finger binding motive i present and likely assue the function of protein-protein interactionl. Prdm11 was described as a candidate for tumor suppresser. However, the function of this gene is still unknown. Our study give evidence a new functional association of Prdm11 in allergic disease and asthma.

overall_design: Total RNA obtained from 1/2 lung of 4 female mice of each analysed group (widltype, wildtype challenged, mutant, mutant challenged)

first: Johannes

last: Beckers

first: Marion

last: Horsch


title: Genome-wide expression profiling analysis of a time course of differentiating adipocytes

status: Public on May 31 2015

summary: Analysis of changes on gene expression levels in differentiating adipocytes treated with differentiation medium (IBMX), insulin and dexamethasone (time points 2d-4d) as well as with maturation medium containing insulin (time points 6d - 18d)

overall_design: Total RNA isolated from adipocytes

first: Jurek

last: Adamski

first: Anna

last: Halama


title: Synergism of calcium sensing receptor and vitamin D receptor mediated signaling in epidermal differentiation [double KO]

first: Yuko

last: Oda

overall_design: n=3 CON and DKO (each sample contain RNA isolated from neonatal epidermis separated from 3 mice)

first: Chialing

last: Tu

first: Thai

last: Nguyen

first: Daniel

last: Bikle


title: Mildly compromised tetrahydrobiopterin biosynthesis mouse mutants exhibit abnormal body fat distribution and abdominal obesity

status: Public on Jun 01 2015

summary: Tetrahydrobiopterin (BH4) is an essential cofactor for several metabolic enzymes, including the aromatic amino acid hydroxylases, alkylglycerol mono-oxygenase and NO synthases. BH4 deficiency due to an autosomal recessive defect in its biosynthetic enzyme 6-pyruvoyltetrahydropterin synthase (PTPS, encoded by the PTS gene) leads to a variant form of hyperphenylalaninemia concomitant with severe deficiency of brain monoamine neurotransmitters. In contrast, augmentation of BH4 by pharmacological supplementation or stimulation of its biosynthesis is thought to correct eNOS dysfunction, to protect from (cardio) vascular disease and/or to prevent from abdominal obesity and development of the metabolic syndrome. We have previously reported that complete Pts knock-out (ko) mice die after birth (Elzaouk et al JBC 2003). Here we generated a murine Pts-knock-in (ki) allele expressing a PTPS-p.Arg15Cys mutant enzyme with low residual activity (12% of wild-type in vitro) and investigated heterozygous Pts-ko/wt, homozygous Pts-ki/ki and compound heterozygous Pts-ki/ko mutant mice. All mice were viable and, depending on the severity of the Pts alleles, exhibited up to 90% reduction of PTPS activity in liver and brain tissues concomitant with high neopterin, but neither an elevation of blood L-Phe, nor a decrease in brain monoamine neurotransmitters dopamine or serotonin. Upon a standard systemic and comprehensive phenotyping of Pts-ki/ki mice, we found alterations in energy metabolites with reduced body mass, higher fat content, lower lean mass, and increased blood glucose and cholesterol in mutant animals. Furthermore, heterozygous Pts-ko/wt and/or homozygous Pts-ki/ki mice exhibited increased body weight and elevated intra-abdominal fat tissue when fed with normal chow or high fat diet. We conclude that a reduced BH4-biosynthetic activity in mice leads to abnormal body fat distribution and abdominal obesity potentially through a mildly compromised eNOS function.

overall_design: Total RNA obtained from 4 male homozgous ki and 4 male wildtype mice


title: Cardiac LXRα protects against pathological cardiac hypertrophy and dysfunction by enhancing glucose uptake and utilization

status: Public on May 30 2015

city: Groningen

first: Herman

last: Sillje

address: Hanzeplein 1

country: Netherlands

institute: University medical center Groningen

summary: Gene profiling analysis was performed to investigate the molecular basis for the cardioprotective effect of cardiac-specific LXRα overexpression.

overall_design: Total RNA obtained from left ventricular tissue from cardiac LXRα transgenic mice (LXRα-Tg) and wild type littermates subjected to 5 weeks of either transverse aortic constriction (TAC) or sham surgery; n=3/group.

first: Megan

middle: V

last: Cannon

first: Rudolf

last: de Boer


title: Synergism of calcium sensing receptor and vitamin D receptor mediated signaling in epidermal differentiation [CaSR KO]


title: The role of miRNA in Wilms' tumorigenesis

status: Public on Jul 01 2015

city: San Antonio

first: Yidong

last: Chen

state: Texas

address: 8403 Floyd Curl Drive, MSC 7784

department: Population Health Sciences

institute: UT Health Science Center at San Antonio

summary: We show that oncogenesis in Wilms’ tumor - the most common pediatric renal cancer- is mediated by small non-coding RNAs miRNAs.Interestingly, several differentially expressed miRNAs target genes that are known to play important role in kidney development.

overall_design: miRNA profile of Wilm's tumor vs. normal kidney with two color microarray protocol

first: Manjeet

last: Rao

first: Jaffar

last: Imam


title: Vitamin D receptor (VDR) regulates epidermal stem cells and cutanous wound healing [BKO]

summary: The vitamin D receptor (VDR) regulates cell proliferation and differentiation including epidermal keratinocytes by modulating transcription of its target genes. We are investigating the role of VDR in epidermal stem cells and their progenies in the regeneration process of epidermis and hair in the skin. VDR null mice are utilized in which VDR is specifically deleted in keratin 14 (K14) expressing keratinocytes by Cre-lox strategy. The impact of VDR deletion was evaluated by comparison of VDR null mice with no cre littermate control mice. The VDR was abundantly expressed in potential epidermal stem cells including basal cells in interfollicular epidermis (IFE), and in CD34 expressing bulge keratinocytes in hair follicles. Gene expression profiles and subsequent pathway analysis of stem cell enriched keratinocyte populations revealed that the VDR deletion significantly suppressed β-catenin signaling as well as VDR signaling. The role of VDR in epidermal stem cells was studied during hair follicle cycling and wound healing processes. The epidermal stem cells were not appropriately stimulated by hair depilation, and did not reinitiate anagen in the hair follicles resulting in a failure of hair regrowth. In addition, the stem cells were not fully activated after full thickness wounds were generated in VDR null skin under a low calcium diet to suppress compensation pathways. Cell proliferation was not fully induced in potential stem cells located in both IFE and hair follicles near the wounding edges, and re-epithelialization rate was delayed in VDR null skin. Gene expression profiling of the wounded skin (3 days after injury) indicated that β-catenin signaling was not fully induced in VDR null skin comparable to that observed in β-catenin null mice.  The β-catenin target genes including Axin2 and cell cycle regulators involved in epidermal stem cell function were not induced in the edges of the wound of VDR null skin. These results demonstrated that VDR plays an essential role in hair cycling and wound healing processes through regulation of β-catenin signaling in epidermal stem cells and their progenies.

overall_design: n=3 CON and KO (each sample contain RNA isolated from wounded skins excised from 3 mice)

first: Tu

last: Chiialing


title: Regulation of the core pre-mRNA splicing machinery by MYC and PRMT5 is essential to sustain lymphomagenesis [fetal liver]

status: Public on May 19 2015

city: Singapore

first: Diana

middle: HP

last: Low

address: #03-06, 61 Biopolis Drive, Proteos

country: Singapore

institute: Institute of Molecular and Cell Biology

summary: Over-expressed MYC binds to virtually all active promoters within a cell, although with different binding affinities, and modulates gene expression, both positively and negatively. Here, we show that during lymphomagenesis in Eµ-myc transgenic mice, MYC directly up-regulates the transcription of the core snRNP assembly genes, including PRMT5, an arginine methyltransferase, that methylates Sm proteins as an early step in lymphomagenesis. This coordinated regulatory effect is direct and is critical for snRNP biogenesis, the maintenance of effective mRNA splicing and cellular viability in cycling cells, in either fibroblasts or B-cells.

overall_design: Total RNA obtained from isolated fetal livers subjected to 24 hours of OHT or EtOH (control).

first: Cheryl

last: Koh

middle: H


title: Murine study of sepsis-induced cardiac gene expression changes in vivo

status: Public on Sep 01 2015

city: Jena

first: S.

