title: Single-cell analyses reveal increasing intratumoral heterogeneity as an essential component of treatment resistance in small cell lung cancer [RNA-Seq]

summary: The natural history of small cell lung cancer (SCLC) includes rapid evolution from exquisite chemosensitivity to insurmountable chemoresistance. The mechanisms underlying treatment-resistance in SCLC remain obscure due to scarcity of tissue samples following relapse. We generated circulating tumor cell (CTC)-derived xenografts (CDXs) from SCLC patients to study intratumoral heterogeneity (ITH) and its contribution to treatment resistance. To investigate this, we performed single-cell RNAseq analyses of chemo-sensitive and -resistant CDXs, as well as longitudinal analyses of CDXs and patient CTCs. We found increased ITH, heterogeneous expression of pathways known to be associated with resistance, and transcriptional diversity of either therapeutic targets or EMT genes between cellular subpopulations following treatment-resistance to either chemotherapy or targeted therapies (PARP or CHK inhibitors). Similarly, serial profiling of patient CTCs directly from blood confirmed increased ITH post-relapse, with gene expression patterns similar to a CDX from the same patient. These data suggest that treatment-resistance in SCLC is characterized by the presence of coexisting subpopulations of tumor cells with heterogeneous gene expression leading to activation of multiple, concurrent resistance mechanisms. These findings emphasize the need for drug development efforts to focus on rational combination therapies for treatment-naïve SCLC tumors to maximize the depth and duration of initial responses and counteract the rapid increase in ITH and emergence of broad therapeutic resistance.

overall_design: small cell lung cancer CTC derived xenograft single cell RNA-sequencing

first: Allison

last: Stewart


title: Impact of chronic extracellular acidosis on gene expression in mammary and pancreatic cancer cell lines

status: Public on Jun 13 2020

city: Copenhagen

first: Jiayi

last: Yao

state: Copenhangen

address: Ole Maaløes Vej 5

country: Denmark

institute: University of Copenhagen

type: Expression profiling by high throughput sequencing

summary: The study aim was to determine whether the microenvironmental acidosis in solid tumors contributes to cancer aggressiveness via changes in gene expression. RNA seq was carried out in parallel to a large array of phenotypical analyses of proliferation, growth, and invasiveness.

overall_design: 3 human cancer cell lines (2 mammary, 1 pancreatic) adapted for 1-2 months to growth at extracellular pH 7.6 and 6.5, respectively, were subjected to RNA sequencing (BGI Hongkong), each in triplicates.

first: Michala

middle: G

last: Rolver

first: Julie

last: Schnipper

first: Renata

last: Ialchina

first: Dominika

last: Czaplinska

first: Stine

middle: F

last: Pedersen

first: Albin

last: Sandelin


title: Trans- and cis-acting effects of the lncRNA Firre on epigenetic and structural features of the inactive X chromosome [ChIP-seq]

status: Public on May 07 2020

city: Seattle

first: Xinxian

last: Deng

state: WA

address: 1959 NE Pacific St.

department: Laboratory Medicine and Pathology

country: USA

institute: University of Washington

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Firre encodes a lncRNA involved in nuclear organization in mammals. Here we find that Firre RNA is transcribed from the active X chromosome (Xa) and exerts trans-acting effects on the inactive X chromosome (Xi). Allelic deletion of Firre on the Xa in a mouse hybrid fibroblast cell line results in a dramatic loss of the histone modification H3K27me3 and of components of the PRC2 complex on the Xi as well as the disruption of the perinucleolar location of the Xi. These features are measurably rescued by ectopic expression of a mouse or human Firre/FIRRE cDNA transgene, strongly supporting a conserved trans-acting role of the Firre transcript in maintaining the Xi heterochromatin environment. Surprisingly, CTCF occupancy is decreased on the Xi upon loss of Firre RNA, but is partially recovered by ectopic transgene expression, suggesting a functional link between Firre RNA and CTCF in maintenance of epigenetic features and/or location of the Xi. Loss of Firre RNA results in dysregulation of genes implicated in cell division and development, but not in reactivation of genes on the Xi, which retains its bipartite structure despite some changes in chromatin contact distribution. Allelic deletion or inversion of Firre on the Xi causes localized redistribution of chromatin contacts, apparently dependent on the orientation of CTCF binding sites clustered at the locus. Thus, the Firre locus and its RNA have roles in the maintenance of epigenetic features and structure of the Xi.

overall_design: H3K27me3 ChIP-seq on F1 hybrid wild-type and CRISPR/cas9-modified Patski cells

first: He

last: Fang

first: Giancarlo

last: Bonora

first: Jordan

middle: P

last: Lewandowski

first: Jitendra

last: Thakur

first: Galina

middle: N

last: Filippova

first: Steven

last: Henikoff

first: Jay

last: Shendure

first: Zhijun

last: Duan

first: John

middle: L

last: Rinn

first: William

middle: S

last: Noble

first: Christine

middle: M

last: Disteche


title: Ribosome sequencing of adenocarcinoma cells - control and FKBP10 SH

status: Public on Apr 13 2020

city: Geneve

first: George

last: Allen

state: Geneve

address: Rue Michel-Servet 1

country: Switzerland

institute: University of Geneva

summary: We report ribosome sequencing of A549 pulmonary adenocarcinomic human alveolar basal epithelial cells. This was carried out with unmodified cells as well as cells with FKBP10 knocked down with shRNA. This data was paired with RNASeq on the same cells and the transcriptional profiles were assessed to understand the effect of FKBP10 SH. This was done firstly by assessing alterations in gene-wide summary plots of global changes in transcription. These demonstrate pervasive extra pausing at the start site and a loss in translational elongation product, largely associated with ribosomal protein genes. Pairing this data with corresponding RNASeq allowed us to look at translational efficiency (TE), which showed the lower rate of elongation in the knockdown was principally attributable to a loss in translational efficiency since transcription levels were largely unchanged.

overall_design: Assessment of transcriptional and translational profiles of A549 lung cancer in controls and FKBP10 SH knockdown

first: Rafael

last: Maciel

first: Giorgio

last: Ramadori

first: Raquel

last: Firnkes

first: Roberto

last: Coppari

first: Zoltan

last: Villyani

first: Martine

last: Collart

first: Olesya

last: Panasenko


title: Caenorhabditis elegans ADAR editing and the ERI-6/7/MOV10 RNAi pathway silence endogenous viral elements and LTR retrotransposons

status: Public on Jan 14 2020

city: Boston

first: Sylvia

last: Fischer

address: 300 Longwood Avenue

department: Division of Infectious Diseases

institute: Boston Children's Hospital

type: Non-coding RNA profiling by high throughput sequencing

summary: To examine the roles of the ADAR genes and the ERI-6/7 helicase in endogenous RNAi pathways, we sequenced small RNA of adr-1; adr-2; eri-6 mutants. We also analyzed the transcriptomes of these mutants using total RNAseq and mRNAseq. mRNAseq was done in mutants depleted for the RNAi factors drh-1 and nrde-3, or control RNAi

overall_design: small RNA, total RNA and mRNA sequencing was done on day 1 adult C. elegans , wild type and mutant or depleted using RNAi

middle: E

first: Gary

last: Ruvkun


title: Intratumoral heterogeneity predicts resistance in CTC-derived models of small cell lung cancer [RNA-Seq]

status: Public on Feb 12 2020

city: Houston

first: Yuanxin

last: Xi

state: TX

address: 1400 Pressler St

department: Bioinformatics and Computational Biology

institute: The University of Texas MD Anderson Cancer Center

summary: Small cell lung cancer (SCLC) is an aggressive malignancy characterized by rapid onset of resistance to platinum chemotherapy. However, the mechanisms underlying platinum-resistance remain obscure in part due to scarcity of tissue samples, particularly from relapsed patients. Here, we generated circulating tumor cell (CTC)-derived xenograft (CDX) models from SCLC patients before or after relapse that faithfully recapitulate patient tumor genomics and platinum response. Platinum-sensitive models were relatively homogeneous, whereas transcriptomic and proteomic analyses revealed enrichment of multiple targetable pathways and intertumoral heterogeneity among resistant models. Single-cell RNAseq profiling further identified greater intratumoral heterogeneity (ITH) associated with platinum-resistance. This included a population of DLL3low cells in resistant CDX models that demonstrated greater chemoresistance, suggesting that subtle shifts in the proportion of DLL3-expressing cells could impact response. Similarly, longitudinal single-cell transcriptional profiling of CTCs from patient blood reveals emergence of molecular markers of resistance and significantly greater ITH after disease relapse. Together, these data suggest that platinum-resistance involves a heterogeneous process of transcriptional fluidity with contributions from both preexisting cellular subpopulations and outgrowth of resistant populations, yielding a diverse cellular composition refractory to single-agent therapeutics.

overall_design: small cell lung cancer CTC derived xenograft RNA-seq

first: Allison

last: Stewart


title: Transcriptomic analysis of silver-resistant Saccharomyces cerevisiae mutant obtained by evolutionary engineering

status: Public on Jan 09 2020

city: Istanbul

first: Halil

middle: ibrahim

last: KISAKESEN

state: Istanbul

address: ITU MOBGAM, SARIYER

department: Molecular Biology, Genetics and Biotechnology

country: Turkey

institute: Istanbul Technical University

summary: Silver-resistant Saccharomyces cerevisiae mutant was obtained by evolutionary engineering method. Briefly, genetic diversity in reference strain, CEN.PK.113-7D, was increased by ethyl methane sulfonate (EMS)-mutagenesis. The mutant population was passaged several times in gradually increasing silver stress. Several mutant individuals were selected from the final population.  Among selected mutant individuals, one of them was much more resistant to silver stress than the reference strain, called as 2E. Whole-genome transcriptomic analysis was performed to identify the silver resistance mechanisms in the silver-resistant mutant strain.

overall_design: Silver-resistant Saccharomyces cerevisiae (2E) mutant strain and reference strain were grown in yeast minimal medium. When cultures’ Optical Density (OD600) reached to about 1, which correspond to the logarithmic growth phase of the yeast cells, total RNA isolation was carried out by using RNeasy Mini Kit (Qiagen). The experiment was performed triplicates. Whole-genome microarray analysis was carried out by using Agilent DNA Microarray Technology.

