title: Effect of retinoic acid on gene expression in CD4 cells stimulated with anti CD3 and CD28

city: Frederick

first: Ven

last: Natarajan

institute: Leidos Biomedical Research Inc

summary:
RNA extracted from CD4 cells was analyzed using affymetrix gene array chips.Data set includes analysis of RNA from DMSO or ATRA treated samples. ATRA induced the expression of a number of genes including LZTFL1.

Retinoic acids, which are metabolites of vitamin A, have been shown to be involved in multiple T cell effector responses through their binding to the retinoic acid receptor, a ligand-activated transcription factor. Because the molecular mechanism of regulation by retinoic acid is still not fully uncovered, we investigated the gene expression profile of all-trans retinoic acid (ATRA)-treated human CD4(+) T cells. Leucine zipper transcription factor-like 1 (LZTFL1) was upregulated by ATRA in a dose- and time-dependent manner. The expression of LZTFL1 depended on both ATRA and TCR signaling. LZTFL1 accumulated in the plasma membrane compartment of human CD4(+) T cells, and, during immunological synapse formation, it transiently redistributed to the T cell and APC contact zone, indicating its role in T cell activation. Live-cell imaging demonstrates that at the initial stage of immunological synapse formation, LZTFL1 is concentrated at the APC contact site, and, during later stages, it relocates to the distal pole. Knockdown of LZTFL1 reduced the basal- and ATRA-induced levels of IL-5 in CD4(+) T cells, and overexpression of LZTFL1 enhanced the TCR-mediated NFAT signaling, suggesting that LZTFL1 is an important regulator of ATRA-induced T cell response. Together, these data indicate that LZTFL1 modulates T cell activation and IL-5 levels.

overall_design: CD4 cells were isolated from human PBMCs and primed with anti-CD3 and IL-2 in presence and absence of retinoic acid. Two days later RNA was extracted and analyzed.

first: Jun

last: Yang


title: Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in epididymal adipose tissue of diet-induced obese mice

status: Public on Feb 25 2016

city: Tsukuba

first: Masuko

last: Kobori

state: Ibaraki

address: 2-1-13 Kannondai

country: Japan

institute: Food Research Institute, National Agriculture and Food Research Organization

summary:
We examined the effect of quercetin on the gene expression and function of epididymal adipose tissue (EAT) in Western diet-induced obese mice. Quercetin suppressed the increase in the number of macrophages and the decrease in the ratio of CD4+ to CD8+ T cells in EAT, and the elevation of plasma leptin and TNFα levels in mice fed the Western diet. Comprehensive gene expression analysis revealed that quercetin suppressed gene expression associated with the accumulation and activation of immune cells, including macrophages and lymphocytes in EAT. It also improved the expression of the oxidative stress-sensitive transcription factor NFκB, NADPH oxidases, and antioxidant enzymes. Quercetin markedly increased gene expression associated with mitochondrial oxidative phosphorylation and mitochondrial DNA Quercetin most likely universally suppresses the accumulation and activation of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation.
Quercetin most likely universally suppresses the accumulation and activation of immune cells, including anti-inflammatory cells, whereas it specifically increased gene expression associated with mitochondrial oxidative phosphorylation. Suppression of oxidative stress and NFκB activity likely contributed to the prevention of the accumulation and activation of immune cells and resulting chronic inflammation.

overall_design: C57BL/6J mice were fed a control diet; a Western diet high in fat, cholesterol, and sucrose; or the same Western diet containing 0.05% quercetin for 18 weeks.

first: M


title: Neonatal bone marrow stroma

status: Public on Feb 11 2016

city: Stanford

first: Rahul

last: Sinha

state: CA

address: 265 Campus Drive

department: ISCBRM

country: USA

institute: Stanford University School of Medicine

summary: Prospectively isolated neonatal bone marrow stroma and endothelium

overall_design: 3 repeats per FACS sorted population

first: J

middle: Y

last: Chen

first: I

middle: L

last: Weissman


title: Myc Depletion in Naïve ESCs Induces a Pluripotent Dormant State Mimicking Embryonic Diapause

city: Heidelberg

first: Roberta

last: Scognamiglio

state: BW

address: Im Neuenheimer Feld 280

department: Stem Cells and Cance

country: Germany

institute: DKFZ

summary: Microarray expression analysis of mouse ESCs treated with the MYCi 10058-F4.

overall_design: Mouse ESCs were analysed after 60h of treatment with DMSO or 10058-F4 (MYCi). The MYCi⇒Released (Resc) group was treated with 10058-F4 for 60h, followed by withdrawal of the inhibitor and culture in 2i medium for additional 48h.

first: Andreas

last: Trumpp


title: Prox1 downregulation is a prerequisite for the maturation and expansion of postnatal murine beta cells

city: Memphis

first: Geoffrey

last: Neale

state: TN

address: 262 Danny Thomas Place

department: Hartwell Center

institute: St Jude Childrens Research Hospital

summary:
Alterations in the expression of key transcription factors can be harmful for pancreatic beta cell homeostasis and could lead to diabetes. This study uncovered that Prox1 overexpression obstructs beta cell maturation and results in severe hyperglycemia.
The function of β-cells is key for glucose homeostasis because they supply insulin to the entire body. Genetic or metabolic conditions that disrupt the complex physiology of β-cells can lead to diabetes mellitus, a prevalent life-threatening disease. Here we investigated whether sustained Prox1 expression is incompatible with β-cell development using a transgenic mouse approach, and report that β-cell maturation is drastically impaired in the presence of high levels of Prox1.

overall_design: We used microarrays to identify gene expression profiles and pathways that are differentially activated when Prox1 is overexpressed in murine pancreatic beta cells.

first: Leena

last: Paul

first: Beatriz

last: Sosa-Pineda


title: Expression data from E12.5 male fatal PGCs, PGCLC in vitro, round spermatids and spermatids like cells produced in vitro

status: Public on Feb 26 2016

city: Nanjing

first: Quan

last: Zhou

state: Jiangsu

address: NO. 140, Hanzhong Road

country: China

institute: Nanjing Medical University

summary: Generation of haploid gametes in vitro can potentially address gamete failure-based infertility.This study reports complete in vitro meiosis from murine ESC-derived PGCLCs resulting in the formation of male spermatid-like cells (SLCs) capable of producing viable fertile offspring via intracytoplasmic sperm injection (ICSI).Our findings provide the basis for generation of haploid spermatids in vitro in human, the generation of transgenic animals, and the use of this system to investigate mechanisms of meiosis.

overall_design:
We used microarrays to compare gene expression profiles of in vivo and in vitro derived PGC cells and round spermatids.
We collected E12.5 male fatal PGCs, PGCLC in vitro, round spermatids and spermatids like cells produced in vitro, each sample has 3 replications.

first: Qi

first: Jiahao

last: Sha

first: Xiao-Yang

last: Zhao


title: Elucidating the Linezolid response of Staphylococcus aureus USA300 by a holistic study

status: Public on Feb 22 2016

city: Greifswald

first: Florian

last: Bonn

address: Jahnstraße 15

department: Institute for Microbiology

institute: University of Greifswald

summary:
The translation inhibitor Linezolid is an important antibiotic of last resort against multiresistant gram-positive pathogens including MRSA. Linezolid is reported to specifically inhibit extracellular virulence factors, but the molecular cause is unknown. To elucidate the physiological response of S. aureus to Linezolid in general and the possible inhibition of virulence factors specifically we performed a holistic study. We added Linezolid to logarithmically growing S. aureus cells and analyzed the Linezolid stress response with transcriptomics, quantitative proteomics and microscopy experiments.
As previously observed in studies on other translation inhibitors S. aureus is adapting its protein biosynthesis machinery to the reduced translation efficiency, for example the synthesis of ribosomal proteins is induced. But we also observed unexpected results like a general decline in the amount of extracellular and membrane proteins. In addition cell shape and size changed after Linezolid stress and cell division was diminished. Finally, the chromosome condensed after LZD stress and lost contact to the membrane.

platform_organism: Staphylococcus aureus subsp. aureus NCTC 8325

platform_organism: Staphylococcus aureus subsp. aureus Mu50

platform_organism: Staphylococcus aureus subsp. aureus N315

platform_organism: Staphylococcus aureus subsp. aureus MRSA252

platform_organism: Staphylococcus aureus subsp. aureus MSSA476

platform_organism: Staphylococcus aureus subsp. aureus USA300

overall_design: sample versus pool design (pool = mixture of equal amounts of all RNA samples analyzed), all RNA samples were isolated as biological triplicates

first: Marc

last: Schaffer

first: Ulrike

last: Mäder

first: Uwe

last: Völker

first: Dörte

last: Becher


title: Transcriptome analysis of two clonally-derived ICC progenitor cell lines [array]

city: Rochester

first: Tamas

last: Ordog

state: MN

address: 200 1st St SW

institute: Mayo Clinic

summary:
Interstitial cells of Cajal (ICC) are electrical pacemakers and mediators of neuromuscular neurotransmission in the gastrointestinal tract. Studies in organotypic cultures of intact gastric muscular wall tissues identified Kit(low)Cd44(+)Cd34(+)Insr(+)Igf1r(+) cells as local ICC progenitors (Lorincz et al., Gastroenterology 2008;134:1083-1093). Subsequently, conditionally immortalized Kit(low)Cd34(+) cells were isolated by immunomagnetic and fluorescent cell sorting and serial cloning from the gastric muscular wall of homozygous, 14-day-old H-2Kb-tsA58 mice and shown to share other phenotypic characteristics with in-situ ICC precursors (2xSCS70 cells; Bardsley et al., Gastroenterology 2010;139:942-952). 2xSCS70 cells were also found to express the ICC marker Ano1, be able to extensively self-renew in the absence of the SV40 tsA58-TAg when cultured in NeuroCult® Neural Stem Cell Proliferation Medium (NSCPM; STEMCELL Technologies) and differentiate into Kit(+) ICC both in vitro and in vivo. Wild-type cells with Kit(low)Ano1(+)Cd44(+)Cd34(+)Insr(+)Igf1r(+) phenotype (2xSCS2F10 cells) were prospectively isolated from primary cultures of dissociated gastric muscular wall tissues from 7-day-old C57BL/6J mice by serial cloning following 150-day expansion in NSCPM containing 5% cell-free chick embryo extract (CEE; Accurate Chemical). Long-term culturing of both cell lines was associated with further decline in Kit expression while expression of Ano1 and other markers of ICC precursors was maintained. Following spontaneous transformation, both 2xSCS70 and 2xSCS2F10 cells grafted into nude mice gave rise to tumors containing Kit(+)cells and otherwise resembling gastrointestinal stromal tumors (GIST), which originate from the ICC lineage (Bardsley et al., Gastroenterology 2010;139:942-952).
This study utilized oligonucleotide microarray analysis to charaterize the transcriptome of non-transformed 2xSCS70 and 2xSCS2F10 cells relative to their source tissues.

overall_design: Total RNA from ICC progenitor cell lines and their source tissue (gastric tunica muscularis from C57BL/6J mice (source of 2xSCS2F10 cells) and H-2Kb-tsA58 mice (source of 2xSCS70 cells) was isolated.  Oligonucleotide micorarray studies were performed using 2-3 Affymetrix Mouse Genome 430.2 GeneChips per sample.