last: Lambeck

address: Erlanger Allee 101

institute: JUH

summary:
We systematically assessed the transcriptomic changes of heart biopsies of mice that had undergone polymicrobial sepsis.
Data indicate strong cardiac in vivo responses during murine sepsis affecting a large amount of pathways and categories including cytokines, mitochondria, immune system and cardiomyocytes.

overall_design: RNA from murine heart muscle tissue (n=4 for sepsis, n=4 for controls) was extracted and subjected to microarray analysis for comparison of transcriptomic responses.

first: Sandro

last: Lindig

first: Sebastian

middle: N

last: Stehr


title: Transcriptome analysis of Cox4-2 knockout mice after OVA challenge

first: Martin

last: Irmler

summary: Cytochrome c oxidase (COX) is a 13-subunit enzyme that is a key complex of the oxidative phosphorylation system of the mitochondria, which generates the vast majority of the energy of the cell.COX subunit IV is the largest nuclear-encode subunit with important regulatory functions concerning energy metabolism. COX4-2 has been knocked out. Our study indicated strong expression of Cox4-2 in lung and therefore we test this mutant line under OVA-challenge conditions expecting a new asthma mouse model.

first: Johannes

last: Beckers

first: Marion

last: Horsch


title: Transcriptional response in normal tissues in mice after 211At administration - dependency of absorbed dose, dose-rate and time

status: Public on May 01 2015

city: Gothenburg

first: Britta

last: Langen

address: Gula stråket 2B

department: Department of Radiation Physics

institute: Sahlgrenska Academy at University of Gothenburg

summary:
RNA microarray analysis of low-dose and dose rate responses versus time after i.v. administration of 211At.
Female BALB/c nude mice were intravenously injected with 1.7 kBq 211At and killed after 1 h, 6 h, or 7 d, or injected with 105 or 7.5 kBq and killed after 1 h and 6 h, respectively.
Controls were mock-treated. Kidneys, liver, lungs, and spleen were excised, flash-frozen, and stored at -80°C.
Total RNA was extracted and subjected to expression analysis using RNA microarray technology.
Enriched biological processes were categorized after cellular function based on Gene Ontology terms.

overall_design: Total RNA was isolated from fresh-frozen tissue samples. Three mice per group were used for 1.7 kBq 211At injections and controls; two mice per group for 105 and 7.5 kBq injections.

first: Nils

last: Rudqvist

first: Toshima

middle: Z

last: Parris

first: Emil

last: Schüler

first: Johan

last: Spetz

first: Khalil

last: Helou

first: Eva

last: Forssell-Aronsson


title: Nuclear receptor LRH-1/NR5A2 is required and targetable for liver endoplasmic reticulum stress resolution

status: Public on May 12 2015

city: Houston

first: Jennifer

middle: L

last: Mamrosh

state: TX

address: 1 Baylor Plaza N610

institute: Baylor College of Medicine

summary: Chronic endoplasmic reticulum (ER) stress results in toxicity that contributes to multiple human disorders. We report a stress resolution pathway initiated by the nuclear receptor LRH-1 that is independent of known unfolded protein response (UPR) pathways. Like mice lacking primary UPR components, hepatic Lrh-1-null mice cannot resolve ER stress, despite a functional UPR. In response to ER stress, LRH-1 induces expression of the kinase Plk3, which phosphorylates and activates the transcription factor ATF2. Plk3-null mice also cannot resolve ER stress, and restoring Plk3 expression in Lrh-1-null cells rescues ER stress resolution. Reduced or heightened ATF2 activity also sensitizes or desensitizes cells to ER stress, respectively. LRH-1 agonist treatment increases ER stress resistance and decreases cell death. We conclude that LRH-1 initiates a novel pathway of ER stress resolution that is independent of the UPR, yet equivalently required. Targeting LRH-1 may be beneficial in human disorders associated with chronic ER stress.

overall_design: 12 total samples. One sample represents one mouse. Three samples were analyzed from the following groups: Lrh-1 f/f (control littermates) treated with vehicle, Lrh-1 f/f treated with tunicamycin (TM; 1mg/kg BW for 24h), Lrh-1 liver-specific KO mice (LKO) treated with vehicle, and Lrh-1 LKO treated with tunicamycin.

first: David

last: Moore


title: LIN28 cooperates with Wnt signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans

status: Public on Apr 29 2015

city: Boston

first: Ho-Chou

last: Tu

state: MA - Massachusetts

address: One Blackfan Circle

department: Hematology/Oncology

institute: Boston Children's Hospital

summary: In this study, we investigated the role of LIN28 in intestinal tumor initiation and invasive progression. We generated animal models with just intestinal LIN28B overexpression, or in combination with Apcmin/+ background. The animals develop intestinal and colorectal tumors with histology ranging from adenoma to adenocarcinoma.

overall_design: total RNA isolated from mouse small intestinal tumors with LIN28B overexpression, or duodenum and colon Apcmin tumors and LIN28B;Apcmin tumors

first: George

middle: Q

last: Daley


title: Developmental LTbR synergistically activates TLR4 mediated inflammatory RelA/NF-kB response

city: New Delhi

first: Balaji

last: Banoth

state: Delhi

address: Aruna Asaf Ali Marg

department: Immunology

country: India

institute: National Institute of Immunology

summary: Developmental signals are known to modulate inflammation. How ever, the mechanistic insight that links developmental and inflammatory signaling remains elusive. In the current study, we identifya critical role of NF-kB system in mediating stimulus specific crosstalk that allows developmental LTbR signals to sustain inflammatory TLR4 induced RelA/NF-kB response and gene expression. LTbR activated non-canonical signaling targets canonical TLR4 induced, nfkb2 encoded p100 not only to deplete inhibitory IkBd/(p100)2, but also to supplement RelA:p52/NF-kB dimers. Robust crosstalk in the gut epithelial cells are important, as crosstalk-defective nfkb2-/- mice succumbed to gut infection by Citrobacter rodentium due to hypo-inflammatory responses. Finally, we present evidence for a crosstalk motif that integrates tissue microenvironment derived developmental cues to ameliorate the pathogen response.

overall_design: Total RNA from WT early passage MEFs stimulated with ligands LPS, LTbR and LPS+LTbR for 24hrs were analyzed for global gene expression levels

first: Soumen

last: Basak


title: Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

status: Public on May 14 2015

city: Los Angeles

first: Giovanni

last: Coppola

address: 1524 Gonda, 695 Charles Young Drive South

department: Psychiatry and Neurology

institute: UCLA

summary: We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin.  Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice.  Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice.  Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin.  In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS.  Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains.

overall_design: 9 strains, 4 replicates per strain, 2 conditions (naïve and axotomy) = 72 samples. 2 samples were excluded because technical outliers (AJ_AX5D_1 and AJ_NAIVE_4 excluded from the normalized data but included in the raw data)

first: T

last: Omura

first: K

first: P

last: Riva

first: A

last: Tedeschi

first: L

last: Rojas

first: J

last: Martin

first: E

middle: A

last: Huebner

first: M

last: Painter

last: Latremoliere

first: Y

last: Yin

last: Barrett

first: B

last: Singh

first: S

last: Lee

last: Crisman

first: F

last: Gao

last: Li

first: D

last: Geschwind

first: G

first: Z

last: He

last: Carmichael

middle: I

last: Benowitz

last: Costigan

first: C

last: Woolf


title: Transcription of Tnfaip3 is regulated by NF-kB and p38 via C/EBPβ in activated macrophages

status: Public on Apr 28 2015

city: Taipei

first: Mong-Hsun

last: Tsai

address: 4F, No. 81, Chang-Xing St.

department: Institute of Biotechnology

country: Taiwan

institute: National Taiwan University

summary:
Macrophages play a pivotal role in the immune system through recognition and elimination of microbial pathogens. Toll-like receptors (TLRs) on macrophages interact with microbial substances and initiate signal transduction through intracellular adapters. TLR4, which is important for the response to lipopolysaccharide (LPS), triggers downstream signaling mediators and eventually activates IkB kinase (IKK) complex and mitogen-activated protein kinases (MAPKs) such as p38. Previous reports revealed that, in addition to NF-kB, the induction of some LPS-inducible genes in macrophages required another transcription factor whose activity depends on p38. However, these transcription factors remained to be identified.
Among these genes, NF-kB and C/EBPβ, a p38 downstream transcription factor, were predicted to co-regulate genes in LPS-stimulated BMDMs. Based on the subsequent results of a chromatin immunoprecipitation assay, we demonstrated that Tnfaip3 is regulated by both NF-kB and p38-dependent C/EBPβ. These results elucidate our understanding of the tight regulation of innate immunity.

