title: Epistatic interaction between the lipase-encoding genes Pnpla2 (ATGL) and Lipe (HSL) causes liposarcoma in mice

city: Bar Harbor

first: Christoph

last: Preuss

state: ME

address: 600 Main Street

institute: The Jackson Laboratory

summary: Liposarcoma is a poorly understood malignancy of fat cells. Lipolysis, a central pathway of adipose tissue metabolism, has been implicated in cancer. Here, we generated tissue-specific single- and combined knockout mice for the two major lipases ATGL and HSL. Notably, double knockout (DAKO) mice developed late onset liposarcoma with complete penetrance, while single knockout mice appeared normal. DAKO whole transcriptome profiles differed from those of single knockout mice, revealing an early-onset tissue-specific response that persisted until the late-onset development of liposarcoma. Cancer-associated markers Gpnmb and G0s2 were among the most highly dysregulated genes in DAKO mice and also in human liposarcomas, suggesting a potential role for these proteins as liposarcoma-specific biomarkers. Taken together, our results demonstrate a novel epistatic interaction linking lipolysis with cancer. DAKO mice provide a promising model for studying early premalignant changes that lead to late-onset disease.

overall_design: Four mouse strains were used: normal controls, mice deficient in adipose tissue for ATGL (ATGLAKO), HSL (HSLAKO) or both (DAKO).  HSLAKO mice were homozygous for a floxed allele of Lipe and harbored a transgene, from which Cre is expressed from a Fabp4 promoter that is active in adipose tissues. Further details about creation of HSLAKO mice are provided in supplemental methods. DAKO mice were created by crossing two single knockout mice ATGLAKO and HSLAKO for at least two generations. Mice expressing the Fabp4-Cre transgene were used as controls. In this study, the targeted allele had been transferred for at least 8 generations to a C57BL/6J background.

first: Grant

last: Mitchell

first: Jiang

middle: W

last: Wu


title: Genome-wide analysis of the altered gene expression in the transgenic mice ectopically expressing the human SRY. [brain]

status: Public on Apr 16 2017

city: San Francisco

first: Yun-Fai

middle: Chris

last: Lau

state: CA

address: 4150 Clement Street

department: Department of Medicine, VA Medical Center

country: USA

institute: University of California, San Francisco

summary: Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse brain. We hypothesize that aberrant expression of the human SRY gene could affect the development and physiology of transgenic mice.  To test this hypothesis we have established a Cre-LoxP transgene activation system, thereby activating and expressing the hSRY transgene at the single-cell embryonic stage. Such transgenic mice were born of similar sizes as non-transgenic littermates, but retard in postnatal growth and all die within two weeks of age. To determine the molecular changes associated with such phenotypes, we have analyzed the transcriptomes of brains of pups expressing (hSRY-ON) and not-expressing (hSRY-OFF) the hSRY transgene. The results provide important information demonstrating that ectopic expression of hSRY resulted in altered expression patterns of numerous genes associating with the development the nervous system and pathogenesis of neurological diseases in the brain.

overall_design: Total RNAs isolated from the brain of P6 male hSRY-ON mice was compared to those of age matched male hSRY-OFF mice.

first: Tatsuo

last: Kido

middle: C


title: Genome-wide analysis of the effect of TUDCA on 1 week transveres aortic constriction (TAC) mouse

status: Public on Apr 12 2017

city: Gwangju

first: Dohan

last: Kim

state: Gwangju

address: oryong dong buk gu, cheomdan

department: Dept. of Life science

country: South Korea

institute: gwangju institute of science and technology

summary: The hypothesis tested in the present study was that ameliorating ER stress by TUDCA could reduce the cardiac remodeling in TAC mice. Results provide important information of the genes that were up- or down-regulated in Veh-TAC operated animals in comparison to Sham, TUDCA -Sham and TUDCA-TAC mice.

overall_design: Total RNA obtained from vehicle treated sham (Veh-Sham)(control), vehicle treated TAC (Veh-TAC), TUDCA treated sham (TUDCA-Sham) and TUDCA treated TAC (TUDCA-TAC) were compared in this study, after 1 week of TUDCA treatment, effect of TUDCA on cardiac remodeling was evaluated.

first: Do

middle: H

first: Shilpa

last: Rani

first: Jin

middle: O

first: Pradeep

middle: K

last: Sreenivasiah


title: Genome-wide analysis of the altered gene expression in the transgenic mice ectopically expressing the human SRY.

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

overall_design: Refer to individual Series


title: Extensive phenotypic characterization of a new transgenic mouse reveals pleiotropic perturbations in physiology due to mesenchymal hGH minigene expression

status: Public on Feb 24 2017

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

country: Germany

institute: Helmholtz Zentrum Muenchen

summary: The human growth hormone (hGH) minigene used for transgene stabilization in mice has been recently identified to be locally expressed in the tissues where transgenes are active and associated with phenotypic alterations. Here we extend these findings by analyzing the effect of the hGH minigene in TgC6hp55 transgenic mice which express the human TNFR1 under the control of the mesenchymal cell-specific CollagenVI promoter. These mice displayed a fully penetrant phenotype characterized by growth enhancement accompanied by perturbations in metabolic, skeletal, histological and other physiological parameters. Notably, this phenotype was independent of TNF-TNFR1 signaling since the genetic ablation of either Tnf or Tradd did not rescue the phenotype. Further analyses showed that the hGH minigene was expressed in several   tissues, also leading to increased hGH protein levels in the serum. Pharmacological blockade of GH signaling prevented the development of the phenotype. Our results indicate that the unplanned expression of the hGH minigene in CollagenVI expressing mesenchymal cells can lead through local and/or systemic mechanisms to enhanced somatic growth followed by a plethora of primary and/or secondary effects such as hyperphagia, hypermetabolism, disturbed glucose homeostasis, altered hematological parameters, increased bone formation and lipid accumulation in metabolically critical tissues.

overall_design: We performed gene expression microarray analysis of liver tissue derived from TgC6hp55 mice and control animals

first: Aimilios

last: Kaklamanos

first: Jan

last: Rozman

first: Manolis

last: Roulis

first: Niki

last: Karagianni

first: Maria

last: Armaka

first: Moya

first: Julia

last: Calzada-Wack

first: Marion

last: Horsch

first: Laura

last: Brachthäuser

first: Birgit

last: Rathkolb

first: Thure

last: Adler

first: Frauke

last: Neff

first: Eckhard

last: Wolf

first: Valerie

last: Gailus-Durner

first: Helmut

last: Fuchs

first: Martin

last: Hrabé de Angelis

first: George

last: Kollias


title: Gene Expression Analysis of Fibrotic Liver

status: Public on Mar 06 2017

city: Houston

first: Travis

last: Hardcastle

state: TX

address: 1901 East Rd.

department: Cancer Biology

institute: MD Anderson Cancer Center

summary: Analysis at the gene epression level of mice that had CCl4 induced liver fibrosis with either FSP1+ cells or aSMA+ cells ablated.

overall_design: Total RNA was collected from mice with healthy, diseased, FSP1 ablated, and aSMA ablated liver

first: Raghu

last: Kalluri

last: LeBleu


title: Global gene expression profile of H37Rv (Mtb) vs ∆mtrB

status: Public on Apr 20 2017

city: Kolkata

first: Manikuntala

last: Kundu

state: West Bengal

address: 93/1, Acharya Prafulla Chandra Road

country: India

institute: Bose Institute

summary: Transcriptional profiling of H37Rv and ∆mtrB strains grown to log phase in MB7H9

overall_design: Comparison of ∆mtrB transcriptional profile with H37Rv as control. Two technical replicates per strain, one experiment.

first: Joyoti

last: Basu

first: Sudipto

last: Saha


title: A systems approach implicates a brain mitochondrial oxidative homeostasis co-expression network in genetic vulnerability to alcohol withdrawal

status: Public on Mar 08 2017

city: Portland

first: Nicole

last: Walter

state: OR

address: 3181 SW Sam Jackson Park Road

department: Behavioral Neuroscience

institute: Oregon Health & Science University

summary:
Differential gene expression between mouse distal chromsome 1 congenic and background and reciprocal congenic and background
Genetic factors significantly affect vulnerability to alcohol dependence (alcoholism). We previously identified a quantitative trait locus on chromosome 1 (Adw1) with a large effect on predisposition to alcohol physiological dependence and associated withdrawal following both chronic and acute alcohol exposure in mice. We fine-mapped these loci to a 1.1-1.7 Mb interval syntenic with human 1q23.2-23.3. Adw1 interval genes show remarkable genetic variation among mice derived from the C57BL/6J and DBA/2J strains, the two most widely studied genetic animal models for alcohol-related traits. Here, we report the creation of a novel recombinant Adw1 congenic model (R2) in which the Adw1 interval from a donor C57BL/6J strain is introgressed onto a uniform, inbred DBA/2J genetic background. As expected, R2 mice demonstrate significantly less severe alcohol withdrawal compared to wild-type littermates. Additionally, comparing R2 and background strain animals, as well as reciprocal congenic (R8) and appropriate background strain animals, we assessed Adw1 dependent brain gene expression using microarray and quantitative PCR analyses. To our knowledge this includes the first Weighted Gene Co-expression Network Analysis using reciprocal congenic models. Importantly, this allows detection of co-expression patterns limited to one or common to both genetic backgrounds with high and low predisposition to alcohol withdrawal severity. The gene expression patterns (modules) in common contain genes related to oxidative phosphorylation, building upon human and animal model studies that implicate involvement of oxidative phosphorylation in alcohol use disorders. Finally, we demonstrate that administration of N-acetylcysteine, an FDA-approved antioxidant, significantly reduces symptoms of alcohol withdrawal (convulsions) in mice, thus validating a phenotypic role for this network. Taken together, these studies support the importance of mitochondrial oxidative homeostasis in alcohol withdrawal and identify this network as a valuable therapeutic target in human alcohol use disorders.

overall_design: Whole brain, naïve, males. n=10 inbred C57BL/6J (B6), n=10 R8 small interval Chr 1 congenic (1.1 Mb D2 interval on B6 background), n=6 inbred DBA/2J (D2), n=6 R2 small interval Chr 1 congenic (10.2 Mb B6 interval on D2 background)

middle: A

first: Deaunne

middle: L

last: Denmark

middle: B

last: Kozell

first: Kari

middle: J

last: Buck


title: Genome-wide analysis of the altered gene expression in the transgenic mice ectopically expressing the human SRY. [liver]

first: Yun-Fai

last: Lau

summary: Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse liver. We hypothesize that aberrant expression of the human SRY gene could affect the development and physiology of transgenic mice. To test this hypothesis we have established a Cre-LoxP transgene activation system, thereby activating and expressing the hSRY transgene at the single-cell embryonic stage. Such transgenic mice were born of similar sizes as non-transgenic littermates, but retard in postnatal growth and all die within two weeks of age. To determine the molecular changes associated with such phenotypes, we have analyzed the transcriptomes of livers of pups expressing (hSRY-ON) and not-expressing (hSRY-OFF) the hSRY transgene. The results provide important information demonstrating that ectopic expression of hSRY resulted in altered expression patterns of numerous genes associating with the development of hepatic system and pathogenesis of hepatic system diseases in the liver.

overall_design: Total RNAs isolated from the liver of P6 male hSRY-ON mice was compared to those of age matched male hSRY-OFF mice.

