title: Second-generation molecular subgrouping of medulloblastoma: an international meta-analysis of Group 3 and Group 4 subtypes

status: Public on Jun 11 2019

city: Newcastle upon Tyne

first: Ed

last: Schwalbe

address: Ellison Place

department: Natural Sciences

institute: Northumbria University

summary: We undertook a meta-analysis based on DNA methylation patterns of Group3/4 subgroup medulloblastoma from three published studies, alongside additional unpublished tumours (total n=1501).

overall_design: We used 267 samples from GSE93646, 356 samples from GSE85212, 725 samples from Northcott et al., 2017 (PMID: 28726821) and 153 previously unpublished samples from the St. Jude collection. Bisulfite-converted DNA from medulloblastoma samples were hybridised to the Illumina Infinium 450k and Infinium MethylationEPIC BeadChips.

first: Edward

first: Tanvi

last: Sharma


title: LINC00261 is an epigenetically-regulated tumor suppressor that is essential for activation of the DNA damage response (AEC/LUAD RNA-seq data set)

status: Public on Mar 01 2019

city: Glendale

first: Crystal

last: Marconett

state: CA

address: 1856 Kirkby Rd

department: Translational Genomics

country: USA

institute: Keck School of Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary: Lung cancer is the leading cause of cancer-related death in the United States. Long non-coding RNAs (lncRNAs) are a class of regulatory molecules whose role in lung carcinogenesis is poorly understood. In this study, we profiled lncRNA expression in lung adenocarcinoma (LUAD) cell lines, compared their expression to that of purified alveolar epithelial type II cells (the purported cell of origin for LUAD), cross-referenced these with lncRNAs altered in primary human tumors, and interrogated for lncRNA whose expression correlated with patient survival. We identified LINC00261, a lncRNA with unknown function in LUAD, adjacent to the pioneering transcription factor FOXA2. Loss of LINC00261 was observed in multiple tumor types, including liver, breast, and gastric cancer. Reintroduction of LINC00261 into human LUAD cell lines inhibited cell migration and slowed proliferation by inducing a G2/M cell cycle arrest while upregulating DNA damage pathway genes and inducing phosphorylation-mediated activation of components of the DNA damage pathway. FOXA2 was able to induce LINC00261 expression, and the entire locus underwent hypermethylation in LUAD, leading to loss of expression. We have thus identified an epigenetically deregulated lncRNA, whose loss of expression in LUAD promotes the malignant phenotype and blocks activation of the DNA damage machinery, predisposing lung cells to cancer development.

overall_design: Primary AEC isolated from three human donor remnant transplant lungs and sixteen (16) lung adenocarcinoma cell lines. Note that PC3 and PC9 are lung adenocarcinoma cell lines from Japan, NOT prostate cancer cell lines

first: Shandy

last: Shahabi

first: Vishaly

last: Kumaran

first: Jonathan

last: Castillo

first: Zhengmin

last: Cong

first: Gopika

last: Nandagopal

first: Daniel

middle: J

last: Mullen

first: Alexander

last: Alvarado

first: Michele

middle: R

last: Correa

first: Autumn

last: Saizan

first: Riya

last: Goel

first: Amrita

last: Bhat

first: Sean

middle: K

last: Lynch

first: Beiyun

last: Zhou

first: Zea

last: Borok


title: LINC00261 is an epigenetically-regulated tumor suppressor that is essential for activation of the DNA damage response [H522-LINC00261 RNA-seq data set]

type: Expression profiling by high throughput sequencing

overall_design: H522 lung adenocarcinoma cell lines were stably transfected with either CMV-LINC00261 expression vector or CMV-NEO control.

last: Goal


title: Comparison of the Transcriptome Profile of four Tissue Specific MSCs: Significance and Therapeutic Implications

status: Public on Jun 15 2018

city: amman

first: DANA

last: HATTAB

address: queen rania street

country: Jordan

institute: CELL THERAPY CENTER

summary:
Performing global gene expression profiling for different types of (Mesenchymal stem cells) MSCs can provide important information that might help in understanding the biology and ontogeny of MSCs. Additionally, it might help in the understanding of the propensity and capacity of MSCs from a particular source to differentiate toward a particular lineage or adopt a certain fate.
We used microarrays to detail the global  gene expression profiling for different types of MSCs including bone marrow (BM), Adipose Tissue (AT), Umbilical cord (UC)  and placenta(PL). The MSCs transcriptome profile was additionally compared to the transcriptome profile of dermal fibroblasts.

overall_design: All MSCs (BM, AT, UC and PL) and fibrpblats were cultured and processed under similar conditions. Platelet lysate was used instead of fetal bovine serum (FBS), as a serum supplement. Affymetrix® Microarray and Human Transcriptome Analysis 2 (HTA 2) chips were used for transcriptome profiling.

first: Dana

last: Alhattab

first: Fatima

last: Jamali

first: Abdalla

last: Awidi


title: Epigenome-wide analysis of DNA methylation in lung tissue shows concordance with blood studies and identifies tobacco smoke-inducible enhancers

status: Public on Feb 07 2018

first: Crystal

last: Marconett

type: Genome binding/occupancy profiling by high throughput sequencing

type: Methylation profiling by high throughput sequencing

summary: Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis

overall_design: NGS data from purified alveolar epithelial type 2 (AT2) cells originating from 2 donor lungs, including whole genome bisulfite sequencing (WGBS) and Chromatin immunoprecipitation (ChIPseq)

first: T

last: Stueve

first: Wen

middle: Q

last: Li

first: Jianxin

last: Shi

first: C

middle: N

last: Zhang

last: Yang

first: D

first: W

last: Wheeler

first: Xing

last: Hua

first: B

first: Z

first: N

last: Caporaso

first: A

middle: C

last: Pesatori

first: J

last: Duan

first: I

middle: A

last: Laird-Offringa

first: M

middle: T

last: Landi


title: RNA sequencing analysis of decidua tissues from unexplained recurrent spontaneous abortion patients and controls with induced abortions

status: Public on Jul 12 2018

city: Nanjing

first: Mingming

last: Yu

address: NO.818 Tianyuan East Road, Jiangning District

department: School of public health

country: China

institute: Nanjing Medical University

summary: Recurrent spontaneous abortion (RSA), defined as the failure of two or more consecutive clinical pregnancies before 20 weeks of gestation, affects approximately 1% of couples attempting to conceive. However, the underlying mechanisms of 50% of cases are unknown. The decidua plays a crucial role during pregnancy, which can provide a delicate balance between immune tolerance and defense to maintain the pregnancy.We performed RNA-seq to identify gene expression alterations in the deciduas of RSA patients and controls. RNA-seq was done using TruSeq Stranded mRNA Library Preparation. Briefly, intact RNA was fragmented, end repaired, adapter ligation and PCR amplified following illumina protocol. Libraries were sequencing by illumins Hiseq 2000. After quality control, sequence data were processed with STAR to generate read alignments with hg19. Raw read counts for annotated genes were obtained with featureCounts with default settings, normalized and analyzed using DEseq2.

overall_design:
Intact RNA isolated from 6 human decidua tissues was fragmented, end repaired, adapter ligation and PCR amplified following illumina protocol. Libraries were sequencing by illumins Hiseq 2000.

