title: Genome-wide profile of 5-hydroxymethylcytosine (5-hmC) in H9 human embryonic stem cells (hESCs)

status: Public on Jan 01 2019

city: santa barbara

first: Guojing

last: Liu

address: 552 University Rd

institute: University of California, santa barbara

summary: The link between single cell variation and population level fate choices lacks an explanation despite extensive observations of gene expression and epigenetic variation among individual cells. Here, we found that single human embryonic stem cells (hESCs) have different and biased differentiation potentials toward either neuroectoderm or mesendoderm depending on their G1 lengths before the onset of differentiation. Single cell variation in G1 length establishes a probability distribution in which increased variation biases stem cells toward neuroectoderm. Although sister stem cells generally share G1 lengths, a variable proportion of cells have asymmetric G1 lengths, which maintains the population dispersion. WNT levels control the G1 length distribution apparently as a means of priming the fate of hESC populations once they undergo differentiation. Global 5-hydroxymethylcytosine levels are regulated by G1 length and thereby link G1 length to differentiation outcomes of hESCs. Our findings suggest G1 length distribution links intra-population heterogeneity to population outcome.

overall_design: Examination of 5-hmC sites in hESCs grown in mTeSR1; Aba-seq is a method for high-resolution mapping of the 5hmC methylome that provides sensitive detection of 5hmC at low-occupancy regions. The method relies on the unique property of the restriction enzyme AbaSI to recognize glucosylated 5hmC with high specificity, compared to 5mC and C

first: Jiwon

last: Jang

first: Alex

last: Chialastri

first: Siddharth

last: Dey

first: Kenneth

last: Kosik


title: Bayogenin 3-O-Cellobioside is a novel anti-blast metabolite produced in rice in response to Pyricularia oryzae infection

status: Public on Feb 23 2019

city: Fuzhou

first: Justice

last: Norvienyeku

state: N/A = Not Applicable

address: shangxia District RD.No#15, Fuzhou

country: China

institute: Fujian Agriculture and Forestry University

type: Expression profiling by high throughput sequencing

summary: Susceptible (CO39 and NPB) and resistant (Pi_gm) rice cultivars were spray inoculated with P. oryzae spore and incubated for 12-hours. Total RNA was extracted from the inoculated rice seedlings (T_Co39, T_NPB, and T_gm) along with their non-inoculated control group C_Co39, C_NPB, and C_gm. The extraction of total RNA from inoculated and non-inoculated control samples was carried-out with RNAprep pure Plant Kit (Tiangen, Beijing) by following processes recommended by the manufacturer. To observe the level of RNA degradation and contamination, the extracted RNA was run on 1% agarose gels. RNA integrity was assessed using the RNA Nano 6000 Assay Kit of the Bioanalyzer 2100 system (Agilent Technologies, CA, USA). RNA concentration was measured with RNA Assay Kit in Qubit 2.0 Fluorometer (Life Technologies, CA, USA). The cDNA library was sequenced on the Illumina sequencing platform (Illumina HiSeq™ 2000) with 150 bp pair-end reads length and 300 bp insert size by Gene Denovo Co. (Guangzhou, China). Novogene in-house Perl script was used to select clean reads by removing adaptor sequences, low quality sequences (reads with more than 50% of bases quality lower than 20) and reads with more than 5% N bases.

sample_organism:
Oryza sativa Indica Group
Oryza sativa Japonica Group

overall_design: mRNA profile of susceptible and resistant rice seedlings inoculated with P. oryzae for 12-hours and non-inoculated control groups were generated through deep sequencing, data was obtained from one biological experiment with three technical replicates using Illumina HiSeq™ 2000.


title: Cyclophilin D-dependent mitochondrial permeability transition amplifies inflammatory reprogramming in endotoxemia

status: Public on Mar 07 2019

city: Morahalom

first: Balazs

last: Horvath

address: Vallalkozok u. 7.

department: NGSP

country: Hungary

institute: SeqOmics Biotechnology Ltd.

summary: We aimed to understand the role of cyclophilin D (CypD)-dependent mitochondrial permeability transition (mPT) in the immunosuppressive phase of lipopolysaccharide (LPS)-induced endotoxic shock. The liver plays an important role in immunity and organ dysfunction; therefore, on liver RNA sequencing (RNAseq) data, Ingenuity® Pathway Analysis (IPA ®) was used to investigate the complex role of mPT formation in inflammatory reprogramming and disease progression. LPS induced significant changes in the expression of 2715 genes, affecting 179 pathways related to mitochondrial dysfunction, defective oxidative phosphorylation, nitric oxide (NO) and reactive oxygen species (ROS) accumulation, nuclear factor, erythroid 2 like 2 (Nrf2), Toll-like receptors (TLRs), and tumor necrosis factor α receptors (TNFRs) mediated processes in wild-type mice. The disruption of CypD reduced the LPS-induced alterations in gene expression and pathways involving TNFRs and TLRs, in addition to improving survival and attenuating oxidative liver damage and the related NO- and ROS-producing pathways. CypD deficiency diminished the suppressive effect of LPS on mitochondrial function, nuclear- and mitochondrial-encoded genes, and mitochondrial DNA (mtDNA) quantity, which could be critical in improving survival. Our data propose that CypD-dependent mPT is an amplifier in inflammatory reprogramming and promotes disease progression. The mortality in human sepsis and shock is associated with mitochondrial dysfunction. Prevention of mPT by CypD disruption reduces inflammatory reprogramming, mitochondrial dysfunction, and lethality; therefore, CypD can be a novel drug target in endotoxic shock and related inflammatory diseases.

overall_design: Comparison of CypD-/- and wild type mice in an endotoxemia model

last: Veres

first: Krisztian

last: Eros

first: Csenge

last: Antus

first: Nikoletta

last: Kalman

first: Fruzsina

last: Fonai

first: Peter

middle: B

last: Jakus

first: Eva

last: Boros

first: Zoltan

last: Hegedus

first: Istvan

last: Nagy

first: Laszlo

last: Tretter

first: Ferenc

last: Gallyas Jr.

last: Sumegi


title: ChIPseq on H3K27ac, H4ac, H3K9ac, H3K4me3, H3K4me1, H3K27me3 and H2AK119Ub on TX1072 WT, Hdac3-/-, and ChIP targeting FLAG on Hdac3-AID-FLAG cell lines, at different time of Dox induction.

city: Paris

first: Aurélie

last: Bousard

address: 26, rue d'Ulm

country: France

institute: Institut Curie

type: Genome binding/occupancy profiling by high throughput sequencing

summary: During development, transcriptional and chromatin modification changes co-occur but the order and causality of events often remain unclear. We explore these questions using the paradigm of X-chromosome inactivation (XCI). We initiate XCI in female, mouse embryonic stem cells by inducingXistand monitor changes in transcription and chromatin by allele-specific profiling. Our unprecedented temporal resolution identifies histone deacetylation and H2AK119 ubiquitination as the earliest chromatin alterations during XCI. Functional dissection of these changes reveals that HDAC3 is pre-bound on the X-chromosome and uponXistcoating, histone deacetylation is required for efficient gene silencing. We also reveal that PRC1-associated H2AK119Ub precedes PRC2-associated H3K27me3 during XCI. These marks accumulate initially at large, intergenic domains and then spread into genes but only in the context of gene silencing and histone deacetylation. Our results reveal a hierarchy of chromatin events at the initiation of XCI and identify their key roles in mediating transcriptional silencing.

overall_design: ChIPseq targeting H3K27ac, H4ac, H3K9ac, H3K4me3, H3K4me1, H3K27me3 and H2AK119Ub have been done on TX1072 WT after different times of Dox induction (0h,4h,8h,12h,24h), in replicates. In HDAC3 -/-, ChIPseq targeting H3K27ac, H4ac have been done after 3 times of Dox induction (0h,8h,24h) in replicate and ChIPseq targeting H3K27me3 and H2AK119Ub  have been done after 2 times of Dox induction (0h,24h),  In Hdac3-AID-Flag cell line, ChIPseq targeting

first: Jan

middle: J

last: Zylicz

first: Kristina

last: Zumer

first: Francois

last: Dossin

first: Eusra

last: Mohammad

first: Simao

last: Teixeira da Rocha

first: Bjorn

last: Shwalb

first: Laurène

last: Syx

first: Florent

last: Digli

first: Damarys

last: Loew

first: Patrick

last: Cramer

first: Edith

last: Heard


title: Transcriptome sequencing of two Lake Baikal endemic (Eulimnogammarus verrucosus and E. cyaneus) and one Holarctic (Gammarus lacustris) transcriptome species from the Baikal region subjected to different stressors

status: Public on May 23 2019

city: Irkutsk

first: Polina

last: Drozdova

state: Irkutsk region

address: Lenin str. 3

department: Institute of Biology

country: Russia

institute: Irkutsk State University

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

sample_organism:
Eulimnogammarus verrucosus
Gammarus lacustris
Eulimnogammarus cyaneus

overall_design: Refer to individual Series


title: C57BL/6 mouse embryo stem cells(mESC)-based transcription change in expression profile microarray with folate deficiency

status: Public on Dec 22 2018

city: taiyuan

first: Li

middle: jian

last: ting

state: shanxi province taiyuan city

institute: Shanxi Medical University

summary:
Different genes were chosen according to folate deficiency in the microarray.
In the study here,C57BL/6C mESC with six consecutive generations under folate-deficiency was used to obtain whole genome-based expression microarray.

overall_design: 6 cell samples in all were included in the experiment, 3 cases such as:C57-W1,C57-W2,C57-W3 (including 3 replicates) with consecutive 6 generations folate-deficiency medium; 3 control such as C57-Y1,C57-Y2,C57-Y3 (also including 3 replicates.)

first: Jianting

last: Li

first: Ting

last: Zhang


title: Cellular gene expression during Hepatitis C Virus replication revealed by Ribosome profiling

status: Public on Mar 02 2019

city: Cork

first: Audrey

middle: M

last: Michel

state: Cork

address: Western Gateway, Western Road

department: School of Biochemistry and Cell Biology

country: Ireland

institute: University College Cork

summary:
Background: Hepatitis C virus (HCV) infects human liver hepatocytes, often leading to liver cirrhosis and hepatocellular carcinoma (HCC). It is believed that chronic infection alters host gene expression and favours HCC development. In particular, HCV replication in Endoplasmic Reticulum (ER) derived membranes induces chronic ER stress. How HCV replication affects host mRNA translation and transcription at a genome wide level is not yet known.
Methods: We used Riboseq (Ribosome Profiling) to analyze transcriptome and translatome changes in Huh-7.5 hepatoma cells replicating HCV for 6 days.
Results: Established viral replication does not cause global changes in host gene expression - only around 30 genes are differentially expressed. Upregulated genes are related to ER stress, HCV replication and HCC development. Some mRNAs (PPP1R15A/GADD34, DDIT3/CHOP, TRIB3) may be subject to uORF mediated translation control in response to stress-induced eIF2 inactivation. Transcriptional downregulation mainly affects mitochondrial respiratory chain complex genes.
Conclusion: After establishing HCV replication, cellular gene expression is reprogrammed towards stress response and HCC development. Downregulation of mitochondrial respiratory chain genes indicates how a virus induces cancer cell-like metabolic reprogramming ("Warburg effect"). Thus, HCV escapes stress response pathways but induces selective gene expression changes which likely are beneficial for chronic infection and cancerogenesis.

overall_design: Transcriptome and translatome changes in Huh-7.5 hepatoma cells replicating HCV for 6 days in comparison to non-infected cells were analyzed, in triplicates, by NGS.

first: Gesche

middle: K

last: Gerresheim

first: Jochen

last: Bathke

first: Dmitri

middle: E

last: Andreev

first: Lyudmila

middle: A

last: Shalamova

first: Oliver

last: Rossbach

first: Pan

last: Hu

first: Dieter

last: Glebe

first: Markus

last: Fricke

first: Manja

last: Marz

first: Alexander

last: Goesmann

first: Stephen

last: Kiniry

first: Pavel

last: Baranov

first: Ivan

middle: N

last: Shatsky

first: Michael

last: Niepmann


title: Gene expression data from LCMV-specific WT and Ezh2-/- follicular T helper cells

status: Public on Dec 25 2018

city: Chongqing

first: Xiangyu

last: Chen

address: 30 Gaotanyan Street

department: Institute of Immunology, PLA

institute: Third Military Medical University

summary: Microarray experiments were performed to elucidate the transcriptome changes due to EZH2 deficiency in  follicular T helper (TFH) cells. These data suggest TFH-lineage associated genes are down-regulated in EZH2-null TFH cells, indicating that EZH2 primes TFH differentiation by regulating canonical genes of TFH cells.

overall_design: WT and EZH2-null TFH cells (2 samples per group, each sample was pooled from at least 5 mice) were sorted at day 8-post LCMV Armstrong infection, followed by total RNA extracted and sent to microarray analysis.

first: Lilin

last: Ye


title: Sensitive, high-throughput single-cell RNA-Seq reveals within-clonal transcript-correlations in yeast populations

status: Public on Feb 04 2019

city: Palo Alto

first: Wu

last: Wei

state: CA

address: 3165 Porter Dr.

country: USA

institute: Stanford Genome Technology Center

summary: Single-cell RNA-seq (scRNA-seq) has revealed extensive cellular heterogeneity within many organisms but few methods have been developed for microbial clonal populations. The yeast genome displays an unusually dense transcript spacing with interleaved and overlapping transcription from both strands, resulting in a minuscule but complex pool of RNA protected by a resilient cell wall. Here, we developed a sensitive, scalable and inexpensive yeast single-cell RNA-seq (yscRNA-seq) method that digitally counts transcript start sites (TSS) in a strand- and isoform-specific manner with unique molecular identifiers (UMI). YscRNA-Seq detects expression of low-abundant, non-coding RNAs and at least half of the protein-coding genome in each cell. From just one single-cell transcriptome experiment of a bulk population, enough heterogeneity is uncovered between individual cells to identify biological associations without the need for perturbation experiments necessary to derive correlations from bulk data. Within cells of a single clonal population, we observe negative expression correlation of sense/antisense pairs while duplicated gene pairs and divergent transcripts co-express. By combining yscRNA-Seq with index sorting, which allows phenotypic characterization, we uncover a linear cell size-dependent change in absolute RNA content. Although we detect an average of ~3.5 molecules per gene, a single cell tends restrict the number of expressed isoforms. Remarkably, there is a highly variable expression within metabolic genes, whose stochastic expression primes cells for fitness benefit towards the corresponding environmental challenge. These findings suggest functional transcript diversity as a mechanism for providing a selective advantage to individual cells within otherwise transcriptionally heterogeneous microbial populations.

overall_design: Yeast single cell RNA-seq (yscRNA-seq) data for S288c and YJM789 strains

first: Mariona

last: Nadal-Ribelles

first: Saiful

last: Islam

first: Pablo

last: Latorre

first: Lars

last: Steinmetz


title: RNA profiling of the liver and gut tissues in zebrafish (Danio rerio) [miRNA]

status: Public on Dec 26 2018

city: Charleston

first: Gary

last: Hardiman

state: SC

address: 135 Cannon Street

department: Medicine

institute: Medical University of South Carolina

type: Non-coding RNA profiling by high throughput sequencing

summary: Compared to other fish models, miRNAs are currently most extensively studied and identified in zebrafish. Approximately 415 dre-miRNAs have been identified and several articles have studied some aspect of miRNA function in zebrafish such as their role in basic development and in disease pathways. However, this field of research is in its infancy and the function of several dre-miRNAs, as well as their tissue-specific expression profile, are yet to be defined.   In this study, the liver and gut were dissected (wildtype/untreated fish), total and small RNA were extracted, mRNA and miRNA libraries constructed and subjected to high throughput sequencing (HTS) using standard approaches. We carried out differential expression (DE) analysis and compared liver miRNA expression to gut using established bioinformatics pipelines. Through bioinformatics analysis, known and putative novel miRNAs were identified. Finally, we constructed a “miRNA matrix” that connects both total RNA-Seq and miRNA-Seq.

overall_design: Examination of miRNome in adult zebrafish tissues, gut and liver under homesostasis.

first: Renaud

last: Ludivine


title: Transcriptomics analysis of the Chlamydomonas reinhardtii diurnal cycle.

status: Public on Jan 03 2019

city: Berkeley

first: Sean

middle: D.

last: Gallaher

state: California

address: 176 Stanley Hall, room 408

department: California Institute for Quantitative Biosciences

institute: UC Berkeley

summary: Here, we report a transcriptomics analysis on a day in the life of Chlamydomonas reinhardtii. Cultures of this unicellular alga were grown in photobioreactors on a 12 h light / 12 h dark cycle. Samples were collected at regular intervals and subjected to a transcriptomics analysis by RNA-Seq.

overall_design: RNA-Seq libraries were prepared from synchronized cultures of Chlamydomonas reinhardtii sampled at regular intervals over the course of a diurnal cycle. Light intensity during the day was 200 PFD.

middle: D

first: Daniela

last: Strenkert


title: RNA expression data from hepatocytes from WT, NemoLPC-KO, Cxcr6-/- and NemoLPC-KOCxcr6-/- mice

status: Public on Dec 07 2018

city: Aachen

first: Bernd

last: Denecke

state: NRW

address: Pauwelsstrasse 30

department: IZKF Aachen

country: Germany

institute: RWTH Aachen University

summary:
We investigated the role of CXCR6 in the NEMOLPC-KO mouse model. Genetic deletion of CXCR6 enhanced hepatocyte death, inflammation and fibrosis in NEMOLPC-KO mice.
This study aimed at characterizing the transcriptomic changes in hepatocytes from these mice compared to controls.

overall_design: 11 total samples were analyzed.

first: A

last: Wehr

last: Liepelt

first: B


title: RNA profiling of the liver and gut tissues in zebrafish (Danio rerio) [mRNA]

overall_design: Examination of transcriptome in an in vivo model organism in two defined tissues, liver and gut.


title: RNASeq analysis of calcification stages (and KPT) in pAVICs

status: Public on Dec 15 2018

city: Milwaukee

first: Punashi

last: Dutta

state: WI

address: 8701 Watertown Plank Road

department: Cardiovascular

institute: Medical College of Wisconsin

summary: In order to assess transcriptome profile of different calcification stages and KPT, RNA-Seq analysis was performed

overall_design: Three biological replicates were used for every condition

first: Madhav Karthik

last: Kodigepalli

first: Stephanie

last: LaHaye

first: Will

last: Thompson

first: Sarah

last: Rains

first: Casey

last: Nagel

first: Kaitlyn

last: Thatcher

first: Robert

last: Hinton

first: Joy

last: Lincoln


title: Single-cell transcriptomics identifies cellular heterogeneity in large skin wounds

status: Public on Dec 05 2018

city: Irvine

first: Maksim

middle: V

last: Plikus

address: 845 Health Sciences Road

department: Developmental and Cell Biology

institute: University of California, Irvine

summary: We report transcriptomes of cells from large skin wounds. Dead cells were removed from post-wounding day (PWD) 12 skin wound tissue using dead cell removal kit (MACS). Remaining live cells were analyzed

overall_design: Examination of single cell heteregeneity in large skin wounds on PWD 12

first: Christian

middle: F

last: Guerrero-Juarez


title: A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation

status: Public on Dec 24 2018

city: Tianjin

first: Dianhao

last: Guo

address: 94 Weijin Road

institute: Nankai University

summary: Retinoic acid (RA) induces rapid differentiation of ESCs, partly by activating expression of the transcription factor Hoxa1, which regulates downstream target genes that promote ESCs differentiation. However, mechanisms of RA-induced Hoxa1 expression and ESCs early differentiation remain largely unknown. Here, we identify a distal enhancer interacting with the Hoxa1 locus through a long-range chromatin loop. Enhancer deletion significantly inhibited expression of RA-induced Hoxa1 and endoderm master control genes such as Gata4 and Gata6. Transcriptome analysis revealed that RA-induced early ESCs differentiation was blocked in Hoxa1 enhancer knockout cells, suggesting a requirement for the enhancer. Restoration of Hoxa1 expression partly rescued expression levels of ~40% of genes whose expression changed following enhancer deletion, and ~18% of promoters of those rescued genes were directly bound by Hoxa1. Our data show that a distal enhancer maintains Hoxa1 expression through long-range chromatin loop and that Hoxa1 directly regulates downstream target gene expression and then orchestrates RA-induced early differentiation of ESCs.

overall_design: Deep sequencing of three different state cell lines gene expression and interaction of hoxa1 with the genome.

first: Guangsong

last: Su

first: Wange

last: Lu


title: Efficient induction of Gcm1 under folate deficiency promotes vertebrate neural development by Wnt/β-catenin pathway activation

status: Public on Dec 27 2018

first: Li

last: ting

summary: Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway leads to defective anteroposterior patterning, resulting in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We report here that in C57BL/6C mouse embryonic stem cells (mESC), folate deficiency activates Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promotes the formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex to regulate the Wnt target gene transactivation through the Wnt-responsive elements. Moreover, the enhanced transcriptional activity of Gcm1 is found to be dependent on CREB binding protein. Lastly, in NTDs mouse models and low folate NTDs human brain samples, Gcm1 and Wnt/β-catenin target genes related to neural tube closure are specifically overexpressed. These results indicate that low folate promotes Wnt/β-catenin signaling via activating Gcm1, leading to aberrant vertebrate neural development

overall_design: Examination of 1 transcription factor in 1 cell type with different treatment

first: Jianting

last: Li


title: Next Generation Sequencing Facilitates Quantitative Analysis of  Transcriptomes at LncRNA and mRNA and miRNA levels between Hep2 cells with stable transfection of MYCT1 and non-transfection of MYCT1

status: Public on Dec 04 2018

city: Shenyang

first: Wei-Neng

last: Fu

state: Liaoning Province

address: No. 77 Puhe Road, Shenyang North New Area

department: Medidcal Genetics

institute: China Medical University

summary:
Purpose: To obtain the differentially expressed LncRNA, mRNAs and miRNAs between the two groups of cells.
Results: We identified 174 LncRNAs, 327 mRNAs and 235 miRNAs differentially expressed in MYCT1-overexpressed Hep2 cells compared to the controls.


title: Tissue-specific progesterone receptor-chromatin binding and the regulation of progesterone-dependent gene expression

status: Public on Dec 01 2018

city: Adelaide

first: James

last: Breen

state: SA

address: 108 North Terrace (Ground Floor)

department: John Curtin School of Medical Research

country: Australia

institute: Australian National University

summary: The activity of PGR and H3K27ac in peri-ovulatory mouse granulosa cells was characterized using chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq)

overall_design: 2 PGR ChIPseq replicates were used, along with a H3K27ac sample and pooled input control

first: D

middle: T

last: Dinh

first: Darryl

middle: L

last: Russell


title: RNA profiling of the liver and gut tissues in zebrafish (Danio rerio)

first: Gary

last: Hardiman


title: RNA sequencing of HepG2 cells treated with estradiol or estrogen receptor agonist

status: Public on Dec 10 2018

city: Oxford

first: Haifei

last: Shi

state: OH

address: 700 E High Street

department: Biology

institute: Miami University

summary: We report differential expressed genes in HepG2 cells treated with control, E2, or an ER agonist

overall_design: Methods: HepG2 cells treated with control, E2, PPT, or DPN for 48 hours. mRNA profiles were generated by deep sequencing, in triplicates, using Illumina NextSeq2000 sequencing system.  The sequence reads that passed quality filters were analyzed at the transcript level with DESeq2.

first: Minqian

last: Shen

first: Jingyi

last: Cao


title: NSD2 is a conserved driver of metastatic prostate cancer progression.

city: Hospitalet de Llobregat

first: Alvaro

last: Aytes

state: Catalonia

address: Granvia 199

department: ProCURE

country: Spain

institute: IDIBELL

summary: Analysis of transcriptome of FACS isolated cancer cells from prostate primary tumors and metastasis from NPK GEM models

overall_design:
Prostate tissue or tumor from pre-metastatic; post-metastatic; and lung, liver and lymph node metastasis from Nkx3.1CreERT2/+ ;Ptenflox/flox;KrasLSL-G12D/+ mice  was harvested, and snap frozen for subsequent molecular analysis. Tumors had been induced by tamoxifen (100mg/kg oral gavage) induced recombination at 2 months of age.
Total RNA obtained from prostate tissues or tumors. Prostate tissues or tumors were harvested and processed for RNA isolation and transcriptome analysis using the MagMAX RNA isolation kit (Ambion).

first: Antonina

last: Mitrofanova

first: Arianna

last: Giacobe

first: Cory

last: Abate-Shen


title: Preclinical efficacy of the MTH1 inhibitor karonudib in B-cell lymphoma

city: Oslo

first: Thea

middle: Kristin

last: Vatsveen

address: Ullernschauseen 70

department: Cancer Research

country: Norway

institute: Oslo University Hospital

summary: Although chemo-immunotherapy has greatly improved survival of B-cell lymphoma patients, treatment resistant and refractory disease represent a major challenge that call for development of new treatment options. Karonudib (TH1579) is a new drug developed to inhibit MTH1, an enzyme which prevents oxidized dNTPs from being incorporated into DNA. Here, we tested the efficacy of karonudib in vitro and in preclinical models of B-cell lymphoma. Karonudib reduced viability in a wide range of B-cell lymphoma cell lines at concentrations that were well tolerated by activated normal B cells. Induction of mitotic arrest was seen as early as 6 h after karonudib treatment, with induction of apoptosis detected after 12 h. These effects were observed independent of TP53 mutational status. Increased incorporation of 8-oxo-dGTP into DNA, in addition to arrest in prometaphase due to failure in spindle assembly were detected in cells exposed to karonudib, suggesting a dual inhibitory mechanism. Karonudib inhibited tumor growth, led to complete remission in the majority of cases and prolonged survival in two different xenograft mouse models of aggressive B-cell lymphoma, including an ABC DLBCL patient-derived xenograft model. Karonudib was well tolerated in vivo, and no weight loss was observed in treated animals. NUDT1, the gene encoding MTH1, was upregulated in tumor biopsies from ABC and GCB DLBCL and BL patients, as compared to B cells from healthy donors. Together, our preclinical findings provide a rational for further clinical testing of karonudib in aggressive B-cell lymphoma.

overall_design: The microarray analyses were performed on GeneChip® Human Gene 2.0 ST Array (Affymetrix, Santa Barbara, CA). Two replicates were run per cell line (BL-41 and Mino) with a week apart. Gene set enrichment analysis was performed using the GSEA software v.3.0. combining both cell line data against predicted gene sets (Hallmark datasets) downloaded from the MSigDB collection. A thousand permutations were performed to test against control and karonudib treated cells. Gene sets with false discovery rate (FDR) q values < 0.1 were regarded as significantly enriched gene sets.

first: Morten

middle: P

last: Oksvold

first: Ulrika

middle: W

last: Berglund

first: Helge

last: Gad

first: Baoyan

last: Bai

first: Trond

last: Stokke

first: Idun

last: Rein

first: Therese

last: Pham

first: Geir

last: Øy

first: Jens

middle: H

last: Norum

first: Erlend

last: Smeland

first: June

last: Myklebust

first: Thomas

last: Helleday

last: Våtsveen


title: The morphological and functional differences and similarities of immune cells between non-human primates and humans

status: Public on Nov 28 2018

city: Beijing

first: wang

last: liang

address: 7A North Yongchang Road BDA

institute: BioChainBJ

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

sample_organism:
Macaca fascicularis
Homo sapiens

platform_organism:
Macaca mulatta
Homo sapiens

overall_design: Refer to individual Series


title: MicroRNAomes of cattle intestinal tissues revealed possible miRNA regulated mechanisms involved in Escherichia coli O157 fecal shedding

city: Edmonton

first: Ou

last: Wang

state: AB

address: 410 Agriculture/Forestry Centre, University of Alberta

department: AFNS

country: Canada

institute: University of Alberta

summary: The current study aimed to investigate whether bovine non-coding RNA play a role in regulating E. coli O157 shedding through studying miRNAomes of the whole gastrointestinal tract including duodenum, proximal jejunum, distal jejunum, cecum, spiral colon, descending colon and rectum. The number of miRNAs detected in each intestinal region ranged from 390 ± 13 to 413 ± 49. Compared between SS and NS, the number of differentially expressed (DE) miRNAs ranged from one to eight, and through the whole gut, seven miRNAs were up-regulated and seven were down-regulated in SS. The distal jejunum and rectum were the regions where the most DE miRNAs were identified (8 and 7, respectively). Functional analysis indicated that the bta-miR-378b, bta-miR-2284j and bta-miR-2284d which were down-regulated in both distal jejunum and rectum of SS, the bta-miR-2887 which was down-regulated in rectum of SS, as well as the bta-miR-211 and bta-miR-29d-3p which were up-regulated in rectum of SS were potentially regulatory to host immune functions, including hematological system development and immune cell trafficking. Our findings suggest that the alternation of miRNA expression in the gut of SS may lead to differential regulation in immune functions involved in E. coli O157 super-shedding in cattle.

overall_design: We performed a differential analysis of microRNA expression of intestinal tissues collected from E. coli O157 super-shedders and non-shedders, targets prediction for interested microRNAs, and functional analysis for interested microRNAs, to study molecular mechanisms of super-shedding phenomenon.

first: Leluo

last: Guan


title: The morphological and functional differences and similarities of immune cells between non-human primates and humans [human]

summary: Comparison of the gene expression profiles of human and cynomolgus monkey PBMCs in response to PHA and LPS

overall_design: The peripheral blood monuclear cells (PBMCs) (1×10^6 cells/ml) obtained from the cynomolgus monkeys or the human donors were treated with PHA (2 μg.ml-1 or 10 μg.ml-1) or LPS (2 μg.ml-1 or 10 μg.ml-1) and incubated at 37 °C for 3 days.

first: Zhi

last: Lin

first: Ying

last: Huang

first: Lan

last: Cui

first: Hua

last: Jiang

first: Di

last: Zhang

first: Yan-wei

last: Yang

first: Xing-chao

last: Geng

first: Bo

last: Li


title: Trascriptome profiling of murine Embryonic Stem cells under different culture conditions

status: Public on Nov 21 2018

city: Padua

first: Graziano

last: Martello

address: viale Colombo 3

department: Department of Biology

country: Italy

institute: University of Padua

summary:
Mouse Embryonic Stem (ES) cells have been cultured under chemically defined conditions in the absence of feeder cells on Gelatin coated dishes, for 5 passages under 4 different combinations of LIF and GSK3 or MEK inhibitors. Their trascriptome have been analysed by RNA sequencing.
The ES cell line used, RexGFPd2, contains a destablised GFP protein in the Zfp42/Rex1 locus and was derived under 2i conditions, as described in Kalkan et al. 2017.

overall_design: Examination of transcriptome by RNA sequencing of mES cells under 4 different culture conditions


title: Synergy between variant PRC1 complexes defines Polycomb-mediated gene repression (ChIP-Seq)

status: Public on Apr 26 2019

first: Nadezda

last: Fursova

address: South Parks Rd

department: Department of Biochemistry

country: United Kingdom

institute: University of Oxford

summary: The Polycomb system modifies chromatin and plays an essential role in repressing gene expression to control normal mammalian development. However, the components and mechanisms that define how Polycomb protein complexes achieve this remain enigmatic. Here we use combinatorial genetic perturbation coupled with quantitative genomics to discover the central determinants of Polycomb-mediated gene repression in mouse embryonic stem cells. We demonstrate that canonical Polycomb repressive complex 1 (PRC1), which mediates higher order chromatin structures, contributes little to gene repression. Instead, we uncover an unexpectedly high degree of synergy between variant PRC1 complexes which is fundamental to gene repression. We further demonstrate that variant PRC1 complexes are responsible for distinct pools of H2A monoubiquitylation that are associated with repression of Polycomb target genes and silencing during X-chromosome inactivation. Together, these discoveries reveal a new variant PRC1-dependent logic for Polycomb-mediated gene repression.

sample_organism:
Drosophila melanogaster
Homo sapiens
Mus musculus

overall_design: Mouse embryonic stem cells in which distinct PCGF-containing PRC1 complexes can be conditionally removed individually or in different combinations ( Pcgf4-/-; Pcgf2fl/fl, Pcgf1fl/fl, Pcgf3fl/fl, Pcgf5fl/fl, Pcgf6fl/fl, Pcgf3/5fl/fl, Pcgf1/3/5fl/fl, Pcgf1/3/5/2fl/fl, Pcgf1/3/5/6fl/fl and Ring1a-/-; Ring1bfl/fl) and Mus domesticus (129S1) x Mus castaneus F1 hybrid ESC line with inducible full-length Xist transgene were profiled for PRC1 (H2AK119ub1 and RING1B, as well as subunits specific for distinct PRC1 complexes - PCGF1, PCGF2, CBX7, and PHC1) and PRC2 (H3K27me3 and SUZ12) binding and activity using spike-in calibrated native (histone modifications) or cross-linked ChIP-seq (Polycomb factors).

first: Neil

last: Blackledge

first: Robert

middle: J

last: Klose


title: Expression data in non-tumor liver tissues from Peruvian patients with hepatocellular carcinoma.

status: Public on Aug 29 2018

city: Toulouse

first: Juan Pablo

last: Cerapio

address: Av 2 Hubert Curien

institute: CRCT

summary:
Most hepatocellular carcinomas in younger patients from Peru arise from non-cirrhotic livers. Histological examination of the non-tumor liver tissues highlights the presence of clear cell foci in a significant fraction of Peruvian patients with hepatocellular carcinoma.
We used microarrays to compare gene expression between non-tumor liver tissues with and without clear cell foci and identified ontologies that are distinctively differentially expressed between subsets.

overall_design: Non-tumor liver tissues were obtained from tumour-free margins of resected surgical pieces. Total RNA was isolated from flash-frozen samples for hybridization on Affymetrix microarrays. We selected non-tumour liver tissues according to the presence or the absence of clear cell foci in non-tumor liver parenchyma in formalin-fixed, paraffin-embedded counterpart samples under haematoxylin–eosin staining.

first: Juan

first: Pascal

last: Pineau


title: Molecular Characterization of a Precision-Cut Rat Liver Slice Model for the Evaluation of Anti-Fibrotic Compounds

status: Public on Oct 04 2018

city: Pennington

first: Ron

last: Ammar

state: New Jersey

address: 311 Pennington Rocky Hill Road

institute: Bristol-Myers Squibb

summary: Precision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the anti-fibrotic effect of experimental compounds in a physiologic environment. In this study using RNAquencing we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. The Alk5 inhibitor SB525334, nintedanib and sorafenib each reversed a subset of genes dysregulated in fibrotic PCLSs and of those genes we identified 608 genes whose expression was reversed by all three compounds. These genes define a molecular signature characterizing many aspects of liver fibrosis pathology and its attenuation in the model. A panel of 12 genes and 4 secreted biomarkers including procollagen I, HA, IGFBP5 and WISP1, were further validated as efficacy endpoints for the evaluation of anti-fibrotic activity of experimental compounds. Finally, we showed that blockade of αV integrins with a small molecule inhibitor attenuated the fibrotic phenotype in the model. Overall, our results suggest that the rat fibrotic PCLS model may represent a valuable system for target validation and to determine the efficacy of experimental compounds.

overall_design: Precision-cut liver tissue slices (PCLS) from BDL rats were treated with drug and profiled with RNA-Seq

first: Xinqiang


title: The morphological and functional differences and similarities of immune cells between non-human primates and humans [monkey]

first: wang

last: liang

first: Zhi


title: Detection of internal N7-methylguanosine (m7G) RNA modifications by mutational profiling sequencing

status: Public on Oct 30 2018

city: Copenhagen N

first: Jeppe

last: Vinther

address: Ole Maaloes Vej 5

country: Denmark

institute: University of Copenhagen

summary: Methylation of guanosine on position N7 (m7G) on internal RNA positions have been found in all domains of life and have been implicated in human disease, but m7G modifications has so far only been mapped in a limited number of RNA molecules. Here, we present m7G Mutational Profiling sequencing (m7G-MaP-seq), which allows high throughput detection of m7G modifications. In our method, m7G modified positions are converted to abasic sites by mild reduction, recorded as cDNA mutations through reverse transcription, sequenced and subsequently detected by identification of positions with increased mutation rates in the reduced sample compared to the control. We show that m7G-MaP-seq efficiently detects m7G modifications in rRNA, including a previously uncharacterised rRNA modification in Arabidopsis thaliana. Furthermore, we identify m7G tRNA modifications in budding yeast, human and arabidopsis tRNA and show that m7G modification occurs before tRNA splicing. We do not find any evidence for internal m7G modifications being present in other small RNA, such as miRNA, snoRNA and sRNA. Likewise, high coverage m7G-MaP-seq analysis of mRNA from E. coli or yeast cells failed to identify any internal m7G modifications.

sample_organism:
Escherichia coli
Arabidopsis thaliana
Saccharomyces cerevisiae
Homo sapiens

overall_design: RNA from E. coli (strain BW25113 and RsmG KO), Saccharomyces cerevisiae (BY4741), HeLa, Arabidopsis Thaliana Columbia-0 . The RNA was treated with NaBH4 or mock-treated, then reverse transcribed.

first: Christel

last: Enroth

first: Line

last: Poulsen

first: Søren

last: Iversen

first: Anders

last: Albrechtsen


title: Microarray-based miRNA expression,identified miRNAs that were regulated by KSHV vIRF1

status: Public on Aug 25 2018

city: NANJING

first: WAN

last: LI

state: JIANGSU

address: 101Longmian Avenue

institute: Nanjing Medical University

summary: HUVECs were transduced with lentiviral vIRF1 or control lentivirus (pHAGE),microarray-based miRNA expression profiling was adopted and identified a set of miRNAs that were differentially expressed between vIRF1- and pHAGE-transduced HUVECs

platform_organism:
Homo sapiens
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Macacine alphaherpesvirus 1
Human betaherpesvirus 5
human gammaherpesvirus 4
Herpesvirus saimiri (strain 11)
JC polyomavirus
Human immunodeficiency virus 1
Human betaherpesvirus 6B
Human gammaherpesvirus 8
Merkel cell polyomavirus
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: HUVECs were transduced with lentiviral vIRF1 compared to HUVECs were transduced with control lentivirus (pHAGE)

first: Wan

first: Qingxia

last: Wang

first: Qi

last: Feng

first: Fei

first: Qin

last: Yan

first: Shou-Jiang

last: Gao

first: Chun

last: Lu


title: Pathway analysis identifies altered mitochondrial metabolism, neurotransmission, structural pathways and complement cascade in retina/RPE/choroid in chick model of form-deprivation myopia

status: Public on Jun 05 2018

city: Melbourne

first: Loretta

last: Giummarra

state: Victoria

address: c/o Psychological Science

department: Psychology & Counselling

institute: La Trobe University

summary: Microarray analysis was performed on retina/RPE/choroid samples taken from the right eyes of male chicks across control and recovery from form deprivation conditions.

overall_design: Examination of mRNA levels in individual retina/RPE/choroid samples across 4 groups (control, 7 days form deprivation (FDM), 6 hours recovery and 24 hours recovery from form deprivation (FDMR)). Each group contains 5 samples that were pooled for this study

first: Sheila

last: Crewther

first: Nina

last: Riddell

first: Melanie

last: Murphy

first: David


title: Molecular subgroups of adult medulloblastoma: a long-term single-institution study

status: Public on Jun 26 2018

city: beijing

first: zhao

last: fu

address: No. 6 Tiantan Xili Dongcheng District

institute: Beijing Neurosurgical Institute

summary: Background. Recent transcriptomic approaches have demonstrated that there are at least 4 distinct subgroups in medulloblastoma (MB); however, survival studies of molecular subgroups in adult MB have been inconclusive because of small sample sizes. The aim of this study is to investigate the molecular subgroups in adult MB and identify their clinical and prognostic implications in a large, single-institution cohort.  Methods. We determined gene expression profiles for 13 primary adult MBs. Bioinformatics tools were used to establish distinct molecular subgroups based on the most informative genes in the dataset. Immunohistochemistry with subgroup-specific antibodies was then used for validation within an independent cohort of 201 formalin-fixed MB tumors, in conjunction with a systematic analysis of clinical and histological characteristics.  Results. Three distinct molecular variants of adult MB were identified: the SHH, WNT, and group 4 subgroups. Validation of these subgroups in the 201-tumor cohort by immunohistochemistry identified significant differences in subgroup-specific demographics, histology, and metastatic status. The SHH subgroup accounted for the majority of the tumors (62%), followed by the group 4 subgroup (28%) and the WNT subgroup (10%). Group 4 tumors had significantly worse progression-free and overall survival compared with tumors of the other molecular subtypes.  Conclusions. We have identified 3 subgroups of adult MB, characterized by distinct expression profiles, clinical features, pathological features, and prognosis. Clinical variables incorporated with molecular subgroup are more significantly informative for predicting adult patient outcome.

overall_design: The Agilent Whole Human Genome Oligo Microarray Kit, 4×44K (Gene Expression Omnibus accession no. GPL6480) was used for gene expression profiling of the samples (n ¼ 13). Data  were extracted with Feature Extraction Software v10.7 (Agilent Technologies). Raw data were normalized by Quantile algorithm,Gene Spring Software v11.0 (Agilent Technologies).  Genes with a fold change ≥2 and P,.05 were selected for further analysis. Pathway annotation was performed by Ingenuity Systems.

first: Fu

last: Zhao

first: Hiroko

last: Ohgaki

first: Lei

last: Xu

first: Felice

last: Giangaspero

first: Chunde

last: Li

first: Peng

first: Zhijun

last: Yang

first: Bo

first: Xingchao

first: Zhenmin

first: Lin

last: Ai

first: Jing

last: Zhang

last: Luo

first: Pinan

last: Liu


title: Differentially expressed lncRNAs and mRNAs in the adipose tissue between cancer associated cachexia mice and normal mice

status: Public on Aug 16 2018

city: Shanghai

first: LEI

last: SHEN

state: State...

address: Feng lin road 180

department: Department of General Surgery

institute: Zhongshan Hospital, Fudan University

summary: Cancer associated cachexia (CAC) causes white adipose tissue (WAT) lose by inhibiting adipogenesis, and promoting lipolysis, fat oxidation and browning. To uncover the specific lncRNAs and mRNAs involved in these processes, we used RNA microarray to identify the transcriptomes and found numerous lncRNAs and mRNAs differentially expressed in the fat tissue between CAC and normal mice.

overall_design: Colon-26 adenocarcinoma (C26) cells were subcutaneously inoculated into the flank of 6 syngeneic BALB/c mice to build cancer associated cachexia mice models. As a control group, 6 non-tumor-bearing littermate mice received the vehicle (PBS) only. All mice were euthanized at day 21 and dissected to harvest adipose tissue. To identify lncRNAs and mRNAs selectively involved in adipose wasting of cancer associated cachexia, inguinal white adipose tissue  were analyzed by microarray assay.

last: Shen


title: Fine-tuning Mybl2 levels are required for proper MET process during somatic reprogramming

status: Public on Jul 17 2018

city: Birmingham

first: Carl

last: Ward

address: Edgbaston

institute: University of Birmingham


title: Tissue and host species specific trasncriptional changes in models of experimental visceral leishmaniasis

status: Public on Apr 20 2018

city: York

first: Paul

last: Kaye

address: Wentworth way

institute: University of York

summary: Transcriptomic and immunopathology analysis on infection of mice with visceral leishmaniasis and a comparison of murine infection compared to hamster

overall_design: Spleen, liver and blood samples were taken at days 15,17,36 and 42 and transcriptionally profiled using a minimum of 4 mice for naïve, and 5 mice for infected factors

first: Helen

last: Ashwin

first: Sandy

last: MacDonald

first: Karin

last: Seifert

first: Sarah

last: Forrester

first: Najmeeyah

last: Brown

first: Sally

last: James

first: Dimitris

last: Lagos

first: Jon

last: Timmis

first: Jeremy

last: Mottram

first: Simon

last: Croft


title: YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer

status: Public on Dec 31 2017

city: Tokyo

first: Izumi

last: Suzuki

state: 東京都

address: 2-1-1 Hongo Bunkyo-ku

country: Japan

institute: Juntendo University

summary: We aimed to clarify the function of YBX2, a germ cell-specific Y-box-binding protein, in endometrial cancer stem cells. Our data demonstrated that expression of YBX2 was essential for a stem cell-like phenotype of endometrial cancer cells. We analyzed enhanced gene expression of IK cells that overexpressed YBX2 (IK-YBX2 cells) by introduction of YBX2 using microarray analysis. The CT45A5 gene was the most upregulated in IK-YBX2 cells, compared with mock cells. Therefore, we focused on CT45A5, which is considered a stemness factor.

overall_design: We analyzed enhanced gene expression of IK-YBX2 cells and mock cells by introduction of YBX2. Microarray analysis was performed by CERI customer service (Saitama, Japan) in accordance with the instructions for One-Color Microarray-Based Gene Expression Analysis, ver 6.0.

first: Sachiko

last: Yoshida

first: Kouichi

last: Tabu

first: Soshi

last: Kusunoki

first: Yumiko

last: Matsumura

first: Hiroto

last: Izumi

first: Kazuo

last: Asanoma

first: Hiroshi

last: Yagi

first: Ichiro

last: Onoyama

first: Kenzo

last: Sonoda

first: Kimitoshi

last: Kohno

first: Tetsuya

last: Taga

first: Atsuo

last: Itakura

first: Satoru

last: Takeda

first: Kiyoko

last: Kato


title: CytoScan HD array data for a patient with Vitamin D deficiency

status: Public on Mar 21 2018

city: Vancouver

first: Lindsay

last: Brown

address: 4480 Oak St

institute: BC Children's and Woman's Health Centre of BC

type: Genome variation profiling by genome tiling array

summary: Chromosome microarray (CMA) was performed to identify a possible CNV or ROH that could be contributing to this patient's clinical phenotype.

overall_design: CytoScan HD arrays were performed according to the manufacturer's directions on DNA extracted from a blood sample. Copy number and ROH analysis was performed using the ChAS software.

first: Julien

last: Marcadier


title: The histone acetyl-tranferase MOF is required for metabolic function in the liver .

status: Public on Jan 31 2018

city: Ann Arbor

first: Aaron

middle: David

last: denDekker

state: MI

address: 1301 Catherine Street

department: Pathology

institute: University of Michigan

summary:
Purpose: Conditional MOF deletion in mouse livers resulted in acute hepatic necrosis.  The goal of this study was to identify transcriptomic changes in the livers of MOF-depeleted mice livers compared to WT.
Methods: Transcriptomic profiles of MOF∆ and WT mouse livers were generated in triplicate.  Sequenced reads were quality filtered using Trimmomatic.  Quality reads were aligned to the mouse genome using TopHat2.  Reads were counted using htseq-count and differentially expressed transcripts were identified using DESeq.
Results: 1408 differentially expressed genes were identified between MOF∆ and WT livers.  774 genes were down-regulated in MOF∆ and primarilly associated with metabolic pathways. Branched chain amino acid and fatty acid metabolic pathways, which are deregulated in non-alcoholic fattly liver disease (NAFLD) prgression were down-regulated. 664 genes were upregulated and associated with increased proliferation.
Conclusions: These data show that MOF is required for maintaining proper metabolic function in the liver and deregulation of MOF may be involved in progression of NAFLD.

overall_design: Liver mRNA profiles of 6-8 week old  old wild type (WT) and MOF∆ mice were generated by deep sequencing, in triplicate, using the Illumina HiSeq 4000 platform.

first: Yali

last: Dou


title: Emi2 is essential for mouse spermatogenesis

status: Public on Dec 01 2017

city: Singapore

first: Diana

middle: HP

last: Low

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

country: Singapore

institute: Institute of Molecular and Cell Biology

summary: Analysis of wildtype and Emi2 knockout testis at various timepoints

overall_design: Total testis obtained at p15,p21,p30 and p60

first: Lakshmi

last: Gopinathan


title: Comparative Transcriptomics of Triple Negative Breast Cancer Stem Cells and Differentiated Tumor Cells Identifies Teneurin-4 as a Potential Therapeutic Target

status: Public on Jan 30 2018

city: Torino

first: Raffaele

last: Calogero

state: To

address: Via Nizza 52

department: Molecular Biotechnology Center

institute: University of Torino

summary: BACKGROUND: Triple-negative breast cancer (TNBC) is insensitive to the most effective therapies for other breast cancers, including endocrine and Her2-directed therapies, thus the lack of specific treatments prompted us to search for new TNBC-associated molecules to be used as targets for cancer therapy. As patients with TNBC usually experience a quicker relapse and metastatic progression compared to other breast cancer subtypes, we hypothesized that cancer stem cells (CSC) could play a central role in TNBC. We thus directed our focus on genes differentially expressed between CSC and differentiated cancer cells of TNBC cell lines. RESULTS: We established tumorsphere cultures from mouse and human mammary cancer cell lines to enrich the CSC population. RNA-Seq was used to identify differences in gene expression between tumorspheres and their monolayer counterparts. Seventy-four transcripts were found up-regulated in the tumorspheres, while forty-two genes were down-regulated. Enrichment analysis of biological processes showed an up-regulation in genes involved in regulation of apoptosis in tumorspheres, and a down-regulation in genes involved in lipid metabolism and cell cycle regulation. By focusing on up-regulated genes coding for cell membrane-associated proteins, we selected Teneurin-4 (TENM4) as a candidate for further studies. Meta-analysis of publicly available datasets revealed that TENM4 mRNA is up-regulated in both lobular and ductal invasive carcinoma specimens compared to normal breast, and that high expression of TENM4 in TNBC patients shows a trend of correlation with a shorter relapse-free survival. 4T1 tumorspheres treated with a siRNA specific to TENM4 showed a decrease in TENM4 mRNA and protein levels, which was reflected by a significant impairment of tumorsphere-forming ability. TENM4 silencing also led to a decrease in Focal Adhesion Kinase (FAK) phosphorylation, which has been previously linked to CSC biology, thus strengthening the possible link between TENM4 and a CSC-like phenotype. CONCLUSIONS: Overall, our results indicate that the stem-like status of TNBC cells is accompanied by altered regulation of apoptosis, cell cycle and lipid metabolism pathways. Furthermore, we identified TENM4 as a potential novel player in CSC biology, and its potential role as a novel target to improve the outcome of TNBC patients in the future.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: 4T1 and HCC1806 cell lines as model for TNBC in mouse and human, respectively. Based on culture conditions previously established for these and other breast cancer cell lines, we successfully generated tumorspheres from the parental cells. For both cell lines three replicates were done for the cell grown in RPMI-1640 supplemented with 10% fetal bovine serum (FBS, Sigma-Aldrich) and Penicillin/Streptomycin solution at 1x dilution (Sigma-Aldrich) (bulk), and those grown in DMEM/Nutrient Mixture F-12 Ham (Sigma-Aldrich) supplemented with 0.4% bovine serum albumin (BSA, Sigma-Aldrich), 20 ng/mL bFGF (PeproTech EC Ltd., London, UK), 20 ng/mL EGF (Sigma-Aldrich) and 5 µg/mL insulin (Sigma-Aldrich).  (spheroids)

first: Roberto

last: Ruiu

first: Maddalena

last: Arigoni

first: Federica

last: Riccardo

first: Laura

last: Conti

first: Stefania

last: Lanzardo

last: Adolfo Calogero

first: Irene

last: Fiore Merighi

last: Cavallo

first: Elena

last: Quaglino


title: Ionizing radiation induces transgenerational effects of DNA methylation in zebrafish

status: Public on Dec 08 2017

city: Olso

first: Jorke

last: Kamstra

address: Ullevålsveien 72

department: Basic Sciences and Aquatic Medicine

institute: Norwegian University of Life Sciences

type: Methylation profiling by high throughput sequencing

summary: Ionizing radiation is known to cause DNA damage, yet the mechanisms underlying potential transgenerational effects of exposure have been scarcely studied. Previously, we observed effects in offspring of zebrafish exposed to gamma radiation during gametogenesis. Here, we hypothesize that these effects are accompanied by changes of DNA methylation possibly inherited by subsequent generations. We assessed DNA methylation in F1 embryos (5.5 hours post fertilization) with whole genome bisulfite sequencing following parental exposure to 8.7 mGy/h for 27 days and found 5658 differentially methylated regions (DMRs). DMRs were predominantly located at known regulatory regions, such as gene promoters and enhancers. Pathway analysis indicated the involvement of DMRs related to similar pathways found with gene expression analysis, such as development, apoptosis and cancers, which could be linked to previous observed developmental defects and genomic instability in the offspring. Follow up of 19 F1 DMRs in F2 and F3 embryos revealed persistent effects up to the F3 generation at 5 regions. These results indicate that ionizing radiation related effects in offspring can be linked to DNA methylation changes that partly can persist over generations. Monitoring DNA methylation could serve as a biomarker to provide an indication of ancestral exposures to ionizing radiation.

overall_design:
6 WGBS samples, 3x F1 Controls and 3x F1 8.7 mGy/h exposed
35 BisPCR2 samples, From F1, F2 and F3 (5x F1 Controls and 5x F1 Exposed), Control DNA (0,25, 50, 75, 100 % methylated)

first: Selma

last: Hurem

first: Leonardo

middle: M

last: Martin

first: Leif

middle: C

last: Lindeman

first: Juliette

last: Legler

first: Deborah

last: Oughton

first: Brit

last: Salbu

first: Jan

last: Lyche

first: Peter

last: Aleström


title: Parental exposure to gamma radiation causes progressively altered transcriptomes that are linked to adverse effects in zebrafish offspring

status: Public on Nov 05 2017

city: Oslo

middle: Martin

department: Basic Sicences and Aquatic medicine

summary: In zebrafish, parental exposure to ionizing radiation has been associated with effects in offspring, such as increased DNA damage and reactive oxygen species. Here, we assessed short (one month) and long term effects (one year) on gene expression in embryonic offspring (5.5 hours post fertilization) from zebrafish exposed during gametogenesis to gamma radiation (8.7 or 53 mGy/h for 27 days, total dose 5.2 or 31 Gy). One month after exposure, a global change in gene expression was observed in offspring from the 53 mGy/h group, followed by embryonic death at late gastrula, whereas offspring from the 8.7 mGy/h group was unaffected. One year after exposure, embryos from the 8.7 mGy/h group exhibited 2455(61.8% downregulated) differentially expressed genes. Overlaps in differentially expressed genes and enriched biological pathways were evident between the 53 mGy/h group one month and 8.7 mGy/h one year after exposure, which could be linked to effects in adults and offspring, such as DNA damage and lipid peroxidation. Interestingly, pathways between the two groups were oppositely regulated. Our results indicate latent effects following ionizing radiation exposure in parents that can be transmitted  to offspring and warrants monitoring effects over subsequent generations.

overall_design: One month after exposure, mRNA from F1 5.5 hpf embryos from parents exposed to 8.7 and 53 mGy/h gamma radiation during gametogenesis was sequenced on the Illumina 4000 platform with three replicas per treatment. One year after exposure, mRNA from F1 embryos from the same parents exposed to 8.7 mGy/h was sequenced with three biological replicates. In both cases, F1 embryos from non-exposed parents were used as control and mRNA sequenced in triplicates, taken at the same time points as the exposed samples.

first: Dag

last: Anders Brede


title: Down-regulation of the TGF-b pseudoreceptor BAMBI enhances TGF-b signaling and promotes invasion of Non-Small Lung Cancer: DNA methylation analysis

status: Public on Nov 30 2017

city: Ulm

first: Ole

last: Ammerpohl

address: Albert-Einstein-Allee 11

institute: UK Ulm

type: Methylation profiling by genome tiling array

summary: Genome wide DNA methylation profiling of lung cancer tissue samples and corresponding normal lung tissue samples of 40 patients. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 480,000 CpGs. Samples included 40 normal lung tissue samples and 40 lung cancer samples.

overall_design: Bisulphite converted DNA from the 80 samples were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

first: O

first: T

last: Goldmann


title: Comparision of La-RNA-binding between wild type La and sumoylation deficient La mutant (K41/200R) in HEK293 cells.

status: Public on Nov 22 2017

city: Charleston

first: Gary

last: Hardiman

address: 135 Cannon Street

department: Medicine

institute: Medical University of South Carolina

summary: We performed a RNA immunoprecipitations experiments using gfp-specific antibodies to precipitate gfp-tagged La proteins from from gfp-La wild type and sumoylation deficient La mutant (K41/200R) cells and found that specific mRNAs are preferentially enriched gfp-La wild type  RIPs when compared to sumoylation deficient La mutant (K41/200R) RIPs.

overall_design: Evaluate role of La-sumoylation in cellular physiology.

first: Tilman

last: Heise


title: Genome-wide transcriptional responses to Deepwater Horizon oil in red drum (Sciaenops ocellatus) embryos and larvae

status: Public on Nov 14 2017

summary:
Purpose:To investigate the transcriptomic profiles in red drum embryos reflective of the DWH oil toxicity at different critical windows of development and to predict the most impacted biological processes and pathways based on differentially expressed gene transcripts at different developmental stages using High Throughput Sequencing (HTS).
Methods:Total mRNA profiles of 24, 48, 72 hpf red drum larvae after slick and source oil exposure were generated by deep sequencing, in triplicate, using Illumina HiSeq2500.
Results:Oil type-dependent transcriptional effects were observed, with more significant by source oil exposure at 24 and 48 h, and similar responses by source and slick at 72 hpf. Informatic analyses indicated source oil exposure started significant perturbation in metabolism, AhR, visual, and cardiac-associated genes as early as 24 hpf.  Both source and slick oil significantly affected EIF2 pathway, nervous and cardiovascular systems from 48 hpf to 72 hpf.

first: Elvis

middle: B

last: Xu

first: Alexis

last: Khursigara

first: Andrew

last: Esbaugh

first: Edward

middle: S

last: Hazard

first: Daniel

last: Schlenk


title: RNA-seq of B16-F10 cells cultured on the ECM of SMCs treated with siRNA and B16-F10 tumor conditioned media

status: Public on Sep 19 2017

city: Bethesda

first: Rosandra

middle: N

last: Kaplan

state: Maryland

address: 10 Center Drive

department: Pediatric Oncology Branch

institute: National Institute of Health

summary: The objective of this study was to profile B16-F10 cells grown in vitro on the extracelllular matrix generated by SMCs treated with siRNA and conditioned media

overall_design: RNA was isolated from two media treatment groups and four siRNA treatment groups

first: Meera

last: Murgai


title: The plasticizer Bisphenol A favors cancer progression in adult zebrafish by perturbing the epigenome: A systems level analysis of the miRNome (miRNA).

status: Public on Oct 16 2017

state: SC

summary: Exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs, are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops disease that resembles human cancer. Using zebrafish as systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 3 week exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6,188 mRNAs and 15 miRNAs were differently expressed (q ≤ 0.1). By analyzing human orthologs of the DE zebrafish genes, signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome in adult zebrafish and has the potential to cause adverse outcomes including cancer.

overall_design: Examination of miRNome changes in an in vivo model organism exposed to a common, environmental compound.

first: Renaud

last: Ludivine


title: The plasticizer Bisphenol A favors cancer progression in adult zebrafish by perturbing the epigenome: A systems level analysis of the miRNome (mRNA).

summary: Exposure to bisphenol A (BPA), an endocrine disruptor (ED), has raised concerns for both human and ecosystem health. Epigenetic factors, including microRNAs, are key regulators of gene expression during cancer. The effect of BPA exposure on the zebrafish epigenome remains poorly characterized. Zebrafish represents an excellent model to study cancer as the organism develops disease that resembles human cancer. Using zebrafish as systems toxicology model, we hypothesized that chronic BPA-exposure impacts the miRNome in adult zebrafish and establishes an epigenome more susceptible to cancer development. After a 21 day exposure to 100 nM BPA, RNA from the liver was extracted to perform high throughput mRNA and miRNA sequencing. Differential expression (DE) analyses comparing BPA-exposed to control specimens were performed using established bioinformatics pipelines. In the BPA-exposed liver, 6,188 mRNAs and 15 miRNAs were differently expressed (q ≤ 0.1). By analyzing human orthologs of the DE zebrafish genes signatures associated with non-alcoholic fatty liver disease (NAFLD), oxidative phosphorylation, mitochondrial dysfunction and cell cycle were uncovered. Chronic exposure to BPA has a significant impact on the liver miRNome in adult zebrafish and has the potential to cause adverse outcomes including cancer.

overall_design: Examination of transcriptome changes in an in vivo model organism exposed to a common, environmental compound.


title: Gene expression of human bone marrow granulocytic differentiation stages

status: Public on Aug 21 2017

city: Frankfurt

first: Jan-Henning

last: Klusmann

address: Theodor-Stern-Kai 7

department: Pediatric Hematology and Oncology

institute: Goehte University Frankfurt

summary: Long non-coding RNAs (lncRNAs) and miRNAs have emerged as crucial regulators of gene expression and cell fate decisions. Here we present an integrated analysis of the ncRNA-landscape of purified human hematopoietic stem cells (HSCs) and their differentiated progenies, including granulocytes, monocytes, T-cells, NK-cells, B-cells, megakaryocytes and erythroid precursors. For each blood cell population, RNA from 5 healthy donors was hybridized onto three microarray platforms (Arraystar lncRNA V2.0, NCode™-miRNA/-ncRNA), yielding a coverage of more than 40,000 lncRNAs, 25,000 mRNAs and 900 miRNAs on 146 arrays. T-distributed stochastic neighbor embedding (t-SNE) on noncoding genes structured the dataset into groups of samples that matched the input populations, demonstrating their unique lncRNA expression profiles. Self-organizing maps (SOMs) revealed clusters of lncRNAs and mRNAs that were coordinately expressed in HSCs and during lineage commitment. Using a “guilt-by-association” approach we assigned putative functions to lncRNAs regulated during differentiation, which predicted LINC00173 as a novel non-coding regulator of granulopoiesis. We knocked down LINC00173 using two independent shRNA constructs, which resulted in diminished granulocytic in vitro differentiation, myeloid colony-formation and function. Next, we uncovered a strong and highly coordinated upregulation of miRNAs, small nucleolar RNAs (snoRNAs) and lncRNAs  within the DLK1-DIO3 locus on chromosome 14 (hsa14) during megakaryocytic maturation.  shRNA-mediated knock-down of noncoding members of the locus reduced erythroid colony-formation and megakaryocytic cell proliferation in vitro implicating the functional importance of this ncRNA locus in megakaryopoiesis. This series only contains the RNAseq data obtained from successive stages of human granulocytic differentiation (myeloblasts, promyelocytes, metamyelocytes and neutrophils) which was obtained to validate the differentiation-dependent expression of LINC00173 in human granulopoiesis. To access the microarray data see GSE98633 and GSE98791.

overall_design: Myeloblasts/promyelocytes (n=4), metamyelocytes (n=3) and neutrophils (n=2) from healthy donor bone marrow were FACS-purified, prepped (Illumina TruSeq stranded) and sequenced on an Illumina HiSeq.

first: Adrian

last: Schwarzer

first: Sarah

last: Grasedieck

first: Mojca

last: Jongen-Lavrencic

first: Florian

last: Kuchenbauer


title: SYSTEMS ANALYSIS OF THE LIVER TRANSCRIPTOME IN ADULT MALE ZEBRAFISH EXPOSED TO THE PLASTICIZER (2-ETHYLHEXYL) PHTHALATE (DEHP).

status: Public on Feb 13 2018

summary: We report the effects of exposure to the endocrine disurptor (2-ethylhexyl) phthalate (DEHP) on transcriptome modification in the livers of  in vivo Zebrafish. Our data indicate changes in fatty acid metabolism and insulin resistance, pathways associated with the development of Non-Alcoholic Fatty Liver Disease (NAFLD).

first: Matthew

last: Huff


title: Ribosome profiling and RNA sequencing of MCF10A cells treated with TGFb

status: Public on Jul 27 2017

city: Amsterdam

first: Koos

last: Rooijers

address: Plesmanlaan 121

department: Gene Regulation

country: Netherlands

institute: Netherlands Cancer Institute

summary: MCF10A were either untreated or treated with TGFb. RNA sequencing and ribosome profiling was performed.

overall_design: Ribosome profiling on 3 biological replicates and matching RNA sequencing on one of the replicates.

first: Fabricio

last: Loayza-Puch

first: Jelle

last: Zijlstra

first: Joachim

last: Oude Vrielink

first: Rui

last: Lopes

first: Alejandro

last: Ugalde

first: Axel

last: Bex

first: Reuven

last: Agami


title: Knockdown and overexpression of SLC3A2 in MCF10A cells

summary: To knock down SLC3A2, MCF10A cells were either transfected with control siRNAs, or siRNAs specifically targetting SLC3A2. Samples were either untreated or treated with TGFb. Ribosome profiling and RNA sequencing was performed on these samples. MCF10A cells with and without SLC3A2 overexpression construct were either untreated or treated with TGFb. Ribosome profiling was performed on these samples.

overall_design: 1 biological replicate of each condition.


title: cGAS surveillance of micronuclei links genome instability to innate immunity

status: Public on Jul 24 2017

city: Stanford

first: Vittorio

last: Sebastiano

state: California

address: 265 Campus Drive

department: OB-GYN/Reproductive, Perinatal and Stem Cell Biology Research

institute: Stanford University

summary: DNA is strictly compartmentalised within the nucleus to prevent autoimmunity despite this cGAS, a cytosolic sensor of dsDNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localises to micronuclei arising from genome instability in a model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. These micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by their own nuclear membrane. Breakdown of the micronuclear envelope, a process associated with chromothripsis, leads to rapid accumulation of cGAS, providing a mechanism by which self-DNA becomes exposed to the cytosol. cGAS binds to and is activated by chromatin and consistent with a mitotic origin, micronuclei formation and the proinflammatory response following DNA-damage are cell-cycle dependent. Furthermore, by combining live-cell laser microdissection with single cell transcriptomics, we establish that induction of interferon stimulated gene expression occurs in micronucleated cells. We therefore conclude that micronuclei represent an important source of immunostimulatory DNA. As micronuclei formed from lagging chromosomes also activate this pathway, cGAS recognition of micronuclei may act as a cell-intrinsic immune surveillance mechanism detecting a range of neoplasia-inducing processes.

overall_design: RNA-seq of 35 individual mouse embryonic fibroblasts 48 h after 1 Gy irradiation: 21 test (with micronuclei) and 14 controls (without micronuclei).

first: Martin

middle: A

last: Reijns

first: Daniel

last: Simpson

first: Nelly

last: Olova

first: Ann

last: Wheeler

first: Andrew

last: Jackson

first: Tamir

last: Chandra


title: Ribosome profiling of MCF10A cells treated with TGFb and esterified leucine

summary: MCF10A-inducible RASV12 cells were treated with TGF-beta for 48hr. As rescue experiment, in one sample cells were treated with esterified leucine for 18hr.

overall_design: 1 replicate per condition

middle: F


title: CDK4/6 inhibitor resistance in prostate cancer

status: Public on May 31 2018

first: Gary

last: Hardiman

summary: CDK4/6 kinase inhibitors have shown great promise in clinical trials in various cancer types and have recently entered clinical trial for advanced prostate cancer. Although patients are expected to respond well to this class of drugs, development of resistance in some patients is anticipated. To pre-empt this and study how prostate cancer may evade CDK4/6 inhibition, new resistance models were generated from LNCaP and LAPC4 prostate cancer cells cells by prolonged culturing in presence of 0.5uM palbociclib. RNA sequencing data was integrated with phospho-proteomics to unravel the molecular underpinnings of acquired resistance to palbociclib and resultant broad CDK4/6 inhibitor resistance.

overall_design: Thirty total sample: three biological replicates of vehicle control and PD treated parental and Palbociclib (PD) resistant cells (PDR) that were generated from LAPC4 and LNCaP cells.

first: Rene

last: de Leeuw

first: Chris

last: McNair

last: Schiewer

first: Neermala

last: Neupane

first: Michael

last: Augello

first: Zhen

last: Li

first: Larry

last: Cheng

first: Justin

last: Drake

first: Akihiro

last: Yoshida

first: J

last: Diehl

first: Sean

last: Courtney

first: E

last: Hazard

middle: T

first: Maha

last: Hussain

first: W

middle: K

last: Kelly

first: Karen

middle: E

last: Knudsen


title: Ribosome profiling of TGFb-treated cells indicates reduced leucine availability

first: Koos

last: Rooijers

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

overall_design: Refer to individual Series


title: The cohesin release factor WAPL restricts chromatin loop extension. [HiC-Seq]

status: Public on May 03 2017

city: Utrecht

first: Robin H.

last: van der Weide

state: Utrecht

address: Uppsalalaan 8

institute: Hubrecht Institute

summary: The spatial organization of chromosomes influences many nuclear processes including gene expression. The cohesin complex shapes the 3D genome by looping together CTCF sites along chromosomes. We show here that chromatin loop size can be increased, and that the duration with which cohesin embraces DNA determines the degree to which loops are enlarged. Cohesin’s DNA release factor WAPL restricts the degree of this loop extension and also prevents looping between incorrectly oriented CTCF sites. We reveal that the SCC2/SCC4 complex promotes the extension of chromatin loops and the formation of topologically associated domains (TADs). Our data support the model that cohesin structures chromosomes through the processive enlargement of loops and that TADs reflect polyclonal collections of loops in the making. Finally, we find that whereas cohesin promotes chromosomal looping, it rather limits nuclear compartmentalization. We conclude that the balanced activity of SCC2/SCC4 and WAPL enables cohesin to correctly structure chromosomes.

overall_design: Hi-C was performed in control, ΔWAPL HAP1 , ΔSCC4 and ΔWAPL/ΔSCC4cells with template replicates. Hi-C was also performed in a ΔWAPL HAP1 biological replicate.

first: Robin

first: Elzo

last: de Wit


title: The Dynamic Epigenetic Landscape of the Retina During Development, Reprogramming, and Tumorigenesis [RNA-Seq_Mm]

city: Memphis

first: Beisi

last: Xu

state: Tennessee

address: 262 Danny Thomas Pl

department: Center for Applied Bioinformatics

institute: St Jude Children's Research Hosipital

summary: In the developing retina, as in many other regions of the central nervous system, multipotent neural progenitor cells undergo unidirectional changes to produce differentiated cells in a precise spatiotemporal order. Here we profile the epigenetic and transcriptional changes that occur during retinal development in mice and humans. Although some progenitor genes and cell cycle genes were epigenetically silenced during retinogenesis, the most dramatic change was derepression of cell type–specific differentiation programs. We identified developmental stage–specific superenhancers and showed that the majority of epigenetic changes during murine retinal development are conserved in the human retina. To determine how the epigenome changes during tumorigenesis and reprogramming, we performed the same integrated epigenetic analysis of murine and human retinoblastomas and iPSCs derived from murine rod photoreceptors.  The retinoblastoma epigenome mapped to the developmental stage when retinal progenitors switch from a neurogenic to a terminal pattern of cell division and murine retinoblastomas initiate earlier in development than human tumors. The epigenome of retinoblastomas was far more similar to that of normal retina than was the epigenome of retinal-derived iPSCs but we were able to identify retinal specific epigenetic memory. Together, these data provide an in depth view of the dynamic epigenome during neurogenesis and how that relates to developmental tumors and epigenetic memory in iPSCs produced from neurons.

overall_design: Examination of 8 different histone modifications and 3 transcription factors, transcriptome, DNA methylation in 23 cell types

first: Issam

last: Aldiri

first: Lu

last: Wang

first: Xiang

last: Chen

first: Daniel

last: Hiler

first: Lyra

last: Griffiths

first: Marc

last: Valentine

first: Abbas

last: Shirinifard

first: Marie-Elizabeth

last: Barabas

first: Jiakun

last: Zhang

first: Dianna

last: Johnson

first: Sharon

last: Frase

first: John

last: Easton

first: Jinghui

first: Elaine

middle: R

last: Mardis

first: Richard

last: Wilson

first: James

last: Downing

last: Dyer


title: Expression profiling of Chromochloris zofingiensis to characterize transcriptome and response to high light

status: Public on Apr 28 2017

city: Berkeley

first: Sean

middle: D.

last: Gallaher

address: 176 Stanley Hall, room 408

department: California Institute for Quantitative Biosciences

institute: UC Berkeley


title: RNA-seqanalysis of deinococcus wild-type and mazEF mutant strains after MMC treatment

status: Public on Apr 11 2017

city: Hangzhou

first: Tao

last: Li

state: Zhejiang

address: Kaixuan road

department: Institute of Nuclear-Agricultural Sciences

country: China

institute: zhejiang university

summary: RNA-seq was used to analysis of mazEF toxin-antitoxin system mediated post-transcriptional inhibition through its endoribonuclease activity. DNA damage agents ,such as MMC, activates the mazEF system leading to cells growth arrest. In the present study, results reveal that a larger number of genes involved in amino acid and carbohydrate metabolism, ion transport and transcription was down-regulated in the wild-type compared with the mazEF-dr mutant.

overall_design: Total RNAs were extrated from wild-type deinococcus radiodurans and mazEF mutant strain with or without MMC treatment.

first: Bing

last: Tian


title: Analysis of genetically diverse macrophages reveals local and domain-wide mechanisms that control transcription factor binding and function

status: Public on May 17 2018

city: La Jolla

first: Christopher

last: Glass

state: CA

address: 9500 Gilman Dr.

department: CMM

institute: University of California, San Diego

summary: Non-coding genetic variation is a major driver of phenotypic diversity and allows investigation of mechanisms that control gene expression. Here, we systematically investigated the effects of >50 million variations from five strains of mice on mRNA, nascent transcription, transcription start sites and transcription factor binding in resting and activated macrophages. We observed substantial differences associated with distinct molecular pathways. Evaluation of genetic variation provided evidence for roles of ~100 TFs in shaping lineage-determining factor binding. Unexpectedly, a substantial fraction of strain-specific factor binding could not be explained by local mutations. Integration of genomic features with chromatin interaction data provided evidence for hundreds of connected cis-regulatory domains associated with differences in transcription factor binding and gene expression. This system and the >250 data sets establish a substantial new resource for investigation of how genetic variation affects cellular phenotypes.

overall_design:
5'GRO-Seq, GRO-Seq, ATAC-Seq, ChIP-seq, RNA-seq, Bisulfite-Seq, Hi-C and PLAC-Seq for diverse strains of mice: BALB/cJ, C57BL/6J, C57BL/6J x PWK/PhJ, C57BL/6J x SPRET/EiJ, NOD/ShiLtJ, PWK/PhJ, SPRET/EiJ

Several  of the Input samples have been used for multiple ChIP samples. Please see 'description' field for a list of the ChIP samples associated with the input sample.

first: Verena

last: Link


title: The cohesin release factor WAPL restricts chromatin loop extension.

first: Robin H.

last: van der Weide


title: Expression data from TGRL lipolysis products treated human brain microvascular endothelial cells

status: Public on Jan 23 2017

city: Davis

first: Hnin

middle: H

last: Aung

address: 451 E Health Science Dr., GBSF 5404

department: Internal Medicine

institute: University of California, Davis

summary:
Lipotoxicity is a metabolic disorder that results from accumulation of lipids, particularly fatty acids, in non-adipose tissue leading to cellular dysfunction, lipid droplet formation, and cell death. Our studies indicate for the first time that the neurovascular circulation also can manifest lipotoxicity, which could have major effects on cognitive function. The penetration of integrative systems biology approaches is limited in this area of research, which reduces our capacity to gain an objective insight into the signal transduction and regulation dynamics at a systems level.
We used microarrays to determine the TGRL lipolysis products induced gene expression and to understand the mechanism underline the vascular inflammation.

overall_design: Total RNA was isolated from human brain microvascular endothelial cells treated with media (M), Lipoprotein lipase (L), triglyceride-rich lipoprotein (TGRL or T), or  TGRL lipolysis products (TL) treatment. Affymetrix microarrays analyses of the pooled total RNA samples (n = 3 per group for Media, LpL, TGRL, and TGRL lipolysis products treatments) were performed.

first: Athanasios

last: Tsoukalas

last: Rutledge

first: Ilias

last: Tagkopoulos


title: The CCR4-NOT complex contributes to repression of Major Histocompatibility Complex class II transcription

status: Public on Mar 15 2017

city: Giessen

first: Jochen

last: Wilhelm

state: Hessen

address: Aulweg 132

department: Institute for Lung Health

institute: Justus-Liebig University Giessen

summary: The multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Accordingly, members of the CCR4-NOT complex have been implicated in a variety of biological functions. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) target genes which are found in a gene cluster on chromosome 6. Increased expression of MHC II genes after knock-down or knock-out of CNOT subunits was seen in a variety of cell systems and also in naïve macrophages from CNOT3 conditional knock-out mice. CNOT2-mediated repression of MHC II genes occurred independent from the master regulator class II transactivator (CIITA) and detectable changes of the chromatin structure at the chromosomal MHC II locus. CNOT2 downregulation resulted in an increased de novo transcription of mRNAs and tethering of CNOT2 to a regulatory region governing MHC II expression resulted in dimished transcription. These results expand the known repertoire of CCR4-NOT members for immune regulation and identify CNOT proteins as a novel group of corepressors serving to restrict inappropriate or exaggerated class II expression, which can be causative for various diseases.

overall_design: Cell culture experiment with HEK 293 cells, transfected either with Luciferase reporter only (control) or with DOX-inducible shRNAs against CCR4-NOT subunits. 1-2 technical replicates.

first: Alfonso

last: Rodríguez-Gil


title: Investigating the effect of NIK SMI1, a small molecule inhibitor of NIK, on TWEAK-stimulated Mouse renal proximal tubule-interstitial epithelial cells (RPTEC)

status: Public on Oct 26 2017

city: South San Francisco

first: Mark

last: McCreary

address: 1 DNA Way, MS 93

department: Bioinformatics

institute: Genentech

summary: Systemic lupus erythematosus (SLE) is often considered a disease driven by autoreactive B cells and anti-nuclear antibodies. However, therapeutic targeting of B cells, for example through BAFF blockade, has been only partially effective in SLE. NF-κB Inducing Kinase (NIK) mediates non-canonical NF-κB signaling downstream of disease relevant TNF family members, such as BAFF, TWEAK, CD40, and OX40. We hypothesized that NIK inhibition might be more efficacious than BAFF blockade in lupus, and therefore generated highly selective and potent small molecule inhibitors (SMI) of NIK to test this hypothesis. RNASeq was used to investigate the effects of one of these SMIs of NIK, NIK SMI1, on TWEAK-stimulated Mouse renal proximal tubule-interstitial epithelial cells (RPTEC).

overall_design: To address the role of NIK in renal TWEAK signaling, we focused on renal proximal tubulo-interstitial epithelial cells (RPTEC), as this cell type is highly relevant to the well described pro-inflammatory role TWEAK plays in the kidney. Mouse RPTEC were cultured as suggested by commercial source. 5x10^6 cells were stimulated with recombinant mouse TWEAK (100 ng/mL, R&D Systems) for 6 and 24 hours in the presence or absence of NIK SMI1 (~IC90 = 3 µM) or vehicle (DMSO) with 3 replicates per treatment. Extracted RNA was analyzed by RNASeq

first: Hans

middle: D

last: Brightbill

first: Eric

last: Suto

first: Nicole

last: Blaquiere

first: Nandhini

last: Ramamoorthi

first: Swathi

last: SujathaBhaskar

first: Emily

last: Gogol

first: Georgette

last: Castanedo

first: Benjamin

last: Jackson

first: Susan

last: Haller

first: Justin

last: Lesch

first: Karen

last: Bents

first: Christine

last: Everett

first: Pawan

last: Kohli

first: Sandra

last: Linge

first: Laura

last: Christian

first: Kathy

last: Barrett

first: Allan

last: Jaochico

first: Leonid

last: Berezhkovskiy

first: Peter

middle: W

last: Fan

first: Kelli

last: Veliz

first: Michael

last: Townsend

first: Jason

last: DeVoss

first: Adam

last: Johnson

first: Robert

last: Godemann

first: Wyne

middle: P

last: Lee

first: Cary

last: Austin

first: Brent

last: McKenzie

last: Hackney

middle: J

last: Crawford

first: Steven

last: Staben

first: Moulay

last: Ismaili

first: Lawren

last: Wu

first: Nico

last: Ghilardi


title: Global gene expression profile of primary mouse brain and glioblastoma tissues

status: Public on Sep 15 2016

first: Yifeng

last: Xia

address: 10010 North Torrey Pines Road

department: Laboratory of Genetics

institute: Salk Insitute

summary: Mouse glioblastomas were induced by lentiviral vector expressing HrasG12V and shRNA against p53. Tumor tissues were isolated from mice reached clinical endpoints. RNA was isolated using the RNeasy kit according to manufacturer’s protocol with the addition of DNase (Qiagen). cDNA libraries were prepared using the TruSeq RNA Sample Prep kit (Illumina). RNA sequencing was performed using a HiSeq 2500 Sequencing System (Illumina).

overall_design: 3 normal mouse brain samples compared to 5 glioblastoma samples by standard RNAseq method.

first: Chad

last: Myskiw


title: Drosophila PGC transcriptome

status: Public on Dec 25 2016

city: Okazaki

first: Shuji

last: Shigenobu

state: Aichi

address: Nishigonaka 38, Myodaiji

institute: National Institute for Basic Biology

summary: To understand transcriptomic dynamics of PGC (primordial germ cells; pole cell) of fruit fly, we used fluorescence-activated cell sorting (FACS) to isolate PGC from the embryos carrying the transgene, EGFP-vasa, which expresses GFP specifically and continuously in the germline throughout the life cycle. The PGCs collected at 11 time points during the embryogenesis were subjected to microarray analyses.

overall_design: RNA from FACS-sorted PGCs collected at 11 different time points were hybridized to a microrray after Cy3/Cy5 labeling.  Four indepent experiments (biological replicates) were conducted for each time point.  A pooled total RNA purified from whole embryos at early to late stage was used as a common reference in all hybridizations.

first: Satoru

last: Kobayashi

first: Kayo

last: Arita


title: mTORC1 and -2 Coordinate Transcriptional and Translational Reprogramming in Resistance to DNA Damage and Replicative Stress in Breast Cancer Cells

status: Public on Dec 20 2016

city: New York

last: Schneider

state: NY

address: 550 First Ave, MSB 238

department: Microbiology

institute: NYU School of Medicine

summary:
mTOR coordinates growth signals with metabolic pathways and protein synthesis and is hyperactivated in many human cancers. We have characterized the coordinated mTORC1 and -2 transcription and translation response using genome-wide translatome and transcriptome profiling on cells inhibited in mTORC1/2 with PP242 or only mTORC1 with RAD001, with or without concurrent IR.
In this dataset, we include the expression data obtained from SUM149 cells treated with RAD001 + IR, RAD001, PP242+IR, PP242, IR, DMSO.  We include both total (transcriptional) data as well as polysome arrays.  These data are used to obtain differentially expressed genes in all treatments compared to DMSO in both polysome and transcriptional data.

overall_design: 35 samples were analyzed.  We examined the following comparisons using Limma with a p-value < 0.05, log fold-change > 1.5: PP242 vs. DMSO, PP242+IR vs. DMSO, RAD001 vs DMSO, RAD001 + IR vs DMSO, IR vs DMSO in polysome samples, total sampes, and using translational efficiency.

first: D

last: Silvera

first: A

last: Ernlund


title: Robust production of human neural cells by establishing neuroepithelial-like stem cells from peripheral blood mononuclear cell-derived feeder-free iPSCs under xeno-free conditions

status: Public on Aug 22 2016

city: Shinjuku-ku

first: Tsukasa

last: Sanosaka

state: Tokyo

address: 35 Shinanomachi

department: Department of Physiology

institute: Keio University School of Medicine

summary: We performed a microarray experiment to analyze the transcriptional profile of human fetal tissue derived neural stem/progenitor cells, human iPSCs, or human iPSC-derived neural stem/progenitor cells generated using xenogenic or xeno-free reagents.

overall_design:
Gene expression patterns were compared among human fetal tissue derived neural stem/progenitor cells, human iPSCs, or human iPSC-derived neural stem/progenitor cells generated using xenogenic or xeno-free reagents.
Samples with a title including "Xf" (201B7-lt-NES (Xf)-1, 201B7-lt-NES (Xf)-2, 1210B2-lt-NES (Xf)-1,1210B2-lt-NES (Xf)-2, 1231A3-lt-NES (Xf)-1, 1231A3-lt-NES (Xf)-2) correspond to human iPSC-derived neural stem/progenitor cells generated using xeno-free reagents, whereas samples with a title including "Con" (201B7-lt-NES (Con)-1, 201B7-lt-NES (Con)-2) correspond to those generated using xenogenic reagents.

first: Miho

last: Isoda

first: Jun

last: Kohyama

last: Iwanami

first: Keiko

last: Sugai

first: R

last: Yamaguchi

first: T

last: Matsumoto

first: Masaya

last: Nakamura

first: Hideyuki

last: Okano


title: Comparison of age-related changes in gene expression of 2 rat skeletal muscles (8 months, 18 months and 24 months)

status: Public on May 12 2016

city: Lausanne

first: Jerome

last: Feige

address: EPFL Innovation Park, Building H

department: Musculo-Skeletal Health

country: Switzerland

institute: Nestle Institute Of Health Sciences

summary: In this study we compared Gastrocnemius and Triceps gene expression with age. Our results show that gene expression is massively modulated with age in Gastroc but on the contrary very stable in Triceps, suggesting that Triceps is resistant to age-related defects.

overall_design: 3 groups of age (8 months, 18 months and 24 months) were analyzed, with 9-10 replicates per group. Gastrocnemius and Triceps were collected for each animal.

first: Alice

last: Pannérec

first: Eugenia

last: Migliavacca

first: Frédéric

last: Raymond

first: Descombes

last: Patrick


title: Progesterone responsive uterine transcriptome in rat

status: Public on May 04 2016

city: Kansas City

first: Pramod

last: Dhakal

state: Kansas

address: 3901 Rainbow Boulevard

department: Pathology and Laboratory Medicine

institute: University of Kansas Medical Center

summary: We have previously shown that Brown Norway (BN) rats are progesterone resistant. Thus this experiment was designed to compare the transcriptomes in uterus that are altered by progesterone challenge between this strain of rat with Holtzman Sprague Dawley (HSD) rats

overall_design: Progesterone was administered @ 40µg/gm body weight to the ovarectomized and 2 weeks rested females and controls received sesame oil (vehicle). Uterus were harvested after 9 hours and analyzed.

first: Michael

last: Soares


title: Comparison of syncytiotrophoblast differentiated from human pluripotent stem cells and that derived from primary cytotrophoblast recovered from term placentae

status: Public on Apr 06 2016

city: Columbia

first: Toshihiko

last: Ezashi

state: MO

address: 240a CS Bond Life Sciences Center

department: Animal Sciences

institute: University of Missouri-Columbia


title: Chromochloris zofingiensis transcriptome

first: Sean

last: Gallaher

summary: The alga Chromochloris zofingiensis was grown under 14 different conditions in an attempt to identify all protein coding genes and compare their expression profiles.

overall_design: Single sample RNA-Seq from 14 growth conditions.

first: Melissa

last: Roth

first: Shawn

last: Cokus

first: Andreas

last: Walter

first: David

last: Lopez

first: Erika

last: Erickson

first: Benjamin

last: Endelman

first: Daniel

last: Westcott

first: Carolyn

last: Larabell

first: Sabeeha

last: Merchant

first: Matteo

last: Pellegrini

first: Krishna

last: Niyogi


title: Primary human trophoblast from term placenta

summary: We compare two groups of transcriptome profiles. They are 1) primary human trophoblasts (PHT) and 2) syncytiotrophoblast from human pluripotent stem cells. This data set represents the former data set and the latter has been deposited separately at GSE72712. Primary human trophoblasts (PHT) were purified cytotrophoblast populations from whole term placentas and then cultured in vitro.  The cytotrophoblasts were cultured for short (9 h) or long (48 h) term that show undifferentiated (PHTu) or differentiated (PHTd) phenotype that led syncytialization, respectively. Transcriptome profiles of PHTu and PHTd were compared with three size fractioned syncytiotrophoblasts and trophoblasts from human pluripotent stem cells that are named ESCd_gt70 (greater than 70 µm), ESCd_40-70 (size between 40 and 70 µm), ESCd_lt40 (smaller than 40 µm) and undifferentiated progenitor (ESCu; see GSE72712).

overall_design: Primary human trophoblasts (PHT) were derived and cultured from three term human placentas obtained by the Obstetrical Specimen Procurement Unit from women after a healthy pregnancy, labor, and delivery at Magee-Womens Hospital of the University of Pittsburgh Medical Center. Isolated PHT lines obtained from three individual (1 female and 2 male) placentas were cultured separately.

first: Yoel

last: Sadovsky

first: R

middle: M

last: Roberts