overall_design: In order to identify p38-activated transcription factors that cooperate with NF-kB in response to LPS stimulation, microarrays were used to identify genes regulated by both NF-kB and p38 using wild-type, IKK-depleted, and p38 inhibitor-treated mouse bone marrow-derived macrophages (BMDMs). In silico analysis of transcription factor binding sites was used to predict the potential synergistic transcription factors from the co-expressed genes.

first: Liang-Chuan

last: Lai

first: Ting-Yu

first: Shang-Duen

last: Wu

first: Li-Chung

last: Hsu


title: Combined MYC and TP53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease [gene expression]

status: Public on Apr 23 2015

city: Newcastle upon Tyne

first: Ed

last: Schwalbe

address: Ellison Place

department: Applied Sciences

institute: Northumbria University

summary:
We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC gene family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this molecular group died of rapidly progressive disease post-relapse. To study this genetic interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of Trp53 function in this model produced aggressive tumors that mimicked the characteristics of relapsed human tumors with combined P53–MYC dysfunction. Restoration of p53 activity, genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53–MYC interactions which emerge at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically.
There are currently no effective therapies for children with relapsed medulloblastoma. While clinical and biological features of the disease at diagnosis are increasingly well understood, biopsy is rarely performed at relapse and few biological data are available to guide more effective treatments. Here, we show that medulloblastomas develop altered biology at relapse which is predictive of disease course and cannot be detected at diagnosis. We have discovered the emergence of P53–MYC interactions at relapse, as biomarkers of clinically aggressive relapsed disease, which can be modelled and targeted therapeutically in genetically-engineered mice. These data provide clear precedent for the incorporation of biopsy at relapse into routine clinical practice, to direct palliative care and the development of improved treatment strategies.

overall_design: mouse model expression profiles from various mouse Medulloblastoma models MYCN/MYC  overexpressing with/without p53 Mutations were compared to human MB expression profiles using Non-negative Matrix Factorization projection in order to sub-type the mouse models

first: Daniel

last: Williamson


title: Role of Capicua in metabolic system

status: Public on Apr 15 2015

city: Daegue

first: Jieon

address: 333. Techno Jungang-daero Hyeongpung-myeon, Dalseong-gun

department: Chemical Engineering

country: South Korea

institute: POSTECH

summary: CIC is a HMG box-containing transcriptional repressor evolutionarily conserved from C. elegans to human. It's known to associate with various types of cancer but physiological function of CIC remain largely unknown. In this study, we characterized Cic hypomorphic (Cic-L-/-) mice and identified critical roles for of CIC in drug metabolism and bile acid homeostasis.

overall_design: Total RNA obtained from isolated liver tissue of Cic-L-/- mouse compared to liver tissue of normal mouse

first: Eunjeong

last: Kim

first: Sungjun

last: Park

first: Nahyun

last: Choi

first: Soeun

first: Jeehyun

last: Yoe

first: Hoeyune

last: Jung

first: Kyong

first: Hyojin

last: Kang

first: John

middle: D

last: Fryer

first: Huda

middle: Y

last: Zoghbi

first: Daehee

last: Hwang

first: Yoontae


title: Microarray gene expression analysis of thyroid hormone receptor in mice liver

city: Bethesda

first: Yuelin

middle: Jack

last: Zhu

state: MD

address: 9000 Rockville Pike

department: Genetics Branch, Center for Cancer Research

institute: NCI

summary: Microarray gene expression was performed on mouse livers. Gene expression profiles were studies on 3 PTU treated and 3 PTU followed by T3 treated mice.

overall_design: Comparing gene expression profiles between 3 PTU treated mice and T3 stimulated mice

first: Bob

last: Walker

first: Sheue-Yann

last: Cheng


title: Identification of the hypothalamic neuronal populations that derive from Pomc-expressing precursors

status: Public on Apr 16 2015

city: Bellaterra

first: Elisenda

last: Sanz

state: Barcelona

address: M1/113 Facultat de Medicina

department: Institut de Neurociencies

country: Spain

institute: Universitat Autonoma de Barcelona

summary: Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny of these critical hypothalamic neuronal populations is largely unknown. Here, we reveal novel cellular fates of the hypothalamic Pomc-expressing precursors by combining mouse genetics with a conditional viral ribosome-tagging approach to phenotype neurons. Our results show that the Pomc-expressing precursors differentiate into discrete neuronal subpopulations that mediate not only energy balance (POMC and AgRP) but also reproductive physiology (Kisspeptin).

overall_design: Punches containing the mediobasal hypothalamus of Pomc-Cre:RiboTag mice and Pomc-Cre mice injected with the RiboTag viral vector (AAV-DIO-RiboTag) were homogenized and incubated with anti-hemagglutin (HA) antibodies and protein A/G magnetic beads to isolate the polysome-associated mRNAS in the Pomc-derived lineage and in adult POMC neurons, respectively. To identify differentially expressed transcripts, RNA from the immunoprecipitates was extracted, amplified, labelled and hybridized to MouseRef-8 v2 expression beadchips.

first: G

middle: S

last: McKnight


title: In vitro activation of Btnl-1 transduced MODE-K cells with different stimuli

status: Public on Mar 31 2015

city: London

first: Lucie

last: Abeler-Dörner

address: Great Maze Pond

department: Immunobiology

institute: King's College London

summary: The experiment was designed to assess how intestinal epithelial cells respond to different soluble factors produced by intraepithelial lymphocytes (IEL) and how this response is altered when the epithelial cells express Btnl1.

overall_design: Total RNA of MODE-K cells transduced with Btnl1-GFP or GFP alone and stimulated with TNF+IL-1_ in comparison to medium and with supernatant from anti-CD3-activated IEL in comparison to supernatant from unstimulated IEL

first: Mahima

last: Swamy

first: Probir

last: Chakravarty

first: Adrian

middle: C

last: Hayday


title: Gene expression analysis in conventional and vitamin C treated iTreg cells

status: Public on Apr 09 2015

city: Chuncheon, Gangwon-Do

first: Kwon Ik

last: Oh

address: 1 Hallymdaehak-gil

department: Pathology

institute: Hallym University College of Medicine

summary: Analysis of the effect of vitamin C on gene expression regulation in iTreg cells. Results provide important information of the response of iTreg cells to vitamin C.

overall_design: Total RNA obtained from iTreg cells cultured for 5 days with or without vitamin C compared to natural Treg and naïve CD4+ T cells

first: Varun

last: Nair

first: Kwon


title: Pigment Epithelium-Derived Factor (PEDF) Inhibits Wnt/β-catenin Signaling in the Liver

status: Public on Mar 30 2015

city: West Haven

first: Petr

last: Protiva

address: 950 Campbell Avenue

institute: Yale University and VA CT Healthcare System

summary:
Gene Set Enrichment Analysis of PEDF knockout livers revealed induction of pathways associated with experimental and human HCC and a transcriptional profile characterized by Wnt/β-catenin activation
Genome-wide expression analysis of liver tissue of wild type vs PEDF knockout animals fed high fat diet

overall_design: Total RNA was extracted from whole liver tissue


title: Distinct activity of Oct4 regulatory elements in naïve and primed pluripotency

status: Public on Mar 19 2015

city: Seoul

first: Hyun Woo

last: Choi

institute: Konkuk University

summary: Naïve and primed pluripotent stem cells (PSCs) and germ cells express the Pou5f1 (Oct4) gene. The Oct4 gene contains two cis-regulatory elements, the distal (DE) and proximal enhancer (PE), which differentially control Oct4 expression in a cell-type- and stage-specific manner. Here, we generated double transgenic mice carrying both Oct4-ΔPE-GFP and Oct4-ΔDE-tdTomato (RFP), enabling us to simultaneously monitor the activity of DE and PE. Oct4 expression is stage-specifically regulated by DE and PE during embryonic and germ cell development. Using this dual reporter system, we successfully cultured pure populations of naïve (GFP+RFP-) and primed (GFP-RFP+) PSCs. We found that GFP+RFP- cells were metastable in serum-containing medium; stable naïve pluripotent cells were observed in medium containing two inhibitors (Meki and GSKi) but lacking serum. Finally, we suggest that the activity of Oct4 DE and PE is regulated by the repressive histone marks H3K9me3 and DNA methylation.