title: Quantitative Trait Locus and Brain Expression of HLA-DPA1 And Shared Immune Alterations in Psychiatric Disorders

city: Irvine

first: Marquis

last: Vawter

address: 837 Health Science Rd

department: Psychiatry

institute: University of California, Irvine

summary: Genome wide association studies of schizophrenia encompassing the major histocompatibility locus (MHC) were highly significant following genome wide correction. This broad region implicates many genes including the MHC complex class II. Within this interval we examined the expression of two MHC II genes (HLA-DPA1 and HLA-DRB1) in brain from individual subjects with schizophrenia (SZ), bipolar disorder (BD), major depressive disorder (MDD), and controls by differential gene expression methods. A third MHC II mRNA, CD74, was studied outside of the MHC II locus, as it interacts within the same immune complex. HLA-DPA1 and CD74 were both reduced in hippocampus, amygdala, and dorsolateral prefrontal cortex regions in SZ and BD compared to controls by specific qPCR assay. We found several novel HLA-DPA1 mRNA variants spanning HLA-DPA1 exons 2-3-4 as suggested by an exon microarray study. The intronic rs9277341 SNP was a significant cis expression quantitative trait locus (eQTL) that was associated with the total expression of HLA-DPA1 in five brain regions. A biomarker study of MHC II mRNAs was conducted in SZ, BD, MDD, and control lymphoblastic cell lines (LCL) by qPCR assay of 87 subjects. There was significantly decreased expression of HLA-DPA1 and CD74 in BD, and trends for reductions in SZ in LCLs. The discovery of multiple splicing variants in brain for HLA-DPA1 is important as the HLA-DPA1 gene is highly conserved, there are no reported splicing variants, and the functions in brain are unknown. Future work on the function and localization of MHC Class II proteins in brain will help to understand the role of alterations in neuropsychiatric disorders. The HLA-DPA1 eQTL is located within a large linkage disequilibrium block that has an irrefutable association with schizophrenia. Future tests in a larger cohort are needed to determine the significance of this eQTL association with schizophrenia. Our findings support the long held hypothesis that alterations in immune function are associated with the pathophysiology of psychiatric disorders.

overall_design: There were 20 anterior cingulate postmortem brain samples that were extracted for total RNA, and analyzed using Affymetrix Exon Array (bipolar disorder subjects n = 9, controls n = 11).

middle: P

first: Brandi

last: Rollins


title: Gene expression of Th cells, macrophages and monocytes derived from WT and Tbx21-/- Th cell-induced colitis

status: Public on Feb 04 2016

city: Berlin

first: Pawel

last: Durek

address: Charitéplatz 1

institute: Deutsches Rheuma-Forschungszentrum

summary: We compared gene expression profiles of Th cells, macrophages and monocytes isolated from the inflamed colon of colitis induced by the transfer of WT versus Tbx21-/- Th cells in Rag1-/- recipients.

overall_design: 4E05 naïve CD4+CD45RBhiCD25- Th cells from WT C57BL/6 or Tbx21-/- mice were transferred into congenic Rag1-/- recipients. When signs of colitis became apparent (day 15-17), a single cell suspension was prepared from the inflamed colonic lamina propria. Using a FACSAria sorter, live, single Th cells (CD3+CD4+), monocytes (CD64+Ly-6Chi) and macrophages (CD64+Ly-6Clow) were sorted. Th cells were stimulated for 3 hours in IMDM with 10% FCS containing PMA (10 ng/ml) and ionomycin (1 µg/ml). Total RNA was extracted using the RNeasy Mini kit (Qiagen). The integrity of isolated RNA was assessed for each sample using an Agilent 2100 Bioanalyzer (Agilent, Waldbronn, Germany) and amount was checked with a NanoDrop ND-1000 spectrophotometer (NanoDrop Technologies, Wilmington, DE). Double-stranded complementary RNA was synthesized from 1 µg total RNA using Message AmpII Biotin (Ambion, USA). Fifteen micrograms of fragmented cRNA of each sample were hybridized to MG 430_2 GeneChips (Affymetrix). Hybridization was performed in a Hybridization Oven 640, and chips were washed and stained in the Fluidics Station 400 (both Affymetrix). Finally, the arrays were scanned with a GeneChip Scanner 3000 using the GCOS software, version 1.4, both Affymetrix. All relevant GCOS data of quality checked microarrays were analyzed with High Performance Chip Data Analysis (HPCDA, unpublished), using the BioRetis database (www.bioretis-analysis.de), as described and validated previously.

first: Jakob

last: Zimmermann

first: Anja

middle: A

last: Kühl

first: Melanie

last: Weber

first: Joachim

middle: R

last: Grün

first: Julia

last: Löffler

first: Claudia

last: Haftmann

first: René

last: Riedel

first: Patrick

last: Maschmeyer

first: Katrin

last: Lehmann

first: Kerstin

last: Westendorf

first: Mir-Farzin

last: Mashregi

first: Max

last: Löhning

first: Matthias

last: Mack

last: Radbruch

first: Hyun-Dong

last: Chang


title: Mouse kidney gene expression regulated by C2

status: Public on Feb 01 2016

city: West Lafayette

first: Chang

last: Kim

state: IN

address: 725 Harrison St

department: Comparative Pathobiology

institute: Purdue

summary: This is to determine in vivo kidney tissue gene expression regulated by acetate feeding  in drinking water into mice for 6 weeks.

overall_design: 3 week old mice--> C2 feeding for 6 weeks in drinking water --> Sacrifice --> Microarray examination of kidney tissues

first: Jeongho

last: Park


title: Genome-wide evaluation of change in lncRNA expression in non-functioning pituitary adenoma using formalin-fixed and paraffin-embedded tissue specimens

status: Public on Feb 06 2016

city: suzhou

first: weikang

last: xing

address: 188 shizi street

institute: The First Affiliated Hospital of Soochow University

summary:
Long noncoding RNAs (lncRNAs) have been implicated in the formation of many different types of tumors. However, expression profiles and potential functions of lncRNAs in non-functioning pituitary adenomas (NFPAs) have not been systematically evaluated.
We evaluated the expression profiles and potential functions of lncRNAs in non-functioning pituitary adenomas (NFPAs).

overall_design: 10 formalin-fixed and paraffin-embedded (FFPE) tissue specimens (5 non-functioning pituitary adenomas (NFPAs) and 5 normal pituitaries(NPs)) were selected for RNA extraction and hybridization on Affymetrix microarrays. The NFPAs team was designed as the Tumor group (T), while the NPs team was designed as Normal group (N).

first: Wei

middle: K

last: Xing

first: Zhen

last: Qi

first: Cheng

last: Huang

last: Zhang

first: Han

middle: Q

last: Gao

first: Yao

last: Li

first: Min

last: Qiu

first: Ling

middle: C

last: Guo

first: Yi

last: Xie

first: Qi

last: Fang

first: Guo

middle: Z

last: Hui


title: Expression data of LPS-induced genes in bone marrow derived macrophages

status: Public on Jun 13 2016

city: New York

first: Yingli

last: Shang

state: NY

address: 535E 70th Street

institute: Hospital for Special Surgery

summary: TLR ligands consistently induce expression of two Hes family members Hes1 and Hey1 in macrophages.To evaluate the effects of these two factors on inflammatory responses, we generated mice lacking both Hes1 and Hey1 (DKO). WT and DKO BMDMs were then untreated or exposed to LPS for 3 hours, and microarray was performed to examine global gene expression profiles to identify Hes1 and Hey1-regulated inflammatory genes

overall_design: Examination of Hes1 and Hey1-regulated inflammatory genes in macrophages

first: Huimin


title: Expression data of mouse embyonic fibroblasts established from Phgdh KO embryos (KO-MEFs) cultured with or without L-Ser

status: Public on Feb 02 2016

city: Fukuoka

first: Shigeki

last: Furuya

address: 6-10-1, Hakozaki, Higashi-ku

institute: Kyushu University

summary:
L-Ser deficiency leads to growth arrest, tissue malformation and embryonic lethality in mice. However, the molecular mechanism by which L-Ser deficiency impairs basic cellular function remains largely unexplored.
We used microarrays to identify genes differentially expressed in KO-MEFs cultured with presence or absence of L-Ser, and tried to understand the underlying mechanism of growth-arrested phenotype of KO mice/MEFs elicited by L-Ser deficiency.

overall_design: Total RNA was extracted from KO-MEFs after 6 h incubation in L-Ser-depleted or -supplemented conditions and was purified. Three biological replicates for each treatment were used for amplification and labeling for microarray chip hybridization.

first: Hisanori

last: Kato


title: Comparison of gene expression in tumor ovarian surface epithelial cells with different p53 status

status: Public on Feb 03 2016

city: Houston

last: Ren

state: Texas

address: One Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: The impact of specific p53 mutations on ovarian tumor development and response to therapeutic treatment remain limited.  Here, using transgenic mouse models of epithelial ovarian cancer (EOC), we demonstrated that the Trp53R172H mutation promotes EOC progression compared to wild-type p53, but with different consequences between heterozygous and homozygous mutation status. EOC expressing heterozygous Trp53R172H mutation has enhanced responsiveness to steroid hormones and at late stage developed mucinous cystadenocarcinoma. These findings open new realms for exploring the interaction between p53 and steroid receptor, and the allelic status of p53 in EOC development and treatment.

overall_design: Comparison of gene expression and molecular signatures of tumor OSE cells with different p53 status.

first: Lisa

last: Mullany

first: Kwong-Kwok

last: Wong

first: Zhilin

last: Liu

first: Guillermina

last: Lozano

first: Alan

middle: J

last: Herron

first: JoAnne

middle: S

last: Richards


title: Functionally relevant prediction model for colorectal cancer

city: Riyadh

first: Musa

last: Gabere

address: Kashmalaan

department: Bioinformatics

country: Saudi Arabia

institute: King Abdullah International Medical Research Center,  NGHA

summary: Filtered selection coupled with support vector machines generate functionally relevant prediction model for colorectal cancer. In this study, we built a model that uses Support Vector Machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300 and 500 genes most relevant to CRC using the Minimum-Redundancy–Maximum-Relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function and sigmoid).

overall_design: We conducted a pair-wise comparison of Tumor vs Normal samples obtained from cancer patients. Array data was processed using Expression Console Patients detail for sample 052311 and 082812 are missing.

first: M

last: Aziz

last: Hussein


title: Expression data of sorted GFP+ and tdTomato+ prostate tumor cells from Pten/Smad4/mTmG mice

first: Guocan

last: Wang

state: TX

address: 1515 Holcombe Blvd, T7.3900

institute: MD Anderson Cancer Center

summary:
Single cells from Ptenpc-/-Smad4pc-/-mTmG+ prostate tumors were isolated into single cells which were FACS-sorted for GFP+ and Tomato+ cells and RNA was purified with TRIzol (Life Technologies).
RNA expression profiling was performed  using the Mouse Genome 430 2.0 Array (Affymetrix) to generate a Ptenpc-/-Smad4pc-/- tumor/Stroma dataset.

overall_design: Two mice (9074, 9076) at 28 weeks old were used to isolate anterior prostate (AP) and dorsolateral prostate (DLP). From each prostate lobe, three populations were extracted for RNA: unsorted, GFP+, Tomato+. Therefore, there are total 12 samples.

first: Xin

last: Lu

first: Ronald

last: DePinho

first: Y


title: Differentially regulated genes in adipocytes derived from Men1-null vs WT mouse embryonic stem cells

city: Bethesda

first: WeiPing

last: Chen

state: MD

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

department: GCL

institute: NIDDK/NIH

summary: MEN1  is a tumor suppressor gene loss of which causes lipoma (fatty tumors under the skin) and many other endocrine and non-endocrine  tumors. It's target genes in fat cells (adipocytes) are unknown. Gene expression in adipocytes that were in vitro differentiated from mouse embryonic stem cells (mESCs) of Men1-nul l(Men1-KO) and WT mice were compared to assess the expression of genes upon menin loss in adipocytes that could lead to the deveopment of lipoma.

