title: SUMO safeguards somatic and pluripotent cell identities by enforcing distinct chromatin states

status: Public on Oct 24 2018

city: Paris

first: Claudia

last: Chica

address: 25-28 Rue du Dr Roux

institute: Institut Pasteur

summary: Purposes: (1) compare the SUMO chromatin landscape between mouse embryonic fibroblasts (MEFs) and embryonic stem cells (ESc) (2) Decipher how hyposumoylation enhances MEF to induced pluripotent stem cells (iPSc) reprogramming (3) Decipher how hyposumoylation enhances ESc to 2C-like cells conversion. Methods : (1) ChIP-seq in MEFs and ESc for SUMO isoforms and histone marks. (2) ChIP-seq for transcription factors and histone marks at day 4 of MEF to iPSc reprogramming comparing wild type (shCtrl) and hyposumoylated cells (shUbc9). ATAC-Seq at day 4 of MEF to iPSc reprogramming comparing wild type (shCtrl) and hyposumoylated cells (shUbc9). RNA-Seq in MEFs, iPSc, at day 4 and day 7 of MEF to iPSc reprogramming comparing wild type (shCtrl) and hyposumoylated cells (shUbc9). (3) RNA-Seq in ESc comparing wild-type (siCtrl) and hyposumoylated cells (siUbc9). Results: (1) SUMO chromatin landscape is highly different between MEFs and ESc and associates to distinct chromatin marks. (2) Hyposumoylation enhances MEFs to iPSc reprogramming by favoring the extinction of the MEF transcriptional program and redistributing pluripotency factors from MEF enhancers toward ES enhancers. (3) Hyposumoylation enhances ES to 2C-like conversion by destabilizing heterochromatin thus resulting in an activation of the 2-cell transcriptional program. Conclusion: SUMO at chromatin is gate-keeper of cell-identity.

overall_design: Duplicates for ChIP-Seq experiments. Triplicates for ATAC-Seq and RNA-Seq experiments. All replicates are provided for raw data. Pocessed data take into account replicate merge.

first: Jack-Christophe

last: Cossec

first: Ilan

last: Theurillat

first: Anne

last: Dejean


title: Sequential regulation of maternal mRNAs through a conserved cis-acting element in their 3’UTRs [II]

status: Public on Sep 05 2018

city: Albany

first: Prashanth

last: Rangan

state: NY

address: 1400 Washington

department: Biological Sciences

country: USA

institute: RNA Institute

type: Expression profiling by high throughput sequencing

summary: Maternal mRNAs are synthesized during oogenesis to initiate the development of future generations. Some maternal mRNAs are determinants of somatic or germline fate and must be translationally repressed until embryogenesis. However, the translational repressors themselves are also temporally regulated. We use polar granule component (pgc), a Drosophila maternal mRNA, as a model system to ask how maternal mRNAs are repressed while the regulatory landscape is continually shifting. pgc, a potent transcriptional silencer and germline determinant, is translationally regulated throughout oogenesis. We find that the 3’UTR of pgc mRNA contains a conserved ten-nucleotide sequence that is bound by different conserved RNA binding proteins (RBPs) at different stages of oogenesis to continuously repress translation except for a brief expression in the stem cell daughter. Pumilio (Pum) binds to this sequence in undifferentiated and early differentiating oocytes and recruits other temporally restricted translational regulators to block pgc translation. After differentiation, Pum levels diminish and Bruno (Bru) levels increase, allowing Bru to bind the same 3’UTR sequence and take over translational repression of pgc mRNA. We have identified a class of maternal mRNAs regulated during oogenesis by both Pum and Bru, including Zelda, activator of the zygotic genome, which contain this core 10-nt regulatory sequence. Our data suggests that this hand off mechanism is more generally utilized to inhibit translation of maternal mRNAs during oogenesis.

overall_design: RNA-seq of Drosophila ovaries enriched for germline stem cells with nosGAL4>UAS-tkv

first: Pooja

last: Flora

first: Siu

last: Wong-Deyrup

first: Elliot

middle: T

last: Martin

first: Ryan

middle: J

last: Palumbo

first: Mohamad

last: Nasrallah

first: Andrew

last: Oligney

first: Patrick

last: Blatt

first: Dhruv

last: Patel

first: Gabriele

last: Fuchs

first: Prash


title: SOX17 regulates uterine epithelial-stromal crosstalk acting via a distal enhancer upstream of Ihh [array]

status: Public on Aug 09 2018

city: RTP

first: Franco

last: Demayo

state: NC

address: 111 TW Alexander Drive

institute: NIEHS

summary: Mammalian embryo development is dependent on the ability of the uterus to allow and support the implantation of the embryo. Here we demonstrate that ablation of Sox17 specifically in the uterine epithelium results in altered uterine epithelial cell proliferation, uterine gland development and embryo implantation. Uteri lacking Sox17 showed reduction in LIF and IHH signaling which are critical for embryo implantation. ChIP-seq analysis demonstrated that SOX17 binds to a region 19kb 5’ to the Ihh locus. In vivo deletion of this enhancer by the CRISPR-Cas technology reduced Ihh expression in uteri and altered proper endometrial epithelial-stromal interactions required for pregnancy leading to compromised fertility. The SOX17 binding peak at 19kb from the Ihh promoter also bound GATA2, FOXA2 and PGR. Bioinformatic analysis of regions overlapping SOX17, GATA2, FOXA2 and PGR bindings shows 737 genes with these common binding sites. This cluster of transcription factors identified in this enhancer region may represent a combination of regulatory elements essential for uterine epithelial gene expression and differentiation.

overall_design: Mice with ablation of Sox17 in the uterine epithelium and littermate controls were mated to male mice of proven fertility. Upon the presence of the post-coital plug (Gestational Day 0.5, GD0.5), mice were sacrificed 3 days later (GD3.5) and uterine horns (embryo were flushed out) were harvested and frozen. RNA was isolated from the uterus. An Agilent RNA microarray was performed on 3 biological samples per genotype.

first: X

last: Wang

last: Li

first: T

first: S

last: Wu

first: R

middle: B

last: Lanz

first: J

middle: P

last: Lydon

last: Jeong

first: F

last: DeMayo


title: Sequential regulation of maternal mRNAs through a conserved cis-acting element in their 3’UTRs [I]

first: Prashanth

last: Rangan

overall_design: Input and Polysome mRNA content from young nosGAL4, nosGAL4>bruRNAi, and nosGAL4>pumRNAi Drosophila ovaries

first: Pooja

last: Flora


title: SOX17 regulates uterine epithelial-stromal crosstalk acting via a distal enhancer upstream of Ihh

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: SOX17 regulates uterine epithelial-stromal crosstalk acting via a distal enhancer upstream of Ihh [ChIP-seq]

overall_design: Sox17 f/f female mice were ovariectomized, rested for 2 weeks, and then administered P4. After 6 h, uterine horns were flash frozen and the tissue was subject to the ChIP-seq assay.


title: Molecular and Physiological Responses of Citrus sinensis Leaves to Long-term Low pH Revealed by RNA-Seq Integrated with Targeted Metabolomics

status: Public on May 12 2018

city: Fuzhou

first: Chen

last: Lisong

address: Shangdian street NO.15

country: China

institute: Fujian Agriculture and Forestry University

summary: Low pH-induced alterations in gene expression profiles and organic acids (OAs) and free amino acids (FAAs) abundances were investigated in Citrus sinensis leaves. We identified 503 downreg-ulated and 349 upregulated genes in low pH-treated leaves. Further analysis indicated that low pH impaired light reaction and carbon fixation in photosynthetic organisms, thereby lowering photosynthesis in leaves. Low pH reduced carbon and carbohydrate metabolisms, OAs biosyn-thesis and ATP production in leaves. Low pH downregulated the biosynthesis of nitrogen com-pounds, proteins and FAAs in leaves, which might be conducive to maintaining energy homeo-stasis during ATP deprivation. Low pH-treated leaves displayed some adaptive responses, in-cluding phosphate recycling, lipid remodeling and phosphate transport. Low pH upregulated the expression of some reactive oxygen species (ROS) and aldehyde detoxifying enzyme (peroxidase and superoxidase) genes and the concentrations of some antioxidants (L-tryptophan, L-proline, nicotinic acid, pantothenic acid and pyroglutamic acid), but it impaired pentose phosphate pathway, VE and secondary metabolite biosynthesis, downregulated the expression of some ROS and aldehyde detoxifying enzyme (ascorbate peroxidase, aldo-keto reductase and 2-alkenal re-ductase) genes and the concentrations of some antioxidants (pyridoxine and γ-aminobutyric acid), thus disturbing the balance between production and detoxification of ROS and aldehydes and causing oxidative damage to leaves.

overall_design: Examination of mRNA levels in control and low-pH-treatment leaves of C. sinensis with two-three biological replicates were generated by deep sequencing, using Illumina HiSeq xten device.

first: NingWei

last: Lai

first: ZhiChao

last: Zheng

first: Dan

last: Hua

first: Jiang

last: Zhang

first: HuanHuan

last: Chen

first: Xin

last: Ye

first: ZengRong

last: Huang

first: Jiuxin

last: Guo

first: LinTong

last: Yang

first: LiSong


title: A global identification of PUM1 and PUM2 mRNA targets and their protein cofactors in human seminoma TCam-2 cells

status: Public on Nov 28 2018

city: Poznan

first: Jadwiga

last: Jaruzelska

address: Strzeszynska 32

country: Poland

institute: Institute of Human Genetics, Polish Academy of Sciences

summary: The functions of human PUM1 and PUM2 are considered to be redundant given that both PUF1 and PUF2 recognize the same PBE motif UGUANAUA.  However pools of mRNAs published so far for PUM1 and PUM2 do not overlap. Therefore we sought to investigate the issue of redundancy in human cells. The both PUM proteins are less conserved in the region that is outside the PUM domain. We sought that interactors could be different. We identified mRNA pools  binding separately PUM1 and PUM2 by RIP-Seq approach, normalized them using the whole TCam-2 cells transcriptome and aligned them with mRNA pools activated or repressed as tested by siRNA PUM1 and PUM2 knockdown.

overall_design: PUM1 and PUM2-regulated RNAs were studied by RIP-Seq and siRNA-mediated PUM1 or PUM2 knockdown followed by RNA-Seq in TCam-2 cell line. RIP-Seq with non-immunized serum and TCam-2 transcriptome or control non-target siRNA were used as controls for RIP-Seq and RNA-Seq respectively. Each experiment was performed in 3 biological replicates.

first: Maciej

last: Smialek

first: Marcin

last: Sajek

first: Erkut

last: Ilaslan

first: Aleksandra

last: Swiercz

first: Damian

middle: M

last: Janecki

last: Kotecki

first: Kamila

last: Kusz-Zamelczyk

first: Tomasz

last: Wozniak

first: Luiza

last: Handschuh

first: Marek

last: Figlerowicz


title: WNK1-dependent transcriptome in decidualized human endometrial stromal cells

status: Public on Aug 20 2018

first: Franco

last: Demayo

summary: We report the transcriptomic profile of primary human endometrial stromal cells subjected to 48-hour transfection with control non-targeting siRNA or siRNA targeting WNK1 followed by 3-day in vitro decidualization treatment.

