title: Identification of a distinct luminal subgroup diagnosing and stratifying early stage prostate cancer by tissue-based single-cell RNA sequencing

status: Public on Oct 20 2020

city: Shenzhen

first: Xiaoshi

last: Ma

address: No.1017, Dongmen North Road, Luohu District

institute: Shenzhen People's Hospital

summary: The highly intra-tumoral heterogeneity and complex cell origination of PCa greatly limited the significance of traditional bulk RNA sequencing in finding better biomarker for disease stratification. In the context of these sequencing strategies, significant gene expression differences in specific cell population might be normalized or even shaded by genes in those less “important” but large in amount cells. Tissue specimens based single-cell RNA sequencing holds great promise for identification of novel stratification biomarkers. However, the preparation of enough viable cells for sequencing, in particular for prostate cancer (PCa), is very challenging when using this technique. In the current study, we, for the first time, employed single-cell RNA sequencing of PCa cells isolated from cancerous prostate tissues of two patients and identified fifteen cell groups including three luminal clusters with different expression profiles. One of these luminal clusters had the highest copy number variation level and marker genes mainly enriched in PCa-related metabolic process, thereafter, was considered as the malignant luminal cells in PCa. Further analysis indicates that the fifth subgroup of these cells highly expressed genes significantly correlated with PCa initiation and early development. In addition, we found this subgroup highly expressed PCa prognosis biomarkers such as AMACR and PCA3. These findings suggest that this cell subgroup might be a critical cell population for PCa diagnosis and stratification. Moreover, by further deciphering the gene expression of this subgroup, we identified another marker gene, HPN, with a 0.930 area under the curve (AUC) score distinguishing normal tissue from PCa lesion using the RNA-seq data from The Cancer Genome Atlas (TCGA). This finding was further validated by immunostaining of HPN in PCa tissue array. The expression of HPN in PCa with Gleason score > 6 is significantly higher than those in Gleason score = 6. Taken together, we provide a valuable resource for interpreting the tumor heterogeneity in PCa, and a novel candidate marker for PCa management.

overall_design: Examination of intra-tumoral heterogeneity of prostate cancer by single-cell RNA sequencing of cancerous prostate tissues from two patients.

first: Jinan

last: Guo

first: Kaisheng

last: Liu

first: Lipeng

last: Chen

first: Dale

first: Shaowei

last: Dong

first: Jinquan

last: Xia

first: Qiaoyun

last: Long

first: Yongjian

last: Yue

first: Pan

first: Fengyan

last: Hu

first: Zhangang

last: Xiao

first: Xinghua

last: Pan

first: Kefeng

first: Zhiqiang

last: Cheng

first: Zunfu

last: Ke

first: Zhe-Sheng

first: Chang

last: Zou


title: Type I interferon responses to ischemic injury begin in the bone marrow of mice and humans and depend on Tet2, Nrf2, and Irf3

status: Public on Sep 12 2020

city: La Jolla

first: David

last: Calcagno

state: CA

address: 9500 Gilman Drive

department: Bioengineering

country: USA

institute: UCSD

type: Expression profiling by high throughput sequencing

summary: Sterile tissue injury is thought to locally activate innate immune responses via damage associated molecular patterns (DAMPs). Whether innate immune pathways are remotely activated remains relatively unexplored. Here, by analyzing ~145,000  single cell transcriptomes at steady state and after myocardial infarction (MI) in mice and humans, we show that the type I interferon (IFN) response, characterized by expression of interferon stimulated genes (ISGs), begins far from the site of injury, in neutrophil and monocyte progenitors within the bone marrow. In the peripheral blood of patients, we observed defined subsets of ISG-expressing neutrophils and monocytes.  In the bone marrow and blood of mice, ISG expression was detected in neutrophils and monocytes and their progenitors; intensified with maturation at steady-state and after MI; and was dependent on Tet2 and Irf3 transcriptional regulators. Within the infarcted heart, ISG-expressing cells were negatively regulated by Nrf2-activation in Ccr2- steady-state cardiac macrophages.  Our results show that IFN signaling begins in the bone marrow, implicate multiple transcription factors in its regulation (Tet2, Irf3, Nrf2), and provide a clinical biomarker (ISG score) for studying IFN signaling in patients.

overall_design: We measured and analyzed >90K single cell transcriptomes of immune cells isolated from bone marrow, blood, and heart at steady-state and after myocardial infarction in mice.

first: Richard

last: Ng Jr

first: Avinash

last: Toomu

first: Claire

last: Zhang

first: Kenneth

last: Huang

first: Aaron

last: Aguirre

first: Ralph

last: Weissleder

first: Lori

last: Daniels

first: Zhenxing

last: Fu

first: Kevin

last: King


title: Gene Expression Profiling Provides Insights into the Moleculor Mechanism of FGFR2+ Fibrocyte-to-Cancer Associated Fibroblast Differentiation in Esophageal Squamous Cell Carcinoma

status: Public on Aug 01 2020

city: HONGKONG

first: LIYI

last: ZHANG

state: HONGKONG

address: 21 SASSOON ROAD

department: CLINICAL ONCOLOGY

country: China

institute: THE UNIVERSITY OF HONGKONG

summary: To obtain an accurate overview of changes occurring during fibrocyte-to-cancer associated fibroblast differentiation in human esophageal squamous cell carcinoma (ESCC), we isolated circulating FGFR2+ fibrocytes and their paired FGFR2+ cancer associated fibroblasts (CAFs) from ESCC patients and compared their gene expression profiles by high-throughput RNA Sequencing. On average, about 55.08 million reads were obtained after eliminating low quality reads and 52.76 million reads (95.79%) were aligned to the human mRNA reference sequences. Transcripts corresponding to a total of 1,016 and 409 genes were found to be upregulated or downregulated at least two-fold in the combined set of two CAF sample pools, respectively. Furthermore, we identified the potential master regulators of CAF-specific extracelluar factors by motif enrichment analysis and addressed the molecular mechanisms underlying CAF differentiation.

overall_design: Whole transcriptome profiles of ESCC-derived FGFR2+ fibrocytes and CAFs were generated by deep sequencing using Illumina GAIIx. FGFR2+ fibrocytes were isolated from blood samples of 9 ESCC patients, while, FGFR2+ CAFs were isolated from marched ESCC tissues. Sample pooling strategy was employed to reduce the effects of individual variation. Samples (total RNA) were pooled into two groups: group 1 combined 5 samples of fibrocytes (Fbc-1) and corresponding paired CAFs (CAF-1), while group 2 combined 4 samples of fibrocytes (Fbc-2) and marched CAFs (CAF-2).

first: Xinyuan

last: Guan

first: Liyi

first: Lei

last: Li


title: RNAseq of ISP CD28+ cells stimulated with ImmunoCult

status: Public on Jul 29 2020

city: South San Francisco

first: Juliette

last: Roels

address: 1 DNA Way

institute: Genentech

summary: The generation of TCRαβ and TCRγδ T cells proceeds through distinct developmental stages in which changing regulatory events control differentiation and lineage outcome. To clarify the underlying mechanisms, we employed RNAseq, ATACseq and ChIPmentation on well-defined thymocyte subsets that represent the continuum of human T cell development. The chromatin accessibility dynamics uncover stage-specific regulatory mechanisms and reveal that human T-lineage commitment is marked by the GATA3- and BCL11B-dependent closing of PU.1 sites. While the ß-selection checkpoint is marked by transcriptional changes and a temporary increase in H3K27me3 without modifications in open chromatin, emerging γδ T cells, that originate from common precursors as ß-selected cells, show dramatic changes in chromatin accessibility which results from strong TCR signaling. Furthermore, we unravel distinct chromatin landscapes between CD4 and CD8 αβ T cells that support their effector functions and reveal gene-specific regulatory mechanism that define mature T cells. This resource provides an important framework for studying gene regulatory mechanisms that drive human normal and malignant T cell development.

first: Anna

last: Kuchmiy

first: Tom

last: Taghon


type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: ATACseq of CD34+ HPCs with viral overexpression of GATA3, TCF1 or BCL11B in conditions with and without Notch ligand DLL4


title: ATACseq of ISP CD28+ cells stimulated with ImmunoCult


title: Human bone marrow and umbilical cord-derived mesenchymal stromal cells activated with TNF-α, IL-1β or IFN-γ

status: Public on Aug 19 2020

city: Medicine Hat

first: Lorena

last: Braid

state: Alberta

address: PO Box 21053, Crescent Heights PO

country: Canada

institute: Aurora BioSolutions Inc.

summary:
We used microarrays to characterize the in vitro response of three populations each of neonatal and adult MSCs to three soluble inflammatory mediators separately, in xeno-free media.
The magnitude of transcriptomic response to each priming condition was compared between MSC sources. Whether resting MSC source differences were attentuated or amplified following activation with cytokines was also explored.

overall_design: Cryopreserved MSCs were obtained from commercial sources: Wharton’s jelly (UC) MSCs from Tissue Regeneration Therapeutics, Inc., and BM MSCs from RoosterBio Inc.. Three populations of each MSC source (2 male and 1 female donors each) were expanded in xeno-free media, and at comparable population doubling levels, were seeded into 3 flasks each for priming. Media was replaced and purified recombinant human cytokines TNF-α, IL-1β or IFN-γ were added to each culture in protein-free media for 24 hours. Conditioned media was collected for quantification of secreted protein content, and RNA was extracted from the resting (unprimed) or primed cells and analyzed by Affymetrix Human Genome U133A 2.0 Array. Batches of experimental culture and GeneChip processing time frames were balanced to eliminate additional variability or bias in the data, and batch information is included.

first: Danielle

middle: M

last: Wiese

middle: R

first: Cindy

middle: C

last: Ruttan

first: Catherine

middle: A

last: Wood

first: Barry

middle: N

last: Ford


title: Differentially expressed genes analysis of wild type K562 cells treated with vandetanib and control (DMSO)

status: Public on Sep 25 2020

city: Xi’an

first: yanmin

last: zhang

state: Shaanxi

address: No. 76, Yanta Weststreet, #54

institute: School of Medicine, Xi’an Jiaotong University, Xi’an, Shaanxi Province

type: Non-coding RNA profiling by high throughput sequencing

summary:
Purpose: The aim of this study was to evaluate the difference of mRNA and lncRNA in K562 cells treated with vandetanib (1.56 μM) and control (DMSO) by high-throughput sequencing results.
Methods: Total RNA was extracted using the RNAfast200 kit according to the manufacturer’s protocol. Then, 200 ng RNA was sequenced with high throughput, and then pathway and GO analysis were used for comprehensive analysis. Finally, RT-PCR method was used to validate in large sample population.
Results: High-throughput sequencing results showed that there were significant differences in mRNA and lncRNA in K562 cells treated with vandetanib (1.56 μM) and control (DMSO).
Conclusions: It is the first time that we have used high-throughput sequencing to study the difference of mRNA and lncRNA in K562 cells treated with vandetanib (1.56 μM) and control (DMSO). The results of sequencing show that the expression of mRNA and lncRNA is quite different in K562 cells treated with vandetanib (1.56 μM) and control (DMSO).

overall_design: Three control (DMSO) treated samples and three vandetanib (1.56 μM) treated samples.