UPDATE: [Jan-29-2026] The titles of GSM3119483-GSM3119485 were changed from 'decidua_induced abortion' to 'decidua_recurrent spontaneous abortion', and the titles of GSM3119486-GSM3119488 were changed from 'decidua_recurrent spontaneous abortion' to 'decidua_induced abortion'. The raw data and processed data associated with each GSM did not change.

first: Guizhen

last: Du


title: Genome-wide profiling of cervical RNA-binding proteins identified HPV regulation of RNASEH2A expression by viral E7 and E2F1

status: Public on Apr 25 2019

city: Bethesda

first: Yanqin

state: Maryland

address: 10 Center Dr.

institute: NIH

summary: RNA-binding proteins (RBPs) have been shown to control mRNA processing, stability, transport, editing and translation. Application of large-scale quantitative technologies has facilitated genome-wide identification of RBPs and linked their defects to human diseases and carcinogenesis. We have recently conducted transcriptome analysis comparing normal cervical tissues with HPV-positive cervical cancer tissues by using two different RNA-seq platforms. As the results, 614 differentially expressed protein-coding transcripts were identified, which are enriched in cancer related pathways and consist of 95 known RBPs. TaqMan RT-qPCR was used to verify altered expression of 26 genes with a cohort of 72 cervical samples, including 24 normal cervical, 25 CIN 2-3, and 23 cervical cancer tissues. LY6K, FAM83A, CELSR3, ASF1B, IQGAP3, SEMA3F, CLDN10, MSX1, CXCL5, ASRGL1, ELAVL2, GRB7, KHSRP, NOVA1, PTBP1 and RNASEH2A were identified being novel candidates in association with cervical lesion progression and carcinogenesis. We further demonstrated that HPV16 or HPV18 infection leads to altered expression of 8 RBP genes (CDKN2A, ELAVL2, GRB7, HSPB1, KHSRP, NOVA1, PTBP1, and RNASEH2A) in human vaginal and foreskin keratinocytes.  While both viral E6 and E7 decrease NOVA1 expression, viral E7 was found to increase the expression of both RNASEH2A and PCNA in an E2F1 dependent manner, two key factors closely associated with the progression of cervical neoplasia. By illustration of the first comprehensive cervical genome expression atlas, we have identified the altered expression of many novel genes due to HPV infection, which could be biomarkers for better diagnosis and treatment of cervical cancer.

overall_design: Gene expression patterns of seven normal cervical tissues were compared with that of seven cervical cancer tissues by two different RNA-seq platforms. Additional 72 clinical samples and HPV-infected keratinocytes were analyzed by RT-qPCR to verify the HPV-infection altered gene expression.

first: Junfen

last: Xu

first: Xiaohong

last: Wang

first: Jun

last: Zhu

first: Zhi-Ming

last: Zheng


title: Evaluation of the post-stroke transcriptome of the mouse cortex using genome-wide RNA-seq

status: Public on Jun 04 2018

city: Edison

first: Ashutosh

last: Dharap

state: NJ

address: 65 James st

department: Neuroscience

institute: HackensackMeridian Health JFK Medical Center

summary: RNA-sequencing was conducted to profile the transcriptome of the post-ischemic mouse cortex at multiple reperfusion time-points. RNA was isolated from sham and middle cerebral artery occlusion (MCAO)-operated mice at different reperfusion time points (6 h, 12 h or 24 h; three independent biological replicates per group), converted into cDNA libraries,  and used for Illumina deep sequencing on a NexSeq500 instrument. The sequencing reads that passed quality filters were analyzed at the transcript isoform level  based on the Tuxedo software package. On average 40.6 million reads were obtained from each sample and genome mapping was on average 82.9% for all samples. We detected 20,748 genes and 56,586 isoforms in the sham group; 22,192 genes and 60,023 isoforms in the 6 h group; 21,771 genes and 59,539 isoforms in the 12 h group; and 21,576 genes and 59,020 isoforms in the 24 h group. Our study represents the first detailed analysis of post-stroke mouse cortex transcriptomes generated using RNA-sequencing technology.

overall_design: Genome-wide transcriptomic profiles of healthy and post-ischemic mouse cortices at various reperfusion time-points (6 h, 12 h, or 24 h) were generated using Illumina sequencing.

first: Sunil

last: Bhattarai


title: Identification of FOSL1 transcriptional targets in mutant KRAS lung adenocarcinoma cells

status: Public on Jun 12 2017

city: Pamplona

first: Silvestre

last: Vicent

address: Avenida Pío XII 55

department: Oncology

country: Spain

institute: Center for Applied Medical Research (CIMA)

summary: Mutant KRAS lung adenocarcinoma cells, H2009, were depleted of FOSL1 by a specific shRNA and its transcriptome was profiled

overall_design: H2009 cells were infected with lentivirus carrying a FOSL1 or a control (GFP) shRNA for 2 days. Then, cells were selected for 3 days using 5ug/ml puromycin. After that, cells were counted and plated at a density of 600,000 cells/well (6-well plate). RNA was harvested on the following day using Trizol.


title: Genome-wide maps of H3K4me3 in C57BL6/J, DBA/2J, and BXD lines for male germ cells, hepatocytes, cardiomyocytes, and mouse ESCs

status: Public on Mar 19 2019

city: Bar Harbor

first: Christopher

middle: Lee

last: Baker

state: ME

address: 600 Main Street

department: Research

institute: The Jackson Laboratory

summary: Here, we have explored how natural genetic variation in mice shapes the epigenome by studying levels of H3K4me3, a mark of active chromatin. We found tissue-specific trans-regulation in four diverse cell types: male germ cells, embryonic stem (ES) cells, hepatocytes and cardiomyocytes. Using recombinant inbred lines, we mapped six major trans-acting histone quantitative trait loci (hQTL) modulating hundreds of H3K4me3 sites in germ cells. These loci act dominantly to suppress H3K4me3, which at recombination hotspots reduces the likelihood of subsequent DNA double-strand breaks during meiosis. QTL locations match clusters of zinc finger genes, making these possible candidates that explain the dominant suppression of H3K4me3. Collectively, these data describe an extensive, tissue-specific set of chromatin regulatory loci that control functionally related chromatin sites.