overall_design: RNA-Seq analysis of HESCs at day 3 of EPC treatment following siNT or siWNK1 treatment

first: Nyssa

middle: R

last: Adams

first: Yasmin

last: Vasquez

first: Qianxing

last: Mo

first: William

last: Gibbons

first: Ertug

last: Kovanci

first: Francesco

last: DeMayo


title: Quantitative whole transcriptomics sequencing of progeria-derived cells point to a key role of nucleotide metabolism in premature aging

status: Public on Apr 30 2018

city: A Coruña

first: María

middle: C

last: Arufe

state: A Coruña

address: As Xubias

department: Fisioterapia, Medicina y Ciencias Biomédicas

country: Spain

institute: UDC

summary:
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived PG and their healthy progenitor lines transcriptome profiling (RNA-seq) to proteomic methods (iTRAQ) and to evaluate these protocols for optimal high-throughput data analysis
Methods: The raw RNA-Seq reads for each sample were aligned to the reference human genome browser (GRCh38.p12 assembly) using Bowtie2 and Tophat2.
Results: An average of 23 million paired-end 100-bp reads was obtained per sample. After alignment, raw sequence read depths were converted to estimate transcript abundance measured as fragments per kilobase of exons per million (FPKM), and the cuffinks of differentially expressed genes and transcripts were calculate with Cuffdidd.
Conclusions: Our study represents a detailed analysis of human PG lines transcriptomes, with biologic replicates, generated by RNA-seq technology. The optimized data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. Our results show that NGS offers a comprehensive and more accurate quantitative and qualitative evaluation of mRNA content within a cell pathological line. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biologic functions.

overall_design: The sequencing data was generated on Hiseq 1500 on a rapid mode flow cell from Illumina.

first: Iván

last: Rodriguez-Lesende

first: Lorenzo

last: Monserrat

first: Juan

last: Fafián-Labora


title: Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure (ChIP-Seq)

status: Public on Jul 30 2018

city: Tokyo

first: Seitaro

last: Nomura

state: Select a State or Province

address: 7-3-1, Hongo, Bunkyo-ku

department: Department of Cardiovascular Medicine

country: Japan

institute: The University of Tokyo

summary: Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive. Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function. During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks. Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy. Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation. Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures. Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.

overall_design: cardiomyocyte H3K27ac ChIP-seq

first: Masahiro

last: Satoh

first: Takanori

last: Fujita

first: Tomoaki

last: Higo

first: Tomokazu

last: Sumida

first: Toshiyuki

last: Ko

first: Toshihiro

last: Yamaguchi

first: Hiroyuki

last: Aburatani

first: Issei

last: Komuro


title: Conjunctival transcriptome profiling of Solomon Islanders with active trachoma but without ocular Chlamydia trachomatis infection.

status: Public on Feb 28 2018

city: London

first: Hristina

middle: Chavdarova

last: Vasileva

state: London

address: Keppel Street

department: CRD

country: United Kingdom

institute: LSHTM

summary:
The prevalence of trachomatous inflammation–follicular (TF) in Solomon Island children aged 1–9 years is high enough to warrant, among other interventions, mass distribution of azithromycin. However, over 90% of those with TF did not have concurrent Chlamydia trachomatis infection.
We analysed the transcriptome of children with TF and Ct infection, children diagnosed with TF but no Ct infection and children with neither TF nor Ct infection to better understand host responses during an episode of TF, and investigate whether it can provide any clues about the aetiology of TF in this context.

overall_design: Purified RNA from children with and without active trachoma was run on Affimetrix GeneChip HTA 2.0. Transcriptome profiles were compared between individuals with ocular Chlamydia trachomatis (Ct) infection and trachomatous inflammation-follicular (TF) (DI group: n=6), individuals with TF but no Ct infection (D group: n=7) and individuals without TF or Ct infection (N group: n=7). Differentially expressed (DE) genes were considered in isolation and also assessed for host response pathway membership.

first: Robert

last: Butcher

first: Chrissy

middle: H

last: Roberts


title: Consistent inverse correlation between DNA methylation of the first intron and gene expression across tissues and species

status: Public on Jul 02 2018

city: Barcelona

first: Dafni

last: Anastasiadi

address: Pg. Marítim de la Barceloneta 37-49

department: Renewable Marine Resources

institute: Institute of Marine Sciences-CSIC

type: Methylation profiling by high throughput sequencing

summary:
Background: DNA methylation is one of the main epigenetic mechanisms for the regulation of gene expression in eukaryotes. In the standard model, methylation in gene promoters has received the most attention since it is generally associated with transcriptional silencing. Nevertheless, recent studies in human tissues reveal that methylation of the region downstream of the transcription start site is highly informative of gene expression. Also, in some cell types and specific genes it has been found that methylation of the first intron, a gene feature typically rich in enhancers, is linked with gene expression. However, a genome-wide, tissue-independent, systematic comparative analysis of the relationship between DNA methylation in the first intron and gene expression across vertebrates has not been explored yet.
Results: The most important findings of this study are: (1) using different tissues from a modern fish, we show a clear genome-wide, tissue-independent quasi-linear inverse relationship between DNA methylation of the first intron and gene expression. (2) This relationship is conserved across vertebrates, since it is also present in the genomes of a model pufferfish, a model frog and different human tissues. Among the gene features, tissues and species interrogated, the first intron’s negative correlation with the gene expression was most consistent. (3) We identified more tissue-specific differentially methylated regions (tDMRs) in the first intron than in any other gene feature. These tDMRs have positive or negative correlation with gene expression, indicative of distinct mechanisms of tissue-specific regulation. (4) Lastly, we identified CpGs in transcription factor binding motifs, enriched in the first intron, the methylation of which tended to increase with the distance from the first exon–first intron boundary, with a concomitant decrease in gene expression.
Conclusions: Our integrative analysis clearly reveals the important and conserved role of the methylation level of the first intron and its inverse association with gene expression regardless of tissue and species. These findings not only contribute to our basic understanding of the epigenetic regulation of gene expression but also identify the first intron as an informative gene feature regarding the relationship between DNA methylation and gene expression where future studies should be focused.

overall_design: Genome wide DNA methylation and gene expression in testis and muscle of wild European sea bass (Dicentrarchus labrax)

first: Anna

last: Esteve-Codina

first: Francesc

last: Piferrer


title: Comparison of transcriptomes of N2 and fog-2(q71) mutant Caenorhabditis elegans

status: Public on May 01 2018

city: College Park

first: Eric

middle: S.

last: Haag

state: MD

address: 4094 Campus Drive

department: Department of Biology

institute: University of Maryland

summary: In this experiment, steady-state mRNA levels were determined for replicated samples of N2 (wild-type reference) and fog-2(q71) homozygous mutant C. elegans. All samples were adult XX animals, which for N2 are self-fertile hermaphrodites and for fog-2(q71) spermless hermaphrodites, i.e. true females.  For the fog-2 mutant animals, only those that had mated with males, and were thus gravid, were picked for RNA isolation. This ensures that all comparisons are between similar, embryo-containing animals. The experiment was motivated by the  role of FOG-2 in post-transcriptional control of gene expression in germ cells, inferred from its the germline-specific phenotype of its loss and from its physical associated with the GLD-1 RNA-binding protein. Specifically, a possible role for FOG-2 in influencing mRNA stability was addressed.

overall_design: Three biological replicate samples of mRNA were prepared for both N2 and fog-2(q71). Each sample was then used to prepare both oligo-dT-primed and random hexamer-primed Illumina short-read sequencing libraries. Oligo-dT and random-primed results were compared to assess possible impacts of fog-2 activity on polyadenylation.

middle: S

first: Scott

middle: L

last: Kuersten


title: An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (ChIP-Seq data set)

status: Public on Jan 02 2018

first: Franco

last: Demayo

summary: The role of Gata2 in regulating the expression of HLA in huamn decidual stromal cells

overall_design: Examination of GATA2 binding in pooled primary human endometrial stromal cells from 6 healthy women upon decidualization with a hormone cocktail of cAMP, E2 and medroxyprogesterone acetate.

first: Xilong

last: Li

first: Francesco

last: DeMayo


title: Transcriptome analysis of immortalized and transformed human IMR90 fibroblasts

status: Public on Apr 23 2018

city: Bordeaux

first: Nicolas

middle: J.

last: Tourasse

address: 146 rue Leo Saignat

department: INSERM U1212, CNRS UMR5320

country: France

institute: University of Bordeaux

summary: RNA polymerase (Pol) III transcribes small untranslated RNAs that are essential for cellular homeostasis and growth. Its activity is regulated by inactivation of tumor suppressor proteins and overexpression of the oncogene c-MYC, but the concerted action of these tumor-promoting factors on Pol III transcription has not yet been assessed. In order to comprehensively analyse the regulation of Pol III transcription during tumorigenesis we employ a model system that relies on the expression of five genetic elements to achieve cellular transformation. Expression of these elements in six distinct transformation intermediate cell lines leads to the inactivation of TP53, RB1, and protein phosphatase 2A, as well as the activation of RAS and the protection of telomeres by TERT, thereby conducting to full tumoral transformation of IMR90 fibroblasts. Transformation is accompanied by moderately enhanced levels of a subset of Pol III-transcribed RNAs (7SK; MRP; H1). In addition, mRNA and/or protein levels of several Pol III subunits and transcription factors are upregulated, including increased protein levels of TFIIIB and TFIIIC subunits, of SNAPC1 and of Pol III subunits. Strikingly, the expression of POLR3G and of SNAPC1 is strongly enhanced during transformation in this cellular transformation model. Collectively, our data indicate that increased expression of several components of the Pol III transcription system accompanied by a 2-fold increase in steady state levels of a subset of Pol III RNAs is sufficient for sustaining tumor formation.

overall_design:
Sequencing data have been deposited to SRA: Study accession SRP102731; BioProject accession PRJNA381003. Total RNA sequencing of six IMR90 fibroblast-derived transformation intermediate cell lines, one biological replicate for each cell line:
IMR90 E6/E7; IMR90 transformed with human papillomavirus (HPV16) proteins E6 and E7
IMR90 E6/E7/RAS; IMR90 transformed with human papillomavirus (HPV16) proteins E6 and E7 and constitutively active RAS (RAS-G12V)
IMR90 E6/E7/small t; IMR90 transformed with human papillomavirus (HPV16) proteins E6 and E7 and SV40 small t antigen
IMR90 E6/E7/RAS/small t; IMR90 transformed with human papillomavirus (HPV16) proteins E6 and E7, constitutively active RAS (RAS-G12V), and SV40 small t antigen
IMR90 E6/E7/RAS/small t/TERT; IMR90 transformed with human papillomavirus (HPV16) proteins E6 and E7, constitutively active RAS (RAS-G12V), SV40 small t antigen, and telomerase catalytic subunit TERT

first: Stéphanie

last: Durrieu-Gaillard

first: Hélène

last: Dumay-Odelot

first: Galina

last: Boldina

first: Delphine

last: Allard

first: Fabrice

last: André

first: Françoise

last: Macari

first: Armelle

last: Choquet

first: Pauline

last: Lagarde

first: Guillaume

last: Drutel

first: Thierry

last: Leste-Lasserre

first: Marion

last: Petitet

first: Tom

last: Lesluyes

first: Lydia

last: Lartigue-Faustin

first: Frédéric

last: Chibon

middle: G

last: Roeder

first: Dominique

last: Joubert

first: Stéphan

last: Vagner

first: Martin

last: Teichmann


title: Identification of genes whose expression is affected by Delta RNAi in spider embryos

status: Public on Apr 13 2018

city: Takatsuki

first: Hiroki

last: Oda

state: Osaka

address: 1-1 Murasaki-cho

institute: JT Biohistory Research Hall

summary: In the spider Parasteatoda tepidariorum embryo, Delta-Notch signaling plays a key role in early development of the opisthosomal region by regulating the balance between the caudal ectoderm and mesoderm fates (Oda et al., 2007, Development 134, 2195-2205). In this microarray experiment, we attempted to identify candidate genes whose expressions are regulated by Delta-Notch signaling during early phases of  the caudal development.