first: Ergi

last: TERZIOGLU

first: Mevlut

last: ARSLAN

middle: I

first: Zeynep

last: CAKAR


title: CD31 positive-extracellular vesicles from patients with type 2 diabetes: a miRNA signature

status: Public on Dec 24 2019

city: Milan

first: Francesco

last: Prattichizzo

address: via Milanese

country: Italy

institute: IRCCS MultiMedica

summary: Comparative profiling of miRNA content within CD31+EVs comparing Ctrl and T2DM patients (5 vs 5 samples with each sample prepared from the pooled plasma of 4 subjects).

overall_design: Plasma samples from 4 subjects were pooled to reach 1 ml. CD31+EVs were isolated from 5 Ctrl preparations and 5 T2DM preparations. RNA was extracted with a commercial kit known to enrich small RNA species (Norgen Biotek Corporation). The same amount of RNA was converted to cDNA by priming with a mixture of looped primers using the manufacturer’s instructions (MegaPlex kit, Applied Biosystem). Nine µl of cDNA were used for mature miR profiling by a real-time PCR instrument equipped with a 348-well reaction plate and human miR Array pool A containing 367 different human miR assays in addition to selected small nucleolar RNAs and negative controls (non-human miRNAs). Only miRNAs expressed in more than one sample were included in the analysis. 2-ct of the average values of each miRNA were used to build the heatmap comparing Ctrl and T2DM with the ClustVis web tool.


title: Transcriptome-wide expression profiling of Sporothrix schenckii yeast and mycelial forms

status: Public on Feb 25 2020

city: Messina

first: Orazio

last: Romeo

address: Viale Ferdinando Stagno d'Alcontres, 31

department: Department of Chemical, Biological, Pharmaceutical and Environmental Sciences

institute: University of Messina

summary: We report the global transcriptomic differences occurring between mold and yeast phases of S. schenckii including changes in gene expression profiles associated with these distinct cellular phenotypes. Moreover, we also propose a new genome annotation which reveals a more complex transcriptional architecture than previously assumed.

overall_design: Examination of 2 different transcriptomes obtained from 2 different fungal morphologies: yeast and mold


title: High-Throughput Transcriptomics Platform for Screening Environmental Chemicals

status: Public on Jan 25 2021

city: RTP

first: Logan

middle: J

last: Everett

state: North Carolina

address: 109 T.W. Alexander Dr

department: Office of Research and Development

institute: U.S. Environmental Protection Agency

summary: New approach methodologies (NAMs) that efficiently provide information about chemical hazard without using whole animals are needed to accelerate the pace of chemical safety assessments. Technological advancements in gene expression assays have made in vitro high-throughput transcriptomics (HTTr) a feasible option for NAMs-based hazard characterization of environmental chemicals. In the present study, we evaluated the Templated Oligo with Sequencing Readout (TempO-Seq) assay for HTTr concentration-response screening of a small set of chemicals in the human-derived MCF7 cell model. Our experimental design included a variety of reference samples and reference chemical treatments in order to objectively evaluate TempO-Seq assay performance. To facilitate analysis of these data, we developed a robust and scalable bioinformatics pipeline using open-source tools. We also developed a novel gene expression signature-based concentration-response modeling approach and compared the results to a previously implemented workflow for concentration-response analysis of transcriptomics data using BMDExpress. Analysis of reference samples and reference chemical treatments demonstrated highly reproducible differential gene expression signatures. In addition, we found that aggregating signals from individual genes into gene signatures prior to concentration-response modeling yielded in vitro transcriptional biological pathway altering concentrations (BPACs) that were closely aligned with previous ToxCast high-throughput screening (HTS) assays. Often these identified signatures were associated with the known molecular target of the chemicals in our test set as the most sensitive components of the overall transcriptional response. This work has resulted in a novel and scalable in vitro HTTr workflow that is suitable for high throughput hazard evaluation of environmental chemicals.

overall_design: We evaluated the Templated Oligo with Sequencing Readout (TempO-Seq) assay for High-throughput transcriptomic screening of a small set of environmental chemicals. This assay yields sequencing reads of exactly 50 base pairs that can be rapidly aligned to generate gene counts, and is compatible with cell lysates prepared in multiwell format. The version of the TempO-Seq assay we evaluated provides nearly whole transcriptome coverage (>20,000 genes). This study encompasses 3 replicates of a 384-well plate design (1,134). The majority of wells contain MCF7 cells exposed to 44 test chemicals at 8 different concentrations (single replicate per test chemical, concentration, and plate), and additional reference samples and controls. Controls include DMSO vehicle treatments (4 per plate) and untreated wells (2 per plate). Reference samples include bulk lysate MCF7 samples (2 DMSO treated and 2 TSA treated samples per plate), reference chemical treatments (3 chemicals at single conc each, per plate), and vendor-provided reference RNA mixtures (UHRR and HBRR).

first: Joshua

middle: A

last: Harrill

first: Derik

last: Haggard

first: Thomas

last: Sheffield

first: Joseph

last: Bundy

first: Clinton

last: Willis

first: Russell

last: Thomas

first: Imran

last: Shah

first: Richard

last: Judson


title: Expression data from airway basal cells and mucociliary-differentiated epithelium of COPD patients and normal subjects

status: Public on Oct 31 2020

city: Philadelphia

first: Umadevi

last: Sajjan

state: PA

address: 3500 N Broad Street

department: Department of Thoracic Medicine and Surgery

institute: Temple University

summary:
Continuous stress caused by smoking induces changes in the cell population of small airway epithelium, with basal cell hyperplasia and goblet cell metaplasia at the expense of ciliated cells, and there is now compiling evidence that basal cells play a key role in the early pathogenesis of Chronic Obtructive Pulmonary Disease (COPD).
We hypothesized that COPD airway basal cells undergo transcriptomic changes during differentiation that are different from those observed in normal cells and can explain the formation of an abnormal epithelium.
We performed microarray analysis of basal cells obtained from healthy non-smoker and COPD subjects and also mucociliary-differentiated cell cultures from the same basal cells. We compared the transcriptome of normal and COPD basal cells, mucociliary-differentiated normal and COPD cell cultures and also of basal cells with corresponding mucociliary-differentiated cultures for both normal and COPD.

overall_design: Basal cells were isolated from tracheobronchial segments of normal donor lungs and explanted lungs from COPD patients at the time of lung transplantation. Tissue was collected from 8 healthy non-smokers and 8 COPD patients. Basal cells were cultured in collagen coated dishes, flow sorted on the expression of a basal cell marker, and then seeded in transwell to promote mucociliary differentitation. Cells were harvested either at subconfluent stage that is 3-4 days after seeding (basal cells) or after 4 weeks of culturing at air-liquid interface (differentiated cells)

first: Fanny

last: Pineau

first: Gabriella

last: Shumyatsky

first: Nicole

last: Owuor

first: Nisha

last: Nalamala

first: Sudhir

last: Bolla

first: Nathaniel

last: Marchetti

first: Steven

last: Kelsen

first: Gerard

last: Criner


title: CPD-seq mapping of UV damage repair in rad16 mutant yeast

status: Public on Nov 27 2019

city: Pullman

first: John

middle: J.

last: Wyrick

address: Biotechnology Life Sciences 241

department: School of Molecular Biosciences

institute: Washington State University

summary: Rad16 is required for global genomic nucleotide excision repair (GG-NER) of UV-induced CPD lesions. Here we have used a novel high-throughput sequencing method known as CPD-seq to map the repair of UV-induced cyclobutane pyrimidine dimers (CPDs) at single nucleotide resolution across the yeast genome in rad16 mutant cells. Analysis of CPD repair indicates that rad16 is generally required for CPD repair in the non-transcribed strand (NTS) of yeast genes and non-transcribed genomic regions.

overall_design: UV repair data was analyzed for mutant yeast cells deleted for the RAD16 gene. (i.e., rad16∆). Yeast cells were irradiated with 125J/m2 and allowed to repair for 0 or 2 hours. Two biological replicates were performed, and the second replicate was resequenced (i.e., 2 sequencing replicates)

first: Peng

last: Mao


title: MAIT cell activation augments adenovirus vector vaccine immunogenicity

status: Public on Oct 01 2020

city: Oxford

first: Nicholas

last: Provine

state: Oxfordshire

address: John Radcliffe Hospital

department: NDM - Experimental Medicine

country: United Kingdom

institute: University of Oxford

summary: Mucosal-associated invariant T (MAIT) cells are innate sensors of viruses, which can augment early immune responses and contribute to protection from lethal infection. Thus, we reasoned MAIT cells may have an adjuvating role in the immunogenicity of replication-incompetent adenovirus vectors, which are novel vaccine platforms for pandemic pathogens such as Ebola virus and SARS-CoV-2. In both mice and human volunteers, immunization with ChAdOx1 (Chimpanzee Adenovirus Ox1) robustly activated MAIT cells. Activation required transduction of plasmacytoid dendritic cells and monocytes to produce IFN- and IL-18, respectively. IFN--induced monocyte-derived TNF was identified as a novel intermediate in this activation pathway, and activation required combinatorial signaling of all three cytokines both in vitro and in vivo. Strikingly, vaccine-induced activation of MAIT cells positively correlated with vaccine-induced T cell responses in human volunteers. Supporting a causal relationship, MAIT cell-deficient mice displayed impaired CD8+ T cell responses to multiple vaccine-encoded antigens. These findings define a novel role for MAIT cells in the immunogenicity of adenovirus vector vaccines, with potential implications for vaccine design.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Four experiments were performed:  1) Human PBMCs were stimulated in vitro for 24 hours using a ChAdOx1 vector, or left untreated (n=4 of each condition) (AD119).  2) C57BL/6J mice were immunized intramuscularly with a ChAdOx1 vector, or left unimmunized. After 24 hours, draining inguinal lymph nodes were harvested (n=5 of each condition) (AD122).  3) Human volunteers were immunized intramuscularly with a ChAdOx1 vector. PBMCs were collected one day prior to and one day following immunization (n=14) (AD142_AD143).  4) C57Bl/6J, Il18rap-/-, Ifnar-/-, and Tnfrsf1a-/-Tnfrsf1b-/- mice were immunized intramuscularly with a ChAdOx1 vector. After 24 hours, draining inguinal lymph nodes from these mice, or unimmunized C57BL/6J control mice were collected (n=4 of each condition) (AD148).    For all four experiments, mucosal-associated invariant T (MAIT) cells were isolated by FACS, RNA was extracted by phenol/chloroform, and cDNA libraries were generated using the Smart-Seq2 protocol.    The comparisons performed were:  Experiments 1-3: MAIT cells from the ChAdOx1-stimulated condition versus unstimulated/naïve/pre-vaccine to identify vaccine-induced genes. Following this, the differentially expressed genes between each of these conditions were compared.    Experiment 4: MAIT cells from vaccinated and unvaccinated C57BL6/J were compared to identify differentially expressed genes in response to vaccination. Then wild-type mice and each of the knockouts were compared to determine which of the vaccine-induced genes were regulated by the particular cytokine pathway perturbed in each knockout mouse.