first: Tatsuo

last: Kido


title: Genome-wide analysis of the altered gene expression in the transgenic mice ectopically expressing the human SRY. [heart]

summary: Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse heart. We hypothesize that aberrant expression of the human SRY gene could affect the development and physiology of transgenic mice.  To test this hypothesis we have established a Cre-LoxP transgene activation system, thereby activating and expressing the hSRY transgene at the single-cell embryonic stage. Such transgenic mice were born of similar sizes as non-transgenic littermates, but retard in postnatal growth and all die within two weeks of age. To determine the molecular changes associated with such phenotypes, we have analyzed the transcriptomes of hearts of pups expressing (hSRY-ON) and not-expressing (hSRY-OFF) the hSRY transgene. The results provide important information demonstrating that ectopic expression of hSRY resulted in altered expression patterns of numerous genes associating with the development of cardiovascular system and pathogenesis of cardiovascular diseases in the heart.

overall_design: Total RNAs isolated from the heart of P6 male hSRY-ON mice was compared to those of age matched male hSRY-OFF mice.


title: Genome-wide analysis of the altered gene expression in the transgenic mice ectopically expressing the human SRY. [lung]

summary: Analysis of the effects of an ectopically expressed human SRY (hSRY) on gene expression in the mouse lung. We hypothesize that aberrant expression of the human SRY gene could affect the development and physiology of transgenic mice.  To test this hypothesis we have established a Cre-LoxP transgene activation system, thereby activating and expressing the hSRY transgene at the single-cell embryonic stage. Such transgenic mice were born of similar sizes as non-transgenic littermates, but retard in postnatal growth and all die within two weeks of age. To determine the molecular changes associated with such phenotypes, we have analyzed the transcriptomes of lungs of pups expressing (hSRY-ON) and not-expressing (hSRY-OFF) the hSRY transgene. The results provide important information demonstrating that ectopic expression of hSRY resulted in altered expression patterns of numerous genes associating with the development of respiratory system and pathogenesis of respiratory diseases in the lung.

overall_design: Total RNAs isolated from the lung of P6 male hSRY-ON mice was compared to those of age matched male hSRY-OFF mice.


title: MMS induced expression changes (Drosophila)

status: Public on Feb 14 2017

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: Despite the high toxicity, alkylating agents are still at the forefront of several clinical protocols used to treat cancers. In this study, we investigated the mechanisms underlying alkylation damage responses, aiming to identify novel strategies to augment alkylating therapy efficacy. In this pursuit, we compared gene expression profiles of evolutionary distant cell types (D. melanogaster Kc167 cells, mouse embryonic fibroblasts and human cancer cells) in response to the alkylating agent methyl-methanesulfonate (MMS). We found that many responses to alkylation damage are conserved across species independent on their tumor/normal phenotypes. Key amongst these observations was the protective role of NRF2-induced GSH production primarily regulating GSH pools essential for MMS detoxification but also controlling activation of unfolded protein response (UPR) needed for mounting survival responses across species. An interesting finding emerged from a non-conserved mammalian-specific induction of mitogen activated protein kinase (MAPK)-dependent inflammatory responses following alkylation, which was not directly related to cell survival but stimulated the production of a pro-inflammatory, invasive and angiogenic secretome in cancer cells. Appropriate blocking of this inflammatory component blocked the invasive phenotype and angiogenesis in vitro and facilitated a controlled tumor killing by alkylation in vivo through inhibition of alkylation-induced angiogenic response, and induction of tumor healing.

overall_design: Gene expression of four indpendently grown cultures of KC167 Drosophila cells. Cell were plated and medium was exchanged 24 hours later for media either without (Ctrl) or with MMS (MMS at 40 µg/mL) treatment. RNA was harvested either 0, 1, 8, 24 or 72 hours following initiation of MMS exposure.

first: Alfeu

last: Zanotto-Filho

first: Ravi

last: Dashnamoorthy

first: Pragathi

last: Masamsetti

first: Eva

last: Loranc

first: Subapriya

last: Rajamanickam

first: Ana

middle: V

last: Chavez-Santoscoy

first: Sonal

middle: S

last: Tonapi

first: Robert

last: Reddick

first: Uthra

last: Suresh

first: Alexander

last: Bishop


title: Cartilage rings contribute to the proper embryonic tracheal epithelial differentiation, metabolism and expression of inflammatory genes

status: Public on Apr 14 2017

city: Los Angeles

first: Brendan

last: Grubbs

address: 4661 W. Sunset Blvd.

department: Obstetrics and Gynecology

institute: University of Southern California

summary: The signaling crosstalk between the tracheal mesenchyme and epithelium has not been researched extensively leaving a substantial gap of knowledge in the mechanisms dictating embryonic development of the proximal airways by the adjacent mesenchyme. Recently, we have reported that embryos lacking mesenchymal expression of Sox9 did not develop tracheal cartilage rings and showed aberrant differentiation of the tracheal epithelium. Herein, we propose that tracheal cartilage provides local inductive signals responsible for the proper differentiation, metabolism, and inflammatory status regulation of the tracheal epithelium. The tracheal epithelium of mesenchyme-specific Sox9D/D mutants showed altered mRNA expression of various epithelial markers such as Pb1fa1, Sftpb, Scgb1a1, and Tff-1. In vitro tracheal epithelial cell cultures confirmed that tracheal chondrocytes secrete factors that inhibit club cell differentiation. Whole gene expression profiling and ingenuity pathway analysis showed that the TNF-a, IFN-g and TGF-b signaling pathways were significantly altered in the Sox9 mutant trachea. Tnf-a and Ifn-g interfered with the differentiation of tracheal epithelial progenitor cells into mature epithelial cell types in vitro. Meanwhile, mesenchymal knockout of Tgf-b1 in vivo resulted in altered differentiation of the tracheal epithelium. Finally, mitochondrial enzymes involved in fat and glycogen metabolism Cox8b and Cox7a1 were strongly up-regulated in the Sox9 mutant trachea, with consequently increased number and size of glycogen storage vacuoles. Our results support an a role for tracheal cartilage in the modulation of the differentiation and metabolism, and the expression of inflammatory related genes in the tracheal epithelium by feeding into the TNF-a, IFN-g and TGF-b signaling pathways.

overall_design: E18.5 lung tracheas were used. RNA was extracted from a pool of three tracheas to get sufficient good quality RNA for expression analysis.  Three mutant trachea pools and 3 control tracheal pools were used. The total of 9 mutants and 9 control embryonic tracheas were collected by 7 different pregnant females and randomly pooled together right before extracting the total RNA.

first: Gianluca

last: Turcatel

first: Matthew

middle: E

last: Thornton


title: A positive feedback-loop regulates transcriptional response to murine pandemic influenza infection

status: Public on Feb 10 2017

city: Jena

first: Himanshu

last: Manchanda

address: Beutenbergstraße 11a

department: Systems Biology and Bioinformatics

institute: Hans Knoell Institute

summary: The biological basis for the increased severity of influenza A viruses during the 2009 influenza pandemic remains unclear. Intra-host evolution of quasispecies and strong inflammation were identified as important hallmarks of severe pandemic H1N1 influenza A virus 2009 (A(H1N1)pdm09) infection. HA-222D/G quasispecies of A(H1N1)pdm09 were shown to  undergo fast evolution and to cause severe influenza in human and mice. Here, we analysed the whole genome transcriptional response of mice infected with the A/Jena/5258/09 (mpJena/5258) virus over a period of 12 days to gain insights into the pathogenesis of A(H1N1)pdm09 HA-222D/G quasispecies on a molecular level. Remarkably, the transcriptional response to severe mpJena/5258 showed biphasic expression profile for the majority of genes which was never shown before. The gene expression analysis shows first peak with 968 differentially expressed genes at day 2 post infection (p.i.), followed by a stagnant recovery phase with 359 differentially expressed genes at day 4 p.i., and a second peak with 1001 differentially expressed genes at day 7 p.i., finally followed by a recovery phase. Using a reverse engineering strategy, a regulatory network was inferred to identify key interactions leading to severe pathogenesis of mpJena/5258. Known regulatory interactions were extracted by Pathway Studio 9.0 and softly integrated during network inference. The results demonstrate a hyper-responsive action and a positive feedback loop of IFN gamma (Ifng), Stat1 and Tlr3 signalling during mpJena/5258 infection. In conclusion, mpJena/5258 infection is associated with biphasic gene expression profile and a positive feedback mechanism of Ifng which correlates with the evolution of HA-222D/G quasispecies and leads to  overwhelming immune response. A significant correlation were found between the co-expression action of three genes (Ifng, Stat1 and Tlr3) with a phenomenological clinical symptom score.

overall_design: Total RNA obtained from isolated lung of each mice subjected to Influenza A virus infection (A/Jena/5258/09) pover a period of 12 days compared with control mice.

first: Nora

last: Seidel

first: Markus

middle: F

last: Blaess

first: Ralf

last: Claus

first: Joerg

last: Linde

first: Andreas

last: Sauerbrei

first: Michaela

last: Schmidtke

first: Reinhard

last: Guthke


title: Adam17 Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling in Mice.

status: Public on Jan 30 2017

city: Munich

first: Bernd

middle: Henrik

last: Northoff

address: Marchioninistr. 15

department: Institute of Laboratory Medicine

institute: Ludwig-Maximilians-University Munich


title: Adam17-Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling (macrophage)

summary: Gene expression analysis in tissues of Adam17 hypomorphic and wildtype control C57BL/6 mice.

overall_design: Gene expression level in primary macrophages of Adam17 hypomorphic (n = 8) and wildtype control C57BL/6 mice (n = 8).

first: Alexandros

last: Nicolaou


title: Microarray expression in whole brain of Hfe-/-xTfr2mut (double mut) vs wildtype (wt) AKR mice

status: Public on Feb 09 2017

city: Callaghan

first: Adrienne

last: Milward

state: NSW

address: Medical Science Building MSB

department: School of Biomedical Sciences and Pharmacy

country: Australia

institute: University of Newcastle

summary:
Transcriptome changes were studied in the brain of 13 week male AKR mice with disruption of two iron regulatory genes, hemochromatosis Hfe and transferrin receptor 2 (Tfr2) compared to age and gender matched wildtype controls.
The characterization of these mice is developed by Delima et al. 2012 (Delima, R. D., A. C. G. Chua, J. E. E. Tirnitz-Parker, E. K. Gan, K. D. Croft, R. M. Graham, J. K. Olynyk and D. Trinder (2012). Disruption of hemochromatosis protein and transferrin receptor 2 causes iron-induced liver injury in mice. Hepatology 56(2): 585-593.)

overall_design: Male mice (n=4 per group) were maintained ad libitum on a standard diet containing approximately 0.02% iron. To maximize iron status, Hfe-/-xTfr2mut mice were switched to an iron-supplemented diet containing 2% carbonyl iron  for three weeks prior to sacrifice at 13 weeks of age. Brain hemispheres were snap-frozen in liquid nitrogen and stored at -80C.

first: Elizabeth

first: Daniel

middle: M

last: Johnstone

first: Moones

last: Heidari


title: A recessive point mutation is responsible for pleiotropic effects in a scube3 mutant mouse

first: Martin

last: Irmler

state: Bayern

address: Ingolstaedter Landstrasse 1

institute: Helmholtz Zentrum München GmbH

summary: We established and characterized a new recessive mutant mouse line kta41 with a point mutation in Scube3 at position 882. The mutant line was detected by screening for morphological abnormalities in the Munich ENU-mutagenesis program. The mutation was mapped by microsatellite markers to mouse chromosome 17, between markers D17MIT29 and D17MIT101. Candidate gene approaches failed due to the low recombination frequency and the high number of genes within the mapped interval. Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys). We did a broad phenotypic analysis of the mutant mouse line in the German Mouse Clinic (GMC), and followed up the found alterations by detailed phenotypic characterization. Scube3-kta41-/- mice show a series of phenotypic alterations, mainly in the skeleton, behavior and neurological abnormalities as well as changes in physiology, metabolism and immune status.