overall_design: The objective of this experiment was a screen for genes whose expressions might be affected by parental RNA interference (pRNAi) against Pt-Delta in spider embryos. Oligonucleotide probes were designed based on accumulated P. tepidariorum EST and cDNA sequences and embedded in a custom microarray (12K). Total RNA was extracted from late stage 5 embryos derived from a mated female before and after injection of dsRNA targeted for Pt-Delta. Gene expression levels were compared between the untreated (normal) and the Pt-Delta pRNAi-treated samples. Probes for a homolog of Drosophila caudal, Pt-cad (GB_ACC: AB096075.1; GI: LOC107437910), served as positive controls to validate this experiment.

first: Yasuko

last: Akiyama-Oda


title: MicroRNAs related with metastasis in cervical squamous cell carcinoma and their clinical significance

status: Public on Apr 06 2018

city: Seongnam-si

first: Ah-Young

last: Kwon

state: Gyeonggi-do

address: 351 Yatap-dong, Bundang-gu

department: Department of Pathology

country: South Korea

institute: College of Medicine, CHA University

summary: We found miRNA expression profiling of uterine cervical squamous cell carcinoma by miRNA microarray and validated the genes as clinical significance of squamous cell carcinoma, especially in metastasis.

overall_design: MiRNA obtained from uterine cervical squamous cell carcinoma, with (SC38, 38 and 41) or without metastasis (SC34, 35 and 37), compared with normal uterine cervical squamous epithelium (NC2 and 13)

first: Hee

last: An


title: Cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure (RNA-Seq)

first: Seitaro

last: Nomura

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Integrative analysis of single-cardiomyocyte RNA-seq of pressure-overload-induced heart failure model mice and heart failure patients with dilated cardiomyopathy, single-cell morphology, cardiac function and genetic perturbation

first: Masahiro

last: Satoh

first: Takanori

last: Fujita

first: Tomoaki

last: Higo

first: Tomokazu

last: Sumida

first: Toshiyuki

last: Ko

first: Toshihiro

last: Yamaguchi

first: Hiroyuki

last: Aburatani

first: Issei

last: Komuro


title: An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F (Affymetrix data set)

first: Franco

last: Demayo

summary: The role of Gata2 in regulating the expression of HLA in human decidual stromal cells

overall_design: Human primary stromal cells from three different patients were grown to approximately 70% confluence and subsequently treated with 100nM medroxyprogesterone acetate, and 1mM 8-bromo-cAMP and transfected with 60nM scrambled, non-targeting (siNT), or GATA2-targeting (siGATA2) siRNA using Lipofectamine RNAiMax lipid per the manufacturer’s instructions. After 72 hours of transfection exposure cells were harvested and RNA isolated using the RNAeasy Mini kit as per manufacterer’s instructions. cRNA labeling was performed according to Agilent Technologies Inc. protocol using the Agilent Quick Amp Labeling Kit following the two-color manufacturer's protocol.

first: Xilong

last: Li

first: Francesco

last: DeMayo


title: OBESITY IS ASSOCIATED WITH IMPAIRED EXPRESSION OF THE GLYCOSYLTRANSFERASE EOGT IN DECIDUALIZING ENDOMETRIUM

city: Coventry

first: Jan

last: Brosens

address: University Hospital Coventry and Warwickshire

department: Warwick Medical School

institute: University of Warwick

summary: In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the feto-maternal interface and, by extension, survival of the conceptus. O-GlcNAcylation is an essential post-translational modification that links glucose sensing to downstream stress resistance. Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-GlcNAc modified proteins, reflecting down-regulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase, OGT) but not the enzyme that removes the modification (O-GlcNAcase, OGA). Notably, EOGT, an endoplasmic reticulum-specific O-GlcNAc transferase that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs. Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions. The most responsive gene downregulated upon EOGT knockdown in decidualizing cells was ENHO, which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index. Taken together, our findings reveal that obesity impairs the EOGT-adropin axis in decidual cells, which in turn provides a new mechanism that links between metabolic disorders to adverse pregnancy outcome.

overall_design: Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-EOGT, either undifferentiated or decidualized with 8-br-cAMP and MPA for 4 days were generated by deep sequencing, in triplicate using Illumina

first: Joanne

last: Muter

first: Emma

last: Lucas

first: Pavle

last: Vrljicak

first: Sascha

last: Ott


title: Cardiomyocyte stress-response gene modules regulate cardiac hypertrophy and failure

first: Seitaro

last: Nomura

overall_design: Refer to individual Series


title: DNA methylation profile in chronic myelomonocytic leukemia associates with distinct clinical, biological and genetic features

status: Public on Nov 17 2017

city: Badalona

first: Roberto

last: Malinverni

state: Barcelona

address: Josep Carreras Building, Ctra de Can Ruti,

institute: Josep Carreras Leukaemia Research Institute

summary: Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. Epigenetic abnormalities are frequent in CMML, including mutations in DNA methylation and histone-modifying enzymes, but the methylation profile is not well characterized in these patients. In this study we performed DNA methylation microarrays in 65 CMML patients and 10 healthy controls. Differential methylation analysis between patients and controls allowed us to identify abnormalities in DNA methylation including hypermethylated genes, large genome regions with aberrant DNA methylation and altered cellular pathways. Hierarchical cluster analysis identified two main clusters that associated with the clinical, biological and genetic features of patients. Group 1 was enriched in patients that presented with adverse clinical and biological characteristics and that had a poorer overall survival and progression free survival. In addition, significant differences in DNA methylation was observed between patients with low risk and intermediate/high risk karyotypes and between TET2 mutant and wild-type patients. These results demonstrate that DNA methylation is altered in CMML and is associated with distinct biological and clinical features. Furthermore, these results may provide a useful basis for identifying new therapeutic targets.

overall_design: DNA methylation profiles of bone marrow from CMML patients and CD34+ enriched blood from healthy controls.

first: Laura

last: Palomo

first: Marta

last: Cabezón

first: Blanca

last: Xicoy

first: Montserrat

last: Arnan

first: Rosa

last: Coll

first: Helena

last: Pomares

first: Francisco

last: Fuster-Tormo

first: Javier

last: Grau

first: Evarist

last: Feliu

first: Francesc

last: Solé

first: Marcus

last: Buschbeck

first: Lurdes

last: Zamora


title: RNA-seq analysis of iPSC-derived heptocytes with mutations in NR1H4

city: Cambridge

first: Aimee

last: Deaton

state: MA

address: 360 Binney St

institute: Amgen Inc

summary: We discovered a rare missense mutation in NR1H4 (R436H), which encodes the farnesoid X receptor (FXR), associating with lower levels of total cholesterol in the Icelandic population. To explore the effects of R436H we used CRISPR-Cas9 to generate homozygous NR1H4 R436H and NR1H4 knockout human iPSC lines which we differentiated to hepatocytes. Hepatocytes were treated with an FXR agonist for 24 hours and transcript abundance measured by RNA-seq. The global response to FXR activation in NR1H4 R436H cells was very similar to that of wild-type cells showing that it is not a loss-of-function mutation. However, we did observe subtle gene expression differences compatible with an effect on lipids when we compared R436H agonist treated hepatocytes to wild-type agonist treated hepatocytes.

overall_design: RNA-seq was performed on wild-type, NR1H4 knockout and NR1H4 R436H iPSC-derived hepatocytes treated with FXR agonist GW4064.

first: Lucas

last: Ward


title: MAPKs control the expression of a novel gene set that defines de activation of human anti-inflammatory macrophages

status: Public on Sep 22 2017

city: Madrid

first: Ángel

last: Corbí

state: Madrid

address: Ramiro de Maeztu, 9

department: Molecular Microbiology and Infection Biology

institute: Consejo Superior de Investigaciones Científicas

summary: LPS treatment is considered as the paradigmatic stimulus for acquisition of the classical macrophage polarization/activation state. However, this definition does not take into account the influence that other macrophage differentiating/priming factors might have on the LPS response. In spite of the pathophysiological relevance of the response of M-CSF-dependent anti-inflammatory human macrophages (M-MØ) to endogenous and pathogenic stimuli, detailed analysis of the gene signature of activated anti-inflammatory M-CSF-dependent macrophages remained to be determined. We have now compared the early transcriptional signatures of human GM-MØ and M-MØ in response to macrophage-activating agents and identified a unique gene set acquired upon activation of anti-inflammatory M-MØ.

overall_design: Macrophages were differentiated from peripheral blood monocytes from 3 healthy donors with M-CSF or GM-CSF to generate anti-inflammatory (M-MØ) or pro-inflammatory (GM-MØ) macrophages, respectively. M-MØ and GM-MØ were stimulated with 10ng/ml LPS for 4h.

first: Víctor

middle: D

last: Cuevas

first: Miguel

middle: A

last: Vega


title: The Epidermal Growth Factor Receptor Critically Regulates Endometrial Function during Early Pregnancy

status: Public on Mar 04 2017

first: Franco

last: Demayo

summary: Infertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.

overall_design: The genomic actions of EGFR and Wnt4 in endometrium were examined by conditional ablation in vivo via PGR-Cre.

first: Francesco

last: DeMayo


title: Transcriptomic analysis of splenic CD4+ cells from tBHQ treated

status: Public on May 23 2017

city: Budapest

first: Viola

last: Tamasi

address: Nagyvarad sqr 4

department: Genetic, Cell- and Immunobiology

country: Hungary

institute: Semmelweis University

summary: We report a transcriptomic analysis from tBHQ (terc-butyl-hydroquinone) treated mice. Mice were treated with this chemical for 20 days using 1.5% mixed in food and allowed water and food ad libitum. After the treatment period, spleen of tBHQ treated and control animals were taken out and CD4+ cells were isolated. Isolated RNA from these cells were subjected to cDNA microarray analysis. Our results show, that tBHQ changes the gene expression of many genes which are involved in metabolic and immune processes. In parallel with transcriptomic analysis, the effect of tBHQ on T cell differentiation was studied. Our results show, that beside changing the gene expression of many genes, tBHQ sensitize effector T cells (Th1, Th2, Th17) and inhibit Treg cells upon stimulation with chemicals.