overall_design: Total RNA obtained from sorted cells by FACS analysis

first: Hyun

middle: W

first: Jin

last: Joo

first: Yean

last: Hong

first: Jong

last: Kim

first: Jeong

last: Lee

first: Hans

middle: R

last: Schöler

middle: T

last: Do


title: Epigenetic Memory Is Not Intrinsic To Transcription Factor-Mediated Reprogramming [Illumina array]

status: Public on Mar 07 2015

city: Duesseldorf

first: Ulf

last: Tiemann

address: Moorenstrasse 5

department: Institute for Stem Cell Research and Regenerative Medicine

institute: Heinrich Heine University Duesseldorf

summary: Somatic cells can be reprogrammed to pluripotency using different methods. In comparison to pluripotent cells obtained through somatic nuclear transfer, induced pluripotent stem cells (iPSCs) exhibit a higher number of epigenetic errors. Furthermore, most of these abnormalities have been described to be intrinsic to the iPSC technology. Here we investigate whether the aberrant epigenetic patterns detected in iPSCs are specific to transcription factor-mediated reprogramming. We used germline stem cells (GSCs), which are the only adult cell type that can be converted into pluripotent cells (gPSCs) under specific culture conditions, and compared GSC-derived iPSCs and gPSCs at the transcriptomic, epigenetic and functional level. Our results show that both reprogramming methods generate indistinguishable states of pluripotency. GSC-derived iPSCs and gPSCs retained similar levels of donor cell-type memory and exhibited comparable numbers of reprogramming errors. Therefore, our study demonstrates that the epigenetic memory detected in iPSCs is not intrinsic to transcription-factor mediated reprogramming.

overall_design: Total RNA from 12 different in vitro mouse cell lines, 2 technical replicates per sample: germline stem cells (GSCs, 2 independent cell lines), GSC-derived induced pluripotent stem cells (iPSCs, 4 independent cell lines), germline-derived pluripotent stem cells (gPSCs, 4 independent cell lines), embryonic stem cells (ESCs), fibroblast-derived induced pluripotent stem cells (Fib-iPSCs)

first: Guangming

last: Wu

first: Adele

middle: G

last: Marthaler

first: Natalia

last: Tapia


title: Global gene expression analyses of paused iPSCs

status: Public on Mar 23 2015

city: Tsukuba, Ibaraki

first: Ken

last: Nishimura

address: 1-1-1 Tennodai

country: Japan

institute: University of Tsukuba

summary: Low Klf4 expression reproducibly gives rise to a homogeneous population of partially reprogrammed iPSCs. Upregulation of Klf4 allows these cells to resume reprogramming, indicating that they are paused iPSCs that remain on the path towards pluripotency. Paused iPSCs with different Klf4 expression levels remain at distinct intermediate stages of reprogramming.

overall_design: Total RNAs were isolated from paused iPSCs cultured with 0, 10, 30 or 100 nM of Shield1 22 days after vector infection.

first: K

last: Hisatake


title: Chronic ethanol exposure results in time and brain-region dependent changes in gene coexpression networks.

status: Public on May 26 2015

city: Austin

first: Elizabeth

last: Osterndorff-Kahanek

address: 2500 Speedway

institute: University of Texas at Austin

summary: We examined global gene expression profiles in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC) and Liver of male C57BL/6J mice exposed to 4 cycles of chronic intermittent ethanol (CIE) vapor. Animals were sacrificed at 0, 8, and 120 hr following the last ethanol exposure.

overall_design:
Mice were exposed to 4 cycles of intermittent vapor [4 days of 16 hours vapor/ 8 hours air] with a week between each cycle.
Before entry into the vapor chambers, animals were injected with pyrazole (1 mMol/kg) and either ethanol (1.6 g/kg) or saline (controls).
Animals were sacrificed at 0, 8, and 120 hr following the last ethanol exposure.
The liver 0 hr control group contained 7 animals. Otherwise there were 8 animals per group (treated, control) at each time point.


title: Let-7 and miR-125 cooperate to promote astrogliogenesis

status: Public on Mar 05 2015

city: San Francisco

first: Robert

last: Blelloch

address: 35 Medical Center Way

department: Urology

institute: University of California, San Francisco

summary: The molecular basis of astrocyte differentiation and maturation is poorly understood. Here we  set out to study miRNA function during the glial progenitor cell (GPC) to astrocyte transition. Inducible deletion of all canonical microRNAs in GPCs in vitro led to a block in the differentiation to astrocytes. In an unbiased screen, the reintroduction of let-7 and miR-125 families of microRNAs rescued differentiation. Let-7 and miR-125 shared many targets and functioned in parallel to JAK-STAT signaling, a known regulator of astrogliogenesis. While individual knockdown of shared targets did not rescue the differentiation phenotype in microRNA-deficient GPCs, overexpression of these targets in wild-type GPCs blocked differentiation. This finding supports the idea that microRNAs simultaneously suppress multiple mRNAs that inhibit differentiation. The microRNA-regulated targets were enriched for genes downregulated during in vivo astrocyte differentiation and upregulated in glioblastomas, consistent with validity of using the in vitro model to study in vivo events. These findings provide insight into the microRNAs and the genes they regulate in this important cell fate transition.

overall_design: Total RNA was obtained from ESC-derived undiff, diff, Dgcr8 knockout and Dgcr8 knckout + let7/miR125 glial progenitor cells (GPCs). Three replicates were included for each sample.

first: Archana

last: Shenoy


title: Genome-wide analysis expression of ileum tumor samples from FVBN/APCmin and iPGC-1β/APCmin

status: Public on Mar 01 2015

first: Elena

last: Bellafante

address: Guy's Campus

department: Women's Health

institute: KCL

summary: Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in intestinal tumors from APCmin mice overexpressing PGC-1β specifically in the intestine.

overall_design: Total RNA obtained from ileum tumor samples from iPGC-1β/APCmin mice was compared to the total RNA extracted from FVBN/APCmin mice.

first: Andria

last: D'Orazio


title: PGC-1β Promotes Enterocyte Lifespan and Tumorigenesis in the Intestine

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

overall_design: Refer to individual Series


title: Genome-wide analysis expression of ileum samples from wild-type and iPGC-1β

summary: Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in enterocytes from transgenic mice overexpressing PGC-1β specifically in the intestine.

overall_design: Total RNA obtained from ileum samples from iPGC-1β mice was compared to the total RNA extracted from their wild-type littermates.

first: Antonio

last: Moschetta


title: Genome-wide analysis expression of ileum samples from PGC-1β fl/? and iKOPGC-1β

summary: Analysis of metabolic pathway gene expression. The hypothesis tested in the present study is to assess mRNA level changes in metabolic genes in enterocytes from intestine specific PGC-1β konckout mice.

overall_design: Total RNA obtained from ileum samples from IKOPGC-1β mice was compared to the total RNA extracted from their wild-type littermates.


title: Genome-wide analysis of bone marrow-derived macrophage (BMDM) priming by Ifng and Ifnb.

status: Public on Mar 26 2015

city: Msida

first: Brendon

last: Scicluna

address: Msida campus

country: Malta

institute: University of Malta

summary: Macrophages are a heterogeneous population of immune cells, which are critical for both the initiation and resolution of inflammation. Pro-inflammatory macrophages can be induced by the Th1 cytokine IFNγ and/or TLR triggers, like LPS. Here, we investigated the effects of IFNγ priming on LPS-induced gene expression in primary mouse macrophages.

overall_design: To investigate the effect of IFNγ priming on LPS-induced gene expression in macrophages, we stimulated bone marrow-derived macrophages with IFNγ or IFNb for 18 hours and subsequently activated them with LPS for 6 hours.