overall_design: Measure H3K4me3 levels using ChIP-seq in founders and progeny of a genetic reference population of mice for QTL mapping

middle: L


title: Signatures of altered gene expression in dorsal root ganglia of a Fabry disease mouse model

status: Public on Jan 01 2018

city: Innsbruck

first: Kai

last: Kummer

address: Schoepfstrasse 41/Eg

department: Institute of Physiology

country: Austria

institute: Medical University of Innsbruck

summary: In the current study we performed mRNA microarray expression profiling of DRG samples from α-Gal A(-/0) mice aged >20 weeks when the disease is fully developed to investigate the mRNA signatures associated with FD peripheral nerve neuropathy. We found that in total 812 genes from the overall 21’736 detected mRNAs were significantly different between DRG samples from wildtype and α-Gal A(-/0) mice (criteria p ≤ 0.01, absolute fold change ≥ 1.2). Of those, 506 genes were significantly upregulated and 306 genes were significantly downregulated as compared to wildtype controls. More stringent filtering (criteria p ≤ 0.01, absolute fold change ≥ 2) of those significantly regulated genes revealed an assessable number of 78 genes in total. Using these criteria 41 genes were significantly upregulated, of which 29 showed FDR corrected p-values ≤ 0.1. Furthermore, 31 genes remained significantly downregulated, of which 27 showed FDR corrected p-values ≤ 0.1.

overall_design: Genome-wide expression profiling was carried out by IMGM Laboratories (Munich, Germany) using Agilent SurePrint G3 Mouse GE 8x60K Microarrays in combination with a one-color based hybridization protocol on lumbar DRGs L3-L5 from α-Gal A(-/0) and wildtype controls. Eight adult mice per group were deeply anesthetized with isoflurane and euthanized by decapitation. Spinal cords were removed, lumbar DRGs L3-L5 harvested and flash-frozen in liquid nitrogen. The DRG tissue from two mice was pooled for the final tissue sample.

first: Theodora

last: Kalpachidou

first: Michaela

last: Kress

first: Michiel

last: Langeslag


first: Crystal

last: Marconett

summary: Smoking-associated DNA hypomethylation has been observed in blood cells and linked to lung cancer risk. However, its cause and mechanistic relationship to lung cancer remain unclear. We studied the association between tobacco smoking and epigenome-wide methylation in non-tumor lung (NTL) tissue from 237 lung cancer cases in the Environment And Genetics in Lung cancer Etiology study, using the Infinium HumanMethylation450 BeadChip. We identified seven smoking-associated hypomethylated CpGs (P < 1.0 × 10-7), which were replicated in NTL data from The Cancer Genome Atlas. Five of these loci were previously reported as hypomethylated in smokers' blood, suggesting that blood-based biomarkers can reflect changes in the target tissue for these loci. Four CpGs border sequences carrying aryl hydrocarbon receptor binding sites and enhancer-specific histone modifications in primary alveolar epithelium and A549 lung adenocarcinoma cells. A549 cell exposure to cigarette smoke condensate increased these enhancer marks significantly and stimulated expression of predicted target xenobiotic response-related genes AHRR (P = 1.13 × 10-62) and CYP1B1 (P < 2.49 × 10-61). Expression of both genes was linked to smoking-related transversion mutations in lung tumors. Thus, smoking-associated hypomethylation may be a consequence of enhancer activation, revealing environmentally-induced regulatory elements implicated in lung carcinogenesis.

overall_design: RNAseq of DMSO or cigarette smoke condensate (CSC)-treated A549 human lung adenocarcinoma cells. Cells were treated for either 48 hours or 2 weeks, as indicated.

first: Theresa

last: Stueve

first: Wen

last: Li

first: Jianxin

last: Shi

first: Tongwu

last: Zhang

first: Chenchen

last: Yang

first: Daniel

last: Mullen

first: C

last: Yan

first: William

last: Wheeler

first: Xing

last: Hua

first: Beiyun

last: Zhou

first: Zea

last: Borok

first: Neil

middle: E

last: Caporaso

first: Angela

last: Pesatori

first: Jubao

last: Duan

first: Ite

first: Maria


title: LINC00261 is an epigenetically-regulated tumor suppressor that is essential for activation of the DNA damage response

first: Crystal

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

overall_design: Refer to individual Series


title: DNA methylation profiling of primary medulloblastoma samples

status: Public on Jun 13 2017

city: Toronto

first: Florence

middle: M G

last: Cavalli

state: Ontario

address: PGCRL, 686 Bay Street

department: Developmental and Stem Cell

country: Canada

institute: The Hospital for Sick Children

summary: Genome wide DNA metylation of 763 primary medulloblastoma samples

overall_design: Bisulphite converted DNA from 763 fresh frozen primary medulloblastoma samples were hybridized to the Illumina Infinium HumanMethylation450 BeadChips according to manufacturer’s instructions.

middle: M

first: Marc

last: Remke

first: Michael

middle: D

last: Taylor


title: DNA methylation and gene expression profiling of primary medulloblastoma samples

type:
Expression profiling by array
Methylation profiling by array


title: Chromatin accessibility dynamics across C. elegans development and ageing [ChIP-seq]

status: Public on Jun 01 2018

city: Cambridge

first: Julie

last: Ahringer

address: Tennis Court Road

department: The Gurdon Institute

country: United Kingdom

institute: University of Cambridge

summary: An essential step for understanding the transcriptional circuits that control development and physiology is the global identification and characterization of regulatory elements. Here we present the first map of regulatory elements across the development and ageing of an animal, identifying 42,245 elements accessible in at least one C. elegans stage. Based on nuclear transcription profiles, we define 15,918 protein-coding promoters and 17,918 putative enhancers, and find that both types of element can drive orientation-independent transcription. Additionally, hundreds of promoters produce transcripts antisense to protein coding genes, suggesting involvement in a widespread regulatory mechanism. We find that the accessibility of most elements is regulated during development and/or ageing and that patterns of accessibility change are linked to specific developmental or physiological processes. The map and characterization of regulatory elements across C. elegans life provides a platform for understanding how transcription controls development and ageing.