overall_design: mESCs (Men1-null and WT) were in vitro differentaited into adipocytes. Positive oil red O staining indicated successful differentiation into adipocytes. The cells were processed for RNA isolation.  RNA preps  were used for microarray analysis.

first: Vaishali

middle: I

last: Parekh

first: Sunita

last: Agarwal


title: Exon array analysis of control vs. FALS MPC

city: Niigata

first: Masato

last: Yano

address: 757, Ichibancho, Asahimachidori, Chuo-ku, Niigata-shi,

department: Division of Neurobiology and Anatomy

institute: Niigata University

summary:
To assess  RNA regulation in FALS for gene expression and alternative processing of RNA in the motor neuron precurssors (MPCs)
Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disorder. Although its neuropathology is well understood, the cellular and molecular mechanisms that lead to the initiation and progression of this disease are yet to be elucidated due to limitations in the currently available human genetic data. In this study, we generated induced pluripotent stem cells (iPSC) from two familial ALS (FALS) patients with a missense mutation in the fused-in sarcoma (FUS) gene carrying the heterozygous FUS H517D mutation, and the isogenic iPSCs with the homozygous FUS H517D mutation obtained by genome editing from the healthy control iPSCs. These cell-derived motor neurons mimicked several neurodegenerative phenotypes. A part of the mutant FUS protein was localized outside the nucleus and co-localized with stress granules under stress conditions. Moreover, FALS motor neurons showed more apoptotic activity than did control motor neurons. Exon array analysis using motor neuron precursor cells (MPCs) combined with CLIP-seq data sets revealed aberrant gene expression and/or splicing pattern in FALS-MPCs. These results suggest that iPSC-derived motor neurons are a useful tool for analyzing the pathogenesis of human motor neuron disorders.

overall_design: RNA from each 3 control and 6 FALS-derived MPCs.  One array per biological replicate.

first: Naoki

last: Ichiyanagi

first: Hideyuki

last: Okano


title: Affymetrix microarray data for the fibroblasts isolated from mice lacking the plasma membrane calcium ATPase isoform 4 and wild type controls

status: Public on Jan 29 2016

city: Louisville

first: Tamer

middle: M

last: Mohamed

state: KY

address: 580 S. Preston St., Baxter II Bldg., Room 122

department: Cardiology

institute: University of Louisville

summary:
The heart responds to pathological overload through myocyte hypertrophy. In our study, we found that this response is regulated by cardiac fibroblasts via a novel paracrine mechanism  involving plasma membrane calcium ATPase 4 (PMCA4). PMCA4 deletion in mice, both systemically and specifically in fibroblasts, reduces the hypertrophic response to pressure overload; however, knocking out PMCA4 specifically in cardiomyocytes does not produce this effect. Mechanistically, our microarray data on fibroblasts isolated from PMCA4 WT and PMCA4 knockout animals showed that cardiac fibroblasts lacking PMCA4 produce higher levels of secreted frizzled related protein 2 (sFRP2), which inhibits the hypertrophic response in neighbouring cardiomyocytes.
Furthermore, we show that treatment with the PMCA4 inhibitor aurintricarboxylic acid (ATA) inhibits and reverses cardiac hypertrophy induced by pressure overload in mice. Our results reveal that PMCA4 regulates the development of cardiac hypertrophy and provide proof of principle for a novel approach to treat this condition.

overall_design: RNA was obtained and pooled from three batches of fibroblasts isolated either from PMCA4 WT and knockout either treated or not treated with 30uM phenylephrine for 72 hours

first: Delvac

last: Oceandy


title: Determination of gene expression changes in HCC cells selected for migration ability.

status: Public on Jan 27 2016

city: Worcester

first: Brian

last: Lewis

state: Massachusetts

address: 364 Plantation Street; LRB 521

department: PGFE

institute: University of Massachusetts Medical School

summary: We determined whole genome expression changes in 2 migratory  cell lines that were derived from a parent HCC cell line.

overall_design: Migratory cell lines, M1 and I1 were compared to the parent cell line BL185 for gene expression profiling.

first: Leanne

middle: G

last: Ahronian


title: Sep15 and TR1 pathways in colon cancer promotion

city: Towson

first: Petra

last: Tsuji

address: 8000 York Rd

department: Biological Sciences

institute: Towson University

summary: Selenoproteins mediate the cancer-preventive properties of the essential nutrient selenium, but also have cancer-promoting effects. We examined the contributions of the 15-kDa selenoprotein (Sep15) and thioredoxin reductase 1 (TR1) to cancer development. Targeted down-regulation of either gene inhibited anchorage-dependent and anchorage-independent growth and cancer metastasis of mouse colon carcinoma CT26 cells. Surprisingly, combined deficiency of Sep15 and TR1 reversed the anti-cancer effects observed with down-regulation of each single gene. We found that inflammation-related genes regulated by Stat-1, especially the interferon-gamma-regulated guanylate-binding proteins, were highly elevated in Sep15-deficient cells. In contrast, the Wnt/Beta-catenin pathway was up-regulated in cells that lacked both TR1 and Sep15. These results suggest that Sep15 and TR1 participate in interfering regulatory pathways in colon cancer cells. Considering the variable expression levels of Sep15 and TR1 found within the human population, and controversial results of recent human clinical trials involving dietary selenium, our results are important to general public health.

overall_design: mRNA was isolated from plasmid-transfected control, shSep15, shTR1, and shTR1/shSep15 knockdown CT26 cells (four replicates of each). Microarray analysis was performed on Affymetrix Mouse 430_2 gene chips. Four arrays were analyzed from different mRNA samples for each construct.


title: Gene expression changes occuring as a result of KLF6 knockdown in murine HCC

summary: We performed whole genome expression profiling using a murine HCC cell line that was either infected with a virus containing shRNA targeting KLF6 or GFP. 3 sets of infections were performed for both shGFP and shKLF6 samples. RNA was isolated from these samples and subsequently analyzed.

overall_design: Determination of gene expression changes in a murine HCC cell line was performed with 3 sets of infections performed for both shGFP and shKLF6. RNA was isolated from these samples and subsequently analyzed using the Affymetrix Mouse Genome 430 2.0 chip.


title: WT and Ikaros-deficient follicular B cells stimulated with anti-IgM

status: Public on Jan 26 2016

city: Illkirch

first: Susan

last: Chan

address: 1, rue Laurent Fries

country: France

institute: IGBMC

summary: We have observed that follicular B cells from mice with a hypomorphic mutation (IkL/L) in the Ikzf1 gene (which encodes the Ikaros transcription factor) exhibit an increased proliferative response to anti-IgM stimulation (Kirstetter et al, Eur J Immunol, 32:720-30, 2002). We asked if Ikaros controls the transcriptional response that unfolds after activation, or if differences in the transcriptional landscape of resting B cells could explain the altered response. To this end, we have determined the transcriptome of unstimulated WT and IkL/L follicular B cells, as well as that of cells stimulated for 3h and 12h with anti-IgM. Samples from 2 independent experients were analyzed.

overall_design:
Follicular splenic B cell were sorted from 6-week old WT or IkL/L mice, and stimulated for 3 or 12h with anti IgM, or cultured without anti-IgM for 3h (unstimulated samples)
2 independant experiments were performed

first: Philippe

last: Kastner


title: Wild-type and Mecp2 -/y callosal projection neurons

status: Public on Jan 22 2016

city: Wako

first: Noriyuki

last: Kishi

state: Saitama

address: 2-1 Hirosawa

department: Lab for Marmoset Models for Brain Diseases

institute: RIKEN Center for Brain Science

summary: Mutations of the transcriptional regulator Mecp2 cause the X-linked autism spectrum disorder Rett syndrome (RTT), and Mecp2 has been implicated in several other neurodevelopmental disorders. To identify potential target genes regulated directly or indirectly by MeCP2, we performed comparative gene expression analysis via oligonucleotide microarrays on Mecp2-/y (Mecp2-null) and wild-type CPN purified via fluorescence-activated cell sorting (FACS).

overall_design: Independent RNA samples were collected from three independent FACS purifications for both wild-type and Mecp2 -/y callosal projection neurons.

first: Jessica

last: MacDonald

first: Julia

last: Ye

first: Bradley

last: Molyneaux

first: Eiman

last: Azim

first: Jeffrey

middle: D

last: Macklis


title: DREAM silencing is part of a neuroprotective mechanism in Huntington's disease

city: Cantoblanco

first: Juan

middle: Carlos

last: Oliveros

state: Madrid

address: Darwin 3

country: Spain

institute: CNB, CSIC

summary: Deregulated intracellular Ca2+ homeostasis underlies synaptic dysfunction and is a common feature in neurodegenerative processes, including Huntington's disease (HD). DREAM/calsenilin/KChIP-3 is a multifunctional Ca2+ binding protein that controls the expression level and/or the activity of several proteins related to Ca2+ homeostasis, neuronal excitability and neuronal survival. We found that expression of endogenous DREAM (DRE antagonist modulator) is reduced in the striatum of R6 mice, in STHdh-Q111/111 knock in striatal neurons and in HD patients. DREAM down regulation in R6 striatum occurs early after birth, well before the onset of motor coordination impairment, and could be part of an endogenous mechanism of neuroprotection, since i) R6/2 mice hemizygous for the DREAM gene (R6/2xDREAM+/-) showed delayed onset of locomotor impairment and prolonged lifespan, ii) motor impairment after chronic administration of 3-NPA was reduced in DREAM knockout mice and enhanced in daDREAM transgenic mice and, iii) lentiviral-mediated DREAM expression in STHdh-Q111/111 knock in cells sensitizes them to oxidative stress. Transcriptomic analysis showed that changes in gene expression in R6/2 striatum were notably reduced in R6/2xDREAM+/- striatum. Chronic administration of repaglinide, a molecule able to bind to DREAM in vitro and to accelerate its clearance in vivo, delayed the onset of motor dysfunction, reduced striatal loss and prolonged the lifespan in R6/2 mice. Furthermore, exposure to repaglinide protected STHdh-Q111/111 knock in striatal neurons sensitized to oxidative stress by lentiviral-mediated DREAM overexpression. Thus, genetic and pharmacological evidences disclose a role for DREAM silencing in early neuroprotective mechanisms in HD.

overall_design: Four biological replicates were independently hybridized to Affymetrix chips (GeneChip Mouse Genome 430 2.0 Array) for each sample type.

first: Jose

last: Naranjo

first: Hongyu

last: Zhang

first: Diego

last: Villar

first: Angela

last: Prieto

first: Pilar

last: Cercos

first: Paz

last: González

first: José

middle: X

last: Dopazo

first: Teresa

first: Alicia

last: de la Cruz

first: Alberto

last: Rabano

first: Carmen

last: Valenzuela

first: Marta

last: Gutierrez-Rodríguez

first: Jia-Yi

last: Li

first: Britt

last: Mellström


title: Transcriptional impact of organophosphate pesticides chlorpyrifos and malathion and their mixture on the juvenile coho salmon olfactory system.