middle: P

first: Marten

last: Hoeksma


title: Microarray analysis of differentially expressed genes in ovarian and fallopian tube epithelium from risk-reducing salpingo-oophorectomies

status: Public on Feb 28 2015

city: Tampere

first: Kristina

last: Veskimäe

address: PO Box 2000

department: Department of Obstetrics and Gynecology

country: Finland

institute: Tampere University Hospital

summary:
Mutations in BRCA1 and BRCA2 genes confer an increased lifetime risk for breast and ovarian cancer. Ovarian cancer risk can be decreased by risk-reducing salpingo-oophorectomy (RRSO). Studies on RRSO material have altered the paradigm of serous ovarian cancer pathogenesis.
The purpose of this study was to identify candidate genes possibly involved in pathogenesis of serous ovarian cancer by carrying out a microarray analysis of differentially expressed genes in BRCA1/2- mutation positive ovarian and fallopian tube epithelium derived from RRSO surgery. Freshly frozen ovarian and fallopian tube samples from nine BRCA1/2 mutation carriers scheduled for RRSO were prospectively collected in comparison with five mutation-negative control patients undergoing salpingo-oophorectomy for benign indications. Microarray analysis of genome-wide gene expression was performed on ovarian and fallopian tube samples from BRCA1/2 and control patients. The validation of microarray data was performed by quantitative real-time polymerase chain reaction (qRT-PCR) in selected cases of RRSO samples, and also high grade serous carcinoma samples collected from patients with BRCA phenotype. From 22,733 genes, 454 transcripts were identified that were differentially expressed in BRCA1/2 mutation carriers when statistically compared to controls pooling all ovarian and fallopian tube samples together. Of these, 299 genes were statistically significantly downregulated and 155 genes were upregulated. Differentially expressed genes in BRCA1/2 samples reported here might be involved in serous ovarian carcinogenesis and provide interesting targets for further studies.

overall_design: Both fallopian tube and ovarian samples were collected from each BRCA1/2 mutation carrier resulting in eighteen mutation positive adnexal samples. Both fallopian tube and ovarian control samples were collected from one control patient while either ovarian or fallopian tube sample was available from four control patients, respectively, resulting in 6 adnexal control samples. High quality RNA was available from nine BRCA1/2-mutation positive ovarian and eight BRCA1/2-mutation positive fallopian tube samples and from three control ovarian and three control fallopian tube samples.

first: Synnöve

last: Staff

first: Francesco

last: Tabaro

first: Matti

last: Nykter

first: Jorma

last: Isola

first: Johanna

last: Mäenpää


title: Early gene expression in salivary gland after isoproterenol treatment

city: San Antonio

first: Yidong

last: Chen

address: 8403 Floyd Curl Drive, MSC 7784

institute: UT Health Science Center at San Antonio

summary: Isoproterenol, a β-adrenergic agonist, has been shown to induce salivary gland hyperplasia.  To gain a better understanding of the underlying molecular changes altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 minutes after isoproterenol injection.  After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. The regulation of up- and down-expression of genes related to cell proliferation/survival provides a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement.

overall_design: For the time-course experiments, male Sprague-Dawley rats (2-3 months old) were injected intra-peritoneally with isoproterenol (20 mg/g body weight) or normal saline (control).  The rats were euthanized at the indicated times and the harvested parotid glands stored at -80C until analyzed. Cells were harvested and processed at the following times: control (saline), immediately after treatment (10 min) and at 30 and 60min after treatment.

first: Alan

last: Lin

first: Hung-I

middle: H

first: Chih-Ko

last: Yeh


title: Characterization of Mouse Otic Sensory Lineage Specific Genes via Embryo-wide Comparative Profiling and Expression Pattern Assessment

status: Public on Feb 12 2015

city: Stanford

first: Byron

last: Hartman

address: 300 Pasteur Drive Edwards R219

department: Otolaryngology - Head and Neck Surgery

institute: Stanford University School of Medicine

summary: E10.5 mouse embryos were dissected into three tissue groups, consiting of: 20 pooled otic vesicles (Ovs), periotic tissues, and whole embryos with the otic regions removed. N=3 for each grouip

overall_design: Total RNA was isolated from dissected mouse tissues

first: Hartman

last: Byron

first: Heller

last: Stefan


title: Chd1 is essential in the endothelial lineage for the emergence of definitive hematopoietic stem/progenitor cells

first: Fong Ming

last: Koh

address: 35 Medical Center Way RMB-912D

department: Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research

summary: Lineage specification during development involves reprogramming of chromatin states, but little is known about how this is regulated in vivo. We previously showed that the chromatin remodeler Chd1 regulates transcriptional output and self-renewal of mouse embryonic stem cells, and is essential for epiblast development. These results raise the question of whether Chd1 regulates the development of other progenitor populations. Here we report that endothelial-specific deletion of Chd1 using Tie2-Cre leads to embryonic lethality by E15.5. Development of the vasculature and of primitive hematopoiesis appears to occur normally in the mutants. However, mutant embryos show signs of anemia as early as E11.5, are depleted of definitive hematopoietic stem /progenitor cells, and display a complete failure of fetal liver erythropoiesis. While mutants at E10.5 appear morphologically normal and can develop hemogenic clusters in the dorsal aorta, the E10.5 mutant endothelium fails to activate a transcriptional program associated with hematopoiesis. This transcriptional program may serve as a resource for the identification of novel markers or regulators of definitive hematopoiesis. Finally, hematopoietic-specific Chd1 deletion using Vav-Cre yields no apparent defects during development or adulthood. These results suggest that Chd1 regulates chromatin-remodeling events critical for a specific developmental window during the transition of endothelial cells to definitive blood progenitors.

overall_design: Analysis of CD31+ tdTomato+ cells sorted from E10.5 whole embryos with an endothelial-specific deletion of Chd1, using 4 biological replicates of 2 genotypes (CreHet controls vs mutants).

first: Fong

middle: M

first: Carlos

middle: O

last: Lizama

first: Priscilla

last: Wong

first: John

last: Hawkins

first: Ann

last: Zovein

first: Miguel

last: Ramalho-Santos


title: Genome-wide analysis of dorsal skin gene expression of control, Krox20-cre:Shp2fl, Krox20-cre; Mek1fstop/+ and double  mutant mice

status: Public on Feb 08 2015

city: Berlin

first: Ozlem

last: Akilli Ozturk

address: Robert-Rosslestr. 10

department: Cancer Research

institute: Max Delbruck Center for Molecular Medicine

summary: Analysis of genes regulated by Shp2 mediated signaling in hair cycle initiation which are rescued by overactivation of Mek1

overall_design: Total RNA from dorsal skin of control mice was compared to transgenic mice

first: Walter

last: Birchmeier


title: Mouse melanoma types with various genotypes

city: Chicago

first: Stefani

last: Spranger

address: 929 E 57th Street

institute: University of Chicago

summary: Only a subset of melanoma patients has evidence for spontaneous T cell infiltration into tumor sites, previously associated with clinical responses. However, the molecular mechanisms explaining absence of a T cell response are not yet defined. Analyses of human melanoma metastases have revealed that T cell signature low tumors show alterations in the Wnt/b-catenin signaling pathway. We utilized an inducible mouse model driven by inducible BrafV600E and PTEN-deletion, with or without active b-catenin (CAT-STA) to test if tumor intrinsic active b-catenin can block anti-tumor immunity. While Braf/PTEN melanomas showed presence of a T cell infiltrate, T cells were nearly completely eliminated in tumors expressing active b-catenin. Adoptive transfer experiments revealed defective T cell priming when tumors expressed active b-catenin. Analysis of the antigen-presenting cell compartment revealed a selective decrease in the CD103+ DC subset within the tumor microenvironment, which could be associated with b-catenin depended inhibition of expression of the chemokine CCL4 within tumor cells. Here we used 3 mice of each genotype BrafV600E/PTEN-/- and BrafV600E/PTEN-/-/Cat-STA and compared their gene-expression profiles.