overall_design: Investigation of effect of tBHQ on splenic CD4+ cells; 4 control-4 tBHQ treated replicates

first: Peter

last: Petschner

first: Krisztina

last: Pálóczi


title: MacroH2A histone variants maintain nuclear organization and heterochromatin architecture

status: Public on Mar 21 2017

first: Roberto

last: Malinverni

summary: Genetic loss-of-function studies in development, cancer and somatic cell reprogramming have suggested that the group of macroH2A histone variants might function through stabilizing the differentiated state by a yet unknown mechanism. Here, we present results demonstrating that macroH2A variants have a major function in maintaining nuclear organization and heterochromatin architecture. Specifically, we find that a substantial amount of macroH2A is associated with heterochromatic repeat sequences. We further identify macroH2A on sites of interstitial heterochromatin decorated by H3K9me3. Loss of macroH2A leads to major defects in nuclear organization including reduced nuclear circularity, disruption of nucleoli and a global loss of dense heterochromatin. Domains formed by repeat sequences when depleted of macroH2A are disorganized, expanded and fragmented and mildly re-expressed. On the molecular level we find that macroH2A is required for the interaction of repeat sequences with the nucleostructural protein Lamin B1. Taken together our results argue that a major function of macroH2A histone variants is to link nucleosome composition to higher order chromatin architecture.

overall_design: ChIPseq of macroH2A1 and macroH2A2 on HepG2 Cell-line

first: Julien

last: Douet

first: David

last: Corujo


title: Clinical Validation of Chemotherapy Predictors Developed on Global MicroRNA Expression in the NCI60 Cell Line Panel Tested in Ovarian Cancer.

status: Public on Feb 01 2017

city: Hoesholm

first: Anker

last: Hansen

address: Venlighedsvej 1

country: Denmark

institute: Medical Prognosis Institute A/S

summary:
summary
Ovarian cancer is the leading cause of death among gynecologic malignancies. This is partly due to a non-durable response to chemotherapy. Prediction of resistance to chemotherapy could be a key role in more personalized treatment. In the current study we aimed to examine if microRNA based predictors could predict resistance to chemotherapy in ovarian cancer, and to investigate if the predictors could be prognostic factors for progression free and overall survival.

Methods
Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel (deposited under accession number E-MTAB-327 in the ArrayExpress database of the European Bioinformatics Institute, 2012). These predictors were then, retrospectively, blindly validated in a cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment.

Results
In a multivariate cox proportional analysis the predictors of chemotherapy-resistance were not able to predict time to progression after end of chemotherapy (hazard ratio: 0.64, 95% CI: 0.36 – 1.12, P=0.117). However, in a multivariate logistic analysis, where time to progression was considered as either more or less than 6 months, the predictors match clinical observed chemotherapy-resistance (odds ratio: 0.19, 95% CI: 0.05-0.73, P=0.015). Neither univariate nor multivariate, time-dependent, cox analysis for progression free survival (PFS) or overall survival (OS) in all 170 patients showed to match predicted resistance to chemotherapy (PFS: hazard ratio: 0.69, 95% CI: 0.40-1.19, P=0.183, OS: hazard ratio: 0.76, 95% CI: 0.42-1.40, P=0.386).

Conclusion
In the current study, microRNA based predictors of chemotherapy-resistance did not demonstrate any convincing correlation to clinical observed chemotherapy-resistance, progression free survival, or overall survival, in patients with epithelial ovarian cancer. However the predictors did reflect relapse more or less than 6 months.

overall_design:
A total of 198 epithelial ovarian cancer patients were analyzed for miRNA expression. Of these, detailed clinical information were available for 170 patients. Predictors of chemotherapy-resistance were developed based on correlation between miRNA expression and differences in measured growth inhibition in a variety of human cancer cell lines in the presence of Carboplatin, Paclitaxel and Docetaxel. These predictors were then, retrospectively, blindly validated in the cohort of 170 epithelial ovarian cancer patients treated with Carboplatin and Paclitaxel or Docetaxel as first line treatment.

Under EU data protection legislation it is a violation of patient privacy to publish de-identified individual patient information. Therefore, clinical data (eg, chemotherapy-resistance, progression free survival, or overall survival discussed in the summary etc.) were not provided.

first: Kira

last: Prahm

first: Claus

last: Høgdall

first: Mona

last: Karlsen

first: Ib

last: Christensen

first: Guy

middle: W

last: Novotny

first: Steen

last: Knudsen

last: Jensen

first: Thomas

first: Mansoor

last: Mirza

first: Anne

last: Ekmann-Gade

first: Lotte

last: Nedergaard

first: Estrid


title: Progesterone receptor transcriptome and cistrome in decidualized human endometrial stromal cells

status: Public on Jan 25 2017

city: RTP

first: Franco

last: Demayo

address: 111 TW Alexander Drive

institute: NIEHS

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


title: MacroH2A1.1 regulates mitochondrial respiration by limiting nuclear NAD+ consumption

status: Public on Aug 18 2017

summary: The macro domain of the histone variant macroH2A1.1 is an evolutionary conserved ADP ribose-binding module of unknown physiological function. We demonstrate that during myogenic differentiation alternative splicing switches the expression of macroH2A1 from the non-ADP ribose binding to the binding isoform. While differentiation commitment is normal in cells lacking macroH2A1.1, we observe two phenotypes: diminished cell fusion correlating with reduced expression of adhesion and migration genes and reduced mitochondrial capacity. While the integrity of the ADP ribose-binding pocket is dispensable for gene regulation and fusion, it is critical to sustain optimal mitochondrial fatty acid oxidation. Rescue experiments using a pharmacological PARP-1 inhibitor and metabolomics support the idea that loss of macroH2A1.1 leads to PARP-1 activation and accelerated NAD+ consumption. As a consequence, the level of nicotinamide mononucleotide, the key metabolite for mitochondrial NAD+ pool regeneration, is reduced and sirtuins fail to maintain mitochondrial proteins in their hypoacetylated and active form. Our results support the idea that chromatin states containing the histone variant macroH2A1.1 contribute to optimal mitochondrial oxidative capacity by channeling the consumption of NAD+ from the nucleus to mitochondria in a manner largely independent on transcriptional regulation.

overall_design: Microarray analysis from 4 biological replicates is performed on C2C12 myotubes at day 4 of differentiation, transfected with either control or macroH2A1.1 siRNAs.

first: Melanija

last: Posavec Marjanović

first: Sarah

last: Hurtado-Bagès

first: Marcus

last: Buschbeck


title: Assessing rejection-related disease in kidney transplant biopsies based on archetypal analysis of molecular phenotypes

status: Public on Jul 10 2017

city: Edmonton

first: Jessica

last: Chang

address: 250 Heritage Medical Research Centre

department: Medicine

country: Canada

institute: University of Alberta

summary: Molecular phenotyping of biopsies affords opportunities for increased precision and improved disease classification to address the limitations of conventional histologic diagnostic systems. We applied archetypal analysis, an unsupervised method similar to cluster analysis, to microarray data from 1208 prospectively collected kidney transplant biopsies from 13 centers. Seven machine learning-generated cross-validated classifier scores per biopsy were used as input for the archetypal analysis. Six archetypes representing extreme phenotypes were generated: no rejection; T cell-mediated rejection (TCMR); three phenotypes associated with antibody-mediated rejection (ABMR) - early-stage, fully-developed, and late-stage; and mixed rejection (TCMR plus early-stage ABMR). Each biopsy was assigned six scores, one for each archetype, that together represent a probabilistic assessment of that biopsy based on its rejection-related molecular properties. Viewed as clusters, the archetypes were similar to existing histologic Banff categories, but there was 32% disagreement, much of it probably reflecting the “noise” in the current histologic assessment system. Graft survival was worst for fully-developed and late-stage ABMR and was better predicted by molecular archetype scores than histologic diagnoses. The results provide a system for precision molecular assessment of biopsies and a new standard for recalibrating conventional diagnostic systems. (ClinicalTrials.gov NTC1299168)

overall_design:
We applied archetypal analysis, an unsupervised method similar to cluster analysis, to microarray data from 1208 prospectively collected kidney transplant biopsies from 13 centers.

Sample characteristics:
Archetype Cluster (1,2,3,4,5,6)
D96: histologic diagnoses (ABMR, ABMRsusp, AKI, BK, Bord., DiabNeph, GN, IFTA, Mixed, NOMOA, Other, TCMR, TG)
g: g-lesion score (0, 1 2 3, NA)
cg: cg-lesion score (0, 1 2 3, NA)
i: i-lesion score (0, 1 2 3, NA)
ci: ci-lesion score (0, 1 2 3, NA)
t: t-lesion score (0, 1 2 3, NA)
ct: ct-lesion score (0, 1 2 3, NA)
v: v-lesion score (0, 1 2 3, NA)
cv: cv-lesion score (0, 1 2 3, NA)
ah: ah-lesion score (0, 1 2 3, NA)
ptc: ptc-lesion score (0, 1 2 3, NA)
C4d: C4d lesion score (0,1,2,3,4,focal mild, neg, not done,pending, pos, pos trace, positive, trace, NA)
In i-IFTA set N=234? (0=no, 1=yes)
MMDx: MMDx diagnoses (ABMR, Mixed, NR, TCMR)
%IFTA (0, <10%, >=10%)

first: Jeff

last: Reeve


title: A cellular model reflecting the phenotypic heterogeneity of squamous cell carcinoma

status: Public on Jan 01 2017

first: Roberto

last: Malinverni

summary: Squamous cell carcinomas have a range of histopathological manifestations. The parameters that determine this clinicallly observed heterogeneity are not fully understood. Here, we report the generation of a cell culture model that reflects part of this heterogeneity. Defined genetic elements have been used to progressively immortalize and transform primary UV-unexposed keratinocytes. When injected into immunosuppressed mice, transformed cells grew as xenografts with distinct histopathological characteristics. We observed solid, sarcomatoid and cystic growth types as three major tissue architectures that were primarily composed of pleomorphic and basaloid cells but in some cases displayed focal apocrine differentiation. We demonstrate that generated cells represent different stages of skin cancerogenesis and as such can be used to identify novel tumor-promoting alterations such as the overxepression of the PADI2 oncogene in solid-type SCC. Importantly, cultured cells maintain the characteristics from xenograft they were derived from while being amenable to manipulation and analysis. The availability of cell lines representing different clinical manifestations opens a new avenue to study stochastic and deterministic factors causing case-to-case heterogeneity departing from the same set of oncogenes and the same genetic background.

overall_design: In order to identify potential drivers of skin carcinogenesis we compared the global gene expression pattern of the Ts4 cells derived from a solid-type xenograft with parental (N), transformed (T) and immortal (IM) cell populations. RNA was extracted from 4 biological replicates ofthe cell in cultures, except for Ts4 cells (3 biological replicates).

