title: WDR5 is a conserved regulator of protein synthesis gene expression

status: Public on Jan 17 2020

city: Nashville

first: Jing

last: Wang

state: TN

address: 2220 Pierce Avenue

institute: Vanderbilt University Medical Center

summary: WDR5 is a highly-conserved nuclear protein that performs multiple scaffolding functions in the context of chromatin. WDR5 is also a promising target for pharmacological inhibition in cancer, with small molecule inhibitors of an arginine-binding pocket of WDR5 (the "WIN" site) showing efficacy against a range of cancer cell lines in vitro. Efforts to understand WDR5, or establish the mechanism of action of WIN site inhibitors, however, are stymied by its many functions in the nucleus, and a lack of knowledge of the conserved gene networks—if any—that are under its control. Here, we have performed comparative genomic analyses to identify the conserved sites of WDR5 binding to chromatin, and the conserved genes regulated by WDR5, across a diverse panel of cancer cell lines. We show that a specific cohort of protein synthesis genes (PSGs) are invariantly bound by WDR5, demonstrate that the WIN site anchors WDR5 to chromatin at these sites, and establish that PSGs are both acute and persistent targets of WIN site blockade. Together, these data reveal that WDR5 plays a predominant transcriptional role in biomass accumulation and reinforce the notion that WIN site inhibitors kill sensitive cancer cells by disrupting protein synthesis homeostasis.

overall_design: ChIP-Seq was used to track the interaction of WDR5 with chromatin in LoVo, Be2C, MC38, and 3T3 cells. ChIP-seq in LoVo cells includes 2 IgG (control) biological replicates, and 2 WDR5 biological replicates. ChIP-seq in Be2C, MC38, and 3T3 cells includes 3 IgG (control) biological replicates and 3 WDR5 biological replicates. For RNA studies, either LoVo or CHP134 cells were treated with the WIN site inhibitor C6, or DMSO (control). SLAM-Seq was used to monitor early transcriptional changes in LoVo cells after 4 hours of treatment with DMSO or 25 uM C6 - 3 DMSO-treated biological replicates and 3 C6-treated biological replicates are included. RNA-Seq was used to monitor transcriptional changes in CHP134 cells after 24 hours of treatment with DMSO or 5 uM C6 - 3 DMSO-treated biological replicates and 3 C6-treated biological replicates are included.

first: William

last: Tansey

first: Audra

last: Foshage

first: April

last: Weissmiller

first: Qi

last: Liu


title: Stress-induced RNA–chromatin interactions promote endothelial dysfunction (iMARGI replicate 2)

status: Public on Aug 17 2020

city: La Jolla

first: Sheng

last: Zhong

state: CA

address: 9500 Gilman Dr

department: Bioengineering

country: USA

institute: University of California San Diego

summary: Chromatin-associated RNA (caRNA) has been proposed as a type of epigenomic modifier. Here, we test whether environmental stress can induce cellular dysfunction through modulating RNA-chromatin interactions. We induce endothelial cell (EC) dysfunction with high glucose and TNFα (H + T), that mimic the common stress in diabetes mellitus. We characterize the H + T-induced changes in gene expression by single cell (sc)RNA-seq, DNA interactions by Hi-C, and RNA-chromatin interactions by iMARGI. H + T induce inter-chromosomal RNA-chromatin interactions, particularly among the super enhancers. To test the causal relationship between H + T-induced RNA-chromatin interactions and the expression of EC dysfunction-related genes, we suppress the LINC00607 RNA. This suppression attenuates the expression of SERPINE1, a critical pro-inflammatory and pro-fibrotic gene. Furthermore, the changes of the co-expression gene network between diabetic and healthy donor-derived ECs corroborate the H + T-induced RNA-chromatin interactions. Taken together, caRNA-mediated dysregulation of gene expression modulates EC dysfunction, a crucial mechanism underlying numerous diseases.

overall_design: Map RNA-DNA interactions in HUVEC human cell lines using iMARGI technique in two samples: control (no treatment) and after 7 days of treatment to mimic endothelial to mesenchymal transition.

first: Riccardo

last: Calandrelli

first: Lixia

last: Xu

first: Yingjun

last: Luo

first: Weixin

last: Wu

first: Xiaochen

last: Fan

first: Tri

last: Nguyen

first: Chien-Ju

last: Chen

first: Kiran

last: Sriram

first: Rama

last: Natarajan

first: Zhen

last: Bouman-Chen


title: RNAseq analysis highlights significant transcriptional changes within the livers of patients with alcoholic hepatitis.

status: Public on Jan 09 2020

city: Baltimore

first: Brandon

last: Peiffer

state: Maryland

address: 720 Rutland ave., Ross 771

department: Surgery

institute: Johns Hopkins

type: Expression profiling by high throughput sequencing

summary: Alcoholic hepatitis (AH) is frequently a severe clinical condition associated with high short-term mortality. This study was meant to serve as a resource for AH investigators in an effort to increase understanding of this disease and treatment research (NIH Project # 5R24AA025017).

overall_design: Explanted livers from patients with acute alcoholic hepatits were sampled by RNAseq, and relative gene abundance was compared to samples derived from donor livers.

first: Zhaoli

last: Sun

first: Jiang

last: Qian


title: DELTA1/NOTCH2-mediated signaling regulates muscle stem cell self-renewal

status: Public on Dec 25 2019

city: Darlinghurst

first: Leonard

last: Goldstein

address: 384 Victoria St

country: Australia

institute: Garvan Institute of Medical Research

summary: How satellite cells and their progenitors balance differentiation and self-renewal to achieve sustainable tissue regeneration is not well understood. A major roadblock to understanding satellite cell fate decisions has been the difficulty to study this process in vivo. By visualizing expression dynamics of myogenic transcription factors during early regeneration in vivo, we identified the time point at which cells undergo decisions to differentiate or self-renew. Single-cell RNA sequencing revealed heterogeneity of satellite cells during both muscle homeostasis and regeneration, including a subpopulation enriched in Notch2 receptor expression. Furthermore, we reveal that differentiating cells express the Dll1 ligand. Using antagonistic antibodies we demonstrate that the DLL1 and NOTCH2 signaling pair is required for satellite cell self-renewal. Thus, differentiating cells provide the self-renewing signal during regeneration, enabling proportional regeneration in response to injury while maintaining the satellite cell pool. These findings have implications for therapeutic control of muscle regeneration.

overall_design: Single-cell RNA-seq study of mouse satellite cells during homeostasis and regeneration at 4 days post injury, including after treatment with antagonistic antibodies against Notch2 (aN2), Dll1 (aDll1) or control antibody (aRW)

first: Valeria

last: Yartseva

middle: D

first: Julia

last: Rodman

first: Lance

last: Kates

first: Mark

middle: Z

first: Ying-Jiun

middle: J

first: Oded

last: Foreman

first: Christopher

middle: W

last: Siebel

first: Zora

last: Modrusan

first: Andrew

middle: S

last: Peterson

first: Ana

last: Jovicic


title: Transcriptome Analysis of Cyclophosphamide Effects on Ovarian Development in Mice

status: Public on Jan 01 2020

city: Changchun

first: Qi

last: Li

address: No 71 Xinmin street

country: China

institute: First Hospital, Jilin University

summary: The role of cyclophosphamide (CTX) as a first-line chemotherapy drug in the reproductive health of young women with cancer has been controversial, especially considered to increase the risk of premature ovarian failure (POF). Therefore, in this study, c57bl/6 mice were treated by a single intraperitoneal injection of CTX.Our study suggests that CTX mainly regulates ovarian development by activate transcription factors, while reduce cholesterol production and lipid metabolism.

overall_design: mRNA profiles of control and cyclophosphamide (CTX) were generated by deep sequencing, in triplicate, using Illumina HiSeq 2000

first: Hao

last: Yu


title: Chromosome topology shapes neuronal non-CG DNA methylation to influence MeCP2-mediated enhancer repression (Bisulfite-Seq)

status: Public on Nov 26 2019

city: brookline

first: Harrison

middle: Wren

last: Gabel

state: Massachusetts

address: 220 longwood avenue

department: Neurbiology

institute: Harvard Medical School

type: Methylation profiling by high throughput sequencing

summary: The genomes of mammalian neurons contain uniquely high levels of non-CG DNA methylation that can be bound by the Rett syndrome protein, MeCP2, to regulate gene expression. How patterns of non-CG methylation at genes are established and the mechanism by which this methylation works with MeCP2 to control gene expression is unclear. Here we find that genes repressed by MeCP2 are found within regions of high non-CG methylation that are defined by domains of chromatin folding. Rather than working directly at transcriptional start sites to regulate these genes, MeCP2 represses enhancer elements that are enriched for methylated cytosines occurring in the CA or CG context. Enhancers repressed by MeCP2 are found within genes that are upregulated upon loss of the protein, providing a regulatory logic for how disruption of MeCP2 can lead to wide-spread changes in gene expression. Hence, we have found that DNA topology can shape non-CG DNA methylation across the genome to dictate MeCP2-mediated enhancer regulation in the brain.

overall_design: Total RNA-seq and ChIP-seq from the brains of MeCP2 KO, OE, and WT mice

first: Adam

last: Clemens

first: Dennis

middle: Y

last: Wu

first: Guoyan

last: Zhao


title: RNA-seq analysis of RNA-binding protein HuR knockout mice oral epithelial tissues

status: Public on Jan 06 2020

city: Albuquerque

first: Viswanathan

last: Palanisamy

state: NM

address: 2325 Camino de Salud NE,

department: Internal Medicine

institute: University of New Mexico

summary:
Purpose:  The goals of this study is to compare NGS-derived oral epithelial transcriptome profiling (RNA-seq) of WT and HuR KO tongue tissues exposed with carcinogen 4-nitroquinoline 1-oxide (4-NQO) induced oral tumorigenesis.
Methods: Oral tongue tissues mRNA profiles of six-weeks old wild-type (WT) and epithelial HuR knockout (HuR−/−) mice exposed with 4NQO were generated by deep sequencing, in triplicate, using Illumina hiseq2500. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks - fill in William
Results: There were no over-represented sequences, derived from primers and adapters from the library, and no bad quality nucleotides, the pre-process step was not necessary. On average, there were 64,096,543 reads per sample of 50 pair bases each. The alignment to the genome average rate of total mapped reads was 98.28%, which is a really good result considering we are working with Mouse data. There is a clear separation of the sample by the groups in the PCA plot and the samples cluster according by the groups in the identity plot. Nonetheless, Group B seems to be more heterogeneous, with sample Group_B-4_S4 showing signs of a hybrid expression profile that encompasses groups A and B.  The system level analysis was made using iPathway Guide from Advaitabio. For system level analysis we used adjusted p value threshold of 0.1. A total of 32 pathways were considered statistically significant in an adjp threshold of 0.05. Interesting to note the presence of terms related to an altered function of the mitochondria. “ECM-receptor interaction” is changed with adj.p of 1.6 x 10-4. GO Biological term “epidermal cell differentiation” ” is changed with adj.p of 7.4  1.6 x 10-8.  The gene Elavl1, although what seems to be a great expression in both group (baseMean = 2431.1 counts) have a log2 fold change of -0.2 and an adjp = 0.2.  Number of DE genes  Group-B_vs_Group-A   adjp ≤ 0.1 =  5,849 DE genes  adjp ≤ 0.01 = 2,258 DE genes
Conclusions: Our study represents the first detailed analysis of HuR WT and HuR-/- oral epithelial tissue transcriptomes, with biologic replicates, generated by RNA-seq technology. Our results show that HuR controls subset of genes responsible for epithelial differentiation and energy metabolism. We conclude that HuR is critical factor in epithelial homeostasis.