first: Weina

last: Ma

first: Yanmin

last: Zhang


title: Temporal and dosage-dependent transcriptional response to SARS-CoV-2 in lung, trachea, brain, olfactory bulb and small intestine of Syrian golden hamsters

status: Public on Nov 11 2020

city: New York

first: Rasmus

last: Moeller

state: NY

address: 1 Gustave L. Levy Place

department: Microbiology

institute: Icahn School of Medicine at Mount Sinai

summary: Here we report the transcriptional response to SARS-CoV-2 in Syrian golden hamsters and compare it to the host response against Influenza A virus. The virus replicates fast to high titers in the respiratory tract followed by a local and systemic inflammatory response. A roust IFN-I reponse is mounted and lasts at leaset fourteen days in distal tissues together with other lasting transcriptional changes.

overall_design: Syrian golden hamsters were infected with a low or a high dose of SARS-CoV-2 for either 1, 2, 4, 6, 8, or 14 days and five tissues were collected and examined by mRNA-sequencing.

first: Benjamin

last: tenOever

last: Møller


title: ATACseq of 11 subsets of human postnatal developing thymocytes

overall_design: ATACseq of 11 ex-vivo sorted postnatal human thymocyte populations from two donors


title: High expressed genes enriched with H3K27me3 in maize genome

city: Nanjing

first: tao

middle: shen

last: tong

address: Weigang street 1st

institute: Nanjing Agricultural University

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

overall_design: Refer to individual Series


title: Zinc Uptake and Storage During the Formation of the Cerebral Cortex in Mice

status: Public on Jul 19 2020

city: PARIS

first: Stephane

last: Le Crom

address: 46 rue Ulm

department: Genomic Core Facility

country: France

institute: IBENS

summary:
The aim of this work was to analyse the transcriptome of the mice cerebral cortex (or neocortex) during embryogenesis and at post-natal age. This complete transcriptomic analysis was dedicated to the analysis of the genes participating in the homeostasis of Zinc during brain development and formation.
Our study represents a detailed analysis of transcriptomes during formation and dvelopment of the brain cortex, with biologic triplicates, generated by RNA-seq technology. This will provide a framework for comparative investigations of expression profiles. Our work offers an accurate quantitative and qualitative evaluation of mRNA content during mice embryogenesis.

overall_design: Total mRNA from cerebral cortices of C57Bl6/J mice were generated in triplicate. Tissues were collected at embryonic days 11 (E11), E13, E17 and on post-natal day 1 pups.

first: Alexandre

last: Bouron

first: Jessy

last: Hasna

first: Sylvain

last: Bohic

first: Corinne

last: Blugeon

first: Sophie

last: Lemoine


title: A map of cis-regulatory elements and 3D genome structures in zebrafish

status: Public on Sep 04 2020

city: CHICAGO

first: Yu

last: Luan

state: Illinois

address: 303 E. Superior Simpson Querrey 7-518

department: Department of Biochemistry and Molecular Genetics

institute: Northwestern University Feinberg School of Medicine

summary: The zebrafish has been widely used for the study of human disease and development, as ~70% of the protein-coding genes are conserved between the two species. Annotation of functional control elements of the zebrafish genome, however, has lagged behind that of other model systems such as mouse and Drosophila. Based on multi-omics approaches taken in the ENCODE and Roadmap Epigenomics projects, we performed RNA-seq, ATAC-seq, ChIP-seq and Hi-C experiments in ten adult and two embryonic tissues to generate a comprehensive map of transcriptomes and regulatory elements in the zebrafish Tuebingen reference strain. Overall, we have identified 235,596 cis-regulatory elements, which potentially shape the tissue-specific and developmental-stage-specific gene expression in zebrafish. A comparison of zebrafish, human, and mouse regulatory elements allowed us to identify both evolutionarily conserved and species-specific regulatory sequences. Furthermore, through the analysis of Hi-C data in zebrafish brain and muscle, we observed different levels of 3D genome organization, including compartment, topological associating domains (TADs), and chromatin loops in zebrafish. A subset of TADs are deeply conserved between zebrafish and human. This work provides an additional epigenomic anchor for the functional annotation of vertebrate genomes and the study of evolutionally conserved elements of 3D genome organization.

overall_design:
13 tissues from adult and  embryonic stage were examined using ChIP-Seq (H3K27ac and H3K4me3), RNA-Seq, 11 of them were examined using ATAC-seq ,WGBS and ChIP-seq (H3K9me3 and H3K9me2), and one scATAC-seq in brain. Additionally we performed HiC experiments in adult muscle and brain.

Please note that, for the samples GSM4661977-GSM4662088,
[1] each processed data generated from both replicates is linked to the corresponding *rep1 sample records
[2] the input sample used for each ChIP sample is indicated in the description field in the corresponding input sample records.

first: Hongbo

last: Yang

first: Tingting

last: Liu

first: Feng

last: Yue


title: Dissecting the transcriptomic landscape of the human intrahepatic cholangiocarcinoma by single cell RNA-sequencing

status: Public on Jun 06 2020

city: Beijing

first: Min

state: Beijing

address: No. 8 East Road, Fengtai District

department: The Fifth Medical Center of Chinese PLA General Hospital

institute: Academy of Military Medical Sciences

summary: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising in the liver, featured with high tumor heterogeneity and dismal prognosis. The cellular disversity and molecular basis of tumor cells interacted with surrounding niche cells remains poorly understood, limiting the development of targeted anti-tumor therapies.

overall_design: To comprehensively elucidate the ICC heterogeneity, we employed single-cell RNA sequencing (scRNA-seq) to profile 31,302 cells of five ICC samples, as well as three paired adjacent non-tumor tissues. Our results identify 31 cell subtypes and the heterogeneous malignant subtype was highly patient-specific, which has differential proliferative, migratory and inflammation phenotype.

first: Hui

first: Bing

first: Xinlong

last: Yan


title: A common genetic trait through multistep hepatocarcinogenesis in a case with chronic hepatitis C

status: Public on Jul 24 2020

city: Minami Uonuma

first: Takeshi

last: Suda

state: Niigata

address: 4132 Urasa

department: Department of Gastroenterology and Hepatology

country: Japan

institute: Uonuma Institute of Community Medicine, Niigata University Medical and Dental Hospital

summary: Common genetic traits are not well defined in hepatocellular carcinoma (HCC), because necroinflammation lasting long in prior to hepatocarcinogenesis embeds highly heterogenous genetic background in hepatocytes over the liver. We experienced a rare case with chronic hepatitis C, in which multiple liver tumors at different stages in multistep hepatocarcinogenesis were observed at the same time. Under the same genetic and etiological backgrounds, comparisons of expression profiles among dysplastic nodules (DN), well differentiated HCC (WEL), and moderately differentiated HCC (MOD) would provide critical genetic information for the initiation and progression of HCC.

overall_design: Liver tissues were obtained by needle biopsy from one of each of nontumorous liver tissues, DN, WEL, and MOD and subjected to expression analyses using GeneChip Human Transcriptome Array 2.0.


title: Human macrophage responses to viral-like particles from non-IBD or IBD colonic resections

status: Public on Jun 01 2020

city: Boston

first: Kate

middle: L

last: Jeffrey

state: MA

address: 50 Blossom Street

department: Medicine

institute: Massachusetts General Hospital

summary: Peripheral blood-derived macrophages were stimulated with viral-like particles isolated from colonic resections from patients with Crohn's disease (CD), ulcerative colitis (UC), or non-IBD controls diagnoses. RNAseq was performed to unbiasedly assess the transcriptional responses to these stimuli and revealed highly divergent macrophage transcriptional programs in response to non-IBD compared to IBD VLP.

overall_design: Peripheral blood mononuclear cells from the blood of three healthy human donors were pooled and differentiated into macrophages with M-CSF over the course of seven days. Mature macrophages were treated with viral-like particle (VLP) isolates from colon resections of patients with Crohn's disease (5 individual patient samples), ulcerative colitis (5 individual patient samples), non-IBD diagnoses (5 individual patient samples), or mock treated (3 replicates of mock treatment). RNA was isolated and RNA-seq was carried out for transcriptional analysis.

first: Fatemeh

last: Adiliaghdam

first: Sreehaas

last: Digumarthi

first: Lai

middle: P

last: Wong

first: Ruslan

last: Sadreyev


title: Comprehensive transcriptome analysis in human liver

city: Shanghai

first: Shengli

last: Li

address: 650 Xinsongjiang Road

institute: Shanghai Jiao Tong University School of Medicine

summary: The complexity of transcriptome in human liver has not been clarified quite clearly so far. Here we collect various types of liver samples, including primary tumor, relapse tumor, benign adjacent, normal liver and tumor cell lines.High-throughput RNA sequecing data was generated for each sample.We assembled transcripts from these data under the guidance of GENCODE transcript annotation (v22).After the assembly, 94,272 genes and 371,388 transcripts were identified. Furthermore, we identified alternative splicing events from these genes and transcripts.

overall_design: Illuminate the complexity of liver transcriptome through high-throughput sequencing data.

first: Shenglin

last: Huang

first: Xianghuo

last: He


title: Transcriptional regulation of human αβ and γδ T cell development is driven by distinct and temporary-restricted epigenetic mechanism

first: Juliette

last: Roels


title: High expressed genes enriched with H3K27me3 in maize genome [RNA-seq]

first: tao

last: tong

summary: H3K27me3 usually enriched with low or no expressed genes in animal or plant genomes. However, some researches  indicate that H3K27me3 can be enriched with high expressed genes in human genome. It's still unknown that whether this kind of gene is appeared in plant genomes and the mechanisms are also unclear. In this study we used ChIP-seq to develop high resolution profiles of H3K27me3 distributions in several tissues or cell-types of maize to better understand the role of this mark in an important crop. The integration of ChIP-seq H3K27me3 profiles with RNA-seq and WGBS-seq data sets suggested that H3K27me3 may play diverse roles in regulation chromatin structure and function. We found that subsets of highly expressed genes are significantly enriched with H3K27me3 in maize. The profiles of several maize mutants reveal functional divergence for the control of H3K27me3 among maize genes. The analysis of existing rice and Arabidopsis data finds that a subset of highly expressed genes in these species are also associated with high levels of H3K27me3. Collectively, our analyses demonstrate that H3K27me3 alone or cooperating with DNA methylation and other chromatin features actively regulates subsets of gene expression, thereby providing new insights in diverse functions of H3K27me3 in plants.

overall_design: BS and M cell were used to exclude false positive genes. Root were used to identify tissue-specific enriched genes.

first: Wenli

last: Zhang

first: Shentong

last: Tao

first: Lifen

last: chen


title: Molecular Functions of Conserved Developmentally-Regulated GTP-Binding Protein Drg1 in Translation

status: Public on Jul 11 2020

city: Urbana

first: Hong

last: Jin

address: 600 S Mathews Ave

department: Biochemistry

institute: University of Illinois at Urbana-Champaign

summary: Developmentally-regulated GTP-binding (Drg) proteins are important for embryonic development, cell growth, proliferation, and differentiation. Despite their highly conserved nature, the functions of Drg proteins in translation are unknown. Here, we performed a wide analysis of ribosome dynamic in S.cerevisiae Rbg1, Rbg2 and Slh1 depleted cells using 5Pseq (Pelechano et al. 2015 PMID 26046441), which allows the study of ribosome dynamics by sequencing the 5' phoshporylated mRNA co-translational degradation itermediates. We demonstrate the yeast Drg ortholog, Rbg1, alleviates ribosome pausing at Arginine/Lysine-rich regions in mRNAs, and mainly targets genes related to ribonucleoprotein complex biogenesis and non-coding RNA processing pathways.