first: Paul

last: Klenerman


title: Stress-induced RNA–chromatin interactions promote endothelial dysfunction

status: Public on Aug 17 2020

city: La Jolla

first: Sheng

last: Zhong

state: CA

address: 9500 Gilman Dr

department: Bioengineering

institute: University of California San Diego

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

overall_design: Refer to individual Series


title: TFIIIC binding to Alu elements controls gene expression via chromatin looping and histone acetylation

status: Public on Nov 21 2019

city: Parma

first: Roberto

last: Ferrari

state: Parma

address: Parco Area delle Scienze 23/A

department: Department of Chemistry, Life Sciences and Environmental Sustainability

institute: University of Parma

summary: How repetitive elements, epigenetic modifications and architectural proteins interact ensuring proper genome expression remains poorly understood. Here we report regulatory mechanisms unveiling a central role of Alu elements (AEs) and RNA polymerase III transcription factor C (TFIIIC) in structurally and functionally modulating the genome via chromatin looping and histone acetylation. Upon serum deprivation, a subset of AEs pre-marked by the Activity-Dependent Neuroprotector Homeobox protein (ADNP) and located near cell cycle genes recruits TFIIIC, which alters their chromatin accessibility by direct acetylation of histone H3 lysine-18 (H3K18). This facilitates the contacts of AEs with distant CTCF sites near promoter of other cell cycle genes, which also become hyperacetylated at H3K18. These changes ensure basal transcription of cell cycle genes and are critical for their re-activation upon serum re-exposure. Our study reveals how direct manipulation of the epigenetic state of AEs by a general transcription factor regulates 3D genome folding and expression.

overall_design: Examination of TFIIIC binding and action during cellular Serum Starvation (SS)

first: Lara

last: de Llobet Cucalon

first: Chiara

last: Di Vona

first: Enrique

last: Vidal

first: Antonios

last: Lioutas

first: Francois

last: De Lilly

first: Javier

last: Quilez Oliete

first: Laura

last: Jochem

first: Erin

last: Cutts

first: Giorgio

last: Dieci

first: Alessandro

last: Vannini

first: Martin

last: Teichmann

first: Susana

last: De la Luna

first: Miguel

last: Beato


title: ZAR1 and ZAR2 are Required for Oocyte Meiotic Maturation by Regulating the Maternal Transcriptome and mRNA Translational Activation

status: Public on Sep 25 2019

city: Hangzhou

first: Li

last: Shen

state: Zhejiang Province

address: 866 Yuhangtang Road

country: China

institute: Life Sciences Institute, Zhejiang University

summary: Zar1 was the first mammalian maternal-effect gene to be identified. Embryos derived from Zar1-null female mice are blocked before zygotic genome activation; however, the underlying mechanism remains unclear. By knocking out Zar1 and its homolog Zar2 in mice, we revealed a novel function of these genes in oocyte meiotic maturation. Zar1/2-deleted oocytes displayed delayed meiotic resumption and polar body-1 emission and a higher incidence of abnormal meiotic spindle formation and chromosome aneuploidy. The grown oocytes of Zar1/2-null mice contained fewer total mRNAs and displayed a reduced level of protein synthesis. Key maturation-associated changes failed to occur in the Zar1/2-null oocytes, including the translational activation of maternal mRNAs encoding the cell cycle proteins cyclin B1 and WEE2, as well as maternal-to-zygotic transition (MZT) licensing factor BTG4. Consequently, maternal mRNA decay was impaired and MZT was abolished. ZAR1/2 bound mRNAs to regulate the translational activity of their 3ʹ-UTRs and interacted with other oocyte proteins, including mRNA-stabilizing protein MSY2 and cytoplasmic lattice components. These results countered the traditional view that ZAR1 only functions after fertilization and highlight a previously unrecognized role of ZAR1/2 in regulating the maternal transcriptome and translational activation in maturing oocytes.

overall_design: WT and Zar1/2-none oocytes (growing, fully grown GV, and MII stages) for two replicates are performed RNA sequencing.

first: Yezhang

last: Zhu


title: Xenobiotic-induced perturbations of cis-regulatory elements associated with sensitivity to liver tumor promotion

status: Public on Oct 07 2019

city: Basel

first: Remi

last: Terranova

address: Fabrikstrasse 2

institute: Novartis Biomedical Research

summary: Liver cancer susceptibility varies between strains of experimental animal models due to multiple genetic and epigenetic factors. We used DNase I hypersensitivity mapping and transcriptomic profiling to investigate cis-regulatory element and transcriptional perturbations associated with the early stages of phenobarbital (PB)-mediated liver tumor promotion in susceptible versus resistant mouse strains (B6C3F1 versus C57BL/6).

overall_design: DNase hypersensitivity and gene expression profiling was performed on livers of animals from two mouse strains (C57BL/6 and B6C3F1). For each strain, animals were split into two groups of 5 animals each. One group received phenobarbital treatment through ad libitum access to drinking water for 91 days and the other group served as control.

first: Jonathan

last: Moggs


title: Transcriptional profile of IL33 & PD1-treated ILC2 from KPC tumor-bearing mice

status: Public on Sep 03 2019

city: New York

first: Vinod

last: Balachandran

state: NY

address: 417 E 68th St

institute: Memorial Sloan Kettering Cancer Center

summary: We investigated the genetic profiles of IL33 and PD1-treated group 2 innate lymphoid cells (ILC2) harvested from KPC tumors and draining lymph nodes in a pancreatic ductal adenocarcinoma (PDAC) mouse model.

overall_design: Examining single cell RNA profiles of fluorescence activated cell-sorted ILC2 cells from untreated KPC pancreatic tumor (control), IL33-treated pancreatic tumor, IL33+PD1-treated pancreatic tumor, IL33-treated draining lymph node & IL33+PD1-treated lymph node

first: Joanne

last: Leung


title: A single cell atlas of human glioma

status: Public on Oct 12 2019

city: San Francisco

first: Aaron

last: Diaz

department: Neurological Surgery

institute: University of California, San Francisco

summary: Although tumor-propagating cells can be derived from glioblastomas (GBMs)of theproneural and mesenchymal subtypes,a gliomastem-like cell (GSC) of the classical subtype has not been identified. It is unclear if mesenchymal GSCs (mGSCs) and/orproneural GSCs (pGSCs) alone are sufficient to  generate the heterogeneity observed in GBM.We performed single-cell/nuclei RNA-sequencing of  28 gliomas, and single-cell ATAC-sequencing for8 cases. We find that GBM GSCs reside ona single axis of variation, rangingfrom proneural to mesenchymal. In silico lineage tracing using both transcriptomics and genetics supports mGSCs as the progenitors of pGSCs.Dual inhibition of pGSC-enrichedand mGSC-enrichedgrowth and survival pathways provides a more complete treatment thancombinations  targetingone GSC phenotype alone.This study sheds light on a long-standing debate regarding  lineage relationships among GSCs and presents a paradigm by which personalized combination  therapies can be derived from single-cell RNA signatures, to overcome intra-tumor heterogeneity.

overall_design:
We performed single-cell RNA sequencing (scRNA-seq), single-nuclei RNA sequencing (snRNA-seq), single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq), and whole-exome DNA sequencing (exome-seq) of specimens from untreated human gliomas.Via in-silico transcriptomic and genetic lineage tracing of these data we defined the lineage relationships between glioma cell types.Integrating this with meta-analysis of sequencing data from The Cancer Genome Atlas (TCGA) (https://cancergenome.nih.gov/) and spatial data from The Ivy Foundation Glioblastoma Atlas Project (Ivy GAP)(http://glioblastoma.alleninstitute.org/), we mapped glioma cells to analogous cell types in the developing brain and to specific tumor-anatomical structures. From the scATAC-seq we elucidated cell-type specific cis-regulatory grammarsand associated transcription factors. Using immunohistochemistry (IHC) and automated image analysisof human GBM microarray we validated learned phenotypes at the protein level. Lastly, we performed an in vitro screen of drug combinations that target genes identified from our single-cell analysisof GSCs.

Raw data not available due to privacy concerns

Please note that processed data files for the GSM4119521-GSM4119530 samples have been updated on Feb 16, 2021.

first: Lin

last: Wang

first: Husam

last: Babikir

first: Soren

last: Muller

first: Garima

last: Yagnik

first: Karin

last: Shamardani

first: Francisca

last: Catalan

first: Gary

last: Kohanbash

first: Beatriz

last: Alvarado

first: Elizabeth

last: Di Lullo

first: Arnold

last: Kriegstein

first: Sumedh

last: Shah

first: Harsh

last: Wadhwa

first: Susan

last: Chang

first: Joanna

last: Philips

first: Manish

middle: K

last: Aghi


title: Genome-wide maps of chromatin state in 5-HT6R knock out mice.

city: Beijing

first: Bingjie

address: Yiheyuan ROAD 5

institute: Peking University

summary:
Purpose:The primary cilia play central roles in transducing or regulating various signaling pathways during brain development. However, the function of primary cilia in mature nerve system is currently largely unknown.We aimed to identify transcriptional changes resulting from depletion of ciliary GPCR 5-HT6R.
Methods: We performed RNA sequencing in the hippocampal tissues from P90 adult konck out mice and wild type mice.
Results:We examined for differential expression genes across 27698 genes expressed in our datasets. At significant cutoffs corresponding to Benjamini and Hochberg adjusted p value < 0.05, we found 429 differential expression genes in 5-HT6R-/- mice compared with WT litter mates.
Conclusions:We discovered that primary cilia were associated with axon initial segment (AIS) morphology, including AIS length and position. Our data strongly suggest that the cilia signaling might have a remarked impact on neuronal excitability by regulating AIS morphology and are likely to be associated with neuronal system diseases.

overall_design: Hippocampus mRNA profiles of 90-day old wild type (WT) and 5-HT6R-/- mice were generated by deep sequencing, in triplicate.