status: Public on Jan 25 2016

city: Seattle

first: James

middle: William

last: MacDonald

state: WA

address: 4225 Roosevelt Way NE

department: Environmental and Occupational Health Sciences

institute: University of Washington

summary: Exposure to environmental concentrations of organophosphate pesticides in Pacific salmon can cause neurobehavioral injuries leading to loss of survival. However, the molecular mechanisms underlying olfactory impairment remain poorly understood. In the current study, we exposed juvenile salmon to three environmentally-relevant doses of chlorpyrifos (CPF) and malathion (MAL) individually and to three concentrations of binary mixtures of both compounds. Brain acetylcholinesterase (AChE) activity was significantly reduced only in the highest dosage of binary mixture group (47% inhibition). Microarray analysis on RNA from coho olfactory rosettes revealed a number of differentially expressed genes in all exposure groups. Overall, there were little overlapping of affected canonical pathways between CPF groups and MAL groups, suggesting the different biofunctions targeted by these two OP pesticides. Several metabolic and signaling pathways also represented the significant toxicological impact of OP pesticides on olfactory system, such as Aryl Hydrocarbon Receptor Signaling, Xenobiotic Metabolism Signaling, Mitochondrial Dysfunction, Pro-Apoptosis, and Oxidative Stress.

overall_design: To determine the effects of chlorpyrifos and malathion separately and as a mixture we performed microarray analysis on juvenile coho salmon olfactory rosettes after exposure.

first: Lu

last: Wang

first: Herbert

last: Espinoza

middle: W

first: Theo

last: Bammler

first: Chase

last: Williams

first: Andrew

last: Yeh

first: Ke'ale

last: Louie

first: Evan

last: Gallagher


title: Gene expression profiling of Mec-1 cells upon chronic silencing of HIF-1a

city: Milan

first: Rosa

last: Bernardi

address: via Olgettina 60

country: Italy

institute: San Raffaele Scientific Institute

summary: This experiment was carried out in the context of a study aimed to identify the function of the transcription facotrs HIF-1a in the pathogenesis of chronic lymphocytic leukemia (CLL).

overall_design: Total RNA obtained from Mec-1 cells transduced with control (CTRL) or HIF-1a-specific shRNA

first: Giovanni

last: Tonon


title: Expression data from SHP specific siRNA or nonspecefic siRNA transfected rat astrocytes

status: Public on Jan 21 2016

city: Suwon

first: jeehoon

last: lee

state: Gyoungido

address: San5, Woncheondong

department: Pharmacology

country: South Korea

institute: Ajou university, School of Medicine

summary: To clarify the effect of SHP in LXRs-mediated signaling pathway, we performed global gene expression analysis of SHP siRNA transfected- or control siRNA transfected- astrocytes after IFN-γ and LXRs agonist. Microarray analysis revealed that expression of several genes encoding inflammatory mediators were reversed in SHP siRNA transfected-astrocytes, when compared with control siRNA transfected-astrocytes.

overall_design: Primary astrocytes were cultured from the cerebral cortices of 1 day-old Sprague-Dawley rats. The astrocytes were transfected with control siRNA or SHP siRNA and treated with IFN-γ in the presence or absence of GW for 3 h.

first: Jeehoon

last: Lee

first: Ilo

last: Jou


title: Expression data from V1 and dI4/dILA spinal interneurons

status: Public on Jan 15 2016

first: Jay

last: Bikoff

institute: Columbia University

summary:
Spinal inhibitory interneurons play crucial roles in shaping motor output, but the molecular heterogeneity contained within cardinal spinal interneuron populations is unclear.
This experiment was designed to identify genes enriched in the Engrailed1 (En1) population of ventral V1 inhibitory interneurons relative to the Ptf1a population of dorsal dI4/dILA interneurons, with the goal of identifying genetic markers for discrete V1 subpopulations.

overall_design: We isolated spinal inhibitory interneurons from either En1-Cre; Rosa.lsl.YFP (V1) or Ptf1a-Cre; Rosa.lsl.YFP (dI4) mice by acutely dissociating e12.5, p0, or p5 spinal cords.  YFP-labeled interneurons were isolated by fluorescence activated cell sorting (FACS), followed by RNA extraction, amplification, and analysis on Affymetrix Mouse 430 2.0 arrays. All experiments were performed in triplicate, with the exception of dI4 interneurons isolated from p5 mice, which were performed in duplicate. En1-Cre mice (Kimmel et al., 2000), Ptf1a-Cre mice (Kawaguchi et al., 2002), and Rosa.lsl.YFP mice (Srinivas et al., 2001) have been described previously.

middle: B

first: Thomas

last: Jessell


title: Genetic Risk Variants for Autoimmune Diseases that Influence Gene Expression in Thymus

city: Oslo

first: Ingvild

last: Gabrielsen

address: Laboratoriebygget 0450 OSLO Postadresse Postboks 4956 Nydalen 0424

department: Department of Medical Genetics

country: Norway

institute: University of Oslo and Oslo University Hospital

summary: Transcription profiling by Illumina HumanWG-6 v3 array of 42 thymic tissue samples

overall_design: Total RNA from 42 human thymic samples were obtained from children undergoing cardiac surgery.

first: Silja

last: Amundsen

first: Hanna

last: Helgeland

first: Siri

middle: T

last: Flåm

first: Nimo

last: Hatinoor

first: Kristian

last: Holm

first: Marte

last: Viken

first: Benedicte

middle: A

last: Lie


title: Beta-catenin stabilization of skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis

status: Public on Jan 12 2016

city: London

first: Ryan

middle: R

last: Driskell

address: 28th Floor Guys Tower

department: Centre for Stem Cells and Regenerative Medicine

country: United Kingdom

institute: King's College London

summary: The Wnt/alpha-catenin pathway plays a central role in epidermal homeostasis and regeneration but how it affects fibroblast fate decisions is unknown. Here, we investigated the effect of targeted alpha-catenin stabilization in dermal fibroblasts. Comparative gene expression profiling of Sca1- and Sca1+ neonatal fibroblasts, from upper and lower dermis respectively, confirmed that Sca1+ cells had a pre-adipocyte signature and revealed differential expression of Wnt/alpha‐catenin-associated genes. By targeting all fibroblasts or selectively targeting Dlk1+ lower dermal fibroblasts, we found that -catenin stabilization between E16.5 and P2 resulted in a reduction in the dermal adipocyte layer with a corresponding increase in dermal fibrosis and an altered hair cycle. The fibrotic phenotype correlated with a reduction in the potential of Sca1+ fibroblasts to undergo adipogenic differentiation ex vivo. Our findings indicate that Wnt/alpha-catenin signaling controls adipogenic cell fate within the lower dermis, which potentially contributes to the pathogenesis of fibrotic skin diseases.

overall_design: The dermis was separated from back skin of PDGFRAeGFP postnatal pups (P2) by incubation with thermolysin (0.25 mg/ml) (Sigma T7902) overnight at 4° and further processed as previously described (Collins et al., 2011). Cells were labeled in PBS + 10% FBS TruStain fcX anti-mouse blocking buffer with the following antibodies: anti-mouse Ly-6A/E (Sca-1)-Alexa Fluor-700  17.  Two populations of cells were collected in triplicate.  The PDGFRaH2BeGFP/Sca1- and the PDGFRaH2BeGFP/Sca1+.  RNA was isolated and prepared for microarray analysis and hybridized to Affymetrix MG430.2A arrays.  C, digested in DMEM + 10% FBS containing 2.5 mg/mL collagenase I (Gibco 17100- 017), and further processed


title: The impact of transgenic Uchl1 on gene expression in germinal center B-cells from ImHABCL6 mice

city: Rochester

first: Asha

last: Nair

address: 200 1ST ST SW

institute: Mayo Clinic

summary: This study seeks to understand the mechanisms behind enhanced lymphomagenesis observed in ImHABCL6/Uchl1 mice compared with ImHABCL6 alone. As the lymphomas arise from germinal center (GC) B-cells, we reasoned that transgenic Uchl1 altered the gene expression patterns in GC B-cells from these animals. We therefore isolated pre-malignant GC B-cells and examined the gene expression patterns to identify pathways affected by the addition of Uchl1.

overall_design: Germinal center B-cells were isolated from from the spleens of ImHABCL6 and ImHABCL6/Uchl1 mutant mice (n= 3 each) after immunization with sheep red blood cells. RNA was extracted and hybridized to affymetrix mouse 430 2.0 arrays.

first: Tibor

last: Bedekovics

first: Paul

last: Galardy


title: Hematopoietic stem cells progressively deficient of glycogen synthase kinase initiate a pre-neoplastic state required for evolution to acute leukemia

status: Public on Jan 11 2016

city: Hamilton

first: Mickie

last: Bhatia

state: Ontario

address: 1200 Main Street West

department: Stem Cell and Cancer Research Institute (SCC-RI)

country: Canada

institute: McMaster University

summary: The cellular origin and molecular progression towards aggressive cancers such as acute myeloid leukemia (AML) remain elusive. Clinically, Myelodysplastic syndromes (MDS) and related myeloproliferative neoplasias (MPN) disorders1-5 are believed to present as a precursor stage to lethal AML development. Despite the identification of cytogenetic abnormalities and increased activation of signaling in human MDS/MPN, specific pathways that either sustain or initiate disease progression and evolve into self-sustaining leukemic-initiating cells (L-ICs)13 have not been elucidated. Here we demonstrate that tissue specific loss of glycogen synthase kinase-3β (GSK3 betaβ) initiates the emergence of stable Pre-leukemic-ICs (PLIC) in vivo. In contrast to deletion or transgenic perturbation of pathways associated with AML eg. β-catenin/Wnt, serial transplantation of PL-IC produced abnormal hematological disease that phenotypically and molecularly resembles human MDS/MPN. PL-ICs were exclusively generated from GSK3 betaβ deficient hematopoietic stem cells (HSCs), indicating that disease initiation events collaborate with existing HSC self-renewal machinery. In the absence of GSK3 betaβ, subsequent deletion of GSK3 betaα caused rapid induction of L-ICs that give rise to lethal AML. As these processes were solely driven by dose-dependent deficiencies in GSK3 beta levels, our results suggest that perturbation of this pathway can sufficiently drive and recapitulate a step-wise progression of disease from HSCs to MDS/MPN and subsequent AML. Our study provides a molecular and cellular foundation to understand AML evolution from pre-leukemic precursors. We suggest that defining the molecular states of pre-neoplastic disease will allow patient stratification at early stages of MDS/MPN onset and aid in the development of therapeutic targeting of causal pathways responsible for the earliest stages of leukemic initiation events.

overall_design: 5 week post-transplanted recipient mice (CD45.1) with either Lin- bone marrow GSK3 alpha +/+ beta +/flx, alpha+/+ beta flx/flx, alpha -/- beta +/+ or  alpha-/- beta fx/flx Rosa26-CreERTM cells (CD45.2) were induced 3 times with intraperitoneal injections of Tamoxifen (75mg/kg) at intervals of two to three days. Mice were sacrificed and analyzed 4 weeks after injection. Bone marrow lineage negative (Lin-), Sca1+, cKit+ cells were sorted from engrafted Lin- bone marrow GSK3 alpha +/+ beta +/flx, alpha+/+ beta flx/flx, alpha -/- beta +/+ or  alpha-/- beta fx/flx cells for RNA extraction. Total RNA from purified populations was extracted and amplified as described previously (Shojaei et al., 2005). Amplified-labeled RNA was hybridized to Affymetrix Mouse Genome 430 2.0 Array.