overall_design: 16 samples for 5Pseq experiments using various yeast strains.

first: Fuxing

last: Zeng

first: Melissa

last: Pires-Alves

first: Christopher

middle: W

last: Hawk

first: Xin

last: Chen


title: Histone mark profiles of 11 subsets of human postnatal developing thymocytes

overall_design: ChIPmentation seq of H3K4me3, H3K27ac and H3K27me3 in 11 ex-vivo sorted postnatal human thymocyte populations from two donors

first: Anna

last: Kuchmiy

first: Tom

last: Taghon


title: MicroRNA expression profile of human hepatic stellate cells LX-2 co-cultured with human umbilical cord mesenchymal stem cells and control group

status: Public on May 24 2020

city: suzhou

first: shouli

last: wang

address: renai road 199, suzhou industrial park

department: pathology

institute: soochow university school of medicine

summary: Hepatic stellate cells(HSCs) are the main effector cells of liver fibrosis. In order to study the effect of mesenchymal stem cells(MSCs) on microRNAs expression of HSCs, we co-cultured HSCs LX-2 activated by TGFβ1 with human umbilical cord MSCs(hUC-MSCs) for 48 hours, and compared the differentially expressed miRNA with LX-2 cultured alone by high-throughput sequencing. The results showed that two mature microRNAs expressed increased, and  nine  expressed decreased.

overall_design: Human HSCs line LX-2 cells were treated with TGFβ1 (10 ng/mL) for 24 h in DMEM without serum for activation. To evaluate the effects of the MSCs on activated HSCs, indirect coculture in Transwell chamber was used. LX-2 cells were cultured in the lower membrane layer, and hUC-MSCs were cultured  in the upper semi-permeable membrane. Cells were divided into two groups: i) experimental group, hUC-MSCs and  LX-2 cells were co-cultured for 48h,  ii) Control group, LX-2 cells were cultured alone, each group with 3 replicates.

first: Shouli

last: Wang

first: Qing

last: Zhou

first: Yuting

last: Kuang


title: Circular RNA expression alteration in peripheral blood of premature infants with periventricular white matter damage

status: Public on May 20 2020

first: Sisi

last: Mo

state: Jiangsu

address: 87 Dingjia Qiao, Gulou District

institute: Zhongda Hospital, Southeast University

summary: Periventricular white matter damage (PWMD) is the principal pathological type of brain damage in premature. It causes irreversible damage to the overall function of the central nervous system resulting in cerebral palsy, convulsions, epilepsy, cognitive, motor dysfunction and other late effects. CircRNAs are participate in the biological processes underlying many nervous system diseases. However, the circRNA expression profile of peripheral venous blood of premature infants with PWMD is not completely understood. Three premature with white matter damage (PWMD group) and three infants without brain injury (Normal group) were enrolled. Peripheral venous blood was collected from both groups for extraction of RNA and circRNA sequencing was performed. The RNA-seq technique was used to screen the differentially expressed circRNA in peripheral blood of infants with PWMD. The accuracy of sequencing results was verified by quantitative reverse transcription polymerase chain reaction (q-PCR) to the differentially express partial circRNA in the sequencing results. Bioinformatics analysis of Host genes was performed with differential circRNA. TargetScan and Miranda were used to predict circRNA-binding miRNAs and mapped into a circRNA-miRNA co-expression network. There were 119 significantly different circRNAs as compared with premature without brain injury, along with 1 circRNA was up-regulated and 4 circRNAs were down-regulated expression in the PWMD group. Combined with the existing research results and bioinformatics analysis results after sequencing, it is suggested that circRNA may regulate the occurrence and development of white matter damage in premature infants by interacting with miRNA. This first study of its kind further identified the expression profile of circRNA in peripheral blood of premature with WMD, and provide a novel targets for further investigation about the molecular mechanisms underlying PWMD and potential therapeutic intervention.

overall_design: CircRNA profile of peripheral venous blood of premature infants with periventricular white matter damage (PWMD) and three infants without brain injury, and each group were generated by Illumina Hiseq 4000.

first: Lixing

last: Qiao


title: A transcriptomic analysis of serial-cultured, tonsil-derived mesenchymal stem cells reveals decreased integrin α3 protein as a potential biomarker of senescent cells

status: Public on Apr 30 2020

city: Cheongju

first: Da Hyeon

last: Choi

address: Major in Microbiology, School of Biological Sciences, College of Natural Sciences

country: South Korea

institute: Chungbuk National University

summary: In this study, we investigated differential genetic expression patterns among TMSCs with different cultivation times and passage numbers. Transcriptomic approaches were used to further identify novel candidate biomarkers of culture-aged, senescent TMSCs. These analyses have led us to propose that genes associated with ECM are differentially altered with aging of TMSCs, and some of these molecules could be used as potential indicators for identifying stem cells with senescence.

overall_design: Total 4 Samples, 2 Sample Groups, 1 Comparisons. (test vs. control) (Control TMSC vs. Culture-aged TMSC)

first: Yoon

middle: S

last: Park

first: Da

middle: H


title: IFN-kappa Suppresses the Replication of Influenza A Virus through IFNAR-MAPK-Fos-CHD6 Axis

status: Public on Apr 09 2020

first: Yongquan

last: He

address: No.2901 Caolang Road

institute: Fudan University

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: Transcriptional response to IFN-κ and IFN-κDual in A549 cell line

summary: Type I interferon (IFN) is the first line of defense against virus infection. By using both in vivo and in vitro influenza infection models, we found that type I IFN-κ, limited the replication of influenza viruses by stimulating a IFNAR-MAPK-cFos-CHD6 axis. Similarly, Zika virus (ZIKV) was also highly sensitive to IFN-κ-mediated suppression. With an IAV infected mouse model, we found that IFN-κ was the earliest responding type I interferon among all known members in mice after H9N2 infection, a low-pathogenic Avian Influenza, whereas this early induction did not occur upon highly pathogenic H7N9 infection. IFN-κ can efficiently contain both low- and high-pathogenic influenza replication in cultured human lung cells, and CHD6 was the major effector responsive molecule for IFN-κ, but not for IFN-α/β. Furthermore, we discovered that both IFNAR1 and IFNAR2 subunits of type I interferon receptor and their downstream axis of p38-cFos are engaged in IFN-κ signaling cascade to acti  vate CHD6, which didn`t require STAT1 activity. In addition, we showed that the pre-treatment with IFN-κ before IAV challenge protected mice from high mortality. Altogether, our study identified an IFN-κ-specific pathway that suppressed influenza A virus in vitro and in vivo. Thus, IFN-κ may have potential as a new prevention and treatment agents against emerging viruses

overall_design:
RNAseq of A549 cells transfected with plasmids encoding WT IFN-κ, IFN-κ Dual, or pSV1.0 empty vector
RNA was isolated 24 hours after transfected. Samples were collected in biological triplicate and pSV1.0 empty vector was control.


title: Histone H3K9 methylation promotes formation of genome compartments in C. elegans via chromosome compaction and perinuclear anchoring (Hi-C)

status: Public on Apr 21 2020

city: Berkeley

first: Barbara

middle: J.

last: Meyer

address: 16 Barker Hall #3204

department: MCB

institute: HHMI/UCB

summary: Genomic regions preferentially associate with regions of similar transcriptional activity, partitioning genomes into active and inactive compartments within the nucleus. Here we explored mechanisms controlling genome compartment organization in C. elegans and investigated roles for compartments in regulating gene expression. The distal arms of C. elegans chromosomes, which are enriched for heterochromatic histone modifications including H3K9me, interact with each other both in cis and in trans, while interacting less frequently with central regions of chromosomes, leading to genome compartmentalization. Arms are anchored to the nuclear periphery via the nuclear envelope protein CEC-4, which binds to H3K9me. By performing genome-wide chromosome conformation capture experiments (Hi-C), we showed that eliminating H3K9me1/me2/me3 through mutations in the methyltransferase genes met-2 and set-25 significantly impaired formation of genome compartments. cec-4 mutations also impaired compartmentalization, but to a lesser extent. We found that H3K9me promotes compartmentalization through two distinct mechanisms: perinuclear anchoring of chromosome arms via CEC-4 to promote their cis association, and an anchoring-independent mechanism that compacts individual chromosome arms. In both met-2 set-25 and cec-4 mutants, no dramatic changes in gene expression were found for genes that switched compartments or for genes that remained in their original compartment, suggesting that compartment strength does not dictate gene expression levels. Furthermore, H3K9me, but not perinuclear anchoring, also contributes to formation of another prominent feature of chromosome organization, megabase-scale topologically associating domains on X that are established by the dosage-compensation condensin complex.  Our results demonstrate that H3K9me plays crucial roles in regulating genome organization at multiple levels.

overall_design: We performed in situ Hi-C on nuclei isolated from mixed stage embryos and processed data as in (Brejc et al., 2017). We performed Hi-C for three biological replicates of GW0638 met-2 set-25 and two biological replicates of RB2301 cec-4 mutant embryos.

first: Qian

last: Bian

first: Erika

last: Anderson

first: Qiming

last: Yang

middle: J


title: The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression to control neurite outgrowth [ChIP-Seq]

status: Public on Apr 08 2020

city: Memphis

first: Hans-Martin

last: Herz

state: TN

address: 262 Danny Thomas Place

institute: St. Jude Children's Research Hospital

summary: Cell type diversity during neuro-ectodermal (NE) differentiation is achieved through selective activation and silencing of neurodevelopmental genes. Here, we show a key role for the histone deacetylase complex MiDAC during neuronal differentiation of mouse embryonic stem cells (mESCs) into NE. We demonstrate that MiDAC functions as a modulator of a neurodevelopmental gene expression program and binds to important regulators of neurite outgrowth. MiDAC mediates the removal of H4K20ac on the promoters and enhancers of pro-neural genes such as the axon guidance ligands Slit3 and Ntn1 while in parallel reducing H3K27ac on promoter-proximal and -distal elements of negative regulators of neurogenesis thereby upregulating and inhibiting gene expression, respectively. Furthermore, neurite outgrowth defects in MiDAC KO neurons can be rescued by restoring Slit3/Robo3-Ntn1/Unc5b signaling. Taken together, our work suggests a crucial role for MiDAC in regulating the secretome of the Slit3/Robo3-Ntn1/Unc5b signaling axes to ensure the proper integrity of neurite development.

overall_design: ChIP-seq was carried out in mESCs for the histone modification marks H3K4me1, H3K4me3, H3K27ac, H3K27me3 and for Dnttip1, a subunit of MiDAC. ChIPs against each histone mark or Dnttip1 were carried out at least in duplicate for each genotype. Genotypes used were WT, Dnttip1 KO and Elmsan1 KO.

first: Baisakhi

last: Mondal

first: Hongjian

last: Jin

first: Satish

last: Kallappagoudar

first: Yurii

last: Sedkov

first: Tanner

last: Martinez

first: Monica

middle: F

last: Sentmanat

first: Greg

last: Poet

first: Chunliang

last: Li

first: Yiping

last: Fan

first: Shondra

last: Pruett-Miller


title: The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression to control neurite outgrowth [RNA-Seq]

overall_design: RNA was isolated from 3 x 10e6 mESCs with the RNeasy Mini Kit (Qiagen, 74106) following the manufacturer’s instructions from each genotype in duplicate. Genotypes: WT, Dnttip1 KO1 (D1E6), Dnttip1 KO2 (D2A7), Elmsan1 KO1 (E2E8) and Elmsan1 KO2 (E2G7).