overall_design: Three replicates of HuR WT and HuR KO tongue tissues exposed with 4-nitroquinoline 1-oxide (4NQO) carcinogen.

first: Palanisamy

last: Viswanathan

first: Gary

last: Hardiman

first: Willian

last: da Silviera


title: miRNA-seq analysis of RNA-binding protein knock-down HNSCC cell-line UMSCC74B

type: Non-coding RNA profiling by high throughput sequencing

summary:
Purpose:  The goals of this study is to compare NGS-derived miRNA profiling (miRNA-seq) of WT and FXR1 KD UMSCC74B cell-line
Methods:  miRNA profiles of UMSCC74B HNSCC cells treated with shControl(WT) and shFXR1 (KD), in duplicate, using Illumina hiseq. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks

overall_design: Examination of miRNA expression between WT and FXR1 knockdown oral cancer cells.

first: E

last: Hazard


title: Gata2 rescue assay

status: Public on Jun 18 2020

city: Madison

first: Emery

middle: H

last: Bresnick

address: 1111 Highland Avenue

institute: University of Wisconsin-Madison

summary: RNA-seq data of primary hematopoietic progenitor cells from -77 knockout mice which expressing Gata2 and controls

first: Koichi

middle: R

last: Katsumura

first: Peng

last: Liu

first: Irene

middle: M

last: Ong


title: Chromosome topology shapes neuronal non-CG DNA methylation to influence MeCP2-mediated enhancer repression (RNA-Seq)


title: Chromosome topology shapes neuronal non-CG DNA methylation to influence MeCP2-mediated enhancer repression

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Chromosome topology shapes neuronal non-CG DNA methylation to influence MeCP2-mediated enhancer repression (ChIP-Seq)

overall_design: ChIP-seq from the brains of MeCP2 KO, OE, and WT mice


title: Rice root: Control vs auxin transport inhibitor N-1-naphthylphthalamic (NPA) treatment; WT vs iaa13 mutant.

status: Public on Oct 28 2019

city: Bunkyo

first: Takaki

last: Yamauchi

country: Japan

institute: The University of Tokyo

summary: Transcriptional analyses of rice roots comparing WT-NPA  with WT+NPA or with iaa13-NPA.

overall_design: Two-condition experiment, WT-NPA vs WT+NPA and WT-NPA vs iaa13-NPA. Biological replicates: 3 replicates.


title: RNA-Seq on the effect of VitaminD on colonic and tumor organoids

status: Public on Jul 21 2019

city: madrid

first: Alba

last: Costales

state: madrid

address: Arturo Duperier, 4

department: cancer genetics

country: Spain

institute: IIB

summary: Stem cell enriched cultures are generated from primary cultures of colorectal cancer patients. Organoids from normal and tumoral tissue are treated with 1,25(OH)2D3 and vehicle for 96 hours. RNA expression is compared among treatments.

overall_design:
Paired samples of healthy and tumoral tissue are obtained from six colorectal cancer patients. After enzymatic and mechanic tissue disgregation 3D cultures were established and treated with 1,25(OH)2D3 and vehicle for 96 hours. Treated organoids from colonic and tumorlal tissue are RNA-sequenced.

UPDATE: [02-07-2024] The Sample titles, tissue characteristics, and treatment characteristics were corrected. The raw data and processed data associated with each Sample GSMxxx accession number did not change.

first: A

last: Barbáchano

last: Fernandez Barral

last: Muñoz

last: Costales-Carrera


title: The transcriptomic differences between Th1, Tr1, Treg, and Tneg cells in Leishmania donovani-infected mice

status: Public on Nov 06 2019

city: Herston

first: Susanna

last: Ng

state: QLD

address: 300 Herston Road

department: Immunology

institute: QIMR Berghofer Medical Research Institute

summary: This study was designed to determine the differences in gene transcripts between CD4+ T helper (Th)1, Tr1, Treg, and Tneg cells in L. donovani-infected mice.

overall_design: Bulk RNA-sequencing was performed on CD4+ T helper (Th)1 (IFNγ+ IL-10-), Tr1 (IFNγ+ IL-10+), Treg (IFNγ- IL-10+), and Tneg (IFNγ- IL-10-) cells sorted from the spleen of n = 5 mice at day 14 of infection with L. donovani. Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin prior to sorting by cytokine capture flow cytometry.

first: Christian

last: Engwerda

first: Chelsea

middle: L

last: Edwards


title: Sexual Dimorphism of Preeclampsia-Dysregulated Transcriptomic Profiles and Endothelial Function in Fetal Endothelial Cells

status: Public on Jul 02 2019

first: chi

last: zhou

state: WI

address: 202 S. Park Street, PAB1, Meriter Hospital

department: Department of OB/Gyn

summary: Preeclampsia-offspring have increased risks of developing cardiovascular disorders in adulthood, implicating that preeclampsia programs fetal vasculature in utero. Fetal sex is associated with the risk of preeclampsia but the underlying mechanisms are unclear. We hypothesize that preeclampsia alters fetal endothelial gene expression and disturbs cytokines and growth factors-induced endothelial function in a fetal sex-specific manner. Methods: RNAseq analysis was performed with female and male unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive and preeclamptic (PE) pregnancies and verified by RT-qPCR. Results: PE dysregulate 926 and 172 genes in female and male P0-HUVECs, respectively. PE differentially dysregulates cardiovascular diseases (i.e. heart failure) and endothelial function (i.e. endothelial cell migration, calcium, eNOS, and iNOS signaling)-associated genes in female and male P0-HUVECs. PE also differentially dysregulates TNF-, TGFβ1-, FGF2-, and VEGFA-regulated gene networks in female and male P0-HUVECs. Conclusions: There are sexual dimorphisms of PE-dysregulated cardiovascular diseases and endothelial function-associated genes/pathways in fetal endothelial cells in association with sexual dimorphisms of PE-dysregulated fetal endothelial function.

overall_design: Examination of unpassaged (P0) human umbilical vein endothelial cells (HUVECs) from normotensive and preeclamptic (PE) pregnancies with female (F) and male (M) fetuses.

first: Chi

last: Zhou

first: Jing

last: Zheng


title: Transcriptional characterization of Arabidopsis thaliana seeds treated with a red- or far red-light pulse

status: Public on Jul 10 2019

city: CABA

first: Carlos

middle: Esteban

last: Hernando

state: Buenos Aires

address: Av. Patricias Argentinas 435

country: Argentina

institute: Fundacion Instituto Leloir

summary: The goal of this study was to compare the transcriptional profile (RNA-seq) of imbibed Arabidopsis thaliana Columbia-0 ecotype seeds that were treated with a 20 min red or far red pulse. The red-light pulse induces germination.

overall_design: Col-0 seeds were sown in clear plastic boxes, each containing 10 mL of 0.8 % (w/v) agar in demineralized water. To establish a minimum and equal photo-equilibrium, seeds were imbibed for 2 hours in darkness and then irradiated for 20 min with a saturated far-red pulse (FRp, calculated Pfr/P= 0.03, 42 µmol.m-2.s-1) in order to minimize the quantities of Pfr formed during their development in the mother plant. Seeds were then stratified at 5 °C in darkness for 3 days, prior to the 20 minutes with a saturated red pulse (Rp, calculated Pfr/P= 0.87, 0.05 µmol.m-2.s-1) or FRp. Three biological replicates of each condition were collected 12 hours after the corresponding R and FR light pulses.

first: J

middle: F

last: Botto

first: C

middle: E


title: Amino acid levels determine metabolism and cyp450 function of stem cell derived hepatocytes and hepatoma cell lines

status: Public on Jan 28 2020

city: Leuven

first: RUBEN

last: BOON

state: Vlaams Brabant

address: Herestraat 49

country: Belgium

institute: KU LEUVEN

summary: We identify nutrient engineering though the supplementation of amino aids to represent a novel tool for inducing differentiation, metabolic remodeling and functional feastures in hepatic cell culture models.

overall_design: Total RNA obtained from human hepatocyte cells subjected to different transcripton factors and amino acid supplementation and compared to untreated primary hepatocytes and hepatoma cell lines

first: Ruben

last: Boon

first: Jennifer

last: One

first: Jonathan

last: De Smedt


title: Transcriptomic profiling of zebrafish livers with nAtf6 overexpression at collected at 78 and 120 hpf

status: Public on May 08 2019

city: Abu Dhabi

first: Kirsten

last: Sadler Edepli

state: Abu Dhabi

department: Biology

country: United Arab Emirates

institute: New York University Abu Dhabi

summary: Activting transcription factor 6 (Atf6) is one of three main mediators of the Unfolded Protein Response and it gets cleaved cleaved in the Golgi and its N-terminal consisting of the bZip domain translocates into the nucleus to generate a transcriptional response (nAtf6). This study carries out RNAseq on an established transgenic overexpression of nAtf6 in zebrafish hepatocytes ( tg(fabp10:nAtf6-cherry; cmlc2:GFP)-C allele).  Samples were collected at 78 and 120 hpf to detect gene expression changes at early and late time points after nAtf6 is overexpressed.

overall_design: We used two  transgenic lines: Tg(fabp10a: CAAX-EGFP) to use as a marker of the liver for dissction and tg(fabp10:nAtf6-cherry; cmlc2:GFP)-C allele to overexpress nAtf6 specifically in hepatocytes.This experiment was conducted by natural spawnings between tg:(fabp10:nAtf6-cherry; cmlc2:GFP)-C  and tg(fabp10a:CAAX-EGFP ). Using GFP to guide microdissscion of 20-25 livers at 78 hpf and 120 hpf . Total RNA isolated using TRIZOL and treated by DNAse I.  Libraries were prepared using RiboZero (for 120 hpf samples) or polyA selection (for 78 hpf samples). Samples from 2 clutches collected at 78 hpf and 3 clutches  at 120 hpf. Samples were sequenced on NextSeq550 (Illumina)

first: Maheshwar

last: Gummala

first: Anjana

last: Ramdas Nair

middle: C

last: Sadler (Edepli)


title: Dissecting the Individual and Collective Regenerative Behavior of Muscle Stem Cells During Aging

status: Public on Aug 30 2019

city: Boston

first: Sundari

last: Chetty

state: MA

address: 185 Cambridge Street

department: Harvard Medical School

institute: Massachusetts General Hospital, Harvard University

summary: We utilize an integrative genomics approach (bulk RNA-Seq, ATAC-Seq)  to show how  Muscle Stem Cells (MuSCs) from distinct age groups (young and aged) are significantly altered during the regenerative response. Transcriptional landscapes during quiescence, activation, proliferation and differentiation from young and aged mice are profiled and chromatin accessibility is compared.