first: Zehui

last: Sun


title: Transcriptome analysis of adductor muscle color in Boihai Red Scallop

status: Public on Apr 15 2019

city: Qingdao

first: JunLin

last: Song

address: Changcheng Road

institute: JunLin Song

summary: Boihai Red is new strains of inter-specific hybridizing the bay scallop (Argopecten irradians irradians) with the Peruvian scallop (Argopecten purpuratus). Orange color variant of adductor muscle have been developed through successive selective breeding in this strain. In the present study, transcriptomic was conducted on orange and white adductor muscle tissues. Transcriptomic analysis showeds 416 differentially expressed genes (DEGs) were identified between white and orange adductor muscle tissues in Boihai Red Scallop, with 216 up regulated and 200 down. In DEGs, apolipophorin, CYP450 and tyrosinase were expressed highly in orange adductor muscle tissues, which related to carotenoids or melanin.  It is probable that not only carotenoids, but also melanin act on orange color of adductor muscle. This study provides valuable genetic resources for understanding underlying mechanisms and pathways of adductor muscle color.

sample_organism: Argopecten irradians irradians x Argopecten purpuratus

overall_design: Total mRNA profiles of orange and white adductor muscle tissues were generated by deep sequencing, in triplicate.

first: Junlin


title: Comprehensive single-cell mRNA profiling reveals a detailed roadmap for pancreatic endocrinogenesis

status: Public on Jun 11 2019

city: Neuherberg

first: Sophie

last: Tritschler

address: Ingolstädter Landstrasse 1

country: Germany

institute: Helmholtz Zentrum Munich

summary: This dataset consists of single-cell RNA-seq (10X) data from 4 embryonic stages (E12.5-15.5) of pancreatic epithelial cells from Neurogenin3 (Ngn3)-Venus fusion (NVF) homozygous mice. Endocrine progenitor cells (NVF+) were enriched by FACS cell sorting.

overall_design: 4 single cell RNA seq experiments were performed using 10X Genomics technology to generate single cell transcriptomic profiles of embryonic pancreatic epithelial cells from a Neurogenin3 (Ngn3)-Venus fusion (NVF) reporter mouse line. Cells were sorted and NVF+ and NVF- cells mixed (50:50) to enrich for endocrine Ngn3+ progenitors. Cells were sampled from pancreata of E12.5,E13.5,E14.5 and E15.5 embryos.

first: Aimee

last: Bastidas-Ponce

first: Dony

last: Leander

first: Katharina

last: Scheibner

first: Marta

last: Tarquis-Medina

first: Ciro

last: Salinno

first: Silvia

last: Schirge

first: Ingo

last: Burtscher

first: Anika

last: Böttcher

first: Fabian

last: Theis

first: Heiko

last: Lickert

first: Mostafa

last: Bakhti


title: Profiling the endothelial translatome in vivo using ‘AngioTag’ zebrafish

status: Public on Mar 29 2019

city: Bethesda

first: Derek

last: Gildea

state: MD

address: 12 South Drive Rm 4009-24

institute: NHGRI/NIH

summary: We profiled the gene expression patterns of undisturbed endothelial cells in living animals using a novel ‘AngioTag’ zebrafish transgenic line that permits isolation of actively translating mRNAs from endothelial cells in their native environment. This transgenic line uses the endothelial cell-specific kdrl promoter to drive expression of an epitope tagged Rpl10a 60S ribosomal subunit protein, allowing for Translating Ribosome Affinity Purification (TRAP) of actively translating endothelial cell mRNAs.  We also collected the whole embryo translatome using the TRAP protocol and a ubiquitously expressed tagged Rpl10a, and the endothelial transcritome by collecting the GFP+ endothelial cells that had the kdrl promoter driving GFP.

overall_design: Examination of 24hpf zebrafish whole embryo translatome, 24hpf zebrafish endothelial translatome, and 24hpf zebrafish endothelial transciptome

first: Brant

last: Weinstein

first: Mayumi

last: Miller


title: Transcriptomic analysis of a caffeine-resistant Saccharomyces cerevisiae strain obtained by evolutionary engineering

status: Public on Dec 28 2018

city: Istanbul

first: Halil

last: KISAKESEN

institute: Istanbul Technical University

summary: A caffeine-resistant Saccharomyces cerevisiae mutant strain was obtained using an evolutionary engineering strategy based on successive batch cultivation at gradually increasing caffeine levels. The mutant strain Caf905-2 was selected at a caffeine concentration where its reference strain could not grow at all. Whole-genome transcriptomic analysis of Caf905-2 was performed with respect to its reference strain.

overall_design: Agilent Yeast One-Color DNA microarray systems were employed for comparative whole-genome transcriptomic analysis of the selected mutant Caf905-2 and its reference strain. Before gene expression analysis, each culture was grown in triplicate in yeast minimal medium (YMM) at 30°C and 150 rpm. Total RNA was isolated, using RNeasy Mini Kit (Qiagen) at early exponential phase of growth (OD600 ~1.0).

first: Yusuf

last: Sürmeli

last: Kısakesen

first: Zeynep

last: Çakar


title: A lineage-resolved molecular atlas of C. elegans embryogenesis at single cell resolution

status: Public on Mar 01 2019

first: Junhyong

last: Kim

address: 433 S University Avenue

department: Biology

institute: University of Pennsylvania

summary: We sequence the transcriptomes of 86,024 single cells from C. elegans embryos, spanning from gastrulation to the beginning of cuticle synthesis. We identify the lineage (from the invariant C. elegans cell lineage) and approximate developmental age of each cell in the single cell data. Using these annotations, we investigate the competing influences of cell lineage and cell fate on gene expression.

overall_design:
Single cell RNA-seq profiles of cells from C. elegans embryos at varying developmental stages (~100-650 minutes post first cleavage).

Please note that the GSM2599701 (in GSE98561) raw data was re-analyzed and the resulting (processed) data is linked to the GSM4318946 records, which is duplicated sample record of GSM2599701 (with the re-analysis details) for the convenient retrieval of the complete raw data from SRA.

first: Jonathan

last: Packer

first: Qin

last: Zhu

first: Chau

last: Huynh

first: Priya

last: Sivaramakrishnan

first: Elicia

last: Preston

first: Hannah

last: Dueck

last: Stefanik

first: Kai

last: Tan

first: Cole

last: Trapnell

first: Robert

middle: H

last: Waterston

first: John

last: Murray


title: Selective roles of vertebrate PCF11 in premature and full-length transcript termination (ChIP-seq)

status: Public on Feb 28 2019

first: Kinga

last: Kamieniarz-Gdula

address: South Parks Road

department: Sir William Dunn School of Pathology

summary: The pervasive nature of RNA polymerase II (Pol II) transcription requires efficient termination. A key player in this process is the cleavage and polyadenylation (CPA) factor PCF11, which directly binds to the Pol II C-terminal domain and dismantles elongating Pol II from DNA in vitro. We demonstrate that PCF11-mediated termination is essential for vertebrate development. A range of genomic analyses, including: mNET-seq, 3’ mRNA-seq, chromatin RNA-seq and ChIP-seq, reveals that PCF11 enhances transcription termination and stimulates early polyadenylation genome-wide. PCF11 binds preferentially between closely spaced genes, where it prevents transcriptional interference and downstream gene silencing. Notably, PCF11 is sub-stoichiometric to the CPA complex. Low levels of PCF11 are maintained by an auto-regulatory mechanism involving premature termination of its own transcript, and are important for normal development. Both in human cell culture and during zebrafish development, PCF11 selectively attenuates the expression of other transcriptional regulators by premature CPA and termination.

overall_design: ChIP-seq in HeLa cells.

first: Michal

middle: R

last: Gdula

first: Karin

last: Panser

first: Andrea

last: Pauli

first: Nick

last: Proudfoot


title: Atlas of RNA sequencing profiles of normal human tissues

status: Public on Oct 04 2018

city: Moscow

first: Maria

middle: Vladimirovna

last: Suntsova

address: Miklukho-Maklaya, 16/10

department: Department of Genetics and Postgenomic Technologies

country: Russia

institute: M.M. Shemyakin and Yu.A. Ovchinnikov  Institute of  bioorganic chemistry of the Russian Academy of Sciences

summary: Comprehensive analysis of molecular pathology requires a collection of reference samples representing normal tissues from healthy donors. There is a shortage now of the gene expression data for human healthy tissues. The available data can either lack biological replicates or represent tissues adjacent to tumors removed during surgery that have signs of pathology and inflammation. For the available limited collections of normal tissues from post mortal donors, there is a problem of data incompatibility, as different datasets were generated using different experimental platforms and cannot be merged in a single panel. Here, for the first time, we construct and deposited a gene expression database of normal human tissues based on uniformly screened original sequencing (Illumina HiSeq 3000) data. A total of 148 solid tissue samples representing 20 organs were taken from post-mortal human healthy donors killed in road accidents no later than 36 hours after death. Blood and bone marrow samples were taken from 6 and 11 healthy volunteers respectively. The materials were collected since 2012 and stored until gene expression profiles were obtained by using the same reagents and protocols. Data consistency was confirmed by hierarchical clustering and principal component analysis (PCA). Our data can be useful to all those working with the analysis of human gene expression.

overall_design: A total of 148 solid tissue samples representing 20 organs were taken from post-mortal human healthy donors killed in road accidents no later than 36 hours after death. Prior to RNA extraction solid normal tissue samples were stored either in RNAlater or as Formalin-Fixed Paraffin-Embedded (FFPE) blocks. Blood and bone marrow samples were taken from 6 and 11 healthy volunteers respectively and subjected immediately to RNA extraction. Following ribosomal RNA depletion and RNA libraries construction transcription profiles of the samples were obtained using Illumina HiSeq 3000.

