title: Molecular subtypes in gastric cancer. [III]

city: Seoul

first: Yong-Min

last: Huh

address: 50 Shinchon-ro

institute: Yonsei University

summary: We identified the molecular subtypes and conserved modules in gastric cancer by unsupervised clustering algorithm. We defined six molecular signatrues of gastric cancer associated with the biological heterogeneity of gastric cancer and clinical outcome of patients.

overall_design: We obtained gene expression profile of gastrectomy samples from 401 gastric cancer patients by HumanHT-12 v3.0 Expression BeadChip array (Illumina). Total RNA was extracted from the fresh-frozen gastrectomy specimens at the Yonsei University Severance Hospital (South Korea) between 2000 and 2010.

first: Jae-Ho

last: Cheong

first: Eunji

last: Jang

first: Hyunki

last: Kim

first: Jungmin

last: Park

first: Jungeun

first: Hyeseon

first: Youngmin

last: Shin

first: Hye-Young

last: Son

first: Yoon

middle: Y

last: Choi

first: Woo

last: Hyung

first: Sung

last: Noh

first: Jin-Suck

last: Suh


title: Dynamic changes of gene expression in the liver during ruminant evolution

status: Public on Sep 15 2022

city: Beijing

first: Siqian

last: Chen

address: 2rd, Yuanmingyuan West Road

department: College of Animal Science and Technology

country: China

institute: China Agricultural University

type: Expression profiling by high throughput sequencing

summary: To investigate the evolutionary changes of  gene expression in ruminants, we performed gene expression profiling analysis using RNA-seq data of liver from three ruminants.

sample_organism:
Bos taurus
Capra hircus
Ovis aries

platform_organism:
Bos taurus
Capra hircus
Ovis aries

overall_design: Comparative gene expression profiling analysis of RNA-seq data for three ruminants.

first: Ying

last: Yu


title: Comparative analysis of the testis tissue transcriptome of 4-year-old yak and cattle-yak

status: Public on Jul 23 2022

city: Lanzhou

first: shaoke

last: guo

state: Gansu

address: West Lake Street

department: Lanzhou institute of husbandry and pharmaceutical sciences

institute: Chinese Academy of Agricultural Sciences

summary: RNA sequence analysis identified a total of 8473 differentially expressed genes (DEGs) (3580 up-regulated, 4893 down-regulated), and GO annotation and KEGG enrichment of differential genes found that DEGS were mostly related to spermatogenesis and apoptosis. Among them, Spermatogonia stem cell (SSCs) marker genes (ITGA5, Gfra1, CD9, SOHLH1, SALL4, ID4 and FOXO1) were significantly up-regulated, differentiation spermatogenic cell marker genes (KIT, UCHL1, Ccna1, TNP1 and TXNDC2) were significantly down-regulated, and genes involved in apoptosis (Fas, CTSK, CTSB, CTSC, CTSO, caspase 3, caspase6, and caspase) were significantly up-regulated. Furthermore, the AS events in cattle-yak are significantly lower than in yak, we speculate that lack of mRNA and protein subtypes may lead to spermatogenic arrest in yak testicle.

sample_organism:
Bos grunniens
Bos grunniens x Bos taurus

overall_design: RNA-seq of yak and cattle-yak testis tissue.

first: Mengli

last: Cao

first: Xian

last: Guo

first: Jie

last: Pei


title: Deciphering the Impact of Genetic Variation on Human Polyadenylation using APARENT2

status: Public on Oct 08 2022

city: seattle

first: Samantha

last: Koplik

email: skoplik@uw.edu, kopliksam@gmail.com

state: Washington

address: 185 Stevens Way

department: Electrical and Computer Engineering

country: USA

institute: University of Washington

summary:
Genetic variants that disrupt polyadenylation can cause or contribute to genetic disorders. Yet, due to the complex cis-regulation of polyadenylation, variant interpretation remains challenging. Here, we introduce a residual neural network model, APARENT2, that can infer 3’-cleavage and polyadenylation from DNA sequence more accurately than any previous model. This model generalizes to the case of alternative polyadenylation (APA) for a variable number of polyadenylation signals. We demonstrate APARENT2’s performance on several variant datasets, including functional reporter data and human 3’ aQTLs from GTEx. We apply neural network interpretation methods to gain insights into disrupted or protective higher-order features of polyadenylation. We fine-tune APARENT2 on human tissue-resolved transcriptomic data to elucidate tissue-specific variant effects. By combining APARENT2 with models of mRNA stability, we extend aQTL effect size predictions to the entire 3’ untranslated region. Finally, we perform in-silico saturation mutagenesis of all human polyadenylation signals and compare the predicted effects of >44 million variants against gnomAD. While loss-of-function variants were generally selected against, we also find specific clinical conditions linked to gain-of-function mutations. For example, we detect an association between gain-of-function mutations in the 3’-end and Autism Spectrum Disorder. To experimentally validate APARENT2’s predictions, we assayed clinically relevant variants in multiple cell lines, including microglia-derived cells.
References and variant APA libraries were cloned into a reporter. APA profiling data was obtained from RNA-seq of 3 different cell lines (HEK293T, SK-N-SH, and HMC3)  with 2 replicates of each library. Polyadenylation  cleavage position was determined for mapped reads, and then UMIs were collapsed to determine measured variant log odds ratio of cleavage.

overall_design: To experimentally validate APARENT2 predictions, we measured the impact of 100 clinically relevant variants (including Autism case variants) in a plasmid reporter MPRA in HEK293T, SK-N-SH and HMC3 cell lines.

first: Johannes

last: Linder

middle: E

first: Anshul

last: Kundaje

first: Georg

last: Seelig


title: Endocrine resistance and breast cancer plasticity are controlled by CoREST

status: Public on Aug 01 2022

city: Miami

first: Liliana

last: Garcia-Martinez

state: Florida

address: 1501 NW 10th Avenue

department: Human Genetics

institute: University of Miami

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Using a new model system to track evolution of resistance from ER+ to ER-, we show that the LSD1/CoREST complex is a key determinant for luminal-to-basal reprogramming independently on LSD1’s enzymatic activity.

overall_design: RNAseq experiments of T47D cells grown in estrogen deprived conditions for 3 days and up to 8 months. RNAseq experiments in T47D cells and long term estrogen deprived conditions after LSD1 KO using CRISPR/Cas9 as well as treatment with  LSD1/CoREST inhibitors SP2509 and Corin. ChIPseq of LSD1/ H3K27ac during resistance evolution (T47D cells in media with estrogen and estrogen deprived (LTED6M, LTED6M CD44 sorted cells and LTED9M)). ChIPseq of ERα, FOXA1, RCOR1, RNApol in T47D cells and RCOR1/SMARCC1/cjun, RNApolII, H3K4me2 in estrogen deprived cells for 9 months or fully reprogrammed cells. LSD1, cjun ChIPseq in T47D cells fully reprogrammed after stable knockdown of cjun. LSD1, cjun, H4K4me2 ChIPseq in fully reprogrammed cells with LSD1 KO by CRISPR/Cas9 . ATACseq in Parental T47D cells with wildtype LSD1 or knockout. ATACseq in reprogrammed cells with wildtype LSD1 or knockout as well as LSD1 knockdown and rescue with wildtype LSD1 or catalytic dead mutant. H3K4me1 and H3K27ac CUT and RUN experiment performed in the same samples used for ATACseq. LSD1 ChIPseq from fresh tissue from a patient that develop recurrent tumor after 5 years of tamoxifen treatment

first: Andrew

middle: M

last: Adams

first: Ho

middle: L

last: Chan

first: Yuichiro

last: Nakata

first: Natalia

last: Weich

first: Stephanie

last: Stransky

first: Mohammed

last: Alshalalfa

first: Zhao

last: Zhang

first: Toni

last: Celià-Terrassa

first: Susan

last: Kesmodel

first: Zhijie

last: Liu

first: Brandon

middle: A

last: Mahal

first: Saverio

last: Minucci

first: Simone

last: Sidoli

first: Daniel

last: Bilbao

first: Ramiro

last: Verdun

first: Lluis

last: Morey


title: Effect of a long non-coding RNA, lnc-FANCI-2 on host transcriptome.

status: Public on Jun 01 2022

city: Bethesda

first: Thomas

middle: Joshua

last: Meyer

state: Maryland

address: 41 Center Drive, Building 41, Room B620

department: National Cancer Institute

institute: National Institutes of Health

summary: To seek the function of lnc-FANCI-2 in high-risk HPV infected cancer cells, we knocked out lnc-FANCI-2 in CaSki cells (HPV16 positive) using CRISPR/Cas9 system.

overall_design: A differential expression analysis of host transcritome in CaSki cells.

first: Zhi-Ming

last: Zheng

first: Haibin

first: Vladimir

last: Majerciak


title: collateral effects

status: Public on Jun 30 2022

city: Shanghai

first: Hui

last: Yang

state: Shanghai

address: 320 Yueyang Road

institute: CAS Center for Excellence in Brain Science and Intelligence Technology

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

overall_design: Refer to individual Series


title: The long noncoding RNA Charme supervises cardiomyocyte maturation by controlling cell differentiation programs in the developing heart

status: Public on Mar 17 2023

city: Rome

first: Monica

last: Ballarino

address: Piazzale Aldo Moro 5

department: Biology and Biotechnologies "Charles Darwin"

country: Italy

institute: Sapienza University of Rome


title: CRISPR activation for SCN2A-related neurodevelopmental disorders

status: Public on Apr 01 2022

city: San Francisco

first: Nadav

last: Ahituv

state: CA

address: 1550 4th Street

institute: UCSF

summary: Here we are testing the effects and measuring mRNA expression  of CRISPRa targeting the promoter of mouse Scn2a in Neuro2a cells

overall_design:
plasmid CRISPRa transfection in mouse Neuroblastoma-2a cells

This dataset includes the preliminary data for the study. GSE302897 includes the final data.