first: Borhane

last: Guezguez

first: Susann

last: Rahmig

first: Zoya

last: Shapovalova

first: Aline

last: Fiebig-Comyn

first: Kevin

middle: F

last: Kelly

first: Bradley

last: Doble


title: Longitudinal Gene Expression Analysis in Human Brain identifies biological processes underlying neuropathology in Down Syndrome

status: Public on Jan 20 2016

city: Tampa

first: Feng

last: Cheng

state: FL

address: 12901 Bruce B Downs Blvd MDC 30

department: Department of Pharmaceutical Science

institute: University of South Florida

summary: Trisomy 21 (Ts21) or Down syndrome (DS) is the most common genetic cause of intellectual disability. To investigate the consequences of Ts21 on human brain development, we have systematically analyzed the transcriptome of dorsolateral prefrontal cortex (DFC) and cerebellar cortex (CBC) using exon array mapping in DS and matched euploid control brains spanning from prenatal development to adulthood. We identify hundreds of differentially expressed (DEX) genes in the DS brains, many of which exhibit temporal changes in expression over the lifespan. To gain insight into how these DEX genes may cause specific DS phenotypes, we identified functional modules of co-expressed genes using several different bioinformatics approaches, including WGCNA and gene ontology analysis.  A module comprised of genes associated with myelination, including those dynamically expressed over the course of oligodendrocyte development, was amongst those with the great levels of differential gene expression. Using Ts65Dn mouse line, the most common rodent  model of DS, w e observed significant and novel defects in oligodendrocyte maturation and myelin ultrastructure; establishing  a correlative proof-of-principle implicating myelin dysgenesis in DS.  Thus, examination of the spatio-temporal transcriptome predicts specific cellular and functional events in the DS brain and is an outstanding resource for determining putative mechanisms involved in the neuropathology of DS.

overall_design: Here, we performed a global unbiased gene expression screen at both gene and exon levels of brain samples representing the continuum of human life from 16 gestational weeks to 42 years-old.  This longitudinal approach uncovered a highly dynamic disruption of the transcriptome, with alterations in gene expression in each brain region changing over time. Bioinformatics analyses of the transcriptome profiles indicate that a wide variety of biological processes are affected in the DS dorsolateral prefrontal cortex (PFC) and cerebellar cortex (CBC), presumably underlying the morphological and cytological abnormalities which arise in these structures during brain development and extending into adulthood.  These spatial and temporal patterns of gene dysregulation identify key genes and groups of genes potentially responsible for the cognitive disability in DS, including substantial abnormalities in gene associated with the oligodendrocyte lineage and myelination. We also provide proof-of-concept experiments by identifying white matter alterations predicted by our transcriptome data in  a widely used trisomic mouse model of DS, Ts65Dn. We have identified. Thus, this longitudinal human brain transcriptome data resource provides a powerful and extensive framework to identify, prioritize and test gene targets and developmental mechanisms underlying the neuropathophysiology of DS

first: Jose

middle: L

last: Olmos-Serrano

first: Hyo

last: Kang

first: William

last: Tyler

first: Mihovil

last: Pletikos

first: Ying

last: Zhu

first: Nathan

middle: P

last: Cramer

first: Zygmunt

last: Galdzicki

first: Joseph

last: Goodliffe

first: Alan

last: Peters

first: Claire

last: Sethares

first: Tarik

last: Haydar

first: Nenad

last: Sestan


title: Stromal-Based Signatures for the Classification of Gastric Cancer [part I]

status: Public on Jan 07 2016

city: Indianapolis

first: Jiangang

last: Liu

address: 893 S Delaware St

department: Tailored Therapeutics

institute: Eli Lilly and Company

summary:
Increasing success is being achieved in the treatment of malignancies with stromal-targeted therapies, predominantly in anti-angiogenesis and immunotherapy, predominantly checkpoint inhibitors. Despite 15 years of clinical trials with anti-VEGF pathway inhibitors for cancer, we still find ourselves lacking reliable predictive biomarkers to select patients for anti-angiogenesis therapy. For the more recent immunotherapy agents, there are many approaches for patient selection under investigation.
Notably, the predictive power of an Ad-VEGF-A164 mouse model to drive a stromal response with similarities to a wound healing response shows relevance for human cancer and was used to generate stromal signatures. We have developed gene signatures for 3 stromal states and leveraged the data from multiple large cohort bioinformatics studies of gastric cancer (TCGA, ACRG) to further understand how these relate to the dominant patient phenotypes identified by previous bioinformatics efforts. We have also designed multiplexed IHC assays that robustly represent the vascular and immune diversity in gastric cancer. Finally, we have used this methodology to arrive at a hypothesis of how angiogenesis and immunotherapy may fit into the experimental approaches for gastric cancer treatments.

overall_design: The Ad-VEGF-A164 flank model was performed as described in Flank tissue from harvest day 0, day 5, day 20, and day 60 was taken for RNA generation. Samples for messenger RNA (mRNA) profiling studies were processed by Asuragen, Inc. (Austin, TX, USA) using GeneChip® Mouse Genome 430 2.0 Array (Affymetrix, Santa Clara, CA) according to the company's standard operating procedures as described previously in detail. A summary of the image signal data, detection calls and gene annotations for every gene interrogated on the arrays were generated using the Affymetrix Statistical Algorithm MAS 5.0 (GCOS v1.3) algorithm  (scaling factor = 1500).

first: Mark

last: Uhlik

first: Beverly

last: Falcon

first: Seema

last: Iyer

first: Julie

last: Stewart

first: Hilal

last: Celikkaya

first: Marguerita

last: O'Mahony

first: Christopher

last: Sevinsky

first: Christina

last: Lowes

first: Larry

last: Douglass

first: Cynthia

last: Jeffries

first: Diane

last: Bodenmiller

first: Sudhakar

last: Chintharlapalli

first: Anthony

last: Fischl

first: Damien

last: Gerald

first: Qi

last: Xue

first: Jee-yun

last: Lee

first: Alberto

last: Santamaria-Pang

first: Yousef

last: Al-Kofahi

first: Yunxia

last: Sui

first: Keyur

last: Desai

first: Thompson

last: Doman

first: Amit

last: Aggarwal

first: Julia

last: Carter

first: Bronislaw

last: Pytowski

first: Shou-ching

last: Jaminet

first: Fiona

last: Ginty

first: Aejaz

last: Nasir

first: Janice

last: Nagy

first: Harold

last: Dvorak

first: Laura

middle: E

last: Benjamin


title: Stromal-Based Signatures for the Classification of Gastric Cancer [part II]

status: Public on Jan 08 2016

first: Jiangang

last: Liu

summary: Increasing success is being achieved in the treatment of malignancies with stromal-targeted therapies, predominantly in anti-angiogenesis and immunotherapy, predominantly checkpoint inhibitors. Despite 15 years of clinical trials with anti-VEGF pathway inhibitors for cancer, we still find ourselves lacking reliable predictive biomarkers to select patients for anti-angiogenesis therapy. For the more recent immunotherapy agents, there are many approaches for patient selection under investigation.  Notably, the predictive power of an Ad-VEGF-A164 mouse model to drive a stromal response with similarities to a wound healing response shows relevance for human cancer and was used to generate stromal signatures. We have developed gene signatures for 3 stromal states and leveraged the data from multiple large cohort bioinformatics studies of gastric cancer (TCGA, ACRG) to further understand how these relate to the dominant patient phenotypes identified by previous bioinformatics efforts. We have also designed multiplexed IHC assays that robustly represent the vascular and immune diversity in gastric cancer. Finally, we have used this methodology to arrive at a hypothesis of how angiogenesis and immunotherapy may fit into the experimental approaches for gastric cancer treatments.

overall_design: The Ad-VEGF-A164 angiogenesis model was performed as previously described. Animals were treated with various anti-VEGF Receptor antibodies via intraperitoneal injection at the doses (DC101 20 mpk or G6 10 mpk) and time points (day 0, day 5, day 20, day 60) to target all of the different populations of tumor-surrogate blood vessels, as they each develop at different time points. At least 5 animals, equally matched, were used per group. At the end of the experiment, angiogenic sites in flanks were photographed and tissues were taken for histology and RNA preparation.

first: Mark

last: Uhlik

first: Beverly

last: Falcon

first: Seema

last: Iyer

first: Julie

last: Stewart

first: Hilal

last: Celikkaya

first: Marguerita

last: O’Mahony

first: Christopher

last: Sevinsky

first: Christina

last: Lowes

first: Larry

last: Douglass

first: Cynthia

last: Jeffries

first: Diane

last: Bodenmiller

first: Sudhakar

last: Chintharlapalli

first: Anthony

last: Fischl

first: Damien

last: Gerald


title: Gene expression profiles of LN3 T-ALL cells, and tumor-associated and WT thymic dendritic cell subsets

city: Austin

first: Lauren

last: Ehrlich

address: 2506 Speedway A5000

department: Molecular Biosciences

institute: The University of Texas at Austin

summary:
Thymic lymphomas develop spontaneously in LN3 mice. As for T-ALL in general, ex vivo LN3 lymphoma cells require stromal support to remain viable in culture. We found that primary stromal cells from thymic lymphomas, but not from wild-type thymi, support ex vivo lymphoma survival. By FACS sorting stromal populations, we identified dendritic cells in the tumor microenvironment as the cells capable of supporting lymphoma survival.
We used microarrays to analyze the gene expression profiles of T-ALL cells and tumor-associated versus wild-type thymic dendritic cell subsets.

overall_design: Sirpa+ and Sirpa-  conventional thymic dendritic cells, as well as CD45+MHCII- T-ALL tumor cells, were isolated from three male LN3 tumor-bearing mice. After enzymatic digestion of the thymi, the dendritic cells and tumor cells were FACS purified, and RNA was extracted and hybridized to Affymetrix Mouse 430 2.0 arrays. Raw data were uploaded to Gene Expression Commons for RMA normalization. Both raw CEL and normalized datasets from the 9 samples are included. Normalized datasets for Sirpa+ and Sirpa-  conventional thymic DC subsets in WT mice at 6 months of age is included here as well. A model within Gene Expression Commons has been created for comparison of these datasets to previously reported WT thymocytes from mice at 6 months of age.  The model within Gene Expression Commons contains 22 populations:  6-month WT Sirpa- DC (average of 2 datasets),   6-month WT Sirpa+ DC (average of 2 datasets), 3 individual tumor-associated Sirpa-DC populations , 3 individual tumor-associated  Sirpa+ DC populations, and 3 individual CD45+MHCII- T-ALL cell populations. In addition WT thymocyte subsets (DN1, DN2, DN3a, DN3b, DN4, DP CD69-, DP CD69+, CD4 CD69+, CD4 CD69-, CD8 CD69+, and CD8 CD69+) are included, each as averages of 3 datasets. WT thymocyte datasets were published in Seita et al.,PLoS ONE (2012), vol. 7 (7) e40321 (GSE34723). WT thymic dendritic cell subsets from 6 month old mice were published in Ki et al., Cell Rep (2014), vol. 9, pp. 402-15 (GSE56928).

first: Todd

last: Triplett

first: Kim

last: Cardenas

first: Jessica

middle: N

last: Lancaster

first: Zicheng

last: Hu

first: Hilary

middle: J

last: Selden

first: Guadalupe

last: Jasso

first: Sadhana

last: Balasubramanyam

first: Kathy

last: Chan

first: LiQi

last: Li

first: Xi

last: Chen

first: Andrea

last: Marcogliese

first: Utpal

last: Dave

first: Paul

last: Love


title: Adiponectin-cre FTO flox/flox and FTO flox/flox mouse white fat tissues

status: Public on Jan 01 2016

city: Taoyuan

first: Chao-Yung

last: Wang

address: 5 Fu-Hsing street

country: Taiwan

institute: Chang Gung Memorial Hospital

summary:
Single nucleotide polymorphisms in intron 1 of the fat mass and obesity-associated (FTO) gene were found to be associated with an increased risk of adult obesity. Enhanced FTO expression in mice leads to hyperphagia, increased fat mass, and higher body weight. Neuronal-specific FTO–deleted mice have an identical lean body weight phenotype to global FTO-deleted mice. The physiological role of adipose FTO in the homeostasis of energy regulation remains to be elucidated.
We used microarrays to elucidate the metabolic pathways that are regulated by FTO in the white fat.