first: Anton

last: Buzdin

first: Maxim

last: Sorokin

first: Nurshat

last: Gaifullin

first: Alexey

last: Reshetun


title: Selective roles of vertebrate PCF11 in premature and full-length transcript termination

status: Public on Feb 25 2019

sample_organism:
Danio rerio
Homo sapiens

platform_organism:
Danio rerio
Homo sapiens


title: ADAR1-editing of cellular and measles virus-derived duplex RNA

status: Public on Dec 04 2018

city: Rochester

first: Christian

middle: Karl

last: Pfaller

state: MN

address: 200 First Street SW

department: Molecular Medicine

institute: Mayo Clinic


title: The methylome of DDR genes and benefit from RT or TMZ in IDH mutant low grade glioma treated in EORTC 22033

status: Public on Jan 31 2018

city: Lausanne

first: Pierre

last: Bady

address: Quartier UNIL-Sorge

department: Swiss Institute of Bioinformatics

institute: CHUV / BCF / SIB

summary: Treatment modalities for patients with low grade glioma (LGG) WHO grade II are controversial. Overall survival ranges from 2 to over 15 years depending on molecular and clinical factors. Hence, risk adjusted treatments are required to preserve cognitive function and quality of life. We aim at identifying mechanisms and associated molecular markers predicting benefit from radiotherapy (RT) or temozolomide (TMZ) on progression free survival in 120 isocitrate dehydrogenase 1 or 2 (IDHmt) mutant LGG treated in the randomized phase III trial EORTC 22033. IDH mutations, the characteristic hallmark of LGG, are associated with a CpG island methylator phenotype (CIMP). Given the genotoxic treatments in this study we determined the DNA methylome of DNA damage response (DDR) genes and assessed the association with progression free survival (PFS). We identified 62 functional CpGs corresponding to 24 of 410 DDR genes in the multidimensional LGG dataset from The Cancer Genome Atlas. Despite the low-powered study, the simulations suggested that seven CpGs, associated with 4 genes could be predictive for PFS in EORTC 22033. Most interestingly, two of the CpGs correspond to MGMT and consisted of the 2 probes used in the MGMT-STP27 classifier. The extent of methylation was predictive for PFS in the TMZ, but not the RT arm. LGG IDHmt and 1p and 19q codeleted that overlap largely with oligodendroglioma displayed a higher extent of MGMT methylation than the IDHmt non-codeleted tumors based on several independent LGG datasets. This is consistent with a better PFS of codeleted patients in the TMZ arm as compared to the non-codeleted patients, while no difference was observed in the RT-arm.

overall_design: Bisulphite converted genomic DNA from the 132 samples were hybridised to the Illumina Infinium 450 Human Methylation Beadchip

first: Sebastian

last: Kurscheid

first: Mauro

last: Delorenzi

first: Thierry

last: Gorlia

first: Pim

last: French

first: Roger

last: Stupp

first: Brigitta

middle: G

last: Baumert

first: Monika

last: Hegi


title: E. coli MazF does not create specialized ribosomes that translate leaderless mRNAs, but instead blocks rRNA maturation and ribosome biogenesis [RNA-seq]

status: Public on Dec 05 2017

city: Boston

first: Peter

last: Culviner

state: MA

address: 677 Huntington Ave

department: IID

institute: Harvard School of Public Health

summary: The purpose of this experiment was to characterize MazF cleavage specificity and locations of cleavage genome-wide in E. coli and also identify any leaderless transcripts .To do this, MazF was expressed in a ΔmazF background and compared to an empty vector. rRNA-subtracted samples were used to assess cleavage in the mRNA, and total RNA samples were used to assess changes in the rRNA.

overall_design: Two replicates of + MazF samples and empty vector samples after 5 minutes of induction (rRNA subtracted), two replicates of + MazF and empty vector samples after 5, 30 and 60 minutes (total RNA).

first: Michael

middle: T

last: Laub


title: An evaluation of the effects of CRISPR/cas9-mediated editing of the Dxz4 locus on regulation of the mouse inactive X chromosome in Patski cells [RNA-seq]

status: Public on Nov 28 2017

city: Seattle

first: Xinxian

last: Deng

address: 1959 NE Pacific St.

department: Laboratory Medicine and Pathology

institute: University of Washington

summary: The mammalian inactive X chromosome (Xi) condenses into a bipartite structure with two superdomains of frequent long-range contacts separated by a boundary or hinge region. Using in situ DNase Hi-C in mouse cells with deletions or inversions within the hinge, we show that the conserved repeat locus Dxz4 alone is sufficient to maintain the bipartite structure and that Dxz4 orientation controls the distribution of long-range contacts on the Xi. Frequent long-range contacts between Dxz4 and the telomeric superdomain are either lost after its deletion or shifted to the centromeric superdomain after its inversion. This massive reversal in contact distribution is consistent with the reversal of CTCF motif orientation at Dxz4. Decondensation of the Xi after Dxz4 deletion is associated with partial restoration of TADs normally attenuated on the Xi, and with an increase in chromatin accessibility and CTCF binding, but few changes in gene expression, in accordance with multiple epigenetic mechanisms ensuring X silencing. We propose that Dxz4 represents a structural platform for frequent long-range contacts with multiple loci in a direction dictated by the orientation of a bank of CTCF motifs at Dxz4, which may work as a ratchet to form the distinctive bipartite structure of the condensed Xi.

overall_design: RNA-seq experiment on F1 hybrid wild-type and CRISPR/cas9-modified Patski cells.

first: Giancarlo

last: Bonora

first: He

last: Fang

first: Vijay

last: Ramani

first: Ruolan

last: Qui

first: Joel

last: Berletch

first: Gala

middle: N

last: Filippova

first: Zhijun

last: Duan

first: Jay

last: Shendure

first: William

last: Noble

first: Christine

last: Disteche


title: An evaluation of the effects of CRISPR/cas9-mediated editing of the Dxz4 locus on regulation of the mouse inactive X chromosome in Patski cells [ChIP-seq]

overall_design: CTCF ChIP-seq on F1 hybrid wild-type and CRISPR/cas9-modified Patski cells.


title: Expression data from edema toxin treated primary hepatocytes from 1–3-day-old neonatal A/J mice

status: Public on Jun 16 2018

city: El Paso

first: Lihong

last: Wu

state: Texas

address: MSB1, Room 3105,5001 El Paso Drive

department: Department of Biomedical Sciences, Paul L. Foster School of Medicine

institute: Texas Tech University Health Sciences Center El Paso

summary:
The activity of known anthrax toxins is insufficient to account the effects on functions of hepatocytes. In vivo and in vitro studies showed that Anthrax edema toxin (EdTx) induce lethal liver and heart damage
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated and down-regulated genes during this process.

overall_design: Primary hepatocytes were selected from 1–3-day-old neonatal A/J miceat for RNA extraction and hybridization on Affymetrix microarrays. To investigate the mechanism underlying the toxicity of EdTx for hepatocytes, we conducted a microarray assay to identify potential genes related to impaired liver function induced by EdTx treatment.

first: Mingtao

last: Zeng


title: Expression data from anthrax lethal toxin treated primary cardiomyocytes from 1-3-day-old neonatal Balb/c mice

status: Public on Jul 07 2018

summary:
The activity of known anthrax lethal toxin is insufficient to account the effects on functions of cardiomyocytes. In vivo and in vitro studies showed that Anthrax lethal toxin (LeTx) induce heart damage
We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated and down-regulated genes during this process.

overall_design: Primary cardiomyocytes were selected from 1-3-day-old neonatal Balb/c miceat for RNA extraction and hybridization on Affymetrix microarrays. To investigate the mechanism underlying the toxicity of LeTx for cardiomyocytes, we conducted a microarray assay to identify potential genes related to impaired heart function induced by LeTx treatment.


title: An evaluation of the effects of CRISPR/cas9-mediated editing of the Dxz4 locus on regulation of the mouse inactive X chromosome in Patski cells [ATAC-seq]

overall_design: ATAC-seq experiment on F1 hybrid wild-type and CRISPR/cas9-modified Patski cells.


title: A unified activation mechanism for mRNA 3’ end processing and splicing mediated by SR superfamily proteins

status: Public on Nov 01 2017

city: Irvine

first: Elmira

last: Forouzmand

address: B228 Medical Science I

department: Department of Microbiology and Molecular Genetics

institute: University of California Irvine

summary: Alternative mRNA processing is a critical mechanism for proteome expansion and gene regulation in higher eukaryotes. The SR family proteins play important roles in splicing regulation. Intriguingly, mammalian genomes encode many poorly characterized SR-like proteins, including subunits of the mRNA 3’ processing factor CFIm, CFIm68 and CFIm59. Here we demonstrate that CFIm functions as an enhancer-dependent activator of mRNA 3’ processing. CFIm regulates global alternative polyadenylation (APA) by specifically binding and activating enhancer-containing poly(A) sites (PAS). Importantly, the CFIm activator functions are mediated by the arginine-serine repeat (RS) domains of CFIm68/59, which bind specifically to an RS-like region in the CPSF subunit Fip1, and this interaction is modulated by phosphorylation. The remarkable functional similarities between CFIm and SR proteins suggest that interactions between RS-like regions in regulatory and core factors may provide a common activation mechanism for mRNA 3’ processing, splicing, and potentially other steps in RNA metabolism.

overall_design: Total RNAs from control HEK293T cells, CFIm59 KO cell lines (2 different cell lines), and CFIm68 KO cell lines (2 different cell llines) were fragmented, and reverse transcribed with an oligo(dT) primer containing a linker sequence. cDNAs were circularized, re-linearized by restriction digestion, and PCR amplified to generate libraries. The libraries were sequenced on HiSeq 2000 (single end 150 nucleotides).

first: Xiuye

last: Wang

first: Yong

last: Zhu

first: Yongsheng

last: Shi


title: Tricyclic Antidepressants Induce Inactivation of Hepatic Stellate Cell (HSC) Myofibroblasts

status: Public on Mar 02 2017

first: Chan

last: Zhou

state: Massachusetts

address: 55 Fruit Street

department: gastroenterology

institute: Mass General Hospital, Harvard Medical School

summary: Hepatic stellate cells (HSCs) are the primary cell type responsible for liver fibrosis, the final common pathway leading to cirrhosis and liver failure for nearly every cause of chronic liver disease. Activation of HSCs in response to injury represents the key step in hepatic fibrogenesis, and is characterized by a phenotypic change from a non-fibrogenic, quiescent HSC to a fibrogenic HSC myofibroblast that secretes extracellular matrix proteins responsible for the fibrotic scar. We developed a small molecule screen to identify compounds that revert fibrotic human HSC myofibroblasts to an inactive phenotype through the quantification of lipid droplets with fluorescent microscopy. Conditions were optimized in a 384-well format using culture in Matrigel as a positive control. We screened 1600 compounds and identified 30 small molecules that induce reversion to an inactive phenotype. Among the hits, we identified five tricyclic antidepressants (TCAs) and showed that this class of drugs also repressed ACTA2 and COL1A1 while promoting PPAR-gamma expression. RNA sequencing analysis implicated extracellular matrix proteins and the sphingolipid pathway as a target of the TCAs.