first: Jingjing

last: Zhao

first: Serena

last: Tamura


title: Association study between gene expression and fiber type composition in skeletal muscle

status: Public on Dec 30 2022

city: Moscow

first: Rinat

middle: I

last: Sultanov

address: Malaya Pirogovskaya, 1a

country: Russia

institute: FRCC of Physical Chemical Medicine of the FMBA of the Russian Federation

summary: Total RNA-seq profiling of skeletal muscle.

overall_design: Total RNA profiles from 24 skeletal muscle samples.

first: Edward

last: Generozov


title: Tuberous sclerosis complex renal lesion pleiotropy arises from multiple aberrant developmental processes

status: Public on Jul 05 2022

city: Ottawa

first: William

last: Stanford

state: Ontario

address: 501 Smyth Road

country: Canada

institute: Ottawa Hospital Research Institute

summary: Tuberous sclerosis complex (TSC) is a multisystem tumor-forming disorder caused by loss of TSC1 or TSC2. Renal manifestations predominately include cysts and angiomyolipomas. Despite a well-described monogenic etiology, the cellular pathogenesis has remained elusive. Here, we report a novel genetically-engineered human renal organoid model which recapitulates pleiotropic features of TSC kidney disease in vitro and upon orthotopic xenotransplantation. We find that loss of TSC1/2 affects multiple developmental processes in the renal epithelial, stromal, and glial compartments. First, loss of TSC1/2 leads to an expanded stroma by favouring stromal cell fate acquisition and alters terminal stromal cell identity. Second, epithelial cells in the TSC1/2-/- organoids exhibit a rapamycin-insensitive epithelial-to-mesenchymal transition. Third, a melanocytic population forms exclusively in TSC1/2-/- organoids, branching from MITF+ Schwann cell precursors of a bona fide neural crest-to-Schwann cell differentiation trajectory. Together, these results illustrate the pleiotropic developmental consequences of biallelic inactivation of TSC1/2 and offer insight into the pathogenesis of TSC kidney lesions.

overall_design: scRNA-seq profiling of WT, TSC1-/-, and TSC2-/- renal organoids at day 9, 13, 17, and 21 of differentiation, from two cell lines (H9 and 168 1d2), preapred in mixes via MULTI-seq.

first: Adam

last: Pietrobon


title: Chromatin and gene-regulatory dynamics of mouse nephron progenitors at single-cell resolution

city: New Orleans

first: Samir

middle: S

last: El-Dahr

state: Louisiana

address: 1430 Tulane Avenue

department: Pediatric Nephrology

institute: Tulane University


title: Increased Inflammatory Low-Density Neutrophils in Morbid Obesity: Gene Expression and Effect of Bariatric Surgery

status: Public on Mar 15 2022

first: Jovanny

last: Zabaleta

state: LA

address: 1700 Tulane Ave

department: Interdisciplinary Oncology

institute: LSUHSC

summary:
Background:
Low-density neutrophils (LDN) are increased in several inflammatory diseases, and may also play a role in low-grade chronic inflammation in obesity. Yet their role in obesity or the effect of bariatric surgery-induced weight loss is unknown.
Methods:
We compared circulating LDN, their function, and gene expression between morbidly obese patients (MOP; BMI > 40 Kg/m2) and normal-weight controls (NWC; BMI < 25 Kg/m2) in a case-control study. Additionally, in a prospective longitudinal study, we measure changes in the frequency of LDN before and after bariatric surgery, and tested possible associations with metabolic and inflammatory parameters.
Findings:
LDN and inflammatory markers were significantly increased in MOP (n=27) compared to NWC (n=20). Transcriptome analysis of LDN from MOP showed an increased neutrophil-related gene expression signature associated with inflammation, neutrophil activation, and immunosuppressive function. However, LDN did not suppress T cells proliferation and produced low levels of ROS. Circulating LDN in MOP significantly decreased after surgery in parallel with BMI, metabolic syndrome and inflammatory markers.
Interpretation:
Obesity increases LDN with inflammatory gene signature. Bariatric surgery has anti-inflammatory effect including reduction of LDN. Gene expression and phenotype suggest that LDN represent a neutrophil subset that may be associated with obesity-associated chronic inflammation that promotes co-morbidities.

overall_design:
We did RNA-seq in circulating LDN from obese patients (n=8) and healthy weight controls (n=5). RNA was extracted, qualified by Agilent 2100 and quanitfied by qubit. Librarires were prepared using the Illumina's TruSeq Stranded mRNA kit and sequenced at 2 x 75bp (50M reads/sample).

UPDATE: [Sept-23-2025] The genders were corrected.

first: Maria

last: Dulfary Sanchez-Pino

last: Richardson

first: Ramesh

last: Thylur

first: Andrew

middle: G

last: Chapple

first: Jiao

last: Liu

first: Yonghyan

last: Kim

first: Michelle

last: Ponder

first: Randi

last: DeArmitt

first: Lyndsey

last: Buckner Baiamonte

first: Dorota

last: Wyczechowska

first: Liqin

first: Amir

last: Al-Khami

first: Jone

last: Garay

first: Rachel

last: Martini

first: Melissa

last: Davis

first: Jessica

last: Koller Gorham

first: James

middle: B

last: Wooldridge

first: Paulo

middle: C

last: Rodriguez

first: Augusto

last: Ochoa


title: An environmentally responsive dichotomy in cell lineages of the root

status: Public on Mar 16 2022

city: Perth

first: Ryan

last: Lister

state: WA

address: 35 Stirling Highway

country: Australia

institute: The University of Western Australia

summary: Plant development is extremely flexible compared to animals, with growth and architecture being continuously shaped by environmental cues. Roots, for instance, adapt their development to the substrate they are anchored to, water and nutrient availability, and the local biome. This plasticity suggests that, at the cellular level, environmental inputs have a substantial impact on cell function and activity. The root is currently viewed as a collection of distinct cell types, organized in stereotypical layers, each arising from stem cells along a linear differentiation trajectory, much like animal lineages. Cells within each layer are often regarded as mostly homogeneous, with a cell type-specific transcriptional signature that gradually shifts as differentiation progresses. Using single-cell RNA-seq combined with spatial mapping, we deeply explored the trajectories of developing cell type lineages at the tip of Arabidopsis roots. Contrary to the current model of cell identity acquisition in the root, we found that most lineage trajectories exhibit a stereotyped bifid topology, with two developmental paths rather than one. One of these paths is characterized by a strong and specific activation of genes involved in responses to environmental stimuli, including those activating the abscisic acid (ABA) pathway. This state affects only a subset of cells in multiple cell types simultaneously, revealing an additional layer of patterning that is independent of ontogeny. This environmentally responsive transcriptional state is robust, persisting in a mutant with disrupted cell type identities, and consistently present across different Arabidopsis ecotypes, and atlases. Furthermore, we show that its establishment is impaired in ABA-deficient and ABA-insensitive mutants. Finally, we demonstrate that the root can adjust the proportion of cells that acquire this state when grown in a model of drought. The discovery of this alternate fate trajectory, induced by a highly active and environmentally responsive cell state, reveals an additional layer of root cell identity that may underpin the adaptability of roots to challenging environments.

overall_design: Single cell RNA-seq profiling of Arabidopsis thaliana root tips from wild-type accessions, mutants, and different growth conditions: Col-0 full MS (x6), Col-0 half MS (x3), Cvi (x3), Ler (x3), Ws-2 (x3), C24 (x3), aba2-3 (x3), pyl11458 (x3), scr-3 (x3), Col-0 control drought (x2), Col-0 drought 50% water (x2), Col-0 drought 20% water (x2).

first: Marina

last: Oliva


title: Transcriptomic changes and toxicologic potential of per/polyflourinated alkyl substances (pfas)  in laboratory animals via gavage

city: Durham

first: Scott

last: Auerbach

state: North Carolina

address: 111 TW Alexander Drive

institute: Division of the National Toxicology Program at NIEHS

summary: The US EPA has identified a number of PFAS and other chemicals of high priority to States and Regional EPA offices that have no available in vivo toxicology data. Based on the list of data-poor chemicals and availability of the chemicals, four were selected for 5-day hepatic and renal transcriptomic assessments in male and female Hsd: Sprague Dawley (SD) rats. These data will be used for determining provisional pathway-based transcriptomic BMDs for use in human health risk estimations. Traditional toxicological endpoints (e.g. organ weights and clinical chemistry) have been added to the studies to provide additional contextualizaing information (i.e., phenotypic anchoring).

overall_design: Male and female SD rats were placed on NTP-2000 diet and housed up to 5 animals per cage. After a 10-14 day quarantine, 8-10 week old animals were randomly assigned to treatment and control groups. Five additional animals were included for sentinel evaluation prior to quarantine release and resampled at study termination. Each of six chemicals was given at nine doses (5 mL/kg dosing volume) to the treatment groups. A vehicle control group was also included for each chemical. Male and female rats received the test formulations via gavage for five consecutive days. All animals were euthanized the day after the last dose was administered.