first: Thomas

last: Gajewski


title: The Functional Role of Gab1 and MAPK Signaling in Hair Cycle and Stem Cell Quisecence


title: Identifying actionable targets through integrative analyses of GEM model and human prostate cancer profiling (Illumina)

status: Public on Feb 20 2015

city: New York

first: Jeffrey

last: Zhao

state: NY

address: 1275 York Avenue

department: Genomics Core

institute: Memorial Sloan Kettering Cancer Center

summary: Here we profile prostate cancers derived from GEM models of prostate cancer representative of human prostate cancer

overall_design: Total RNA was isolated from established prostate cancers in 3 GEM models of prostate cancer - PB-MYC, Pten-/-, Pten-/- p53-/-

first: Brett

last: Carver


title: N17 Modifies Mutant Huntingtin Nuclear Pathogenesis and Severity of Disease in HD BAC Transgenic Mice

status: Public on Feb 05 2015

city: Los Angeles

first: X.

middle: William

last: Yang

address: 695 Charles E. Young Dr. South, Gonda 3524

department: Semel Institute

institute: University of California, Los Angeles

summary: Longitudinal microarray data from BACHD-ΔN17 mice with wildtype littermate controls

overall_design: Total RNA from cortex and striatum of wildtype and BACHD-ΔN17 mice collected at 2mo, 7mo, and 11mo was used for microarray on the Illumina MouseRef8v.2 platform.

first: Xiaofeng

last: Gu

last: Cantle

first: Erin

last: Greiner

first: Chung-Ying

last: Lee

first: Albert

last: Barth

first: Fuying

last: Gao

first: Chang

last: Park

first: Zhiqiang

last: Zhang

first: Susana

last: Sandoval-Miller

first: Richard

middle: L

first: Marc

last: Diamond

first: Istvan

last: Mody

first: Giovanni

last: Coppola

first: Xiangdong


title: Interleukin-7 co-ordinates proliferation, differentiation and TCRA recombination during thymocyte β-selection

city: Toronto

first: Paul

last: Kowalski

state: Ontario

address: PGCRL - 686 Bay St

department: Developmental and Stem Cell Biology

country: Canada

institute: The Hospital for Sick Children

summary: We used Illumina global gene expression profiling to compare IL7-regulated pathways in post-beta-selected DN3b and DN4 versus pre-beta-selected DN3a cell stages. We found that IL7 induced fewer genes in both DN3b and DN4 cells (800 and 300 respectively, versus 1800 in DN3a). We found several direct JAK/STAT target genes were significantly induced in all 3 stages. This group included Bcl2 and Cish, Socs2 and Socs3, feedback regulators of JAK-STAT signaling, as well as Pim1, Tfrc (Cd71) and Ccnd2. Thus, in addition to inducing survival genes, here we show that IL7 acutely regulates expression of trophic receptors and cell cycle regulators in pre- and post-beta-selection DN thymocytes.

overall_design: DN3a, DN3b and DN4 thymocytes were sorted from Il7r+/+ mice (4 independent sorts), rested for 1h at 370 C in a humidified atmosphere with 5% CO2, and then left untreated or stimulated with IL7 (10 ng/ml, Stem Cell Technologies) for 3h before isolating total cellular RNA using the RNeasy isolation kit (Qiagen). Quality control and quantitation was done on a Bioanalyzer 2100 (Agilent). Genome-wide expression profiling was carried out using Illumina mouse Ref8v2 beadchips according to standard protocols at The Centre for Applied Genomics (TCAG, www.tcag.ca) core facility at the Hospital for Sick Children. Data processing and other statistical analyses were performed using R Bio-conductor 2.13.0. Raw signals from 25697 probes were pre-processed to perform background subtraction, quantile normalization and log2 transformation before using moderated T-tests within Bioconductor package Limma (Linear Models for Microarray Data). Empirical Bayes smoothing was applied to the standard errors. Paired T-tests were used to identify IL7-induced changes in gene expression in each subset and the false discovery rate (FDR) was estimated using the Benjamini-Hochberg method to correct for multiple testing. Pearson correlations showed that technical replicates showed very high correlations between chips. For genes that were represented by multiple probesets on the array, we selected the ones with the highest ANOVA F-statistics (lowest FDR-adjusted q-value).

first: Amine

last: Boudil

first: Irina

last: Matei

first: Han-Yu

last: Shih

first: Goce

last: Bogdanoski

first: Julie

last: Yuan

first: Stephen

last: Chang

first: Bertrand

last: Montpellier

middle: E

first: Veronique

last: Voisin

first: Shaheena

last: Bashir

first: Gary

last: Bader

first: Michael

last: Krangel

first: Cynthia

middle: J

last: Guidos


title: Progesterone-mediated effects on gene expression and oocyte-cumulus complex transport in the mouse fallopian tube

status: Public on Jan 31 2015

city: GÖTEBORG

first: Anna

last: Bylander

address: Guldhedsgatan 10A

department: Biomedicine

institute: Göteborgsuniversitet

summary: The fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation. Progesterone and the classical progesterone receptor (PGR) are known to be involved in regulating both tubal ciliary beating and muscular contractions, possibly involving both genomic and non-genomic  actions. To provide more clues on the mechanisms involved,  we investigated the effect of progesterone on gene expression in mice fallopian tubes in vitro at early (20 min) and later (2 h, 8 h) time-points using microarray and/or quantitative PCR.  In parallel, oocyte cumulus complex transport was investigated in ovulating mice injected with one of the PGR antagonists, Org 31710 or CDB2194. Microarray analyses did not reveal any apparently regulated genes 20 min after progesterone treatment, in agreement with a proposed non-genomic action of progesterone controlling ciliary beating.  After 2 h, 11 genes were significantly up-regulated. Analyses by quantitative PCR at 2 h and 8 h showed a consistent up-regulation of endothelin 1 (Edn1) and a down-regulation of its receptor Ednra by progesterone. We also show that treatment with progesterone receptor antagonist before ovulation accelerates the transport of the oocyte cumulus complex. This is the first study showing that progesterone regulates Edn1 and Ednra in the fallopian tube. Together with previous studies on endothelin-mediated effects on muscular contractions in the fallopian tube, the results from this study suggest that endothelin is a mediator of the progesterone-controlled effects on muscular contraction, and eventually gamete transport, in the fallopian tube.

overall_design: 16 pooled samples from mice fallopian tubes were exposed in vitro to progesterone for up to 2 hours.

first: Lina

last: Gunnarsson

first: Ruijin

last: Shao

first: Håkan

last: Billig

first: D

last: Larsson


title: Assessment of the role of the BCRs in transgenic models of chronic lymphocytic leukemia

status: Public on Dec 31 2014

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

institute: IOR

summary:
we evaluated the capacity of different types of antigen/BCR interactions to induce leukemia in a transgenic mouse model of CLL
Key words; B-cell antigen receptor (BCR), chronic lymphocytic leukaemia (CLL), T-cell leukemia (TCL)

overall_design: GEP analysis of 7 leukemias with an anti-Sm BCR and 9 leukemias with an anti-PtC BCR

first: Stefano

last: Iacovelli

first: Andrea

last: Rinaldi

first: Dimitar

last: Efremov


title: Genome-wide analysis of P15 dorsal root ganglion gene expression of control and Isl1-Cre//c-Maf mutant mice

city: Heidelberg

first: Hagen

last: Wende

address: Im Neuenheimer Feld 366

department: Institute of Pharmacology

institute: Heidelberg University

summary: The sense of touch relies on the detection of mechanical stimuli by specialized sensory neurons. Mechanosensory neurons are generated from neural crest cells, but the scarcity of molecular data has made it difficult to analyze their development and to define the basis of their diversity and function. The transcription factor c-Maf is crucial for mechanosensory function in mice and humans. In particular, c-Maf is required for the development and function of mechanosensory neurons terminating in lanceolate endings, Meissner corpuscles and Pacinian corpuscles. c-Maf is a key transcription factor directing the development and function of rapidly-adapting mechanoreceptors and their end organs.

overall_design: Total RNA of pools from L3,4,5,6 DRGs of 15-day-old control mice was compared to total RNA of pools from L3,4,5,6 DRGs of 15-day-old Isl1-Cre//c-Maf conditional mutant mice.