overall_design: ChIP-seq was used to profile H3K4me3, H3K4me1, H3K36me3, and H3K27me3 across development

first: Przemysław

last: Stempor

first: Jürgen

last: Jänes


title: Microarray-based DNA methylation profiles of primary medulloblastomas

status: Public on May 29 2017

first: Ed

last: Schwalbe

type: Methylation profiling by genome tiling array

summary:
Identification of novel molecular subgroups
Background:
International consensus recognises four medulloblastoma molecular subgroups - WNT, SHH, Group 3 and Group 4  - each defined by their characteristic genome-wide transcriptomic and DNA methylomic profiles.  Subgroups harbor distinct clinico-pathological and molecular features, underpin current disease sub-classification and initial subgroup-directed therapies are underway in clinical trials (i.e. reduced risk-adapted treatments for favorable-risk WNT patients; SMO inhibitors for SHH patients). However, significant biological heterogeneity and differences in survival are apparent within each subgroup, which remain to be resolved.
Methods:
We undertook comprehensive molecular profiling and unsupervised class discovery (non-negative matrix factorization, t-SNE) of test and validation cohorts to identify consensus primary molecular subgroups within childhood medulloblastoma (<16.0 years), and characterize their clinical and biological significance. Survival modeling was performed in clinically-annotated centrally-reviewed patients (>3.0 years).
Findings:
Seven robust and reproducible primary molecular subgroups of childhood medulloblastoma were identified, characterized by distinct biological/clinical features. For instance, SHH comprised two age-dependent subgroups, while Grp3 and Grp4 each split into two subgroups with significantly different survival rates. Survival analysis identified secondary features predictive of outcome. Cross-validated subgroup-dependent models incorporating these novel subgroups along with secondary features and established disease risk-factors, outperformed current disease risk-stratification schemes. These schema stratified patients into four clinical risk-groups - favorable-risk (91% 5-year survival, 25% of patients), standard-risk (81%, 23%), high-risk (42%, 38%) and very high-risk (28%, 13%)  - to be considered for treatment reduction, intensification or novel therapies respectively.
Interpretation:
The discovery of seven novel, clinically-significant, subgroups significantly improves disease risk-stratification and provides a new foundation for future research and clinical investigations.

overall_design: DNA methylation profiles of 428 medullblastoma were generated from fresh-frozen and formalin-fixed paraffin-embedded materal using the Illumina 450k methylation microarray

first: E

first: D

last: Williamson

first: S

last: Clifford


title: The Transcriptome of the Didelphys virginiana Opossum Kidney OK Proximal Tubule Cell Line

status: Public on Aug 07 2017

city: Pittsburgh

first: Uma

last: Chandran

state: PA

address: 5150 Center Ave

department: BioMedical Informatics

institute: University of Pittsburgh

summary: The OK cell line derived from kidney of a female opossum Didelphys virginiana has proven to be a useful model in which to investigate the unique regulation of ion transport and membrane trafficking mechanisms in the proximal tubule (PT). Sequence data and comparison of the transcriptome of this cell line to eutherian mammal PTs would further broaden the utility of this culture model. However, genomic sequence for Didelphys virginiana is not available and although a draft genome sequence for the opossum Monodelphis domestica (sequenced in 2012 by the Broad Institute) exists, its relatedness and similarity of the transcriptome to the Didelphys virginiana species is not known. The Monodelphis domestica sequence is not highly annotated, and the majority of transcripts are predicted rather than experimentally validated. Using deep RNA sequencing of the Didelphys virginiana OK cell line we characterized its transcriptome using de novo transcriptome assembly and alignment to the Monodelphis domestica genome. The quality of the de novo assembled transcriptome was assessed by the extent of homology to sequences in nucleotide and protein databases. Gene expression levels in the OK cell line, from both the de novo transcriptome and genes aligned to the Monodelphis domestica genome, were compared to publicly available rat kidney nephron segment expression data. Our studies demonstrate the expression in OK cells of numerous PT specific ion transporters and other key proteins relevant for rodent and human PT function. The sequence and expression data reported here provide a new and important resource for studies on the regulation of PT mRNA and protein expression.

overall_design: de novo and Monodelphis Domestica reference genome based transcriptome assembly and gene expression analysis of 60M paired end reads of one OK cell line sample. Replicate analysis was completed from additional 60M reads from same sample.

first: Megan

last: Eshbach

first: Rahil

last: Sethi

first: Raghunandan

last: Avula

first: Janette

last: Lamb

first: Deborah

last: Hollingshead

first: David

last: Finegold

first: Joseph

last: Locker

first: Ora

last: Weisz


title: ATAC-seq data

status: Public on Sep 05 2018

city: Seattle

first: Diego

last: Calderon

address: 3720 15th Ave NE

institute: University of Washington

summary: The immune system depends on a balanced interplay among a variety of specialized cell types transitioning between resting and stimulated states. While epigenome mapping efforts have focused on resting ex vivo immune cells, efforts to characterize stimulation-induced chromatin changes of diverse cell types has been limited. Thus, we collected ATAC-seq and RNA-seq data from immune cell types under resting and stimulated conditions from blood of healthy individuals, and cell types from fetal thymus samples.

overall_design: 175 ATAC-seq samples of 25 blood cell types from healthy donors.

first: Michelle

last: Nguyen

first: Anja

last: Mezger


title: Pleiotropic Analysis of Lung Cancer and Blood Triglycerides

status: Public on Nov 06 2016

first: Crystal

last: Marconett

summary: Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10-6) and blood triglycerides (P = 1.39x10-5). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10-4) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21, Pcombined = 5.20x10-9). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.

overall_design: Whole genome bisulfite sequencing of purified human primary AT2 cells from remnant transplant lungs of 2 donors.

first: Verena

last: Zuber

first: Jianxin

last: Shi

first: Xing

last: Hua

first: William

last: Wheeler

first: Chenchen

last: Yang

first: Lei

last: Song

first: Anders

last: Dale

first: Mariana

last: Laplana

first: Angela

last: Risch

first: Aree

last: Witoelar

first: Wesley

last: Thompson

first: Andrew

last: Schork

first: Francesco

last: Betella

first: Yunpeng

last: Wang

first: Srdjan

last: Djurovic

first: Beiyun

last: Zhou

first: Zea

last: Borok

first: Henricus

middle: F

last: van der Heijden

first: Jacqueline

last: de Graff

first: Dorine

last: Swinkels

first: Katja

last: Aben

first: James

last: McKay

first: Rayjean

last: Hung

first: Heike

last: Bikeboller

first: Victoria

last: Stevens

first: Demetrius

last: Albanes

first: Neil

last: Caporaso

first: Younghun

last: Han

first: Yongyue

last: Wei

first: Maria

last: Panadero

first: Jose

middle: I

last: Mayordomo

last: Christiani

first: Lambertus

last: Kiemeney

first: Ole

last: Andreassen

first: Richard

last: Houlston

first: Christopher

last: Amos

first: Nilanjan

last: Chatterjee

first: Ite


title: Altered gene expression in prefrontal cortex of a Fabry disease mouse model

status: Public on Jul 01 2018

first: Kai

last: Kummer

summary: In the current study we performed mRNA microarray expression profiling of PFC samples from α-Gal A(-/0) mice aged >20 weeks when the disease is fully developed to investigate the mRNA signatures associated with FD cognitive symptoms. We found that in total 381 genes from the overall 21’393 detected mRNAs were significantly different between PFC samples from wildtype and α-Gal A(-/0) mice (criteria p ≤ 0.01, absolute fold change ≥ 1.2). Of those, 135 genes were significantly upregulated and 246 genes were significantly downregulated as compared to wildtype controls. More stringent filtering (criteria p ≤ 0.01, absolute fold change ≥ 2) of those significantly regulated genes revealed an assessable number of 50 genes in total . Using these criteria 19 genes were significantly upregulated, of which 11 showed FDR corrected p ≤ 0.1. Furthermore, 31 genes were significantly downregulated, of which 17 showed FDR corrected p ≤ 0.1.