overall_design: FTO flox/flox and Adiponectin-cre FTO flox/flox (AFO) mice were fed with chow diet. White fat tissues from epididymal adipose pad were harvested under ad lib condition for RNA isolation. Three independent pools of FTO flox/flox and AFO mouse white fat RNA were included in the study.

first: Shian-Sen

last: Shie

first: Ming-Shien

last: Wen

first: Kuo-Chun

last: Hung

first: I-Chang

last: Hsieh

first: Ta-Sen

last: Yeh

first: Delon

last: Wu


title: Hypoxia-induced alterations of G2 checkpoint regulators

status: Public on Jan 04 2016

first: Heidi

last: Lyng

address: Montebello

department: Department of Radiation Biology

institute: Oslo University Hospital

summary: Hypoxia promotes an aggressive tumor phenotype with increased genomic instability, partially due to downregulation of DNA repair pathways. However, in addition to DNA repair, genome stability is also controlled by cell cycle checkpoints. An important issue is therefore whether hypoxia also can alter the DNA damage cell cycle checkpoints. Here, we show that hypoxia (24h 0.2% O2) alters the expression of several G2 checkpoint regulators, as examined by microarray gene expression analysis and immunoblotting of U2OS cells. While some of the changes reflected hypoxia-induced inhibition of cell cycle progression, flow cytometric bar-coding analysis of individual cells showed that the levels of several G2 checkpoint regulators  were reduced in G2 phase cells after hypoxic exposure, in particular cyclin B1. These effects were accompanied by decreased Cyclin dependent kinase (CDK) activity in G2 phase cells after hypoxia. Furthermore, cells pre-exposed to hypoxia showed a longer G2 checkpoint arrest upon treatment with ionizing radiation. Similar results were found following other hypoxic conditions (~0.03 % O2 20h and 0.2% O2 72h). These results demonstrate that the DNA damage G2 checkpoint can be altered as a consequence of hypoxia, and we propose that such alterations may influence the genome stability of hypoxic tumors.

overall_design: We measured gene expression changes in U2OS cells after treatment with 0.2% hypoxia for 24 hours. The data were used in the exploration of hyopxia induced alterations in the G2 checkpoint.

first: Grete

last: Hasvold

first: Christin

last: Lund-Andersen

first: Malin

last: Lando

first: Sebastian

last: Patzke

first: Sissel

last: Hauge

first: ZhenHe

last: Suo

first: Randi

last: Syljuåsen


title: Gene expression data from mouse tracheal mesenchymal cells before and 48hrs after SO2 injury

city: Durham

first: Xia

last: Gao

state: NC

address: 353 Nanaline Duke Bldg. Research Dr.

institute: Duke University

summary:
The conducting airway epithelium of the rodent and human lung is underlaid by mesenchymal cells that include vasculature, smooth muscle, fibroblasts and cartilage. The goal of this project is to identify cellular and molecular changes in the mesenchyme after injury to the epithelium by exposure to SO2 and which may participate in repair of the epithelium
We used Affymetrix microarray analysis to compare transcripts in tracheal mesenchyme before and after SO2 injury.

overall_design: Mice tracheal epithelium and mesenchyme were separate for RNA extraction before and 48hrs after SO2 injury. Sample from 4 mice were pooled  for each biological experiment. The experiments were repeated three times for triplicate samples.

first: Brigid

last: Hogan


title: Gene expression data from mouse tracheal epithelial cells isolated before and 48hrs after SO2 injury

summary:
The conducting airway epithelium of the rodent and human lung is made up of about equal proportions of ciliated and secretory cells. In addition, in regions where the epithelium is pseudostratfied, ~30% of the epithelium consists of undifferentiated basal cells (BCs). Evidence suggests that these BCs are multipotent stem cells that can self renew over the long term and give rise to both ciliated and secretory lineages. The goal of this project is to identify cellular and molecular mechanisms by which the basal cells normally maintain the epithelium and repair it after injury.
We used Affymetrix microarray analysis to compare transcripts in tracheal epithelium before and after SO2 injury.

overall_design: Mice tracheal epithelium and mesenchyme were separate for RNA extraction before and 48hrs after SO2 injury. Cells from tracheas of 4 male C57Bl/6 mice were pooled  for each biological experiment. The experiments were repeated three times for triplicate samples.


title: Gene expression data from mouse tracheal cells before and 48hrs after SO2 injury

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

overall_design: Refer to individual Series


title: Identification of novel type 2 diabetes candidate genes involved in the crosstalk between the mitochondrial and the insulin signaling systems: TP53inp2 (DOR) RNAi knock-downs

city: Barcelona

first: Josep M

last: Mercader

state: Catalunya

address: C/Jordi Girona 29 08034

department: Life Science Department

institute: Barcelona Supercomputing Center

summary: Type 2 diabetes (T2D) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. There is growing evidence supporting that a crosstalk between mitochondria and the insulin-signaling cascade could be involved in the etiology of TD2 and insulin resistance. In this study, we investigated the molecular basis of this crosstalk by using systems biology approaches. We combined, filtered and interrogated different types of functional interaction data, such as direct protein-protein interactions, co-expression analyses and metabolic and signaling dependencies. As a result, we constructed the mitochondria-insulin (MITIN) network, which highlights 286 genes as candidate functional linkers between these two systems. The results of internal gene expression analysis of three independent experimental models of mitochondria and insulin signaling perturbations further support the connecting roles of these genes. In addition, we further assessed whether these genes are involved in the etiology of T2D using the largest genome-wide meta-analysis from the DIAGRAM consortium, involving 8,130 T2D cases and 38,987 controls. We found significant enrichment of T2D-associated SNPs in the genomic context of our linker genes, including four already confirmed and 14 additional SNPs, which when combined were also associated with increased fasting glucose levels according to MAGIC genome-wide meta-analysis (p = 2.8 x 10-7). This study highlights the potential of combining systems biology, experimental, and genome-wide meta-analyses mining for identifying novel genetic variants that increase vulnerability to complex diseases.

overall_design:
Four C2C12 myoblast biological replicates infected with lentivirus encoding DOR siRNA vs. four biological controls (C2C12 myoblasts infected with lentivirus encoding scrambled RNA) were analyzed.

Contributors:
DIAGRAM Consortium
MITIN Consortium

first: Josep

middle: M

first: Montserrat

last: Puiggros

first: Ayellet

middle: V

last: Segrè

first: Evarist

last: Planet

first: Eleonora

last: Sorianello

first: David

last: Sebastian

first: Sergio

last: Rodriguez-Cuenca

first: Vicent

last: Ribas

first: Sílvia

last: Bonàs-Guarch

first: Sorin

last: Draghici

first: Chenjing

last: Yang

last: Mora

first: Antoni

last: Vidal-Puig

first: Josée

last: Dupuis

first: Jose

middle: C

last: Florez

first: Antonio

last: Zorzano

last: Torrents


title: ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells

city: Taipei

first: Mong-Hsun

last: Tsai

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

department: Institute of Biotechnology

institute: National Taiwan University

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


title: Identification of novel type 2 diabetes candidate genes involved in the crosstalk between the mitochondrial and the insulin signaling systems

first: Josep M

last: Mercader


title: Hey target gene regulation in murine ES cells and cardiomyocytes [Affymetrix]

city: Wuerzburg

first: Manfred

last: Gessler

address: Am Hubland

department: Developmental Biochemistry

institute: Biocenter, University of Wuerzburg

summary: We used an in vitro cardiomyocyte differentiation system with inducible Hey1 or Hey2 expression to study target gene regulation in cardiomyocytes (CM) generated from murine embryonic stem cells (ESC). The effects of Hey1 and Hey2 are largely redundant, but cell type specific. The number of regulated genes is comparable between ESC and CM, but the total number of binding sites is much higher, especially in ESC, targeting mainly genes involved in transcriptional regulation and developmental processes. Repression by Hey generally correlates with the extent of Hey-binding to target promoters, subsequent Hdac recruitment and lower histone acetylation. Functionally, treatment with the Hdac inhibitor TSA abolished Hey target gene regulation. However, in CM the repressive effect of Hey-binding is lost for a subset of genes. These lack Hey-dependent histone deacetylation in CM and are enriched for binding sites of cardiac specific activators like Srf, Nkx2-5, and Gata4.

overall_design: Control cells and cells with Hey1 or Hey2 overexpression, no replicates

last: Weber

first: Julia

last: Heisig

first: Susanne

last: Kneitz


title: ADAM9 Up-regulates N-Cadherin via MiR-218 Suppression in Lung Adenocarcinoma Cells [miRNA]

summary: Lung cancer is the leading cause of cancer death worldwide. Brain metastasis is a major cause of morbidity and mortality in lung cancer. CDH2 (N-cadherin, a mesenchymal marker in epithelial-mesenchymal transition) and ADAM9 (a member of type I transmembrane proteins) have been reported relating to lung cancer brain metastasis, however, it is still not clear whether any interaction between them to mediate lung cancer brain metastasis. Since microRNAs were discovered to regulate many biological functions and disease processes (e.g., cancer) by down-regulating their target genes, microRNA microarrays were used to identify ADAM9 regulated miRNAs that target CDH2 in aggressive lung cancer cells. Luciferase assays and immunoblotting proved that CDH2 was a target gene of miR-218. The expression of miR-218 was generated from pri-mir-218-1, located in SLIT2, in low invasive lung adenocarcinoma while it was inhibited in aggressive lung adenocarcinoma. Down-regulation of ADAM9 could up-regulate SLIT2 and miR-218, thus down-regulate CDH2 expression. This study elucidated the mechanism of ADAM9 activating CDH2 may be due to release the inhibition of miR-218 on CDH2 in lung adenocarcinoma.

overall_design: For each of the cell lines bm#2, bm#7, and F4, one microarray was analyzed.

first: Yuh-Ping

last: Sher

first: Li-Ju

last: Wang

first: Ting-Ting

last: Kuo

first: Eric

middle: Y

last: Chuang

first: Liang-Chuan

last: Lai


title: Stromal-Based Signatures for the Classification of Gastric Cancer

first: Jiangang

last: Liu


title: Identification of novel type 2 diabetes candidate genes involved in the crosstalk between the mitochondrial and the insulin signaling systems: Pgc1b knock-out hearts

overall_design:
Three biological replicates of Pgc1b knockout hearts and three biological replicates of control wild-type hearts were analyzed.