first: Neus

last: Cantariño

first: M

middle: T

last: Fernández-Figueras

first: Vanesa

last: Valero

first: Eva

last: Musulén

first: Juan

last: Martín-Caballero

first: Agustí

last: Toll

first: Sonia

middle: V

last: Forcales


title: FOXO1 is required for binding of PR on IRF4, novel transcriptional regulator of endometrial stromal decidualization


title: A switch from neuronal network development to maintenance during postnatal development of rat prefrontal cortex

city: Nijmegen

first: Jo Huiqing

last: Zhou

address: Geert Grooteplein 26/28

country: Netherlands

institute: Radboud University

type: Non-coding RNA profiling by high throughput sequencing

summary: To unravel the gene expression changes during postnatal prefrontal cortex development,  RNA-seq was performed in the rat medial prefrontal cortex at five time points from early life to adulthood (postnatal day 8, 14, 21, 35 and 70) and differential expression of protein-coding genes, lincRNAs and alternative exons was analyzed. A switch from neuronal network development to maintenance during postnatal rat prefrontal cortex development was shown.

overall_design: Comparison of gene expression between 5 different developmental time points (postnatal day 8, 14, 21, 35 and 70) in medial prefrontal cortex of Wistar rats. 5 samples per time point.

first: Jo

last: Huiqing Zhou


title: Transcriptome Profiling of the Rumen Epithelial Tissues of Beef Cattle Differing in Residual Feed Intake

first: Guanxiang

last: Liang

state: Alberta

address: 410 Agriculture/Forestry Centre

summary: We functionally analyzed the rumen epithelial transcriptomes from low- and high- feed efficient beef steers to identify differences that might contribute to variation in feed efficiency.

overall_design: RNA-seq was performed on the rumen epithelial tissues of 9 low RFI and 9 high RFI animals to obtain transcriptomes for functional analysis using bioinformatics.

first: Rebecca

last: Kong

first: Guangxiang


title: Liver transcriptome profiles correlates with viral control during hepatitis B virus infection

status: Public on Mar 31 2016

city: Shanghai

first: Jiming

last: Zhang

address: 12 Middle Wulumuqi Road

department: Department of Infectious Diseases

institute: Huashang Hospital, Fudan University

summary: The natural history of chronic hepatitis B virus (HBV) infection could be divided in different phases by transaminase and HBV replication levels. However, it remains unknown how the intrahepatic transcriptomes in patients are correlated with the clinical phases. Here, we determined the intrahepatic transcriptomes of chronic hepatitis B patients and examined the role of specific groups of genes, including immune-related genes, in the control of hepatitis B virus infection.

overall_design: The transcriptomes of 83 chronic hepatitis B patients (22 immune tolerant, 50 immune clearance, and 11 inactive carrier state) were analyzed by performing microarray analysis of liver biopsies.KEGG pathway analysis showed that immune response genes and interferon-stimulated genes were up-regulated in the immune clearance phase. Although immune tolerant patients and inactive state carriers had significantly different serum viral loads, the hepatic transcriptomes of the two groups were largely similar and only significantly differed in the expression of 109 genes (p < 0.01). Thus, we hypothesized that some of the 109 genes may be involved in HBV control and identified genes of interest by performing systematic screening using specific siRNAs. We showed that silencing candidate genes such as EVA1A resulted in significantly increased viral replication. Conversely, overexpression of candidate genes suppressed virus replication. Conclusions: The immune related pathways were up-regulated in the immune clearance phase but not in the inactive carrier phase. A number of host genes unrelated to immune pathways were expressed in the inactive carrier phase and these may participate in the control of hepatitis B virus replication, resulting in low viral replication.

first: Mengji

last: Lu

first: Hongyan

last: Liu

first: Jia

last: Jia


title: Genetic regulation of barley gene expression in response to the powdery mildew fungus, Blumeria graminis f. sp. hordei (Bgh)

status: Public on Oct 04 2016

city: Ames

first: PLEXdb Curator

middle: Sudhansu

state: IA

address: 1023  Crop Genomes Informatics Lab (Iowa State University)

department: Virtual Reality Application Center

institute: Iowa State University

summary: Expression analysis was performed on total RNA from the Q21861 and SM89010 barley lines, and 75 derived doubled haploid progeny, with CI 16137 included as an internal Mla1 allele control.   Samples were blocked by time-point and completely randomized within each block.  For each sample, seven day old seedlings were inoculated with Blumeria graminis f. sp. hordei (Bgh) isolate 5874 (AVRa1, AVRa6, AVRa12), and first leaves were collected at 16 and 32 hours after inoculation (HAI).   ****[PLEXdb(http://www.plexdb.org) has submitted this series at GEO on behalf of the original contributor,  Roger Wise.  The equivalent experiment is BB96 at PLEXdb.]

overall_design: genotype: Q21861 - time: 16 hai(4-replications);  genotype: Q21861 - time: 32 hai(4-replications);  genotype: SM89010 - time: 16 hai(4-replications);  genotype: SM89010 - time: 32 hai(4-replications);  genotype: QxSM001 - time: 16 hai(1-replications);  genotype: QxSM001 - time: 32 hai(1-replications);  genotype: QxSM002 - time: 16 hai(1-replications);  genotype: QxSM002 - time: 32 hai(1-replications);  genotype: QxSM003 - time: 16 hai(1-replications);  genotype: QxSM003 - time: 32 hai(1-replications);  genotype: QxSM005 - time: 16 hai(1-replications);  genotype: QxSM005 - time: 32 hai(1-replications);  genotype: QxSM008 - time: 16 hai(1-replications);  genotype: QxSM008 - time: 32 hai(1-replications);  genotype: QxSM010 - time: 16 hai(1-replications);  genotype: QxSM010 - time: 32 hai(1-replications);  genotype: QxSM011 - time: 16 hai(1-replications);  genotype: QxSM011 - time: 32 hai(1-replications);  genotype: QxSM013 - time: 16 hai(1-replications);  genotype: QxSM013 - time: 32 hai(1-replications);  genotype: QxSM014 - time: 16 hai(1-replications);  genotype: QxSM014 - time: 32 hai(1-replications);  genotype: QxSM015 - time: 16 hai(1-replications);  genotype: QxSM015 - time: 32 hai(1-replications);  genotype: QxSM016 - time: 16 hai(1-replications);  genotype: QxSM016 - time: 32 hai(1-replications);  genotype: QxSM017 - time: 16 hai(1-replications);  genotype: QxSM017 - time: 32 hai(1-replications);  genotype: QxSM018 - time: 16 hai(1-replications);  genotype: QxSM018 - time: 32 hai(1-replications);  genotype: QxSM019 - time: 16 hai(1-replications);  genotype: QxSM019 - time: 32 hai(1-replications);  genotype: QxSM023 - time: 16 hai(1-replications);  genotype: QxSM023 - time: 32 hai(1-replications);  genotype: QxSM026 - time: 16 hai(1-replications);  genotype: QxSM026 - time: 32 hai(1-replications);  genotype: QxSM028 - time: 16 hai(1-replications);  genotype: QxSM028 - time: 32 hai(1-replications);  genotype: QxSM029 - time: 16 hai(1-replications);  genotype: QxSM029 - time: 32 hai(1-replications);  genotype: QxSM030 - time: 16 hai(1-replications);  genotype: QxSM030 - time: 32 hai(1-replications);  genotype: QxSM031 - time: 16 hai(1-replications);  genotype: QxSM031 - time: 32 hai(1-replications);  genotype: QxSM033 - time: 16 hai(1-replications);  genotype: QxSM033 - time: 32 hai(1-replications);  genotype: QxSM034 - time: 16 hai(1-replications);  genotype: QxSM034 - time: 32 hai(1-replications);  genotype: QxSM035 - time: 16 hai(1-replications);  genotype: QxSM035 - time: 32 hai(1-replications);  genotype: QxSM036 - time: 16 hai(1-replications);  genotype: QxSM036 - time: 32 hai(1-replications);  genotype: QxSM037 - time: 16 hai(1-replications);  genotype: QxSM037 - time: 32 hai(1-replications);  genotype: QxSM038 - time: 16 hai(1-replications);  genotype: QxSM038 - time: 32 hai(1-replications);  genotype: QxSM039 - time: 16 hai(1-replications);  genotype: QxSM039 - time: 32 hai(1-replications);  genotype: QxSM041 - time: 16 hai(1-replications);  genotype: QxSM041 - time: 32 hai(1-replications);  genotype: QxSM042 - time: 16 hai(1-replications);  genotype: QxSM042 - time: 32 hai(1-replications);  genotype: QxSM043 - time: 16 hai(1-replications);  genotype: QxSM043 - time: 32 hai(1-replications);  genotype: QxSM045 - time: 16 hai(1-replications);  genotype: QxSM045 - time: 32 hai(1-replications);  genotype: QxSM046 - time: 16 hai(1-replications);  genotype: QxSM046 - time: 32 hai(1-replications);  genotype: QxSM047 - time: 16 hai(1-replications);  genotype: QxSM047 - time: 32 hai(1-replications);  genotype: QxSM048 - time: 16 hai(1-replications);  genotype: QxSM048 - time: 32 hai(1-replications);  genotype: QxSM049 - time: 16 hai(1-replications);  genotype: QxSM049 - time: 32 hai(1-replications);  genotype: QxSM050 - time: 16 hai(1-replications);  genotype: QxSM050 - time: 32 hai(1-replications);  genotype: QxSM052 - time: 16 hai(1-replications);  genotype: QxSM052 - time: 32 hai(1-replications);  genotype: QxSM054 - time: 16 hai(1-replications);  genotype: QxSM054 - time: 32 hai(1-replications);  genotype: QxSM055 - time: 16 hai(1-replications);  genotype: QxSM055 - time: 32 hai(1-replications);  genotype: QxSM056 - time: 16 hai(1-replications);  genotype: QxSM056 - time: 32 hai(1-replications);  genotype: QxSM057 - time: 16 hai(1-replications);  genotype: QxSM057 - time: 32 hai(1-replications);  genotype: QxSM058 - time: 16 hai(1-replications);  genotype: QxSM058 - time: 32 hai(1-replications);  genotype: QxSM059 - time: 16 hai(1-replications);  genotype: QxSM059 - time: 32 hai(1-replications);  genotype: QxSM060 - time: 16 hai(1-replications);  genotype: QxSM060 - time: 32 hai(1-replications);  genotype: QxSM061 - time: 16 hai(1-replications);  genotype: QxSM061 - time: 32 hai(1-replications);  genotype: QxSM062 - time: 16 hai(1-replications);  genotype: QxSM062 - time: 32 hai(1-replications);  genotype: QxSM063 - time: 16 hai(1-replications);  genotype: QxSM063 - time: 32 hai(1-replications);  genotype: QxSM065 - time: 16 hai(1-replications);  genotype: QxSM065 - time: 32 hai(1-replications);  genotype: QxSM066 - time: 16 hai(1-replications);  genotype: QxSM066 - time: 32 hai(1-replications);  genotype: QxSM067 - time: 16 hai(1-replications);  genotype: QxSM067 - time: 32 hai(1-replications);  genotype: QxSM068 - time: 16 hai(1-replications);  genotype: QxSM068 - time: 32 hai(1-replications);  genotype: QxSM069 - time: 16 hai(1-replications);  genotype: QxSM069 - time: 32 hai(1-replications);  genotype: QxSM070 - time: 16 hai(1-replications);  genotype: QxSM070 - time: 32 hai(1-replications);  genotype: QxSM073 - time: 16 hai(1-replications);  genotype: QxSM073 - time: 32 hai(1-replications);  genotype: QxSM074 - time: 16 hai(1-replications);  genotype: QxSM074 - time: 32 hai(1-replications);  genotype: QxSM075 - time: 16 hai(1-replications);  genotype: QxSM075 - time: 32 hai(1-replications);  genotype: QxSM076 - time: 16 hai(1-replications);  genotype: QxSM076 - time: 32 hai(1-replications);  genotype: QxSM077 - time: 16 hai(1-replications);  genotype: QxSM077 - time: 32 hai(1-replications);  genotype: QxSM078 - time: 16 hai(1-replications);  genotype: QxSM078 - time: 32 hai(1-replications);  genotype: QxSM079 - time: 16 hai(1-replications);  genotype: QxSM079 - time: 32 hai(1-replications);  genotype: QxSM080 - time: 16 hai(1-replications);  genotype: QxSM080 - time: 32 hai(1-replications);  genotype: QxSM082 - time: 16 hai(1-replications);  genotype: QxSM082 - time: 32 hai(1-replications);  genotype: QxSM083 - time: 16 hai(1-replications);  genotype: QxSM083 - time: 32 hai(1-replications);  genotype: QxSM084 - time: 16 hai(1-replications);  genotype: QxSM084 - time: 32 hai(1-replications);  genotype: QxSM085 - time: 16 hai(1-replications);  genotype: QxSM085 - time: 32 hai(1-replications);  genotype: QxSM086 - time: 16 hai(1-replications);  genotype: QxSM086 - time: 32 hai(1-replications);  genotype: QxSM087 - time: 16 hai(1-replications);  genotype: QxSM087 - time: 32 hai(1-replications);  genotype: QxSM088 - time: 16 hai(1-replications);  genotype: QxSM088 - time: 32 hai(1-replications);  genotype: QxSM089 - time: 16 hai(1-replications);  genotype: QxSM089 - time: 32 hai(1-replications);  genotype: QxSM090 - time: 16 hai(1-replications);  genotype: QxSM090 - time: 32 hai(1-replications);  genotype: QxSM091 - time: 16 hai(1-replications);  genotype: QxSM091 - time: 32 hai(1-replications);  genotype: QxSM093 - time: 16 hai(1-replications);  genotype: QxSM093 - time: 32 hai(1-replications);  genotype: QxSM094 - time: 16 hai(1-replications);  genotype: QxSM094 - time: 32 hai(1-replications);  genotype: QxSM095 - time: 16 hai(1-replications);  genotype: QxSM095 - time: 32 hai(1-replications);  genotype: QxSM097 - time: 16 hai(1-replications);  genotype: QxSM097 - time: 32 hai(1-replications);  genotype: CI 16137 - time: 16 hai(1-replications);  genotype: CI 16137 - time: 32 hai(1-replications)