overall_design: Genome-wide expression profiling was carried out by IMGM Laboratories (Munich, Germany) using Agilent SurePrint G3 Mouse GE 8x60K Microarrays in combination with a one-color based hybridization protocol on PFCs from α-Gal A(-/0) and wildtype controls. Four adult mice per group were deeply anesthetized with isoflurane and euthanized by decapitation. Brains were removed, PFCs harvested and flash-frozen in liquid nitrogen.

first: Theodora

last: Kalpachidou

first: Miodrag

last: Mitric

first: Michiel

last: Langeslag

first: Michaela

last: Kress


title: Insights into electrosensory organ development, physiology and evolution from a lateral line organ-enriched transcriptome

status: Public on Mar 27 2017

first: Clare

last: Baker

address: Anatomy Building, Downing Street

department: PDN

summary: The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor Xenopus is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish (Polyodon spathula). Validation of a subset reveals expression in developing ampullary organs of transcription factor genes critical for hair cell development, and genes essential for glutamate release at hair cell ribbon synapses, suggesting close developmental, physiological and evolutionary links between non-teleost electroreceptors and hair cells. We identify an ampullary organ-specific proneural transcription factor, and candidates for the voltage-sensing L-type Cav channel and rectifying Kv channel predicted from skate (cartilaginous fish) ampullary organ electrophysiology. Overall, our results illuminate ampullary organ development, physiology and evolution.

overall_design: mRNA profiles of pooled opercular and fin tissue (3 biological replicates each), manually dissected from stage 46 larval paddlefish (Polyodon spathula), were generated by deep sequencing using the Illumina HiSeq 2500 platform (multiplex paired-end, 2x100 bp).


title: Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes

status: Public on Nov 03 2016

first: Crystal

last: Marconett

summary: Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. To address this, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes.  Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as unique to AT1 cells, while SCNN1G within lung is restricted to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence of mouse alveoli verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells. These new AT1 cell-specific genes, with GRAMD2 as a leading candidate, will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.

overall_design: RNAseq of purified primary human alveolar epithelial type 2 (AT2) and in vitro differentiated type 1 (AT1-like) cells.

first: Beiyun

last: Zhou

first: Mitsuhiro

last: Sunohara

first: Tiffany

last: Pouldar

first: HongJun

last: Wang

first: Yixin

last: Liu

first: Megan

last: Rieger

first: Evelyn

last: Tran

first: Per

last: Flodby

first: Kimberly

last: Siegmund

first: Edward

last: Crandall

last: Laird-Offringa

first: Zea

last: Borok


title: Cross-species transcriptome profiling identifies new alveolar epithelial type I cell-specific genes

summary: Diseases involving the distal lung alveolar epithelium include chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and lung adenocarcinoma. Accurate labeling of specific cell types is critical for determining the contribution of each to pathogenesis of these diseases. The distal lung alveolar epithelium is comprised of two cell types, alveolar epithelial type 1 (AT1) and type 2 (AT2) cells. While cell type-specific markers, most prominently surfactant protein C (SFTPC), have allowed detailed lineage tracing studies of AT2 cell differentiation and their roles in disease, studies of AT1 cells have been hampered by lack of genes with expression unique to AT1 cells. In this study, we performed genome-wide expression profiling of multiple rat organs alongside purified rat AT2, AT1 and in vitro differentiated AT1-like cells, resulting in identification of 54 candidate AT1 cell markers. Cross-referencing with genes upregulated in human in vitro differentiated AT1-like cells narrowed the potential list to 18 candidate genes.  Testing the top four candidate genes at RNA and protein levels revealed GRAM domain 2 (GRAMD2), a protein of unknown function, as highly specific to AT1 cells. RNAseq confirmed that GRAMD2 is transcriptionally silent in human AT2 cells. Immunofluorescence verified that GRAMD2 expression is restricted to the plasma membrane of AT1 cells and is not expressed in bronchial epithelial cells, while RT-PCR confirmed that it is not expressed in endothelial cells. Utilizing GRAMD2 as a new AT1 cell-specific gene will enhance AT1 cell isolation, investigation of alveolar epithelial cell differentiation potential, and contribution of AT1 cells to distal lung diseases.

overall_design: Two preps of purified AT1 cells  (92%, and 93% pure, respectively) were isolated from Sprague-Dawley male rats and RNA was extracted using Trizol. In addition, RNA was extracted from bronchoalveolar lavage cells and 14 rat tissues: kidney, spleen, ileum, duodenum, colon, stomach, skin, brain, testis, skeletal muscle, trachea, heart, salivary gland, and liver.

first: Ite


title: GRP78 regulates ER homeostasis and distal epithelial cell survival during lung development

status: Public on Jan 15 2016

summary: Bronchopulmonary dysplasia (BPD), a chronic lung disease of prematurity, has been linked to endoplasmic reticulum (ER) stress. To investigate a causal role for ER stress in BPD pathogenesis, we generated mice (cGrp78f/f) with lung epithelial cell-specific knockout (KO) of Grp78, a gene encoding the ER chaperone 78-kDa glucose-regulated protein (GRP78), a master regulator of ER homeostasis and the unfolded protein response (UPR). Lung epithelial-specific Grp78 KO disrupted lung morphogenesis, causing developmental arrest, increased alveolar epithelial type II cell apoptosis and decreased surfactant protein and type I cell marker expression in perinatal lungs. cGrp78f/f pups died immediately after birth, likely due to respiratory distress. Importantly, Grp78 KO triggered UPR activation with marked induction of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). Increased expression of genes involved in oxidative stress and cell death and decreased expression of genes encoding antioxidant enzymes suggest a role for oxidative stress in alveolar epithelial cell (AEC) apoptosis. Increased Smad3 phosphorylation and expression of transforming growth factor-β (TGF-β)/Smad3 targets Cdkn1a (encoding p21) and Gadd45a suggest that interactions among the apoptotic arm of the UPR, oxidative stress and TGF-β/Smad signaling pathways contribute to Grp78 KO-induced AEC apoptosis and developmental arrest. Chemical chaperone taursodeoxycholic acid reduced UPR activation and apoptosis in cGrp78f/f lungs cultured ex vivo, confirming a role for ER stress in observed AEC abnormalities. These results demonstrate a key role for GRP78 in AEC survival and gene expression during lung development through modulation of ER stress and suggest the UPR as a potential therapeutic target in BPD.