overall_design: Total RNA obtained from 4 homozygote male mice and 4 male wild type controls

first: Johannes

last: Beckers

first: Marion

last: Horsch


title: Sexually dimorphic induction of microglial-associated neuroinflammation with hippocampal aging

status: Public on Jan 10 2017

city: Hershey

first: Penn State

last: COM

state: PA

address: 500 University Drive

department: Genome Sciences Facility

institute: Penn State College of Medicine

summary: Hippocampal gene expression in male and female young (3 months) adult (12 months) and old (24 months) C57BL6 mice.

overall_design: Total RNA from mouse (C57BL6) hippocampi [male and female, young (3 months) adult (12 months) and old (24 months) n=4/group)] was analyzed with Illumina Mouse Ref8 microarrays to identify age and sex differences in gene expression.

first: Colleen

last: Mangold

first: Benjamin

last: Wronowsk

first: Mei

last: Du

first: Dustin

middle: R

last: Masser

first: Niran

last: Hadad

first: Georgina

last: Bixler

first: Robert

last: Brucklacher

first: Matthew

last: Ford

first: William

last: Sonntag

first: Willard

last: Freeman


title: Cell lines iPSC CRL1831 (induced pluripotent stem cells) and CSC DLD1 (cancer stem-like cells)  derived from normal colon CRL1831 and colorectal cancer DLD-1 cells in 3D cell culture conditions and subjected to ionizing radiation doses

status: Public on Jan 07 2017

city: Vilnius

first: Egle

last: Strainiene

state: Lithuania

address: P.Baublio 3b

country: Lithuania

institute: National Cancer Institute

summary:
Gene expression profile of two reporgrammed cell lines iPSC CRL1831 (induced pluripotent stem cells) and CSC DLD1 (cancer stem-like cells)  derived from normal colon CRL1831 and colorectal cancer DLD-1 cells, after transfer to 3D cell culture conditions and cell lines treated with single or fractionated ionizing radiation doses under 3D cell culture conditions.
There are no data that cancer metastases arise due to specific mutations of cancer cells. Therefore ongoing investigation of reprogrammed cancer cells grown in three-dimensional (3D) cell culture models might provide researchers with essential data studying tumor oncogenesis and metastases formation. 3D culture models were shown to mimic in vivo cell microenvironment more accurately than the standard two-dimensional cell monolayer (2D) cultures. Also, growing evidence suggests that 2D and 3D cultured cells gene expression pattern variance following irradiation is highly dependent on cancer cell state and their interaction with microenvironment.

overall_design: RNA was harvested from two – normal and colorectal cancer cell lines cultivated under 2D cell culture conditions, non-treated and from 3D cell culture conditions, 4h after treatment of single (2 Gy) or fractionated (3x2 Gy) ionizing radiation dose and from non-treated cells.

first: E

first: M

last: Binkis


title: Adam17-Deficiency Promotes Atherosclerosis by Enhanced TNFR2 Signaling (aorta)

first: Bernd

last: Northoff

overall_design: Gene expression level in aortas of Adam17 hypomorphic (n = 8) and wildtype control C57BL/6 mice (n = 7).

first: Alexandros

last: Nicolaou


title: Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

status: Public on Jan 03 2017

city: Bellinzona

first: Francesco

last: Bertoni

state: Ticino

address: Via V. Vela 6

department: Lymphoma & Genomics Research Program

country: Switzerland

institute: IOR

summary: we evaluated the mechanism behind NOTCH activation in prostate cancer

overall_design: GEP analysis of mice WT, Pten pc+/+; Ptenpc-/-; Ptenpc-/- treated with Gamma-secretase inhibitor

first: Revandkar

last: Ajinkya

first: Andrea

last: Rinaldi

last: Alimonti


title: Selection for Drinking in the Dark Alters Brain Gene Coexpression Networks

status: Public on Jan 16 2017

first: Priscila

last: Darakjian

address: 3181 SW Sam Jackson Park Road, L470

institute: Oregon Health and Science University

summary: Heterogeneous stock (HS/NPT) mice have been used to create lines selectively bred in replicate for elevated drinking in the dark (DID). Both selected lines routinely reach a blood ethanol (EtOH) concentration (BEC) of 1.00 mg/ml or greater at the end of the 4-hour period of access in Day 2. The mechanisms through which genetic differences influence DID are currently unclear. Therefore, the current study examines the transcriptome, the first stage at which genetic variability affects neurobiology. Rather than focusing solely on differential expression (DE), we also examine changes in the ways that gene transcripts collectively interact with each other, as revealed by changes in coexpression patterns.

overall_design: Naïve mice (N = 48/group) were genotyped using the Mouse Universal Genotyping Array, which provided 3,683 informative markers. Quantitative trait locus (QTL) analysis used a marker-by-marker strategy with the threshold for a significant logarithm of odds (LOD) set at 10.6. Gene expression in the ventral striatum was measured using the Illumina Mouse 8.2 array. Differential gene expression and the weighted gene coexpression network analysis (WGCNA) were implemented largely as described elsewhere.

first: Ovidiu

middle: D

last: Iancu

first: Denesa

last: Oberbeck

first: Pamela

last: Metten

first: Shannon

last: McWeeney

first: John

last: Crabbe

last: Hitzemann


title: Nanoparticle exposure of persistently herpesvirus-infected cells reactivates latent virus and restores a signature observed during acute virus infection in vitro and in vivo

status: Public on Dec 19 2016

first: Johannes

last: Beckers

summary:
Both inhalation of environmental (nano)particles (NP) and persistent herpesvirus-infection have been implicated to contribute to the development of chronic lung disease. We hypothesized that the combination of NP exposure and virus infection leads to a different outcome than each factor alone. To test this hypothesis, we applied different carbonaceous NP in the model system of murine gammaherpesvirus 68 (MHV-68), which serves as a small animal model for gammaherpesvirus pathogenesis in vitro and in vivo. NP exposure of latently infected cells induced lytic virus production, while virus growth after de novo infection was not affected.
To investigate the effect of pulmonary NP exposure in vivo, latently infected mice were instilled with carbonaceous NP or left untreated. After 24 hours, lung tissue was harvested for analysis. Immunohistochemistry demonstrated an increase in lytic viral proteins after exposure to NP. Simultaneously, gene expression analysis revealed a signature with considerable parallels to the one seen during acute infection. Analysis of the metabolome demonstrated an enrichment of phospholipids in latently infected mice after short-time exposure to NP, matching profoundly with the pattern observed during acute virus infection. Furthermore, the effect of NP exposure on virus reactivation could also be observed in human cells latently infected with Epstein-Barr-Virus (EBV). Our results indicate that the combination of NP exposure and persistent herpesvirus infection restores a molecular signature found in acute virus infection, boosts production of lytic viral proteins, and induces an inflammatory response in the lung – a pattern which might finally result in tissue damage and fibrotic alterations.

overall_design: Expression data of lung tissue from mice exposed to nanoparticles and/or murine gammaherpesvirus 68 (MHV-68).

first: Christine

last: Sattler

first: Franco

last: Moritz

first: Shanze

last: Chen

first: Beatrix

last: Steer

first: David

last: Kutschke

first: Martin

last: Irmler

first: Oliver

last: Eickelberg

first: Philippe

last: Schmitt-Kopplin

first: Heiko

last: Adler

first: Tobias

last: Stoeger


title: Genome-wide analysis of whole-lung and alveolar macrophages before and after gut microbiome depletion

status: Public on Dec 09 2016

city: Msida

first: Brendon

last: Scicluna

address: Msida campus

country: Malta

institute: University of Malta

summary: Pneumonia accounts for more deaths than any other infectious disease worldwide. The intestinal microbiota has emerged as a key defense system by local support of mucosal immunity as well as proposed modulatory effects on systemic immunity. We here investigated the transcriptomes of whole-lungs and alveolar macrophages between untreated and antibiotic treated mice.

overall_design: Broad spectrum antuibiotics were used to deplete the gut microbiome of C57BL6 mice. Whole lungs and alveolar macrophages were isolated and differential gene expression analysis was performed on untreated and antibiotic treated samples.

middle: P

first: Tim

last: Schuijt


title: Microarray analysis of WT, SKO, PKO and DKO liver samples

status: Public on Dec 13 2016

city: San Diego

first: Xiaolin

last: Luo

address: 9500 Gilman Dr.

department: Pathology

institute: University of California San Diego

summary: Microarray analysis of WT (Pten2fl/fl:Shp2fl/fl:Alb-Cre-), SKO (Shp2hep-/-, or Shp2fl/fl:Alb-Cre+), PKO (Ptenhep-/-, or Pten2fl/fl:Alb-Cre+) and DKO (Ptenfl/fl:Shp2fl/fl:Alb-Cre+) liver samples to gain global molecular insights how shp2 and pten is involved in liver tumorigenesis.

overall_design: Two liver samples from WT, SKO, PKO and DKO were subjected to microarray using illumina system

first: Gen-Sheng

last: Feng


title: Differential activation of OT-1 CD8+ T cells by CD40-activated B cells and dendritic cells

status: Public on Dec 31 2016

city: Montréal

first: Mélissa

last: Mathieu

state: Québec

address: 900 rue Saint Denis

department: CRCHUM

country: Canada

institute: University of Montreal

summary: To determine if CD40-activated B or dendritic cells can induce a similar or different genetic profile in OT-1 CD8+ T cells in early time points following activation

overall_design: CD40-activated B and dendritic cells were cultured in vitro, matured with LPS and loaded with the SIINFEKL peptide (OVA 257-264). OT-1 T cells (CD8+ specifically recognizing the SIINFEKL peptide in the context of H2-Kb) were cocultured either with peptide pulsed CD40-activated B cells or dendritic cells for 24h.  Following coculture, activated OT-1 T cells were sorted based on high expression of CD69 (CD8+CD69+). RNA from sorted cells was extracted using TRIZOL followed Qiagen RNA Cleanup and processed for hybridization to the Illumina mouse-ref8-v2.0 expression beadchip according to the manufacturers protocol.

first: Livia

last: Odagiu

first: Léa

last: Gaudot

first: Jean-François

last: Daudelin

first: Réjean

last: Lapointe

first: Nathalie

last: Labrecque


title: Alpha-Synuclein (Snca) regulates ovariectomy-induced bone loss by altering the expression of genes in specific bone network modules

status: Public on Dec 01 2016

city: Charlottesville

first: Charles

last: Farber

state: VA

department: Center for Public Health Genomics

institute: University of Virginia

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

overall_design: Refer to individual Series


title: Host response in murine fecal peritonitis differs upon the specific fecal microbiota

first: Falk

last: Gonnert

state: Thuringen

address: Erlanger Allee 101

department: Department of Anaesthesiology and Intensive Care Medicine

institute: Jena University Hospital

summary:
We systematically assessed the transcriptomic changes of circulating leukocytes from whole blood of mice that had undergone polymicrobial sepsis.
We systematically assessed the transcriptomic changes of liver tissue of mice that had undergone polymicrobial sepsis.
Data indicate strong dissimilarities in early gene expression during murine sepsis affecting several pathways such as Toll-like receptor signalling, MAPK signalling, cytokine-cytokine receptor interaction, chemokine-signalling, and apoptosis during murine sepsis.