overall_design: Bulk RNA-Seq and ATAC-Seq at timepoints 0, 1 day, 3 day, 5 day, day 7, and day 21 post-injury for both young and aged mouse MuSCs

first: Anna

last: Shcherbina

last: Aguilar


title: Transcriptomic profiling of zebrafish livers at 5 dpf with nAtf6 overexpression or in response to ethanol exposures


title: Transcriptomic analysis of cardiomyocyte differentiation from human induced pluripotent stem cells (hiPSCs) in 2D and 3D culture

status: Public on Jun 24 2019

city: Lisboa

first: Leonilde

middle: Morais

last: Moreira

address: A. Rovisco Pais

country: Portugal

institute: Instituto Superior Tecnico

summary: Tridimensional cardiac differentiation from hiPSCs has been largely described in the literature. However, the exact impact that 3D culture has throughout the entire process of cardiac differentiation remains poorly defined. We developed a robust and efficient 3D platform for cardiomyocyte differentiation from hiPSCs, based on the temporal modulation of WNT signalling using small molecules. 3D aggregates of hiPSCs were generated by forced aggregation in microwells and subsequently differentiated. In order to determine the differences in gene expression profile due to 3D culture throughout the different stages of cardiac differentiation, we compared transcriptional changes between cells in 3D aggregates and standard 2D monolayer cardiac differentiation. Analysis of these data suggests a faster commitment of hiPSCs toward the cardiac lineage and also higher degree of cardiomyocyte functional maturation after 20 days of culture in the 3D aggregates when compared with the 2D monolayer.

overall_design: Cells from different time points of cardiac differentiation (day 0, 1, 3, 5, 7, 9, 12, 15, 18 and 20), from 3D and 2D culture conditions were collected for RNA-seq. Three biological replicates were obtained for each time point. Deep sequencing was performed in the Illumina platform.

first: Mariana

middle: A

last: Branco

first: João

last: Cotovio

last: Rodrigues

first: Tiago

middle: G

last: Fernandes

first: Joaquim

last: Cabral

first: Margarida

last: Diogo


title: Endosteal Niche E-selectin Induces Mesenchymal-Epithelial Transition and Wnt Activation in Cancer Cells to Promote Bone Metastasis

status: Public on Feb 22 2019

city: Plainsboro

first: Yong

last: Wei

state: NJ

address: LTL227 Wathington Road

department: Molecular Biology

institute: Princeton University

summary: E-selectin binding induces transcriptome changes in breast cancer cells to promote bone metastasis

overall_design: Two Breast cancer cell lines, with GLG1 KO derivatives, seeded on IgG- or E-Selectin- coated plates for 12 h.

first: Mark

middle: B

last: Esposito


title: RNA is essential for PRC2 chromatin occupancy and function in human pluripotent stem cells

status: Public on May 31 2020

city: Boulder

first: Tom

last: Cech

state: CO

address: 3415 Colorado Avenue

department: BioFrontiers Institute

institute: University of Colorado Boulder, Boulder

summary: Many chromatin-binding proteins and protein complexes that regulate transcription also bind RNA. One of these, Polycomb repressive complex 2 (PRC2), deposits the H3K27me3 mark of facultative heterochromatin and is required for stem cell differentiation. PRC2 binds RNAs broadly in vivo and in vitro. Yet, whether this RNA binding has any biological importance remains unsettled. Here we tackle this question in human induced pluripotent stem cells using multiple complementary approaches. Perturbation of RNA-PRC2 interaction by RNaseA, by a chemical inhibitor of transcription, or by an RNA-binding-defective mutant all disrupted PRC2 chromatin occupancy and localization genome-wide. The physiological relevance of PRC2-RNA interactions is further underscored by the dramatic cardiomyocyte differentiation defect upon genetic disruption. We conclude that PRC2 requires RNA binding for chromatin localization in human pluripotent stem cells and in turn for defining cellular state.

overall_design: Two independent CRSIPR clones of each of the two edited cell lines (WT or mutant EZH2) were analyzed. For ChIP-seq and fRIP-seq, two or three technical replicates of the pulldown were sequenced on each lysate; For RNA-seq on undifferentiated cells, two technical replicates of libary construction were sequenced for each clone; For RNA-seq on differentiated cells, three biological replicates generated from independent differentiation experiments were sequenced for each clone.

first: Yicheng

last: Long

first: Taeyoung

last: Hwang

first: John

last: Rinn

first: Thomas


title: Tinagl1 Suppresses Triple-negative Breast Cancer Progression by Simultaneously Targeting Integrin/FAK and EGFR Signaling Pathways

status: Public on Dec 31 2018

summary: Enforced Tinagl1 expression in lung metastatic MDA-MB231 subline LM2 cells suppresses lung metastasis by inhibiting EGFR and Integrin/FAK activation

overall_design: Breast cancer cell line with Tinagl1 or empty vector were injected into NSG female mice intravenously. Lung metastatic lesions were dissected for microarray analysis

first: Minhong

last: Shen

first: Wei

last: Yong


title: Acetylation of spliceosome protein PHF5A modulates stress responses and colorectal carcinogenesis through alternative splicing mediated upregulation of KDM3A

status: Public on Nov 22 2018

city: New York

first: Xin

last: Yang

address: 1130 Saint Nicholas Ave, ICRC building

department: Institute for Cancer Genetics

institute: Columbia University

summary: The process utilized by cancer cells for adapting to cellular stress is a key point for carcinogenesis. Alternative pre-mRNA splicing induced post-transcriptional gene expression regulation is one of the pathways for tumors maintaining proliferation rates accompanying the malignant phenotype under stress. However, the protein post-translational modification, especially protein acetylation on pre-mRNA splicing processes under stress is unknown. Here, we uncovered a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient starvation. PHD finger-like domain-containing protein 5A (PHF5A/SF3b14b), a component of U2 snRNPs, can be acetylated at lysine 29 in response to multiple cellular stresses. P300 and HDAC6 regulate PHF5A acetylation levels. PHF5A acetylation strengthens the interaction among U2 snRNPs, and affects global pre-mRNA splicing pattern and extensive gene expression. PHF5A hyperacetylation induced alternative splicing stabilizes KDM3A mRNA and promotes its protein expression. Pathologically, PHF5A K29 hyperacetylation and KDM3A upregulation axis are correlated with poor prognosis of colon cancer patients. Our findings uncovered a novel mechanism of anti-stress pathway that acetylation on PHF5A promotes the cancer cells capacity for stress resistance and consequently contributes to colon carcinogenesis.

overall_design: 6 samples. HCT116 colon cancer cells were stable expression PHF5A WT or PHF5A K29Q, Cells' RNA was harvested using Trizol reagent. 3 ug of total RNA is used for the construction of sequencing libraries by Hiseq 4000 PE150.

first: Zhe

last: Wang

first: Jianyuan

last: Luo


title: TGFb treated EpRAS cells undergoing hysteretic vs non-hysteretic EMT gene expression analysis.

status: Public on Nov 08 2018

summary: EpRAS cells undergo EMT transition through hysteresis showing bistability of the system. The hysteresis transition is controlled by the negative feedback loop between miR-200s and Zeb1. Disruption of the feedback loop through the deletion of Z-box2 in the miR-200s cluster-2 promoter region changes the transition to unimodal without hysteresis. To determine the consequence of cells undergoing through hysteresis or unimodal transitions of EMT, herein we determined the transcriptomic profiles of EpRAS wild type and EpRAS-delZbox2 mutant cells, (designated as EpRAS-C2-2). To induce EMT, the cells were treated with 100pM TGFbeta for 3 days. Mock PBS treatment is used as control.

overall_design: 2x2 design. Comparison of two cells (EpRAS wild-type vs EpRAS mutant cells, in which the Z-box-2 of the miR-200c promoter is deleted and disrupts the negative feedback loop with Zeb1) and two treatment conditions, control and TGFb.

first: Toni

last: Celià-Terrassa


title: Expression profiles of whole skin samples from keratinocyte-specific TRAF6 deficient mice treated with and without IMQ treatment

status: Public on Oct 16 2018

city: Kyoto

first: Teruki

last: Dainichi

state: Kyoto

address: 54 Kawahara-cho Shogoin Sakyo-ku

department: Dernatology

institute: Kyoto University Graduate School of Medicine

summary:
Tumor necrosis factor receptor associated factor 6 (TRAF6) is an adaptor protein that regulates NF-κB and MAPK signaling pathway and is reported to affect immune response and cell death in immune cells. However, the roles of TRAF6 in epithelium have not been well investigated. Using a mouse model of imiquimod-induced psoriasis dermatitis, we show that TRAF6 in epithelial cells totally regulates IL-17-mediated inflammation in the skin. Mice lacking TRAF6 in keratinocytes were unable to activate dendritic cells and failed to produce IL-23 or initiate IL-17 production from γδ T cells at the imiquimod-treated sites. Subcutaneous administrations of IL-23 restored IL-17 production in the mutant animals, suggesting that the induction of IL-23 production is the major TRAF6-dependent contribution of keratinocytes to this process. Therefore, the epithelial TRAF6 signaling is supposed to play an essential role in instructing and propagating the cutaneous immune response.
To broadly characterize the impact of the lack of TRAF6 in keratinocytes on the skin inflammation, we analyzed gene expression in IMQ-treated whole ears of Traf6EKO mice and Traf6f/f mice using a cDNA microarray.

overall_design: Total RNAs prepared from the ears of Traf6 epithelial knockout (Traf6EKO ) mice and Traf6f/f mice treated with imiquimod (IMQ) for 2 consecutive days (n = 2) were subjected to the microarray analysis. Total RNA from skin samples was immediately isolated with Trizol according to the manufacturer's protocol. An amplified sense-strand DNA product was synthesized with the Ambion WT Expression Kit (Life Technologies, Carlsbad, CA, USA), was fragmented and labelled by the WT Terminal Labelling and Controls Kit (Affymetrix, Santa Clara, CA, USA) and was hybridized to a Mouse Gene 1.0 ST Array (Affymetrix, Santa Clara, CA, USA).