overall_design: Whole-genome expression profiling was performed using MouseRef-8 v2.0 Expression BeadChips (Illumina) on RNA isolated from lungs of four Grp78f/f and three cGrp78f/f mice at E18.

first: Changgong

last: Li

first: Hongjun

first: Parviz

last: Minoo

first: Amy

middle: S

last: Lee


title: Transcriptome profiling of spleen, blood and hemi-brain of social stressed C57B6 mice exhibiting PTSD like features

status: Public on Dec 31 2015

city: Fort Detrick

first: seid

last: muhie

state: MD

address: 568 Doughten Dr

department: Systems Biology Enterprise

institute: USACEHR

summary: Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD). C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor's barrier avoidance, startled jumping, and retarded locomotion. Transcripts in spleen, blood and hemi-brain of stressed and control C57B/6 mice were analyzed using Agilent's mouse genome-wide arrays.

overall_design:
C57B6 mice were exposed to SJL aggressor mice for periods of 5 days and 10 days (6 hours each day) to induce anxiety/stress which parallels to PTSD in human.
Organs, blood and brain regions were collected after 24 hours and 1.5 week of post 5 days social defeat period; and 24 hour and 6 weeks post 10 days social stress period.

first: Seid

last: Muhie

first: Rasha

last: Hammamieh

first: Marti

last: Jett


title: Transcriptome characterization of social stressed C57B6 mice exhibiting PTSD like features

status: Public on Apr 20 2015


title: Transcriptional profiles of wild-type NCTC11168 and Cj0480c mutant grown without fucose

status: Public on Jan 01 2014

city: SARANAC LAKE

first: Wayne

last: Muraoka

state: NY

address: 154 Algonquin Ave

institute: Trudeau Institute

summary: Strain specific growth of C. jejuni on fucose has been linked to a plasticity region of the chromosome (PR2) and confers a competitive advantage during intestinal colonization.  Growth on fucose induces gene expression of PR2 genes, but the regulatory mechanism of the structural genes involved with fucose utilization is unknown.  A mutant was constructed to examine the role of Cj0480c, a putative IclR-type transcriptional regulator, on PR2 gene expression.  Transcriptional profiles of wild-type C. jejuni and the Cj0480c mutant strain grown without fucose may provide insight in to the extent of the fucose regulon and genes that are necessary for fucose utilization.

overall_design: The design utilized an available two color microarray slide for the entire transcriptome of Campylobacter jejuni wild type strain NCTC 11168. Each sample represents one competitive hybridization: wild-type NCTC 11168 v.s. Cj0480c isogenic mutant. There were four biological replicates of each sample with a dye swap introduced in alternating replicates. Samples were  independently grown, treated and harvested.

first: Qijing

last: Zhang


title: Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration

status: Public on Sep 11 2014

city: Chapel Hill

first: Hong

last: Dang

state: North Carolina

address: 125 Mason Farm Rd, Cb#7248

department: Marsico Lung Institute

institute: University of North Carolina at Chapel Hill

summary:
Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells.  The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93;  Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; and Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84. Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, dehydrated airway surface liquid and mucus, and reduced mucus clearance associated with accumulation of mucus plugs/plaques.  The data provided here represents mRNA expression data from disseccted whole trachea (distal and proximal ends cut 3-4 cartliage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42].  PND 0 trachea are histologically normal, a tracheal mucus plug/obstruction develops around PND 3, the plug is receding to more distal airways by PND 10, and the trachea is again histologically normal by PND 42.  The data from the WT mice provides a global look at mRNA changes across time, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to mucus obstruction to be queried.
The data presented for the purified is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages.

overall_design: 30 total macrophage samples were analyzed;  three from each timepoint (postnatal day 0, 3, 10, and 42) for both wildtype and Scnn1b-transgenic mice grown in specific-pathogen-free facilities and from postnatal day 42 wildtype and Scnn1b-transgenic mice maintained in a germ-free facility.  In our manuscript, we were most interested in changes between WT and Scnn1b-Tg mice, however, the data can also be used to evaluate changes in gene expression across time (postnatal day 0, 3, 10, and 42).  This data can also be used to evaluate the differences in macrophage biology at postnatal day 42 when mice are grown in specific-pathogen-free versus germ-free environments.

first: Yogesh

last: Saini

first: Alessandra

last: Livraghi-Butrico

first: Wanda

last: O'Neal

first: Richard

last: Boucher


title: Expression data from prostate cancer cell lines C4-2B (enzalutamide sensitive) and  C4-2B-MDVR (enzalutamide resistant) cells

status: Public on Apr 09 2015

city: Sacramento

first: allen

last: Gao

state: California

address: 4645 2nd Ave Research 3

institute: UC Davis

summary:
Prostate cancer C4-2B cells were cultured in enzalutamide in a dose-escalation manner. After sixty passages cells were resistant to enzalutamide, with a specific sets of genes been deregulated.
We performed global gene expression analysis by cDNA microarrays to identify genes responsible for enzalutamide resistance in C4-2B-MDVR cells.

overall_design: Enzalutamide resistant C4-2B-MDVR cells were selected from C4-2B cells during long time enzalutamide treatment. Genes responsible for enzalutamide resistance were identified using C4-2B vs. C4-2B-MDVR RNA extraction and hybridization on Affymetrix microarrays.

first: Chengfei

last: Liu

first: Allen


title: Brain transcriptome profiles in mouse model simulating features of post-traumatic stress disorder

summary: Social stress mouse models were used to simulate human post-traumatic stress disorder (PTSD).  C57B/6 mice exposed to SJL aggressor mice exhibited behaviors accepted as PTSD-in-mouse phenotype: 'frozen' motion, aggressor’s barrier avoidance, startled jumping, and retarded locomotion.  Transcripts in hippocampus, amygdala, medial prefrontal cortex, ventral striatum (nucleus acumbens), septal region, corpus striatum, hemi-brain, blood, spleen and heart of stressed and control C57B/6 mice were analyzed using Agilent’s mouse genome-wide arrays.

overall_design:
C57B6 mice were exposed to SJL aggressor mice for periods of 5 days and 10days (6 hours each day) to induce anxiety/stress which parallels to PTSD in human
Organs, blood and brain regions were collected after 24 hours and 1.5 week of post 5 days social defeat period; and 24 hour and 6 weeks post 10 days social stress period.