overall_design:
Sepsis can be induced in mice by injecting stool in peritoneal cavity of mice. These models are also known as Peritoneal Contamination and Infection (PCI) models. Heterologous samples were used to understand septic response after injecting fecal slurry from human. Homologous samples were used to understand septic response after injecting fecal slurry from mouse.
[blood_het] RNA from murine circulating leukocytes from whole blood (n=4 for sepsis) was extracted and subjected to microarray analysis for comparison of transcriptomic responses.
[blood_hom] RNA from murine circulating leukocytes from whole blood (n=3 for sepsis) was extracted and subjected to microarray analysis for comparison of transcriptomic responses.
[liver_het] RNA from liver tissue (n=4 for sepsis) was extracted and subjected to microarray analysis for comparison of transcriptomic responses.
[liver_hom] RNA from liver tissue (n=3 for sepsis) was extracted and subjected to microarray analysis for comparison of transcriptomic responses.

first: Vijaykumar

middle: Y

last: Muley

last: Sommerfeld


title: Gene expression profile of liver tissue from carbon tetrachloride (CCl4)-treated mouse cultured ex vivo

status: Public on Dec 16 2016

city: Dallas

first: Yujin

last: Hoshida

address: 5323 Harry Hines Blvd

institute: University of Texas Southwestern Medical Center

summary:
Gene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated and control mice were obtained before and after organotypic ex vivo tissue culture.
keywords: liver tissue, mouse, gene-expression microarray, Illumina, ex vivo tissue culture

overall_design: Animals received humane care according to the criteria outlined in the “Guide for the Care and Use of Laboratory Animals” of the National Academy of Sciences. All animals were maintained in accordance with the institutional guidelines of the Massachusetts General Hospital Subcommittee on Research Animal Care. Strain A/J male mice (Jackson Laboratory, Bar Harbor, ME) were treated three times a week for 18 weeks with either 0.1cc of a 40 percent solution of CCl4 (Sigma) in olive oil or with vehicle control by oral gavage.  Mice were sacrificed and the liver was harvested for RNA extraction (day 0) or organotypic ex vivo tissue culture. Fresh liver tissues were sectioned into 300mm-thick slices and cultured for 24h (day 1) or 48h (day 2) with DMEM/F12 media (Sigma) supplemented with 10% FBS, 100U/mL penicillin, 100mg/mL streptomycin, and 2.5mg/mL amphotericin B. RNA was isolated using TRIzol reagent, and subjected to expression profiling.

first: Bryan

middle: C

last: Fuchs


title: Cardioprotection and lifespan extension by the natural polyamine spermidine

status: Public on Nov 13 2016

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

institute: Helmholtz Zentrum Muenchen

summary:
Aging is associated with an increased risk of cardiovascular disease and death. Here we show that oral supplementation of the natural polyamine spermidine extends lifespan, while it exerts cardioprotective effects through reduction of cardiac hypertrophy and preservation of diastolic function in old mice. Spermidine feeding enhanced cardiac autophagy, mitophagy, mitochondrial respiration and mechano-elastical properties of cardiomyocytes in vivo, coinciding with increased titin phosphorylation and suppressed subclinical inflammation. Spermidine failed to promote cardioprotection in mice lacking the autophagy-related gene Atg5 in cardiomyocytes.
In Dahl salt-sensitive rats fed high-salt diet, a model for hypertension-induced congestive heart failure, spermidine reduced systemic blood pressure, increased titin phosphorylation and prevented cardiac hypertrophy and a decline in diastolic function, thus delaying the progression to heart failure. Finally, high dietary spermidine intake correlated with reduced blood pressure and a lower incidence of cardiovascular disease in humans. Our results suggest a novel and generic strategy against cardiovascular disease.

overall_design: Expression data of heart tissue from three groups: young mice, aged mice and aged mice treated with spermidine

last: Eisenberg

first: Mahmoud

last: Abdellatif

first: Sabrina

last: Schroeder

first: Uwe

last: Primessnig

first: Slaven

last: Stekovic

last: Pendl

first: Alexandra

last: Harger

first: Julia

last: Schipke

first: Andreas

last: Zimmermann

first: Albrecht

last: Schmidt

first: Mingming

last: Tong

first: Christoph

last: Ruckenstuhl

first: Christopher

last: Dammbrueck

first: Angelina

last: Gross

first: Viktoria

last: Herbst

last: Magnes

first: Gert

last: Trausinger

first: Sophie

last: Narath

last: Meinitzer

first: Zehan

last: Hu

first: Alexander

last: Kirsch

first: Kathrin

last: Eller

first: Didac-Carmona

last: Gutierrez

last: Büttner

first: Federico

last: Pietrocola

first: Oskar

last: Knittelfelder

first: Patrick

last: Rockenfeller

first: Corinna

last: Simonini

first: Alexandros

last: Rahn

first: Marion

last: Horsch

first: Kristin

last: Moreth

first: Helmut

first: Valerie

last: Gailus-Durner

first: Martin

middle: H

last: de Angelis

first: Frauke

last: Neff

first: Tarek

last: Moustafa

first: Guenter

last: Haemmerle

first: Manuel

last: Mayr

first: Peter

last: Willeit

last: von Frieling-Salewsky

first: Burkert

last: Pieske

first: Luca

last: Scorrano

first: Thomas

last: Pieber

first: Raimund

last: Pechlaner


title: Genome-wide analysis of primary intestinal epithelial cells with or without Cosmc from 2-month-old mice

status: Public on Dec 18 2016

city: Boston

first: Matthew

last: Kudelka

state: MA

address: Center for Life Sciences, Rm. 11090 - 3 Blackfan Circle

institute: Emory University/Beth Israel Deaconess Medical Center

summary: Analysis of mucin-type O-glycan regulation of gene expression in murine intestinal epithelial cells isolated from a mouse. The hypothesis tested in the current study was that loss of Cosmc (by Cre/Lox: Vil-Cre+ X Cosmcflox/+), which is required for core 1-based O-glycan extension, influences gene expression. Transcripts from colorectum and from small intestine were compared to also evaluate whether O-glycans control different genes in different regions of the gut. We had particular interest in identifying transcripts or pathways important in regulating the microbiota or influencing intestinal inflammation. Results provide important information on how cell surface glycosylation controls gene transcription in in vivo.

overall_design: Total RNA obtained from isolated intestinal epithelia from colorectum (CR) or small intestine (SI) (method: Neufert et al., Journal of Clinical Investigation, 2013) from 2-month-old Vil-Cre+ or Vil-Cre+;Cosmcflox/y mice.

first: Carlos

last: Moreno

first: Richard

last: Cummings


title: Combined transcriptional profiling during systemic candidiasis reveals organ-specific host-pathogen interactions [mouse tissues 12,24,72 h]

status: Public on Nov 18 2016

first: Ilse

middle: Denise

last: Jacobsen

address: Beutenbergstr. 11a

institute: Leibniz Institute for Natural Product Research and Infection Biology

summary: The opportunistic fungal pathogen Candida albicans is a common cause of life-threatening nosocomial bloodstream infections. In the murine model of systemic candidiasis the kidney is the primary target organ while the fungal load declines over time in liver and spleen. To get a better understanding of the organ-specific differences in host-pathogen interaction during systemic murine candidiasis, we performed a time-course gene expression profiling to investigate the differential responses of murine kidney, liver and spleen and determined the fungal transcriptome in liver and kidney. We clearly demonstrate a delayed immune response on the transcriptional level in kidney accompanied by late induction of fungal stress response genes in this organ. In contrast, early upregulation of the proinflammatory response in the liver was associated with a fungal transcriptional profile resembling that of phagocytosed cells, suggesting that the resident phagocytic system contributes significantly to fungal control in the liver. Although no visible filamentation occurred in the liver, C. albicans hypha-associated genes were upregulated, indicating an uncoupling of gene expression and morphology during infection of this organ. In vitro the induction of hypha-associated gene expression in yeast cells led to altered interaction with macrophages, suggesting that the observed transcriptional changes affect host-pathogen interaction in vivo. Consistently, the combination of host and pathogen transcriptional data in an inference network model implied that C. albicans cell wall remodeling and metabolism were connected to the immune responses in kidney and liver. Furthermore, the network suggested links between fungal iron acquisition and amino acid metabolism in the kidney and host organ homeostasis. Thus, this work provides novel insights into the organ-specific host-pathogen interactions during systemic C. albicans infection.

overall_design: 54 mouse samples, time points: 12h, 24, 72h post infection with Candida albiacns, PBS control included

first: Betty

last: Hebecker

first: Sebastian

last: Vlaic

first: Michael

last: Bauer

first: Sascha

middle: O

last: Brunke

first: Theresia

last: Conrad

first: Jörg

last: Linde

first: Bernhard

last: Hube


title: Early born neurons are abnormally positioned in the doublecortin knockout hippocampus

status: Public on Oct 31 2016

city: Paris

first: Fiona

last: Francis

address: 17 rue du Fer à Moulin

department: Inserm UMRS-839

country: France

institute: Institut du Fer à Moulin

summary:
Human doublecortin (DCX) mutations are associated with severe brain malformations leading to aberrant neuron positioning (heterotopia), intellectual disability and epilepsy. The Dcx protein plays a key role in neuronal migration, and hippocampal pyramidal neurons in Dcx knockout (KO) mice are disorganized. The single CA3 pyramidal cell layer observed in wild type (WT) is present as two abnormal layers in the KO, and CA3 KO pyramidal neurons are more excitable than WT. Dcx KO mice also exhibit spontaneous epileptic activity originating in the hippocampus. It is unknown however, how hyperexcitability arises and why two CA3 layers are observed.  Transcriptome analyses were performed to search for perturbed postnatal gene expression, comparing Dcx KO CA3 pyramidal cell layers with WT. Gene expression changes common to both KO layers indicated mitochondria and Golgi apparatus anomalies, as well as increased cell stress. Intriguingly, gene expression analyses also suggested that the KO layers differ significantly from each other, particularly in terms of maturity.  Layer-specific molecular markers and BrdU birthdating to mark the final positions of neurons born at distinct timepoints revealed inverted layering of the CA3 region in Dcx KO animals. Notably, many early-born ‘outer boundary’ neurons are located in an inner position in the Dcx KO CA3, superficial to other pyramidal neurons. This abnormal positioning likely affects cell morphology and connectivity, influencing network function. Dissecting this Dcx KO phenotype sheds light on coordinated developmental mechanisms of neuronal subpopulations, as well as gene expression patterns contributing to a bi-layered malformation associated with epilepsy.
Expression profiling by array

overall_design: 15 laser microdissection samples analyzed corresponding to 5 wild type mouse brain hippocampi CA3 region, 5 doublecortin knockout mouse brain hippocampi internal part of CA3 region and from the same 5 knockout animals, mouse brain hippocampi external part of CA3 region

first: Melissa

last: Stouffer


title: A new model for long-range chromatin reorganization linked to enhancer activation [Agilent_RNA]

status: Public on Nov 04 2016

city: Edinburgh

first: Nezha

middle: Suzanne

last: Benabdallah

state: Midlothian

address: Crewe Road South

department: Institute of Genetics and Cancer

country: United Kingdom

institute: University of Edinburgh

type: Expression profiling by genome tiling array

summary:
The most prominent model for long-range enhancer regulation involves direct enhancer-promoter interaction by looping out the intervening chromatin. Using a synthetic biology approach, we have determined that a chromatin unfolding bteween Shh and its enhancers is regulated specifically by the Shh-Brain-Enhancers and is mediated by the recruitment of Poly (ADP-Ribose) Polymerase 1.  This ‘chromatin unfolding’ model represents a new mechanism of long-range enhancer-promoter communication in addition to the looping and tracking models.
RNA-on-chip for probing nuclear RNA on the Shh regulatory region on ESCs and NPC showed no spreading of nuclear RNA in the regulatory region upon Shh activation.