first: Roger

last: Wise


title: A Gata2 dependent transcription network regulates progesterone signaling and endometrial function

status: Public on Oct 05 2016

first: Franco

last: Demayo

summary: Gata2 dependent genes in mouse uteri were identified by the conditional ablation of Gata2 using the (PR-cre) mouse upon acute progesterone administration.

overall_design: Mice were ovariectomized at 6 weeks of age. Two weeks later, ovariectomized mice were injected with either vehicle (sesame oil) or progesterone (in sesame oil, 1 mg per mouse in 100 μl) and mice were sacrificed 6 hours after the injection, uterine tissues were snap frozen and stored at -80°C. Total RNA was extracted from uterine tissues using the Qiagen RNAeasy total RNA isolation kit. The RNA was pooled from the uteri of 3 mice per genotype and subject to microarray analysis.

first: C

last: Rubel

first: S

last: Wu

first: L

last: Lin

first: T

last: Wang

first: X

last: Li

first: R

last: Kommagani

middle: B

last: Lanz

first: H

last: Franco

last: Camper

first: Q

last: Tong

first: J

last: Jeong

middle: P

last: Lydon

first: F

middle: J

last: DeMayo


title: Progesterone Receptor- and FOXO1-dependent transcriptomes decidualized human endometrial stromal cells

summary: We report the gene expression profile of primary human endometrial stromal cells treated for 48 hours with control non-targeting, PGR-targeting, or FOXO1-targeting siRNA prior to decidualization stimulus for 72 hours.

overall_design: RNA-seq in decidualizing human endometrial stromal cells

first: Franscesco

first: Erik

middle: C

last: Mazur

first: Yasmin

middle: M

last: Vasquez

first: Ramakrishna

first: Lichun

last: Jiang

first: Rui

last: Chen

first: Rainer

first: Ertug

last: Kovanci

first: William

middle: E

last: Gibbons


title: 03-311 Trastzumab preoperative Trial of Early Stage HER2+ BRCA

status: Public on Feb 09 2016

city: Cleveland

first: Vinay

last: Varadan

state: OH

address: 2103 Cornell Rd

department: Case Comprehensive Cancer Center

institute: Case Western Reserve University

summary:
Tumor core biopsies were obtained at baseline and after brief-exposure to single-agent trastuzumab from patients enrolled on the 03-311 trial.   Gene expression profiling was conducted on these tumor biopsies to identify signatures of response to preoperative therapy.
This study was initiated to identify biomarkers of response to preoperative trastuzumab-conotaining therapy. We performed transcriptional profiling of patient tumor biopsies obtained at baseline and post brief-exposure to trastuzumab to test the hypothesis that transcriptional changes upon brief-exposure to therapy can provide an early readout of subsequent response.

overall_design:
A total of 50 patients generated quality microarray data at both both baseline and post-exposure timepoints. These 100 samples were analyzed for changes in immune subsets and pathway activities that correlated with subsequent response at surgery.

Clinical response was assessed at the completion of preoperative therapy. Pathologic complete response (pCR) was scored by institutional pathologists and was defined as the absence of residual invasive disease in both the breast and any sampled axillary nodes; patients who failed to achieve pCR were grouped as objective responders (OBJR) category, which included complete and partial response (CR+PR), and non-responders (NOR) category including stable and progressive disease.

first: Lyndsay

middle: N

last: Harris


title: An ancient fecundability-associated polymorphism creates a new GATA2 binding site in a distal enhancer of HLA-F

status: Public on Jan 02 2018

first: Franco

last: Demayo

overall_design: Refer to individual Series


title: Effects of Pseudomonas aeruginosa ATCC27853 ingestion on Drosophila melanogaster

status: Public on Apr 09 2016

city: Bucharest

first: Attila

middle: Cristian

last: Ratiu

address: Intrarea Portocalelor, No. 1-3

department: Department of Genetics

country: Romania

institute: University of Bucharest

summary: Drosophila melanogaster is a validated eukaryotic model for immunity-concerned studies in the post-genomic era. In the present study we performed oral experimental infection of D. melanogaster with Pseudomonas aeruginosa (strain ATCC27853). By using a whole genome microarray approach, we intended to identify significant alterations in the expression profile of relevant genes amenable to qualify as new models for the investigation of specific host-parasite interactions.

overall_design: Wild type Oregon males and respectively γCOPS057302/TM6,Tb and γCOP14a/γCOP14a mutant males were feed with P. aeruginosa suspension (treated replicates) or with sucrose solution (untreated replicates). As a reference, we used Oregon untreated replicates (20 biological replicates). For the target groups we used four biological replicates and one target replicate per array.

first: Alexandru

last: Ecovoiu

first: Bettina

last: Fischer

first: Ilda

last: Barbu

first: Carmen

last: Chifiriuc


title: NCIC CTG MA.22  phase I/II trial of epirubicin and docetaxel in locally advanced breast cancer on 2-weekly or 3-weekly schedules

status: Public on Nov 11 2015

city: Sudbury

first: Baoqing

last: Guo

state: ON

address: 41 Ramsey Lake Road

department: Tumor Biology

institute: Advanced Medical Research Institute of Canada

summary:
This phase I/II neoadjuvant trial determined maximally-tolerated doses (MTD), dose-limiting toxicities (DLT), response-to-therapy, and explored the role of new response biomarkers.
The combination regimens were delivered with acceptable toxicity, good clinical response, inducing changes in tumor RNA content and integrity.  Pre-treatment gene expressions impacted clinical response, including several near 17q12, which with ERBB2, may better identify chemoresponsiveness.

overall_design:
The NCIC Clinical Trials Group MA.22 phase I/II clinical trial (ClinicalTrials.gov identifier NCT00066443) sought to determine the optimal dosing regimens for docetaxel/epirubicin combination chemotherapy in women with locally advanced (over 95% of patients) or inflammatory breast cancer. The protocol was approved by Health Canada and local Ethics Review Boards, and patients provided written, informed consent.
Various doses of epirubicin and docetaxel were administered to patients in either a standard q3 weekly (Schedule A) or dose dense q2 weekly (Schedule B) regimen.  Doses for Schedule A were 75 mg/m2 IV of docetaxel and 75, 90, 105, or 120 mg/m2 IV of epirubicin (with 6 mg of pegfilgrastim per cycle on day 2 to prevent neutropenia).  Doses for both docetaxel and epirubicin in Schedule B were 50, 60, and 70 mg/m2 IV (with identical pegfilgrastim support). For each schedule, phase I was dose finding for phase II. Patients were allocated to the various phases and dosing regimens of the trial without randomization. None of the patients received trastuzumab in the initial years of the study and HER2+ patients were not enrolled on study, once trastuzumab funding became available.   Six tumor biopsy cores were obtained pre-, mid-, and post-treatment: 3 cores for pathologic assessment; 3 cores for microarray studies. Total RNA was isolated from these cores and RNA integrity was assessed using Agilent Bioanalyzer. One of the RNA samples with the best quality was used for microarray study. One colour microarray of Agilent whole human genome nucleotide arrays was conducted with one array per patient.

The current data set represents pre-treatment set.