overall_design: HSCs and HSCs stimulated with TGF-beta were treated with the TCA, nortriptyline or ethanol vehicle for 48 hours. RNA-seq was performed in duplicate for each condition

first: Jennifer

middle: Y

last: Chen

first: Joshua

middle: V

last: Pondick

first: Alan

middle: C

last: Mullen


title: Transcriptomic analysis of a Saccharomyces cerevisiae mutant with improved coniferyl aldehyde resistance

status: Public on Aug 31 2018

first: Halil

last: KISAKESEN

address: ITU MOBGAM, SARIYER

department: Molecular Biology, Genetics and Biotechnology

summary: A Saccharomyces cerevisiae mutant with improved coniferyl aldehyde resistance was obtained by using an evolutionary engineering strategy, based on successive batch cultivation under gradually increased coniferyl aldehyde concentration. The mutant strain BH13 was selected which could grow at a coniferyl aldehyde concentration that the reference strain could not grow at all. Whole-genome transcriptomic analysis of BH13 with respect to the reference strain was performed to identify differences in gene expression levels between the two strains.

overall_design: To perform the comparative whole-genome transcriptomic analysis of the selected mutant BH13 with respect to the reference strain, Agilent Yeast One-Color DNA microarray systems were used. Prior to gene expression analysis, three replicates of each culture were grown in yeast minimal medium (YMM) at 30°C and 150 rpm. Total RNA isolation was carried out by using RNeasy Mini Kit (Qiagen) at logarithmic phase of growth (OD600 ~1.0)

first: Burcu

last: Hacısalihoglu

last: Kisakesen

first: Zeynep

middle: P

last: Çakar


title: Developmental effects of maternal dietary vitamin A deficiency and P450 cytochrome 1b1 deletion in mice

status: Public on Oct 12 2016

city: Madison

first: Colin

last: Jefcoate

state: WI

address: 1111 Highland Ave

department: Cell and Regenerative Biology

institute: UW-Madison

summary: Wild type C57Bl/6J, Cyp1b1-null, and a substrain of Cyp1b1-null that are resistant to diet-induced obesity (Resistant Cyp1b1-null) timed mated pregnant dams were administered either a defined vitamin A sufficient diet or matched vitamin A deficient diet from embryonic day 4.5. Offspring liver gene expression was examined at birth (post-natal day 0) and at weaning (post-natal day 21).

overall_design: Nine comparison experiment. C57Bl/6J WT vitamin A sufficient birth (PN0) control with WT vitamin A deficient PN0 and Cyp1b1-null vitamin A sufficient PN0. Cyp1b1-null vitamin A sufficient PN0 with Cyp1b1-null vitamin A deficient PN0. WT vitamin A sufficient weaning (PN21) control with WT vitamin A deficient PN21 and Cyp1b1-null vitamin A sufficient PN21 and R-Cyp1b1-null vitamin A sufficient PN21. Cyp1b1-null vitamin A sufficient PN21 with Cyp1b1-null vitamin A deficent PN21.R-Cyp1b1-null vitamin A sufficient PN21 with R-Cyp1b1-null vitamin A deficient PN21. WT vitamin A sufficient PN0 with WT vitamin A sufficient PN21.

first: C


title: Effect of iBET762+ on transcriptome of 20861 and 20863 W12 cells

status: Public on Aug 22 2016

first: Alison

middle: Anne

last: McBride

address: 33 North Drive

department: DIR

institute: NIAID

summary: To determine the effect of iBET762+, a bromodomain BET inhibitor, on the transcription of 20861 and 20863 cells. These cells are subclones of W12 cells, derived from cervical intraepithelial neoplastic lesion. 20861 contains integrated HPV16 DNA and 20863 contains extrachromosomal HPV16 DNA. iBET762+ decreases expression of the HPV16 E6 and E7 oncogenes in both cell lines and this is expected to have dramatic effects on the cellular transcriptome

overall_design: Isolate mRNA from 20861 and 20863 cells after 44 hours treatment with 1 micromolar iBET762- (the inactive enantiomer) or iBET762+. Three biological replicates from independent experiments.


title: An evaluation of the effects of CRISPR/cas9-mediated editing of the Dxz4 locus on regulation of the mouse inactive X chromosome in Patski cells [DNase HiC]

first: Xinxian

last: Deng

state: WA

overall_design: in situ DNase Hi-C assay on F1 hybrid wild-type and CRISPR/cas9-modified Patski cells.

first: Giancarlo

last: Bonora

first: He

last: Fang

first: Vijay

last: Ramani

first: Ruolan

last: Qui

first: Joel

last: Berletch

first: Gala

last: Filippova

first: Zhijun

last: Duan

first: Jay

last: Shendure

first: William

middle: S

last: Noble

first: Christine

last: Disteche


title: A faithful in vivo model of human MLL-AF4 proB acute lymphoblastic leukemia

status: Public on Nov 23 2016

city: Cincinnati

first: Shan

last: Lin

state: OH

address: 3333 Burnet Avenue, CCHMC

department: EHCB

institute: Cincinnati Children's Hospital Medical Center

summary: Transcriptome analysis by RNAseq of leukemia model promoted by MLL-Af4 or MLL-AF9 fusion proteins. We find each fusion protein promotes a specific gene signature correlating to those identified in patients

overall_design: Human CD34+ hematopoietic stem and progenitor cells were transduced with retrovirus expressing MLL-Af4 or MLL-AF9. Transduced cells were transplanted into immunodeficient mice to induce lymphoid leukemia or placed in myeloid in vitro culture. CD19+ lymphoid leukemia cells (3 AF9, 6 Af4),  control health CD19+CD34+ proB cells (n=3) and 4 pairs of Af4 and AF9 CD33+CD19- myeloid culture cells were collected for RNA-seq

first: James

last: Mulloy

first: Roger

last: Luo

first: Michael

middle: J

last: Thirman


title: CPD-seq mapping of UV damage formation and repair in yeast

status: Public on Aug 19 2016

city: Pullman

first: John

last: Wyrick

address: Biotechnology Life Sciences 241

department: School of Molecular Biosciences

institute: Washington State University

summary: UV-induced DNA lesions are an important contributor to mutagenesis and cancer, but it is not fully understood how the chromosomal landscape influences UV lesion formation and repair. We have used a novel high-throughput sequencing method to precisely map UV-induced cyclobutane pyrimidine dimers (CPDs) at nucleotide resolution throughout the yeast genome. Analysis of CPD formation reveals that nucleosomal DNA having an inward rotational setting is protected from CPD lesions. In strongly positioned nucleosomes, this nucleosome 'photofootprint' overrides intrinsic dipyrimidine sequence preferences for CPD formation. CPD formation is also inhibited by DNA-bound transcription factors, in effect protecting important DNA elements from UV damage. Analysis of CPD repair revealed a clear signature of efficient transcription-coupled nucleotide excision repair. Repair was less efficient at translational positions near a nucleosome dyad and at heterochromatic regions in the yeast genome. These findings define the roles of nucleosomes and transcription factors in UV damage formation and repair.

overall_design: UV mapping data was analyzed for yeast cells irradiated with 125J/m2 and allowed to repair for 0hr (2 samples), 20 minutes, 1 hour, or 2 hours. Data is also included for naked DNA irradiated with UV 60 or 90 J/m2

first: Peng

last: Mao


title: Gene expression profile in CD4+ T-cell infection with a SIV mutant related to altered humoral immune responses

status: Public on Jan 01 2016

city: Shinjuku-ku

first: Hiroyuki

last: Yamamoto

state: Tokyo

address: 1-23-1 Toyama

department: AIDS Research Center

country: Japan

institute: National Institute of Infectious Diseases

summary: A mutant simian immunodeficiency (SIVmac239) virus, found to be selected within chronically SIV-infected Burmese rhesus monkeys with relatively enhanced SIV-specific antibody responses, was reconstituted as a molecular clone. The virus (SIV Nef G63E) was then subjected to a preliminary analysis for their intracellular signal transduction and gene expression modulation patterns (as compared with wild type SIVmac239) within infected CD4+ T cells. Analysis implicated that the mutant virus had a moderately enhanced cytopathic phenotype.

overall_design: A SIV mutation (SIVmac239 Nef G63E) found to be enriched in rhesus monkeys with enhanced SIV-specific antibody responses was reconstituted on a pBR-based SIV molecular clone pBRmac239. HSC-F cynomolgus macaque central memory Th2-like T cells were infected with mutant and wild type SIVmac239 at MOI 5 in triplicate along with uninfected controls (i.e. a total of 9 samples) for 24 hours and subjected to analysis of their gene expression patterns.


title: Identification of circulating microRNAs as potential biomarkers for detecting acute ischemic stroke

status: Public on Aug 12 2015

city: Nanjing

first: Pengfei

last: Li

state: Jiangsu

address: NO.155 Hanzhong Road, Baixia District

department: Clinical Laboratory

institute: Jiangsu Province Hospital of TCM

summary: In order to determine the serum microRNAs profile from middle-old aged patients with acute ischemic stroke and investigate possible diagnostic value of these differential microRNAs.The blood samples of 117 IS patients and 82 healthy people were collected. Differential miRNAs in serum from IS and control were screened with miRNA microarray analysis, and the expression of selected miRNAs were validated by quantitative reverse-transcriptase polymerase chain reaction assays (qRT-PCR). Results: We discovered 115 differentially expressed miRNAs, among which miR-32-3p, miR-106-5p, miR-532-5p were found be related to IS for the first time. Conclusions: In the present study, we identified the changed expression pattern of miRNAs in IS. Serum miR-32-3p, miR-106-5p, miR-1246 and miR-532-5p may serve as potential diagnostic biomarkers for IS.

platform_organism:
Homo sapiens
Human alphaherpesvirus 1
Human alphaherpesvirus 2
Cytomegalovirus
Lymphocryptovirus
Rhadinovirus
JC polyomavirus
Human immunodeficiency virus 1
Merkel cell polyomavirus
Betapolyomavirus hominis
Betapolyomavirus macacae

overall_design: During the initial screening stage, we divided the serum samples into five groups (10 serum samples were pooled to form a group). Group A1: A denotes thrombotic stroke and 1 denotes hepertension. Group A14: A denotes thrombotic stroke, 1 denotes hepertension and 4 denotes hyperlipidemia. Group B2: B denotes embolic stroke and 2 denotes heart disease. Group B12: B denotes embolic stroke, 1 denotes hepertension and 2 denotes heart disease. Group 0: healthy control group.