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (Rat)

status: Public on Apr 15 2013

first: Crystal

last: Marconett

address: 1856 Kirkby Rd

summary: Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), Days 2, 4, and 6 in culture (differentiating) and Day 8 in culture (AT1-like cells).

overall_design:
1ug of RNA was subjected to cRNA conversion using Illumina TotalPrep RNA kit and hybridized to the HT12v4 array
Analysis of gene expression during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells

first: Beiyun

last: Zhou

first: Megan

last: Rieger

first: Suhaida

last: Selamat

first: Mickael

last: Dubourd

first: Sean

last: Lynch

first: Kimberly

last: Siegmund

first: Benjamin

middle: P

last: Berman

first: Zea

last: Borok

first: Ite

last: Laird-Offringa


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation

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

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: Refer to individual Series


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (ChIP-Seq)

summary: Analysis of chromatin state during differentiation of alveolar epithelial type 2 (AT2) cells into AT1 cells. Timepoints taken at Day 0 (AT2 cell), and Day 8 in culture (AT1-like cells).

overall_design: Examination of 2 different histone modifications in 2 cell types.


title: LEAFY target genes reveal a link between flower development and biotic stimulus response (II)

status: Public on May 11 2011

city: Philadelphia

first: Cara

middle: Michele

last: Winter

address: 421 Curie Blvd.

institute: University of Pennsylvania

summary:
The transition from vegetative growth to flower formation is critical for the survival of flowering plants. The plant-specific transcription factor LEAFY (LFY) has central, evolutionarily conserved roles in this process, both in the formation of the first flower and later in floral patterning. We performed genome-wide binding and expression studies to elucidate the molecular mechanisms by which LFY executes these roles. Our study reveals that LFY directs an intricate regulatory network in control of floral homeotic gene expression and, unexpectedly, controls the expression of genes regulating the response to external stimuli in Arabidopsis. We further show that LFY dampens responses to a bacterial MAMP (microbe-associated molecular pattern) and to pathogen challenge. Our findings suggest a molecular mechanism for the coordination of reproductive stage development and disease response programs in plants. Regulation of these distinct survival programs by a single transcription factor may ensure optimal allocation of plant resources for reproductive fitness.
Genome binding/occupancy profiling by genome tiling array used to identity genes bound by endogenous LFY in inflorescences.

overall_design: ChIP-chip of 19-day-old WT (Landsberg erecta) inflorescences using a LFY antibody. Five biological replicate immunoprecipated samples were compared to their corresponding genomic input DNA (taken prior to immunoprecipitation). As a negative control, one 19-day-old Ify6 (Landsberg erecta) IP and its corresponding Input sample were also hybridized.

first: Doris

last: Wagner


title: mRNA expression data from whole trachea dissected from either wild-type mice or Scnn1b-Tg mice at post-natal days 0, 3, 10, and 42

first: Hong

last: Dang

summary:
Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells.  The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93;  Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84; and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction.  The data provided here represents mRNA expression data from dissected whole trachea (distal and proximal ends were cut 3-4 cartilage rings below the larynx and just above the bifurcation, respectively) from male WT and Scnn1b-Tg littermates (C57Bl/6N Tac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42].  Histologically, PND 0 trachea are normal, a tracheal mucus plug/obstruction develops around PND 3 and typically recedes to the intrapulmonary airways after PND 10, and the trachea is again histologically normal by PND 42.  The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-Tg line provides mRNA data that allows differential gene expression due to airway mucus obstruction to be queried.
The data presented for the trachea is part of a larger body of work evaluating gene expression in whole lung, trachea, and purified macrophages.

overall_design: 24 Total tracheal samples were analyzed;  three from each timepoint.  In our manuscript, we were most interested in changes between WT and Scnn1b-Tg mice, however, the data can also be used to evaluate changes in gene expression across time (PND 0, 3, 10, and 42).  It should be noted that a significant difference in RNA expression quality parameters was noted for the 10 day trachea data.

first: Yogesh

last: Saini

first: Alessandra

last: Livraghi-Butrico

first: Wanda

middle: K


title: mRNA expression data from either wild-type mice or Scnn1b-transgenic mice at post-natal days 0, 3, 10, and 42


title: LEAFY target genes reveal a link between flower development and biotic stimulus response

type: Genome binding/occupancy profiling by genome tiling array


title: Transcriptional profiles of NCTC11168 grown with or without 25mM fucose

first: Wayne

last: Muraoka

summary: Strain specific growth of C. jejuni on fucose has been linked to a plasticity region of the chromosome (PR2) and confers a competitive advantage during intestinal colonization.  Growth on fucose induces gene expression of PR2 genes, but the regulatory mechanism of the structural genes involved with fucose utilization is unknown.  Additionally, the mechanism of fucose dissimilation by C. jejuni is not known since no fucose catabolism homologs are found in the C. jejuni genome. Transcriptional profiles of C. jejuni grown with and without fucose may provide insight in to the genes that are necessary for fucose utilization.

overall_design: The design utilized an available two color microarray slide for the entire transcriptome of Campylobacter jejuni wild type strain NCTC 11168. Each sample represents one competitive hybridization: sham-treated NCTC 11168 v.s. 25mM fucose treated NCTC 11168. There were four biological replicates of each sample with a dye swap introduced in alternating replicates. Samples were  independently grown, treated and harvested.

first: Qijing

last: Zhang


title: LEAFY target genes reveal a link between flower development and biotic stimulus response (I)

summary:
The transition from vegetative growth to flower formation is critical for the survival of flowering plants. The plant-specific transcription factor LEAFY (LFY) has central, evolutionarily conserved roles in this process, both in the formation of the first flower and later in floral patterning. We performed genome-wide binding and expression studies to elucidate the molecular mechanisms by which LFY executes these roles. Our study reveals that LFY directs an intricate regulatory network in control of floral homeotic gene expression and, unexpectedly, controls the expression of genes regulating the response to external stimuli in Arabidopsis. We further show that LFY dampens responses to a bacterial MAMP (microbe-associated molecular pattern) and to pathogen challenge. Our findings suggest a molecular mechanism for the coordination of reproductive stage development and disease response programs in plants. Regulation of these distinct survival programs by a single transcription factor may ensure optimal allocation of plant resources for reproductive fitness.
Genome binding/occupancy profiling by genome tiling array used to identity genes bound by induced LFY in 9-day-old seedlings.