overall_design: Comparison of ESCs and NPC nuclear RNA profiles on Shh region

first: Iain

last: Williamson

first: Robert

last: Illingworth

first: Shelagh

last: Boyle

first: Graeme

last: Grimes

first: Pierre

last: Therizols

first: Wendy

middle: A

last: Bickmore


title: STAT1 signaling in astrocytes is essential for control of infection in the central nervous system

status: Public on Oct 20 2016

city: Philadelphia

first: daniel

last: beiting

address: 380 S. University Ave

department: Pathobiology

institute: University of Pennsylvania

summary: The local production of IFN-γ is important to control Toxoplasma gondii in the brain but the basis for these protective effects are not fully understood. The studies presented here reveal that the ability of IFN-γ to inhibit parasite replication in astrocytes in vitro is dependent on signal transducer and activator of transcription 1 (STAT1) and that mice that specifically lack STAT1 in astrocytes are unable to limit parasite replication in the central nervous system (CNS). This susceptibility is associated with a loss of anti-microbial pathways but also altered local immune responses that include decreased T cell production of IFN-γ and elevated expression of inhibitory receptors. These results identify a critical role for astrocytes in limiting the replication of an important opportunistic pathogen and highlight their role in coordinating local anti-parasitic responses.

overall_design: Three conditions were analyzed. Primary mouse astrocytes derived from mixed glial cultures from the cerebral cortex of 1-3 day old neonatal mice were either left untreated, or were stimulated with 10ng/ml of recombinant mouse IFNg or IFNa for 12 hours.  Two biological replicates were used for each condition.

first: Daniel

last: Beiting

first: Christopher

last: Hunter

first: Shinya

last: Hidano


title: Transintestinal cholesterol transport is important in mice and humans and controls  ezetimibe induced fecal neutral sterol excretion

city: Groningen

first: vincent

last: bloks

department: Pediatrics

country: Netherlands

institute: UMCG

summary: Except for conversion to bile salts, there is no major cholesterol degradation pathway in mammals. Efficient excretion from the body is therefore a crucial element in cholesterol homeostasis. Yet, the existence and importance of these pathways in humans is a matter of debate. We quantified cholesterol fluxes in 15 male volunteers using a cholesterol balance approach. Ten participants repeated the protocol after 4-weeks treatment with ezetimibe, an inhibitor of intestinal and biliary cholesterol absorption. Under basal conditions, about 65% of daily fecal neutral sterol excretion was bile-derived, with the remainder being contributed by direct transintestinal cholesterol excretion (TICE). Surprisingly, ezetimibe induced a fourfold increase in cholesterol elimination via TICE. Mouse studies revealed that most of ezetimibe-induced TICE flux is mediated by the cholesterol transporter Abcg5/Abcg8. In conclusion, TICE is active in humans and may serve as a novel target to stimulate cholesterol elimination in patients at risk for cardiovascular disease.

overall_design:
8 controls and 5 EZE-treated mice.

For microarray analysis, intestinal (proximal)  RNA was prepared from EZE 0.005%-compound and regular chow fed  C57BL/6J mice using TRI-reagent (Sigma-Aldrich, St. Louis, MO, USA). RNA quality and concentration was assessed with an Biorad Experion Bioanalyzer. Starting with 200 ng of RNA, with an RNA Quality Indicator of at least 7. RNA was amplified and labeled using the Illumina TotalPrep RNA Amplification Kit (Applied Biosystems, Nieuwekerk ad IJssel, The Netherlands). The MouseRef-8 v2.0 expression beadchip  arrays, containing 25697 transcripts (Illumina, San Diego, USA), were processed according to the manufactures protocol and slides were scanned immediately. Quality control, normalization (quantile), batch correction (Combat), prefiltering (fold change 1.1) and statistics (IBMT) were performed in MADMAX. A list of significant changed annotated genes between EZE (n = 5) and WT (n = 8), including False Discovery Rates (FDR)-corrected p-values (10%) was generated. Identification of KEGG pathway enrichment analysis among responsive genes was performed using the DAVID Functional Annotation Clustering tool.

first: L

last: Jakulj

first: T

last: van Dijk

first: R

last: Kootte

last: Boer

first: V

middle: W

last: Bloks

first: M

last: Nieuwdorp

last: Boverhof

first: U

last: Beuers

first: E

last: Stroes

first: Y

last: Paalvast

first: J

last: de Boer

last: Schonewille

first: A

middle: K

last: Groen


title: IL-15R-alpha controls hepatic stellate cell fibrogenic potential during murine chronic liver injury

status: Public on Sep 21 2016

first: Yujin

last: Hoshida

summary:
Gene-expression profiles of hepatic stellate cells isolated from IL15R-alpha knockout mouse
IL-15 and its high affinity receptor IL-15Rα are widely expressed in immune cells including dendritic cells and macrophages and non-immune cells such as hepatocytes, oval cells and hepatic stellate cells (HSC). IL-15 signaling has important functions in natural killers (NK), natural killers T (NKT) and cytotoxic T (CD8+T) cell homeostasis and also in liver regeneration. We hypothesized that IL-15 may have a protective role during liver fibrosis progression due to its role in NK cell homeostasis. We compared fibrosis progression in IL-15Rα knockout mice (IL-15RαKO) to wild type mice using two mechanistically distinct models, chronic carbon tetrachloride (CCl4) exposure and bile duct ligation (BDL). Enhanced fibrosis progression was observed in IL-15RαKO mice in both models. Furthermore, using congenic bone marrow transplantation (BMT), we demonstrated an unexpected role for IL-15 signaling in hepatic resident cells for the maintenance of liver NK and CD8+T cell populations. Using this approach, transplanting IL-15RKO hematopoietic cells results in NK defect that surprisingly is not reflected in a change of fibrosis progression. However, chimeric mice with defect of IL-15R on liver resident cells have similar NK defects and significant more fibrosis after CCL4 liver injury. This supports a direct protective, anti-fibrogenic role for IL-15R on one of the radioresistant liver cell populations (hepatocytes, HSC and sessile Kupffer cells). Microarray analysis of IL15RKO HSC suggests up-regulation of collagen transcripts and down-regulation of pathways involved in cell proliferation/survival. Finally, activated HSCs isolated from IL-15RKO mice show increased collagen secretion and as predicted, no changes in the growth curves. In summary, IL-15Rα signaling has an anti-fibrotic effect through both BM-derived and hepatic resident cells. These findings establish a rationale to explore IL-15 signaling in HSC as a potential therapeutic target in liver fibrogenesis.

overall_design:
Six week-old female IL-15RKO and wild type (WT) B6/129 mice were purchased from Jackson Laboratories (Bar Harbor, ME). All procedures were performed in accordance with the Institutional Animal Care and Use Committee Protocols of the Mount Sinai School of Medicine. Mouse HSCs were isolated from WT and IL-15RKO mice using an established method with modifications. Briefly, the mouse liver was perfused in situ with pronase and collagenase, followed by Percoll (GE) density gradient centrifugation. HSC cultures were maintained in Dulbecco's Modified Eagle Medium with 20% Fetal Bovine Serum. RNA was isolated from primary mouse hepatic stellate cell (Passage 0) with Triazol reagent (Invitrogen) followed by a cleanup procedure using QIAGEN RNeasy minicolumns according to manufacturer’s protocol. RNA samples were processed for hybridization on the MouseRef-8 v2.0 Expression Beadchip (Illumina) by the Genomics Core Facility of Mount Sinai School of Medicine. Raw data were taken from iScan Control Software (Illumina) and analyzed using Genomestudio Software (Illumina) with quantile normalization.
hepatic stellate cell, mouse, gene-expression microarray, Illumina, IL15R-alpha knockout

first: Jingjing

last: Jiao

first: Maria

middle: I

last: Fiel

first: Adeeb

last: Rahmman

first: Jennifer

last: Miller

first: Kensuke

last: Kojima

first: Tatiana

last: de Paula

first: Diana

last: Veter

first: David

last: Sastre

first: Ka

last: Lee

first: Miriam

last: Merad

first: Scott

middle: L

last: Friedman

first: Costica

last: Aloman


title: Analysis of hepatic transcript profile and plasma lipid profile in early lactating dairy cows fed grape seed and grape marc meal extract

status: Public on Sep 02 2016

city: Gießen

first: Robert

last: Ringseis

address: Heinrich-Buff-Ring 26-32

department: Institute of Animal Nutrition and Nutrition Physiology

institute: JLU Gießen

summary: As polyphenols are exerting a broad spectrum of metabolic effects, we hypothesize that feeding of GSGME might influence other metabolic pathways in the liver which could account for the positive effects of GSGME observed in cows during early lactation. In order to investigate this hypothesis, we used using a genome-wide transcript profiling technique to explore changes in the hepatic transcriptome of cows supplemented with GSGME during the transition period. Transcriptomic analysis of the liver revealed 207 differentially expressed transcripts (fold change > 1.3 or < -1.3, P < 0.05), from which 156 (155 mRNAs, 1 miRNA) were up- and 51 (43 mRNAs, 8 miRNAs) were down-regulated, between cows fed GSGME and control cows. Gene set enrichment analysis of the 155 up-regulated mRNAs showed that the most enriched gene ontology (GO) biological process terms were dealing with cell cycle regulation, such as M phase, cell cycle phase, mitotic cell phase and microtubule cytoskeleton and the most enriched KEGG database pathways were p53 signaling and cell cycle. Functional analysis of the 43 down-regulated mRNAs revealed that 13 genes (XBP1, HSPA5, HERPUD1, DNAJC5G, CALR, PDIA4, DNAJB11, PHLDA1, PPP1R3C, GADD45B, BAG3, HYOU1, MANF) are involved in ER stress-induced UPR. Moreover, several of the down-regulated mRNAs, like CXCL14 and CCL3L1L and the acute phase protein SAA4, play an important role in inflammatory processes. Accordingly, protein folding, response to unfolded protein, response to protein stimulus, unfolded protein binding, chemokine activity, chemokine receptor binding and heat shock protein binding were identified as one of the most enriched GO biological process and molecular function terms assigned to the down-regulated genes. In line with the transcriptomics data the plasma concentrations of the acute phase proteins SAA and haptoglobin were reduced in cows fed GSGME compared to control cows. Collectively, our findings from transcriptome analysis of down-regulated mRNAs and functional analysis of mRNAs targeted by the up-regulated mir-376c clearly indicate that GSGME is able to inhibit inflammatory processes and ER stress in the liver of dairy cows during early lactation. Moreover, our findings indicate that at least some of the GSGME effects on the hepatic transcriptome of dairy cows are mediated by miRNA-mRNA interactions.

overall_design: For microarray analysis, six RNA samples each of the control group and the GSGME group were used for hybridization to the Affymetrix GeneChip Bovine Gene 1.0 ST array.