MA.22 clinical trial accrued T3N0, any N2 or N3, and T4 breast cancer patients (according to the classification described at; http://emedicine.medscape.com/article/2007112-overview). However, since the current study does not focus on the tumor grade/stage, the information was not provided in the current records.

first: Maureen

last: Trudeau

first: Judith-Anne

last: Chapman

first: Mark

last: Clemons

first: Rebecca

last: Dent

first: Roberta

last: Jong

first: Harriette

last: Kahn

first: Lois

last: Shepherd

first: Kathleen

middle: I

last: Pritchard

first: Jianfeng

last: Xu

first: Lei

last: Han

first: Patti

last: O’Brien

first: Amadeo

last: Parissenti


title: Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus

status: Public on Jan 22 2016

first: Jo Huiqing

last: Zhou

summary: To more concretely elucidate the long-term effects of chronic SSRI exposure during adulthood,  the long-term consequences of chronic fluoxetine (12 mg/kg) versus vehicle treatment during adulthood (postnatal day (PND) 67-88) on gene expression in the hippocampus were investigated. The study showed that adult chronic fluoxetine exposure causes on the long-term changes in the expression of genes related to, amongst others, myelination

overall_design: Comparison of gene expression in hippocampus tissue of fluoxetine and methylcellulose-exposed rats  (postnatal day 128). 2 rats pooled per sample, 2 samples per treatment group

first: Jo

middle: H


title: Prospective biomarker analysis of the randomized CHER-LOB study evaluating the dual anti-HER2 treatment with chemotherapy plus trastuzumab and lapatinib as neoadjuvant therapy for HER2-positive breast cancer [expression]

status: Public on Oct 06 2015

city: Modena

first: Enrico

last: Tagliafico

state: MO

address: Via Campi 287

department: Center for Genome Research

country: Italy

institute: University of Modena and Reggio Emilia

summary:
The CHER-LOB randomized phase II study showed that the combination of lapatinib and trastuzumab plus chemotherapy increases the pathologic complete remission (pCR) rate as compared to chemotherapy plus either trastuzumab or lapatinib. An extensive biomarker programme was prospectively planned to identify potential predictors of sensitivity to different treatments and evaluate treatment effect on tumor biomarkers.
A mutation in PIK3CA exon 20 or 9 was documented in 20% of the cases. Overall, the pCR rates were similar in PIK3CA wild type and PIK3CA mutated patients (33.3% vs 22.7%; p=0.323). However, for patients receiving trastuzumab plus lapatinib, the probability of pCR was higher in PIK3CA wild type tumors (48.4% vs 12.5%; p=0.06). Ki67, pAKT and apoptosis measured on the residual disease were significantly reduced from baseline. The degree of Ki67 inhibition was significantly higher in patients receiving the dual anti-HER2 blockade. In conclusion, PIK3CA mutations seem to identify patients less likely to benefit from dual anti-HER2 inhibition. p95-HER2 and markers of PI3K pathway deregulation are not confirmed as markers of different sensitivity to trastuzumab or lapatinib.

overall_design: 121 HER2-positive breast cancer patients were randomly assigned to neoadjuvant chemotherapy plus either trastuzumab, lapatinib or both trastuzumab and lapatinib. Pre-treatment, fresh-frozen tissue samples were collected for genomic analyses. 88 samples passed quality control for RNA and were profiled with Affymetrix technology using the HG-U133 Plus 2.0 GeneChip array.

first: Valentina

last: Guarneri

first: Maria

last: Dieci

first: Antonio

last: Frassoldati

first: Antonino

last: Maiorana

first: Guido

last: Ficarra

first: Stefania

last: Bettelli

first: Silvio

last: Bicciato

first: Daniele

middle: G

last: Generali

first: Katia

last: Cagossi

first: Giancarlo

last: Bisagni

first: Samanta

last: Sarti

last: Musolino

first: Catherine

last: Ellis

first: Rocco

last: Crescenzo

first: PierFranco

last: Conte


title: Prospective biomarker analysis of the randomized CHER-LOB study evaluating the dual anti-HER2 treatment with chemotherapy plus trastuzumab and lapatinib as neoadjuvant therapy for HER2-positive breast cancer

type:
Expression profiling by array
Genome variation profiling by SNP array


title: RNA sequencing for Comparisons of Vibrio Cholerae Wild Type and VchM Knock Out

status: Public on Oct 26 2015

city: Minneapolis

first: Shijia

last: Zhu

state: Minnesota

address: 1200 Washington Avenue S Suite #175

department: Department of Laboratory Medicine and Pathology

institute: University of Minnesota Medical School

summary: DNA methylation is a key epigenetic regulator in all domains of life, yet the effects of most bacterial DNA methyltransferases on cellular processes are largely undefined. Here, we used diverse techniques, including bisulfite sequencing, transcriptomics, and transposon insertion site sequencing to extensively characterize a 5-methylcytosine (5mC) methyltransferase, VchM, in the cholera pathogen, Vibrio cholerae. We have comprehensively defined VchM's DNA targets, its genetic interactions and the gene networks that it regulates. Although VchM is a relatively new component of the V. cholerae genome, it is required for optimal V. cholerae growth in vitro and during infection. Unexpectedly, the usually essential σE cell envelope stress pathway is dispensable in ΔvchM V. cholerae, likely due to its lower activation in this mutant and the capacity for VchM methylation to limit expression of some cell envelope modifying genes. Our work illuminates how an acquired DNA methyltransferase can become integrated within complex cell circuits to control critical housekeeping processes.

overall_design: Duplicates were used for all samples. For each strain background (C6706 and O395), there were control (Wildtype) samples and experimental samples (VchM knockout)

first: Michael

last: Chao

first: Gang

last: Fang

first: Matthew

middle: K

last: Waldor


title: Bisulfite Sequencing for Studying 5mC DNA Methylation Distribution in Vibrio Cholerae

overall_design: Duplicates samples were analyzed for wildtype cells grown under 3 conditions: exponential phase, stationary phase and rabbit intestinal infection


title: Gene Expression Analysis in Hep2 human cancer cells upon deadenylase silencing

status: Public on Oct 01 2015

city: Larissa

first: Nikolaos

last: Balatsos

state: Thessaly

address: Ploutonos 26 & Aiolou str

department: Biochemistry and Biotechnology

country: Greece

institute: University of Thessaly

summary: The first and rate-limiting step in eukaryotic mRNA decay is the shortening of the poly(A) tail catalyzed by a family of enzymes known as deadenylases. In humans, several deadenylases have been recognized so far, yet it is not clear what the advantage is to have many enzymes catalyzing the same reaction. It is hypothesized that specific deadenylases may target unique subsets of mRNAs, or multiple deadenylases can act on the same mRNA, with discrete but overlapping functions. To understand the biological significance of the diversity of these enzymes we silenced the expression of several deadenylases, including PARN, NOC, CNOT6, CNOT7 and CNOT8, in human cells of cancer origin (Hep2; epithelial carcinoma cells), and analyze the impact on gene expression with microarrays.

overall_design: The selected deadenylases were silenced with sequence-specific short hairpin RNAs delivered in Hep2 cells using cationic liposomes. Wild type cells, as well as cells transfected with empty vector or shRNA with no homology to known gene sequences, were used as controls and data normalization. Puromycin selection was performed 12h post transfection. Cells were harvested 72h upon transfection, RNA was extracted and gene expression was analyzed.

first: Panagiotis

last: Maragozidis

first: Diana

last: Scutelnic

first: Athanasios

last: Kyritsis

first: Demetra

middle: S

last: Chatzileontiadou

first: Konstantinos

last: Gourgoulianis

middle: A


title: Effects of Age and Estrogen on Skeletal Gene Expression in Humans as Assessed by RNA Sequencing

status: Public on Sep 09 2015

city: Rochester

first: Sundeep

last: Khosla

state: MN

address: 200 1st St SW

department: Endocrinology Research

institute: Mayo Clinic

summary: Here we present an RNAseq analysis of human bone samples, obtained from iliac crest needle biopsies, to yield the first in vivo interrogation of all genes and pathways that may be altered in bone with aging and E therapy in humans.

overall_design: 58 healthy women were studied, including 19 young women (mean age ± SD, 30.3 ± 5.4 years), 19 old women (73.1 ± 6.6 years), and 20 old women treated with 3 weeks of E therapy (70.5 ± 5.2 years).  Using generally accepted criteria (false discovery rate [q] < 0.10), aging altered a total of 678 genes and 12 pathways, including a subset known to regulate bone metabolism (e.g., Notch).

first: David

last: Monroe


title: Gene Expression Analysis in NCI-H520 human cancer cells upon deadenylase silencing

summary: The first and rate-limiting step in eukaryotic mRNA decay is the shortening of the poly(A) tail catalyzed by a family of enzymes known as deadenylases. In humans, several deadenylases have been recognized so far, yet it is not clear what the advantage is to have many enzymes catalyzing the same reaction. It is hypothesized that specific deadenylases may target unique subsets of mRNAs, or multiple deadenylases can act on the same mRNA, with discrete but overlapping functions. To understand the biological significance of the diversity of these enzymes we silenced the expression of several deadenylases, including PARN, NOC, CNOT6, CNOT6L, and CNOT7, in human cells of cancer origin (NCI-H520; squamous lung cancer), and analyze the impact on gene expression with microarrays.

overall_design: The selected deadenylases were silenced with sequence-specific short hairpin RNAs delivered in NCI-H520 cells using cationic liposomes. Wild type cells, as well as cells transfected with empty vector or shRNA with no homology to known gene sequences, were used as controls and data normalization. Puromycin selection was performed 12h post transfection. Cells were harvested 72h upon transfection, RNA was extracted and gene expression was analyzed.


title: Combined Genome and Transcriptome Sequencing to Identify Allelic Selection in Epithelial Ovarian Cancer

status: Public on Dec 12 2015

city: Doha

first: Najeeb

last: Halabi

address: Education City

country: Qatar

institute: Weill Cornell Medicine in Qatar

type: Genome variation profiling by high throughput sequencing

summary: Identifying genes where a variant allele is preferentially expressed in tumors could lead to a better understanding of cancer biology and optimization of targeted therapy. However, tumor sample heterogeneity complicates standard approaches for detecting preferential allele expression. We therefore developed a novel approach combining genome and transcriptome sequencing data from the same sample that corrects for sample heterogeneity and identifies significant preferentially expressed alleles. We applied this analysis to epithelial ovarian cancer samples consisting of matched primary ovary and peritoneum and lymph node metastasis. We find that preferentially expressed variant alleles include germline and somatic variants, are shared at a relatively high frequency between patients and are in gene networks known to be involved in cancer processes. Analysis at a patient level identifies patient-specific preferentially expressed alleles in genes that are targets for known drugs. Analysis at a site level identifies patterns of site specific preferential allele expression with similar pathways being impacted in the primary and metastasis sites. We conclude that genes with preferentially expressed variant alleles can act as cancer drivers and that targeting those alleles could lead to new therapeutic strategies.

overall_design: Three cancer patients, three tumor samples per patient from different sites, two normal tissue samples from two different patients, four cell lines.

first: Arash

last: Rafii


title: caArray_gray-00248: Genomic and transcriptional aberrations linked to breast cancer pathophysiologies

status: Public on May 20 2015

city: Rockville

first: Mervi

last: Heiskanen

address: 9609 Medical Center Drive, 1W378

department: CBIIT

institute: NCI

summary: We measured baseline gene expression profiles for a set of breast tumors.

overall_design:
gray-00248
Assay Type: Gene Expression
Provider: Affymetrix
Array Designs: U133AAofAv2
Organism: Homo sapiens (ncbitax)
Tissue Sites: mammary gland
Material Types: synthetic_RNA, total_RNA
Disease States: breast cancer


title: Loss of endometrial plasticity in recurrent pregnancy loss (RNA-Seq)

status: Public on Sep 16 2015

city: Coventry

first: Jan

last: Brosens

address: University Hospital Coventry and Warwickshire

institute: University of Warwick

summary: In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women.  The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages.

overall_design: 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss.