first: Reiko

last: Matsumoto


title: Subtle changes in chromatin loop contact propensity are associated with differential gene regulation and expression

status: Public on Jan 24 2019

city: La Jolla

first: Kelly

middle: Ann

last: Frazer

address: 9500 Gilman Drive

department: Pediatrics

institute: UC San Diego

summary: We quantitatively interrogate these relationships by comparing Hi-C and molecular phenotype data across cell types and haplotypes. While chromatin loops consistently form across different cell types, subtle quantitative differences in contact frequency are associated with larger changes in gene expression and H3K27ac. Across haplotypes, we find larger differences in contact frequency at imprinted and copy number variable loci. We find most changes in contact frequency are smaller across haplotypes than cell types; however, the proportional relationship between these changes and those in gene expression and regulation are consistent. This suggests that subtle changes in contact propensity have a biologically meaningful role in gene regulation and could be a mechanism by which regulatory genetic variants in loop anchors mediate effects on expression. The raw data files for these processed files can be obtained through dbGaP accession phs000924.

overall_design:
Examination of phased HiC, RNA-seq, H3K27AC ChIP-seq, and ATAC-seq across two cell types and seven individuals.  Multiple replicates for non-hic data are separate.  HiC replicates have been merged
Raw data requires controlled access and is deposited at dbGaP
http://www.ncbi.nlm.nih.gov/gap/?term=phs000924

first: William

last: Greenwald

first: He

last: Li

first: Paola

last: Benaglio

first: David

last: Jakubosky

first: Hiroko

last: Matsui

first: Anthony

last: Schmitt

first: Siddarth

last: Selvaraj

first: Matteo

last: D'Antonio

first: Agnieszka

last: D'Antonio-Chronowska

first: Erin

middle: N

last: Smith


title: Expression data from Triticum aestivum near isogenic lines (TugelaDn0, RWA susceptible; TugelaDn1, RWA resistant; TugelaDn2, RWA resistant; TugelaDn5, RWA resistant) after infestation by Diuraphis noxia biotype SA1

status: Public on Sep 22 2018

city: Stellenbosch

first: Anna-Maria

last: Botha-Oberholster

state: WP

address: Genetics, JC Smuts Building Rm 214, Stellenbosch

department: Genetics

country: South Africa

institute: Stellenbosch University

summary:
The wheat Nils expression profiles differ because of their response to aphid feeding (i.e., antibiosis - Dn1; tolerance - Dn2; antixenosis and antibiosis - Dn5)
We used GeneChip Wheat Genome Array (Affymetrix, USA) analysis to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.

overall_design: Plants of each cultivar were infested with 10 aphids and incubated for 48 h. All leaves except the first leaf were harvested into liquid N2 and stored at 280°C prior to RNA isolation. Data analysis was conducted using CranBioconductor and using a linear mixed statistical model (Botha et al. 2014, Biology Open (2014) 3, 1116–1126 doi:10.1242/bio.201410280).

last: Botha


title: Dynamic m6A mRNA methylation reveals novel insights into mechanisms of chemical carcinogenesis

status: Public on Dec 01 2018

first: Shuibin

last: Lin

address: 1 Blackfan Circle

institute: Boston Childrens Hospital

summary: m6A epitranscriptome profiling in four different chemical carcinogen induced transformation models uncovered the dynamic changes of m6A modifications during chemical carcinogenesis.

overall_design: m6A MeRIP-Seq was used to identify the differential methylated mRNAs during chemical carcinogenesis.

first: Weidong

last: Ji


title: Dll1-mediated crosstalk between mammary gland stem cells   and their macrophageal niche

status: Public on Oct 05 2018

first: Yong

last: Wei

summary:
MaSC enriched P4 subpopulation with high/low expression of Dll1, were isolated from mammary gland of Dll1-mCherry mice, and sorted for high/low Dll1 expression based on mCherry red fluroscense.
Mammary gland associated macrophages were isolated from Dll1cKO mice (C57/B6 strain) and the wild type littermates.
Total RNA samples were prepared from these samples and the transcription profiles were compared between these samples to conclude that Dll1 in MaSC is critical to mediate interaction to macrophageal niche and in turn supports the proper MaSC function.

overall_design: Pair of MaSC samples: Dll-hi and Dll-lo; and pair of macrophage samples from Dll1 wild type and conditional KO mice

first: Chakrabarti

last: Rumela

first: Wei

last: Yong


title: Transcriptome analysis of NKG2CBright compared to NKG2CNeg from multigravida decidua samples

status: Public on Apr 04 2018

city: Jerusalem

first: Moriya

last: Gamliel

address: Ein Kerem

country: Israel

institute: Hebrew University

summary: In multigravidae, a specific dNK cell population characterized by NKG2CBright expression is expanded, suggesting that this reflects a population of memory dNK generated during the first pregnancy.  Purpose: To gain further insight into the transcriptome profile of the expanded memory NKG2CBright dNK population found only in multigravida decidua samples

overall_design: Flow cytometry based dNK cell sorting (based on CD56 and NKG2C) was done in order to purify CD56PosCD3NegCD16NegNKG2CBright and CD56PosCD3NegCD16NegNKG2CNeg subsets.

first: Mandelboim

last: Ofer


title: Deep sequencing of endogenous mRNA from Homo sapiens from four age categories in blood

status: Public on Jan 08 2018

city: Jena

first: JenAge

last: Project

address: Beutenbergstr. 11

country: Germany

institute: Leibniz Institute for Age Research - Fritz Lipmann Institute

summary:
Comparison of temporal gene expression profiles to identify genes/pathways changing during ageing.

Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)

overall_design:
32 samples in sum; 4 age groups (24-29,45-50, 60-65, 75-80 years); tissue blood; 8 samples per group

Please note that the submitters are not allowed by law to make the raw data public in any database, and therefore raw data files are not available for this record.

first: Christiane

last: Frahm

first: Madlen

last: Günther

first: Steffen

last: Priebe

first: Marco

last: Groth

first: Matthias

last: Platzer

first: Otto

last: Witte


title: Glutaminolysis is a metabolic dependency in FLT3 ITD Acute Myeloid Leukemia unmasked by FLT3 Tyrosine Kinase Inhibition

status: Public on Mar 07 2018

city: Toronto

first: Shabana

last: Vohra

state: Ontario

address: 101 College St

country: Canada

institute: University Health Network

summary: FLT3ITD are common mutations in Acute Myeloid Leukemia (AML) and carry a particularly bad prognosis. Although new generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3-mutated AML patients remains poor and demands the identification of novel, specific and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide CRISPR/Cas9 screen, we identify GLS, the first enzyme in glutamine metabolism, as synthetically lethal with FLT3 TKI treatment. Using complementary metabolomic and gene-expression analysis, we demonstrate that glutamine metabolism, through its ability to support both mitochondrial function and cellular redox metabolism, becomes a metabolic dependency of FLT3ITD AML, specifically unmasked by FLT3-TKI treatment. We extend these findings to AML subtypes driven by other tyrosine kinase activating mutations, and validate the role of GLS as a clinically actionable therapeutic target in both primary AML and in vivo models. Our work highlights the role of metabolic adaptations as a resistance mechanism to several TKI inhibitors, and suggests glutaminolysis as a therapeutically targetable vulnerability when combined with specific TKI in FLT3ITD and other TK activating mutation driven leukemias.

overall_design: Gene expression analysis by RNA-Seq of FLT3ITD mutant cell lines MV411 and MOLM13 treated with AC220 1nM vs vehicle control and of BCR-ABL mutated K562 cells treated with Imatinib 2uM vs vehicle control.

first: Brian

last: Huntly

first: Paolo

last: Gallipoli


title: Deep sequencing of mRNA from Mus musculus at two different timepoints in skin (ear clip)

address: Beutenbergstraße 11

department: Core Facility - Next Generation Sequencing

institute: Leibniz Institute on Aging - FLI

summary: longitudinal gene expression profiles

overall_design: 16 samples in sum; 2 age groups (avg.  24.1 and avg. 29.6 months); tissue: skin (ear clip); 8 samples per group

first: Peer

last: Irizar

first: Daniela

last: Esser

last: Guenther

first: Christoph

last: Kaleta

first: Hans

last: Kestler

first: Jule

last: Müller


title: Deep sequencing of endogenous mRNA from Homo sapiens from four age categories in two different tissues (blood, skin)

summary:
Background: Comparison of temporal gene expression profiles

Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de)

overall_design:
91 samples in sum; 4 age groups (24-29,45-50, 60-65, 75-80 years); 2 tissues (skin, blood); around 20 samples per group

Consent forms do not allow for public access to raw data.


title: Human iPSC-derived retinal pigment epithelium: a model system for identifying and functionally characterizing causal variants at AMD risk loci

status: Public on Mar 30 2019

first: Kelly

last: Frazer

summary: We evaluate whether human induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells can be used to prioritize and functionally characterize causal variants at age-related macular degeneration (AMD) risk loci. We generated iPSC-RPE from six subjects and show that they have morphological and molecular characteristics similar to native RPE. We generated RNA-seq, ATAC-seq, and H3K27ac ChIP-seq data and observe high similarity in gene expression and enriched transcription factor motif profiles between iPSC-RPE and human fetal-RPE. We performed fine-mapping of AMD risk loci by integrating molecular data from the iPSC-RPE, adult retina, and adult RPE, which identified rs943080 as the probable causal variant at VEGFA. We show that rs943080 is associated with altered chromatin accessibility of a distal ATAC-seq peak, decreased overall gene expression of VEGFA, and allele specific expression of a non-coding transcript. These results provide insight into the mechanism underlying the association of the VEGFA locus with AMD. Raw data requires controlled access and is deposited at dbGaP      http://www.ncbi.nlm.nih.gov/gap/?term=phs000924

overall_design:
In this study, we differentiated iPSC-RPE from iPSC from six human subjects. We performed RNA-seq, ATAC-seq, and H3K27ac ChIP-seq on these iPSC-RPE as well as one human fetal RPE sample.
NOTE from submitter: SRP107882 (raw data will be uploaded to this project through dbGaP in a new version of the project).

first: Erin

last: Smith

first: Agnieszka

last: D'Antonio-Chronowska

first: William

middle: W

last: Greenwald

first: Victor

last: Borja

first: Lana

last: Aguiar

first: Robert

last: Pogue

first: Hiroko

last: Matsui

first: Shyamanga

last: Borooah

first: Matteo

last: D’Antonio

first: Radha

last: Ayyagari


title: Bone marrow stroma confers breast cancer cell resistant to cisplatin treatment

status: Public on Dec 27 2017

first: Yong

last: Wei

summary: The transcriptome changes of breast cancer cell SUM1315, with or without co-culture with bone marrow stroma cells, upon cisplatin (CDDP) treatment.