first: Carmen

last: Birchmeier


title: Dynamic Changes in E-protein Activity are Essential for Treg cell Development

city: Bethesda

first: Timothy

last: Myers

address: 50 South Drive, Room 5509

department: Research Technologies Branch

institute: National Institute of Allergy and Infectious Diseases

summary: To gain a molecular view of E-proteins with respect to the development of Foxp3+ T cells, we perform microarray studies that would identify transcription factors that are up-regulated as E-proteins levels fall and and Foxp3 expression rises.  We hypothesize that such transcription factors activate the synthesis of key proteins necessary for the development of Foxp3+ cells in the thymus (or in the periphery).  Among the possible proteins (negatively regulated by E-protein are those involved in IL-2 signaling, since the latter has been shown to be critical for the development of Foxp3+ cells in the thymus.  In the planned studies we will extract mRNA from sorted Foxp3+GFP+ thymocytes from wild type (WT) mice and similar cells from E-protein deficient thymocytes.  However, since Foxp3+ thymocytes in WT mice already have reduced E-protein levels, differences between thymocytes from these mice and E-protein deficient mice might be minimal.  We therefore will also extract mRNA from Foxp3-negative thymocytes from WT mice whose E-proteins levels have not fallen sufficient low to allow Foxp3 expression and Foxp3-negative thymocytes from E-protein deficient mice whose E-proteins are necessarily low but have not expressed Foxp3 for unrelated reasons.

overall_design: Isolate mRNA from sorted Foxp3+ and Foxp3- thymocytes from either wild type (WT) mice and from E-protein deficient (E2A and HEB knockout) thymocytes; 2 replicates of each of the 4 conditions

first: Ping

last: Gao

first: Joan

middle: Z

last: Yang

first: Ivan

last: Fuss

first: Qi

last: Zhang

first: Paul

last: Gardina

first: Fuping

first: Warren

last: Strober


title: Genome-wide analysis of dorsal skin gene expression of control and K14-cre:Gab1fl mutant mice

first: Ozlem

last: Akilli Ozturk

summary: Analysis of genes regulated by Gab1 mediated signaling in hair cycle initiation

overall_design: Total RNA from dorsal skin of control mice was compared to K14-cre; Gab1fl conditional mutant mice

first: Walter


city: La Jolla

first: Gen-Sheng

last: Feng

address: 9500 Gilman Dr.

institute: University of California San Diego

summary: Microarray analysis of Shp2hep-/- and Shp2Floxed/Floxed liver samples to gain global molecular insights how Shp2 is involved in hepatic metabolism.

overall_design: Two liver samples from both Shp2hep-/- and Shp2Floxed/Floxed were subjected to microarray using Illumina system, Shp2hep-/- were albumin-cre postitive.

first: Shuangwei

last: Li


title: Time- and dose rate-related effects of internal 177Lu exposure on gene expression in mouse kidney tissue

status: Public on Dec 17 2014

city: Göteborg

first: Emil

last: Schüler

address: Gula stråket 2B

institute: University of Gothenburg

summary: Transcriptomic profiling of normal mouse kidney cortex and medulla following 177Lu irradiation

overall_design: Total RNA was isolated from fresh-frozen tissue samples

first: Nils

last: Rudqvist

first: Toshima

last: Parris

first: Britta

last: Langen

first: Johan

last: Spetz

first: Khalil

last: Helou

first: Eva

last: Forssell-Aronsson


title: Gene expression profile of WT and TAK1 KO livers.

status: Public on Dec 22 2014

first: Ekihiro

last: Seki

address: 8700 Beverly Blvd., DAVIS, Suite 2099

department: Medicine

institute: Cedars-Sinai Medical Center

summary: The effect of ablation of Tak1 gene in the liver was characterized.

overall_design: RNA was extracted from 1-month-old WT and hepatocyte specific TAK1-deleted mice

first: Sayaka

last: Inokuchi

first: Dorothy

middle: D

last: Sears

first: Yoon

last: Roh

first: Michael

last: Karin

first: David

middle: A

last: Brenner


title: Identifying actionable targets through integrative analyses of GEM model and human prostate cancer profiling

first: Jeffrey

last: Zhao

type:
Expression profiling by array
Genome variation profiling by array

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

overall_design: Refer to individual Series


title: Genome-wide analysis of gene expression during somatic cell reprogramming

status: Public on Dec 10 2014

first: Andras

last: Nagy

address: 25 Orde street

department: Mount Sinai Hospital

institute: Lunenfeld Tanenbaum Research Institute

summary: Reprogrammed mouse embryonic fibroblasts generated clonal cell lines were analysed during maintained expression of the four reprogramming transcription factors (C-Myc, Oct4, Sox2, Klf4). The transgene expressing clonal cell lines segregated in to two Nanog positive cell types, F-class and C-class, that both differentiate in to three germ layers. The emergence of F-class cells is dependent on the expression of all four factors with a necessity for high levels of transgene expression. The F-class cells represent a novel and stable cell state.

overall_design: Mouse embryonic fibroblasts were reprogrammed using four transcription factors (C-Myc, Oct4, Sox2, Klf4) and clonal cell lines established. Cell lines were maintained in doxycycline supplemented media to sustain transgene expression. Global gene expression profile analysis was performed on the clonal cell lines at day16, with respect to embryonic stem cells and parental fibroblast cells. F-class cells (clone 1) were maintained for a further two weeks and found not to acquire expression of ESC associated genes.

first: Peter

last: Tonge


title: Genome-wide expression analysis of self renewing hematopoietic stem cells (HSC) in control and CD70TG mice.

city: Leiden

last: 't Hoen

address: PO Box 9600

department: Center for Human and Clinical Genetics

institute: Leiden University Medical Center

summary:
To study the effect of CD27 triggering on HSC biology
Ageing of the hematopoietic stem cell (HSC) compartment is characterized by an accumulation of less productive HSCs with impaired lymphoid differentiation capacity, which contributes to age-dependent hematological abnormalities including anemia, myeloproliferative disorders and a decline in adaptive immunity. Since HSCs express the costimulatory receptor CD27 and because inflammation has been associated with HSC ageing, we investigated the effect of stimulation of CD27 by its inflammatory ligand CD70 on HSC maintenance. We found that CD27-triggering during CD70-driven immune activation in young mice enhances HSC self-renewal, leading to accumulation of HSCs to levels comparable with old control mice. These findings indicate that CD27-signaling accelerates HSC ageing, which is supported by the observation that CD27-triggering negatively affects HSC differentiation to the lymphoid lineage and increases myeloid differentiation. This functional change was mirrored by a corresponding difference in gene expression, as microarray analysis indicated that CD27-triggered HSCs have a strongly myeloid-biased gene signature. CD27 signaling also induced enrichment of genes associated with biological processes involved in cellular responses to DNA damage/repair and reactive oxygen species (ROS), which are associated with HSC ageing and related to increased proliferation. Therefore, we postulate that CD27 triggering during chronic inflammation contributes directly to ageing of the hematopoietic compartment.

overall_design: FACS sorted fractions of long term (CD34-) and short-term (CD34+) HCS from control (IFNgamma-/-) and CD70TG (IFNgamma-/-xCD70TG) mice. RNA from two mice was pooled on each microarray and 4 independent replicates were used per condition.

first: Alexander

last: de Bruin

first: Martijn

last: Nolte


title: Effect of p21 overexpression on skeletal muscle mRNA expression.

status: Public on Dec 04 2014

city: Iowa City

first: Daniel

last: Fox

state: IA

address: 4400 PBDB, 500 Newton Rd.

department: Internal Medicine

institute: University of Iowa

summary: For additional details see Bongers et al, Spermine Oxidase Maintains Basal Skeletal Muscle Gene Expression and Fiber Size, and Is Strongly Repressed by Conditions that Cause Skeletal Muscle Atrophy  . Am J Physiol Endocrinol Metab. 2014 [under review]

overall_design: Bilateral tibialis anterior muscles of C57BL/6 mice were harvested seven days after transfection with p21 or control plasmid.

first: D

middle: K

first: C

last: Adams


title: Effect of  spermine oxidase and p21 overexpression on skeletal muscle mRNA expression.


title: Cigarette smoke-induced iBALT mediates macrophage activation in a B cell-dependent manner in COPD