title: RNA-Seq of sorted E10.5 and E11.5 AGM cell populations from Gata3-GFP embryos

status: Public on May 25 2020

city: Cambridge

first: Evangelia

last: Diamanti

address: Wellcome Trust / MRC Building, Hills Road

department: Haematology

country: United Kingdom

institute: University of Cambridge

summary: The aim of this study was to examine the whole transcriptome of pools of 20 cells of Gata3-expressing AGM subpopulations (haematopoietic [HC], mesenchymal [MC], sympathetic nervous system [SNS], and endothelial [EC]) and compare them to  their non-Gata3 expressing counterparts

overall_design: Cells were sorted into:  Gata3+ EC: GFP+ Cdh5+ CD41- CD45-, Gata3- EC:  GFP- Cdh5+ CD41- CD45-, Gata3+ HC: GFP+ CD41+ CD45+, Gata3- HC: GFP- CD41+ CD45+, Gata3+ MC: GFP+ Pdgfrb+, Gata3- MC: GFP- Pdgfrb+, Gata3+ SNS: GFP+ Ngfr+ and Gata3- SNS: GFP- Ngfr+. Each population was then sorted into the lysis buffer in a 96-well plate at 20 cells per well.

first: Nada

last: Zaidan

first: Katrin

last: Ottersbach


title: Transcriptional response of mice infected with H9N2 or H7N9

first: Yongquan

last: He

overall_design:
Mice were intranasally (i.n) inoculated with either 3.5x10e5 TCID50 of H7N9 virus, or 1.7x10e7 EID50 of H9N2 virus, or PBS (control group) in a volume of 50 microliters
Infected mice were sacrificed at various time points ranging from 6hrs to day 14 post virus challenge for collection of lung tissues from which RNA were extracted and analyzed.
Mice challenged with H7N9 IAV, H9N2 IAV, or PBS. 3 mice were pooled at indicated time for immune response analysis

first: Weihui

last: Fu


title: The regulation of gene expression by LSD1 in MCF-7 cells

status: Public on Oct 16 2020

city: Singapore

first: Ying

state: --- Select a state ---

address: 14 Medical Dr, Singapore

country: Singapore

institute: Cancer Science Institute of Singapore

summary: We performed RNA-Seq analysis of differentially expressed genes in WT and LSD1 KD MCF-7 cells to understand the regulation of gene expression by LSD1.In addition, we report the ChIP-Seq analysis of LSD, H3K4me1 and H3K4me2 binding sites in the genome of WT and LSD1 KD MCF-7 cells.

overall_design: Examination of genome-wide transcripts in WT and LSD1 KD MCF-7 cells. Examination of LSD1, HEK4me1 and H3K4me2 occpupancy in WT versus LSD1 KD MCF-7 cells.

first: Yang

last: Shi

first: Wanqiang

last: Sheng

first: Henry

last: Yang


title: Genome-wide gene methylation study in primary cultured airway smooth muscle cells

status: Public on Mar 30 2020

city: Chicago

first: Emma

last: Thompson

state: IL

address: 920 E 58th St, CLSC Rm 501

department: Human Genetics

institute: The University of Chicago

summary: We generated genome-wide methylation data from primary cultured airway smooth muscle cells (ASMCs) exposed to IL-13, IL-17, IL-13+IL-17, and vehicle. This data was generated in combination with genome-wide expression data from the same individuals.

overall_design: Examination of genome-wide gen methylation in response to cytokines and comparison to asthma status (N=280).

middle: E

first: William

last: Wentworth-Sheilds


title: Single-nucleus RNA-seq identifies transcriptional heterogeneity in multinucleated skeletal myofibers

status: Public on Oct 11 2020

city: Cincinnati

first: Nathan

last: Salomonis

state: OH

address: 3333 Burnet Avenue

department: Biomedical Informatics

institute: Cincinnati Children's Hospital

summary: While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the emergence of distinct myonuclear populations in postnatal development and their reactivation in aging muscle. Our datasets also provided a platform for discovery of novel genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.

overall_design: Single-nucleus RNA-seq of tibialis anteior muscle of BL6 wild-type mice across the lifespan: 10 days, 21 days, 5 months (TA and soleus), 24 months, 30 months

first: Michael

last: Petrany

first: Casey

middle: O

last: Swoboda

first: Chengyi

last: Sun

first: Kashish

last: Chetal

first: Xiaoting

last: Chen

first: Matthew

middle: T

last: Weirauch

first: Douglas

last: Millay


title: RNA-seq identifies lncRNAs in hyperreactive and hyporeactive platelets

status: Public on Apr 02 2020

city: Yantai

first: Yeying

state: Shandong

address: Guanhai road No.346

institute: Binzhou medical univerisity

summary: Platelets are blood cells who play critical roles in numerous biological and disease processes. This study was designed to identify lncRNAs that may play a role in platelet reactivity. In this study, by using large-scale deep sequencing, we determined the expression profiles of lncRNAs in both hyperreactive and hyporeactive human platelets. To determine the potential link between the expression of lncRNAs and the function of platelets, the expression profiles of hyperreactive and hyporeactive platelets were compared. Compared with hyperreactive platelets, deep sequencing analysis demonstrated that differential lncRNA expression was a remarkable characteristic in hyporeactive platelets.

overall_design: To determine the expression profiles of lncRNAs and mRNAs in platelets, RNAs from both hyperreactive and hyporeactive platelets were used. Three micrograms of RNA per sample were used as the input material for the RNA sample preparations. The expression profiles of lncRNAs and mRNAs were determined by genome-wide large-scale next-generation deep sequencing by using the Illumina platforms.

first: Rongrong

last: Liu

first: Xiangwen

last: Xia


title: The histone deacetylase complex MiDAC regulates a neurodevelopmental gene expression to control neurite outgrowth

first: Hans-Martin

last: Herz

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

overall_design: Refer to individual Series


title: Genome-wide gene expression study in primary cultured airway smooth muscle cells

summary: We generated genome-wide expression data from primary cultured airway smooth muscle cells (ASMCs) exposed to IL-13, IL-17, IL-13+IL-17, and vehicle. This data was generated in combination with genome-wide methylation data from the same individuals.

overall_design: Examination of genome-wide gene expression in response to cytokines and comparison to asthma status (N=67).


title: Comparative single-cell transcriptomics of complete insect nervous systems

status: Public on Feb 07 2020

city: St Augustine

first: Leonid

last: Moroz

state: FL

address: 9505 Ocean Shore Blvd

institute: University of Florida

summary: Molecular profiles of neurons influence information processing, but bridging the gap between genes, circuits and behavior has been very difficult. Furthermore, the behavioral state of an animal continuously changes across development and as a result of sensory experience. How behavioral state influences molecular cell state is poorly understood. Here we present a complete atlas of the Drosophila larval nervous system. We develop polyseq, a python analysis package, and use single molecule RNA-FISH to validate our scRNAseq findings. To investigate how internal state affects cell state, we altered internal state with high-throughput behaviour protocols designed to mimic wasp sting and over activation of the memory system. We found nervous system-wide gene expression changes related to cell state. This work advances our understanding of how genes, neurons, and circuits generate behavior.

overall_design: Single cell genomics and modulation of internal state reveal how genes, neurons, and circuits produce behavior.

first: Benjamin

last: Cocanougher

first: Andrea

middle: B

last: Kohn


title: Analysis of gene expression in lung adenocarcinoma cells following over-expression of miR-30a-5p or miR-30a-3p

status: Public on Feb 26 2020

city: Philadelphia

first: Ramkrishna

last: Mitra

state: Pennsylvania

address: 233 S 10th street

institute: Thomas Jefferson University

summary: RNA-sequencing was performed to gain insight into the transcriptome-wide molecular changes induced by miR-30a-5p or miR-30a-3p over-expression in lung adenocarcinoma cells. Following transfection of miR-30a-5p or miR-30a-3p miRNA mimic or control RNA, RNA-sequencing was performed. This high-throughput data revealed elevated expression of both miR-30a-5p and miR-30a-3p reduced the expression of genes and pathways known to induce proliferation and movement in lung adenocarcinoma cells.

overall_design: miR-30a-5p or miR-30a-3p was transfected in lung adenocarcinoma cells and gene expression profiles were generated using RNA-sequencing.

first: Christine

middle: M

last: Eischen


title: Specialized ribosomal protein genes promote drug resistance through modulation of translation

status: Public on Mar 09 2020

city: sherbrooke

first: Mustafa

last: Malik Ghulam

state: quebec

address: 3201 rue mignault

institute: university of sherbrooke

summary: Ribosomes are ubiquitous ribonucleoprotein complexes required for protein synthesis. We show that in budding yeast exposure to drugs alters ribosome composition leading to modification of translation pattern and increased resistance to drug. Exposure to staurosporine repressed translation of cell wall protein genes. Expression of the major paralog of uL30/RPL7 increased cell sensitivity to staurosporine while expression of the minor paralog induced resistance. Remarkably, we found that differences in paralogs function was due to difference in the translation pattern. The minor paralog promoted the translation of cell wall genes with long open reading frames (ORFs), which are normally under-translated in the presence of the major paralog, leading to drug resistance. Reducing the ORF length repressed the minor paralog and staurosporine effects on translation. Together the data reveal a natural mechanism for the optimization of translation through changes in the identity of ribosomal protein genes.

overall_design: Total RNA and ribosome associated RNA from wild type cells and cells carrying two copies of either uL30A/RPL7A or uL30B/RPL7B  grown in presence or absence of saturosporine was sequenced.

first: Sherif

last: Elela


title: Histone H3K9 methylation promotes formation of genome compartments in C. elegans via chromosome compaction and perinuclear anchoring

first: Barbara

last: Meyer

state: CA


title: Histone H3K9 methylation promotes formation of genome compartments in C. elegans via chromosome compaction and perinuclear anchoring (ChIP-seq)

overall_design: We performed two ChIP-seq replicates with GW0638 met-2 set-25 and one replicate with RB2301 cec-4.

first: Qian

last: Bian

first: Erika

middle: C

last: Anderson

first: Qiming

last: Yang


title: Rx-TGx: Toxicogenomic Study Of Pharmaceuticals Using RNA-Seq

status: Public on Feb 24 2020

city: West Point

first: Alexei

middle: A

last: Podtelezhnikov

state: PA

address: 770 Sumneytown Pike

department: Non-clinical Drug Safety

institute: Merck & Co., Inc.

summary: The robust transcriptional plasticity of liver mediated through xenobiotic receptors underlies its ability to respond rapidly and effectively to diverse chemical stressors. Thus, drug-induced gene expression changes in liver serve not only as biomarkers of liver injury, but also as mechanistic sentinels of adaptation in metabolism, detoxification and tissue protection from chemicals. Modern RNA sequencing methods offer an unmatched opportunity to quantitatively monitor these processes in parallel and to contextualize the spectrum of dose-dependent stress, adaptation, protection and injury responses induced in liver by drug treatments. Using this approach, we profiled the transcriptional changes in rat liver following daily oral administration of 95 different compounds, many of which are known to be associated with clinical risk for drug induced liver injury (DILI) by diverse mechanisms.