first: Denise

last: Gessner

first: Anne

last: Winkler

first: Christian

last: Koch

first: Georg

last: Dusel

first: Gerhard

last: Liebisch

first: Klaus

last: Eder


title: Transcriptomic analysis of the effect of ASO-mediated (50ug/day) CD33 knock-down on the microglial gene network in an APP/PS1 mouse model of Alzheimer’s disease. [LNA-012]

status: Public on Sep 30 2016

city: Paramus

first: Mary

middle: E

last: Hamby

state: New Jersey

address: 215 College Road

department: Neuroinflammation Disease Biology Unit

institute: Lundbeck Research USA

summary: Microglia, the resident innate immune cells of the central nervous system (CNS), are increasingly recognized  as critical for normal CNS function as well as for the pathophysiology of CNS disorders, including Alzheimer's disease (AD).  Advances in transcriptomic analyses, such as weighted gene co-expression network analysis, reveal that the most perturbed gene networks identified in AD brains fall squarely within microglial pathways and these findings are consistent with genetic and epigenetic genome-wide association studies linking specific microglial genes to AD risk.  Increased expression of full-length CD33 increases AD risk and CD33 is a component of the microglial gene network, yet relatively little is known about the significance of CD33 in this gene network or in microglial biology.  To gain further insight into these questions, we first identified and characterized locked nucleic acid (LNA) antisense oligonucleotides (ASOs) as tools to knock down CD33 in APP/PS1 mice in vivo.  We report here that CD33 LNA ASO results in robust knockdown of CD33 mRNA the frontal cortex and hippocampus of APP/PS1 mice and that this knockdown causes changes to the AD-associated microglial gene network. This work suggests that CD33 may be a viable therapeutic target in AD.

overall_design: The double transgenic APP/PS1 mouse model of AD (first described by Mathias Jucker's group) was treated either with a CD33-specific ASO (N=14), a non-target Control ASO (N=13), or PBS vehicle (N=9). Wild-type littermates were also treated with PBS vehicle (N=12). Animals were dosed with 50ug/day of ASO (pump delivers 6uL/day) for 14 days starting at 18 weeks of age and were sacrificed as described at 22 weeks of age. Number of microarray samples for analysis were as follows. Frontal cortex: APP/PS1-CD33 ASO, 11; APP/PS1-CON ASO, 13; APP/PS1-PBS, 9; WT-PBS, 12. Hippocampus: APP/PS1-CD33 ASO,12; APP/PS1-CON ASO, 13; APP/PS1-PBS, 9; WT-PBS,12.

first: Sean

last: Pintchovski

first: Shaun

last: Fallon

first: Jiaping

last: Gu

first: Joseph

last: Tamm

first: Aicha

last: Abdourahman

first: Thomas

last: Möller

first: Paul

last: Wes


title: Time-dependent transcriptomic profiles of mouse hippocampus in kainic acid-induced mesial temporal lobe epilepsy (MTLE)

summary: Mesial Temporal Lobe Epilepsy (MTLE) is a chronic disease characterized by recurrent unprovoked partial seizures. Current treatments lack long-term efficacy and typically act only to ameliorate the symptomology, rather than to modify the course of the disease. Chronic kainic acid (KA)-induced models of MTLE mimic prominent histopathological and electroencephalographic features of human MTLE, including hippocampal sclerosis, CA1 neuronal loss, astrogliosis, microgliosis, and electrographic hippocampal discharges.   Here we examined the transcriptional profiles of the hippocampus of KA - vs sham-injected mice from epileptogenesis to the stabilization of spontaneous recurring seizures. KA (1 nmol) or saline (sham) was injected unilaterally into the dorsal hippocampus of 12 week old C57BL/6J mice, and the ipsilateral (IL) and contralateral (CL) hippocampi were isolated for whole-genome expression profiling (Illumina microarray) or immunohistochemistry 7, 28 and 60 d later. Differential gene expression analysis of the IL hippocampus indicated that 1349, 484, and 439 genes were significantly (fdr<0.05) altered in KA compared to sham at 7, 28 and 60 d, respectively. 108 genes were altered at all time-points assessed, while others were altered in a time-dependent manner, indicative of distinct hippocampal gene expression profiles across the course of disease. Ingenuity Pathway Analysis revealed that specific immune cell and inflammatory signaling pathways were upregulated at 7 and 28 d, in support of a role of neuroinflammation in the disease etiology. The top canonical pathways profile at 60 d was quite distinct from that at 7 and 28 d, although certain inflammatory pathways were still prevalent, indicative of pathways involved in the maintenance of the disease. Consistent with a role of neuroinflammation in MTLE, immunohistochemical analyses demonstrated time-dependent changes in both the intensity of immunoreactivity and number of Iba1- and GFAP-positive cells.   To reveal gene networks not apparent with differential expression data alone, weighted gene co-expression analysis (WGCNA) was performed. A gene network that highly associated with 7 d IL-KA (but not 28 and 60 d) was identified, which may point to changes involved in the process of epileptogenesis. Another gene network revealed a group of genes highly associated with changes occurring at 28 and 60 d, but not 7 d, which may point to molecules involved in the generation of spontaneous recurring seizures. Collectively, results indicate that specific pathways, including many associated with neuroinflammation, are activated in a time-dependent manner in MTLE.

overall_design: 40 animals were in the study; 80 samples were analyzed via Illumina beadchip microarray, a total which included 2 samples (IL and CL hippocampus) from each animal. Of the 80 samples,the n were as follows: IL-KA-7d, 8; CL-KA-7d, 8; IL-KA-28d, 9; CL-KA-28d, 9; IL-KA-60d, 9; CL-KA-60d, 9; IL-sham-7d, 4; CL-sham-7d, 4; IL-sham-28d, 5; CL-sham-28d, 5; IL-KA-60d, 5; CL-KA-60d, 5.

first: Megan

middle: J

last: DenBleyker

first: Steve

last: Leiser

first: Jordi

last: Serrats

first: Glenn

last: Terry

middle: B

last: Nelson

first: Stevin

last: Zorn

first: Brian

last: Campbell

first: Nathalie

last: Breysse


title: Gene expression profiling of WT or Dicer KO iNKT cells and T cells

status: Public on Nov 17 2016

city: Milano

first: Michela

last: Riba

address: via Olgettina 60

department: COSR, Center for Omics Sciences

country: Italy

institute: IRCCS, Ospdale San Raffaele

summary: iNKT cells are a T lymphocyte subset displaying an innate effector phenotype that is acquired through a thymic developmental program controlled by microRNAs (miRNAs). iNKT cells lacking all miRNAs by the deletion of Dicer (Dicer KO) are markedly reduced and display a complete maturation block. In this study, we sought to gain insight into the miRNA-regulated genetic program required for iNKT cell development. By systemic analysis, we identified transcripts differentially expressed between thymic WT or Dicer KO iNKT cells and targeted by the iNKT cell-specific miRNAs. TGF-βRII, a molecule critically implicated in iNKT cell maturation, was found upregulated in Dicer KO iNKT cells together with increased TGF-β-dependent signaling. miRNAs belonging to the paralog miR-106a~363, miR-106b~25 and miR-17~92 clusters were predicted to target TGF-βRII mRNA during iNKT cell development. Thymic iNKT cells lacking all three miRNA clusters displayed both increased TGF-βRII expression and signaling and a maturation block, recapitulating those found in Dicer KO iNKT cells. Consistently, inhibition of TGF-β-dependent signaling in the absence of miRNAs, by crossing TGF-βRII KO and Dicer KO mice, rescued iNKT cell maturation. Collectively, our results highlight a fundamental requirement of the modulation of TGF-β-dependent signaling by miRNAs for iNKT cell development

overall_design: invariant NKT cells (divided in stage 1-2 or stage 3 cells) and T lymphocytes were sorted from HSAlow enriched thymi of WT and Dicer KO 4-week old mice, in triplicate

first: Maya

last: Fedeli

first: Jose

middle: M

last: Garcia Manteiga

first: Lei

last: Tian

first: Valentina

last: Viganò

first: Grazisa

last: Rossetti

first: Massimiliano

last: Pagani

first: Changchun

last: Xiao

first: Adrian

last: Liston

first: Sergio

last: Abrignani

first: Davide

last: Cittaro

first: Elia

last: Stupka

first: Paolo

last: Provero

last: Dellabona

first: Giulia

last: Casorati


title: Bone gene expression profiles after ovariectomy in multiple inbred strains

first: Charles

middle: R

last: Farber

summary: The peri- and postmenopausal periods in women are associated with decreases in circulating estrogen levels, marked acceleration of age-related bone loss and increased risk of fracture.  However, despite the clinical importance of postmenopausal bone loss, our molecular understanding of this process is incomplete.  Here, we used co-expression network analysis to gain novel insight into the molecular mechanisms mediating bone loss in ovariectomized (OVX) mice, a model of human menopause.  Expression profiles from intact and OVX mice from a panel of inbred strains were used to generate a co-expression network consisting of 29 modules.  Genes in network module 25 were decreased by OVX in all strains.  Module 25 was enriched for genes involved in the response to oxidative stress, a process known to be an upstream causal factor for OVX-induced bone loss.  It was also found that module 25 homologs were co-expressed in human bone marrow and were enriched for genes with evidence of genetic association with bone mineral density (BMD) in women.  Alpha synuclein (Snca) was the most highly connected “hub” genes in module 25 and its in vivo knockout resulted in a 40% reduction in OVX-induced bone loss.  Furthermore, protection was associated with the targeted alteration of genes in specific network modules, including module 10.  Our results identify a gene module associated with OVX-induced bone loss and demonstrate that Snca regulates ovariectomy-induced bone loss by controlling bone network dynamics.

overall_design: Lumbar verebrae (L5) were isolated from three inbred strains of mice (C57BL/6J, C3H/HeJ and BALB/cJ) four-weeks post SHAM surgery or ovariectomies (OVX).  A total of 23 samples were profiled (N=3-4 strain/surgical group).


title: Network and pathway microarray expression analysis of cardiac-specific estrogen receptor alpha knockout mice

status: Public on Aug 12 2016

city: Saint Louis

first: Kooresh

middle: Isaac

last: Shoghi

state: MO

address: 510 South Kingshighway Blvd.

department: Department of Radiology

institute: Washington University School of Medicine

summary: Analysis of estrogen receptor alpha function in the heart at gene expression level. The hypothesis tested in the present study was that absence of estrogen receptor alpha may induce cardiometabolic alterations. Results provide information of the responses to the absence of Estrogen receptor alpha such as core pathways that are affected, up- or down-regulated specific  metabolic functions.

overall_design: Cardiac RNA isolated from 18 weeks old mice heart, both males and female cardiac-specific estrogen receptor alpha knockout mice compared to their corresponding age and sex matched controls.

first: Sriram

last: Devanathan

first: Timothy

last: Whitehead

first: George

middle: G

last: Schweitzer

first: Brian

middle: N

last: Finck


title: Imipramine Blue: A potent therapeutic regimen that suppresses breast cancer growth and metastasis

status: Public on Aug 10 2016

city: San Antonio

first: Yidong

last: Chen

address: 8403 Floyd Curl Drive, MSC 7784

department: Population Health Sciences

institute: UT Health Science Center at San Antonio

summary: Imipramine Blue a novel inhibitor that we recently synthesiszed suppressed breast cancer growth and progression by silencing FOXM1 and its associated signaling.

overall_design: Breast cancer cell-line MDA-MB-231 treated with vehicle (DMSO) and IB, with 2 biological replciates each.

first: Subapriya

last: Rajamanickam

first: Manjeet

last: Rao


title: Bone gene expression profiles in alpha-synuclein (Snca) knockout mice after ovariectomy

overall_design: Lumbar verebrae (L5) were isolated from Snca wild-type and global knockout four-weeks post SHAM surgery or ovariectomies (OVX).  A total of 16 samples were profiled (N=4/genotype/surgical group).