first: Auerbach

last: Scott


title: Nuclear access of DNlg3 c-terminal fragment and its function in regulating innate immune response genes

status: Public on Dec 06 2022

city: Nanjing

first: Hao

last: Xie

state: Jiangsu

address: 2#, Sipailou street

institute: Southeast University

summary: Neuroligins (NLGNs) are one of the autism susceptibility genes, however, the mechanism that how dysfunction of NLGNs leads to Autism remains unclear. More and more studies have shown that the transcriptome alteration may be one of the important factors to generate Autism. Therefore, we are very concerned about whether Neuroligins would affect transcriptional regulation, which may at last lead to Autism. As a single-transmembrane receptor, proteolytic cleavage is one of the most important posttranslational modifications of NLGN proteins. In this study, we demonstrated the existence of DNlg3 C-terminal fragment. Studies in the S2 cells and 293T cells showed the evidence for nuclear access of the DNlg3 C-terminal fragment. Then we identified the possible targets of DNlg3 C-terminal fragment after its nuclear access by RNA-seq. The bioinformatics analysis indicated the transcriptome alteration between dnlg3 null flies and wild type flies focused on genes for the innate immune responses. These results were consistent with the infection hypotheses for autism. Our study revealed the nuclear access ability of DNlg3 c-terminal fragment and its possible function in transcriptional regulation of the innate immune response genes. This work provides the new links between synaptic adhesion molecule NLGNs and immune activation, which may help us to get a deeper understanding on the relationship between NLGNs and Autism.

overall_design: Total RNA from 100 adult flies’ heads in w1118 or dnlg3KO88/dnlg3KO127 were extracted for deep sequencing, in triplicate, using Illumina HiSeqTM 2000.

first: Si

last: Liu

first: Ping

last: Wang

first: Ming

last: Fang


title: Differential transcriptome between low and high-grade gliomas

status: Public on Nov 30 2021

city: Alicante

first: Luis

last: Valor

state: Alicante

address: Av. Pintor Baeza, 12

country: Spain

institute: ISABIAL

summary: Glioblastoma (GB) is the most aggressive form of glioma and is characterized by a poor prognosis and high recurrence, despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB, we performed differential expression analysis between low and high-grade gliomas by using RNA-seq.

overall_design: Differential expression between high and low-grade gliomas


title: RNA-Seq of 24 hours post fertilization zebrafish Kcng4b loss-of-function embryos

status: Public on Jan 31 2022

city: Singapore

first: Hyungwon

last: Choi

address: 14 Medical Drive, MD6 #08-01

country: Singapore

institute: National University of Singapore

summary: Comparison of transcriptome of 24 hours post fertilisation wild-type zebrafish embryos and that of embryos depleted of Kcng4b using anti-Kcng4b CRISPR (5’- GGCAGAGAAGGAATTCAGCA-3’, gRNA target site in exon 3) and splice site-blocking MO (5′-TGCATTCGCCCTGTAAAAGAACAAA-3′) targeting kcng4b intron 2-exon 3 (I2E3) junction.

overall_design: Wild-type zebrafish embryos and that of embryos depleted of Kcng4b

first: Hongyuan

last: Shen

first: Vladimir

last: Korzh


title: Transcriptomic profile of liver fibrosis in mice induced by CCl4

status: Public on Nov 25 2021

city: Nanning

first: xing

last: lin

address: Shuangyong Road

institute: Guangxi medical university

summary: This study is aimed to investigate the underlying mechanisms of didymin on anti-hepatic fibrosis. In brief, mice were randomly devided into three groups,including normal, CCl4 and didymin groups. Except the normal group, mice were intra-peritonelly administrated with 20% CCl4 for 10 weeks to induce liver fibrosis; after modeling successfully, mice in didymin group were subsequently intragastrically administrated with didymin for 6 weeks. Finally, the transcriptomic analysis was performed to acquire the differently expressed genes amog the three groups, trying to figure out the potential targets, which regulated by didymin.

overall_design: Mice were randomly devided into three groups, including normal group, CCl4 group (20% CCl4 for 10 weeks, ip) and didymin group (20% CCl4 for 10 weeks, ip + didymin for 6 weeks, ig).

first: Yan

last: Li

first: Yuhua

last: Xiong

first: bin

first: Cuiyu


title: Single cell multi-omics reveals early elevated function and multiple fates within human progenitors of exhausted CD8+ T cells

status: Public on Feb 11 2022

city: Kensington

first: Jerome

last: Samir

state: NSW

address: Level 5, Wallace Wurth Building, High Street

department: IVPP

institute: Kirby Institute

summary: T-cell exhaustion is a hallmark of hepatitis C virus (HCV) infection and limits protective immunity in chronic viral infections and cancer. Limited knowledge exists of the initial viral and immune dynamics that characterise exhaustion in humans. We studied longitudinal blood samples from a unique cohort of subjects with primary infection using single cell multi-omics to identify the functions and phenotypes of HCV-specific CD8+ T cells. Early elevated IFN-γ response against the transmitted virus was associated with the rate of immune escape, larger clonal expansion, and early onset of exhaustion. Irrespective of disease outcome we discovered heterogenous subsets of progenitors of exhaustion, based on the level of PD-1 expression and loss of AP-1 transcription factors. Intra clonal analysis revealed distinct trajectories with multiple fates and evolutionary plasticity of precursor cells. These findings challenge current paradigm on the contribution of CD8+ T cells to HCV disease outcome and provide data for future studies on T-cell differentiation in human infections.

overall_design: Longitudinally sampled single HCV-specific CD8+ human T cells

first: Fabio

last: Luciani

first: Curtis

last: Cai


title: Epigenome analysis of intracranial mesenchymal tumors with FET-CREB fusions

status: Public on Nov 18 2021

city: Stanford

first: David

middle: A.

last: Solomon

address: 300 Pasteur Dr, Lane L216

department: Pathology

institute: Stanford University School of Medicine

type: Methylation profiling by genome tiling array

summary: Genome-wide DNA methylation profiling of 20 intracranial mesenchymal tumors with FET-CREB fusions encompassing both intracranial myxoid mesenchymal tumors and intracranial angiomatoid fibrous histiocytoma-like neoplasms. The Illumina Infinium EPIC 850k Human DNA Methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpG sites of genomic DNA extracted from formalin-fixed, paraffin-embedded tumor tissue of 20 intracranial mesenchymal tumors with FET-CREB fusions.

overall_design: Bisulfite converted genomic DNA extracted from the 20 tumor samples was hybridized to Illumina Infinium EPIC 850k Human DNA Methylation Beadchip


title: RNA seq data of CD8+ T cells in peripheral blood lymphocytes from melanoma and lung cancer patients

status: Public on Nov 17 2021

city: Avon

first: Beiyan

last: Zhou

state: Connecticut

address: 263 Farmington Ave, Immunology

department: Immunology

institute: UCONN Health

summary: CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of cancers. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. We built an ICI response prediction model using scRNA seq data, and for validation of the model here we profiled transcriptome of CD8+ T cells in peripheral blood lymphocytes of 4 melanoma and 4 lung cancer patients that responded to ICI or not using RNA sequencing.

overall_design: CD8+ T cells in peripheral blood lymphocytes from 4 melanoma and 4 lung cancer patients were sorted and profiled with RNA sequencing

first: Chuan

first: Brian

last: Gastman


title: CD8+ T cells in peripheral blood lymphocytes and tumor-infiltrating lymphocytes of melanoma patients: additional validation data

status: Public on Nov 16 2021

summary: CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of cancers. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. We built an ICI response prediction model using scRNA seq data, and for validation of the model here we conduct single cell RNA sequencing of CD8+ T cells in peripheral blood or tumor lymphocytes of 2 additional melanoma patients.

overall_design: CD8+ T cells in peripheral blood lymphocytes and  tumor-infiltrating lymphocytes from 2 melanoma patients were sorted and profiled with single-cell RNA sequencing.


title: Bulk RNA seq profile of CD8+ T cells in peripheral blood lymphocytes from 28 melanoma patients

summary: CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of cancers. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. We built an ICI response prediction model using scRNA seq data, and for validation of the model here we profiled transcriptome of CD8+ T cells in peripheral blood lymphocytes of 28 melanoma patients that responded to ICI or not using bulk RNA sequencing.

overall_design: CD8+ T cells in peripheral blood lymphocytes from 28 melanoma patients were sorted and profiled with RNA sequencing


title: CD8+ T cells in peripheral blood lymphocytes and tumor-infiltrating lymphocytes of melanoma patients

summary: CD8+ T cells are the primary target of immune checkpoint inhibitor (ICI) therapy in the treatment of melanoma. ICI therapy only benefits a subset of patients and complicating this issue is a reliable prediction method that does not require invasive biopsies. In the hope of remedying this challenge, we conducted single-cell transcriptomic analyses of CD8+ T cells in peripheral blood lymphocytes (CD8-mPBLs) and, importantly, tumor-infiltrating lymphocytes (CD8-mTILs) from 8 patients with metastatic melanoma.

overall_design: CD8+ T cells in peripheral blood lymphocytes and  tumor-infiltrating lymphocytes from 8 melanoma patients were sorted and profiled with single-cell RNA sequencing.


title: Hematopoiesis under telomeric attrition at the single-cell resolution [ATAC-seq]

status: Public on Oct 23 2021

city: Los Angeles

first: Feiyang

last: Ma

address: 610, Charles Young Dr East, TLSB 3000C

department: Molecular Biology Institute

institute: UCLA

summary: The molecular mechanisms that drive hematopoietic stem cell (HSC) functional decline under conditions of stress are not completely understood. Here, in light of the recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells (HSCs) under telomeric stress, as that induced by pathogenic germline mutations in telomerase complex genes. These analyses revealed that telomere attrition maintains HSCs in a state of persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of interferon (IFN) signaling response, which directly comprises HSCs’ self-renewal capabilities and eventually leads to their exhaustion. Telomerase reactivation completely restored HSC transcriptional homeostasis at the single-cell level, overcame enhanced megakaryocytic differentiation and significantly ameliorated HSCs’ repopulation capacity in the setting of competitive transplantation, suggesting that HSCs can repristinate their function upon telomere damage resolution. This study challenges the long-standing hypothesis that telomere attrition limits the proliferative potential of HSCs by inducing apoptosis or senescence and suggests that early intervention targeting the IFN axis could prevent bone marrow failure syndromes in patients with pathogenic mutations affecting telomere maintenance.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: To understand how telomeric attrition affects the function of hematopoietic stem cells (HSCs) and leads to degenerative defects in bone marrow (BM) by scATAC-seq

first: Natthakan

last: Thongon

first: Andrea

last: Santoni

first: Matteo

last: Pellegrini

first: Simona

last: Colla


title: Cell-specific alterations in the activation of the Pitx1 regulatory landscape caused by the loss of a single enhancer

status: Public on Nov 04 2021

city: Geneva

first: Guillaume

last: Andrey

address: Rue Michel-Servet 1

department: Department of Genetic Medicine and Development

country: Switzerland

institute: University of Geneva

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

overall_design: Refer to individual Series


title: RNA sequencing of Timothy syndrome human cortical and subpalial organoids

status: Public on Oct 20 2021

first: Aaron

last: Gordon

address: 695 Charles E. Young Drive South, Gonda 2306, Los Angeles, CA  90095-1761

department: Neurology

summary: We derived iPSC from individuals with Timothy syndorme and controls and differentiated them into 3D cortical and subpalial  organoids.

overall_design:
Differentiation was performed across 4 control and 3 timothy syndrome lines to generate both cortical and subpalial organoids.