overall_design: 2x2 design of 4 samples, (CNT, CDDP) x (SUM1315 alone, SUM+MC3T3E1)

first: Hanqiu

last: Zhen


title: Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors

status: Public on Dec 13 2017

first: Shabana

last: Vohra

summary: Loss of function mutations of the histone acetyltransferase CREBBP have recently been described at high frequencies across a spectrum of lymphoid malignancies. The multiple effects of this epigenetic regulator on developmental and homeostatic processes have been extensively studied, however, exactly how CREBBP functions as a tumour suppressor remains unclear. Here we use a murine model to demonstrate that loss of Crebbp in haematopoietic stem and progenitor cells (HSPCs) leads to increased development of B-cell lymphoproliferative disorders (LPD). We identify a pre-malignant (PM) B220+ Mac1+ stem cell which ultimately transforms to LPD and shed light on the mechanisms of malignant evolution by comparing lymphoid progenitors, pre-malignant and malignant cells at the clonal, transcriptional, epigenetic and genetic levels. We demonstrate that loss of Crebbp in HSPCs facilitates the development of lymphoid malignancies by generating a hyperproliferative population of lymphoid progenitors with an altered response to DNA-damage and enhanced self-renewal properties. Global genomic profiling revealed that epigenetic alterations observed in lymphoid progenitors correlated highly with transcriptional changes observed in frank LPD. Taken together, these findings define the tumour suppressor functions of Crebbp and shed light on the cellular origins and subsequent evolution of lymphoid malignancies.

overall_design: Chip seq analysis for Crebbp, three histone modifications (H3K27Ac, H3K18Ac and H3K56Ac) and gene expression analysis by RNA-Seq between mice deficient for Crebbp (Crebbp-/-) at various stages of lymphoproliferative disease (LPD) vs wild type (WT) B cells or WT LPDs.

first: Brian

last: Huntly


title: Expression data from Xenopus laevis juvenile inner ear tissue

status: Public on Aug 01 2017

city: Cleveland

first: Selene

last: Virk

state: OH

address: 2103 Cornell Road

institute: Case Western Reserve University

summary: The genes involved in inner ear development have yet to be fully characterized. Previous gene-based analyses have primarily focused on the early developmental stages following induction and initial formation of the inner ear. The inner ear continues to grow and develop until the auditory and vestibular systems reach full maturity; all of the genes involved in this process have yet to be identified. The aim of this study is to identify additional candidate genes for inner ear development. Microarrays were used to produce expression profiles from the post-metamorphic juvenile stage of the Xenopus laevis inner ear.

overall_design: Xenopus inner ears were isolated from juvenile animals for RNA extraction and hybridization to Affymetrix GeneChip microarrays.

first: Elba

last: Serrano

first: Casilda

last: Trujillo-Provencio


title: Genome-wide profiling of gene (mRNA) and miRNA expression during mouse embryonic heart development [mRNA]

status: Public on Jul 31 2017

city: Cologne

first: Agapios

last: Sachinidis

state: NRW

address: Robert-Kochstr. 39

department: Institute of Neurophysiology

institute: University of Cologne

summary:
Affymetrix whole genome gene and miRNA chips during the development period (from E10.5 to E19.5) and additionally included expression data of adult and old murine heart tissues
For a more comprehensive understanding of the potential effects of miRNA for heart development, we carried out the first study of time-resolved parallel profiling of mRNA and microRNA levels in the developing murine heart and identify the dynamical activation or repression of numerous biological processes and signalling pathways

overall_design: mRNA and miRNA (total RNA)  from mouse heart tissues of the developing embryos (from E10.5 to E19.5) and adult (10 weeks old mice) as well as old  (14 months old mice) were isolated and gene and miRNA expression was analysed by the Affymetrix (Mouse430 2.0) and Affymetrix miRNA 3.0 arrays.

first: Matthias

last: Fuschik


title: Genome-wide map of HAEC chromatin landscape under resting and TNFa, IL1b, and OxPAPC stimulation, with corresponding transcription factor binding and RNA expression

status: Public on Jun 06 2017

city: Tucson

first: Casey

last: Romanoski

state: AZ

address: 1657 E. Helen St.

department: Cellular & Molecular Medicine

institute: University of Arizona

summary: We report the dynamic enhancer landscape of HAEC at baseline and under inflammatory stimulation, and also show the cistromes of ETS, AP-1 as well as key signal dependent transcription factors, with corresponding gene expression. We also describe the inflammatory transcriptional profile caused by inhibition of the ETS factor ERG with siRNA.

overall_design: We use ChIP-seq for two histone modifications and ATAC-seq datasets to describe EC enhancers, poly-A selected RNA sequencing to show gene expression, and ChIP-seq to characterize the binding profile of EC transcription factors in relation to enhancers. ERG siRNA knockdown followed by RNA-seq was used to characterize the ERG knockdown phenotype.

first: Nicholas

middle: T

last: Hogan


title: Genome-wide profiling of gene (mRNA) amd miRNA expression during mouse embryonic heart development

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

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

platform_organism:
Mus musculus
synthetic construct

overall_design: Refer to individual Series


title: Genome-wide profiling of gene (mRNA) amd miRNA expression during mouse embryonic heart development [miRNA]

summary:
Affymetrix whole genome gene (mRNA) and miRNA expression data  during the development period (from E10.5 to E19.5) and  expression data of adult (10 weeks old mice) as well as old  (14 months old mice) murine heart tissues
For a more comprehensive understanding of the potential effects of miRNA for heart development, we carried out the first study of time-resolved parallel profiling of mRNA and miRNA levels in the developing murine heart and identify the dynamical activation or repression of numerous biological processes and signalling pathways

last: Futschik


title: Transcriptome profiles of mouse mammary stem cells and progenitor cells 2

status: Public on May 05 2017

summary: MaSC, Luminal progenitor enriched subpopulations were sorted based on CD24/CD29 expression from mammary epithelial cells of virgin female mice . (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035), and the transcirptome profiles were determined and compared.

overall_design: Comparison of two MaSC (P4) and Luminal progenitor (P5) enriched subpopulations

first: B

last: Tiede

first: T

last: Celia-Terrassa

first: Y


title: Transcriptome characterization of IFNa response in MaSC and luminal progenitor cells

summary: Transcriptome response to IFNa treatment in MaSC, Luminal progenitor cells were studied. The MaSC, Luminal progenitor cells enriched subpopulations were sorted based on CD24/CD29 expression from mammary epithelial cells of virgin female mice . (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035). The cells were cultured in mammosphere condition in vitro and treated with Ifna for 8 days. The total RNA samples are collected and compared using microarray analysis.

overall_design: 2x2 design. Comparison of two subpopulations MaSC (P4) and Luminal progenitor (P5) enriched subpopulations and two treatment conditions, control and IFNa treated.

first: Toni

last: Celià-Terrassa


title: microRNA profiles of mouse mammary stem cells and luminal cells

summary: MaSC and luminal enriched subpopulations were sorted based on CD24/CD29 expression from mammary epithelial cells of virgin female mice . (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035), and the microRNA profiles were determined using microRNA array and compared.

overall_design: Comparison of two MaSC (P4) and Luminal (P5) enriched subpopulations


title: Microarray-based DNA methylation profiles of primary medulloblastomas

status: Public on May 29 2017

city: Newcastle upon Tyne

first: Ed

last: Schwalbe

address: Ellison Place

department: Applied Sciences

country: United Kingdom

institute: Northumbria University

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: miR-199a regulates human mammary epthelial cell function

first: Yong

last: Wei

summary: miR-199a expression was enforced in HMLE cells using lentiviral vector pLEX. The transcriptome profiles changes following miR-199a expression was studied.

overall_design: simple pair design: empty vector control vs. miR199a OE


title: Transcriptome characterization of the mouse Lgr5+_MaSCs

summary: Lgr5 positive and negative MaSC enriched P4 subpopulation were isolated from virgin Lgr5-EGFP-IRES-CreERT2 mice. The transcriptome profiles of the cells are compared to elucidate the molecular mechanism Lgr5+_MaSCs as a more defined MaSCs subpopulation within the P4 (MaSC and basal progenitor enriched popuation).

overall_design: Pair of MaSC samples: Lgr5 positive vs negative


title: Inner ear expression data from pooled inner ear tissue from stages 50,51,52 Xenopus laevis larval inner ears

status: Public on Dec 31 2016

summary: The inner ear continues to grow and develop until the auditory and vestibular systems reach full maturity and all of the genes involved in this process have yet to be identified. Previous gene based analysis have primarily focused on the early developmental stages following induction and initial formation of the inner ear. The aim of this study is to identify new candidate genes for inner ear development. Microarrays were used to produce expression profiles from larval stages 50,51,52  of the Xenopus laevis inner ear.  The data produced from this work represent an annotated resource that can be utilized by the Xenopus community to provide candidates for further functional analysis.

overall_design: Xenopus inner ears were isolated from larval animals for RNA extraction and hybridization to Affymetrix GeneChip microarrays.


title: Cross-species comparison of epigenetic poising in the mammalian germ line

status: Public on May 07 2016

city: New Haven

first: Bluma

middle: J

last: Lesch

state: CT

address: 333 Cedar Street

institute: Yale University

summary: In the mouse, germ cells and embryonic stem cells maintain an epigenetically poised (bivalent) state, defined by the simultaneous presence of the opposing histone modifications H3K4me3 and H3K27me3 and by transcriptional repression, at the promoters of many developmental regulatory genes. We compared genome-wide chromatin state in male germ cells of five mammalian and one avian species. We identified a set of 405 genes whose promoters retain poised chromatin in the mammalian germ line throughout mammalian evolution.

sample_organism:
Gallus gallus
Macaca mulatta
Homo sapiens
Bos taurus
Mus musculus
Monodelphis domestica

overall_design: ChIP-seq of H3K4me3 and H3K27me3, along with RNA-seq, in sorted meiotic and post-meiotic male germ cells of human (3 biological replicates), rhesus (2 biological replicates), mouse (1 replicate), bull (1 replicate), opossum (2 replicates), and chicken (1 replicate). Raw data is in SRA under accession numbers SRP057141, SRP028905, and SRP028906 (BioProjects PRJNA281061, PRJNA214839 and PRJNA214840).

first: David

last: Page


title: Gender Differences in Global but not Targeted Demethylation in iPSC Reprogramming

status: Public on Jan 27 2017

city: Cambridge

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary: Global DNA demethylation is an integral part of reprogramming processes in vivo and in vitro, but whether it occurs in the derivation of induced pluripotent stem cells (iPSCs) is not known. Here we show that iPSC reprogramming involves both global and targeted demethylation, which are separable mechanistically and by their biological outcomes. Cells at intermediate-late stages of reprogramming undergo transient genome-wide demethylation, which is more pronounced in female cells. Global demethylation requires AID-mediated downregulation of UHRF1 protein and abolishing demethylation leaves thousands of hypermethylated regions in the iPSCs genome. Independently of AID and global demethylation, regulatory regions, particularly ESC enhancers and super-enhancers, are specifically targeted for hypomethylation in association with transcription of the pluripotency network. Our results show that global and targeted DNA demethylation are conserved and distinct reprogramming processes, presumably because of their respective roles in epigenetic memory erasure and in the establishment of cell identity.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: mRNA-seq and BS-seq of different time-points during iPSC reprogramming

first: Inês

last: Milagre

first: Thomas

last: Stubbs

first: Michelle

last: King

first: Julia

last: Spindel

first: Fátima

last: Santos

first: Martin

last: Bachman

first: Anne

last: Segonds-Pichon

first: Shankar

last: Balasubramanian

first: Simon

last: Andrews

first: Wendy

last: Dean

first: Wolf

last: Reik


title: Inner ear expression data from pooled inner ear tissue from stages 56,57,58 Xenopus laevis larval inner ears

status: Public on Feb 29 2016

first: Selene

last: Virk

summary: The inner ear continues to grow and develop until the auditory and vestibular systems reach full maturity and all of the genes involved in this process have yet to be identified. Previous gene based analysis have primarily focused on the early developmental stages following induction and initial formation of the inner ear. The aim of this study is to identify new candidate genes for inner ear development. Microarrays were used to produce expression profiles from larval stages 56,57,58 of the Xenopus laevis inner ear.  The data produced from this work represent an annotated resource that can be utilized by the Xenopus community to provide candidates for further functional analysis.

first: Elba

last: Serrano

first: Casilda

last: Trujillo-Provencio


title: LCOR regulates transcription of human mammary epithelial and breast cancer cells

first: Yong

last: Wei

address: LTL227 Wathington Road

institute: Princeton University

summary: Normal human mammary epithelial cell (HMLE) and breast cancer MDA-MB-231 cells are engineered to knockdown or enforce expression of variety of LCOR gene products. In addition to wild-type cDNA, functional domain deficient mutants were used to elucidate mechanism of LCOR incorporated transcriptional regulation. The transcriptome profiles were determined and compared.

overall_design: Two sets of experiments: (1) LKO vector control vs LCOR-KD in two cell types to determine the outcome of LCOR deficiency. (2) LEX vector control vs. (wild-type, LSKAA mutant, △HTH mutant) LCOR to confirm the LCOR outcome (as identified by KD) and determine the functional impact of individual domain.

first: T

last: Celià-Terrassa


title: 4TO7 cells: miR-23b/27b/24 overexpression vs control

status: Public on Dec 23 2014

summary: Transcriptional profiling of 4TO7 cells featuring ectopic expression of miR-23b/27b/24 compared to vector control cells. Gene expression changes will be examined as potential direct targets of the miRNAs for use in later studies on metastasis suppression or activation.

overall_design: Two-condition experiment, miRNA overexpressing cells vs vector control. Biological replicates: 2 transfection replicates each.

first: Brian

last: Ell


title: Silencing RNA-binding  protein CELF1 inhibits tumor growth and alters gene expression in oral squamous cell carcinoma

status: Public on Sep 01 2015

city: Albuquerque

first: Viswanathan

last: Palanisamy

state: NM

address: 2325 Camino de Salud NE,

department: Internal Medicine

institute: University of New Mexico

summary:
RNA-binding proteins (RBPs) are critical regulators of gene expression, but only a small fraction have been studied for their role in malignancy.  Here we report a systematic analysis of RBP CUGBP Elav-Like Family member 1 (CELF1 alias CUGBP1) roles in mRNA alternative splicing, translation and turnover in oral cancer cells. CELF1 is overexpressed in carcinogen-induced oral cancer tumorigenesis mouse model and specific inhibition of CELF1 reduces  tumor growth in vivo. Deep transcriptomic analysis revealed that hundreds of mRNAs were differentially regulated as a function of CELF1 expression in oral cancer cells.  More importantly, the presence of CELF1 promoted alternative splicing of several target mRNAs which are known to be involved in various cancer biological processes. Using a pulse SILAC-based quantitative proteomic approach, we observed hundreds of proteins whose translation was controlled by CELF1 and those altered proteins were implicated in malignancy.  Altogether, these data provided a comprehensive view of the CELF1 mRNA regulatory network in OSCC and suggests that CELF1 is a viable target for therapeutic intervention.
Significance  Post-transcriptional mechanisms that regulate cancer cells which are believed to constitute the driving force of many malignancies are poorly understood. We show that oral squamous cell carcinoma (OSCC) emerge as a result of an over expressed RNA-binding protein CELF1, a protein implicated in mRNA turnover, alternative splicing and translation. The resulting mRNA expression repertoire regulates networks of genes whose expression changes regulate oral cancer pathogenesis. Inhibition of CELF1 mitigated OSCC tumor-forming capacity and offers an attractive therapeutic option for oral malignancies.

overall_design: Transcriptomic analysis of UMSCC-74B oral cancer cells as a function of CELF1 protein expression.

first: Reniqua

middle: P

last: House

first: E

middle: S

last: Hazard


title: Temporal regulatory interactions of lipid metabolism and inflammation in defining macrophage inflammatory phenotype

status: Public on Jan 04 2017

first: Nathanael

middle: Judge

last: Spann

state: CA

address: 9500 Gilman Drive CMMW 219A

department: Cellular and Molecular Medicine

institute: UCSD

summary: Systematic analyses of the temporal dynamics of transcriptomes and chromatin landscapes of macrophages during timecourse of TLR4-mediated inflammatory response. As a multifunctional effector cell, macrophages play pivotal roles in both the induction and resolution components of varied inflammatory processes. During the course of an inflammation response, macrophages engage in a homeostatic program characterized by tightly coordinated modulation of temporal outputs of both lipid metabolism and inflammation. We demonstrate inversely biphasic temporal dynamics of specific fatty acid metabolic and inflammatory gene expression profiles, associated with concordant temporal reprogramming of macrophage fatty acid profiles. In part, the late phase of the macrophage inflammatory response is characterized by tailoring of fatty acid related gene expressions, facilitating both significant induction of anti-inflammatory unsaturated fatty acid production and associated resolution of inflammation. We demonstrate the biphasic temporal dynamics of macrophage inflammation, specifically anti-inflammatory omega-3 and omega-9 unsaturated fatty acid levels, are transcriptionally driven genome-wide by an unexpected shift from an LXR to SREBP1-dominant regulatory program in the late phase inflammatory response. Collectively, our findings reveal a novel Srebp1-driven mechanism allowing the intimate inverse temporal relationship between the transcriptional regulation of inflammatory and fatty acid metabolic outputs; whereby modulation key transcriptional regulators (LXR, SREBP1 and NF-kB) of these pathways coordinate appropriate temporal tailoring of local enhancer associated reprogramming and eventual pathway regulatory interactions, during the course of TLR4-dependent inflammatory response in macrophages. This specific Srebp-driven, temporal reprogramming of macrophage fatty acid metabolism, characterized by late phase induction of anti-inflammatory unsaturated fatty acid production, is necessary for appropriate resolution of inflammation. Thus, this study suggests that selective reprogramming of macrophage lipid metabolism can serve as a viable therapeutic intervention aimed at ameliorating chronic inflammation and varied metabolic syndrome associated states.

overall_design: Chromatin mark H3K27Ac, H3K4me2 and transcription factors SREBP1, LXR, p65, PU.1 and RNA polymerase2 were assessed by ChIP-Seq and RNA-Seq were used to measure gene expression in the timepoints after inflammatory stimuli

first: Yumiko

last: Oishi-Tanaka

first: Verena

last: Link

first: Evan

middle: D

last: Muse

first: Tobias

last: Strid

first: Chantle

last: Edillor

first: Minna

middle: U

last: Kaikkonen

first: Michael

last: Lam

first: Jenhan

last: Tao

first: Ichiro

last: Manabe

first: Matthew

last: Kolar

first: Alan

last: Saghatelian

first: Christopher

middle: K

last: Glass


title: Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition

status: Public on Feb 01 2016

city: Charlestown

first: Aaron

last: Hata

address: 149 13th Street

department: Cancer Center

institute: Massachusetts General Hospital

summary: Although mechanisms of acquired resistance of EGFR mutant non-small cell lung cancers to EGFR inhibitors have been identified, little is known about how resistant clones evolve during drug therapy. Here, we observe that acquired resistance caused by the T790M gatekeeper mutation can occur either by selection of pre-existing T790M clones or via genetic evolution of initially T790M-negative drug tolerant cells. The path to resistance impacts the biology of the resistant clone, as those that evolved from drug tolerant cells had a diminished apoptotic response to third generation EGFR inhibitors that target T790M EGFR; treatment with navitoclax, an inhibitor of BCL-XL and BCL-2 restored sensitivity. We corroborated these findings using cultures derived directly from EGFR inhibitor-resistant patient tumors. These findings provide evidence that clinically relevant drug resistant cancer cells can both pre-exist and evolve from drug tolerant cells, and point to therapeutic opportunities to prevent or overcome resistance in the clinic.

overall_design: Examination of mRNA levels of PC9 parental, drug-tolerant, PC9-GR2 and PC9-GR3 cells after treatment with vehicle, gefitinib or WZ4002 for 24 hours.

first: A

first: F

last: Ji

first: R

middle: I

last: Sadreyev

first: J

last: Engelman


title: HMLEN cells with Vector Control vs SNAIL vs SNAIL/FBXO11

status: Public on Dec 01 2014

city: Plainsboro

first: Yong

last: Wei

summary: Transcriptional profiling of mouse HMLEN breast cancer cells (HMLE cells transformed with -Neu oncogene) stably tranduced with pLEX-MCS based lentivirus. Three groups were compared, Vector cells, SNAIL expressing cells; and SNAIL+FBXO11 expressing cells. SNAIL expression induced strong EMT phenotype while SNAIL/FBXO11 reversed cells back to epithelial cells.

overall_design: Three-condition experiments Vector vs SNAIL vs SNAIL/FBXO11.  Two replicates per each condition.

first: H

last: Zheng

first: Y


title: miR-199a-LCOR axis regulation of mammary gland stem cell and breast cancer stem cell transcriptional programs

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


title: 4T1 cells with Control vs SNAIL vs SNAIL/FBXO11

summary: Transcriptional profiling of mouse 4T1 breast cancer cells stably tranduced with pLEX-MCS based lentivirus. Three groups were compared, Vector cells, SNAIL expressing cells; and SNAIL+FBXO11 expressing cells. SNAIL expression induced strong EMT phenotype while SNAIL/FBXO11 reversed cells back to epithelial cells.

overall_design: Three-condition experiments Vector vs SNAIL vs SNAIL/FBXO11.  No replicate.


title: Transcriptome profiles of mouse mammary stem cells and progenitor cells

status: Public on Aug 19 2014

summary: MaSC, Luminal progenitor enriched subpopulations were isolated from virgin and pregnant mice based on using both surface marker or internal reporter transgene (GFP) expression. (Tiede BJ et al., 2009, PLoS ONE 4(11): e8035. doi:10.1371/journal.pone.0008035), and the transcirptome profiles were determined and compared.

overall_design: Two MaSC differential methods: CD24/CD29 & GFP reporter; two physiolgical condition: virgin vs pregnant; the combination of ((P4, GFPhi)  vs (P5, P6, GFPlo)) x (vg vs pg)

first: B

last: Tiede


title: Snd1-Mtdh interaction regulates cell survival under camptothecin-induced replication stress

status: Public on Aug 12 2014

summary: PyMT tumor cells with indicated status of Mtdh and Snd1 were treated with camptothecin (CPT) and the transcirptome profiles were determined and compared

overall_design: two sets of experiments: (1) vector control vs Snd1-KD under CPT treament (2) PyMT/Mtdh-KO cells reconstituted with either WT or Snd1-binding deficient mutant Mtdh (W391D) under CPT treatment

first: Wan

last: Liling

first: Wei

last: Yong


title: ΔNp63 promotes stem cell activity in mammary gland development and basal-like breast cancer by enhancing Fzd7 expression and Wnt signaling

overall_design: Refer to individual Series


title: Whole-genome mRNA expression profiling of cultured lymphoblastoid cell lines (LCLs) and whole blood from patients with global developmental delay and autistic features and unrelated normal controls

status: Public on Aug 01 2014

city: Riyadh

first: Dilek

last: Colak

address: MBC03, PO Box 3354

department: Biostatistics, Epidemiology and Scientific Computing

country: Saudi Arabia

institute: KFSHRC


title: Array based comparative genomic hybridisation analysis of 1 Mb resolution of 21 follicular lymphomas (FL), 31 transformed diffuse large B-cells lymphomas (DLBCL), 29 de novo DLBCL (10 of GC and 19 non-GC related immunophenotype).

status: Public on Apr 18 2014

city: Stockholm

first: Anna

last: Kwiecinska

address: CCK R8:00

department: Oncology-Pathology

country: Sweden

institute: Karolinska Institute

summary:
Follicular lymphoma (FL) is one of the most common types of indolent B-cell lymphoma in Western countries. FL commonly transforms to more aggressive diffuse large B-cell lymphoma (DLBCL) at reported frequencies between 15 - 60%.
We have used microarray comparative genomic hybridisation (aCGH) at 1 Mb resolution to study copy number changes in paired tumor samples (primary FL and a subsequent tDLBCL) as well as de novo DLBCL cases to outline genetic mechanisms of transformation from follicular lymphoma to diffuse large B-cell lymphoma.

overall_design: Single hybridization per case. 21 FL, 31 transformed DLBCL, 29 de novo DLBCL (10 GC and 19 non-GC DLBCL). Tumor labelled with Cy5 and reference with Cy3. Mixture of 20 normal male or female genomic DNA was used in sex-mismatched hybridization.

first: K

last: Ichimura

first: M

last: Berglund

last: Dinets

first: L

last: Sulaiman

first: V

last: Collins

first: C

last: Larrson

last: Porwit

first: S

last: Bajalica Lagercrantz


title: Expression data from LCL samples from patients with global developmental delay and autistic features and normal controls

summary: We analyzed the whole-genome mRNA expression profiling of cultured lymphoblastoid cell lines (LCLs) from patients (n=2), carriers (n=2), and unrelated normal controls (n=3), all performed in duplicates using Affymetrix GeneChip Human Exon 1.0 ST arrays, to identify genes and pathways that are significantly dysregulated in affected individuals. Moreover, we have performed global transcriptional profiling in whole blood from patients (n=2) and healthy controls (n=13) using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Global transcriptional profiling of affected individuals and controls revealed significant alterations of genes and pathways in a pattern consistent with previous microarray studies of autism spectrum disorder patients.

overall_design: Genome-wide gene-level expression changes for samples from cultured lymphoblastoid cell lines from patients with global developmental delay and autistic features (n=2), carriers (n=2), and unrelated healthy controls (n=3), all performed in duplicate, using Affymetrix GeneChip® Human Exon 1.0 ST arrays.

first: Namik

last: Kaya


title: Short-term exposure to diesel exhaust is associated with dynamic changes in DNA methylation of circulating mononuclear cells in asthmatics

status: Public on Apr 08 2014

city: Vancouver

first: Michael

middle: S.

last: Kobor

state: BC

address: 950 West 28th Avenue

department: Medical Genetics

institute: Centre for Molecular Medicine and Therapeutics / University of British Columbia

summary: DNA methylation in asthmatics after short-term exposure to diesel exhaust

overall_design: This cohort consist of genomic DNA extracted from 16 individuals under 6 distinct conditions, bisulphite converted and hybridized to the Illumina Infinium HumanMethylation450 Beadchip for genome wide DNA methylation profiling.

first: Ruiwei

last: Jiang

first: Meaghan

last: Jones

first: Francesco

last: Sava

first: Chris

last: Carlsten


title: ∆Np63 regulates stem cell activity in mammary gland development

first: Yong

last: Wei

department: Molecular Biology

summary: MaSC, luminal progenitor enriched subpopulations and total MECs as well, were isolated from both wild type and ∆Np63 KO heterozygous mouse and the transcriptome profiles were determined and compared.

overall_design: Three populations: P4, P5 and MECs; two genotypes: WT vs ∆Np63 heterozygous.

first: Rumela

last: Chakrabarti


title: RAW264.7 cells: RANKL vs Bone Metastasis Tumor Cell Condidtioned Media

status: Public on Oct 14 2013

summary: Transcriptional profiling of differential miRNA expression in mouse RAW264.7 preosteoclast cells comparing control untreated cells with RAW264.7 cells treated for 6 days. Treatment conditiones tested included 50ng/mL RANKL or indicated bone metastasis tumor cell conditioned media from 4T1, 4T1.2, TSU-PR1, and TSU-PR1-B2 cell lines.

platform_organism:
Caenorhabditis elegans
Drosophila melanogaster
Danio rerio
Homo sapiens
Mus musculus
Rattus norvegicus

overall_design: Two-condition experiment, Control cells vs. treated cells.

first: Brian

last: Ell

first: Yibin

last: Kang


title: Gene expression changes in primary Sertoli cells treated with MEK1/2 inhibitor

status: Public on Feb 01 2014

city: Stanford

first: Kazuteru

last: Hasegawa

address: Lorry Lokey Stem Cell Research Building (SIM1), G2165 265 Campus Drive

institute: Stanford University

summary: To investigate the gene expression regualted by MEK1/2-ERK1/2 signaling in Sertoli cells, we cultured primary Seroli cells and treated  bFGF and PD0325901, which are activator and inhibitor of the signaling, respectively.

overall_design: Isolated primary Sertoli cells were incubated with 20ng bFGF, 10uM PD0325901 or vehicle for 24 hours and then gene expression changes were measured with microarray analysis

first: Yumiko

last: Saga


title: Novel approach to select genes from RMA normalized microarray data using functional hearing tests in aging mice.

status: Public on Aug 06 2013

city: Tampa

first: Robert

last: Frisina

state: FL

address: 4202. E. Fowler Avenue ENB 118

department: Department of Chemical & Biomedical Engineering

institute: university of south florida

summary: Presbycusis – age-related hearing loss – is the number one communicative disorder of our aged population. Here we analyzed gene expression for a set of GABA receptors in the cochlea of aging CBA mice using the Affymetrix GeneChip MOE430A. Functional phenotypic hearing measures distortion-product otoacoustic emission (DPOAE) amplitudes (four age groups) were made. The gene expression  changes from RMA normalized microarray data (40 replicates) were first subjected to one-way ANOVA, and then linear regression was performed. In addition, the log signal ratio was converted to fold change, and selected gene expression changes were confirmed by relative real-time PCR. Major findings: expression of GABA-A receptor subunit 6was upregulated with age and hearing loss, whereas subunit 1 was repressed. In addition, GABA-A receptor associated protein like-1 and GABA-A receptor associated protein like-2 were strongly downregulated with age and hearing impairment. Lastly, gene expression measures were correlated with pathway/network relationships relevant to the inner ear using Pathway Architect, to identify key pathways consistent with the gene expression changes observed.

overall_design: In the study of expression changes GABA receptors in the in cochlea of young adult and aging presbycusis mice total of forty chips were used. The normal aging mice were in four groups young adults controls with good hearing (8 mice, 8 MOE430A GeneChips), Middle aged group  with good hearing  ( 17 mice, 17 MOE430A GeneChips), Mild Presbycusis (old) with limited hearing loss (9 mice, 9 MOE430A GeneChips) and Severe Presbycusis (old) (6 mice, 6 MOE430A GeneChips). Each Mice cochlea to each GeneChips, Samples was not pooled. The hearing potential evidence of each mouse is accompanied with each mice DPOAE amplitude.

first: Mary

last: D'Souza

first: Xiaoxia

last: Zhu


title: Expression data in wt or mutant Drosophila melanogaster embryos

status: Public on Jul 20 2013

city: Toulouse

first: serge

last: plaza

address: 118 route de Narbonne

department: Developmental Biology Center

country: France

institute: toulouseII University

summary: Terminal differentiation of epidermal cells in Drosophila embryos requires the activity of a transcription factor. Svb is necessary and sufficient to induce this process. pri is a regulator of Svb activity, converting it from a repressor into an activator. To characterize the downstream Svb and pri effectors in cell morphogenesis, we performed microarrays in wt, svb -/- (no gene) and pri -/- (svb repressor) mutant conditions.

overall_design: Embryos were selected at a precise 13-15h (after egg laying) stage of development, and manually genotyped for each condition: wt (W samples), svb -/- (R samples) and pri -/- (P samples). 5 independent replicates of 200 embryos are used for each condition. RNA were extracted and hybridized on Affymetrix microarrays.

first: Delphine

last: Menoret


title: MDA-MB-231 cell: infected with lentivirus to stably express mut-Elf5 vs WT-Elf5

status: Public on Sep 20 2012

country: USA

summary: Elf5 induced transcriptional changes in MDA-MB-231 origin, control (mut Elf5) vs WT ELF5

overall_design: Two-condition experiment, control (mut-Elf5) vs WT-Elf5. Each has 3 biological repeats.


title: Elf5 inhibits epithelial mesenchymal transition in development and cancer metastasis through transcriptional repression of Snail2

summary:
Elf5 (or ESE-2) is an ETS transcription factor that is abundantly expressed in the mammary epithelium, where it plays a critical role in dictating cell fate and lineage choices. These changes are in part mediated by alterations in the expression and activity of critical components of the Jak/Stat pathway. While the biological function of Elf5 in mammary gland development has been well characterized, its role in breast cancer remains to be elucidated. Here we show that loss of Elf5 leads to features associated with epithelial-mesenchymal transition (EMT) in the mouse mammary gland during pregnancy and lactation. These cellular changes in Elf5-null mammary epithelia are also reflected at the molecular level by the global enrichment of EMT-related gene signatures. ELF5 is expressed in higher level in weakly metastatic breast cancer cells that retained epithelial features compared to highly metastatic cells with mesenchymal features.  ELF5 knockdown in T47D breast cancer cells resulted in EMT and increased migration. Conversely, ectopic expression of Elf5 revert mesenchymal-like MDA-MB-231 cells and its lung-tropic variant LM2 to an epithelial phenotype, with reduced migration, invasion and lung metastatic abilities. Finally, we showed that Elf5 binds directly to the promoter of the EMT transcriptional factor Snail2 (Slug) and repress its expression. Taken together, these data established a novel function for Elf5 in inhibiting EMT in normal mammary epithelium and in breast cancer through direct targeting of Snail2.