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum Muenchen

summary:
Chronic obstructive pulmonary disease (COPD) is characterized by a progressive decline in lung function, caused by exposure to exogenous particles, mainly cigarette smoke (CS). COPD pathogenesis is initiated and perpetuated by an abnormal CS-induced inflammatory response of the lungs, involving both innate and adaptive immunity. Specifically, B cells organized in iBALT structures, as well as macrophages, accumulate in the lungs and contribute to CS-induced emphysema, but the mechanisms thereof remain unclear.
Here, we demonstrate that B cell-deficient mice are significantly protected against CS-induced emphysema. Chronic CS exposure led to increased lung compliance, total lung capacity, and mean linear chord length in WT, but not B cell-deficient mice, associated with an increased size and number of iBALT structures. The increased accumulation of macrophages around iBALT and in emphysematous alveolar areas in CS-exposed WT mice coincided with upregulated MMP12 expression. In vitro co-culture experiments using B cells and macrophages demonstrated that B cell-derived IL-10 drives macrophage activation and MMP12 upregulation. In summary, B cell function in iBALT formation in CS-induced emphysema provides a new innovative mechanism, which could be explored as a target for therapeutic intervention in COPD patients.

overall_design: Expression data of mice treated with cigarette smoke. Lung tissue was analysed at four and six months of age.

first: Gerrit

last: John-Schuster

first: Katrin

last: Hager

first: Martin

last: Irmler

first: Thomas

last: Conlon

first: Oliver

last: Eickelberg

first: Ali

last: Yildirim


title: Transcriptional profiling of microdissected ventromedial hypothalamus in Nkx2-1 f/f vs. Nkx2-1 f/f; Sf1Cre female mice

status: Public on Nov 27 2014

city: San Francisco

first: Holly

last: Ingraham

address: 1550 4th St., Rock Hall 284E

department: Cellular and Molecular Pharmacology

institute: University of California San Francisco

summary: Microdissected ventromedial hypothalamus (VMH) was profiled to identify transcriptional changes after Nkx2-1 ablation in female mice. Total RNA was extracted from conditional mutants (Nkx2-1 f/f; Sf1Cre) and floxed controls (Nkx2-1 f/f) at postnatal day 10 (P10) and profiled using Mouse ref8 v2.0 Illumina chips and reagents (n=4/group).

overall_design: The tissue profiled is microdissected ventromedial hypothalamus from P10 female mice. Controls and mutants are analyzed in quadruplicate.

first: Stephanie

last: Correa

last: Newstrom

first: James

last: Warne

first: Pierre

last: Flandin

first: Clement

middle: C

last: Cheung

last: Lin-Moore

first: Andrew

last: Pierce

first: Giovanni

last: Coppola

first: Allison

last: Xu

first: John

last: Rubenstein


title: Nutritional Strategy to Prevent Fatty Liver and Insulin Resistance Independent of Obesity by Reducing GIP Responses

status: Public on Dec 05 2014

last: Beckers

summary:
High intakes of carbohydrates, particularly sucrose, in Western societies are associated with the development of non-alcoholic fatty liver (NAFL) and diabetes mellitus. It is unclear whether this is related to the carbohydrate quantity or the hormonal responses, particularly Glucose-dependent Insulinotropic Polypeptide (GIP) which is released in the proximal intestine. We, therefore, used the glucose-fructose dimer as proximally resorbed, 1,4-linked sucrose or distally resorbed 1,6-linked palatinose. Palatinose compared to sucrose, indeed, resulted in slower glucose absorption and reduced postprandial insulin and GIP levels. After 22 weeks of isocaloric diets, palatinose feeding prevented hepatic steatosis (48.5%) compared to sucrose and improved glucose tolerance, without differences in body composition and food intake.
Ablation of GIP receptor (GIPR) signaling in Gipr-/- mice completely prevented the deleterious metabolic effects of sucrose feeding. Furthermore, our microarray analysis indicated that sucrose increased the hepatic expression of Suppressor of Cytokine Signaling 2 (SOCS2), which is involved in the growth hormone signaling pathway and participates in the development of NAFL. Our results suggest that the site of glucose absorption and the GIP response determine liver fat accumulation and insulin resistance. GIP may play a role in sucrose induced fatty liver by regulating the expression of SOCS2.

overall_design: Expression data from liver tissue of mice fed with isocaloric diets containing either sucrose or palatinose

first: Farnaz

last: Keyhani-Nejad

first: Andreas

last: Birkenfeld

last: Pfeiffer


title: Transcriptome analysis from Nd2-mutant and control fibroblasts

status: Public on Nov 22 2014

city: Leipzig

first: Marianne

last: Schauer

address: Johannissallee 30

department: Department of Dermatology

institute: University Leipzig

summary: Background: Mutations of mitochondrial (mt)DNA cause a variety of human diseases and are also implicated in ageing processes.   Results: Primary fibroblasts of the conplastic mouse strain C57BL/6J-mtALR/LTJ with a mutation at position nt4738 resulting in a single nucleotide exchange (leucine to methionine) in the mitochondrial NADH dehydrogenase subunit 2 (Nd2) gene of the respiratory chain show higher enzyme activity and ATP production and lower ROS production than control fibroblasts. Furthermore, Nd2-mutant fibroblasts show a higher proliferation rate and a reduction of senescence markers. Transcriptome analysis reveals members of the p38MAPK pathway as being significantly downregulated in Nd2-mutant mice as compared with controls. In line with this, inhibition of p38MAPK with SB203580 enhanced the proliferation and  reduced cytokine secretion in senescent Nd2-mutant fibroblasts.  Conclusion: Taken together, we report Nd2 as a new mitochondrial gene with age-protective function in mice, and possibly in humans, which interferes with age-related signaling pathways.

overall_design: MouseRef-8 v2.0 Expression BeadChips of 8 samples of skin fibroblasts; 4 samples of fibroblasts from 4 mice of C57BL/6J-mtALR/LtJ (Nd2-mutant) and 4 samples of fibroblasts from 4 mice of C57BL/6J-mtAKR/J (control)

first: Manfred

last: Kunz


title: Effect of spermine oxidase overexpression on skeletal muscle mRNA expression.

first: Daniel

last: Fox

overall_design: Bilateral tibialis anterior muscles of C57BL/6 mice were harvested seven days after transfection with spermine oxidase or control plasmid.

first: D

first: C

last: Adams


title: p53 and ATF4 Mediate Distinct and Additive Mechanisms to Skeletal Muscle Atrophy During Limb Immobilization

status: Public on Nov 05 2014

summary:
p53 regulates a distinct subset of skeletal muscle mRNAs during immobilization-induced skeletal muscle atrophy
For additional details see Fox et al, p53 and ATF4 mediate distinct and additive pathways to skeletal muscle atrophy during limb immobilization. Am J Physiol Endocrinol Metab. 2014 Aug 1;307(3):E245-61.

overall_design: Bilateral tibialis anterior muscles were harvested at three days for the following conditions: 1) hindlimb immobilization of C57BL/6 mice; 2) hindlimb immobilization of p53 mKO and littermate control mice; 3) transfection of wild type mice with p53 plasmid or control plasmid

first: Christopher


title: Gene expression in macrophages derived form wild-type and Ndfst1-deficient mice before and after foam cell conversion

status: Public on Nov 04 2014

first: Philip

middle: Leo Stefan Maria

last: Gordts

department: CMM

institute: UCSD

summary: In order to examine the role of macrophage heparan sulfate proteoglycans in atherogenesis, we inactivated the biosynthetic gene N-acetylglucosamine N-deacetylase-N-sulfotransferase 1 (Ndst1) in macrophages. In order to determine the impact of altering Ndst1 expression, we crossbred mice bearing a conditional loxP-flanked (“floxed”) allele of Ndst1 (Ndst1f/f) to transgenic mice expressing the bacterial Cre recombinase under control of the lysozyme 2 promoter (LysMCre) to drive inactivation of the gene in myeloid cells. We compared the transcriptome of bone marrow derived macrophages from Ndst1f/fLysMCre- and Ndst1f/fLysMCre+ macrophages in basal growth medium and after foam cell conversion using 50µg/ml of aggregated LDL (agLDL) to asses the impact of altered macrophage heparan sulfate sulfation on gene expression.

overall_design: Total RNA obtained from bone marrow derived macrophages (BMDM) derived form two wild-type and two Ndfst1-deficient mice before and after foam cell conversion and analyzed in diplicate (n=4 for each conditions; total of 4 conditions)

first: Ayca

last: Erbilgin

first: Aldons

last: Lusis

first: Jeffrey

last: Esko