first: Chunbing

last: Zhang


title: Nucleophosmin binding on the mouse X chromosomes

status: Public on Aug 11 2015

first: Xinxian

last: Deng

type: Genome binding/occupancy profiling by genome tiling array

summary: In mammals, one of the female X chromosomes and all imprinted genes are expressed exclusively from a single allele in somatic cells. To evaluate structural changes associated with allelic silencing, we have applied a recently developed Hi-C assay that uses DNase I for chromatin fragmentation to mouse F1 hybrid systems. Results We find radically different conformations for the two female mouse X chromosomes. The inactive X has two superdomains of frequent intrachromosomal contacts separated by a boundary/hinge region. Comparison with the recently reported bipartite 3D structure of the human inactive X shows that the genomic content of the superdomains differs between species, but part of the hinge is conserved and located near the Dxz4/DXZ4 locus. In mouse, the hinge region also contains a minisatellite Ds-TR, and both Dxz4 and Ds-TR appear to be anchored to the nucleolus. Genes that escape X inactivation do not cluster but are located near the periphery of the 3D structure, as are regions enriched in CTCF or RNA polymerase. Fewer short-range intrachromosomal contacts are detected for the inactive alleles of genes subject to X inactivation, compared to the active alleles and to genes that escape X inactivation. This pattern is also evident for imprinted genes, in which more chromatin contacts are detected for the expressed allele. Conclusions By applying a novel Hi-C method to map allelic chromatin contacts, we discover a specific bipartite organization of the mouse inactive X chromosome that probably plays an important role in maintenance of gene silencing.

overall_design: Examination of Nucleophosmin-binding profiles in male and female mouse livers

first: Fan

last: Yang

middle: M


title: Disruption of Drp1 in the liver protects mice against diet-induced obesity through induction of fibroblast growth factor 21

status: Public on Jun 01 2015

city: Fukuoka

first: Lixiang

last: Wang

state: Fukuoka

address: 3-1-1, Maidashi, Higashi-ku

department: Department of Medicine and Bioregulatory Science

institute: Graduate School of Medical Sciences, Kyushu University

summary: Mitochondria and the endoplasmic reticulum (ER) physically interact by close structural juxtaposition, via the mitochondrial-associated ER membrane. Recently, great advances have been made in the understanding of inter-organelle communication between the ER and mitochondria. To clarify the role of mitochondrial dynamics in this communication, we generated mice lacking the mitochondrial fission protein dynamin-related protein 1 (Drp1) in the liver (Drp1LiKO). While intake of a high-fat diet (HFD) resulted in histological changes characterized by hepatic steatosis, inflammation, apoptosis, necrosis and fibrosis, reminiscent of nonalcoholic steatohepatitis, Drp1LiKO mice showed decreased fat mass and were protected from HFD-induced obesity. Analysis of liver gene expression profiles demonstrated marked elevation of ER stress markers. In addition, we observed increased expression of fibroblast growth factor 21 (Fgf21) through induction of activating transcription factor 4 and X-box binding protein 1, master regulators of the integrated stress response.

overall_design:
Mice were given ad libitum access to a normal chow diet (NCD) containing 5.4% fat (CRF-1; Orient Yeast, Tokyo, Japan). For the high-fat diet (HFD) study, 4-week-old mice were fed a diet consisting of 24% fat (lard fat, 45% kcal fat, D12451; Research Diets, New Brunswick, NJ) for 24 weeks. Experiments were conducted between 10:00 a.m. and 11:00 a.m. after a 17-hour fasting period. Refeeding samples were collected between 2:00 p.m. and 3:00 p.m. after a 4-hour refeeding period following an overnight fast.

Total RNA was isolated from mouse liver using TRIzol Reagent (Invitrogen Corporation, Carlsbad, CA, USA) and purified using the SV Total RNA Isolation System (Promega Corporation, Madison, WI, USA) following the manufacturer’s instructions. Gene expression profiling was performed using the Whole Mouse Genome Microarray 4x44K v2 platform containing 39,430 probes (Agilent Technologies).

first: Masatoshi

last: Nomura


title: Bipartite structure of the inactive mouse X chromosome

status: Public on Jul 16 2015

summary: A subset of genomic regions, including one of the female X chromosomes and all imprinted genes, are expressed exclusively from a single allele in somatic cells of mammals. To evaluate structural changes associated with allelic silencing, we used mouse F1 hybrid systems in which X inactivation is skewed and alleles can be distinguished based on single nucleotide polymorphisms to analyze chromatin contacts by a new Hi-C assay that uses DNase I for chromatin fragmentation. Both DNase Hi-C and in situ DNase Hi-C reveal a radically different conformation between the two female mouse X chromosomes. Two superdomains of frequent intrachromosomal contacts separated by a hinge region are specifically observed on the inactive X chromosome both in vivo (brain) and in vitro (Patski cells). A bipartite 3D organization of the inactive X has been also reported in human lymphoblastoid cells, suggesting that this conserved structure probably plays an important role in maintenance of gene silencing on the inactive X. Interestingly, we found that the genomic content of the superdomains differs between species, but that part of the hinge region is conserved and located near the Dxz4/DXZ4 locus that binds CTCF on the inactive X. In mouse, the hinge region also contains a minisatellite Ds-TR adjacent to a promoter with strong CTCF binding. Both Dxz4 and Ds-TR bind nucleophosmin and are enriched in nucleolus-associated chromatin, suggesting anchoring to the nucleolus. Genes that escape X inactivation do not cluster but are preferentially located near the periphery of the 3D structure. Regions enriched in CTCF or RNA polymerase are also preferentially located on the periphery of the inactive X while LINE1 elements are preferentially on the interior. Genes subject to silencing exhibit fewer detectable intrachromosomal contacts than escape genes. This transcription-coupled pattern is also evident for imprinted genes, in which more chromatin contacts are detected on the expressed allele, suggesting greater constraint on the organization of expressed genomic regions.

overall_design: DNase Hi-C assay and in situ Dnase Hi-C assay in F1 hybrid mouse brain and Patski cells

first: Wenxiu

last: Ma

first: Vijay

last: Ramani

first: Zhijun

last: Duan


title: Genome wide mapping of long noncoding (lnc) RNAs in hepatic stellate cells

status: Public on Mar 23 2016

first: Chan

last: Zhou

summary: Hepatic stellate cells are the primary cell type responsible for development of fibrosis in chronic liver disease.  We used directional RNA sequencing (RNA-seq) and chromatin immunoprecipitation and sequencing (ChIP-seq) to identify the lncRNAs expressed in human HSCs. We also identified the lncRNAs that change in expression with differentiation of nonfibrotic quiescent HSCs into fibrotic HSC myofibroblasts and those that are regulated by TGF-beta signaling. ChIP-seq was also performed to identify DNA regions occupied by H3K27ac to define super-enhancers in HSC myofibroblasts.  This study identified lncRNAs expressed HSCs that may regulate fibrosis.

overall_design: Analysis of genome-wide lncRNA expression using RNA-seq and ChiP-seq in human HSCs under four different conditions

first: Samuel

last: York

first: Alan

last: Mullen


title: The effect of listening to music on human transcriptome

status: Public on Apr 13 2015

city: Helsinki

first: Irma

last: Jarvela

address: Biomedicum Helsinki, PO Box 63, Room B311b

department: Medical Genetics

country: Finland

institute: University of Helsinki

summary: The aim of the dataset was to study the effect of music exposure  on human blood transcriptome.

overall_design:
Total RNAs from peripheral blood of samples were compared before and after listening to a 20 minutes of classical music. Samples were collected from 48 samples before and after music exposure.

***On March 3, 2025, the submitter requested removal of the samples due to patient privacy concerns.***

first: Chakravarthi

last: Kanduri

first: Minna

last: Ahvenainen

first: Liisa

last: Ukkola-Vuoti

first: Pirre

last: Raijas

first: Harri

last: Lähdesmaki

last: Järvelä


title: ADAR1-editing in HeLa, p150-KO and ADAR1-KO transcriptomes

status: Public on Dec 04 2018

first: Christian

last: Pfaller

summary: RNAseq analysis of cell lines with ADAR1-p150 and ADAR1-p110 knock-outs and primary human tissue samples (from GSE57353 and GSE99392 data sets) to identify sites of ADAR1 editing

overall_design: 12 samples: 3 cell lines (HeLa, HeLa-p150KO, HeLa-ADAR1KO) with four conditions each (no treatment, MeV-vac2(GFP)-infected, MeV-CKO(GFP)-infected, IFNA/D-treated). One biological replicate per sample. In addition, raw data files of 9 samples from series GSE57353 and GSE99392 were re-analyzed using the same data processing pipeline.

first: Roberto

last: Cattaneo


title: Whole genome characterisation of chemoresistant ovarian cancer [Illumina_450K_Methylation]

status: Public on May 19 2015

city: Herston

first: Ann-Marie

last: Patch

state: QLD

address: 300 Herston Road

country: Australia

institute: QIMR Berghofer Medical Research Institute

type: Methylation profiling by genome tiling array

summary: Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

overall_design:
Genomic DNA (500ng) was bisulfite converted using EZ DNA methylation Kit (Zimo Research) following the manufacturer’s protocol with modification for Illumina Infinium Methyaltion arrays. Samples were hybridized to Infinium Human Methylation 450K BeadChips (Illumina) according to the manufacturer’s protocol. Arrays were scanned on Iscan (Illumina). Data was background corrected, normalized to internal controls and QC was performed at the probe and sample level. COMBAT was used to remove batch effects (Johnson et al., 2007).