overall_design: Rats received repeted daily dosing of pharmaceuticals; sacrificed 24 hour after the last dose; total RNA extracted from fresh frozen livers.

first: James

last: Monroe

first: Frank

middle: D

last: Sistare

first: Keith

middle: Q

last: Tanis


title: Genome-wide gene expression and methylation studies in primary cultured airway smooth muscle cells

first: Emma

last: Thompson

type:
Expression profiling by array
Methylation profiling by array


title: Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection [II]

status: Public on Mar 01 2020

first: Xiao

last: Ge

address: No. 800 Dongchuan Road

institute: Shanghai JiaoTong University

summary: CTCF is a key insulator-binding protein and mammalian genomes contain numerous CTCF-binding sites (CBSs), many of which are organized in tandem arrays. Here we provide direct evidence that CBSs, if located between enhancers and promoters in the clustered Pcdh and b-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CBS or not. Moreover, computational simulation and experimental capture revealed balanced promoter usage in vivo in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem variable CBSs. Finally, gene expression levels are negatively correlated with CBS insulators located between enhancers and promoters on a genome-wide scale. Thus, single CBS insulators ensure proper enhancer insulation and promoter activation while tandem-arrayed CBS insulators determine balanced promoter choice. This finding has interesting implications on the role of topological insulators in 3D genome folding and developmental gene regulation.

overall_design:
QHR-4C profiles of P0 wild type (WT) and CBS-deletion mouse cortex were generated by deep sequencing using Illumina HiSeq X-ten

CBS deletion mouse lines used in this study (UCSC mouse July 2007(mm9) referance genome):
CBSa del chr18:38,001,106-chr18:38,001,113
CBSbcd del chr18:38,011,224-chr18:38,037,839
CBSbc del chr18:38,011,224-chr18:38,013,147
CBSde del chr18:38,036,567-chr18:38,040,872
CBSd del chr18:38,036,568-chr18:38,037,818
CBSb-e del chr18:38011471-chr18:38040871
CBSe del chr18:38,039,423-chr18:38,040,879

Please note that the GSM4046041-GSM4046056 sample records have been moved to GSE211024 on Aug 11, 2022 as per submitter's request.

first: Zhilian

last: Jia

first: Yonghu

last: Wu

first: Qiang


title: Male Fathead Minnow Transcriptomes in Milwaukee Estuary System

status: Public on Jan 31 2020

city: Vicksburg

first: Emily

middle: Alice

last: Woolard

state: Mississippi

address: 3909 Halls Ferry Rd

institute: U.S. Army Engineer and Research Development Center

summary: Contaminants of Emerging Concern (CECs) can be measured in waters across the United States, including the tributaries of the Great Lakes. The extent to which these contaminants affect gene expression in aquatic wildlife is unclear. This dataset presents the full hepatic transcriptomes of laboratory reared fathead minnows (Pimephales promelas) caged at multiple sites within the Milwaukee Estuary area of concern and control sites. Following 4 days of in situ exposure, liver tissue was removed from males at each site for RNA extraction and sequencing, yielding a total of 116 samples from which libraries were prepared, pooled, and sequenced. For each exposure site, 179 chemical analytes were also assessed. These data were created with the intention of inviting research on possible transcriptomic changes observed in aquatic species exposed to CECs. Access to both full sequencing reads of animal samples as well as water contaminant data across multiple Great Lakes sites will allow others to explore the health of these ecosystems, in support of the aims of the Great Lakes Restoration Initiative.

overall_design: 116 total liver samples were RNA sequenced. 80 samples are from 7 different exposure sites, and the remainder 36 are from control sites. Fathead minnows were deployed at sites and exposed to water for 4 days. Following exposure, animals were removed, transferred to laboratory, and had livers removed from males and frozen at -80C until sequencing.

first: Mitchell

last: Wilbanks

first: John

last: Mylroie

first: Kathleen

last: Jenson

first: Michael

last: Kahl

first: David

last: Feifarek

first: Shane

last: Poole

first: Eric

last: Randolph

first: Jenna

last: Cavallin

first: Daniel

middle: L

last: Villeneuve

first: Gerald

last: Ankley

first: Natalia

last: Garcia-Reyero

first: Edward

last: Perkins

first: Lyle

last: Burgoon


title: Age-dependent decline of TET1-mediated DNA hydroxy-methylation impairs myelin regeneration after injury

status: Public on Mar 14 2020

city: New York

first: Sarah

last: Moyon

state: NY

address: 85 St Nicholas Terrace

department: Neuroscience

institute: CUNY ASRC

type: Methylation profiling by high throughput sequencing

summary: Adult myelination is recognized as essential for brain function and response to injury and yet, its molecular understanding is mostly inferred from developmental studies. In this study, we identify DNA hydroxy-methylation, an epigenetic mark catalyzed by Ten-Eleven translocation (TET) enzymes, as necessary for adult, but not for developmental, myelin formation. While hydroxy-methylation and high levels of TET1 were detected in young adult mice during myelin regeneration after lysolecithin-induced demyelination, this process was defective in older mice. Lineage specific ablation of the enzyme Tet1 (but not of Tet2) recapitulated the age-related decline of TET1 and inefficient remyelination, without impacting developmental myelination. Genome-wide DNA hydroxy-methylation profiling of adult progenitors and mature oligodendrocytes, identified solute carriers regulating neuronal-glial communication as gene targets, whose expression was dramatically decreased in mutants and in older mice. We conclude that TET1-mediated hydroxy-methylation is critical for adult myelination in response to injury.

overall_design: Transcriptomic profiles and DNA hydroxymethylation whole-genome profiles of FAC-sorted P60 Pdgfra-EGFP and P60 Plp-EGFP purified cell samples from mouse brains were generated by RNA-Sequencing and Reduced Representation Hydroxymethylation Profiling (RRHP), respectively (in triplicates).

first: Rebecca

last: Frawley

first: Katy

last: Cole

first: Boguslawa

last: Sadowski

first: Dennis

last: Huang

first: Yong-Hui

last: Jiang

last: Lyons

first: Wiebke

last: Moebius

first: Patrizia

last: Casaccia


title: Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

status: Public on Mar 02 2020

city: Shanghai

first: Xiao

last: Ge


title: Analysis of genes differentially expressed depending on Oct4/Nanog induction and of chromatin interactions to define the HoxB landscape in ESCs and mouse embryos

status: Public on Jan 01 2020

city: Madrid

first: Fatima

last: Sanchez-Cabo

address: Melchor Fernandez Almagro

country: Spain

institute: CNIC


title: The intestinal microbiota programs DNA methylation to control tissue homeostasis and inflammation

status: Public on Feb 06 2020

city: Heidelberg

first: Guenter

last: Raddatz

address: Im Neuenheimer Feld 580

country: Germany

institute: German Center for Cancer Research


title: Analysis of genes differentially expressed depending on Oct4/Nanog induction

summary: The goal is to examine the transcriptome of Oct4 and Nanog conditional expressing mouse embryos at different developmental stages.

overall_design: In order to analyse the transcriptome, Oct4 and Nanog mouse embryos were collected at E7.5 and E9.5 in 3 biological replicates per stage.

first: Elena

last: Lopez-Jimenez

first: Miguel

last: Manzanares

first: Fátima

last: Sánchez-Cabo


title: Single-cell RNA-sequencing of spleen memory CD4+ T cells

status: Public on Dec 05 2019

city: Basel

first: DBM Bioinformatics

last: Core Facility

state: BS

address: Hebelstrasse 20

department: Departement of Biomedicine

country: Switzerland

institute: University of Basel

summary: We performed a single-cell transcriptome analysis of 3 biological independent splenic samples from pooled mice sorted for LCMV-specific memory CD4 T cells.

overall_design: Cells negative for dump and positive for CD4, CD44 and gp66 were sorted for each replicate, and used for single cell RNA Seq (10x genomics platform)

first: Marco

last: Kuenzli

first: David

last: Schreiner

first: Julien

last: Roux

first: Carolyn

last: King


title: Embryonic Atrazine Exposure Causes Behavioral, Transcriptomic, Epigenetic, and Pathological Alterations in Adult Zebrafish Brain

status: Public on Dec 31 2019

city: West Lafayette

first: Jennifer

last: Freeman

state: IN

address: 550 Stadium Mall Drive

department: School of Health Sciences

institute: Purdue University


title: Comparative phenotypic assessment of cardiac pathology, physiology, and gene expression in C3H/HeJ, C57BL/6J, and B6C3F1/J mice

status: Public on Nov 15 2019

city: Durham

first: Scott

last: Auerbach

state: North Carolina

address: 111 TW Alexander Drive

institute: Division of the National Toxicology Program at NIEHS

summary: Human cardiomyopathies often lead to heart failure, a major cause of morbidity and mortality in industrialized nations. Described here is a phenotypic characterization of cardiac function and genome-wide expression from C3H/HeJ, C57BL/6J, and B6C3F1/J male mice. Histopathologic analysis identified a low-grade background cardiomyopathy (murine progressive cardiomyopathy) in eight of nine male C3H/HeJ mice (age nine to ten weeks), but not in male C57BL/6J and in only of ten male B6C3F1/J mice. The C3H/HeJ mouse had an increased heart rate and a shorter RR interval compared to the B6C3F1/J and C57BL/6J mice. Cardiac genomic studies indicated the B6C3F1/J mice exhibited an intermediate gene expression phenotype relative to the 2 parental strains. Disease-centric enrichment analysis indicated a number of cardiomyopathy-associated genes were induced in B6C3F1/J and C3H/HeJ mice, including Myh7, My14, and Lmna and also indicated differential expression of genes associated with metabolic (e.g., Pdk2) and hypoxic stress (e.g. Hif1a). A novel coexpression and integrated pathway network analysis indicated Prkaa2, Pdk2, Rhoj, and Sgcb are likely to play a central role in the pathophysiology of murine progressive cardiomyopathy in C3H/HeJ mice. Our studies indicate that genetically determined baseline differences in cardiac phenotype have the potential to influence the results of cardiotoxicity studies.

overall_design: Ten C3H/HeJ, ten B6C3F1/J, and ten C57BL/6J male mice from The Jackson Laboratories, Bar Harbor, Maine were used for these studies. Surgery to implant a Data Sciences radiotelemetry transmitter in the abdominal cavity was performed on mice anesthetized with tribromoethanol (Avertine) 250 mg/kg IP at seven weeks of age. After collection of phenotype measurements (two to two and a half weeks post-surgery; nine and a half weeks of age),animals were euthanized with CO2; the heart was collected for histopathologic analysis, and a piece of the heart apex was collected for RNA analysis. RNA was extracted from the hearts of five control C3H/HeJ, C57BL/6J, and B6C3F1/J mice.

first: Reuben

last: Thomas

first: Ruchir

last: Shar

first: Hong

last: Xu

first: Molly

middle: K

last: Vallant

first: Abraham

last: Nyska

first: June

last: Dunnick


title: Immune landscape of viral- and carcinogen-drived head and neck cancer

status: Public on Nov 13 2019

city: Pittsburgh

first: Anthony

middle: Richard

last: Cillo

address: The Assembly, Room 4070C Bay 10, 5051 Centre Ave

department: Immunology

institute: University of Pittsburgh

summary: Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environmental carcinogens or malignant transformation by human papillomavirus (HPV). Here, we assessed the transcriptional profiles of 131,224 single cells from peripheral and intra-tumoral CD45+ immune populations from HPV– and HPV+ HNSCC and healthy donors. A spectrum of transcriptional signatures in immune lineages ranging from similar to highly divergent was present in the tumor microenvironments (TME) in HPV– and HPV+ HNSCC. CD8+ and regulatory CD4+ T cells were similar in HPV– and HPV+ HNSCC, compared to significant differences between helper CD4+ T cells, B cells and myeloid cells. Further dissection of the major immune lineages identified unique cell states and differentiation trajectories. We contextualized our results by performing multispectral immunofluorescence and evaluating putative cell-cell communication based on spatial proximity, and found longer progression free survival in patients with enrichment of a CD4+ T follicular helper cell signature.

overall_design: Total of 63 samples were analyzed by scRNAseq. Of these, 26 samples were paired peripheral blood mononuclear cells and tumor infiltrating immune cells from HNSCC patients (18 HPV- and 8 HPV+), 6 were peripheral blood mononuclear cells from healthy donors, and 5 were tissue resident immune cells from healthy donor tonsils.

middle: R

first: Tullia

last: Bruno

first: Robert

last: Ferris

first: Dario

last: Vignali


title: RNA sequencing of aortic tissue of Klotho knock-out mice treated with a minimal and a high magnesium diet

status: Public on Nov 04 2019

city: Nijmegen

first: Jeroen

last: de Baaij

address: Geert Grooteplein Zuid 28

department: Physiology

country: Netherlands

institute: Radboudumc

summary: Klotho knock-out mice are an important model for CKD-induced calcification. In CKD, serum magnesium (Mg2+) inversely correlates with vascular calcification. This study aims to determine the effects of Mg2+ on aortic calcification in Klotho knock-out mice. Klotho knock-out mice were treated with either a minimal or a high Mg2+ diet from birth. After eight weeks, serum biochemistry was studied and organs were harvested. Protective effects of Mg2+ were characterized by RNA-sequencing of aortic tissue. Micro-CT analysis was performed to study bone integrity. High Mg2+ diet prevented vascular calcification and reduced aortic gene expression of Runx2 and matrix Gla protein, demonstrating the protective effect on pro-osteogenic signaling. Differential expression of inflammation and extracellular matrix remodeling genes accompany the beneficial effects of Mg2+ on calcification. High dietary Mg2+ did not affect serum parathyroid hormone, vitamin D3 and calcium. High Mg2+ intake prevented calcification despite increasing fibroblast growth factor-23 and phosphate concentration in knock-out mice. In addition, mice on the high Mg2+ diet had a 20% reduced femoral bone mineral density and increased osteoid formation indicating osteomalacia, while osteoclast activity was decreased in Klotho knock-out mice. In Saos-2 osteoblasts, Mg2+ supplementation reduced mineralization independent of osteoblastic matrix production, alkaline phosphatase activity and maturation markers alpha-1 type-I collagen and sclerostin. In conclusion, high dietary Mg2+ prevents calcification in Klotho knock-out mice. These effects are potentially mediated by reduction of inflammatory and extracellular matrix remodeling pathways in the aorta. Mg2+ treatment is promising to prevent vascular calcification, but the risk for osteomalacia should be considered.

overall_design: Both wild-type (n=6 for each diet) and Klotho knock-out (n=6 for each diet) mice were treated with either a minimal (0.05% w/w) or a high magnesium diet (0.48% w/w) and treated for 8 weeks from brith to ensure maximal exposure. After 8 weeks the mice were sacrificed and the aorta was harvested, cleaned and snap-frozen in liquid nitrogen. Samples were homogenized in TRIreagent for RNA isolation and RNA was sequenced at BaseClear Leiden B.V. The Netherlands. Wild-type mice on a minimal magnesium diet served as control group for the analysis.

first: Anique

last: ter Braake

middle: H

first: Joost

middle: G

last: Hoenderop

first: Wynand

last: Alkema


title: Functional enhancers shape extrachromosomal oncogene amplifications

status: Public on Nov 25 2019

city: Cleveland

first: Peter

last: Scacheri

address: 2109 Adelbert Road

department: Genetics and Genome Sciences

institute: Case Western Reserve University

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct


title: RNA-seq Transcriptome Analysis of AD169 and AD169-ΔUL26 infected MRC5 fibroblasts.

status: Public on Sep 12 2019

city: Rochester

first: Joshua

last: Munger

state: New York

address: 601 Elmwood Ave, Room 3-8828

department: Biochemistry & Biophysics

institute: University of Rochester

summary: We employed RNA-seq to map the transcriptome of human MRC5 fibroblasts during HCMV infection with AD169 and AD169-ΔUL26 strains. These data will highlight the ways in which the HCMV UL26 protein alters host gene transcripton during infection.

overall_design: Infect quiescent MRC5 fibroblasts with HCMV AD169 and AD169-ΔUL26 strains, in 15-cm dishes at MOI = 3 and harvest samples for RNA-seq at 48 hpi.

first: Xenia

last: Schafer


title: mRNAseq in control (WT) and Nes:Cre_Qk cKO

status: Public on Apr 17 2019

city: Niigata

first: Masato

last: Yano

address: 757, Ichibancho, Asahimachidori, Chuo-ku, Niigata-shi,

department: Division of Neurobiology and Anatomy

institute: Niigata University

summary:
We sequenced mRNA from mouse E14.5 embryonic cortex to compare gene expression level and alternative splicing events between 2 control (WT) and 2 Qk cKO.
A set of tissue specific splicing factors are thought to govern alternative splicing events during neural progenitors (NPC) to neuron transition by regulating neuron specific exons. Here we proposed one such a factor, RNA-binding protein Qki5, which is specifically expressed in neural stem cells. We performed mRNAseq analysis by using mRNAs obtained from developing cerebral cortices in Qk conditional knockout  (cKO) mice. Expectedly, we found huge numbers of alternative splicing changes between control and conditional knock-out relative to that of transcripts level changes. Furthermore, DAVID and Meta-scape analysis revealed that affected spliced genes are involved in axon-development and microtubule-based process. Among these, Ninein protein coding mRNA is listed as a Qk protein dependent alternative splicing targets. Interestingly, this exon encodes very long poly-peptides (2,121 nt) and is known as a previously defined dynamic RNA switch during NPC-to-neuron transition. In addition, we validated that the regulation of this large exon is consistent with Qki5 dependent alternative exon inclusion mode obtained from our previous Qki5 HITS-CLIP analysis. Together Qki5 will add to a list factor of alternative splicing in NPC-to-neuron transition.

overall_design: mRNA profiles obtained from 2 different control(WT) and 2 Qk cKO were generated by deep sequencing using Illumina NextSeq500.

first: Yoshika

last: Hayakawa-Yano


title: MicroRNA array analysis of Pbx1-deficient and control murine HSCs and Flk2neg MPPs

status: Public on Apr 01 2019

city: Rozzano

first: Francesca

last: Ficara

state: MI

address: via Manzoni 56

country: Italy

institute: CNR/Istituto Clinico Humanitas

summary: The balance of self-renewal and differentiation is crucial to ensure the homeostasis of the hematopoietic system, and is a key hallmark of hematopoietic stem cells (HSCs); however, the underlying molecular pathways are not completely understood, including the role of micro-RNAs. To assess micro-RNA contributions, we performed micro-RNA profiling of HSCs and their immediate downstream progeny multi-potent progenitors (MPPs) from wild type control and Pbx1-conditional knockout mice, whose HSCs display a profound self-renewal defect.

overall_design: RNA was extracted HSCs and Flk2-MPPs sorted from the BM of Polyinosinic-polycytidylic acid [poly(I:C)]-treated Mx1Cre+Pbx1f/f and Mx1Cre-Pbx1f/f control mice (four experimental groups, 4-5 samples from individual mice/group). miRNA profiling was performed using the Megaplex TaqMan Assay system coupled with PreAmplification step, Rodent Pool A. The expression level of 376 miRNAs plus 8 controls was obtained.

first: Laura

last: Crisafulli


title: CRISPRi proliferation dropout screen of EGFR cis-regulatory elements

summary: Here we have used using a pooled proliferation dropout screen with KRAB-dCas9 to determine the contribution of cis-regulatory elements around EGFR to cell fitness in EGFR unamplified (GSC23) and amplified (GBM3565) glioblastoma .

overall_design: Pooled CRISPR interference screen using KRAB-dCas9 tiling densely across regulatory elements

first: Andrew

last: Morton

first: Zachary

middle: J

last: Faber


title: Differential DNA Methylation in High Grade Serous Ovarian Cancer (HGSOC) is associated with Tumor Behavior

status: Public on Jul 01 2019

city: Iowa City

first: Henry

last: Reyes

state: Iowa

address: 200 Hawkins Drive

department: OBGYN

institute: University of Iowa

type: Methylation profiling by genome tiling array

summary:
Introduction/ Background: The epigenome represents and adds another facet of complexity to cancer that needs to be understood to categorize patients into those at risk of disease, recurrence, or treatment failure.  Our goal is to compare DNA methylation status between controls vs HGSOC, and relate it with clinical outcomes.
Methodology: A retrospective review of our institution’s advanced/ recurrent HGSOC patients yielded 99 cases with good quality DNA and RNA.  12 normal fallopian tubes were also collected and used as controls. Infinium Illumina methylationEPIC was used to characterize DNA methylation status and RNA seq to evaluate gene expression. T- tests were used to compare methylation patterns between controls vs HGSOC, primary vs recurrent, and optimal vs suboptimal surgical outcomes. Spearman’s rank correlation was used to evaluate association between degree of methylation and expression of identified genes. Validation of our findings used the cancer genome atlas (TCGA) database followed by C-statistics to assess degree of agreement.
Results: Out of 66,069 methylation probes that interrogate known genes, 5,852 probes were significantly different between normal and HGSOC. This includes genes that are enriched in several pathways such as the RAS signaling pathway. A similar analysis of the TCGA database showed 2,075 differentially methylated probes. 1,891 probes were significant in both datasets giving a 70.1% degree of agreement. When comparing differential DNA methylation between primary and recurrent disease, there were 57 probes which represent 17 genes that were significantly different. When comparing optimal vs suboptimal surgical outcomes, 99 probes were significantly different wherein 29 genes show expected inverse correlation between methylation status and gene expression.
Conclusions: There are significant differences in methylation patterns between HGSOC and fallopian tubes, primary vs recurrent tissues, and optimal vs sub-optimal surgical outcomes. Cataloging these phenomena in a well characterized clinical population will aid in determining groupings for precision medicine treatment cohorts in the future.

overall_design: DNA methylation profiles of 99 HGSOC tumor samples and 12 normal fallopian tube controls were generated using Infinium Illumina methylationEPIC arrays

first: Jesus

last: Gonzalez-Bosquet

first: Eric

last: Devor


title: A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment.

status: Public on Mar 27 2019

city: Zwijnaarde

first: Liesbet

last: Martens

address: Technologiepark 927

department: VIB Inflammation Research Center

country: Belgium

institute: VIB-University of Ghent

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

overall_design: Refer to individual Series


title: Analysis of chromatin interactions to define the HoxB landscape in ESCs and mouse embryos

first: Fatima

last: Sanchez-Cabo

summary: The goal is to examine the interactions at chromatin level between two specific Oct4/Nanog binding-sites in the vicinity of Hoxb1 in ESCs and E9.5 mouse embryos.

overall_design: In order to analyse the specific interactions at chromatin level between Oct4/Nanog binding-sites near Hoxb1 gene, G4 cells and mouse embryos were collected at E9.5 by biological duplicates per site and model.

first: Elena

last: Lopez-Jimenez

first: Raquel

last: Rouco

first: Miguel

last: Manzanares


title: RNA Sequencing Data in control and Acvr1:Nfatc1Cre mouse aortic valve tissues (4 months old)

status: Public on Nov 02 2019

city: Ann Arbor

first: Richard

last: McEachin

state: United States

address: 2800 Plymouth Road

department: DCM&B

institute: University of Michigan

summary: Aortic valves were microdissected from control and Acvr1:Nfatc1Cre mutants (n=3) and subjected to RNA-seq assay

overall_design: Expression profiling by high throughput sequencing

first: Vesa

last: Kaartinen


title: An Exome-Wide Association Study Identifies New Susceptibility Loci for the Risk of Nicotine Dependence in African-American Populations

status: Public on Apr 10 2020

city: Hangzhou

first: Yi

last: Xu

state: Zhejiang

address: No. 17, Dazhi Road, old Zhejiang, Shangcheng District

department: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases

institute: The First Affiliated Hospital, Zhejiang University School of Medicine

type:
Genome variation profiling by array
SNP genotyping by SNP array

summary: Cigarette smoking is one of the largest causes of preventable death worldwide. Smoking behaviors, including age at smoking initiation (ASI), smoking dependence (SD), and smoking cessation (SC), are all complex phenotypes determined by both genetic and environmental factors as well as their interactions. To identify susceptibility loci for each smoking phenotype, numerous studies have been conducted, with approaches including genome-wide linkage scans, candidate gene-based association analysis, and genome-wide association study (GWAS). Therefore, we conducted an exome-wide association study to identify new susceptibility loci for the risk of nicotine dependence in African-American populations.

overall_design: To reveal the molecular mechanism underling each smoking phenotype, we used high-throughput approaches such as exome-based association study to identify genetic variants that contribute to nicotine dependence and other smoking-related phenotypes. First, we evaluated each common variant individually with a univariate statistic; i.e., logistic and linear regression models. Second, rare variants were grouped by genomic regions and analysed using burden tests, i.e., the Weighted Sum Statistic (WSS). Third, we tested for combined effects of rare and common variants with a unified statistical test that allows both types of variants to contribute fully to the overall test statistic.

first: Ming

last: Li


title: Embryonic Atrazine Exposure Causes Behavioral, Transcriptomic, Epigenetic, and Pathological Alterations in Adult Zebrafish Brain [male]

first: Jennifer

last: Freeman

summary: According to the developmental origins of health and disease (DOHaD) hypothesis, exposure to environmental stressors during early development can cause genetic, epigenetic, or functional changes in tissues that increase disease risk later in life. Atrazine (ATZ) is a commonly used pesticide that frequently contaminates rural and urban water sources at levels above the 3 ppb maximum contaminant level set by the US Environmental Protection Agency. Exposure to ATZ is linked to endocrine disruption, cancer, changes in genome methylation, and alterations in neurochemistry and behavior. This study tests the hypothesis that embryonic exposure to ATZ results in sex-specific changes in behavior, the adult brain transcriptome, and adult body and brain pathology, according to the DOHaD hypothesis. Zebrafish (Danio rerio) embryos were exposed to 0, 0.3, 3, or 30 ppb (ppb; µg/L) ATZ during the period from fertilization through 72 hours post fertilization (hpf), and then were rinsed and raised to maturity with no further exposure. At 9 months post fertilization (mpf), a novel tank test, a light-dark box, and an open field test evaluated adult behavior. Transcriptomic analysis investigated ATZ related differences in gene expression and the brain was evaluated histopathologically for morphometric alterations in the area of the dorsal telencephalon, posterior tuberculum, and raphe populations. At 14 mpf, the body length, weight, and brain weight was measured to evaluate effects of ATZ on mature body and brain size. The 9 mpf adult behavioral tests found non-monotonic, sex-specific behavior changes, with male zebrafish having decreased activity and female zebrafish having increased signs of anxiety. Transcriptomic analysis identified sex-specific alterations, with females having altered expression of genes in pathways related to cancer and organismal injury and males having altered gene expression in organismal development and reproductive system development and function pathways. Morphometric analysis identified a decreased number of cells in male raphe populations and adult zebrafish also had non-monotonic, sex-specific alterations in body length, body weight, and brain weight. This results suggests that developmental exposure to ATZ does cause sex-specific alterations in adult neural function.

overall_design: We treated zebrafish embryos from approximately 1 hour post fertilization through 72 hours post fertilization (embryogenesis) with 0, 0.3, 3, or 30 ppb atrazine. Following the 72 hour exposure period, larvae were rinsed and reared to 9 months post fertilization. After zebrafish were euthanized, the brains were removed and processed for transcriptomic analysis.

first: Katharine

last: Horzmann

first: Li

middle: F

last: Lin

first: Boghos

last: Taslakjian

first: Chongli

last: Yuan


title: Ferritin regulation upon ETS-4/SPDEF depletion promotes cold survival in C. elegans

status: Public on May 29 2019

city: Oslo

first: Rafal

last: Ciosk

state: Oslo

address: Blindernveien 31

department: Department of Biosciences

country: Norway

institute: University of Oslo

summary: In this study, we subjected wild type worms and worms deficient in ETS-4, ETS-4 and DAF16, ETS-4 and PQM-1, to cold treatment  and analyzed their transcriptional profiles by RNAseq.

overall_design: Wild type and mutants with or without cold treatment were subject to RNAseq

first: Tina

last: Pekec

first: Yanwu

last: Guo


title: Frailty in middle age is associated with race-specific changes to the transcriptome.

status: Public on Aug 21 2019

city: Baltimore

first: Supriyo

last: De

state: Maryland

address: 251 Bayview Blvd

department: Laboratory of Genetics and Genomics

institute: NIA-IRP, NIH

summary: Frailty is an aging-associated syndrome resulting from diminished capacity to respond to stressors, disrupted homeostasis. It is a significant risk factor for disability and mortality. Although frailty is usually studied in old age, it is present in mid-life. Given the increases in mortality statistics among middle-aged Americans, understanding molecular drivers of frailty in a younger, diverse cohort may facilitate identifying pathways for early intervention. We analyzed frailty-associated, genome-wide transcriptional changes in middle-aged African Americans (AAs) and whites. Next generation RNA sequencing was completed using total RNA from peripheral blood mononuclear cells. We analyzed differential gene expression patterns and completed a parametric analysis of gene set enrichment (PAGE). Differential gene expression was validated using RT-qPCR. We identified 5,082 genes differentially expressed with frailty. Frailty altered gene expression patterns and biological pathways differently in AAs and whites, including inflammatory and immune response pathways. The validation study showed a significant two-way interaction between frailty, race, and expression of the cytokine IL1B and the transcription factor EGR1. The glucose transporter, SLC2A6, the neutrophil receptor, FCGR3B, and the accessory protein, C17orf56, were decreased with frailty. These results suggest that there may be demographic dependent, divergent biological pathways underlying frailty diagnosis in middle-aged adults.

overall_design: Total RNA was sequenced from PBMCs from middle-aged non-frail (mean age=48) and frail (mean age=47.8) African Americans and whites.

first: Calais

middle: S

last: Prince

first: Nicole

last: Noren Hooten

first: Nicolle

last: Mode

first: Yongqing

last: Zhang

first: Ngozi

last: Ejiogu

first: Kevin

last: Becker

first: Alan

last: Zonderman

first: Michele

last: Evans


title: microRNA and mRNA gene expression signature in JK and JinB8 cell lines

status: Public on Sep 30 2019

city: BETHESDA

first: abdel

last: Elkahloun

address: 50, SOUTH DRIVE

institute: NHGRI-NIH

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


title: A global transcriptome analysis of human epidermal keratinocytes upon overexpression of microRNA-34a or microRNA-34c

status: Public on Sep 04 2019

city: Stockholm

first: Ning

last: Xu

address: CMM L8:02

country: Sweden

institute: Karolinska Institutet

summary:
miR-34a and miR-34c were found up-regulated at wound-edges of human venous ulcer compared to nomal wound and the intact skin; however their biological role in keratinocytes during wound repair has not been studied.
To study the genes regulated by miR-34a and miR-34c, we transfected miR-34a and miR-34c mimic into human primary epidermal keratinocytes to overexpress them.
We performed a global transcriptome analysis of keratinocytes upon overexpression of miR-34a or miR-34c using Affymetrix arrays.

overall_design: Expression profiling of primary human epidermal keratinocytes transfected with 20nM miR-34a mimics (miR-34a) or 20nM miR-34c mimics (miR-34c) or 20nM control oligos (miR-con) for 48 hours was performed using Affymetrix GeneTitan system.

middle: X

last: Landén


title: A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment. [scRNA-Seq]

first: Liesbet

last: Martens

summary: While the roles of parenchymal microglia in brain homeostasis and disease are fairly clear, other brain-resident myeloid cells remain less understood. By dissecting border regions and combining single-cell RNA sequencing with high-dimensional cytometry, bulk RNA-sequencing, fate-mapping and microscopy, we reveal the diversity of non-parenchymal brain macrophages. Border-associated macrophages (BAMs) residing in the dura mater, subdural meninges and choroid plexus consisted of distinct subsets with tissue-specific transcriptional signatures, and their cellular composition changed during postnatal development. BAMs exhibited a mixed ontogeny and subsets displayed distinct self-renewal capacities upon depletion and repopulation. Single-cell and fate-mapping analysis both suggested there is a unique microglial subset residing on the apical surface of the choroid plexus epithelium. Finally, gene network analysis and conditional deletion revealed IRF8 as a master regulator that drives the maturation and diversity of brain macrophages. Our results provide a framework for understanding host-macrophage interactions in the healthy and diseased brain.

overall_design: sample of WT choroid plexus, sample of WT dura mater, sample of WT enriched SDM, sample of WT whole brain, sample of 9 months old APP/PS1 mice, sample of 16 months old APP/PS1 mice, sample of 16 months old WT mice, sample of Irf8 KO whole brain, sample of Irf8 KO choroid plexus, sample of Irf8 WT whole brain, sample of Irf8 WT choroid plexus, sample of dura mater with standard protocol and with ActD protocol, sample of choroid plexus with standard protocol and ActD protocol.

first: Hannah

last: Van Hove

first: Isabelle

last: Scheyltjens

first: Karen

last: De Vlaminck

first: Ana

last: Pombo Antunes

first: Sofie

last: De Prijck

first: Niels

last: Vandamme

first: Sebastiaan

last: De Schepper

first: Gert

last: Van Isterdael

first: Charlotte

last: Scott

first: Jeroen

last: Aerts

first: Geert

last: Berx

first: Guy

middle: E

last: Boeckxstaens

first: Roosmarijn

last: Vandenbroucke

first: Lars

last: Vereecke

first: Diederik

last: Moechars

first: Martin

last: Guilliams

first: Jo

last: Van Ginderachter

first: Yvan

last: Saeys

first: Kiavash

last: Movahedi


title: Analysis of Exosomal microRNA from SG and FaDu cells

status: Public on May 31 2019

city: Taipei

first: Hsieh

last: Chia-Hsin

address: No.155, Sec.2, Linong Stree

country: Taiwan

institute: National Yang-Ming University

summary: Tumor-secreted exosomes have been noted to be critically involved in remodeling tumor microenvironments. In this study we investigated whether Snail-expressing cancer cells-secreted exosomes modulate the inflammasome activity in macrophages.