>>>Raw data not available due to patient privacy concerns<<<

first: Fikri

last: Birey

first: Daniel

last: Geschwind

first: Sergiu

last: Pasca


title: Aberrant type 1 immunity drives mucosal fungal infection susceptibility

status: Public on Aug 11 2021

city: Bethesda

first: Michail

last: Lionakis

address: 9000 Rockville Pike

institute: National Institutes of Health

summary: The objective of this study was to understand the impact of autoimmune regulator (AIRE) on immunity against oral Candida albicans infection. Previous work indicated that autoantibodies against IL-17 and IL-22 may contribute to host susceptibility; however, there is not a 100% correlation between autoantibodies and mucosal candidiasis in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) patients, indicating that other pathways may be affected. Using a mouse model that very closely mimics what is seen in APECED patients, oral epithelial cells were sorted and RNA extracted from them to perform RNA-seq analysis to determine what other pathways may be involved. These data show that the type II interferon pathway is highly upregulated in Aire-deficient mice, while the IL-17R pathway is intact.

overall_design:
Mouse:
RNA-seq of sorted tongue epithelial cells from Aire WT and deficient mice during mucosal Candida albicans infection.
For this study, oral epithelial cells (Live CD45- CD31- CD102- EpCAM+) were sorted with a FACS Aria cell sorter (>95% purity) and RNA extracted from 3 Aire WT and 3 Aire-deficient mice that had been orally infected with Candida albicans one day prior to the study.

Human:
RNA-seq of oral mucosal tissue from healthy donors and APECED patients.
For this study, oral mucosal gingival biopsies were obtained from 4 uninfected healthy donors and 5 uninfected APECED patients and RNA extracted for RNA-seq analysis.

first: Timothy

middle: J

last: Break

last: Martin

first: Niki

last: Moutsopoulos


title: piwi-interacting RNA sequencing of 2 paired clear cell renal cell carcinoma tissues and adjacent normal tissues

status: Public on Sep 08 2021

city: hangzhou

first: Lifeng

last: Ding

state: zhejiang

address: qingchun dong road 3#

department: department of urology

institute: Zhejiang university school of medcine sir run run shaw hosptial

type: Non-coding RNA profiling by high throughput sequencing

summary: Clear cell renal cell carcinoma is one of the most common diagnostic tumor, with nearly one third patients diagnosed as metastatic ccRCC. Although increasing number of studies have revealed that piwi-interacting RNAs were aberrantly expressed in diverse type of cancers, few of them explored the detailed molecular mechanism of piRNAs in carcinogenesis, particular in ccRCC. In this study, differentially expressed piRNAs associated with ccRCC was selected by using piRNA-sequencing combined with analyzing TCGA data, from which piR-57125 was identified. PiR-57125 was found remarkably downregulated in ccRCC samples. Functionally, knockdown of piR-57125 promoted migration and invasion of ccRCC, while overexpression of piR-57125 suppressed ccRCC metastasis. In vivo lung metastasis model also confirmed the same results. CCL3 was identified as the direct target of piR-57125 which could reverse the inhibition effect of piR-57125 in ccRCC metastasis. Further studies revealed that piR-57125 modulated ccRCC metastasis through AKT/ERK pathway. Those data indicate that piR-57125 restrains ccRCC metastasis through directly targeting CCL3 and inhibiting AKT/ERK pathway, and could be a potential therapeutic target for ccRCC.

overall_design: piRNA profiling in 2 paired clear cell renal cell carcinoma tissues.

first: Gonghui

last: Li

first: Ruyue

last: Wang

first: Danyang

last: Shen


title: PHF5A coordinates p300 for epigenetic regulation of lipogenesis to promote hepatocellular carcinoma progression

status: Public on Oct 01 2021

city: 北京

first: YU

last: ZHANG

state: non-US Resident

address: XUEYUANLU No.38 Haidian District, PKUHSC Anatomy Building

institute: Peking Univ.

summary: PHD-finger protein 5A (PHF5A) is a component of U2snRNP, which plays a critical role in mRNA splicing for recognizing the branch site. However, whether it also plays other functions independent of RNA splicing remains elusive.  Here, we find that expression levels of PHF5A are significantly upregulated in hepatocellular carcinoma (HCC). Down-regulation of PHF5A restrains liver cancer cell proliferation in vitro and in vivo. RNA-sequencing analysis reveals that fatty-acid biosynthetic enzymes are major downstream targets of PHF5A in HCC. Through metabolomics analysis, we find that inhibition of PHF5A reduces free fatty acid and phospholipid synthesis, further suppressing plasma membrane function. Mechanistically, PHF5A acts as a transcription co-factor of the p300 acetyltransferase for the H3K27 acetylation (Ac) and promotes H3K27Ac-dependent lipogenic genes expression. Our findings demonstrated a surprising splicing-independent role of PHF5A in transcriptional regulation of lipid metabolism for HCC progression and provided a new strategy for HCC therapy by blocking the interaction of PHF5A and p300.

overall_design: 4 samples. HepG2 liver cancer cells were transfected with siControl or siPHF5A, Cells' RNA was harvested using Trizol reagent. 3 ug of total RNA is used for the construction of sequencing libraries by Hiseq 4000 PE150.

first: Xin

last: Yang

first: Zhe

first: Jianyuan

last: Luo


title: Whole‐Genome Differentially Hydroxymethylated DNA Regions among Twins Discordant for Cardiovascular Death

status: Public on Aug 06 2021

city: Winston Salem

first: Ming

last: Leung

state: NC

address: 1 Medical Center Blvd

department: Comprehensive Cancer Center

institute: Atrium Health Wake Forest

type: Methylation profiling by high throughput sequencing

summary: We assessed whether DNA hydroxymethylation is prospectively associated with the risk for cardiovascular death independent of germline, age, and blood cell type composion.

overall_design: Male twin pairs middle-aged in 1969-1973 and discordant for cardiovascular death through December 31, 2014 were included. Hydroxymethylation was quantified in buffy coat DNA collected in 1986–1987. Differentially hydroxymethylated regions (DhMRs) were identified after controlling for blood leukocyte subtypes and age among 12 monozygotic (MZ) pairs. The regions were used to create a binary linear classifier that predicted cardiovascular death among 19 dizygotic pairs.

first: Jun

last: Dai


title: The effect of FBS and cyclic mechanical stretch on serum starved mesenchymal stem cells

status: Public on Dec 02 2021

city: Zunyi

first: Jiao

state: Guizhou

address: No.6 West Xuefu Road

institute: Zunyi Medical University

summary:
Purpose: Cyclic mechanical stretch (CMS) promoted proliferation of serum starved mesenchymal stem cells (MSCs) by inhibiting miR-337 expression, similar to FBS. In order to reveal the underlying mechanisms of both CMS and FBS on MSC activation, as well as the regulatory role of miR-337, this research performed high-throughput RNA sequencing (RNA-seq) on MSCs isolated from both wild-type (ET)- and miR-337 knockout- (miR-337-/-) rats.
Methods: MSCs isolated form 2-month-old wild-type (WT) and miR-337 knockout (-/-) rats and cultured in vitro to passage 3. After serum starvation for 8h, MSCs were treated with FBS or 10% CMS for another 24h before deep sequencing in triplicate, using Illumina GAIIx. The sequence reads that passed quality filters were analyzed at the transcript isoform level.
Results: Using an optimized data analysis workflow, we mapped about 40 million sequence reads per sample. We identified 2472 differentially expressed genes (DEGs) between CMS-stimulated vs. SSt conditions, 2468 DEGs FBS-treated vs. SSt groups. However, only 97 DEGs were identified between CMS and FBS groups, indicating that CMS and FBS groups are more similar to each other and both CMS and FBS groups are quite different from the SSt group. Analysis of DEGs between CMS- or FBS-treated and SSt -treated group revealed that CMS and FBS stimulation activated similar biological processes, of which, PI3K-Akt-mTOR pathway was highly enriched. However, PI3K-Akt-mTOR pathway was not enriched in miR-337-/- MSCs, indicating constitutive activation of this pathway.
Conclusions: Our RNA-seq data revealed that both CMS and FBS activates quiescent MSCs through regulating similar genes and pathways. miR-337 is one of the main factors that regulate MSC activation by targeting PI3K-Akt pathway.

overall_design: MSCs isolated from WT and miR-337-/- rats underwent the treatment of CMS, FBS or serum starvation

first: Xiaoling

last: Zhang


title: Notch controls urothelial integrity in the mouse bladder.