Contributor: The Australian Ovarian Cancer Study Group

first: Ann

first: Elizabeth

middle: L

last: Christie

first: Dariush

last: Etemadmoghadam

first: Dale

middle: W

last: Garsed

first: Joshy

last: George

first: Sian

last: Fereday

first: Katia

last: Nones

first: Prue

last: Cowin

first: Kathryn

last: Alsop

first: Peter

last: Bailey

first: Karin

last: Kassahn

first: Felicity

last: Newell

first: Michael

last: Quinn

first: Stephen

last: Kazakoff

first: Kelly

last: Quek

first: Charlotte

last: Wilhelm-Benartzi

first: Ed

last: Curry

first: Huei

last: San

first: San

last: Leong

first: Anne

last: Hamilton

first: Linda

last: Mileshkin

first: George

last: Au-Yeung

first: Catherine

last: Kennedy

first: Jillian

last: Hung

first: Yoke

middle: E

last: Chiew

first: Paul

last: Harnett

last: Friedlander

first: Jan

last: Pyman

last: Cordner

first: Patricia

last: O'Brien

first: Jodie

last: Leditschke

first: Greg

last: Young

first: Kate

last: Strachan

last: Waring

first: Walid

last: Azar

first: Chris

last: Mitchell

first: Nadia

last: Traficante

first: Joy

last: Hendley

first: Heather

last: Thorne

first: Mark

last: Shackleton

first: David

last: Miller

first: Gisela


title: Whole genome characterisation of chemoresistant ovarian cancer

first: Ann-Marie

last: Patch

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

Patients with high-grade serous ovarian cancer (HGSC) have experienced little improvement in overall survival, and standard treatment has not advanced beyond platinum-based combination chemotherapy, during the past 30 years. To understand the drivers of clinical phenotypes better, here we use whole-genome sequencing of tumour and germline DNA samples from 92 patients with primary refractory, resistant, sensitive and matched acquired resistant disease. We show that gene breakage commonly inactivates the tumour suppressors RB1, NF1, RAD51B and PTEN in HGSC, and contributes to acquired chemotherapy resistance. CCNE1 amplification was common in primary resistant and refractory disease. We observed several molecular events associated with acquired resistance, including multiple independent reversions of germline BRCA1 or BRCA2 mutations in individual patients, loss of BRCA1 promoter methylation, an alteration in molecular subtype, and recurrent promoter fusion associated with overexpression of the drug efflux pump MDR1.

overall_design:
Refer to individual Series

Contributor: The Australian Ovarian Cancer Study Group

first: Ann

first: Elizabeth

last: Christie

first: Dariush

last: Etemadmoghadam

first: Dale

last: Garsed

first: Joshy

last: George

first: Sian

last: Fereday

first: Katia

last: Nones

first: Prue

last: Cowin

first: Kathryn

last: Alsop

first: Peter

last: Bailey

first: Karin

last: Kassahn

first: Felicity

last: Newell

first: Michael

last: Quinn

first: Stephen

last: Kazakoff

first: Kelly

last: Quek

first: Charlotte

last: Wilhelm-Benartzi

first: Ed

last: Curry

first: Huei

last: San

first: San

last: Leong

first: Anne

last: Hamilton

first: Linda

last: Mileshkin

first: George

last: Au-Yeung

first: Catherine

last: Kennedy

last: Hung

last: Chiew

middle: K


title: Microarray analysis of rat brain following chronic treatment with antipsychotic drugs or mood stabilizers

status: Public on Mar 16 2015

city: Groton

first: Thomas

middle: A

last: Lanz

state: CT

address: Eastern Point Rd

department: Multi-Omics & Biomarkers

institute: Pfizer

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

overall_design: Refer to individual Series


title: Effects of Firre knockdown on mouse gene expression

status: Public on Mar 05 2015

first: Xinxian

last: Deng

summary: In mammals, genes located on the X chromosome are present in one copy in XY males and two in XX females. To balance the dosage of X-linked gene expression between the sexes one of the two X chromosomes in females is silenced by X inactivation initiated by up-regulation of the lncRNA (long non-coding RNA) Xist and recruitment of specific chromatin modifiers for silencing. The inactivated X chromosome becomes heterochromatic and visits a specific nuclear compartment adjacent to the nucleolus. We report a novel role for the X-linked lncRNA Firre in anchoring the inactive mouse X chromosome and preserving one of its main epigenetic features, trimethylation of histone H3 at lysine 27 (H3K27me3). Similar to Dxz4, Firre is expressed from a macrosatellite repeat locus associated with a cluster of CTCF and cohesin binding specifically on the inactive X. CTCF binding initially present in both male and female mouse embryonic stem cells was found to be lost from the active X during development. The Firre and Dxz4 loci on the inactive X were preferentially located adjacent to the nucleolus. Knockdown of Firre RNA disrupted perinucleolar targeting and H3K27me3 levels in mouse fibroblasts, demonstrating an important role for this lncRNA in maintenance of one of the main epigenetic features of the X chromosome. There was no X-linked gene reactivation after Firre knockdown; however, a compensatory increase in the expression of chromatin modifier genes implicated in X silencing was observed. In female ES cells Firre RNA knockdown did not disrupt Xist expression/coating nor silencing of G6pdx during differentiation, suggesting that Firre does not play a role in the onset of X inactivation. We conclude that the X-linked lncRNA Firre helps position the inactive X chromosome near the nucleolus and preserve one of its main epigenetic features.

overall_design: Examination of allelic expression in Patski cells upon Firre knockdown.

first: Fan

last: Yang

first: Wenxiu

last: Ma

first: William

last: Noble

first: Jay

last: Shendure

first: Christine

last: Disteche


title: Microarray profiling of rats treated for 21 days with Lithium chloride (0.2% in chow), Lamotrigine (30 mg/kg), or appropriately matched vehicles

summary: SD rats were dosed with gold mood stabilizer therapies, lithium or lamotrigine, at doses aimed at achieving therapeutically relevant drug exposures.  Tissues were collected after 21 days of delivery to examine the impact of this treatment on gene expression in frontal cortex, hippocampus and striatum.

overall_design: n=5 per group.  LiCl was delivered in chow (0.2%), and compared with a vehicle chow group.  Lamotrigine was administered via subcutaneous injection once daily and compared with a vehicle injection.  All drugs were administered for 21 days.

first: Robin

last: Kleiman


title: Microarray profiling of rats treated for 21 days with haloperidol (0.25 mg/kg/d), risperidone (5 mg/kg/d) or vehicle

summary: SD rats were dosed with gold standard antipsychotic therapies, haloperidol or risperidone, at doses aimed at achieving therapeutically relevant drug exposures.  Tissues were collected after 21 days of delivery to examine the impact of this treatment on gene expression in frontal cortex, hippocampus and striatum.

overall_design: n=5 per group.  Rats were implanted with osmotic minipumps at 9-11 weeks of age, prepared with compound or vehicle.  Tissue was collected after 21 days of constant drug delivery.


title: Regulation of mouse X inactivation (ChIP-Seq)

status: Public on Feb 20 2015

summary: X chromosome inactivation (XCI) silences most genes on one X chromosome in female mammals, but some genes escape XCI. To identify escape gene in vivo and to explore molecular mechanisms that regulate this process we analyzed the allele-specific expression and chromatin structure of X-linked genes in mouse tissues and cells with skewed XCI and distinguishable alleles based on single nucleotide polymorphisms. Using a new method to estimate allelic expression, we demonstrate a continuum between complete silencing and significant expression from the inactive X (Xi). Few genes (2-3%) escape XCI to a significant level and only a minority differs between mouse tissues, suggesting stringent silencing and escape controls. Allelic profiles of DNase I hypersensitivity and RNA polymerase II occupancy of genes on the Xi correlate with escape from XCI. Allelic binding profiles of the DNA binding protein CCCTC-binding factor (CTCF) in different cell types indicate that CTCF binding at the promoter correlates with escape. Importantly, CTCF binding at the boundary between escape and silenced domains may prevent the spreading of active escape chromatin into silenced domains.

overall_design: Examination of CTCF and RNA PolIIS5p occupancy in mouse hybrid cells and adult tissues.

first: Joel

middle: B

last: Berletch


title: Female-specific CTCF binding on the inactive X chromosome in mouse

status: Public on Feb 26 2015

sample_organism:
Mus musculus
Mus musculus x Mus spretus

overall_design: Examination of allelic protein-binding or histone modification profiles in Patski cells.


title: Escape from X inactivation in mouse tissues (RNA-Seq)

overall_design: Examination of allelic expression in mouse hybrid tissues.


title: Gene regulation in human epidermal keratinocytes by a Rho kinase inhibitor (Y-27632)

status: Public on Mar 31 2014

city: Bethesda

first: Alison

last: McBride

summary: We previously demonstrated that the lifespan of primary human keratinocytes could be extended indefinitely by culture in the presence of the Rho kinase (ROCK) inhibitor Y-27632. Here, gene expression analysis of primary human epidermal keratinocytes cells grown in the presence of Y-27632 demonstrates that ROCK inhibition primarily inhibits keratinocyte differentiation.

overall_design: mRNA profiles of primary HEKs treated with and without the rho kinase inhibitor Y-27632 were generated by microarray analysis using Illumina BeadChip.

first: Moon

last: Jang


title: Gene expression data from cervical spinal cord regions of MPTP-intoxicated mouse by acupuncture

status: Public on Oct 23 2010

city: Seoul

first: Sabina

last: Lim

address: #1 Hoegi-dong Dongdaemoon-gu

country: South Korea

institute: East-West Medical Research Institute, Kyung Hee University

summary:
It has been shown that acupuncture at acupoints GB34 and LR3 inhibits the degeneration of nigrostriatal neurons in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. This preventative effect of peripheral acupuncture stimulation is hypothesized to be transmitted through the spinal cord to the nigrostriatal neurons.
The gene expression profile changes following acupuncture at the acupoints were investigated in the cervical spinal cord of an MPTP-induced parkinsonism model using an Affymetrix genechip mouse gene 1.0 ST array.

overall_design: C57BL/6 mice were divided into four experimental groups; ① C: Control, ② M: MPTP-treatment only, ③ MA: MPTP- and acupuncture-treatment at acupoints GB34 and LR3, ④ MNA: MPTP- and acupuncture-treatment at non-acupoints. Total RNA was isolated from the cervical spinal cord regions of each experimental group (4 experimental group × 2 samples of each experimental group = total 8 samples).

first: Yeong-Gon

last: Choi

first: Sujung

last: Yeo

first: Yeon-Mi

last: Hong


title: The effects of ectopic UCP1 expression on gene expression in skeletal muscle

status: Public on Feb 19 2015

city: Wageningen

first: Evert

middle: M.

last: van Schothorst

address: De Elst 1

country: Netherlands

institute: Wageningen University


title: Single cell RNA-seq analysis of oligodendroglioma

status: Public on Nov 06 2016

city: Rehovot

first: Itay

last: Tirosh

address: Herzl 234

country: Israel

institute: WEIZMANN INSTITUTE OF SCIENCE

summary: To understand the diversity of expression states within oligodendroglioma tumors, we obtained six freshly resected samples, profiled ~1000 cells from each tumor and examined their diversity.

overall_design:
Tumors were disaggregated, sorted into single cells, and profiled by Smart-seq2.

**GSM1812084 to GSM1815456: Submitter declares reads will be made available through dbGaP.**

**Sample records after GSM1815456: Submitter declares reads will be submitted to controlled access SRA and/or dbGaP. The sample records that follow GSM1815456 are incomplete.**

first: Andy

last: Venteicher

first: Mario

last: Suva

first: Aviv

last: Regev


title: Studies of regulation of mouse X inactivation and genes escaping XCI

first: Xinxian

last: Deng

address: 1959 NE Pacific St.

institute: University of Washington

platform_organism:
Mus musculus
Mus musculus x Mus spretus