title: Transcriptomic analysis of the effect of ASO-mediated CD33 knock-down on the microglial gene network in an APP/PS1 mouse model of Alzheimer’s disease. [LNA-006]

first: Mary

last: Hamby

overall_design: The double transgenic APP/PS1 mouse model of AD (first described by Mathias Jucker’s group) was treated either with a CD33-specific ASO  (N=10), a non-target Control ASO (N=10), or PBS vehicle (N=10). Wild-type littermates were also treated with PBS vehicle (N=10). Animals were dosed with 75ug/day of ASO (pump delivered 6uL/day) for 14 days starting at 18 weeks of age and were sacrificed at ~20.5 weeks of age (~ 17 days after start of 14 day ASO infusion). N for microarray analysis is as follows: For Hippocampus, APP/PS1_ CD33 ASO, n=9; APP/PS1_CON ASO, n=11; APP/PS1_PBS, n=8; WT_PBS, n=11; and for frontal cortex, APP/PS1_ CD33 ASO, n=10; APP/PS1_CON ASO, n=11; APP/PS1_PBS, n=8; WT_PBS, n=11.

first: Sean

last: Pintchovski

first: Shaun

last: Fallon

first: Jiaping

last: Gu

first: Joseph

last: Tamm

first: Aicha

last: Abdourahman

first: Thomas

last: Möller

first: Paul

middle: D

last: Wes


title: Whole genome transcriptome analysis of tumor-specific CD8 T cells in pre-malignant lesions

status: Public on Aug 11 2016

city: New York

first: Andrea

last: Schietinger

state: NY

address: 1275 York Avenue

department: Immunology

institute: Memorial Sloan Kettering Cancer Center

summary:
Gene expression analysis of tumor-specific CD8 T cells encountering a tumor-specific antigen in pre-malignant lesions in the liver at different time points post tumor initiation. The overall goal of this mouse study was to elucidate the molecular program in tumor-specific T cells encountering a tumor-specific antigen in pre-malignant lesions. The study identifies the genes and pathways that are dysregulated in tumor-specific T cells associated with T cell unresponsiveness in tumors.
To identify the genes and pathways that are dysregulated in tumor-specific T cells. Gene signatures of the following sample groups were compared:  1. Naïve CD8 T cells; 2. Effector CD8 T cells; 3. Dysfunctional tumor-specific CD8 T cells isolated from pre-malignant lesions 8-12 days after tumor induction. 4. Dysfunctional tumor-specific CD8 T cells isolated from pre-malignant lesions 32-34 days after tumor initiation.  The mouse tumor model that was used is an autochthonous, tamoxifen-inducible liver cancer model (ASTxCre-ERT2; AST=Albumin-floxStop-SV40 large T antigen; Cre-ERT2 = TAM-dependent Cre-recombinase) in which the SV40 large T antigen serves as the oncogenic driver and tumor-specific antigen; SV40-I TCR transgenic mice, whose CD8 T cells express a Db-restricted TCR specific for the Tag epitope I were used as source of naïve tumor-specific CD8 T cells (TCRSV40-I)

overall_design: Total RNA was isolated from flow-sorted transgenic CD8 TCRSV40-I T cells from the following sample groups: Naïve, effector, D8-12-pre-malignant lesions, and D32-34 pre-malignant lesions.

first: Philip

last: Greenberg

first: Ryan

middle: S

last: Basom

first: Jeffrey

last: Delrow


title: In vivo differentiation of induced pluripotent stem cells into neural stem cells by chimera formation

status: Public on Oct 05 2016

city: Seoul

first: Hyun Woo

last: Choi

institute: Konkuk University

summary: Like embryonic stem cells, induced pluripotent stem cells (iPSCs) can differentiate into all three germ layers in an in vitro system. Here, we developed a new technology for obtaining neural stem cells (NSCs) from iPSCs through chimera formation, in an in vivo environment. iPSCs contributed to the neural lineage in the chimera, which could be efficiently purified and directly cultured as NSCs in vitro. The iPSC-derived, in vivo-differentiated NSCs expressed NSC markers, and their gene-expression pattern more closely resembled that of brain-derived NSCs than in vitro-differentiated NSCs. This system could be applied for differentiating pluripotent stem cells into specialized cell type whose differentiation protocols are not well established.

overall_design: Brain-NSCs (from 13.5dpc fetuses, ROSA26/OG2 heterozygous double transgenic), iPS-NSCs #1, #3 (In vitro differentiated), iPS-cNSCs (In vivo differentiated, chimeric), NED-NSCs (normal embryo-derived),   MEFs (from 13.5dpc fetuses, ROSA26/OG2 heterozygous double transgenic), and ESCs (OG2 heterozygous double transgenic) were used for analysis.

first: Hyun-Woo

first: Jong-Soo

last: Kim

first: Yean-Ju

last: Hong

first: Hyuk

last: Song

first: Ssang-Gu

last: Cho

first: Hojae

last: Bae

first: Changsung

first: Jeong-Tae

last: Do


title: Reprogramming Mouse Fibroblasts into Engraftable Myeloerythroid and Lymphoid Progenitors: Induction and Underlying Mechanisms (BeadChip)

city: Singapore

first: Chadi

last: El Farran

address: 61 Biopolis Drive

country: Singapore

institute: Institute of Molecular and Cell Biology

summary: Here we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally-distant lineage (fibroblasts) into “induced hematopoietic progenitors” (iHPs). We analyzed transcriptomic data for cell undergoing the transdifferentiation process at several time-points of the process.

overall_design: We performed microarray transcriptome analysis of wild-type fibroblasts (MEFs), intermediate populations undergoing SLRH reprogramming (4 dpi  and 14 dpi), reprogrammed 26 dpi iHPs (CD45+ or Kit+) and finally bone marrow (BM) (CD45+ or Kit+) cells as a positive control

first: C

last: EL Farran

first: H

last: Cheng

last: Fang

first: T

last: Liu

first: Y

middle: H

last: Loh

first: B

last: Lim


title: Transcriptomic analysis of the effect of ASO-mediated CD33 knock-down on the microglial gene network in an APP/PS1 mouse model of Alzheimer's disease.

first: Mary

last: Hamby

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

overall_design: Refer to individual Series


title: The Role of PTHrP in Osteoblast Response to Microgravity: Implications for Osteoporosis Development.

status: Public on Aug 09 2016

city: Montréal

first: Anne

last: Camirand

state: QC

address: 1001 Décarie Blvd mail drop EM 1.3229

institute: McGill University

summary: Prolonged skeletal unloading through bedrest results in bone loss similar to that observed in elderly osteoporotic patients, but with an accelerated timeframe.  This rapid effect on weight-bearing bones is also observed in astronauts who lose up to 2% of their bone mass per month spent in Space. Despite important implications for Spaceflight travellers and bedridden patients on Earth, the exact mechanisms involved in disuse osteoporosis have not been elucidated.  Parathyroid hormone-related protein (PTHrP) regulates many physiological processes including skeletal development, and has been proposed as a gravisensor.  To investigate the role of PTHrP in microgravity-induced bone loss, trabecular osteoblasts (TOs) from Pthrp+/+ and -/- mice were exposed to simulated microgravity for 6 days.  Viability of TOs decreased in inverse proportion to PTHrP expression levels. Microarray analysis of Pthrp+/+ TOs after 6 days at 0g revealed expression changes in genes encoding prolactins,apoptosis and survival molecules, bone metabolism and extra-cellular matrix composition proteins, chemokines, IGF family and Wnt-related signalling molecules.  Importantly, 88% of 0g-induced expression changes in Pthrp+/+ cells overlap those observed in Pthrp-/- cells in normal gravity.  Pulsatile treatment with PTHrP1-36 peptide during microgravity exposure reversed a large proportion of 0g-induced changes in Pthrp+/+ TOs.  Our results confirm PTHrP efficacy as an anabolic agent to prevent microgravity-induced cell death in TOs.

overall_design: Total RNA samples extracted from Pthrp+/+and -/- trabecular osteoblasts (TOs) exposed for 6 days to simulated 0g in Synthecon rotating cell, or left 6 days in culture at 1g.  Cells had either been treated with a pulsatile treatment (2 h/day) of PTHrP1-36 peptide (10-8M) or received a change in growth medium.  In total: 8 different conditions with 2 replicates each, i.e. Pthrp+/+ TOs at 0g or 1g with or without PTHrP1-36 treatment, and Pthrp-/- TOs at  0g or 1 g,with or without PTHrP1-36 treatment.

first: Andrew

middle: C

last: Karaplis


title: Gene expression profiles in TICAM1 knockout and wild-type MEFs

status: Public on Jul 29 2016

city: Toledo

first: Saurabh

last: Chattopadhyay

state: OH

address: 3000 Arlington Ave

department: MMI

institute: University of Toledo

summary: TICAM1 knockout and wild-type (TICAM1 knockout MEFs with restored TICAM1 expression) MEFs were treated by c-di-GMP or DMSO for 4 hours. Total RNA was analyzed via Illumina Mouse Ref-8 V2. Changes in gene induction, especially of interferon-stimulated genes, between c-di-GMP and DMSO treated cells were examined.

overall_design: Total RNA from c-di-GMP or DMSO treated wild-type MEFs, c-di-GMP or DMSO treated TICAM1 knockout MEFs were analyzed. Gene expression was compared between c-di-GMP treated and DMSO treated samples.

first: Ganes

last: Sen


title: RUNX1-ETO (RE) murine hematopoietic stem/progenitor cells (HSPCs) treated with GM-CSF

status: Public on Sep 23 2016

city: La Jolla

first: Dong-Er

last: Zhang

state: CA

address: 3855 Health Sciences Drive

institute: UCSD Moores Cancer Center

summary: GM-CSF signaling was previously reported to have a negative effect on a murine model of (8;21)-induced leukemia. Gene expression profiling of MigR1 (Mig) control and RUNX1-ETO (RE), the oncofusion protein generated from t(8;21), murine Lin-/c-Kit+ hematopoietic stem/progenitor cells (HSPCs) was conducted to further elucidate the mechanisms mediating the negative effect induced by GM-CSF signaling in t(8;21) cells,

overall_design: Gene expression profiling of control MigR1 (Mig) and MigR1-RUNX1-ETO (RE) Lin-/c-Kit+murine hematopoietic stem/progenitor cells (HSPCs) with and without 10ng/mL GM-CSF treatment

first: S

last: Weng

last: Matsuura

middle: T

last: Mowery

middle: A

last: Stoner

first: K

last: Lam

first: D

last: Ran

first: A

last: Davis

first: M

last: Lo


title: IL-13 Overexpression in IL4Ra^Flox Alb^Cre mice

status: Public on Jul 08 2016

city: Bethesda

first: Richard

middle: Lee

last: Gieseck

state: MD

address: 4 Memorial Drive

department: NIAID

institute: NIH

summary: The goal of this study was to determine the response of albumin positive cells to IL-13 overexpression.

overall_design: 14 samples were analyzed. 4 Wildtype eGFP samples, 4 Alb-Cre eGFP samples, 3 IL-13 WT samples, and 3 Alb-Cre IL-13 samples.

first: Thirumalai

last: Ramalingam

first: Kevin

last: Hart

last: Vannella

first: David

last: Cantu

first: Wei-Yu

last: Lu

first: Sofia

last: Ferreira-Gonzalez

first: Stuart

last: Forbes

first: Ludovic

last: Vallier

first: Thomas

last: Wynn


title: Gene profiling in the colon after depletion and activation of TLR3 and TLR7 signals

status: Public on Jul 05 2016

first: YUNYONG

last: PARK

address: 84 Heukseok-ro

institute: ChuangAng University

summary: TLR3 and TLR7 are critical recognition receptor which reacts with viruses. TLR3 and TLR7 contribute to many immunological pathway. Especially, TLR3 and TLR7 are clearly involved in the regulation of innate immunity in the gut. To identify the downstream target of TLR 3 and TLR7 in the IBD, we carried out microarray.

overall_design: The colon tissues were isolated from four different groups. None-no treatment, after DSS treated, after DSS+antiviral treatment, after DSS+TLR3+7 agonists.