status: Public on Apr 07 2020

first: Vasilis

last: Dionellis

address: 30, quai Ernest-Ansermet

summary: The Notch signaling pathway mediates cell-cell communication regulating cell differentiation and proliferation and cell fate decisions in various tissues. In the urinary bladder, Notch acts as a tumor suppressor in mice, while mutations in Notch pathway components have been identified in human bladder cancer as well. Here we report that the genetic inactivation of Notch in mice leads to downregulation of cell-cell and cell-ECM interaction components, including proteins previously implicated in interstitial cystitis/bladder pain syndrome (IC/BPS), structural defects and mucosal sloughing, inflammation, and leaky urine-blood barrier. Molecular profiling of ailing mouse bladders showed similarities with IC/BPS patient tissue, which also presented low Notch pathway activity as indicated by reduced expression of canonical Notch targets. Urothelial integrity was reconstituted upon exogenous reactivation of the Notch pathway, implying a direct involvement of Notch. Despite damage and inflammation, urothelial cells failed to proliferate, uncovering a possible role for α4 integrin in urothelial homeostasis. Our data uncover a broad role for Notch in bladder homeostasis involving urothelial cell crosstalk with the microenvironment.

overall_design: Two wild-type and three Nicastrin KO mice were analyzed.

first: Varvara

last: Paraskevopoulou

first: Vangelis

last: Bonis

first: Nikolaos

last: Paschalidis

first: Pelagia

last: Melissa

first: Evangelia

last: Chavdoula

first: Eleni

last: Vasilaki

first: Ioannis

last: Pateras

first: Apostolos

last: Klinakis


title: Single-cell dissection of the primary motor cortex in ALS and FTLD patients.

status: Public on Jul 09 2021

city: Cambridge

first: Myriam

last: Heiman

state: Massachusetts

address: 77 Massachusetts Ave., Bldg 46-4285

department: Brain and Cognitive Sciences

institute: Massachusetts Institute of Technology

summary: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable and fatal neurodegenerative conditions. While distinct, they share many clinical, genetic, and pathological characteristics, and both show highly vulnerable layer 5 extratelencephalic-projecting cortical populations, including Betz cells in ALS2 and von Economo neurons (VENs) in FTLD.  Here, we report the first single-cell atlas of the human primary motor cortex and its changes in ALS and FTLD across ~380,000 nuclei from 64 control, sporadic and C9orf72-associated ALS and FTLD individuals. We identify 46 transcriptionally distinct cellular subtypes including two Betz-cell subtypes, and observe a previously-unappreciated molecular similarity between Betz cells and VENs of the frontal insula. Most dysregulated genes and pathways were shared, including stress response, ribosome function, oxidative phosphorylation, synaptic vesicle cycle, endoplasmic reticulum protein processing, and autophagy. Betz cells and SCN4B+ long-range projecting L3/L5 cells are the most transcriptionally affected in both ALS and FTLD. Lastly, the VEN/Betz-cell-enriched dysregulated gene POU3F1 co-localizes with TDP-43 aggregates in Betz cells.

overall_design:
Single-nucleus RNA-seq profiling of the human primary motor cortex in amyotrophic lateral sclerosis and frontotemporal lobar degeneration

**This dataset has been replaced by BioProject PRJNA1073234**

first: S

last: Pineda

first: Hyeseung

last: Lee

first: Manolis

last: Kellis


title: Rapid remodeling of poised chromatin landscapes and transcription factor repurposing facilitate gene induction in natural killer cells

status: Public on Oct 28 2020

first: Hong-wei

last: Sun

state: MD

address: 9000 Rockville Pile

department: Office of Science & Technology

institute: NIAMS

summary: Innate immune responses rely on rapid and precise orchestration of gene regulation mediated by accessibility of regulatory regions to key transcription factors.  However, the extent to which acute activation alters accessibility and the roles of distinct classes of transcription factors in this process are unsatisfactorily understood. Here, we investigated and integrated epigenomic modifications and transcriptomic changes occurring upon activation of natural killer (NK) cells.

overall_design: We stimulated splenic NK cells with cytokines IL-2 and IL-12 ex vivo for six hours and performed bulk RNA-seq on both resting and activatd NK cells for transcriptomic analysis, in parellel using ATAC-seq and ChIP-seq (p300, STATs, and histone modifications) for epigenomic profiling. To understand the dynamic chromatin landscapes in vivo, we measured chromatin accessibility of NK cells isolated from mice infected by Toxoplasma gondii for three and seven days using FastATAC-seq. We performed single cell RNA-seq on the infeceted NK cells form the same experiment to study the heterogeniety of immune responses in spleen and peritoneal cavity upon Toxoplasma infection.

first: H

last: Shih

first: G

last: Sciume

first: Y

last: Mikami

last: Nagashima

middle: W

middle: R

last: Brooks

first: D

last: Jankovic

first: C

last: Yao

first: AV

last: Villarino

first: F

middle: P

last: Davis

last: Kanno

first: J

last: O'Shea


title: ChIP-seq dataset for epigenomics landscape of colorectal cancer

status: Public on May 22 2021

first: Ayush

middle: T

last: Raman

state: MA

address: 75 Ames St

department: Epigenomics Program

institute: Broad Institute of MIT and Harvard

summary: Cancer cells utilize genetic and epigenetic aberrations for their excessive growth. Although we have sufficient understanding of the genomic alterations in colorectal cancer, we have incomplete knowledge of epigenomic aberrations and their impact on tumor growth. In order to comprehensively define the epigenetic patterns specific to colorectal cancer, we generated profiles for 6 histone modification marks, including H3K4me1 (enhancer), H3K27Ac (active enhancer), H3K9me3 (heterochromatin), H3K27me3 (polycomb repression), H3K79me2 (transcription) and H3K4me3 (promoter), using a high-throughput ChIP-Seq methodology developed in house applicable to frozen tumors. Chromatin state transitions specifically pointed to drastic changes in enhancer patterns, consistent with some prior studies. Furthermore, we identified the best combinatorial chromatin states that could most efficiently distinguish and predict CRC from normal colon. In a more detailed investigation into patterns of active enhancers using normal colon, adenomas and colorectal cancers, we identified specific changes in enhancers from normal tissue to these neoplastic lesions. Importantly, we noted gains of enhancers in a large number of genomic loci in colon cancer compared to adjacent normal tissues. In summary, we have identified aberrant enhancer gains as a major feature of colorectal cancer and propose this to be utilized as a therapeutic approach.

overall_design: ChIP-seq samples across six different marks -- H3K4me1 (n = 32; 16  Normal and 16 Tumor), H3K9me3 (n = 30 samples; 14 Normal and 16 Tumor),  H3K27ac (n = 68 samples; 15 Normal, 34 Tumor, 4 FAPP Normal, 4 Adenoma and  11 CCLE cell lines), H3K79me2 (n = 31 samples; 17 normal and 14 Tumor),  H3K4me3 (n = 33 samples; 17 Normal and 16 Tumor) and H3K27me3 (n = 29; 14  normal and 15 Tumor). Raw fastq reads for all ChIP-seq experiments were processed by using a snakemake-based pipeline (https://zenodo.org/record/819971). The raw reads were first processed by using FastQC, and uniquely mapped reads were aligned to the hg19 reference genome by using Bowtie Ver. 1.1.2. Duplicate reads were removed by using SAMBLASTER(7) before compression to bam files. To directly compare ChIP-seq samples, uniquely mapped reads for each mark were downsampled per condition to 15 million, sorted, and indexed using samtools ver. 1.5. To visualize ChIP-seq libraries on the IGV genome browser, we used deepTools Version 2a.4.0, which generated bigWig files by scaling the bam files to reads per kilobase per million (RPKM). Super ChIP-seq tracks were generated by merging BAM files from each phenotype, sorting and indexing using SAMtools, and scaling to RPKM using deepTools. We used the Model-based analysis of ChIP-seq (MACS) version 1.4.2(10) peak calling algorithm to identify peaks for the sharp marks H3K4me1, H3K27ac, and H3K4me3; we used MACS version 2.1.0 to identify peaks for broad marks H3K9me3, H3K79me2, and H3K27me3. The peak enrichment was calculated over a whole genome "input" background with a p-value of < 1e-5. Super-enhancers were identified using the ranking of super-enhancers (ROSE) algorithm based on H3K27ac ChIP-seq data.

first: Elias

last: Orouji

first: Anand

middle: K

last: Singh

first: Kunal

last: Rai


title: Dynamic gene expression atlas of goose granulosa cells during development stage

status: Public on Oct 16 2019

city: Chongqing

first: Gao

last: Guangliang

address: Street Address, No. 51 Changlong Avenue Rongchang County

institute: Chongqing Academy of Animal Sciences

summary: the nine developmental stage, including small white follicles (SWF), large white follicles (LWF), small yellow follicles (SYF), large yellow follicles (LYF), the fifth largest follicle (F5), fourth largest follicle (F4), third largest follicle (F3), second largest follicle (F2) and the largest follicle (F1), respectively.

overall_design: According to the data of reproduction performance, ten high-yield female geese under egg-laying peak period (45 week) were selected as experimental animals, and then those geese were slaughtered before egg-laying 2 hours to gain the nine developmental stages of ovarian follicle. We randomly selected complete nine follicles tissue samples of five individuals of them to perform hematoxylin-eosin (HE) for histological staining. According to diameter, those follicles were separate into the SWF (2-4mm), LWF (4-6mm), SYF (6-8mm), LYF (8-10mm), fifth largest follicle (F5), fourth largest follicle (F4), third largest follicle (F3), second largest follicle (F2) and the largest follicle (F1), respectively.