first: Yi-Wah

last: Chan

first: Emma

last: Lucas


title: Loss of endometrial plasticity in recurrent pregnancy loss (MeDIP-Seq)

summary: Decidual transformation of the human endometrium is not dependent on embryo implantation. Instead, this process is initiated during the mid-luteal phase of each cycle in response to the postovulatory rise in progesterone and increasing endometrial cAMP levels. Consequently, decidualization is a reiterative process directly linked to cyclic activation of mesenchymal stem cells (MSCs) and subsequent differentiation into mature stromal cells in regenerating endometrium. We reasoned that aberrant remodeling of the HESC epigenome would disrupt decidualization in RPL patients and account for the functional memory of HESCs in culture. To explore this possibility, we performed MeDIP-seq, which involves immunoprecipitation of DNA with a 5-methylcytosine antibody followed by deep sequencing, on primary HESC cultures established from four RPL patients and four control subjects.

overall_design: Eight samples were analyzed: derived from four control and four recurrent pregnancy loss (RPL) patient cultures.

first: Sascha

last: Ott

first: Nigel

last: Dyer

first: Giulia

last: Grimaldi


title: DNA methylation-based prognosis and epidrivers in hepatocellular carcinoma

status: Public on Mar 07 2015

city: New York

first: Augusto

last: Villanueva

address: 1425 Madison Ave

institute: Icahn School of Medicine at Mount Sinai

summary:
Genome-wide expression analysis of 228 hepatocellular carcinoma and 168 cirrhotic samples as part of a integrated study of gene expression and DNA-methylation de-regulation in patients with hepatocellular carcinoma
Analysis of whole-genome transcriptome changes in human samples from hepatocellular carcinoma patients

overall_design: Fresh-frozen tissue (primary hepatocellular carcinoma and non-tumor cirrhosis) from patients treated with surgical resection.

first: Josep

last: Llovet


title: Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers

status: Public on May 01 2015

first: Jo Huiqing

last: Zhou

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


title: Progesterone receptor transcriptome and cistrome in decidualized human endometrial stromal cells [ChIP]

status: Public on Jun 05 2015

city: Houston

first: Francesco

last: DeMayo

state: Texas

address: 1 Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: We report the whole genome binding profile of PGR and FOSL2

overall_design: ChIP-seq in decidualizing human endometrial stromal cells

first: Franscesco

first: Yasmin

last: Vasquez


title: TIGIT+ Tregs

status: Public on Dec 12 2014

city: Boston

first: CBDM

last: Lab

address: 77 Avenue Louis Pasteur

department: Microbiology and Immunobiology

institute: Harvard Medical School

summary: TIGIT+ Tregs suppress Th1 and Th17 responses while sparing Th2 responses. Analysis of global gene expression of TIGIT+ vs. TIGIT- Tregs from naive mice reveled that TIGIT+ Tregs display an activated phenotype and are enriched for Treg signature genes including the Treg effector molecule Fgl2 which enables them to selectively spare Th2 responses.

overall_design:
TIGIT+ and TIGIT- Tregs were sorted from naïve Foxp3-GFP KI mice (pooled spleen and lymph nodes)
TIGIT: T cell immunoreceptor with Ig and ITIM domains

first: Nicole

last: Joller

first: Vijay

last: Kuchroo

first: Diane

last: Mathis

first: Christophe

last: Benoist


title: Loss of endometrial plasticity in recurrent pregnancy loss

first: Jan

overall_design: Refer to individual Series


title: Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (RNA-Seq)

address: Geert Grooteplein 26/28

summary: Tightly controlled gene expression orchestrated by the transcription factor p63 during epithelial differentiation is important for development of epithelial-related structures such as epidermis, limb and craniofacial regions. How p63 regulates spatial and temporal expression of its target genes during these developmental processes is however not yet clear. By epigenomics profiling in stem cells established from one of these epithelial structures, the epidermis, we provide a global map of p63-bound regulatory elements that are categorized as single enhancers and clustered enhancers during epidermal differentiation. Transcriptomics analysis shows dynamic gene expression patterns during epidermal differentiation that correlates with the activity of p63-bound enhancers rather than with p63 binding itself. Only a subset of p63-bound enhancers is active in epidermal stem cells, and inactive p63-bound enhancers appear to function in gene regulation during the development of other epithelial tissues. Our data suggest a paradigm that p63 bookmarks genomic loci during the commitment of the epithelial lineage and regulates gene expression in different epithelial tissues through tissue-specific active enhancers. The catalogue of differentially expressed epidermal genes including non-coding RNAs and epithelial enhancers reported here provides a rich resource for studies of epithelial development and related diseases.

overall_design: Comparison of gene expression at different stages of keratinocyte differentiation

first: Jo

last: H. Zhou


title: A Cbx8-containing Polycomb complex facilitates gene activation during ES cell differentiation [ChIP-Seq]

status: Public on Nov 04 2014

city: Badalona

first: Roberto

last: Malinverni

address: Josep Carreras Building, Ctra de Can Ruti,

institute: Josep Carreras Leukaemia Research Institute

summary: Polycomb proteins play an essential role in maintaining the repression of developmental genes in self-renewing embryonic stem cells. The exact mechanism allowing the derepression of polycomb target genes during cell differentiation remains unclear. Here, we show that several differentiation genes transiently recruit a Cbx8-containing Polycomb repressive complex (PRC) 1 during their early activation. Depletion of Cbx8 partially impairs the transcriptional activation of these genes. This correlates with a reduction in low but detectable levels of histone H3 lysine 27 acetylation. Prolonged gene activation results in eviction of PRC1 despite persisting H3K27me3. The composition of PRC1 is highly modular and changes when ES cells commit to differentiation. We further demonstrate that the exchange of Cbx7 for Cbx8 is required for the effective activation of differentiation genes. Taken together our results establish a function for a Cbx8-containing complex in facilitating the transition from a Polycomb-repressed chromatin state to an active state. As this affects several key regulatory differentiation genes this mechanism is likely to contribute to the robust execution of differentiation programs.

overall_design: Examination of cbx8 in ES E14 mouse cells in 2 condition before and after 72h stimulation with retinoic acid compared with IgG

first: Catherine

last: Creppe

first: Anna

last: Palau

first: Vanesa

last: Valero

first: Marcus

last: Buschbeck


title: Genome-wide DNA methylation aberrations in human atherosclerosis (sequencing)

status: Public on Aug 12 2014

city: L'Hospitalet de Llobregat

first: Manel

last: Esteller

address: Hospital Duran i Reynals Av. Gran Via s/n km, 2.7

department: PEBC

institute: IDIBELL

summary: Epigenetics may help understanding the molecular mechanisms of atherosclerosis as genetic predisposition explains only part of cardiovascular disease risk. In particular, DNA methylation, a reversible and highly regulative DNA modification could contribute to disease onset and progression as it functions as effector for environmental impacts, including dietary and life-style, similarly to risk factors for cardiovascular diseases. We addressed this issue by performing whole-genome shotgun bisulfite sequencing and high-resolution DNAmethylation array analysis of healthy and diseased donor-matched atherosclerotic DNA methylomes.

overall_design: Sequencing of bisulfite converted DNA and array based analysis of atherosclerotic lesions and normal carotid tissue.

first: Holger

last: Heyn


title: Transcription factor p63 bookmarks genomic loci in epithelial cells and regulates a subset of target genes during epidermal differentiation through dynamic enhancers (ChIP-Seq)

city: Nijmegen

first: Jo Huiqing

institute: Radboud University

overall_design: Different stages of keratinocyte differentiation


title: A Cbx8-containing Polycomb complex facilitates gene activation during ES cell differentiation [Agilent Array]

overall_design: Four biological replicates were used for each condition (untreated and after 72h of retinoic acid stimulation) and samples were prepared and hybridized to SurePrint G3 Gene Expression Microarrays (Agilent technologies) following the supplier's instructions. Analyses were essentially performed as described (Uribesalgo et al. 2011) selecting differentially expressed probes with a FDR of 0.05 and fold change of > 1.5.


title: Expression Data from transNOAH breast cancer trial

status: Public on Jan 21 2014

city: Penzberg

first: Anton

last: Belousov

address: Nonnenwald 2

department: NCS-TTB

country: Germany

institute: Roche

summary:
These data can be used for evaluation of the clinical utility of the research-based PAM50 subtype predictor in predicting pathological complete response (pCR) and event-free survival (EFS) in women enrolled in the NeOAdjuvant Herceptin (NOAH) trial.
The NeOAdjuvant Herceptin [NOAH] trial demonstrated that trastuzumab significantly improves pCR rates and 3-year event-free survival (EFS) in combination with neoadjuvant chemotherapy compared with neoadjuvant chemotherapy alone in patients with HER2+ breast cancer.

overall_design:
Gene expression profiling was performed using RNA from formalin-fixed paraffin-embedded core biopsies from 114 pre-treated patients with HER2-positive (HER2+) tumors randomized to receive neoadjuvant doxorubicin/paclitaxel (AT) followed by cyclophosphamide/methotrexate/fluorouracil (CMF), or the same regimen in combination with trastuzumab for 1 year. A control cohort of 42 patients with HER2-negative tumors treated with AT-CMF was also included.

This dataset represents 156 patients who had provided the samples at baseline (pre-treatment).

first: Aleix

last: Prat


title: Genome-wide DNA methylation aberrations in human atherosclerosis (450K)


title: Expression data from the subclones of Lewis Lung Carcinoma (LLC) cells

status: Public on Jul 13 2014

first: Serkan

last: KIR

address: 450 Brookline Ave

country: USA

institute: Dana-Farber Cancer Inst.

summary:
Medium conditioned by LLC cells stimulates thermogenic gene expression when added onto primary adipocytes. We generated single cell colonies from parental LLC cells. Media conditioned by the subclones stimulated thermogenic gene expression in primary adipocytes at varying degrees.
Subclones 2, 3, 6 and 28 produce significantly larger amount of thermogenic activity than the subclones 18, 19, 23 and 24. We compared gene expression profiles of these subclones to identify secreted factors enriched in the more thermogenic clones.

overall_design: LLC subclones were cultured under conditioned medium preparation conditiones and total RNA was extracted from biological replicates.

last: Kir

first: Bruce

last: Spiegelman


title: Genome-wide DNA methylation aberrations in human atherosclerosis


title: Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: the INTERCOM study

status: Public on Sep 15 2013

city: Edmonton

first: Jessica

last: Chang

address: 250 Heritage Medical Research Centre

institute: University of Alberta

summary: The authors report that in INTERCOM, a prospective international study of 300 kidney transplant biopsies, a microarray-based molecular score for T cell-mediated rejection changed the assessment of 26% of all biopsies, illustrating the potential of precision diagnostics to impact practice.

overall_design:
Microarray analysis of 300 kidney transplant biopsies (non-TCMR, TCMR) and 6 nephrectomies.

Note: The Sample 'characteristics' were updated on June 11, 2022.

first: Philip

middle: F

last: Halloran

first: Andre

last: Pereira


title: Gata2 is a master regulator of endometrial function and progesterone signaling

status: Public on Jan 01 2014

city: RTP

first: Franco

last: Demayo

state: NC

address: 111 TW Alexander Drive

institute: NIEHS