first: Yun-Yong

last: Park

first: Mi-Na

last: Kweon


title: Tip5/Baz2a Regulates Chromatin Architecture and Gene Expression to Maintain Self-renewal and Pluripotency of Embryonic Stem Cells [microarray]

status: Public on Jul 14 2016

city: San Francisco

first: Hunter

last: Richards

address: 513 Parnassus Ave., HSW 863

department: Orofacial Sciences

institute: UCSF

summary: It is unclear how gene networks that regulate self-renewal and pluripotency of embryonic stem (ES) cells are established. We searched for factors that contribute to forming functional chromatin architecture in ES cells and identified Tip5 (also called Baz2a) as a genome organizer, folding chromatin and recruiting chromatin remodeling/epigenetic factors to genes. Tip5 binds specialized genomic sequences called base-unpairing regions (BURs) and localizes near heterochromatin. Through chromatin looping Tip5 recruits the polycomb-repressive complex 2 (PRC2) subunits and Jarid2 to target genes far from Tip5-bound BURs and alters their histone profiles. In ES cells Tip5 represses PRC2-bound developmental genes and regulates non-PRC2-bound genes that are enriched for G-protein coupled receptor signaling. Tip5 knockdown caused misexpression of these genes important for ES cell maintenance, leading to rapid ES cell differentiation and impaired pluripotency. These data suggest that Tip5 regulates multiple processes through ES cell-specific genome organization to maintain ES cell stemness.

overall_design: Total RNA harvested from wild-type E14 cells was and compared to Tip5-knockdown E14 cells at passage 3 after each transfection of triplicate

first: Hye-Jung

last: Han

middle: W


title: Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype

status: Public on Jul 01 2016

city: Basel

first: Matthias

middle: Sebastian

last: Matter

state: BS

address: Schönbeinstrasse 40

department: Institute of Pathology

institute: University of Basel

summary: The majority of hepatocellular carcinoma (HCC) develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or non-alcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT-1 (AKT) and b-catenin (CAT) followed by induction of chronic liver inflammation by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) and carbon tetrachloride (CCl4). Also, the impact of DDC-induced chronic liver inflammation was compared between two liver tumor models using a combination of AKT-CAT or AKT-NRASG12V. Treatment with DDC and CCl4 significantly facilitated the adenoma-to-carcinoma conversion and accelerated the growth of AKT-CAT tumors. Furthermore, DDC treatment altered the morphology of AKT-CAT tumors and caused loss of lipid droplets. Transcriptome analysis of AKT-CAT tumors revealed that cellular growth and proliferation was mainly affected by chronic inflammation. Integration with transcriptome profiles from human HCCs further demonstrated that AKT-CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT-NRASG12V tumors and primarily enhanced already existent tumor characteristics as supported by transcriptome analysis. However, it also reduced lipid droplets in AKT-NRASG12V tumors.   Conclusion: Our study suggests that liver tumor phenotype is defined by a combination of driving oncogenes but also the nature of chronic liver inflammation.

overall_design: Total RNA isolated from AKT-CAT, AKT-CAT+DDC, AKT-CAT+CCl4, AKT-NRAS, AKT-NRAS+DCC, tumoral and non-tumoral tissue as well as PBS and DDC control tissue


title: Effect of interferon-gamma (IFNg) deficiency in murine small intestine (ileum)

status: Public on Jul 16 2016

city: Corvallis

first: Natalia

last: Shulzhenko

state: Oregon

address: 700 SW 30th St, 105 Dryden Hall

institute: Oregon State University

summary: Gene expression profiling of C57Bl/6 wild type and IFNg-deficient whole ileum at 8 weeks of age

overall_design: 5 wild type control, 5 IFNg knockout


title: Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages

status: Public on Jun 29 2016

city: Neuherberg

first: Johannes

last: Beckers

address: Ingolstaedter Landstr. 1

department: Institute of Experimental Genetics

institute: Helmholtz Zentrum Muenchen

summary:
The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes known to be involved in shaping adaptive immune responses, but their role for innate immune signaling is elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages which are highly specialized tissue macrophages of the alveolar surface of the lung.
Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits LMP2, LMP7, and MECL-1. In contrast, IL-4 triggered alternative (M2) activation was accompanied by posttranscriptional upregulation of LMP2 and LMP7. Accordingly, immunoproteasome activity increased in M1 cells, and to some extent under M2 conditions. Analyzing the polarization capability from LMP7 deficient mice revealed no effect on the LPS/IFNγ triggered M1 profile, but uncovered a distorted M2 profile for IL-4 stimulated LMP7-/- alveolar macrophages as characterized by increased M2 marker gene expression and CCL17 cytokine release. This shift in immunoproteasome-dependent M2 polarization was accompanied by amplified AKT/STAT6 activation and IRF4 expression in LMP7-/- alveolar macrophages. IL-13 stimulation of LMP7 deficient cells induced a similar M2 skewed profile and IL4Rα protein expression was generally elevated in LMP7-/- alveolar macrophages, indicating that amplified IL4R signaling in immunoproteasome defective cells may contribute to augmented M2 polarization. Importantly, treatment with an LMP7-specific proteasome inhibitor recapitulated the findings of genetic LMP7 inactivation. Our results thus suggest a novel role of immunoproteasome function for regulating innate immune function of macrophages by limiting IL4R expression and signaling.

overall_design: Expression data of M0 and M2 macrophages derived from Lmp7 k.o. and control animals

first: Shanze

last: Chen

first: Ilona

middle: E

last: Kammerl

first: Oliver

last: Vosyka

first: Tobias

last: Baumann

first: Youjia

last: Yu

first: Yiquan

last: Wu

first: Martin

last: Irmler

first: Hermen

last: Overkleeft

last: Eickelberg

first: Silke

last: Meiners

last: Stoeger


title: Transcriptomic analysis of the effect of ASO-mediated (40ug/day) CD33 knock-down on the microglial gene network in an APP/PS1 mouse model of Alzheimer’s disease. [LNA-013]

first: Mary

last: Hamby

summary: Microglia, the resident innate immune cells of the central nervous system (CNS), are increasingly recognized  as critical for normal CNS function as well as for the pathophysiology of CNS disorders, including Alzheimer's disease (AD).  Advances in transcriptomic analyses, such as weighted gene co-expression network analysis, reveal that the most perturbed gene networks identified in AD brains fall squarely within microglial pathways and these findings are consistent with genetic and epigenetic genome-wide association studies linking specific microglial genes to AD risk.  Increased expression of full-length CD33 increases AD risk and CD33 is a component of the microglial gene network, yet relatively little is known about the significance of CD33 in this gene network or in microglial biology.  To gain further insight into these questions, we first identified and characterized locked nucleic acid (LNA) antisense oligonucleotides (ASOs) as tools to knock down CD33 in APP/PS1 mice in vivo.  We report here that CD33 LNA ASO results in robust knockdown of CD33 mRNA the frontal cortex and hippocampus of APP/PS1 mice and that this knockdown causes changes to the AD-associated microglial gene network. This work suggests that CD33 may be a viable therapeutic target in AD.

overall_design: The double transgenic APP/PS1 mouse model of AD (first described by Mathias Jucker’s group) was treated either with a CD33-specific ASO or a non-target Control ASO. Animals were dosed with 40ug/day of ASO (pump delivers 6uL/day) for either 14 days (CD33-specific ASO (N=10) (from week 18-20) ; non-target Control ASO (N=9)) or 28 days (from week 18 -22) (CD33-specific ASO (N=14) ; non-target Control ASO (N=14)) starting at 18 weeks of age and were sacrificed as described at 22 weeks of age. Number of samples for microarray profiling were as follows. In the hippocampus: 14 day CD33 ASO, 9; 14 day CON ASO, 9; 28day CD33 ASO, 13; 28 day CON ASO, 13. In the frontal cortex: 14 day CD33 ASO, 9, 14 day CON ASO, 9; 28 day CD33 ASO, 14, 28 day CON ASO, 14.

first: Sean

last: Pintchovski

first: Shaun

last: Fallon

first: Jiaping

last: Gu

first: Joseph

last: Tamm

first: Aicha

last: Abdourahman

first: Thomas

last: Möller

first: Paul

last: Wes


title: Genome-wide analysis of livers of control and Lats1/2 deficient neonatal mice [Microarray expression]

city: DaeJon

first: Da-Hye

last: Lee

address: 335 Gwahangno

department: Biological science

institute: KAIST

summary: Lats1-/-;Lats2fl/fl;Alb-Cre pups and control pups were sacrificed at 1 day after birth

overall_design: Total mRNA obtained from livers in control and Lats1/2 deficient neonatal mice


title: IRF-5 and IRF-8 govern the response of Human Plasmacytoid Dendritic Cells following TLR9 ligation

status: Public on Jun 01 2016

city: Hilden

first: Folkert

last: Steinhagen

address: Breddert 37

institute: National Cancer Institute

summary: Synthetic oligonucleotides (ODNs) containing CpG motifs stimulate human plasmacytoid dendritic cells (pDCs) to produce type-1 interferons (IFN) and pro-inflammatory cytokines. Previous studies demonstrated that interferon regulatory factors (IRFs) played a central role in mediating CpG-induced pDC activation. This work explores the inverse effects of IRF-5 and IRF-8 on CpG dependent gene expression. Results from RNA interference and microarray studies indicate that IRF-5 up-regulates TLR9-driven gene expression whereas IRF-8 down-regulates the same genes. Several findings support the conclusion that IRF-8 inhibits TLR9 dependent gene expression by directly blocking the activity of IRF-5. First, the inhibitory activity of IRF-8 is only observed when IRF-5 is present. Second, proximity ligation analysis shows that IRF-8 and IRF-5 co-localize within the cytoplasm of resting human pDC and co-translocate to the nucleus after CpG stimulation. Taken together, these findings suggest that two transcription factors with opposing functions control TLR9 signaling in human pDCs.

overall_design: CAL-1 cells were transfected with siRNA targeting IRF-5 (IRF-5si) and left unstimulated (n=4, technical repeats) or stimulated with K-type CpG ODN (n=4, technical repeats). CAL-1 cells were transfected with siRNA targeting IRF-8 (IRF-8si) and left unstimulated (n=4, technical repeats) or stimulated with K-type CpG ODN (n=4, technical repeats). CAL-1 cells were transfected with control siRNA (Contsi) and left unstimulated (n=4, technical repeats) or stimulated with K-type CpG ODN (n=4, technical repeats).


title: Adverse Health Effects of Cylindrospermopsin in Laboratory Animal (mouse) Studies in Single Day Study using Illumina Array

status: Public on Jun 24 2016

city: RTP

first: Neil

last: Chernoff

state: NC

address: 109 TW Alexander Dr

institute: US EPA

summary: The goal of this project was to determine gene expression changes in the liver at different times post treatment with the common freshwater cyanobacterial toxin, cylindrospermopsin (CYN).  The liver is generally considered to be the primary target of this toxin and all the data has been derived from livers of exposed animals as well as concurrent controls.  Preliminary gene expression effects have been reported (Chernoff et al., 2010) and the current data extend the time course from 1 hour post exposure to 1-day post cessation of a 5-day period dosing period.

overall_design: Gene expression changes were determined in the livers of pregnant mice exposed to toxic levels of cyanobacterial toxin, cylindrospermopsin.  Animals were exposed to a dose of CYN that elicited significant hepatic toxicity.  This single dose study analyzed liver samples collected at 1, 3, 6, 12 and 24 hours post dose. Gene expression changes were analyzed on the Illumina MouserRef-8v2.0 expression beadchip.