first: Guangliang

last: Gao

first: Keshan

last: Zhang

first: Xianzhi

last: Zhao

first: Qin

last: Li

first: Qigui

last: Wang


title: Role of LEDGF/p75 in MLL chemoresistance

status: Public on Jan 14 2021

city: Columbus

first: Alessandro

last: Canella

state: OH

address: 700 Children’s Drive

department: Institute for Genomic Medicine

institute: Nationwide Children's Hospital

summary:
The study has been focused on the characterization of the role of LEDGF/p75 in chemiresistance in pediatric leukemia
Abstract: MLL is an aggressive subtype of leukemia with a poor prognosis that mostly affects pediatric patients. MLL-rearranged fusion proteins (MLLr) induce aberrant target gene expression resulting in leukemogenesis. MLL and its fusions are tethered to chromatin by LEDGF/p75, a transcriptional co-activator that specifically recognizes H3K36me2/3. LEDGF/p75 is ubiquitously expressed and associated with regulation of gene expression, autoimmune responses and HIV replication. LEDGF/p75 was proven to be essential for leukemogenesis in MLL. Apart from MLL, LEDGF/p75 has been linked to lung, breast and prostate cancer. Intriguingly, LEDGF/p75 interacts with Med-1, which co-localizes with BRD4. Both are known as co-activators of super-enhancers. Here, we describe LEDGF/p75-dependent chemoresistance of MLLr cell lines. Investigation of the underlying mechanism revealed a role of LEDGF/p75 in the cell cycle and in survival pathways and showed that LEDGF/p75 protects against apoptosis during chemotherapy. Remarkably, LEDGF/p75 levels also affected expression of BRD4 and Med1. Altogether, our data suggest a role of LEDGF/p75 in cancer survival, stem cell renewal, and activation of nuclear super enhancers.

overall_design: 2 groups of #4 samples each. In group 1 we have analyzed ThpI cells shMOCK as a control group in comparison with group 2 constituted by ThpI cells shLEDGF/p75

first: Siska

last: Van Belle

first: Tine

last: Brouns

first: Giovanni

last: Nigita

first: Marianne

last: Carlon

first: Frauke

last: Christ

first: Zeger

last: Debyser


title: Beneficial effects of Allulose for age-associated sarcopenia

status: Public on May 27 2021

city: Daegu

first: Youngji

last: Han

address: Daehakro 80

country: South Korea

institute: Kyungpook National University

summary: Allulose has been shown to moderate obese related dysmetabolism. In previous study, we found that allulose increased the muscle weight in diet-induced obese mice. It is there for hypothesized that allulose alleviated sarcopenia. The 12 month old mice were fed AIN93G with allulose. Allulose supplementation improved the muscle loss in aging mice.

overall_design: Total RNA of muscle tissue was obtained from normal diet, normal diet and with-allulose in aging mice model and mRNA expression-associated with protein turnover and inflammation was measured.


title: Histone 3 K9 and K27 acetylation of enhancers in response to thyroid hormone

status: Public on Jul 01 2019

city: Odense

first: Lars

last: Grøntved

address: Campusvej 55

department: Biochemistry and Molecular Biology

country: Denmark

institute: University of Southern Denmark

summary: Hormone dependent activation of enhancers includes histone hyperacetylation and mediator recruitment. Histone hyperacetylation is often explained by a bimodal switch mod-el, where histone deacetylases (HDACs) disassociates from chromatin and histone acetyl transferases (HATs) are recruited. This model builds on decades of research on steroid re-ceptor regulation of transcription. We have used a genomics approach to study enhancer hyperacetylation by the thyroid hormone receptor (TR) and present a revised model. 1) at poised constitutively TR bound enhancers, HATs occupy chromatin irrespective of thyroid hormone (T3) levels, whereas HDAC occupancy is regulated by T3, suggesting that HDACs functions as a histone acetylation rheostat. 2) at enhancers established in a T3 dependent manner, TR is recruited to chromatin together with HATs. 3) a number of enhancers are hy-peracetylated secondary to TR activation. Collectively, this demonstrates various mechanisms controlling hormone dependent transcription and adds significant details to the otherwise simple bimodal switch model.

overall_design: ChIP-seq was performed in replicates from a pool of four individual ChIPs from livers of four individual mice. Some ChIP-seq's were not performed in replicates. The RNA-seq was performed on four indepedent biological replicates.

first: Stine

last: Præstholm


title: Cell-specific alterations in the activation of the Pitx1 regulatory landscape caused by the loss of a single enhancer (Capture Hi-C)

first: Guillaume

last: Andrey

summary: Developmental genes often reply on multiple transcriptional enhancers to achieve correct expression during embryogenesis. These enhancers can have partially redundant activities, thus it is difficult to ascertain the direct impact of the loss of a single one of them as often only mild, if any, phenotypes are seen. In this work we use the testbed locus Pitx1 to characterise the regulatory and cell specific alterations following the loss of one of its enhancers Pen in vivo. We combine single cell transcriptomics and in embryo cell tracing and observe the global decrease perviously observed in deletion of Pen hindlimbs results from an accumulation of low to non-expressing cells that affects more proximal rather than distal limb and leads to a clubfoot phenotype product of a localised heterochrony and loss of irregular connective tissue. We also analyse the contribution of the enhancer to the overall locus structure and activity and we suggest that in some cases redundant enhancers may locally enforce a robust activation of their gene’s regulatory landscape.

overall_design:
We used capture Hi-C enriching a 3,3Mb region at the Pitx1 locus in Mus musculus. We analysed two biological replicates of Pitx1-GFP postive and negative cells and two biological replicates of Pitx1-GFP-ΔPen GFP postive and negative cells from hindlimb tissue to compare the structural changes at the locus.

UPDATE: [Sep-30-2025] The titles and characteristics were swapped between Samples GSM5151750 and GSM5151751, and between Samples GSM5151752 and GSM5151753. The raw data and processed data associated with each GSMxxx accession number did not change.

first: Olimpia

last: Bompadre

first: Raquel

last: Rouco


title: Molecular subtypes in gastric cancer.

status: Public on Mar 20 2018

city: Seoul

first: Yong-Min

last: Huh

address: 50 Shinchon-ro

institute: Yonsei University


title: Single cell RNA sequencing of murine bone marrow derived macrophages and adipose tissue macrophages from lean and obese mice

status: Public on Apr 24 2019

first: Beiyan

last: Zhou

address: 263 Farmington Ave, Immunology

summary: Macrophages are key to innate immunity and tissue homeostasis. Plasticity of macrophages allows rapid and highly orchestrated responses to various pathogenic and physiological challenges. Capturing the dynamic intracellular programs employed by macrophages during encounters with various stimuli presents a demanding technical challenge, and failures to fully characterize some of these responses has stalled development of disease-specific therapy. Powered by single-cell RNA sequencing (scRNA-seq), we expanded current t-distributed stochastic neighbor embedding (t-SNE) single-cell transcriptome algorithms and established a novel platform, MacSpectrum (macspec.github.io), with newly generated indexes (Macrophage Polarization Index, MPI and Macrophage Maturation Index, MMI) that allow not only macrophage subpopulation characterization under various conditions but also disease-specific signature gene set identification. Our MacSpectrum model will provide a comprehensive system to annotate macrophage function and dissect their diversified programs under sophisticated conditions in vivo, which represents a major challenge in macrophage biology. Single cell RNA sequeicing profiles of 6979 M0 BMDMs , 4736 M1 BMDMs,  6391 M2 BMDMs, 1710 lean ATMs, and 1758 obese ATMs were generated.

overall_design: Bone marrow cells were collected from femur and tibia bone of mice fed on regular chow diet , and were induced for differentiation to monocytes in bone marrow derived macrophage (BMDM) growth medium (Iscove's Modified Dulbecco's Medium (IMDM) + 10% FBS + 15% L-929 cell (ATCC, CCL-1)); the  BMDMs were then stimulated with 100 ng/mL LPS and 50 ng/ml IFNγ for M1 activation, or 20 ng/mL IL4 and 20 ng/mL IL13 for M2 activation. Unstimulated BMDMs were collected as M0 state. CD45+ CD11b+ F4/80+ macrophages (ATM) were isolated from adipose tissue of mice fed on regular chow diet (lean) or high-fat diet (obese)  using a BD Biosciences FACS Aria II cell sorter. Single cell transcriptome profiles of the BMDMs and ATMs were generated on a GemCode Single Cell Instrument (10x Genomics) using Chromium™ Single Cell 3' Reagent Kit v2 (10x Genomics) and were sequenced on an illumia HiSeq 4000.

first: Chuan


title: Molecular subtypes in gastric cancer. [II]

summary: We identified the molecular subtypes and conserved modules in gastric cancer by unsupervised clustering algorithm. We defined five molecular subtypes and six molecular signatrues of gastric cancer associated with the biological heterogeneity of gastric cancer and clinical outcome of patients.

overall_design: We obtained gene expression profile of gastrectomy samples from 357 gastric cancer patients by HumanHT-12 v3.0 Expression BeadChip array (Illumina). Total RNA was extracted from the fresh-frozen gastrectomy specimens at the Yonsei University Severance Hospital (South Korea) between 2000 and 2010.

first: Jae-Ho

last: Cheong

first: Eunji

last: Jang

first: Hyunki

last: Kim

first: Jungmin

last: Park

first: Jungeun

first: Hyeseon

first: Youngmin

last: Shin

first: Hye-Young

last: Son

first: Yoon

last: Choi

first: Woo

last: Hyung

first: Sung

last: Noh

first: Jin-Suck

last: Suh


title: Molecular subtypes in gastric cancer. [I]

overall_design: We obtained gene expression profile of gastrectomy samples from 76 gastric cancer patients by HumanHT-12 v3.0 Expression BeadChip array (Illumina). Total RNA was extracted from the fresh-frozen gastrectomy specimens at the Yonsei University Severance Hospital (South Korea) between 2000 and 2010.