Contributors:
DIAGRAM Consortium
MITIN Consortium

first: Josep

first: Montserrat

last: Puiggros

first: Ayellet

last: Segrè

first: Evarist

last: Planet

first: Eleonora

last: Sorianello

first: David

last: Sebastian

first: Sergio

last: Rodriguez-Cuenca

first: Vicent

last: Ribas

first: Sílvia

last: Bonàs-Guarch

first: Sorin

last: Draghici

last: Yang

last: Mora

last: Vidal-Puig


title: Identification of drugs that enhance skin repair using dermal stem cell-based screens [Rat]

status: Public on Dec 24 2015

city: Toronto

first: Freda

last: Miller

state: ON

address: 686 Bay St

institute: Hospital for Sick Children

summary: Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on SKPs (skin-derived precursors) a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated 5 such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKPs self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy.

overall_design: We obtained three independent isolates of SKPs from newborn Sprague-Dawley rat pups. Secondary SKPs spheres were dissociated, treated with 100 nM of alprostadil, trimebutine maleate or 100 nM of both trimebutine maleate and trametinib for 24 hour. RNA samples deriving from these cells were analyzed on the Affymetrix GeneChip Rat Gene 2.0 ST Array.

first: Sibel

last: Naska

first: Scott

last: Yuzwa

first: Adam

last: Johnston

first: Smitha

last: Paul

first: Kristen

last: Smith

first: Maryline

last: Paris

first: Michael

last: Sefton

first: Alessandro

last: Datti

middle: D

last: Kaplan


title: Expression data from tumors generated from genome-engineered mice

status: Public on Dec 25 2015

city: Hiroshima

first: Hiroaki

last: Niitsu

address: 1-2-3 Kasumi, Minamiku

department: Department of gastroenterological surgery

institute: Hiroshima University

summary:
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 30–40% of human colorectal cancers (CRC). However, specific therapeutics against KRAS-mutated CRC have not been established. We have previously reported mouse models for colon cancer with and without Kras mutations (CDX2P-G22Cre;Apcflox/flox; KrasG12D and CDX2P-G22Cre;Apcflox/flox mice, respectively).
Herein, we aimed to identify candidate genes as novel therapeutic targets or biomarkers for KRAS-mutated CRC by comparing the gene expression profiles of these two mouse models.

overall_design: At an age of 6–8 weeks, 3 tumours were harvested from each of the two mouse models and gene expression profiles were generated using microarrays  (GeneChip Mouse Genome 430 2.0 Array; Affymetrix, Santa Clara, CA)

first: Takao

last: Hinoi

first: Yasuo

last: Kawaguchi

first: Kazuhiro

last: Sentani

first: Ryo

last: Yuge

first: Yasuhiko

last: Kitadai

first: Yusuke

last: Sotomaru

first: Tomohiro

last: Adachi

first: Yasufumi

last: Saito

first: Masashi

last: Miguchi

first: Masatoshi

last: Kochi

first: Haruki

last: Sada

first: Manabu

last: Shimomura

first: Naohide

last: Oue

first: Wataru

last: Yasui

first: Hideki

last: Ohdan


title: Expression and Splicing Analysis of Myotonic Dystrophy and Other Dystrophic Muscle

status: Public on Jan 05 2016

city: Houston

first: Mario

last: Sirito

address: 1515 Holcombe blvd

department: Cancer Genetics

institute: M. D. Anderson Cancer Center

summary: The prevailing patho-mechanistic paradigm for myotonic dystrophy (DM) is that the aberrant presence of embryonic isoforms is responsible for many, if not most, aspects of the pleiotropic disease phenotype.  In order to identify such aberrantly expressed isoforms in skeletal muscle of DM type 1 (DM1) and type 2 (DM2) patients, we utilized the Affymetrix exon array to characterize the largest collection of DM samples analyzed to date, and included non-DM dystrophic muscle samples (NMD) as disease controls.

overall_design:
For the exon array profiling on the Human Exon 1.0 ST array (Affymetrix Santa Clara, CA) we used a panel of 28 skeletal muscle biopsies from DM1 (n=8), DM2 (n=10), Becker muscular dystrophy, BMD, (n=3), Duchenne muscular dystrophy, DMD (n=1), Tibial muscular dystrophy, TMD, (n=2) and normal skeletal muscle (n=4).  Normal control RNAs were purchased commercially.
.CEL files were generated with a pre-commercial version of the Affymetrix processing software, and the headers might be non-standard. In our lab, users of the Partek software could use them, whereas users of GeneSpring had to modify the header information.

first: Linda

last: Bachinski

first: Keith

last: Baggerly

first: Valorie

last: Neubauer

first: Tamara

last: Nixon

first: Olayinka

last: Raheem

first: Anna

last: Unruh

first: Jiexin

last: Zhang

first: Lalitha

last: Nagarajan

first: Lubov

last: Timchenko

first: Guillaume

last: Bassez

first: Bruno

last: Eymard

first: Josep

last: Gamez

first: Tetsuo

last: Ashizawa

first: Jerry

last: Mendelli

first: Bjarne

last: Udd

first: Ralf

last: Krahe


title: Identification of drugs that enhance skin repair using dermal stem cell-based screens

first: Freda

last: Miller

sample_organism:
Mus musculus
Rattus norvegicus

platform_organism:
Mus musculus
Rattus norvegicus


title: Activation of IFN/STAT1 signaling is a hallmark of response to chemotherapy in patient-derived xenografts of triple-negative breast cancer

status: Public on Dec 31 2015

city: Evry

first: stefano

last: cairo

address: 4 rue Pierre Fontaine

institute: Xentech

summary:
By using patient-derived xenografts (PDXs) as living surrogate of the clinical practice, we identify here induction of genes related to the IFN pathway as an early and specific predictor of tumor response to treatment.
Gene expression profile of tumor cells after laser-capture microdissection of residual tumor foci to characterize the molecular changes occurring in residual tumor cells surviving chemotherapy

overall_design: RNA was extracted from microdissected areas using the RNeasy Mini kit (Qiagen, Valencia, CA). This approach allowed isolating foci of human tumor cells from the murine stroma. Gene expression analysis was performed with Affymetrix Exon 1.0 ST microarrays. Hybridization, data normalization and statistical analysis were outsourced to GenoSplice Technology (Paris, France).

first: Marie-Emmanuelle

last: Legrier

first: Olivier

last: Déas

first: Jean-Gabriel

last: Judde

first: Pierre

last: De La Grange


title: Sleeping Beauty Expression data from mouse

city: Singapore

first: Tuan Zea

last: Tan

address: 14 Medical Drive, #11-01, Singapore

department: Cancer Science Institute Singapore

country: Singapore

institute: National University of Singapore

summary: We extracted RNA of 39 mouse tissue of various genotypes and performed expression microarrays.  Subsequently a screen was conducted using the Sleeping Beauty (SB) transposon to identify breast cancer candidate genes.

overall_design: 39 mouse samples expression data.

first: Jean-Paul

last: Thiery


title: RING1 links retinoic acid signaling to the early proximal-distal specification of forelimb bud via Meis2 repression (mRNA)

status: Public on Dec 28 2015

city: Yokohama

first: Takaho

middle: A.

last: Endo

state: Kanagawa

address: 1-7-22 Suehiro, Tsurumi

department: IMS

institute: RIKEN

summary:
Polycomb group (PcG) proteins play a pivotal role in silencing of development-related genes and contribute to maintain various stem and precursor cells and regulate their differentiation. However, it is not well understood how PcG factors regulate dynamic and complex morphogenetic processes particularly in mammals. In this study, we focused on proximal-distal (PD) patterning of forelimb bud to elucidate how PcG factors contribute to regulation of morphogenetic processes that depends on developmental signals. Depletion of RING1 proteins, which are common components of both canonical and variant Polycomb repressive complex-1 (PRC1), led to dramatic deficiencies in forelimb formation.
By using Ring1-deficient forelimb buds, we revealed the early defects in distal specification, which is due to the functional coupling of RING1 and retinoic acid (RA) signaling. RING1 activity is shown to antagonize with RA signals at Meis2 and likely Meis1, which are superior suppressors of distal formation program, in the prospective distal region of outgrowing forelimb bud. This study exhibits a first example showing how PcG factors interplay with developmental signals to mediate compartmentalization of elongating anlagen by regulating the expression of developmental genes.

overall_design: Mouse E10.5 proximal or distal forelimb buds of Ring1A-KO, Ring1A/B-dKO and RA-treated wild type were used for RNA extraction and hybridization on Affymetrix microarrays.

first: N

last: Yakushiji-Kaminatsui

first: T

first: H

last: Koseki


title: miRNA expression profiling in prostate cancer and non-neoplastic tissues

status: Public on Dec 23 2015

city: Milan

first: Matteo

last: Dugo

address: via Olgettina 60

department: Department of Medical Oncology

institute: IRCCS Ospedale San Raffaele

summary: miRNA expression profiles were evaluated in a series of 64 prostate clinical specimens, including 32 cancer and 32 non-neoplastic tissues. For 26 individuals, paired cancer and non-neplastic tissue was available.

overall_design: Tumor and non-neoplastic tissues were obtained, with appropriate informed consent and Institutional Review Board approval, from untreated prostate cancer patients subjected to radical prostatectomy. Freshly frozen surgical blocks were carefully dissected by the pathologist using H&E-stained sections as a template to identify areas containing at least 70% of tumor or normal cells. The total series comprises 64 clinical specimens, of which 32 from cancer areas and 32 from benign areas. For 26 patients, matched tumor and normal samples were available.

first: Paolo

last: Gandellini

first: Loris

last: De Cecco


title: Expression data of Myh6-MeCP2 transgenic mice

status: Public on Dec 22 2015

city: Freiburg

last: Gilsbach

address: Albertstr. 25

institute: Institute of Pharmacology

summary:
Hearts of Myh6-MeCP2 transgenic mice and wildtype littermates were rapidly dissected and flash frozen.
We used Affymetrix microarrays to assess gene expression changes induced by overexpression of MeCP2 under the control of a cardiomycyte specific promoter.

overall_design: Hearts were dissected 2-3 weeks after birth from transgenic Myh6-MeCP2 mice and littermates to study gene expression alterations.

first: Sandra

last: Mayer

first: Lutz

last: Hein


title: Basal gene expression in proliferating ASCs

status: Public on Dec 21 2015

city: Oslo

first: Philippe

last: Collas

address: PO Box 1112 Blindern

department: Institute of Basic Medical Sciences

institute: University of Oslo

summary: The aim of this study was to characterize basal gene expression for proliferating adipose tissue MSCs, cultured at normal cell culture conditions.

overall_design: RNA was isolated from ASCs from 3 different donors cultured at normal conditions (DMEM/F12,10% FBS) for 3 weeks.

first: Agate

last: Noer

first: Torunn

last: Rønningen


title: Transcriptional responses to high glucose in adipose tissue stem cells


title: Expression data from the human whole blood samples

city: Rotterdam

first: Dmitry

last: Zubakov

state: ZH

address: Dr. Molewaterplein, 50

department: FMB

country: Netherlands

institute: Erasmus Medical Centre Rotterdam

summary:
Microarray expression profiling approach was used to identify age-related mRNA markers.
In this dataset, we include the expression data obtained from whole venous blood samples collected from ERF (Erasmus Rucphen Family study) donors of different age. Two age groups - young (~25 y.o.) and old (~ 60 y.o.) were analyzed using Partek GS software.

overall_design: A total of 47 samples, representing two age categories were compared to each other (young vs old).

first: D


title: Renal Cell Carcinomas in Vinylidene Chloride Exposed Male B63FC1 Mice Are Characterized by Oxidative Stress and TP53 Overexpression

city: RTP

first: NIEHS

last: Microarray Core

address: 111 T.W. Alexander Drive

department: DIR

institute: NIEHS

summary: Vinylidene Chloride has been widely used in the production of plastics and flame retardants. Exposure of B6C3F1 to VDC in the 2-year National Toxicology Program carcinogenicity bioassay resulted in a dose-dependent increase in renal cell hyperplasias, adenomas, and carcinomas (RCCs). Global gene expression analysis showed overrepresentation of pathways associated with chronic xenobiotic and oxidative stress in RCCs from VDC-exposed B6C3F1 mice, as well as cMyc overexpression and dysregulation of Tp53 cell cycle checkpoint and DNA damage repair pathways. Trend analysis comparing RCC, VDC-exposed kidney, and vehicle control kidney showed a conservation of pathway dysregulation in terms of overrepresentation of xenobiotic and oxidative stress, and DNA damage and cell cycle checkpoint pathways in both VDC-exposed kidney and RCC, suggesting that these mechanisms play a role in the development of RCC in VDC-exposed mice.

overall_design: Compare mouse renal cell carcinoma versus treated kidney and vehicle control normal kidney, 6 replicates each group.