overall_design: Exosomes have been successfully purified from cell culture conditioned medium by differential ultracentrifugation.

first: Muh-Hwa

last: Yang

first: Chia-Hsin

last: Hsieh


title: HNF1A deficiency impairs β-cell fate, granule maturation and function

status: Public on Mar 16 2019

city: New York

first: Dieter

last: Egli

address: 701 West 168th Street

country: USA

institute: Columbia University

summary: Mutations in HNF1A cause Maturity Onset Diabetes of the Young type 3, the second most frequent form of diabetes caused by single gene mutation. We generated human pancreatic stem cell-derived endocrine cells with mutations in HNF1A and show that HNF1A deficiency impairs scβ-cell fate, insulin granule maturation and the secretion of insulin in a glucose responsive manner. Single-cell RNA sequencing reveals that HNF1A orchestrates a network of genes involved in glucose metabolism, zinc transport, calcium ion binding and hormone exocytosis. Furthermore, in both patients and stem cell-derived β-cells, HNF1A deficiency altered the stoichiometry of secreted c-peptide to insulin. Sulfonylurea, used in the treatment of these patients, restored both insulin secretion and stoichiometry. Significantly, uncoupling of c-peptide and insulin secretion as described here questions the common practice in using c-peptide as a proxy to evaluate β-cell function. We also demonstrate that correction of the HNF1A locus restores function, providing a path to cell therapy.

overall_design:
Human embryonic stem cells with different HNF1A genotypes (WT, KO1, KO2, R200Q homozygous) were differentiated into islet-like clusters of endocrine cells for 27-28 days in vitro. First set of 6 samples, clusters of islet-like cells were dissociated into single cells and analyzed by single cell RNA sequencing. There are two WT, two KO and two R200Q samples.

Second set of 5 samples, clusters of islet-like cells were dissociated into single cells and insulin producing cells were purified by FACS sorting for INS-GFP. Cells were analyzed by bulk RNA sequencing. There are three WT and two KO.

first: Bryan

last: González

first: Haoquan

last: Zhao

first: Jaeyop

last: Lee

first: Charles

last: LeDuc

first: Chris

middle: N

last: Goulbourne

first: Xiaojuan

last: Chen

first: Wendy

last: Chung

first: Agata

last: Jurczyk

first: Jesper

last: Gromada

first: Yufeng

last: Shen

first: Robin

last: Goland

first: Rudolph

last: Leibel


title: HNF1A deficiency impairs β-cell fate, granule maturation and function (scRNA-seq of 309 hESC-derived cells: Differentiation day 25)

status: Public on Apr 12 2019

overall_design: Human embryonic stem cells with different HNF1A genotypes (WT, KO1 and KO2, HET) were differentiated into islet-like clusters of endocrine cells for 25 days in vitro. Clusters of islet-like cells were dissociated into single cells and insulin producing cells were purified by FACS sorting for INS-GFP. Cells were analyzed by single cell RNA sequencing.


title: Expression data from wt, pop2, pbp1, and mpt5-deletion yeast cells.

status: Public on Mar 01 2019

city: Tsukuba

first: Kenji

last: Irie

state: Ibaraki

address: 1-1-1 Tennodai

institute: University of Tsukuba

summary: The S. cerevisiae Pop2 protein is an exonuclease in the Ccr4-Not complex that is a conserved regulator of gene expression. Pop2 regulates gene expression post-transcriptionally by shortening the poly(A) tail of mRNA. A previous study has shown that Pop2 is phosphorylated at threonine 97 (T97) by Yak1 protein kinase in response to glucose limitation. However, the physiological importance of Pop2 phosphorylation remains unknown. In this study, we found that Pop2 is phosphorylated at serine 39 (S39) under unstressed conditions. The dephosphorylation of S39 was occurred within 1 min after glucose depletion, and the addition of glucose to the glucose-deprived culture recovered this phosphorylation, suggesting that Pop2 phosphorylation at S39 is regulated by glucose. We previously reported that Pop2 takes a part in the cell wall integrity pathway by regulation of LRG1 mRNA; however, S39 phosphorylation of Pop2 is not involved in LRG1 expression. On the other hand, Pop2 phosphorylation at S39 is involved in the expression of HSP12 and HSP26, encoding small heat shock proteins. In medium supplemented with glucose, Pop2 might be phosphorylated at S39 by Pho85 kinase to repress the expression of HSP12 and HSP26. Glucose starvation inactivated Pho85, which resulted in the derepression of HSP12 and HSP26. Thus, Pop2 phosphorylation at S39 is important for Pop2 to repress the expression of stress response genes, HSP12 and HSP26, in the presence of glucose. Our results suggest that Pop2 phosphorylation by Pho85 kinase is a part of the glucose sensing system in yeast.

platform_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae

overall_design: Wild type, pop2, pbp1, mpt5 cells were grown in YPD medium to mid-log phase, then shifted to YPGL medium. Total RNAs ere extracted and subjected to microarray analysis.

first: Yasuyuki

last: Suda


title: Next Generation Sequencing Facilitates Quantitative Analysis of 0 and 5 Gy HuR binding RNAs

status: Public on Feb 22 2019

city: suzhou

first: zhang

middle: shu

last: yu

address: No. 199, Ren'ai Road

department: soochow university

country: China

institute: Soochow University

summary:
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of RNA. The goals of this study are to compare HuR binding RNAs between 0 or 5 Gy irradiation, and analyze its effect on RNA expression.
Methods: Human skin fibroblast cell line WS1 cells were treated with 0 or 5 Gy irradiation. After 24 h, RNA expression was measured using using Illumina HiSeq4000. Meanwhile, RIP was performed using HuR antibody. HuR bound mRNAs after 0 or 5 Gy irradiation was  measured using using Illumina HiSeq4000.
Results: RIP-sequencing reveals HuR binding RNAs between 0 or 5 Gy irradiation in WS1 cells. RNA sequencing reveals dyeregulated RNAs between 0 and 5 Gy irradiation.
Conclusions: Our study represents the first detailed analysis of HuR binding RNAs between 0 and 5 Gy irradiation generated by RNA-seq technology. This study contributes to our understanding of the role of HuR inresponse to radiation.

overall_design: The goals of this study are to compare HuR binding RNAs between 0 or 5 Gy irradiation, and analyze its effect on mRNA expression. The binding of HuR to the RNAs between 0 and 5 Gy irradiation were generated by RIP and deep sequencing,  using Illumina HiSeq4000. Meanwhile, RNA expression was also measured using Illumina HiSeq4000.

first: Shuyu

last: Zhang


title: Gene expression profiles of glomerular endothelial cells support their role in the glomerulopathy of diabetic mice

status: Public on Dec 01 2018

first: Chengguo

last: Wei

address: 1428 Madison Ave1468 Madison Ave

department: Medicine

institute: Icahn School of Medicine at Mount Sinai

summary: Endothelial dysfunction promotes the pathogenesis of diabetic nephropathy (DN), which is considered to be an early event in disease progression. However, the molecular changes associated with glomerular endothelial cell (GEC) injury in early DN are not well defined. Most gene expression studies have relied on the indirect assessment of GEC injury from isolated glomeruli or renal cortices. Here, we present transcriptomic analysis of isolated GECs, using streptozotocin-induced diabetic wildtype (STZ-WT) and diabetic eNOS-null (STZ-eNOS−/−) mice as models of mild and advanced DN, respectively. GECs of both models in comparison to their respective nondiabetic controls showed significant alterations in the regulation of apoptosis, oxidative stress, and proliferation. The extent of these changes was greater in STZ-eNOS−/− than in STZ-WT GECs. Additionally, genes in STZ-eNOS−/− GECs indicated further dysregulation in angiogenesis and epigenetic regulation. Moreover, a biphasic change in the number of GECs, characterized by an initial increase and subsequent decrease over time, was observed only in STZ-eNOS−/− mice. This is consistent with an early compensatory angiogenic process followed by increased apoptosis, leading to an overall decrease in GEC survival in DN progression. From the genes altered in angiogenesis in STZ-eNOS−/− GECs, we identified potential candidate genes, Lrg1 and Gpr56, whose function may augment diabetes-induced angiogenesis. Thus, our results support a role for GEC in DN by providing direct evidence for alterations of GEC gene expression and molecular pathways. Candidate genes of specific pathways, such as Lrg1 and Gpr56, can be further explored for potential therapeutic targeting to mitigate the initiation and progression of DN.

overall_design: RNA-seq of eNOS-null mice with or without STZ treatment

first: Jia

last: Fu

first: Weijia

first: Detlef

last: Schlondorff

first: Jinshan

last: Wu

first: Minchao

last: Cai

first: Wu

last: He

first: Margaret

last: Baron

first: Peter

middle: Y

last: Chuang

first: Zhihong

last: Liu

first: John

middle: C

first: Kyung


title: West Virgina Chemical Spill: 5-Day Rat Toxicogenomic Studies

status: Public on Oct 15 2018

city: Durham

first: Scott

last: Auerbach

address: 111 TW Alexander Drive

institute: Division of the National Toxicology Program at NIEHS

summary: As part of the West Virginia Chemical Spill research program, NTP evaluated three chemicals that were spilled into the Elk Rever in West Virginia for their ability to cause toxicity or biological changes in a short-term toxicogenomic study

overall_design:
At each of six dosages (0.1,1,10,100,300 and 500 mg/kg body weight(bw) for MCHM and crude MCHM) together with vehicle control (MCHM,crude MCHM,PPH 0 mg/kg;corn oil), 6-8 week old male, Harlan Sprague Dawley rats received the test article via gavage for 5 consecutive days.
contributor: National Toxicology Program


title: Fatal Asthma and Non-Asthma Donor-Derived Airway Smooth Muscle Transcriptome Response to Glucocorticoid Treatment

status: Public on Dec 31 2018

city: Philadelphia

first: Blanca

last: Himes

address: 423 Guardian Dr

department: Department of Biostatistics, Epidemiology and Informatics

institute: University of Pennsylvania

summary:
Asthma is a chronic inflammatory respiratory disease affecting over 300 million people around the world. Some asthma patients remain poorly controlled by conventional therapies and experience more life-threatening exacerbations. While patients with severe, refractory disease represent a heterogeneous group, a feature shared by most includes glucocorticoid insensitivity.  We sought to characterize differences in the airway smooth muscle transcriptome response to glucocorticoids in fatal asthma vs. non-asthma donors.
RNA-Seq was used to measure airway smooth muscle transcript expression differences between 9 donors with fatal asthma and 8 non-asthma donors. Cells from each donor were treated with budesonide or with vehicle control.  Poly(A)-selected RNA-Seq libraries were prepared with the Illumina TruSeq method. An Illumina HiSeq 2500 instrument was used to generate 125 base pair paired-end reads.

overall_design: Transcriptome profiles obtained via RNA-Seq for airway smooth muscle cells from 9 fatal asthma and 8 non-asthma donors treated with budesonide (100nM for 24h) or vehicle control were compared