This SuperSeries is composed of the SubSeries listed below.

overall_design: Refer to individual Series.


title: Expression data from patients with global developmental delay and autistic features and normal controls

first: Dilek

last: Colak

overall_design: Whole-genome mRNA expression profiles of samples from whole blood from patients with global developmental delay and autistic features (n=2) and healthy controls (n=13) using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays.


title: LM2 cell: infected with lentivirus to stably express Elf5 vs GFP

summary: Elf5 induced transcriptional changes in high lung metastasis subline LM2 (MDA-MB-231 origin), control (GFP) vs ELF5

overall_design: Two-condition experiment, control (GFP) vs Elf5. Each has duplicate biological repeats.


title: Stage-dependent gene expression change in Sertoli cells regulated by retinoic acid signaling

status: Public on Jul 01 2012

summary: To identifiy stage-dependent genes in Sertoli cells, we performed expression microarray analysis of the adult whole testes, cultured primary Sertoli cells, Sertoli cells directly isolated from wild-type and Nanos3 (germ-less) testes,seminiferous tubules at stages I-III, IV-VI, VII-VIII and IX-XII. Next to examine the relationship between stage-dependent gene expression change and retinoic acid signaling, we performed expression microarray analysis of the cultured primary Sertoli cells treated with retinoic acid and stage-specific seminiferous tubules injected with lentivirus containing Venus or dominat negative form of RARa, a dominant receptor for retinoic acid in Sertoli cells.

overall_design: Biological duplicates were examined at each sample

first: Saga

last: Yumiko


title: Function, targets and evolution of Caenorhabditis elegans piRNAs

status: Public on Jun 18 2012

city: Darlinghurst

first: Leonard

last: Goldstein

address: 384 Victoria St

country: Australia

institute: Garvan Institute of Medical Research


title: Function, targets and evolution of Caenorhabditis elegans piRNAs (mRNA)

summary: piRNAs are required to maintain germline integrity and fertility but their mechanism of action is poorly understood. Here we demonstrate that C. elegans piRNAs silence transcripts in trans through imperfectly complementary sites. We find that target silencing is independent of Piwi endonuclease activity or “slicing”. Instead, we show that piRNAs initiate a localized secondary endogenous small interfering RNA (endo-siRNA) response. Endogenous protein-coding gene, pseudogene and transposon transcripts exhibit Piwi-dependent endo-siRNAs at sites complementary to piRNAs and are derepressed in Piwi mutants. Genomic loci of piRNA biogenesis are depleted of protein-coding genes but not pseudogenes or transposons. Our data suggest that nematode piRNA clusters are evolving to generate piRNAs against active mobile elements. Thus, piRNAs provide heritable, sequence-specific triggers for RNAi in C. elegans.

overall_design: Affymetrix mRNA expression data from wild-type and two independent prg-1;prg-2 double mutant C. elegans strains (mRNA)

first: Marloes

last: Bagijn

first: Alexandra

last: Sapetschnig

first: Eva-Maria

last: Weick

first: Samir

last: Bouasker

first: Nicolas

last: Lehrbach

first: Martin

last: Simard

first: Eric

last: Miska


title: Function, targets and evolution of Caenorhabditis elegans piRNAs (small RNA-Seq)

overall_design: 7 small RNA libraries were sequenced as part of 25 flow cell lanes on the Illumina GA II platform. Samples were treated with tobacco acid pyrophosphatase to allow cloning of small RNAs with a 5'-triphosphate. Samples were labelled for multiplexing using 4-bp 5'-barcodes or barcodes included in Illumina TruSeq adapters. In most cases a single flow cell lane included several multiplexed libraries.


title: piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans

status: Public on Jun 25 2012

summary: Transgenerational effects likely have wide-ranging implications for human health, biological adaptation and evolution, however their mechanism and biology remain poorly understood. Here we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain epi-allelic inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches we find that a core set of nuclear RNAi and chromatin factors are required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 otholog HPL-2 and two putative histone methyltransferases, SET-25 and SET-32. Most surprisingly, piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present the first report of multigenerational epigenetic inheritance induced by piRNAs in any organism.

overall_design: Seven C. elegans small RNA libraries from three distinct experiments (A, B, C) were sequenced using Illumina sequencing technology. Five small RNA libraries were prepared according to library construction protocol 1 and sequenced as part of 22 flow cell lanes on the Illumina GA IIx platform. Samples were labelled for multiplexing using 4-bp 5'-barcodes, a single flow cell lane included several multiplexed libraries. Two small RNA libraries were prepared according to library construction protocol 2 and sequenced on the Illumina MiSeq platform.

first: Alyson

last: Ashe

first: Jacinth

last: Mitchell

first: Amy

middle: C

last: Cording

first: Ana-Lisa

last: Doebley

first: Jérémie

last: Le Pen

first: Greta

last: Pintacuda

first: Aisa

last: Sakaguchi

first: Peter

last: Sarkies

first: Shawn

last: Ahmed


title: Novel viruses naturally infecting Caenorhabditis nematodes trigger a small RNA response

status: Public on Jan 01 2011

first: Leonard

last: Goldstein

summary: C. elegans has served as a laboratory model organism due to its ease of manipulation and the availability of both forward and reverse genetics. In recent years, efforts to study host-pathogen interactions in C. elegans have increased. For example, analysis of infections by bacteria such as Pseudomonas, Salmonella or Serratia has revealed the existence of innate immune pathways in C. elegans that are also conserved in vertebrates. To date, there has been no natural virus infection reported in C. elegans or C. briggsae. Here we describe evidence of natural virus infection in wild isolates of both C. elegans and C. briggsae. Two highly divergent but related RNA viruses in the family Nodaviridae, tentatively named Orsay nodavirus and Santeuil nodavirus, were detected and their genomes partially sequenced. Infected worm lysates passed through 0.2 um filters could be used to infect uninfected worms, which could be further passaged for many generations. Furthermore, the viruses were subject to processing by the RNAi machinery as evidenced by the detection of virally derived small RNAs. Infection of mutant worms defective in small RNA pathways yielded more robust levels of viral RNA as compared to infection of isogenic N2 reference worms. These data demonstrate that nodaviruses are natural parasites of nematodes in the wild. Further study of the interactions between these viruses and nematodes is likely to provide insight into the natural ecology of nematodes and may reveal novel innate immune mechanisms that respond to viral infection.

overall_design: Two small RNA libraries (18-30 nt) from nodavirus-infected and cured C. elegans wild isolate JU1580 were sequenced on the Illumina Genome Analyzer II platform. Samples were treated with tobacco acid pyrophosphatase to allow cloning of small RNA molecules with 5'-triphosphates. Each sample was labelled with a unique four base pair barcode and libraries were multiplexed together with a third library (not included in this submission). The multiplexed libraries were sequenced in triplicate.

first: Marie-Anne

last: Félix

first: Joséphine

last: Piffaretti

first: Guang

last: Wu

first: Isabelle

last: Nuez

first: Tony

last: Bélicard

first: Yanfang

last: Jiang

first: Guoyan

last: Zhao

first: Mabel

last: Sanroman

middle: A

first: David

last: Wang


title: Modulation of the immune response of turbot (Scophthalmus maximus) after infection with viral haemorragic septicaemia virus

status: Public on Feb 14 2012

city: Bergen

first: Pablo

last: Balseiro

address: Thormøhlensgate 53

department: Institutt for Biovitenskap

country: Norway

institute: Universitet i Bergen

summary: Turbot (Scophthalmus maximus) is a valuable resource for aquaculture in Galicia (NW Spain). Since it has been observed that viral hemorraghic septicaemia can affect turbot, among other finfish, increase of knowledge in molecular factors affected by the exposure to pathogen could help to develop strategies of VHSV prevention and treatment. In this study, it has been used a custom oligo-microarray by Agilent to identify genes differentially expressed in several turbot families showing different susceptibility to VHSV. Fishes from each family (n=30) were injected with either VHSV (Resistant) or control medium (Naive) and monitored for 30 days, when each group was splitted in two new groups and rechallenged with VHSV (Infected) or control medium (Control). Gene expression at the head kidney was evaluated, showing than an important proportion of the variation of the gene expression profiles is explained by the genetic background (family). After infection, fish showed an up-regulation of the interferon-induced Mx2 gene, the IL-8 gene and the VHSV-induced protein 5 gene compared with control groups. Familes with high mortality after VHSV infection showed lower levels of expression of molecules secreted in the mucus and, by contrast, higher expression of genes involved in viral entrance into target cells.

overall_design: 4 different families of turbot were subjected to challenged with VHSV and splitted after 30 days in 2

first: Patricia

last: Díaz

first: Alejandro

last: Romero

first: Sonia

last: Dios

first: Beatriz

last: Novoa

first: Antonio

last: Figueras


title: Characterisation of microRNA expression in post-natal mouse mammary gland development [miRNA]

status: Public on Sep 30 2009

summary:
Background: The differential expression pattern of microRNAs (miRNAs) during mammary gland development might provide insights into their role in regulating the homeostasis of the breast epithelium. Our aim was to analyse these regulatory functions by deriving a comprehensive tissue-specific combined miRNA and mRNA expression profile of post-natal mouse mammary gland development. We measured the expression of 318 individual murine miRNAs by bead-based flow-cytometric profiling of whole mouse mammary glands throughout a 16-point developmental time course, including juvenile, puberty, mature virgin, gestation, lactation, and involution stages. In parallel whole-genome mRNA expression data were obtained.
Results: One third (n = 102) of all murine miRNAs analysed were present during mammary gland development. MicroRNAs were represented in seven temporally co-expressed clusters, which were enriched for both miRNAs belonging to the same family and breast cancer-associated miRNAs. Global miRNA and mRNA expression was significantly reduced during lactation and the early stages of involution after weaning. For most detected miRNA families we did not observe systematic changes in the expression of predicted targets. For miRNA families whose targets did show significant changes, we observed inverse patterns of miRNA and target expression. The datasets are made publicly available and the combined expression profiles represent an important community resource for mammary gland biology research.
Conclusions: MicroRNAs were expressed in co-regulated clusters during mammary gland development. Breast cancer-associated miRNAs were significantly enriched in these clusters. The mechanism and functional consequences of this miRNA co-regulation and its correlation with mRNA expression provide new avenues for research into mammary gland biology and generates candidates for functional validation.

overall_design: Developmental time course over 16 time points with 1-3 independent biological replicates per time point and three pairs of technical replicates, 40 samples in total

first: Stefanie

last: Sassen

first: John

last: Stingl

first: Cherie

last: Blenkiron

last: Le Quesne

first: Inma

last: Spiteri

first: Konstantina

last: Karagavriilidou

first: Christine

last: Watson

first: Simon

last: Tavaré

first: Eric

last: Miska

first: Carlos

last: Caldas