title: Gene expression profiling of murine embryonic and epiblast stem cells under IQ1 treatment and Ctnnb1 K49 acetylation conditions

status: Public on Dec 12 2017

city: Osaka-Sayama

first: Toshiyuki

last: Takehara

state: Osaka

address: 377-2, Ohno-Higashi

department: Faculty of Medicine

country: Japan

institute: Kindai Universty Hospital

summary: Naïve pluripotency represents the ground state of mammalian development, but the molecular mechanisms controlling its establishment remain incompletely defined. To clarify the role of β-catenin (Ctnnb1) acetylation, we performed microarray-based transcriptome profiling of murine embryonic stem cells (ESCs, naïve) and epiblast stem cells (EpiSCs, primed) under different culture conditions. Particular focus was placed on the acetylation of Ctnnb1 at lysine 49 (K49) and its modulation by IQ1, a small molecule that inhibits Ep300 function and enhances K49 acetylation. This dataset enables comparison of gene expression signatures between naïve and primed states and provides insights into the induction of naïve-like characteristics in EpiSCs following IQ1 treatment.

overall_design: Naïve pluripotency is the developmental ground state. To define transcriptional programs associated with β-catenin (Ctnnb1) lysine-49 acetylation, we performed microarray profiling of mouse embryonic stem cells (ESCs; naïve), epiblast stem cells (EpiSCs; primed), and EpiSCs exposed to IQ1 to increase K49 acetylation. The dataset enables direct comparison of naïve versus primed states and assessment of IQ1-driven conversion toward a naïve-like transcriptome.

first: Takeshi

last: Teramura

first: Hirofumi

last: Suemori


title: Distinct Polycomb Response Elements control chromatin state and gene activation of the vestigial gene

status: Public on May 01 2019

city: Seattle

first: Kamran

last: Ahmad

address: Fred Hutchinson Cancer Center, 1100 Fairview Ave North, A1-162

department: Basic Sciences

institute: Fred Hutchinson Cancer Center

summary: Patterned expression of many developmental genes is thought to rely on chromatin-mediated repression. Regulatory DNA sequences called Polycomb Response Elements (PREs) play critical roles in repression. While PREs in transgenes can nucleate trimethylation on lysine 27 of the histone H3 tail (H3K27me3), none have been demonstrated to be necessary at endogenous chromatin domains. This is thought to be due to the fact that most endogenous H3K27me3 domains contain many PREs, and individual PREs may be redundant. We show here that PREs near the wing selector gene vestigial have distinctive roles at their endogenous locus, even though both PREs are repressors in transgenes. First, a PRE near the promoter is required for vestigial activation and not for repression. Second, only the distal PRE contributes to H3K27me3, but even removal of both PREs does not eliminate H3K27me3 across the vestigial domain. Thus, endogenous chromatin domains appear to be intrinsically marked by H3K27me3, and PREs can enhance this chromatin modification at inactive genes.

overall_design: We dissected Drosophila larval tissues and generated chromatin profiles using Cleavage under targets and Release using nuclease (CUT&RUN), in which controlled cleavage by an antibody-tethered micrococcal nuclease releases specific protein-DNA complexes into the supernatant for paired-end sequencing.

first: Kami

first: Amy

last: Spens


title: Murine livers: Control vs. Liver Fibrosis

status: Public on Apr 28 2015

city: Harbin

first: Qiang

last: Gao

state: Heilongjiang

address: XueFu Road

department: Department of Pharmacology

institute: Harbin Medical University

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

summary: To identify the possible roles of long non-coding RNAs (lncRNAs) in regulating liver fiboris (LF) and the potential of lncRNAs as molecular markers for LF, we globally detected hepatic lncRNA expression proﬁle along with mRNA expression proﬁle of ICR mouse LF models which were induced by intraperitoneal injection of tetrachloromethane (CCl4) dissolved in corn oil and controls which were only injected with corn oil using microarray analysis.

overall_design: The lncRNA expression profile along with mRNA expression profile of 7 control and 7 LF livers were analyzed by Arraystar Mouse LncRNA Microarray V3.0. One liver per array.

first: Xuguang

last: Li

first: Jianhui

last: Hao

first: Li

last: Fan

first: Yan

last: Liu


title: Single cell RNA-seq of brain glioblastoma samples

status: Public on Jul 08 2021

city: Uppsala

first: L.

last: He

address: Dag Hammarskjölds Väg 20

country: Sweden

institute: Uppsala University

summary: Glioblastomas (GBM) are the most aggressive type of brain tumors with a dismal prognosis. The effectiveness of anti-tumor drugs is thwarted by brain endothelial cells (ECs) in the tumor microenvironment. However, the characteristics of ECs remains poorly inventoried at the single-cell level. We performed single-cell RNA sequencing (scRNA-seq) for ECs from 4 GBMs and matching non-malignant brain samples, and identified distinct EC phenotypes in GBM.

overall_design: We profiled freshly isolated cells from tumor core and paired surrounding peripheral tissue in 4 glioblastoma patients. Single-cell suspensions, magnetic-activated cell sorting (MACS) enriched for CD31+ cells, were subjected to scRNA-seq using a 10X genomics-based single-cell protocol.

first: Lei

last: Zhang

first: Xie

last: Yuan

first: Anna

last: Dimberg

first: Liang

last: Wang

first: Christer

last: Betsholtz


title: Developmental Acquisition of Regulomes Underlies Innate Lymphoid Cell Functionality

status: Public on May 05 2016

first: Yuka

last: Kanno

address: 10 Center Drive, Rm13C120

department: NIAMS

institute: NIH

summary: Innate lymphoid cells (ILCs) play key roles in host defense, barrier integrity, and  homeostasis, and they mirror adaptive CD4+ T helper (Th) cell subtypes in both  usages of effector molecules and transcription factors. To better understand ILC  subsets and their relationship with Th cells, we measured genome-wide chromatin  accessibility. We found that chromatin in proximity to effector genes was selectively  accessible in ILCs prior to high-level transcription upon activation. Accessibility of these  regions was acquired in a stepwise manner during development and changed little  after in vitro or in vivo activation. Conversely, dramatic chromatin remodeling occurred  in naïve CD4+ T cells during Th cell differentiation using a type 2-infection model. This  alteration results in a substantial convergence of Th2 cells toward ILC2 regulomes. Our  data indicate extensive sharing of regulatory circuitry across the innate and adaptive  compartments of the immune system, in spite of their divergent developing pathways.

overall_design: Integrated analysis of epigenome and transcriptome data from innate lymphoid cells and their progenitors

first: H

middle: Y

last: Shih

first: G

last: Sciume

first: Y

last: Mikami

first: L

last: Guo

last: Sun

first: S

last: Brooks

first: J

middle: F

last: Urban

first: F

last: Davis

last: O'Shea


title: Expression profiling of murine MYCN-driven  neuroendocrine tumor from LSL-MYCN;hGFAP-Cre mice.

status: Public on Mar 01 2016

city: Essen

first: Alexander

last: Schramm

address: Hufelandstr. 55

department: Childrens Hospital

country: Germany

institute: University Hospital Essen

summary:
MYCN overexpression is a hallmark of many tumors originating from neural cell precursors.
We generated a transgenic mouse with Cre-conditional induction of MYCN in glial fibre acidic protein (GFAP) expressing cells resulting in the development of neuroendocrine tumors of the pancreas and the brain.

overall_design:
The expression profiles of nine tumors from pancreas and three brain tumors were compared to non-malignant pancreas controls (GSM771025.CEL-GSM771027.CEL) from wildtype mice
Expression profiles of tumors and controls were analysed using GSEA and ANOVA.

first: Johannes

last: Schulte

first: Ulrich

last: Schüller


title: MiR-150 Suppresses MLL-AF9 Associated Leukemia Through Simultaneously Targeting Multiple Oncogenes

status: Public on Jul 20 2011

city: Avon

first: Beiyan

last: Zhou

institute: UCONN Health

summary: This study report that miR-150, a key hematopoietic regulatory microRNA (miRNA) and one of the most downregulated miRNAs in MLL-associated leukemias, acts as a tumor suppressor to block the leukemogenic potency of leukemic stem cells.  When expression of miR-150 was restored, a significantly suppressed leukemic stem cell potency of MLL-AF9 cells was observed both in vivo and in vitro. To investigate the tumor suppressive function of miR-150 in MLL-AF9 cells, we isolated three batches of MLL-AF9 cells infected with MDH empty vector or MDH-miR-150 expression retrovirus. Total RNA were extracted and applied for Agilent array analysis. Gene profiling analysis demonstrated that elevated miR-150 altered various aspects of gene expression patterns in MLL-AF9 cells, including stem cell signatures, cancer pathways, and cell survival.

overall_design: miR-150-MLL-AF9 and MDH-MLL-AF9 isolated cells were compared for gene expression patterns. Triplicates using three batches of FACS sorted cells were compared in pairs on the array. MDH-MLL-AF9 samples were labeld with Cy3 and miR-150-MLL-AF9 samples were labled with Cy5.

first: Guoqing

last: Zhuang


title: Innate immune response to the pfizer mrna cov-2-sars vaccine

status: Public on Jun 25 2021

city: Stanford

first: Madeleine

last: Scott

state: CA

address: 729 Lagunita Dr

institute: Stanford

summary: Purpose: to analyze the human periheral response to the prime (baseline, BL) and boost (Day 21 after BL) of the pfizer vaccine

overall_design:
Human blood before and after vaccination.