first: Mark

last: Hoenerhoff

first: Arun

last: Pandiri


title: Gene expression profiling of normal lung cells and K-RasG12V driven hyperplasias

status: Public on Dec 14 2015

city: Madrid

first: Chiara

last: Ambrogio

address: Melchor Fernandez Almagro 3

department: Molecular Oncology

institute: CNIO

summary: We aimed to analyze the transcriptional profile of lung epithelial cells early after the expression of a resident K-RasG12V oncogene. This approach was based on the rationale that valuable therapeutic targets should be easier to detect in the first stages of tumor development due to tumor heterogeneity which occurr at late stages.

overall_design: We used a GEM model of lung adenocarcinoma driven by a resident K-RasG12V oncogene. In this GEM, the K-RasG12V allele also expresses a color marker that allows identification of K-RasG12V expressing cells at the single cell level in tissue sections. Thanks to this strategy we isolated early K-RasG12V-driven hyperplastic lesions (about 500 cells) and analyzed their gene expression profiling by Affymetrix GeneChip hybridization. Normal cells were isolated accordingly by LCM in the same lung sections.

first: Gonzalo

last: Gómez-López

first: Mattia

last: Falcone

first: August

last: Vidal

first: Ernest

last: Nadal

first: Nicola

last: Crosetto

first: Rafael

last: Blasco

first: Pablo

last: Fernandez-Marcos

first: Montserrat

last: Sanchez-Céspedes

first: Xiaomei

last: Ren

first: Zhen

last: Wang

first: Ke

last: Ding

first: Manuel

last: Hidalgo

last: Serrano

first: Alberto

last: Villanueva

first: David

last: Santamaría

first: Mariano

last: Barbacid


title: Gene expression profiling of advanced murine K-RasG12V lung adenocarcinomas

last: Ambrogio

summary: We aimed to analyze the transcriptional profile of full-blown murine lung adenocarcinomas driven by K-RasG12V oncogene.

overall_design: We used a GEM model of lung adenocarcinoma driven by a resident K-RasG12V oncogene. On average, tumors were collected 10 months after Adeno-CRE infection.

last: Fernández-Marcos

last: Sánchez-Céspedes


title: TGFβ confers resistance to radiotherapy in non-small cell lung cancer

status: Public on Dec 15 2015

city: Mountain View

first: Afshin

last: Beheshti

state: CA

address: Moffett Blvd

institute: NASA Ames Research Center

summary: Radiotherapy is standard of care for inoperable non-small cell lung cancers (NSCLC) but  adenocarcinoma NSCLC respond more poorly than squamous cell NSCLC. Transforming  growth factor β (TGFβ) activity is induced by radiation and plays a recently recognized role in  the DNA damage response. Here we show in murine lung tumor model that radiation activates  TGFβ acutely and persistently and that TGFβ neutralizing antibody, 1D11, systemic treatment  increased tumor control following either fractionated or single high dose radiation regimes.  TGFβ dependent genes in the irradiated tumor indicated crosstalk between innate and adaptive  immunity but therapeutic benefit of 1D11 in irradiated tumors in immunocompromised mice  suggested that innate immune cells are more influential than the adaptive immune response.  Irradiated tumors in which TGFβ was blocked were highly hypoxic, exhibit pronounced  microvascular damage and promoted neither cancer-associated fibroblasts nor recruit bone  marrow derived cells (BMDC). Tumor educated immature BMDC were significant sources of  TGFβ and inhibiting BMDC recruitment achieved tumor growth control in response to RT  comparable to TGFβ inhibition. Thus, radiation-induced TGFβ both compromises tumor control  by RT and promotes reestablishment of the tumor microenvironment. Concordant with the  critical role of TGFβ activity in RT, radiation resistant NSCLC adenocarcinomas exhibit higher  TGFβ activity compared to squamous cell NSCLC, which suggests a rationale for using TGFβ  inhibition to augment radiotherapy.

overall_design: Lewis lung cancer (LLC) model were established in  6 to 8 week-old C57BL/6 female mice by subcutaneous injection. When tumors were 60-80 mm3, Mice were randomized to achieve comparable mean tumor size for each treatment group as indicated below.  Tumor growth were monitored and tumors were collected and characterized by gene expression profiling and immunostaining.

first: Shisuo

last: Du

first: Haoxu

last: Ouyang

first: Ilenia

last: Pellicciotta

first: Roger

last: Ho

first: Renate

last: Parry

first: Mary

middle: H

last: Barcellos-Hoff


title: Gene expression profiling of normal murine lung cells, K-RasG12V driven lung hyperplasias and full-blown lung adenocarcinomas

first: Chiara

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

overall_design: Refer to individual Series


title: Gene expression profile comparison of DC subsets

status: Public on Dec 10 2015

city: La Jolla

first: Monica

last: Macal

address: 9500 Gilman Dr 0322

institute: UC San Diego

summary:
To evaluate gene expression profiles on different dendritic cell subsets isolated from spleens of mice
We used whole genome microarrays to identify genes specific to pDCs and not other DC subsets in the absence of disease

overall_design: pDCs, CD11b+ cDCs, and CD8+ cDCs were FACS-purified from spleens of healthy C57bl/6 mice

first: Elina

middle: I

last: Zuniga


title: Preference of mitochondrial respiration over the Warbürg effect in breast tumor initiating cells in conditions of oxygen and glucose deprivation.

status: Public on Dec 13 2015

first: Jesús

last: Sánchez Ruiz

address: Calle Melchor Fdez Almagro 3

summary:
Background: cancer cells rely on glycolysis as main ATP source (Warbürg effect). Tumor-initiating cells (TICs) are the fraction of cells that give raise and repopulate tumors. TICs are exposed to prolonged periods of oxygen and glucose deprivation (OGD), as they live in a hypoxic niche and they withstand prolonged lack of blood vessels during initial tumorigenesis or metastasis formation (avascular phase). Warbürg effect is energetically inefficient; we hypothesize that TICs might have differential metabolic features. Tumor eradication requires killing TICS; finding such features would have therapeutic implications.
Methodology/principal findings: 106 MDA-MB-231 breast-cancer cells (hereafter Wt) were exposed for 5 weeks to 0.2% oxygen and 0.1g/l glucose, recovering 9 clones. Both flow-cytometry (50-fold enrichment in the CD24-/CD44+/CD133+ population) and xenografts in NOD/SCID mice using 100 cells (75% vs. 16% engraftment) suggest that OGD-resistant clones are true TICs (hereafter “TIC clones”). TIC clones showed a 30-fold higher replication and viability (BRDU incorporation, colony assay) than Wt. When exposed to OGD, ATP-production dropped 5-fold in WT, but was maintained in TIC clones by increasing 5-fold the fatty acid and oxygen consumption. These properties were explained by lack of upregulation of HIF-1 alpha and PDK1, as well as an increase in ATP-synthase. Analysis with metabolic inhibitors (2-deoxyglucose, antimycin-A) confirmed glycolysis and mitochondrial respiration as main routes of metabolism for Wt and TIC clones respectively. Metabolomics revealed that glutamine catabolism generated the NADPH required to quench reactive oxygen species generated during mitochondrial respiration in TIC clones. Glutamine deprivation or mitochondrial blockers were able to abrogate the viability of TIC clones.
Conclusions/significance: the TIC-fraction of a cancer cell population withstands prolonged OGD by switching from the Warbürg effect to mitochondrial respiration. Targeting this metabolic feature abrogates the survival of TICs.

overall_design: Mitochondrial metabolism in cancer-stem cells.

first: Enrico

last: Arpaia

first: Paloma

last: Navarro

first: Francisco

last: Rupérez

first: Ramon

last: Colomer

first: Luis

last: Lombardía

first: Tamara

last: Mondéjar

first: Coral

last: Barbas

first: Miguel

last: Quintela-Fandino


title: MicroRNA expression profiles for paediatric brain tumours

city: London

first: Denise

last: Sheer

address: Blizard Institute, 4 Newark Street

department: Neuroscience & Trauma

institute: Barts & The London School of Medicine & Dentistry

summary: In this study, we screened a cohort of 57 paediatric brain tumours, with a wide range of pathologies to identify microRNA profiles

overall_design: We analysed the microRNA profiles in paediatric brain tumours as compared to normal adult brain. Our cohort included 14 pilocytic astrocytomas, 3 diffuse astrocytomas, 2 anaplastic astrocytomas, 5 glioblastomas, 14 ependymomas, 9 medulloblastomas, 5 atypical teratoid/rhabdoid tumours, 4 choroid plexus papillomas, 1 papillary glioneuronal, and 7 adult brain controls.


title: Gene expression analysis in Fmr1KO mice identifies an immunological signature in brain tissue and mGluR5-related signaling in primary neuronal cultures.

city: Boston

first: Alvin

middle: T.

last: Kho

state: MA

address: 320 Longwood Avenue

department: Informatics Program

institute: Boston Children's Hospital

summary: Transcriptome profile of whole tissue and cultured neuronal cells from the hippocampus and cortex from pooled littermate embryos (at 17-18 days post conception) of 2 mouse genotypes C57BL/6 congenic WT and Fmr1 KO.

overall_design:
Fragile X mouse model, whole tissue and cultured neuronal cells from the hippocampus and cortex
Pooled whole tissue or cultured cells from the central nervous system of embryonic mouse littermates of 2 genotypes.

first: Daria

last: Prilutsky

middle: T

first: Nathan

last: Palmer

first: Asha

last: Bhakar

first: Mark

last: Bear

first: Isaac

middle: S

last: Kohane


title: Insulin resistance in high fat diet mouse

status: Public on Dec 07 2015

city: Camperdown, Sydney

first: Rima

last: Chaudhuri

state: NSW

address: D17 Johns Hopkins Drive

department: Charles Perkins Center

country: Australia

institute: University of Sydney

summary:
Recent discovery reveals HFD insult can cause insulin resistance very rapidly, but the underlying mechanism is still not well understood. We performed a short term experiment in a Diet Induced Insulin resistance mouse model.
Objective: Insulin resistance (IR) is one of the earliest predictors of type 2 diabetes. However, diagnosis of IR is limited. High fat fed mouse models provide key insights into IR. We hypothesized that early features of IR are associated with persistent changes in gene expression (GE) and endeavoured to (a) develop novel methods for improving signal:noise in analysis of human GE using mouse models; (b) identify a GE motif that accurately diagnoses IR in humans; and (c) identify novel biology associated with IR in humans. Methods: We integrated human muscle GE data with longitudinal mouse GE data and developed an unbiased three-level cross-species analysis platform (single-gene, gene-set and networks) to generate a gene expression motif (GEM) indicative of IR. A logistic regression classification model validated GEM in 3 independent human datasets (n =115). Results: This GEM of 93 genes substantially improved diagnosis of IR compared to routine clinical measures across multiple independent datasets. Individuals misclassified by GEM possessed other metabolic features raising the possibility that they represent a separate metabolic subclass. The GEM was enriched in pathways previously implicated in insulin action and revealed novel associations between β-catenin and Jak1 and IR. Functional analyses using small molecule inhibitors showed an important role for these proteins in insulin action. Conclusions: This study shows that systems approaches for identifying molecular signatures provides a powerful way to stratify individuals into discrete metabolic groups. Moreover, we speculate that the β-catenin pathway may represent a novel biomarker for IR in humans that warrant future investigation.

overall_design: Comparison of gene expression in muscle tissue during High Fat Diet (HFD) time course (day 5 and day 42). Chow diet will serve as control for HFD. 4 samples per group serve as experimental replicates.

first: Zora

last: Modrusan


title: Cross-species Gene Expression Analysis Identifies a Novel Set of Genes Implicated in Human Insulin Sensitivity

status: Public on Dec 09 2015

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus