title: Longitudinal DNA methylation differences precede type 1 diabetes

status: Public on Mar 09 2020

city: Aurora

first: Lauren

last: Vanderlinden

state: Colorado

address: 13001 E. 17th Place, Mail Stop B119

department: Department of Biostatistics and Informatics

institute: Colorado School of Public Health

summary: DNA methylation may be involved in development of type 1 diabetes (T1D), but previous epigenome-wide association studies were conducted among cases with clinically diagnosed diabetes. Using multiple pre-disease peripheral blood samples on the Illumina 450K and EPIC platforms, we investigated longitudinal methylation differences between 87 T1D cases and 87 controls from the prospective Diabetes Autoimmunity Study in the Young (DAISY) cohort. Change in methylation with age differed between cases and controls in 10 regions. Average longitudinal methylation differed between cases and controls at two genomic positions and 28 regions. Some methylation differences were detectable and consistent as early as birth, including before and after the onset of preclinical islet autoimmunity. Results map to transcription factors, other protein coding genes, and non-coding regions of the genome with regulatory potential. The identification of methylation differences that predate islet autoimmunity and clinical diagnosis may suggest a role for epigenetics in T1D pathogenesis.

overall_design: There are a total of 87 T1D cases and 87 T1D controls.  Each subject has somewhere between 1 and 5 time points collected.  There are no technical replicates included in the final analyzed dataset.

first: Randi

last: Johnson

first: Fran

last: Dong

first: Patrick

last: Carry

first: Jennifer

last: Seifert

first: Kathleen

last: Waugh

first: Hanan

last: Shorrosh

first: Tasha

last: Fingerlin

first: Brigitte

middle: I

last: Frohnert

first: Ivana

last: Yang

first: Katerina

last: Kechris

first: Marian

last: Rewers

first: Jill

last: Norris


title: Transcriptomic analysis of APC knock down HCEC 1CT cells compared to the wild type HCEC 1CT cells.

status: Public on Sep 25 2020

city: Yuseong-gu

first: Jeong-Ryeol

last: Gong

state: Daejeon

address: 291, Daehak-ro

country: South Korea

institute: KAIST

type: Expression profiling by high throughput sequencing

summary: In order to investigate sophisticated events during cancer initiation, we established early colorectal cancer development model. We performed scRNA-seq and analyzed the scRNA-seq dataset. scRNA-seq was conducted at 3- and 7-days after transduction of shRNA targeting APC (shAPC) and scrambled shRNA (shScr) on HCEC 1CT cells.

overall_design: scRNA-Seq of the shScr and shAPC cell lines in hCEC 1CT cells

first: Jihye

last: Choi

first: Chae

middle: Y

last: Hwang

first: Soobeom

last: Lee

first: Kwang-Hyun

last: Cho


title: Plant 22-nt siRNAs mediate translational repression and stress adaptation

status: Public on Feb 14 2020

city: Shenzhen

first: Bosheng

last: Li

state: Guangdong

address: SUStech Huiyuan #1 406

department: MCDB

country: China

institute: SUSTC (current, may different with previous institution )

type: Non-coding RNA profiling by high throughput sequencing

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

overall_design: Refer to individual Series


summary: Small interfering RNAs (siRNAs) are critical for proper development and immunity in eukaryotes1. Plants produce siRNAs with lengths of 21-, 22-, or 24- nucleotides (nt), wherein the 21- and 24-nt siRNAs mediate mRNA cleavage and DNA methylation2,3, respectively. However, the biological functions of 22-nt siRNAs remain elusive. Here we report the identification and characterization of a group of endogenous 22-nt siRNAs generated from the action of DICER-LIKE 2 (DCL2). When cytoplasmic RNA decay and DCL4 are deficient, the massive accumulation of 22-nt siRNAs causes pleiotropic growth disorders, including severe dwarfism, meristem defect, and pigmentation. Notably, two genes that encode nitrate reductases, NIA1 and NIA2, produce nearly half of the total of 22-nt siRNAs. Production of 22-nt siRNA triggers explosive self-amplification that leads to a small RNA storm, and induces dramatic translational repression both gene-specifically and globally. 22-nt siRNAs are also found to preferentially accumulate upon nitrogen deficiency, which acts to restrain plant growth and promote stress responses. Thus, our research uncovers the unique properties of 22-nt siRNAs, a previously unexplored class of plant siRNAs, and highlights the length of small RNA as a major functional determinant.

overall_design: Col-0 and dcl4-2 were grown on the MS medium with (MS) or without (MS-N) nitrogen for 10 days. whole seedlings of 10-day-old plant were collected at 15:00 for total RNA extraction. Three biological replicates were prepared for each genotype. Library preparation and high-throughput sequencing were conducted in accordance with the manufacturers’ instructions. Total RNA was extracted using the miRNeasy Mini Kit (Qiagen). Sequencing libraries were prepared using the NEBNext® Small RNA Library Prep Set for Illumina. RNA quality and library quality were examined by a Bioanalyzer 2100 instrument (Agilent), and single-end, 50-bp deep sequencing was performed on an Illumina HiSeq4000 platform.

first: Huihui

last: Wu

first: Hongwei

last: Guo


overall_design: Col-0, ein5-1, ski2-2, dcl4-2, dcl2-1, ein5-1 dcl4-2, ein5-1 dcl2-1, ein5-1 dcl4-2 dcl2-1, ski2-2 dcl4-2, ski2-2 dcl2-1 and ski2-2 dcl4-2 dcl2-1 were grown on the MS medium for 6 days and then were transferred to the soil for another 14 days. Aerial parts of 20-day-old plant were collected at 15:00 for total RNA extraction. Three biological replicates were prepared for each genotype. Library preparation and high-throughput sequencing were conducted in accordance with the manufacturers’ instructions. Total RNA was extracted using the RNeasy Plant Mini Kit (Qiagen). Sequencing libraries were prepared using the TruSeq mRNA preparation kit (Illumina). RNA quality and library quality were examined by a Bioanalyzer 2100 instrument (Agilent), and paired-end, 150-bp deep sequencing was performed on an Illumina HiSeqX ten platform.


overall_design: Col-0, ein5-1 dcl4-2 and ein5-1 dcl4-2 dcl2-1were grown on the MS medium for 6 days and then were transferred to the soil for another 14 days. Aerial parts of 20-day-old plant were collected at 15:00 for AGO1-associated small RNA isolation. Two biological replicates were prepared for each genotype. Library preparation and high-throughput sequencing were conducted in accordance with the manufacturers’ instructions. Total RNA was extracted using the Trizol and precipitated by ethonal. Sequencing libraries were prepared using the NEBNext® Small RNA Library Prep Set for Illumina. RNA quality and library quality were examined by a Bioanalyzer 2100 instrument (Agilent), and paired-end, 150-bp deep sequencing was performed on an Illumina Nova6000 platform.


overall_design: Col-0, ein5-1, ski2-2, dcl4-2, dcl2-1, ein5-1 dcl4-2, ein5-1 dcl2-1, ein5-1 dcl4-2 dcl2-1, ski2-2 dcl4-2, ski2-2 dcl2-1, ski2-2 dcl4-2 dcl2-1, ein5-1 dcl4-2 ago1-45, ski2-2 dcl4-2 ago1-45, ein5-1 dcl4-2 ago1-27 and ski2-2 dcl4-2 ago1-27 were grown on the MS medium for 6 days and then were transferred to the soil for another 14 days. Aerial parts were collected for small RNA extraction. Three or four biological replicates were prepared for each genotype. Library preparation and high-throughput sequencing were conducted in accordance with the manufacturers’ instructions. Total small RNA was extracted using the miRNeasy Mini Kit (Qiagen). Sequencing libraries were prepared using the NEBNext® Small RNA Library Prep Set for Illumina. RNA quality and library quality were examined by a Bioanalyzer 2100 instrument (Agilent), and single-end, 50-bp deep sequencing was performed on an Illumina HiSeq 4000 platform.


title: Rhodobacter capsulatus SB1003 under singlet oxygen stress

status: Public on Jan 24 2020

city: Gießen

first: Gabriele

last: Klug

address: Heinrich-Buff-Ring 26-32

department: Molecular- and Microbiology

country: Germany

institute: Justus-Liebig University Gießen

summary: Global transcriptome analyses at growth before and after 10 min of photooxidative stress were applied to monitor stress dependent gene expression in the alpha-proteobacterium Rhodobacter capsulatus. Transcriptome profiles of pigmented cultures with high aeration were monitored before and after the onset of singlet oxygen stress.

overall_design: Total RNA from exponentially grown cultures (OD660 of 0.4) of Rhodobacter capsulatus wild type SB1003 has been isolated  in triplicates using the hot phenol method and was analyzed by RNA-seq.

first: Petra

last: Dersch

first: Michael

last: Beckstette

first: Aaron

middle: M

last: Nuss

first: Marcel

last: Volk


title: Stem cell derived human microglia transplanted in mouse brain to study human disease

status: Public on Oct 16 2019

city: Leuven

first: Mark

last: Fiers

address: Herestraat 49

department: Center for Brain and Disease

country: Belgium

institute: VIB

summary: While genetics highlight the role of microglia in Alzheimer’s disease (AD), one third of putative AD-risk genes lack adequate mouse orthologs. Here, we successfully engraft human microglia derived from embryonic stem cells in the mouse brain. The cells recapitulate transcriptionally human primary microglia ex vivo and show expression of human specific AD-risk genes. Oligomeric Amyloid-β induces a divergent response in human vs. mouse microglia. This model can be used to study the role of microglia in neurological diseases.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: To control for variability across different experiments, tissue from three mice was pooled in all experimental conditions, from different litters and transplanted with H9-microglia produced in independent batches of in vitro differentiation. Across the manuscript we report both the number of mice/differentiations pooled, as well as the number of sequencing pools. In summary, 1) we sequenced 2,246 transplanted H9-microglia (n=3/1, 3 mice in 1 combined sequencing pool), 4496 H9-derived monocytes (n=2/1, 2 differentiations in 1 combined sequencing pool) and 3385 microglia in vitro (n=2/1), and 22,846 human primary microglia obtained from cortical surgical resections. 2) We sequenced 4880 transplanted H9-microglia (n=3x2/2) and 9942 host mouse cells (n=3x2/2) and assessed their differential response to oligomeric amyloid beta.

first: Renzo

last: Mancuso

first: Johanna

last: Van Den Daele

first: Nicola

last: Fattorelli

first: Leen

last: Wolfs

first: Sriram

last: Balusu

first: Oliver

last: Burton

first: Annerieke

last: Sierksma

first: Yannick

last: Fourne

first: Suresh

last: Poovathingal

first: Amaia

last: Arranz-Mendiguren

first: Carlo

last: Sala Frigerio

first: Christel

last: Claes

first: Lutgarde

last: Serneels

first: Tom

last: Theys

first: Hugh

last: Perry

first: Catherine

last: Verfaillie

first: Bart

last: De Strooper


title: LncRNA and mRNA expression profiles in High-grade serous ovarian cancer, Low-grade serous ovarian cancer and Normal fallopian tube

status: Public on Feb 12 2020

city: Jinan

first: Xiaoxue

last: Tian

state: Shandong Province

address: 44 Wenhua Xi Road

department: Department of Cell Biology

institute: Shandong University

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

summary: Ovarian cancer is the most lethal gynecologic cancer. High-grade serous ovarian carcinoma (HGSOC) is the most common histologic subtype, accounting for three quarters of ovarian cancer. To clarify the changes of gene expression in serous ovarian cancer, we performed lncRNA and mRNA microarrays to identify differentially expressed lncRNAs and mRNAs in High-grade and Low-grade serous ovarian carcinoma compared with Normal fallopian tube.

overall_design: The High-grade and Low-grade serous ovarian carcinoma specimens were from primary ovarian cancer patients with no surgery or chemotherapy previously and fallopian tube tissues were from patients who received a total hysterectomy and bilateral salpingo-oophorectomy for uterine diseases or benign neoplastic adnexal pathologic changes. Fresh tissue samples were collected within 2 hours of surgery. Total RNA was extracted with Trizol and subjected to microarray assay.

first: Zhaojian

last: Liu


title: NFAT5-sensitive upregulation of COX2 in endometrial ishikawa cells

status: Public on Aug 01 2020

city: Tübingen

first: Jakob

last: Admard

address: Calwerstr. 7

department: Institut für Medizinische Genetik und Angewandte Genomik

institute: Universitätsklinikum Tübingen

summary: Expression profiling by high throughput sequencing

overall_design: Endometrial cancer (ishikawa) mRNA profiles of paired control (NT) and NFAT5-overexpression transfection for 24h were generated by deep sequencing, in quadruplicate, using Illumina

first: M

last: Salker

first: T

last: Okumura

first: Y

last: Singh

first: F

last: Lang


title: Identification of miR-194-5p target genes in gastric cancer

status: Public on Oct 01 2019

city: Shiyan

first: Qin

last: Shanshan

address: Renmin Road 30, Maojian District

institute: Institute of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Medicine

summary: Increasing studies report that miR-194-5p plays a tumor suppressor role in gastric cancer (GC). Previous studies have revealed that miR-194 inhibited gastric cancer progression through different pathways by affecting the expression level of different target genes. For example, miR-194 have been reported to be able to regulate the expression of FOXM1, NR2F2, BMI1, SDAD1, RBX1, KDM5B, ZEB1 and AKT2 etc. It suggested that miR-194 may play complicated roles in GC. To figure out the mechanism of miR-194' tumor suppressor role in GC, we performed RNA sequencing in two different GC cell lines. Our studies showed that miR-194 tends to regulated target genes by binding on their 3' untranslated regions with either 7-mer-A1 or 7-mer-m8 or 8-mer. Approximately 138 genes were downregulated in both SGC7901 and BGC823 cell lines that transfected with miR-194-5p mimics compared to negative control siRNAs. Most of the downregulated genes have not reported yet.

overall_design: To reveal the possible target genes of miR-194-5p in gastric cancer, we transfected miR-194 mimics and corresponding negative control siRNAs in the SGC7901 and BGC823 cell lines. The potent miR-194-5p target genes were identified by deep sequencing, using Illumina HiSeq 4000.

first: Shanshan

last: Qin

first: Dandan

last: Li


title: The genomic landscape of Mongolian hepatocellular carcinoma

status: Public on Aug 04 2020

city: BALTIMORE

first: Luigi

last: Ferrucci

state: MD

address: 251 BAYVIEW BLVD.

department: Translational Gerontology Branch

country: USA

institute: National Institute on Aging, National Institutes of Health

summary: Mongolia has the highest reported incidence of (and mortality from) hepatocellular carcinoma (HCC) in the world. This is the first molecular study aiming to characterize the genomic landscape of Mongolian HCC.

overall_design:
Paired tumor/non-tumor liver tissue samples from a cohort of 76 hepatocellular carcinoma patients undergoing surgery between 2015 and 2016 at the National Cancer Center of Mongolia were sequenced with RNA-Seq and Whole Exome Sequencing (WES). This submission consists of 140 RNA-seq samples from 70 HCC tumors and matched nontumor tissue. Due to patient privacy concerns, patient phenotype and WES data has been submitted to dbGaP under accession phs002000.v1.p1.

Grant: ZIA BC010313
Funding: NCI Intramural Research Program of the Center for Cancer Research
Title: Molecular signatures for liver cancer diagnosis and treatment stratification
Grantee: Xin W. Wang

Grant: ZIA BC010876
Funding: NCI Intramural Research Program of the Center for Cancer Research
Title: The role of cancer stem cells in liver cancer heterogeneity and subtypes
Grantee: Xin W. Wang

Grant: ZIA BC010877
Funding: NCI Intramural Research Program of the Center for Cancer Research
Title: The identification of human hepatocellular carcinoma metastasis genes
Grantee: Xin W. Wang

Grant: ZIA BC011870
Funding: NCI Intramural Research Program of the Center for Cancer Research
Title: Liver Cancer Program
Grantee: Xin W. Wang

first: Xin

middle: W

last: Wang


title: Recombinant human GDF2 protein effect on human hepatic stellate cell line LX2

status: Public on Sep 05 2019

city: Shanghai

first: Peng

address: Chongqing nanlu 280

department: Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education

institute: Shanghai JiaoTong University School of Medicine

summary:
Analysis of human hepatic stellate cell line LX2 stimulated for 24h in serum-free DMEM medium containing 0 or 50 ng/ml recombinant human GDF2 protein. Results provide insight into the activation effects of GDF2 on human hepatic stellate cell.
We used microarrays to detail the global programme of gene expression underlying activation of hepatic stellate cells and identified liver-fibrosis-related genes genes during this process.

overall_design: LX-2 cells were serum-starved for 12 hours and treated with 0 or 50 ng/ml recombinant human BMP9 proteins for another 24 hours. Total RNA was extracted and then hybridized onto an Affymetrix gene microarray We divided cell samples according to rhBMP9 treatment concentration: i.e. LX2 with 0ng/ml rhBMP9, LX2 with 50ng/ml rhBMP9.


title: Human skeletal muscle transcriptome (39 independent analyses)

status: Public on Aug 01 2019

city: Stirling

first: James

last: Timmons

address: Bridge of Allan

country: United Kingdom

institute: Augur Precision Medicine LTD

summary:
The annotation of the Affymetrix HTA 2.0 array was updated to optimise the detection of RNA in human skeletal muscle  samples by removing invalid and low signal-high-variance probes
Human primary skeletal muscle cells were isolated from muscle biopsies from healthy adults as previously described (Crossland et al. 2016; Crossland et al. 2017). Myogenic cell enrichment used magnetic-activated cell sorting (MACS) and anti-CD56 microbeads (130-050-401; Miltenyi Biotec). Myogenic purity was assessed through measurement of fractional desmin positivity (Crossland et al. 2016; Crossland et al. 2017). Cells were washed in PBS and fixed in ice-cold 1:1 acetone/methanol, before being blocked in 5% (v/v) goat serum for 30 min at room temperature. Cells were subsequently incubated with rabbit anti-desmin monoclonal antibody (ab32362; Abcam) for 1h at room temperature, washed, and incubated with anti-rabbit TRITC-conjugated secondary antibody as previously detailed (Crossland et al. 2016; Crossland et al. 2017). Finally, cells were washed in PBS and mounted/DAPI-stained using FluoroshieldTM mounting medium with DAPI. Myoblasts at passage 5-6 were cultured on Collagen Type I-coated 6-well dishes in Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12 (DMEM/F-12; Life Technologies) containing 20% (v/v) fetal bovine serum (FBS, Sigma-Aldrich), 1% (v/v) antibiotic-antimycotic (AbAm) solution and 4mM L-glutamine (Life Technologies). Cells were maintained at 37oC with 5% CO2. Once cells reached ~95% confluency, differentiation was induced by switching the medium to DMEM/F-12 containing 2% (v/v) horse serum (Sigma-Aldrich), 4mM L-glutamine and 1% (v/v) AbAm solution (Life Technologies). Six days following the initiation of differentiation, a media change was carried out, using differentiation media supplemented with long R3 IGF-1 (10 ng/ml; Sigma-Aldrich), with or without 100 nM rapamycin (Sigma-Aldrich). DMSO (final concentration 0.01% (v/v)) was used as a vehicle control for rapamycin. Samples were collected at 0h baseline and following 4h and 24h treatment.

overall_design: The samples are profiles from cultured human primary myotubes (32 independent analyses + 7 baselines (8th sample, GSM3753798 is an outlier))

middle: A


title: Time-dependent changes of microglial exosomal miRNAs expression signatures following repetitive mild traumatic brain injury

status: Public on Jul 10 2019

city: Tianjin

first: Xintong

last: Ge

address: 154, Anshan Road

department: Department of Neurosurgery

institute: Tianjin Medical University General Hospital

summary:
To acquire the time profiling of miRNA levels in microglial exosomes from injured brain after rmTBI, we employed a developed rmTBI mice model, and harvested the microglial exosomes at 1, 3, 7, 14, 21, 28, 35 and 42 DPI. The exosomes were first identified by TEM scanning, NTA measurement and Western Blot. miRNA microArray was performed to detect the miRNA levels in microglial exosomes after rmTBI. 3, 14 and 42 DPI were selected to respectively represents the time-point of acute phase, sub-acute phase and chronic phase after rmTBI.
10 miRNAs had an expression change of more than two-folds (up- or down-regualted) with a P value less than 0.05 at the 3 time-points. Among them, the expression changes of miR-124-3p were particularly evident. In addition, miR-124-3p was the only miRNA that up-regulated at 3 and 14 DPI, and down-regulated (reversely expressed) at 42 DPI, suggesting that its low expression in the chronic phase after rmTBI may exert a reverse impact on neural pathology, compared with that in the acute and sub-acute phase.

first: Jianning

last: Zhang

first: Ping

last: Lei


title: Transcriptome analysis of cells carrying Type II Csp231I restriction-modification (RM) system reveal the crosstalk between two unrelated transcription factors - C protein and Rac prophage repressor

status: Public on Jul 30 2019

city: Gdańsk

first: Marcin

last: Jakalski

address: Dębinki 7

department: 3P Medicine Laboratory

country: Poland

institute: Medical University of Gdańsk

summary: Our transcriptome analysis supported by other in vivo and in vitro assays showed that C protein can directly silence the RacR repressor and thus affect the Rac prophage-related genes.

overall_design: Cultures of E. coli MG1655 carrying following plasmids: pMCsp231 (additional protective MTase gene on ACYC177 derivative), and plasmid with RMs of interest: WT (p18) and two variants: C-R+ (p30) and C+R- (p24), were grown in LB medium.

first: Alessandro

last: Negri

last: Jąkalski

first: Aleksandra

last: Szczuka

first: Leszek

middle: P

last: Pryszcz

first: Iwona

last: Mruk


title: Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis

status: Public on Jul 17 2019

city: Philadelphia

first: daniel

last: beiting

state: PA

address: 380 S. University Ave

department: Pathobiology

institute: University of Pennsylvania

summary: Patients infected with Leishmania braziliensis develop chronic lesions that often fail to respond to treatment. To determine whether genes whose expression is highly variable in lesions might influence disease outcome, we obtained biopsies of lesions from patients prior to drug treatment, performed transcriptomic profiling, and identified highly variable genes whose expression correlated with treatment outcome. Amongst the most variable genes were components of the cytolytic pathway, the expression of which appeared to be driven by parasite load in the skin. We demonstrated that treatment failure can be directly linked to the cytolytic pathway activated during infection. Using this host-pathogen biomarker profile, we show that treatment outcome can be predicted before the start of treatment. These findings not only raise the possibility of point-of-care diagnostic screening to identify patients at high risk of treatment failure and provide a rationale for a precision medicine approach to drug selection in cutaneous leishmaniasis, but more broadly also demonstrate the value of identifying genes of high variability in other diseases to better understand and predict diverse clinical outcomes.

overall_design: Biopsies from the lesion of patients infected with Leishmania braziliensis (n=21) and healthy skin from not-infected individuals (n=7)

first: Phillip

last: Scott

first: Daniel

last: Beiting

first: Camila

last: Amorim


title: Rhesus macaque acute SIV infection and SIV LCV co-infection studies

status: Public on Sep 27 2019

city: Bethesda

first: Douglas Scott

last: Merrell

address: 4301 Jones Bridge Road

department: Dept. of Microbiology and Immunology

institute: Uniformed Services University


title: Transcriptome of liver tissue at ZT01, ZT05, ZT09, ZT13, ZT17 and ZT21

status: Public on Jan 30 2020

city: New Haven

first: Andrés

last: Hidalgo

address: 10 Amistad Street

institute: Yale University

summary: Our study looks at the liver circadian transcriptome.

overall_design: Livers were harvested from WT mice, in normal light-controlled mouse facility. Five mice per group were experimented upon, but only the best quality RNA from three of the mice from each group was submitted for whole RNA next generation sequencing

first: A

first: I

last: Ballesteros

last: Rubio-Ponce


title: The splicing factor hnRNP M is a critical regulator for innate immune gene expression in macrophages

status: Public on Sep 18 2019

city: Bryan

first: Robert

middle: O

last: Watson

state: TX

address: 8447 Riverside Pkwy

department: Microbial Pathogenesis and Immunology

institute: Texas A&M Health Science Center

summary:
Purpose: The goals of this study are to compare hnRNP M shRNA knockdown macrophages to scramble shRNA control macrophages in uninfected cells and Salmonella Typhimurium-infecetd cells to unbiasly look at gene expression changes that are regulated by the splicing factor, hnRNP M during resting state and during an innate immune response.
Methods: Macrophage mRNA profiles of uninfected and Salmonella Typhimurium-infected hnRNP M knockdown cells lines and SCR shRNA control RAW264.7 macrophages were generated by  sequencing, in triplicate, using Illumina 1.9 system. The sequence reads that passed quality filters were analyzed at the gene expression level with CLC Genomics Workbench 8 with Transcriptomeics Analysis followed by statistical analysi with Empiciral Analysis of DGE and (EDGE test) and Baggerly's test. qRT–PCR validation was performed using SYBR Green assays.
Results: Using CLC Genomics Workbench 8 transcriptomics workflow, we mapped about 30 million sequence reads per sample to the mouse genome (GRCm38). Approximately 140 transcripts showed differential expression between the scramble control and hnRNP M knockdown macrophages in uninfected cells, with a fold change ≥1.5 and p value <0.05. Additionally, ~150 transcripts showed differential expression between the scramble control and hnRNP M knockdown macrophages in Salmonella-Typhimurium cells, with a fold change ≥1.5 and p value <0.05. Altered expression of genes was confirmed with qRT–PCR, demonstrating the effectiveness of the RNA-seq method.
Conclusions: Our study demonstrates hnRNP M-dependent differential gene expression in the context of the innate immune response.

overall_design: Transcriptome profiles of uninfected and Salmonella Typhimurium-infected hnRNP M shRNA knockdown and scramble control shRNA knockdown RAW 264.7 macrophages were generated by sequencing, in triplicate, using Illumina 1.9.

first: Kelsi

last: West

first: Kristin


title: A comprehensive spatial-temporal transcriptomic analysis of differentiating nascent mouse lens epithelial and fiber cells

status: Public on Oct 02 2018

city: Bronx

first: Ales

last: Cvekl

state: NY

address: 1300 Morris Park Avenue, Ullman 123

department: The Departments Ophthalmology and Visual Sciences, Genetics

institute: Albert Einstein College of Medicine

summary: The lens is comprised of the anterior lens epithelium and posterior lens fibers, which form the bulk of the lens. The RNAseq data enables identification of lens epithelium and fiber differentially expressed genes and temporally differentially expressed genes which were also validated by qRTPCR. The present RNA-seq data serves as a comprehensive reference resource for deciphering molecular principles of normal mammalian lens differentiation, mapping a full spectrum of signaling pathways and DNA-binding transcription factors operating in both lens compartments, and predicting novel pathways required to establish lens transparency.

overall_design: The lens epithelium and fiber were collected from E14.5, E16.5, E18.5 CD1 mouse embryos and P0.5 mice. Three biological replicates were prepared. The RNA were used for total RNAseq library construction and sent for 100bp paired end sequencing on illumina Hiseq 2500. The genes detected by RNAseq were then validated by qRTPCR.

first: Yilin

last: Zhao

first: Deyou

last: Zheng


title: Coprophagia of rabbit puppies stimulate Immune System Development

status: Public on May 02 2019

city: Castanet-Tolosan

first: Laurent

last: Cauquil

address: 24 chemin de Borde Rouge

country: France

institute: INRA

summary: The rabbits ingest the mother's droppings at the nest. This behaviour contributes to the transmission of the maternal microbiota to its progeny, it is involved in the maturation of the digestive ecosystem of the rabbits and reduces mortality. In view of these observations, it is possible to assume that the digestive system is involved. To support this hypothesis, gene expression is measured using an expression chip. The aim is to detect over- or under-expressed genes under certain conditions and to link them in particular to immunity.

overall_design: Ileum gene expression of 57 rabbits was measured at 2 different times (35d and 49d old) and for 3 different conditions of breeding (FF: fecal pellets add to the net; NF: no fecal pellets add to the net; FFab: fecal pellets from doe under antibiotics add to the net).

first: Véronique

last: Duranthon

first: Sylvie

last: Combes


title: Profiling of chromatin accessibility and identification of general cis-regulatory mechanisms that control two ocular lens differentiation pathways

status: Public on May 13 2019

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We performed ATAC-seq for microdissected lens epithelium and fiber from E14.5 and P0.5  mouse lenses.Through investigating dynamics of chromatin changes during mouse lens fiber and epithelium differentiation, we identified spatial-temporal differential accessible regions and the enriched known and novel motifs. We also discovered some novel and known enhancers for the transcription factors and structural genes that are important in lens development. Additionally, a cross examination of Pax6 ChIP-seq with ATAC-seq data revealed novel Pax6 binding mechanisms.

overall_design: Examination of chromatin profiles in lens epithelium and fiber at E14.5 and P0.5 mouse lenses


title: Cell type-dependent control of enhancer and p53 transcriptional activity by p63

status: Public on Feb 11 2019

city: Albany

first: Morgan

last: Sammons

address: 1400 Washington Ave, Life Sciences 2075

department: Biological Sciences

institute: University at Albany - SUNY

summary: In this work, we demonstrate that the p53-induced transcriptome is dependent on pre-establishment of cell type-dependent cis-regulatory networks. The epithelial-specific p53 transcriptome is strongly dependent on p63, which acts as a pioneer factor for epithelial-specific enhancers. These results suggest a broad mechanism for regulating the p53-dependent cellular response to stress through differential regulation of cis-regulatory elements and identify p63 as a direct and critical regulator of enhancer activity in epithelial cell types.

overall_design: p53 transcriptome: RNA-Seq and ChIP-Seq

first: Faraz

last: Ahmed

first: Gizem

last: Karsli Uzunbas


title: Wnt/β-catenin signaling regulates VE-cadherin-mediated anastomosis of brain capillaries by counteracting S1pr1 signaling

status: Public on Oct 12 2018

city: bad nauheim

first: Stefan

last: Günther

address: ludwigtr. 43

institute: MPI for heart and lung research

summary: Canonical Wnt signaling is crucial for vascularization of the central nervous system and blood-brain barrier (BBB) formation. BBB formation and modulation are not only important for development, but also relevant for vascular and neurodegenerative diseases. However, beyond the early requirement of Wnt signaling for brain capillary development, there is little understanding of how Wnt signaling further contributes to brain angiogenesis and BBB formation.  By combining high resolution in vivo imaging with temporally and spatially controlled manipulation of Wnt signaling, we were able to dissect different requirements for Wnt signaling during brain angiogenesis and BBB formation.   In the absence of Wnt signaling, premature Sphingosine-1-phosphate receptor (S1pr) signaling leads to a reduction of VE-cadherin and Esama at cell-cell junctions. Wnt signaling most likely suppresses S1pr signaling during angiogenesis to enable the dynamic junction formation during anastomosis, whereas later S1pr signaling regulates BBB maturation and VE-cadherin stabilization. Our data provides a novel link between brain capillary angiogenesis and BBB formation and identifies Wnt signaling as coordinator of the timing and as regulator of anastomosis.

overall_design: Isolation of the zebrafish CtA endothelial cells from 36hpf-old Tg(fli1a:Gal4)ubs3;(UAS:Kaede)rk8 embryos treated with IWR-1 or DMSO

first: Benoit

last: Vanhollebeke

first: Wiebke

last: Herzog

first: Pauline

last: Cabochette

last: Guenther


title: Gene expression data in U87MG cell line transfected with miR-490 overexpression vector PC-490 or its control PCDNA3.1 (+).

status: Public on Aug 24 2018

city: New Delhi

first: Dr. Ritu

last: Kulshreshtha

state: New Delhi

address: Room 134, Block I

department: Dept of Biochemical Engineering and Biotechnology

country: India

institute: Indian Institute of Technology

summary:
miR-490 is robustly downregulated in GBM tumour samples. This study identifies the genes differentially expressed upon miR-490 overexpression in U87MG glioblastoma cell line.
GeneChip PrimeView Human Gene Expression Array was used to assess mRNA expression profile in response to miR-490 overexpression in U87MG cell line.

overall_design: U87MG cells were transfected with either miR-490 overexpression vector PC-490 or its control vector PCDNA. The cells were harvested for RNA isolation 48 hours post-transfection. RNA was used for the gene expression analysis using GeneChip PrimeView system.

first: Omkar

middle: S

last: Vinchure

first: Ritu


title: Hypersensitive interferon responses in lupus keratinocytes reveal key mechanistic determinants in cutaneous lupus

status: Public on Jan 15 2019

city: Ann Arbor

first: Lam

last: Tsoi

state: MI

address: Medical Sciences 1 Bldg. 1301 E. Catherine

institute: University of Michigan

summary: SLE patients exhibit increased interferon signatures in their skin secondary to increased production and a robust, skewed IFN response that is regulated by PITX1. Targeting of these exaggerated pathways may prove to be beneficial to prevent and treat hyperinflammatory responses in SLE skin.

overall_design: A cohort of 72 RNA-sequencing samples from 14 individuals (7 SLE and 7 healthy controls) was analyzed to study the transcriptomic effects of type I and type II IFNs on SLE vs. control keratinocytes.

first: M

middle: J

last: Kahlenberg

middle: C


title: Microglial gene expression after TGFb1 treatment in vitro

status: Public on Sep 01 2018

city: Rostock

first: Björn

last: Spittau

address: Gertrudenstraße 9

department: Institute of Anaomy

institute: University of Rostock

summary: Primary microglia derived from P0/P1 pus of C57BL/6 mice were cultured under serum-free conditions and were treated with recombinant human TGFb1 (5 ng/ml) for 24 h. RNA was isolated using the TRIzol method.


title: Gene expression data of bezafibrate treated CD8+ T cells

status: Public on Aug 17 2018

city: kyoto

first: partha sarathi

last: chowdhury

address: Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan

country: Japan

institute: kyoto university

summary:
Activation of PPAR by bezafibrate synergize with PD-1 blockade. We found that PPAR activation enhanced the anti-apoptotic property of CD8+ T cells and increased its number in tumor site. PPAR target genes includes various genes associated with metabolic pathways. Using the microarray assay we found that fatty acid oxidation related genes and immune function related genes are involved in the enhnacement of antitumor immunity.
Microarrays have been used to identify the genes, which include metabolic as well genes related to immune function, regulated by PPAR activation.

overall_design: We used in vitro system to identfy the genes. In vitro stimulated naive CD8+ T cells were treated with bezafibrate and DMSO. Cells were expanded in the presence of IL-2 and bezafibrate until day 13. We used two groups for analysis: Control (DMSO) and Treat (bezafibrate).

first: Partha

last: Chowdhury

first: Tasuku

last: Honjo


title: Transcriptomic comparison of 4/74 and D23580 Salmonella enterica strains under infection-relevant conditions

status: Public on Sep 10 2018

city: Hinxton

first: Alexander

last: Predeus

address: Wellcome Trust Genome Campus

institute: Wellcome Sanger Institute

summary: RNA-sequencing of two Salmonella Enterica strains (4/74, D23580) under in vitro growth conditions (EEP, MEP, LEP, ESP, LSP, 25ºC, NaCl, bile shock, low Fe2+ shock, anaerobic shock, anaerobic growth, oxygen shock, NonSPI2, InSPI2, peroxide shock, and nitric oxide shock) and murine RAW264.7 macrophages.

sample_organism: Salmonella enterica subsp. enterica serovar Typhimurium str. D23580

sample_organism: Salmonella enterica subsp. enterica serovar Typhimurium str. ST4/74

overall_design: For 4/74, three biological replicates in ESP, anaerobic growth, NonSPI2, InSPI2, and macrophages; for D23580, three biological replicates in ESP, anaerobic growth, NonSPI2, InSPI2, and macrophages. The EEP, MEP, LEP, LSP, 25ºC, NaCl, bile shock, low Fe2+ shock, anaerobic shock, anaerobic growth, oxygen shock, NonSPI2, peroxide shock, and nitric oxide shock conditions were not replicated. There were two biological replicates of D23580 ΔpBT1 in ESP.

first: Rocío

last: Canals

first: Disa

middle: L

last: Hammarlöf

first: Carsten

last: Kröger

first: Siân

middle: V

last: Owen

first: Wai

last: Fong

first: Lizeth

last: Lacharme-Lora

first: Xiaojun

last: Zhu

first: Nicolas

last: Wenner

first: Sarah

middle: E

last: Carden

first: Jared

last: Honeycutt

first: Denise

last: Monack

first: Robert

last: Kingsley

first: Philip

last: Brownridge

first: Roy

middle: R

last: Chaudhuri

first: Will

last: Rowe

first: Karsten

last: Hokamp

first: Melita

last: Gordon

first: Jay

last: Hinton


title: Transcriptome of cardiac tissue from WT mice, cardiac macrophages depleted mice, and mice deficient for Mertk and LxR

status: Public on Oct 27 2018

first: Andrés

last: Hidalgo

summary: Our study aims to analyze the effect in whole cardiac transcriptome of cardiac macrophage depletion and the lack of receptors implicated in phagocytosis.

overall_design: Standard RNA extraction procedures were performed in whole cardiac tissue from those mice.

first: A

first: J

last: Nicolas-Avila


title: Analysis of human leukocyte antigen (HLA) allotype-specific response in abacavir-exposed keratinocyte

status: Public on Mar 01 2018

city: Kamakura

first: Satoshi

last: Kondo

state: Kanagawa

address: 10-1 tebiro 6-chome

institute: Toray Industries,Inc.

summary: Abacavir, a nucleoside reverse-transcriptase inhibitor used for the treatment of human immunodeficiency virus (HIV) infection, develops hypersensitivity in patients carrying HLA-B*57:01 allele through drug antigen presentation. We found that abacavir exposure induced HLA allotype-specific innate immune response in keratinocyte derived from HLA-B*57:01 transgenic mice. Therefore, the mechanism of the novel response was analyzed comprehensively.

overall_design: Gene expression profile of HLA allotype-specific response of abacavir-exposed keratinocyte derived from HLA-B*57:01 transgenic mice, compared to that of keratinocyte derived from HLA-B*57:03 transgenic mice (negative control).

first: Sota

last: Fujimori

first: Shigeki

last: Aoki

first: Kousei

last: Ito


title: Genetic variations as a result of overexperssion of TRPV3 in BEAS-2B cells

status: Public on Apr 26 2018

city: Salt Lake City

first: Christopher

last: Reilly

state: UT

address: 30 S 2000 E, Room 201 Skaggs Hall

department: Pharmacology and Toxicology

institute: University of Utah

summary: The goal of our study was to determine the effect of overexpressing TRPV3 in the lung epithelial cell line BEAS-2Bs.  BEAS-2B cells, were transfected with hTRPV3 in pcDNA3.1V5/His and stable overexperssion was achieved using antibiotic selection (G418). Comparisons were between treatments in wild-type cells vs those overexperssing TRPV3.

overall_design: BEAS-2B cells and TRPV3-overexpressing BEAS-2B cells were compared.

first: Cassandra

last: Rice


title: Gene family Diversification in conserved miRNAs target sites in Tomato revealed as layers of interaction with a nuclear-replicating virus.

status: Public on Sep 28 2018

city: Bari

first: Vitantonio

last: Pantaleo

address: Via Amendola 165/a

country: Italy

institute: Institute for Sustainable Plant Protection

summary: In the present study we diagnosed cleaved transcripts in either healthy or virus infected plants, by sRNAome and metagenome of degraded mRNAs. We integrated the experimentally obtained data with publicly available annotations and we gained a deep insight into the parallel evolution of gene families and the transcriptional regulation mediated by miRNAs in Tomato. Gene expression is finely regulated to specific paralogues in gene families such as the squamosa-promoter binding protein-like, the Auxin Response Factor, the Class III homeodomain-leucine zipper, the Argonaute gene families, just to name a few. In some cases, different miRNA are expressed to target different copies of the same family. Size fractionated small RNA from total RNA extracts of Solanum lycopesicum cv. "Money Maker"  were ligated to adapters, purified again and reverse transcribed. After PCR amplification the sample was subjected to Illumina high throughput pyrosequencing. The kit used is TrueSeq Small RNA kit, Illumina. Please see www.illumina.com for details of the sequencing technology. PARE libraries were generated starting from Poly(A) fraction used for sRNA isolation. The protocol used have been previously described in German et al., 2009, Nature protocols. Please see www.illumina.com for details of the sequencing technology.

overall_design: Short RNA fractionation and characterization and PARE analysis in mock-inoculated and geminivirus-infected tomato plants.

first: Laura

last: Miozzi


title: Global gene expression profile in human glioma tissue and adjacent normal tissue samples

status: Public on Jul 21 2018

city: Rupnagar

first: Javed

middle: N

last: Agrewala

state: Punjab

address: Indian Institute of Technology [IIT] Rupnagar-140001, Punjab, INDIA

department: Centre for Biomedical Engineering

institute: Indian Institute of Technology [IIT]

summary: Differential gene expression was assesed of genes related to tumor associated macrophages in human gliomas

overall_design: The total RNA from tissue was extracted from fresh tumor and normal tissue using an RNeasy kit (Qiagen, Limburg, Netherlands), according to the manufacturer's protocol. RNA purity and integrity was analyzed by BioAnalyser 2100 (Agilent Technologies, Santa Clara, CA). Gene expression profiling was performed using GeneChip® Human 2.0 ST Array Affymetrix (Santa Clara, CA). Target preparation for Affymetrix Gene chipsTM was performed according to the manufacturer’s instruction.

first: Aurobind

last: Vidyarthi

first: Tapan

last: Agnihotri

first: Nargis

last: Khan

first: Manoj

middle: K

last: Tewari

first: Bishan

middle: D

last: Radotra


title: Expression data from CHRNA5 knockdown A549 lung cancer cells compared with control

status: Public on Sep 20 2017

city: Jinan

first: Xiaoli

last: Ma

address: 105# Jiefang Road

institute: Jinan Central Hospital affiliated to Shandong University

summary:
Nicotine and nicotinic acetylcholine receptors (nAChRs) are considred to be involved in the progression of lung carcinomas. α5-nAChR is believed to be associated with lung cancer risk and onset, however its function and physiologic roles is far from clear.
We use microarry to detail the global programme of gene expression underlying knockdown CHRNA5, encoding α5-nAChR, in human lung cancer A549 cells compared with control.

overall_design: RNA was isolated from lung cancer cells transfected with scrambled siRNA or α5-nAChR -specific siRNA (3 replicates each).RNA samples were analyzed by microarray expression profiling using the Affymetrix array. We sought to obtain gene profiling coupled with functional pathway analysis

first: Haiji

last: Sun


title: Transcriptome of lung tissue from C57BL/6 mice with or without neutrophil depletion at ZT04 and ZT16

first: Andrés

last: Hidalgo

summary: Our study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)).

overall_design: Lungs were harvested from neutrophil-depleted (antibody or DT) or non-depleted mice, in normal light-controlled mouse facility (ZT4) or 12h inverted light cabinets (ZT16). Experiments were carried out over 3 batches (July 2017, September 2017, and April 2018), with 3 or 4 mice per group. Antibody-depleted and non-depleted mice were tested for the July 2017 and September 2017 batches, whereas DT-depleted mice were tested only in April 2018.

first: A

first: J

last: Li


title: Cdc6-2 functions as a master regulator in mediating DNA damage response

status: Public on May 15 2018

city: Copenhagen N

first: Mengmeng

address: Ole Maaløes Vej 5

country: Denmark

institute: copenhagen university

summary: Transcriptome sequencing was carried out with an Illumina HiSeq platform to investigate the differently expressed genes in wild type strain E233S1 and cdc6-2 deletion mutant ∆cdc6-2 with or without 2 µM NQO treatment for 6 hours

overall_design: Examination of  different gene expression in E233S1 and ∆cdc6-2 with or without NQO treatment

first: Qunxin

last: She


title: Expression analysis of  Kit+ derived from wild type C57B/L6 Mouse bone marrow cells Transduced with CSF3R mutants by RNA seq.

status: Public on Jan 01 2018

city: Cincinnati

first: Mohammad

last: Azam

state: OH

address: 3333 Burnet Avenue

department: Division of Experimental Hematology

institute: Cincinnati Childrens Hospital and Medical Center

summary: We performed whole genome expression analysis of Kit+ derived from wild type C57B/L6 Mouse bone marrow cells Trabsduced with control vector and CSF3R mutants by RNA seq.

overall_design: The experiment was designed to test the gene expression differences between leukemogenic (proximal and double muatnt) and non leukemogenic (truncation) mutants of CSF3R.


title: Expression data from growth plate cartilage of control and immobilized embryonic chickens

status: Public on Dec 31 2016

city: Stirling

first: James

last: Timmons

address: Bridge of Allan

institute: Augur Precision Medicine LTD

summary: Affymetrix Chicken Gene 1.0 ST Array (ChiGene-1_1-st) profiles were generated from growth plate cartilage derived from the distal femur and proximal tibia of embryonic chickens at three developmental stages (day 12, 13 and 15) corresponding to stages prior to and immediately after the acqusition of mechano-responsive cartilage growth in the femur but not tibia (which does not respond to mechanical stimuli until later stages). Additionally, array profiles were generated from growth plate cartilage from the distal femur and proximal tibia of E15 chicks which were pharmacologically immobilized by decamethonium bromide treatment, which reduces longitudinal growth of the femur only at this stage.

overall_design: Three developmental stages, two tissue types and two treatments with 3 biological replicates per group.

first: Andrew

last: Pitsillides


title: Human adipose tissue profiled before and after 16 weeks of intense exercise training with a modest energy deficit

status: Public on Aug 05 2016

summary: The "IDEAL" trial - 3 groups of diet (1, 2, and 3) at two time points (Pre- and Post-diet). 3 diets differed in the amount and type of protein consumed. Diet 1: adequate protein, low dairy (APLD: 15% daily calories from protein, 0-1 servings of dairy); diet 2: adequate protein, moderate dairy (APMD: 15% daily calories from protein, 3-4 servings/d); diet 3: high protein, high dairy (HPHD: 30% daily calories from protein, 6-7 servings of dairy).

overall_design: Randomized controlled trial, repeated measures design, all groups exercised, main difference was nutrition. There are matching muscle sample profiles

first: Andrea

last: Josse


title: Three classes of recurrent DNA break clusters in brain progenitors identified by 3D proximity-based break joining assay

status: Public on Jan 19 2018

city: Heidelberg

first: Pei-Chi

last: Wei

state: Baden-Württemberg

address: Im Neuenheim Feld 280

department: Structural and functional genomics

institute: German Cancer Research Center

summary: We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations. Cellular heterogeneity in 3D genome organization allowed unequivocal identification of RDCs on 14 different chromosomes using HTGTS baits on three mouse chromosomes. Additional candidate RDCs were also implicated, however, suggesting that some RDCs were missed. To more completely identify RDCs, we exploited our finding that joining of two DSBs occurs more frequently if they lie on the same cis chromosome. Thus, we used CRISPR/Cas9 to introduce specific DSBs into each mouse chromosome in NSPCs that were used as bait for HTGTS libraries. This analysis confirmed all 27 previously identified RDCs and identified many new ones. NSPC RDCs fall into three groups based on length, organization, transcription level, and replication timing of genes within them. While mostly less robust, the largest group of newly defined RDCs share many intriguing characteristics with the original 27. Our findings also revealed RDCs in NSPCs in the absence of induced replication stress, and support the idea that the latter treatment augments an already active endogenous process.

overall_design: We introduced HTGTS bait DSBs at all mouse autosomes and X chromoosme to map RDCs via proximity in C-NHEJ deficient NSPCs.

first: Cheng-Sheng

last: Lee

first: Zhou

last: Du

first: Bjoern

last: Schwer

first: Yuxiang

last: Zhang

first: Jennifer

last: Kao

first: Jeffrey

last: Zurita

first: Frederick

last: Alt


title: Transcriptome analysis of inflammation-related gene expression in endothelial cells activated by complement MASP-1

status: Public on Sep 14 2017

city: Budapest

first: Zsuzsanna

last: Németh

address: Kútvölgyi út 4.

country: Hungary

institute: Semmelweis University

summary: Transcriptional profiling of human umbilical vein endothelial cells, treated with MASP-1, thrombin, LPS, histamine, TNFalpha, MASP-1+SB203580 (p38-MAPK inhibitor) or MASP-1+Bay-117082 (NFKB inhibitor). Goal was to determine the effect of MASP-1 on HUVECs, to compare this with the effect of other endothelial cell activators and to determine the MASP-1 induced signalling pathways.

overall_design: Two-color microarray experiment, with several different treatments. 13 samples were analyzed. 2h MASP-1 treatment: 4 biological replicates; TNFalpha treatment: 2 replicates; 1h MASP-1, 6h MASP-1, LPS, histamine, thrombin, SB203580, Bay-117082 treatment: 1-1 replicate

first: Endre

last: Schwaner

last: Nemeth

first: Peter

last: K Jani

first: Erika

last: Kajdacsi

first: Marta

last: L Debreczeni

first: Zoltan

last: Doleschall

first: Jozsef

last: Dobo

last: Gal

first: Janos

last: Rigo Jr

first: Kinga

last: Andras

first: Tamas

last: Hegedus

first: Laszlo

last: Cervenak


title: Aire-KO MEChi RNAseq profiling

status: Public on Sep 23 2016

city: Nantes

first: Matthieu

last: Giraud

address: 30 bd Jean Monnet

department: CRTI

institute: INSERM _ Université de Nantes

summary:
Background: In order to become functionally competent but harmless mediators of the immune system, T cells undergo a strict educational program in the thymus, where they learn to discriminate between self and non-self. This educational program is, to a large extent, mediated by medullary thymic epithelial cells (mTECs) that have a unique capacity to express, and subsequently present a large fraction of body antigens. While the scope of promiscuously expressed genes by mTECs is well established, relatively little is known about the expression of variants that are generated by co- and post-transcriptional processes.
Results: Our study reveals that in comparison to other cell types, mTECs display significantly higher levels of alternative splicing, as well as A-to-I and C-to-U RNA editing, which thereby further expand the diversity of their self-antigen repertoire. Interestingly, Aire, the key mediator of mTECs promiscuous gene expression, plays a limited role in the regulation of these transcriptional processes.
Conclusions: Our results highlight RNA processing as another layer by which the immune system assures a comprehensive self-representation in the thymus which is required for the establishment of self-tolerance and prevention of autoimmunity.

Identification of the number of genes expressed in Aire-KO MEChi

overall_design: ~100ng of total RNA was isolated by Trizol extraction from MHC-II high mTECs from a pool of 3 Aire-KO mice. Poly-A-selected transcriptome libraries were generated using the non-directionnal TruSeq V3 RNA Sample Prep Kit (without additional pre-amplification) following the manufacturer's protocols.  Enrichment of DNA fragment with adapter molecules on both ends was done using 15 cycles of PCR amplification using the Illumina PCR mix and primer cocktail. Paired-end (2 × 100 bp) sequencing was performed using the Illumina HiSeq2000 machine.

first: Jakub

last: Abramson


title: The major risk factors for Alzheimer’s disease: Age, Sex and Genes, modulate the microglia response to Aβ plaques (CDEP)

status: Public on Apr 23 2019

city: Leuven

first: Bart

last: de Strooper

address: Campus Gasthuisberg, Herestraat 49, bus 602

department: VIB-KU Leuven Center for Brain & Disease Research

institute: KULeuven

summary: Microglia are involved in Alzheimer’s disease (AD) by adopting activated phenotypes. How ageing in the absence or presence of β-amyloid (Aβ) deposition in different brain areas affects this response and whether sex and AD risk genes are involved, remains however largely unknown. Here we analyzed the gene expression profiles of more than 10,000 individual microglia cells isolated from cortex and hippocampus of male and female AppNL-G-F at 4 different stages of Aβ deposition and in age-matched control mice. We demonstrate that microglia adopt two major activated states during normal aging and after exposure to amyloid plaques. One of the responses (activated response microglia, ARM) is enhanced in particular by amyloid plaques and is strongly enriched with AD risk genes. The ARM response is not homogeneous, as subgroups of microglia overexpressing MHC type II and tissue repair genes (Dkk2, Gpnmb, Spp1) are induced upon prolonged Aβ exposure. Microglia in female mice advance faster in the activation trajectories. Similar activated states were also found in a second AD model and in human brain. We demonstrate that abolishing the expression of Apoe, the major genetic risk factor for AD, impairs the establishment of ARMs, while the second microglia response type, enriched for interferon response genes, remains unaffected. Our data indicate that ARMs are the converging point of multiple AD risk factors.

overall_design: RNA-Seq of cortical and hippocampal microglia in  male APP/PS1-Apoe(null), APP/PS1, C57Bl/6 and C57Bl/6-Apoe(null) mice ;  at month 18

first: Carlo

last: Frigerio

first: Leen

last: Wolfs

first: Nicola

last: Fattorelli

last: Thrupp

first: Iryna

last: Voytyuk

first: Inga

last: Schmidt

first: Renzo

last: Mancuso

first: Wei-Ting

last: Chen

first: Maya

last: Woodbury

first: Gyan

last: Srivastava

first: Thomas

last: Möller

first: Eloise

last: Hudry

first: Sudeshna

last: Das

first: Takaomi

last: Saido

first: Eric

last: Karran

first: Bradley

last: Hyman

first: V

middle: H

last: Perry

first: Mark

last: Fiers

last: De Strooper


title: Blood, adipose and muscle samples taken from monozygotic twin pairs with age range 32-37

status: Public on Apr 20 2016

first: James

last: Timmons

summary: FITFATTWIN study identified from the FinnTwin16 Cohort, which is a population based, longitudinal study of Finnish twins born between October 1974 and December 1979. The participants had no chronic disease affecting the ability to exercise, no acute disease, and no drug or alcohol abuse.

overall_design: A total of 46 men (23 monozygotic twin pairs) identified from the FITFATTWIN study  and from this 41 individuals gave successfully PaxGene samples. In addition to fasting venous blood samples (PaxGene tubes), muscle and adipose tissue biopsies were taken for some of the twins. Gene expression profiling performed on 70 samples out of which 61 samples passed the QC.

first: Urho

last: Kajula


title: Transcriptomic comparison of Drosophila snRNP biogenesis mutants reveals mutant-specific changes in pre-mRNA processing: implications for Spinal Muscular Atrophy

status: Public on May 05 2016

city: Chapel Hill

last: Garcia

state: NC

address: 3344 Genome Science Bldg

department: Lineberger Comprehensive Cancer Center

institute: University of North Carolina at Chapel Hill

summary:
RNA-seq analysis of Drosophila snRNP biogenesis mutants.
In brief, the Phax and Ars2 mutant RNA-seq was used in combination with Series GSE49587 (Smn mutant and wild-type Oregon-R RNA-seq) to classify transcriptome changes as snRNP-dependent or mutant specific. Additional flies with Smn transgenes, containing Smn mutations that cause Spinal Muscular Atrophy (SMA) in humans, were then used to determine whether the snRNP-dependent or mutant specific changes were present in intermediate models of SMA.

overall_design: RNA-seq of total and polyA-RNA from whole larvae of snRNP biogenesis mutants and total RNA from whole prepupae of Smn point mutants (SMA-causing mutations).

first: Arnold

middle: G

last: Matera

first: Kavita

last: Praveen


title: Derivation and Evaluation of Putative Adverse Outcome Pathways for the Effects of Cyclooxygenase Inhibitors on Reproductive Processes in Fish

status: Public on Jan 14 2016

city: Costa Mesa

first: Alvine

last: Mehinto

address: 3535 Harbor Blvd, Suite 110

institute: Southern California Coastal Water Research Project

summary: Cyclooxygenase (COX) inhibition is of concern in fish because COX inhibitors (e.g., ibuprofen) are ubiquitous in aquatic systems/fish tissues, and can disrupt synthesis of prostaglandins that modulate a variety of essential biological functions including reproduction. Transcriptomic data and publicly available high throughput toxicity data were utilized to develop putative adverse outcome pathways (AOPs) for molecular initiating event (MIE) of COX inhibition. Effects of a waterborne exposure to indomethacin (IN; 100 µg/L), ibuprofen (IB; 200 µg/L) and celecoxib (CX; 20 µg/L) on liver metabolome and ovarian gene expression (using oligonucleotide microarrays) in sexually mature fathead minnows were examined. Metabolomic profiles of IN, IB and CX were not significantly different from control or one another. Exposure to IB and CX resulted in differential expression of comparable numbers of genes (IB = 433, CX= 545). In contrast, 2558 genes were differentially expressed in IN-treated fish. Functional analyses (canonical pathway and gene set enrichment) indicated extensive effects of IN on prostaglandin synthesis pathway, oocyte meiosis and several other processes consistent with physiological roles of prostaglandins. Transcriptomic data was congruent with apical endpoint data - IN reduced plasma prostaglandin F2 alpha concentrations, and ovarian COX activity, whereas IB and CX did not. Putative AOPs pathways for COX inhibition (MIE) leading to reproductive failure (adverse outcome) via reduction of: 1) ovulation, 2) reproductive behaviors mediated by exogenous and endogenous prostaglandins, and 3) oocyte maturation were developed.

overall_design: Adult fathead minnow were exposed to either 100 µg/L indomethacin, 200 µg/L ibuprofen, 20 µg/L celecoxib or UV-treated Lake Superior (control) water for 96 hours.  After exposure, microarray analyses were conducted using the female gonads (n=7-8 per treatment) and metabolomic analyses were conducted using the livers of all the exposed fish.

first: Dalma

last: Martinovic-Weigelt

first: Gerald

last: Ankley

first: Jason

last: Berninger

first: Timothy

last: Collette

first: John

last: Davis

first: Nancy

last: Denslow

first: Elizabeth

last: Durhan

first: Evan

last: Eid

first: Drew

last: Ekman

first: Kathleen

last: Jensen

first: Mike

last: Kahl

first: Carlie

last: LaLone

first: Daniel

last: Villeneuve


title: Alzheimer, MCI and control samples from AddneuroMed Cohort (batch 1)

status: Public on Aug 05 2015

first: James

last: Timmons

summary: Alzheimer case-control samples originate from the EU funded AddNeuroMed Cohort, which is a large cross-European AD biomarker study relying on human blood as the source of RNA.

overall_design: The design is case-control. Cases are either Alzheimer's disease patients, subjects with mild cognitive impairment or age and gender matched controls.

first: Angela

last: Hodges

first: Robert

last: Howard


title: Alzheimer, Mild Cognitive impairment and control samples from AddneuroMed Cohort

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

overall_design: Refer to individual Series


title: Uppsala Longitudinal Study of Adult Men (ULSAM)

summary: The Uppsala Longitudinal Study of Adult Men is a population-based study aimed at identifying risk factors for cardiovascular disease. At the time of biopsy all subjects were ~ 70yr of age

overall_design:
We extracted RNA from muscle tissue taken from 129 subjects, when they were aged ~70yr and characterised as disease-free (note the above average longevity in Swedes born circa 1920 compared with US and UK populations). From these samples, 108 yielded RNA of sufficient quality to profile on Affymetrix gene-chips.
Only survival data are used in the paper.
There are no data from cardiovascular disease subjects; we only profiled the healthy subjects and followed for 20yrs.

first: Thomas

last: Gustafsson


title: Stockholm dataset for prototype muscle age diagnostic

summary: Muscle biopsy samples  from healthy male subjects at the baseline belonging to either <29y or >59y age range. These samples were used to design a prototype of multi-tissue molecular diagnostic of healthy physiological age, which was then validated in multiple independent studies using gold standard external validation methods

overall_design: Resting skeletal muscle samples after an overnight fast related to GSE18583


title: Transcriptomics to discover splice variants involved in the browning of adipose tissue

summary: Adipose tissue is the major depot for energy storage. Recent studies have shown that at least three types of adipocytes can be distinguished depending on their anatomical locations : 1) The classic brown adipocytes, i.e., brown adipose tissue (BAT); 2) The 'brite' (brown-in-white) adipocytes, i.e. inguinal white adipose tissue (iWAT); 3) The 'true' white adipocytes, i.e., epididymal white adipose tissue (eWAT).  Two strains of mice (SV129 and C57BL/6J) were used in this study. SV strain is resistant to obesity and latter is prone to obesity. Pre-adipocyte cells were isolated from subcutaneous tissue (iWAT) to create four groups of cell cultures per strain of mouse.

overall_design: Cells were cultured for either 3 days or 7 days. At 3 days the cells are still proliferating and are not considered mature adipocytes, whereas adipocytes at day 7 are considered as mature. One of the 7 days cell cultures was treated with norepinephrine (NE) and another 7 days cell culture was treated with rosiglitazone (R) for the entire experiment. The remaining two cell cultures (3 and 7 days) were remained untreated. One untreated cell culture was harvested after 3 days of growth, whilst the rest were harvested after 7 days of growth.

first: Jamie


title: A comparison of Illumina and Ion Torrent sequencing platforms in the context of differential gene expression

status: Public on Aug 04 2017

city: Philadelphia

first: Nicholas

last: Lahens

address: Smilow Center for Translational Research 10-110 3400 Civic Center Blvd, Bldg 421

department: ITMAT

institute: University of Pennsylvania

summary:
Background: Though Illumina has largely dominated the RNA-Seq field, the simultaneous availability of Ion Torrent has left scientists wondering which platform is most effective for differential gene expression (DGE) analysis. Previous investigations of this question have typically used reference samples derived from cell lines and brain tissue, and do not involve biological variability. While these comparisons might inform studies of tissue-specific expression, marked by large-scale transcriptional differences, this is not the common use case.

Results: Here we employ a standard treatment/control experimental design, which enables us to evaluate these platforms in the context of the expression differences common in differential gene expression experiments. Specifically, we assessed the hepatic inflammatory response of mice by assaying liver RNA from control and IL-1β treated animals with both the Illumina HiSeq and the Ion Torrent Proton sequencing platforms. We found the greatest difference between the platforms at the level of read alignment, a moderate level of concordance at the level of DGE analysis, and nearly identical results at the level of differentially affected pathways. Interestingly, we also observed a strong interaction between sequencing platform and choice of aligner. By aligning both real and simulated Illumina and Ion Torrent data with the twelve most commonly-cited aligners in the literature, we observed that different aligner and platform combinations were better suited to probing different genomic features; for example, disentangling the source of expression in gene-pseudogene pairs.

Conclusions: Taken together, our results indicate that while Illumina and Ion Torrent have similar capacities to detect changes in biology from a treatment/control experiment, these platforms may be tailored to interrogate different transcriptional phenomena through careful selection of alignment software.

overall_design: Liver RNA from mice treated with IL-1β or saline. Both treatment conditions have 5 biological replicates.

middle: F

first: Emanuela

last: Ricciotti

first: Olga

last: Smirnova

first: Erik

last: Toorens

first: Eun

last: Kim

first: Giacomo

last: Baruzzo

first: Katharina

last: Hayer

first: Tapan

last: Ganguly

first: Jonathan

last: Schug

first: Gregory

last: Grant


title: Alzheimer, Mild Cognitive impairment and control samples from AddneuroMed Cohort (batch 2)


title: Expression data from wild type and Gata6-deficient tissue resident peritoneal macrophages

status: Public on May 09 2014

city: Cardiff

first: Philip

last: Taylor

address: Tenovus Building, Heath Park

department: School of Medicine

institute: Cardiff University

summary: Tissue resident macrophages are notoriously heterogeneous, exhibiting discrete phenotypes as a consequence of tissue- and micro-anatomical niche-specific functions, but the molecular basis for this is not understood. We resolved a restricted transcriptional profile for the self-renewing population of peritoneal resident macrophages, which is expressed during homeostasis and inflammation and distinct from other MØ. Prominent within this profile was the expression of Gata6. This study represents a characterisation of the role of Gata6 in peritoneal resident macrophage phenotype. We used microarrays to determine the patterns of gene expression in peritoneal resident MØ in the absence of GATA-6 against wild type.

overall_design: Conditional 'floxed' Gata6 deficient sex-matched mice between 7 weeks old were compared against wild type


title: The Heritage (HEalth, RIsk factors, exercise Training And GEnetics) family study

status: Public on Jun 12 2013

summary:
The overall objective of the heritage project is to study the role of the genotype in cardiovascular,metabolic and hormonal responses to aerobic exercise training and the contribution of regular exercise to changes in several cardiovascular disease and diabetes risk factors.

PLEASE NOTE THE POST-TRAINING GENE CHIP FILES HAVE NEVER BEEN RELEASED ON GEO. PLEASE ALSO NOTE THAT DUE TO THE OUTDATED INSULIN ASSAY UTILISED IN THE HERITAGE STUDY, THE INSULIN DATA WAS NOT COMPARABLE WITH ANY MORE RECENT MODERN STUDIES.

overall_design:
The study cohort in this analysis consists of 473 Caucasian subjects (230 male and 243 female) from 99 nuclear families who completed ≥58 of the prescribed 60 exercise-training sessions.The phenotypic expression of each individual’s genotype is assessed under two well-defined environmental conditions, the pre- and post-training conditions. Here we have made the pre-training data available as used in the article Phillips BE, Williams JP, Gustafsson T, Bouchard C, Rankinen T, et al. (2013) Molecular Networks of Human Muscle Adaptation to Exercise and Age. PLoS Genet 9(3): e1003389. doi:10.1371/journal.pgen.1003389
52 U133+2 profiles (17–63 yr) generated from pre-exercise muscle biopsy samples from the HERITAGE Family Study.
Heritage_pre dataset.


title: Expression data from FACS purified nociceptor neurons from peripheral sensory ganglia

status: Public on Aug 28 2013

city: Boston

first: Isaac

middle: M

last: Chiu

state: MA

address: 3 Blackfan Circle

department: Neurology

institute: Boston Children's Hospital

summary:
The goal of this study was to analyze global gene expression in specific populations of nociceptor sensory neurons, the neurons that detect damaging/noxious stimuli.
The dorsal root ganglia (DRG), trigeminal ganglia, and nodose ganglia are anatomically distinct peripheral sensory ganglia that contain nociceptors which innervate skin, gut, lungs, and other distinct organ tissues.  We used flow cytometry to purify nociceptors from these ganglia and profiled their global gene expression signatures to compare gene expression between these different anatomically distinct nociceptors.

overall_design: Nav1.8-Cre were bred with Rosa26-TdTomato to generate Nav1.8-Cre/R26-TdTomato reporter progeny, where all peripheral nociceptor neurons are genetically marked with red fluroescence due to specific expression of the TTX- resistant sodium channel Nav1.8.  Lumbar region dorsal root ganglia (DRG), trigeminal ganglia, and nodose ganglia were dissected from mice (3 mice were pooled/sample).  Highly red fluorescent neurons were Facs purified, RNA extracted, and processed for microarray analysis.

first: Clifford

last: Woolf


title: DERBY BBSRC RET Study: Impact of resistance exercise on human skeletal muscle gene expression

first: James

last: Timmons

summary: The aim of this work was to produce a molecular signature of human muscle responses to supervised resistance training and examine how such a profile relates to established aerobic exercise adaptation gene networks.

overall_design:
Subjects were recruited from an age range of 18 to 75 y. Before beginning the study all subjects were screened using a medical questionnaire, physical examination and resting ECG with exclusions for overt muscle wasting (>2 SD below age norms)[85], metabolic, respiratory/cardiovascular disorders or other major contraindications to a healthy status. All subjects had normal blood chemistry and were normotensive (BP <140/90). All subjects performed routine activities of daily living and recreation but did not participate in moderate to high intensity aerobic exercise and none had participated in RET in the last 24 months. Body composition was measured at screening and following RET by dual energy X-ray absorptiometry (DEXA) (Lunar Prodigy II, GE Medical Systems). Subject positioning on the DEXA bed was optimized to allow the region of interest (ROI) body compartments to be analyzed separately. The upper leg ROI was selected as the area inferior to the lowest visible point of the coccyx to the mid-point of the patella.
The dataset comprises 44 pre-exercise and 44 post-exercise samples. In addition there is a baseline sample NB021_pre-training (D13_NB021F). Therefore there are 89 samples in total.  (Note: Singleton baseline sample NB021_pre-training was normalized only using all baseline samples.)
Derby dataset.

first: Bethan

last: Phillips

middle: A


title: Expression data from post-transplant lymphoproliferative disorder (PTLD) patient samples

status: Public on Jun 23 2012

first: Julio

last: Finalet

address: Herestraat 49

summary:
In this study we focussed on malignant post-transplant lymphomas.
Post-transplant lymphoma is strongly associated with Epstein-Barr Virus (EBV) infection in contrast to lymphoma arising in an immunocompetent population. Nevertheless, about 1 in 3 PTLD cases are negative for EBV.
We used a microarray to define the gene expression profile of different PTLDs to elucidate the pathogenesis of EBV(+) and EBV(-) PTLD and to define whether EBV(-) PTLD is biologically different from EBV(-) lymphoma arising in an immunocompetent host.

overall_design: PTLD patient samples were randomly selected for RNA extraction and hybridization on an Affymetrix platform. The post-transplant tumors consisted of homogenous sheets of neoplastic cells ensuring reliability of the gene expression data.

first: Thomas

last: Tousseyn

first: Julie

last: Morscio

last: Ferreiro

first: Daan

last: Dierickx

first: An

last: Herreman

first: Xavier

last: Sagaert

first: Patrick

last: Matthys

first: Iwona

last: Wlodarska

first: Peter

last: van Loo

first: Christiane

last: De Wolf-Peeters

first: Gregor

last: Verhoef

first: Jan

last: Cools

first: Emilie

last: Bittoun


title: Human mesenchymal stem cell-derived matrices for enhanced osteoregeneration

status: Public on Feb 17 2012

city: Temple

first: Joni

last: Ylostalo

address: 5701 Airport Rd., Module C

department: Institute for Regenerative Medicine

institute: Texas A&M

summary: The methodology for the repair of critical-sized or non-union bone lesions has unpredictable efficacy due in part to our incomplete knowledge of bone repair and the biocompatibility of bone substitutes. Although human mesenchymal stem cells (hMSCs) differentiate into osteoblasts, which promote bone growth, their ability to repair bone has been unpredictable. We hypothesized that given the multi-stage process of osteogenesis, hMSC-mediated repair might be maximal at a specific time-point of healing. Utilizing a mouse model of calvarial healing, we demonstrate that the osteo-repair capacity of hMSCs can be substantially augmented by treatment with an inhibitor of peroxisome-proliferator-activated-receptor-γ, but efficacy is confined to the rapid osteogenic phase. Upon entry into the bone-remodeling phase, hMSC retention signals are lost, resulting in truncation of healing. To solve this limitation, we prepared a scaffold consisting of hMSC-derived extracellular matrix (ECM) containing the necessary biomolecules for extended site-specific hMSC retention. When inhibitor-treated hMSCs were co-administered with ECM, they remained at the injury well into the remodeling phase of healing, which resulted in reproducible and complete repair of critical-sized defects in 3 weeks. These data suggest that hMSC-derived ECM and inhibitor-treated hMSCs could be employed at optimal times to substantially and reproducibly improve bone repair.

overall_design: To gain insight into the superior healing potential of GW-hMSCs and also what might be accounting for their extended engraftment, microarray analyses on the RNA extracted from the calvarial tissue recovered after days 5 and 14 were performed. Equal amounts of total RNA from 4 animals per group and time point were pooled and animals receiving control (DMSO) or peroxisome proliferator-activated receptor-gamma inhibitor GW9662-treated hMSCs were compared with the assumption that murine cross-hybridization would be constant throughout the samples and thus be subtracted from the analysis.

first: Bret

last: Clough

first: Katie

last: Coble

first: Carl

last: Gregory

first: Ulf

last: Krause

first: Suzanne

last: Zeitouni


title: Identification of in vivo DNA-binding mechanisms of Pax6 and reconstruction of Pax6-dependent gene regulatory networks during lens and forebrain development

status: Public on Jul 09 2015

city: Bronx

first: Shira

last: Rockowitz

address: 1300 Morris Park Ave

institute: Albert Einstein College of Medicine

summary: The transcription factor Pax6 is comprised of the paired domain (PD) and homeodomain (HD). In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific subpopulations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification. Pax6 also regulates the entire lens developmental program. To reconstruct Pax6-dependent gene regulatory networks (GRNs), ChIP-seq studies were performed using lens and forebrain chromatin from mice. A total of 3,723 (forebrain) and 3,514 (lens) Pax6-containing peaks were identified, with ~70% of them found in both tissues and thereafter called “common” peaks. Analysis of Pax6-bound peaks identified motifs that closely resemble Pax6-PD, -PD/HD and -HD established binding sequences. Mapping of H3K4me1, H3K4me3, H3K27ac, H3K27me3 and RNA polymerase II revealed distinct types of tissue-specific enhancers bound by Pax6. Pax6 directly regulates cortical neurogenesis through activation (e.g. Dmrta1 and Ngn2) and repression (e.g. Ascl1, Fezf2, and Gsx2) of transcription factors. In lens, Pax6 directly regulates cell cycle exit control via components of FGF (Fgfr2, Ccnd1, and Prox1) and Wnt (Dkk3, Wnt7a, Lrp6, Bcl9l, and Ccnd1) signaling pathways. Collectively, these studies provide genome-wide analysis of Pax6-dependent GRNs in lens and forebrain and establish novel roles of Pax6 in organogenesis.

overall_design: Examination of Pax6 in mouse embryonic forebrain and newborn lens. We performed ChIP-seq on mouse E12.5 embryonic forebrain and newborn lens. Genome-wide binding sites of Pax6, H3K4me1, H3K4me3, H3K27ac, H3K27me3, and Pol2 were generated. We also performed RNA-seq on mouse E12.5 embryonic forebrain and newborn lens epithelial cells and fibers.

first: Jian

last: Sun

first: Qing

last: Xie

first: Ruth

last: Ashery-Padan

first: Deyou

last: Zheng

first: Ales

last: Cvekl


title: Long Neural Genes Harbor Recurrent DNA Break Clusters in Neural Stem/Progenitor Cells

status: Public on Feb 15 2016

city: San Francisco

first: Bjoern

last: Schwer

state: CA

institute: University of California, San Francisco

summary: Repair of DNA double-strand breaks (DSBs) by non-homologous end-joining is critical for neural development, and brain cells frequently contain somatic genomic variations that might involve DSB intermediates. We now use an unbiased, high-throughput approach to identify genomic regions harboring recurrent DSBs in primary neural stem/progenitor cells (NSPCs).  We identify 27 recurrent DSB clusters (RDCs) and, remarkably, all occur within gene bodies.  Most of these NSPC RDCs were detected only upon mild, aphidicolin-induced replication stress, providing a nucleotide-resolution view of replication-associated genomic fragile sites.  The vast majority of RDCs occur in long, transcribed, and late-replicating genes.  Moreover, almost 90% of identified RDC-containing genes are involved in synapse function and/or neural cell adhesion, with a substantial fraction also implicated in tumor suppression and/or mental disorders.  Our characterization of NSPC RDCs reveals a basis of gene fragility and suggests potential impacts of DNA breaks on neurodevelopment and neural functions.

overall_design: We performed high-throughput, genome-wide, translocation sequencing (HTGTS) and GRO-seq in primary mouse neural stem/progenitor cells of the indicated genotypes.

first: Pei-Chi

last: Wei

first: Amelia

last: Chang

first: Jennifer

last: Kao

first: Zhou

last: Du

first: Robin

last: Meyers

first: Frederick

middle: W

last: Alt


title: A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype (resting muscle after endurance training)

status: Public on Feb 10 2012

first: James

last: Timmons

summary: The molecular pathways which are activated and contribute to physiological remodeling of skeletal muscle in response to endurance exercise have not been fully characterized. We previously reported that ~800 gene transcripts are regulated following 6 weeks of supervised endurance training in young sedentary males, referred to as the training responsive transcriptome (TRT). Here we utilized this database together with data on biological variation in muscle adaptation to aerobic endurance training in both humans and a novel out-bred rodent model to study the potential regulatory molecules that coordinate this complex network of genes. We identified three DNA sequences representing RUNX1, SOX9, and PAX3 transcription factor binding sites as over-represented in the TRT. In turn, miRNA profiling indicated that several miRNAs targeting RUNX1, SOX9 and PAX3 were down-regulated by endurance training. The TRT was then examined by contrasting subjects who demonstrated the least vs. the greatest improvement in aerobic capacity (low vs. high responders), and at least 100 of the 800 TRT genes were differentially regulated, thus suggesting regulation of these genes may be important for improving aerobic capacity. In high responders, pro-angiogenic and tissue developmental networks emerged as key candidates for coordinating tissue aerobic adaptation. Beyond RNA level validation there were several DNA variants that associated with VO(2)max trainability in the HERITAGE Family Study but these did not pass conservative Bonferroni adjustment. In addition, in a rat model selected across 10 generations for high aerobic training responsiveness, we found that both the TRT and a homologous subset of the human high responder genes were regulated to a greater degree in high responder rodent skeletal muscle. This analysis provides a comprehensive map of the transcriptomic features important for aerobic exercise-induced improvements in maximal oxygen consumption.

overall_design: This data is from skeletal muscle post 6 weeks of endurance exercise training matching the samples (pre-training, fasting) provided in GSE18583

first: Iain

last: Gallagher


title: Developmental arrest of Drosophila survival motor neuron (Smn) mutants accounts for differences in expression of minor intron-containing genes

status: Public on Aug 07 2013

first: Eric

last: Garcia

summary: RNA-seq was used to analyze mRNA levels and splicing differences between wild-type (Oregon R) and Smn null mutant larvae.

overall_design:
Illumina RNA-seq of Oregon R and Smn mutant age-matched larvae from RNA extracted on day four post egg laying.

Conclusions from this study used the publicly available modENCODE data from Graveley et al. Nature 2011 (in addition to our RNA-seq data). We downloaded their SRA files, dumped them to fastq files, and put them through our same analysis pipelines. The renalysis data and details are provided in 'reanalysis.tar' and readme_reanalysis.txt.

The Cufflinks processed file outputs (22 files in 'Cufflinks_outputs.tar') are derived from all of our raw sample files and all of the developmental data mentioned in the readme.txt file. The file format and content description is provided in the 'readme_for_Cufflinks.txt'

Unlike Cufflinks cuffdiff analysis that merged our data with the developmental data, the MISO and DEXSeq analysis was carried out in parallel with analysis of our samples. This generated two additional  files for the DEXSeq developmental analysis (DEXSeq output; paired end developmental Graveley et al. Nature 2011):
L2_L3P1_2_DEUtable.txt
L312hr_L3P1_2_DEUtable.txt
Please note that MISO lacks the capacity to incorporate replicates, which contributed to the abundance of these file types.

MISO output file names are prepended with the respective sample/raw data names. For example,  EG003_EG007.*miso_bf.txt.gz are MISO comparison of Ore-R R1 (EG003) and Smn R1 (EG007).

first: A

last: Matera

first: E


title: A transcriptional map of the impact of endurance exercise training on skeletal muscle phenotype

overall_design: Refer to individual Series. The P-odd number samples are baseline pre-training, while the P-even numbers are baseline post supervised endurance exercise training. The arrays were produced as part of a collaboration written and established by J Timmons (PI) between Pfizer UK LTD and Karolinska in 1998. Original array profiles were produced in 2001 (U95 arrays) on a subset of 'responders' and the informatics analysis carried out by Ola Larsson and J Timmons in 2004. The full cohort was re-profiled by J Timmons in 2006 using U133+2 arrays (as deposited here).


title: Skin Electrovaccination: Effects on Transgene Expression, DNA Persistence and Local Tissue Environment

status: Public on Sep 11 2009

summary:
Background: The use of electrical pulses to enhance uptake of molecules into living cells have been used for decades. This technique, often referred to as electroporation, has become an increasingly popular method to enhance in vivo DNA delivery for both gene. therapy applications as well as for delivery of vaccines against both infectious diseases and cancer. In vivo electrovaccination is currently being investigated in several clinical trials, including DNA delivery to healthy volunteers. However, the mode of action at molecular level is not yet fully understood.
Methodology/Principal Findings: This study investigates intradermal DNA electrovaccination in detail and describes the effects on expression of the vaccine antigen, plasmid persistence and the local tissue environment. Gene profiling of the vaccination site is currently being evaluated in clinical trials, the data provided will be of high significance.. Conclusions/Significance: This study provides important insights to how DNA delivery by intradermal electrovaccination affects the local immunological responses of the skin, transgene expression and clearance of the plasmid. As the described vaccination approach showed that the combination of DNA and electroporation induced a significant up-regulation of pro-inflammatory genes. In vivo imaging of luciferase activity after electrovaccination demonstrated a rapid onset (minutes) and a long duration (months) of transgene expression. However, when the more immunogenic prostate specific antigen (PSA) was co-administered, PSA-specific T cells were induced and concurrently the luciferase expression became undetectable. Electroporation did not affect the long-term persistence of the PSA-expressing plasmid.

overall_design: untreated mice (n=4), and mice subjected to DNA vaccination followed by electroporation (n=3)

first: Anna-Karin

last: Roos


title: Genome-wide profiling characterizes CRCs with genetic instability and specific routes to HLA class I loss and immunoescape

status: Public on Feb 28 2011

city: Granada

first: Francisco

last: Ruiz-Cabello

address: Avenida Fuerzas Armadas 2

country: Spain

institute: Hospital Universitario Virgen de las Nieves

summary: We compared the expression of genes related to inflammatory cytotoxic functions between MSI and MSS (HLA class I negative and positive) gastrointestinal adenocarcinomas (GIACs), seeking evidence of differences in inflammatory mediators and cytotoxic T-cell responses. Twenty-two GIACs were divided into three study groups as a function of HLA class I expression and MSI phenotype. Comparison between eight high-level MSI (MSI-H) and 8 MSS/HLA+ (control) cancers identified 2170 differentially expressed genes (p< 0.05) after microarray analysis on the Affymetrix HG-U133-Plus-PM plate. We grouped genes in Gene Ontology functional categories: apoptotic programme (119 genes, p=5.1·10-7),  leukocyte activation (32 genes, p=0.01), T cell activation (20 genes, p= 0.01), and cytokine production (19 genes, p= 0.04). Real-time RT-PCR and immunohistochemical evaluation  were used to confirm  some  microarray data, finding that increased mRNA levels of pro-inflammatory cytokines and cytotoxic mediators were associated with  greater infiltration by CD8+ T lymphocytes in the MSI-H group (p<0.001). Finally, tumours with immunohistochemical HLA class I negative pattern were not grouped together but rather in accordance with features of the gene expression profile of MSI or MSS tumours. As expected, genes associated with antigen processing machinery and MHC class I molecules (TAP2, B2m) were downregulated in MSS/HLA-ABC negative CRCs.  In conclusion, microarray and immunohistochemical data may be useful to comprehensively assess tumour-host interactions and differentiate MSI from MSS cancers. The two types of tumours, MSI/HLA- and MSS/HLA-, showed marked differences in the composition and intensity of infiltrating leukocytes, suggesting that their immune escape strategies involve distinct pathways.

overall_design: Case-control study. Samples were selected according to immunological criteria: those with total loss of HLA antigens and  those without alterations in the expression of HLA molecules. In addition, the microsatellite instability genotype of all the samples was also analyzed, resulting in microsatellite stability (MSS) and microsatellite instability (MSI) samples. Therefore, three groups of samples were selected: MSS/HLA+, MSS/HLA-, and MSI. The MSS/HLA+ group was used as the control.

first: Mónica

last: Bernal

first: Fernando

last: García-Alcalde

first: Ángel

last: Concha

first: Armando

last: Blanco

first: Federico

last: Garrido


title: Baseline skeletal muscle gene expression

status: Public on Feb 04 2010

summary:
Muscle biopsy samples were obtained from two groups of male subjects prior to endurance training. The samples were used to predict training responses.
Baseline gene expression involving 30 probe sets was able to classify subjects into high and low responders.

overall_design: Resting skeletal muscle sample after an overnight fast.

first: Steen

last: Knudsen


title: Gene expression profiles of Hodgkin’s lymphoma cell lines with different sensitivity to cytotoxic drugs

status: Public on Jan 10 2011

city: Halle (Saale)

first: Martin

middle: Sebastian

last: Staege

state: Sachsen-Anhalt

address: Ernst-Grube-Str. 40

department: Universitätsklinik u. Poliklinik für Kinder- u. Jugendmedizin

summary:
By using high-density DNA microarrays, we analyzed the gene-expression profile of Hodgkin's lymphoma cell lines.
Furthermore, we tested the sensitivity of these cell lines for cytotoxic drugs (cisplatin, etoposide, melphalan) and compared the gene-expression profile of chemotherapy-resistant and -sensitive cell lines.
Staege et al., Exp Hematol 2008;36:886-896

overall_design: RNA was extracted from established Hodgkin's lymphoma cell lines and hybridized with Affymetrix HG_U133A microarrays.

first: Ursula

last: Banning-Eichenseer

first: Stefan

last: Burdach

first: Guenther

last: Richter

first: Dieter

last: Koerholz


title: The major risk factors for Alzheimer’s disease: Age, Sex and Genes, modulate the microglia response to Aβ plaques (KW)

status: Public on Apr 23 2019

first: Bart

last: de Strooper

summary: Microglia are involved in Alzheimer’s disease (AD) by adopting activated phenotypes. How ageing in the absence or presence of β-amyloid (Aβ) deposition in different brain areas affects this response and whether sex and AD risk genes are involved, remains however largely unknown. Here we analyzed the gene expression profiles of more than 10,000 individual microglia cells isolated from cortex and hippocampus of male and female AppNL-G-F at 4 different stages of Aβ deposition and in age-matched control mice. We demonstrate that microglia adopt two major activated states during normal aging and after exposure to amyloid plaques. One of the responses (activated response microglia, ARM) is enhanced in particular by amyloid plaques and is strongly enriched with AD risk genes. The ARM response is not homogeneous, as subgroups of microglia overexpressing MHC type II and tissue repair genes (Dkk2, Gpnmb, Spp1) are induced upon prolonged Aβ exposure. Microglia in female mice advance faster in the activation trajectories. Similar activated states were also found in a second AD model and in human brain. We demonstrate that abolishing the expression of Apoe, the major genetic risk factor for AD, impairs the establishment of ARMs, while the second microglia response type, enriched for interferon response genes, remains unaffected. Our data indicate that ARMs are the converging point of multiple AD risk factors.

overall_design: RNA-Seq of cortical and hippocampal microglia in female and male C57Bl/6 wild type mice and in AppNL-G-F mice M3, M6, M12, M21 (32 experimental conditions, 2 mice per condition - data pooled).

first: Carlo

middle: S

last: Frigerio

first: Leen

last: Wolfs

first: Nicola

last: Fattorelli

last: Thrupp

first: Iryna

last: Voytyuk

first: Inga

last: Schmidt

first: Renzo

last: Mancuso

first: Wei-Ting

last: Chen

first: Maya

last: Woodbury

first: Gyan

last: Srivastava

first: Thomas

last: Möller

first: Eloise

last: Hudry

first: Sudeshna

last: Das

first: Takaomi

last: Saido

last: Karran

first: Bradley

last: Hyman

first: V

last: Perry

first: Mark

last: Fiers

last: De Strooper


title: The major risk factors for Alzheimer’s disease: Age, Sex and Genes, modulate the microglia response to Aβ plaques

first: Bart

last: de Strooper

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

overall_design: Refer to individual Series


title: A three-dimensional map of the human genome at kilobase resolution reveals prinicples of chromatin looping

status: Public on Dec 11 2014

city: Houston

first: Suhas

last: Rao

address: 1 Baylor Plaza

department: Molecular and Human Genetics

institute: Baylor College of Medicine

summary: We use in situ Hi-C to probe the three-dimensional architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1-kilobase resolution. We find that genomes are partitioned into local domains, which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ~10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs ‘facing’ one another. The inactive X-chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.

overall_design:
in situ Hi-C and dilution Hi-C were used to probe the three-dimensional structure of the genome in eight diverse human cell types and one mouse cell type.

Detailed information about all files (and file formats) uploaded to GEO for this study can be found in the supplementary file 'GSE63525_OVERALL_README.rtf'.

first: Miriam

last: Huntley

first: Erez

last: Lieberman Aiden


title: Exon-level analyses of neuroblastoma

status: Public on Jun 18 2012

city: Essen

first: Alexander

last: Schramm

address: Hufelandstr. 55

department: Childrens Hospital

institute: University Hospital Essen

type:
Expression profiling by array
Third-party reanalysis

summary: In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol.

overall_design: This submission contains 87 exon array profiles and are used together with exon array data from 26 Samples in GSE21713 (see 'Relation' links below) to predict the outcome of patients with neuroblastoma. The resulting dataset, which is linked below as a supplementary file ('GSE32664_complete_RMA_data.txt'), was used for the subsequent analyses.

first: A

first: P

last: Mestdagh

first: J

last: Vandesompele

first: B

last: Schowe

first: K

last: Morik

last: Eggert

last: Schulte