UPDATE: [Sep-30-2025] The GSE169159_raw_counts_with_genenames.csv file was updated to correct sample mislabeling.

first: Prabhu

last: Arunachalam

first: Thomas

last: Hagan


title: Modeling regulatory relationships in Arabidopsis immune signaling network.

status: Public on Jul 22 2010

city: Sapporo

first: Masanao

last: Sato

state: Hokkaido

address: Kita 9 jo Nishi 9 chome, Kita-ku, Sappro

institute: Hokkaido University

summary:
Expression profiles of 22 reference Arabidopsis immunity mutants were collected using the Arabidopsis Pathoarray 464_001 (GPL3638) in order to build a network model predicting the Arabidopsis immune signaling network.  Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways.  Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network.  The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network.  Here, we demonstrate that use of mRNA profiling to collect and analyze detailed descriptions of changes in the network state resulting from specific network perturbations is a powerful and economical strategy to elucidate regulatory relationships among the components of a complex signaling network.  Specifically, we studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2). This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with the Pto DC3000 AvrRpt2 and used as detailed descriptions of the network states resulting from specific genetic perturbations.  Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data.  The resulting network model accurately predicted 22 of 23 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate.  The network model revealed two striking features: (i) the components of the network are highly interconnected; (ii) negative regulatory relationships are common between signaling sectors.  One case of a novel negative regulatory relationship, between the early microbe-associated molecular pattern (MAMP)-activated sector and the salicylic acid (SA)-mediated sector, was further validated.  We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector-switching" network, which effectively balances two apparently conflicting demands, robustness against pathogenic perturbations and moderation of negative impacts of immune responses on plant fitness.

Keywords: Responses of reference Arabidopsis immunity mutants to Pseudomonas syringae pv. tomato DC3000 carrying avrRpt2

overall_design: This experiment consists of two (group00) or three (group01-04) biological replicates of each genotype (total 25 genotypes [3 are multiple mutants, which were removed for the network modeling, but were used for normalization]). For each genotype, two leaves per plant were pooled from three pots to prepare total RNA.

first: Fumiaki

last: Katagiri


title: Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

status: Public on Sep 18 2013

first: Jessica

last: Nordlund

address: Academic Hospital, Entrance 70, 3rd floor

department: Medical Sciences

summary: We surveyed the DNA methylation levels of 435,941 CpG sites in samples from 764 children at diagnosis of ALL and from 27 children at relapse. This survey uncovered four characteristic methylation signatures. First, compared with control blood cells, the methylomes of ALL cells shared 9,406 predominantly hypermethylated CpG sites, independent of cytogenetic background. Second, each cytogenetic subtype of ALL displayed a unique set of hyper- and hypomethylated CpG sites. The CpG sites that constituted these two signatures differed in their functional genomic enrichment to regions with marks of active or repressed chromatin. Third, we identified subtype-specific differential methylation in promoter and enhancer regions that were strongly correlated with gene expression. Fourth, a set of 6,612 CpG sites was predominantly hypermethylated in ALL cells at relapse, compared with matched samples at diagnosis. Analysis of relapse-free survival identified CpG sites with subtype-specific differential methylation that divided the patients into different risk groups, depending on their methylation status.

overall_design:
The DNA methylation levels of primary pediatric ALL samples taken at diagnosis (n= 764), remission(n=86), first relapse (n=27), second relapse (n=5), fractionated blood cells from healthy blood donors (n=51), and methylation +/- controls (n=11) were analyzed with the Illumina Infinium HumanMethylation 450k BeadChips. One ALL sample was run in duplicate (technical replicate).

[UPDATE] 04-26-2024: The raw data and processed data were removed from this dataset due to patient privacy concerns.

first: Christofer

middle: L

last: Bäcklin

first: Gudmar

last: Lönnerholm

first: Ann

last: Syvänen


title: Natural variation in RPS2-mediated resistance: correlating gene-expression profiles to phenotypic responses.

status: Public on Aug 09 2007

summary:
Natural variation within plant species is an important resource for discovery of genes controlling biological traits. Gene-expression profiling of natural variation is increasingly used to identify genes affecting a trait. Here, we explored variation among Arabidopsis thaliana accessions with respect to defense against Pseudomonas syringae pv. tomato DC3000 (Pst), with a focus on R-gene mediated resistance triggered by the Pst type III effector protein AvrRpt2. We explored variation at two phenotypic levels: growth of the bacteria and hypersensitive response (HR) measured by electrolyte leakage. Considerable variation among accessions was found at both phenotypic levels. The genetic variation among accessions affected both growth of Pst with (Pst avrRpt2) and without (Pst) the AvrRpt2 effector, with some variation being specific for the bacterial strains, and other variation affecting both strains in a similar manner. Variation in HR was not correlated with variation in bacterial growth. Additionally we examine variation in gene-expression profiles after mock- and Pst avrRpt2-inoculated plants, obtained using a dedicated microarray Gene-expression profiling at 6 h post inoculation identified clusters of genes from which expression levels are correlated with bacterial growth and electrolyte leakage. The expression levels of some of these clusters correlate with more than one phenotypic characteristic, such as growth of both Pst and Pst avrRpt2, whereas other clusters were correlated with just one biological parameter. Thus we demonstrate that variation in gene-expression profiles among Arabidopsis accessions is correlated with variation in phenotypic responses.
Keywords: Comparisons of Arabidopsis thaliana accessions with respect to inoculation with Pseudomonas syringae pv tomato avrRpt2.

overall_design: We compared gene-expression six hours after mock- or Pst avrRtp2-inoculation of nine Arabidopsis thaliana accessions (Col-0, Cvi-1, Est-1, Kas-1, Kin-0, Ler-0, Mt-0, Tsu-1, Ws-2), using three replicates per accession-treatment combination.

first: Remco

middle: M

last: Van Poecke


title: Gene expression level changes during the formation of a-synuclein newly formed fibrils and their maturation into LB-like inclusions in a neuronal seeding model

status: Public on Jan 15 2020

city: Lausanne

first: Hilal

last: Lashuel

address: Station 19, AI2142, Batiment AI

institute: EPFL

summary: Parkinson’s disease (PD) is characterized by the accumulation of misfolded and aggregated alpha-synuclein (α-syn) into intraneuronal inclusions named Lewy bodies (LB). Although it is widely believed that α-syn plays a central role in the pathogenesis of PD, the processes that govern α-syn fibrillization and LB formation remain poorly understood. In this work, we sought to dissect the spatiotemporal events involved in the biogenesis of the LBs at the genetic, molecular, biochemical, structural, and cellular levels. Towards this goal, we further developed a seeding-based model of α-syn fibrillization to generate a neuronal model that reproduces all the key events leading to LB formation; including seeding, fibrillization, and the formation of inclusions that recapitulate many of the biochemical, structural, and organizational features of bona fide LBs. Using an integrative omics, biochemical and imaging approach, we dissected the molecular events associated with the different stages of LB formation and their contribution to neuronal dysfunction and degeneration. In addition, we demonstrate that LB formation involves a complex interplay between α-syn fibrillization, post-translational modifications, and interactions between α-syn aggregates and membranous organelles, including mitochondria, the autophagosome and endolysosome. Finally, we show that the process of LB formation, rather than simply fibril formation, is the major driver of neurodegeneration through disruption of cellular functions and inducing mitochondria damage and deficits, and synaptic dysfunctions. We believe that this model represents a powerful platform to further investigate the mechanisms of LB formation and clearance and to screen and evaluate novel therapeutics targeting α-syn aggregation and LB formation.

overall_design: Primary hippocampal neurons were treated with WT PFFs or PBS buffer up to 21 days.

first: Anne-Laure

last: Mahul-Mellier

first: Marion

last: Leleu


title: Copy number variations in mouse mammary tumours driven by mutant Pik3ca^H1047R expression

status: Public on Jun 04 2016

first: Vincent

last: Roh

address: Bugnon 25A

institute: SIB

type: Genome variation profiling by genome tiling array

summary: Profiling of mouse mammary tumours that have developed in a mouse model expressing mutant Pik3ca^H1047R at endogenous level under control of the MMTV promoter (Tikoo et al., PLoS one 2012). Copy number variations in tumours (compared to matching liver DNA) were detected using Agilent Sureprint microarrays.

overall_design: DNA samples prepared from 11 tumours developed in Pik3ca^H1047R mice (biological replicates). For each sample the reference is the matching liver DNA of each animal.

first: Wayne

middle: A

last: Phillips


title: Evaluation of performance of Arabidopsis Pathoarray 464_001: comparison with ATH1

status: Public on Apr 08 2006

summary:
To evaluate technical reproducibility of Arabidopsis Pathoarray 464_001 (GPL3638), two slides were hybridized with labeled amplified RNA prepared from identical RNA. The RNA was prepared from Pseudomonas syringae ES4326- and 5mM MgSO4- injected samples (Psm 24h set C and mock 24h set C. See also GSE4429, GSM99793 and GSM99794).
Keywords: Evaluation of a custom microarray performance

overall_design: We analyzed 2 slides for Psm 24h set C sample and 2 for mock 24h set C sample.


title: Evaluation of the performance of the Arabidopsis Pathoarray 464_001: an example of detailed analysis of mutants

status: Public on Aug 18 2006

summary:
The Arabidopsis Pathoarray 464_001 (GPL3638) was used to compare response of wild-type, rps2-101C (Bent et al., 1994; Mindorinos et al., 1994) and ndr1-1 (Century et al., 1995) to Pseudomonas syringae strain expressing avrRpt2.  The two mutants are compromised in RPS2-mediated resistance but distinct difference between them has not been described.  The results suggested that ndr1-1 affects a defense signaling pathway(s) in addition to the RPS2-dependent pathway, and indicate that the microarray is a powerful tool for systems analysis of the Arabidopsis disease signaling network.
Keywords: Evaluation of the Arabidopsis Pathoarray 464_001 performance

overall_design: This experiment consists of two biological replicates of four samples (Col-0, rps2-101C, ndr1-1 and ndr1-1blind.  The ndr1-1blind was included as a fourth genotype whose identity was unknown to the experimenter and identified as ndr1-1 by genotyping.)  The profiles of the two ndr1-1 were used to set false discovery rate empirically in significant analysis of microarray (Tusher et al., 2001).  A more conservative FDR than the FDR determined empirically using two ndr1-1 was used to analyze other pairwise comparisons.  For each genotype, two leaves per plant were pooled from three pots to prepare total RNA.