overall_design: ChIP-chip of 9-day-old 35S::LFY-GR dexamethasone-treated seedlings using a LFY antibody. Three biological replicate immunoprecipated samples were compared to their corresponding genomic input DNA (taken prior to immunoprecipitation). As a negative control, three biological replicates of 9-day-old WT (Landsberg erecta) IP and their corresponding Input samples were also hybridized (9-day-old Ler seedlings express very low levels of LFY).


title: Integrated transcriptomic and epigenomic analysis of primary human lung cell differentiation (Human)

city: Glendale

first: Crystal

last: Marconett

institute: Keck School of Medicine


title: Knockout mice reveal key roles for claudin-18 in alveolar fluid homeostasis.

status: Public on Apr 06 2014

summary: Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJ), where they serve as regulators of paracellular permeability to ions and solutes. Claudin-18, a member of the large claudin family, is highly expressed in lung epithelium. To elucidate the role of claudin-18 in alveolar epithelial barrier function and fluid homeostasis, we generated claudin-18 knockout (C18 KO) mice. Increased alveolar fluid clearance (AFC) observed in C18 KO mice may have accounted for absence of lung edema despite increased alveolar solute permeability compared to wild type (WT) controls. Higher AFC in C18 KO mice was associated with higher Na-K-ATPase activity and increased expression of the Na-K-ATPase β1 subunit compared to WT controls. Consistent with in vivo findings, alveolar epithelial cell (AEC) monolayers derived from C18 KO mice exhibited lower transepithelial electrical resistance (RT) accompanied by increased solute and ion permeability without changes in ion selectivity. Expression of claudin-3 and claudin-4 was markedly increased in whole lung and in freshly isolated AEC from C18 KO mice, while claudin-5 was unchanged. In contrast, occludin, another major component of the TJ complex, was significantly decreased in C18 KO lung. Further analysis revealed rearrangements in the F-actin cytoskeleton in C18 KO MAECM. These findings demonstrate a crucial non-redundant role for claudin-18 in regulation of alveolar epithelial tight junction composition and permeability to ions and solutes.  Importantly, increased AFC in C18 KO mice identifies additional roles for claudin-18 in alveolar fluid homeostasis beyond its direct contributions to barrier properties of the alveolar epithelium.

overall_design: Animals with a ubiquitous knockout (C18 KO) were obtained by crossing mice harboring a conditional (floxed) allele of claudin-18 (Cldn18F/F) with CMV-cre deleter mice to delete exons 2 and 3 by Cre/loxP recombination.

first: Guanglei

last: Li

first: Per

last: Flodby

first: Jiao

last: Luo

first: Hidenori

last: Kage

first: Arnold

last: Sipos

first: Danping

last: Gao

first: LaMonta

last: Beard

first: Lucas

last: DeMaio

first: Yong

middle: H

last: Kim

first: Kwang-Jin

first: Parviz

last: Minoo

first: Janice

last: Liebler

first: Beiyun

last: Zhou

first: Edward

last: Crandall


title: LEAFY target genes reveal a link between flower development and biotic stimulus response (III)

first: Cara

last: Winter

summary:
The transition from vegetative growth to flower formation is critical for the survival of flowering plants. The plant-specific transcription factor LEAFY (LFY) has central, evolutionarily conserved roles in this process, both in the formation of the first flower and later in floral patterning. We performed genome-wide binding and expression studies to elucidate the molecular mechanisms by which LFY executes these roles. Our study reveals that LFY directs an intricate regulatory network in control of floral homeotic gene expression and, unexpectedly, controls the expression of genes regulating the response to external stimuli in Arabidopsis. We further show that LFY dampens responses to a bacterial MAMP (microbe-associated molecular pattern) and to pathogen challenge. Our findings suggest a molecular mechanism for the coordination of reproductive stage development and disease response programs in plants. Regulation of these distinct survival programs by a single transcription factor may ensure optimal allocation of plant resources for reproductive fitness.
Expression array analysis used to identify genes differentially expressed upon LFY induction in 9-day-old shoot apices.

overall_design: Expression array analysis of 9-day-old 35S::LFY-GR dexamethasone-treated seedlings compared to 9-day-old WT dexamethasone-treated seedlings. Four biological replicate samples.

first: Doris

last: Wagner


title: Gene expression in whole lung and pulmonary macrophages reflects the dynamic pathology associated with airway surface dehydration [left lobe only]

first: Hong

last: Dang

summary:
Scnn1b-Tg mice overexpress the beta subunit of the epithelial sodium channel (Scnn1b) in airway Club cells.  The general phenotype of these mice is described in three published manuscripts (Mall et al. 2004, Nature Medicine, 10(5):487-93;  Mall et al. 2008, Am J Respir Crit Care Med. 177(7):730-42; Livraghi-Butrico et al. 2012, Physiol. Genomics 44(8):470-84;  and Livraghi-Butrico et al. 2012, Mucosal Immunology 5(4):397-408). Briefly, overexpression of the Scnn1b transgene in airway Club cells leads to hyperabsorption of sodium from the airway surface liquid, which causes airway surface liquid and mucus dehydration, resulting in reduced mucus clearance and airway mucus obstruction.  The data provided here represents mRNA expression data from disseccted whole lung from male WT and Scnn1b-transgenic littermates (C57Bl/6NTac background) at 4 time points [postnatal days (PND) 0, 3, 10, and 42].  Histologically, PND 0 lungs are normal, at PND 3 the intrapulmonary airways exhibit transient and spotty Club cell necrosis, and by PND 10 airway mucus obstruction is evident in the proximal portion of the intrapulmonary main stem bronchus. At PND 42, Scnn1b-Tg lungs are charactyerized by chronic low level inflammation, with activated macrophages, neutrophilia, eosinophilia and increased incidence of bronchus-associated lymphoid tissue.  The data from the WT mice provides a global look at mRNA post-natal developmental changes, while the data from the Scnn1b-transgenic line allows differential gene expression due to airway surface liquid dehydration and mucus obstruction to be queried.
The data presented for the lung is part of a larger body of work evaluating gene expression in lung (left lobe only), trachea, and purified macrophages (from bronchoalveolar lavage fluid).

overall_design: 24 Total lung (left lobe only) samples were analyzed;  three from each timepoint for each genotype (wild type and Scnn1b-transgenic).  In our manuscript, we were most interested in changes between WT and Scnn1b-Tg mice, however, the data can also be used to evaluate changes in gene expression across time (PND 0, 3, 10, and 42).  We generated the following pairwise comparisons: Scnn1b-Tg vs WT mice for each PND time point; Intra-strain comparison between PND 3, or 10, or 42 vs PND 0.

first: Yogesh

last: Saini

first: Alessandra

last: Livraghi-Butrico

first: Wanda

last: O'Neal

first: Richard

last: Boucher