title: Differential gene expression analysis by assessing expression variation between tissue specimen of prostate cancer (PCa) and benign prostate hyperplasia (BPH) on a custom expression microarray

status: Public on Jun 17 2020

city: Leipzig

first: Kristin

last: Reiche

address: Perlickstr. 1

institute: Fraunhofer Institute for Cell Therapy and Immunology

summary:
We assessed differential gene expression in tissue specimens of PCa and BPH patients who underwent radical prostatectomy by customized expression microarrays (Agilent).
To detect gene signatures of diagnostic and prognostic value, we assessed fresh frozen radical prostatectomy (RP) samples of PCa and BPH patients by transcriptome-wide sequencing and Agilent custom microarrays.
We stratified PCa patients according to seven clinical risk groups based on Gleason Score (GS), the presence of regional lymph node metastases (pN) and the occurrence of death of disease (DoD): (i) very low  risk (group V: GS<7, pN0), (ii) low risk (group L: GS=7, pN0), (iii) medium risk (group M: GS<=7, pN1), (iv) high risk survivors without lymph node infiltration (group H-s: GS>7, pN0), (v) high risk non-survivors without lymph node infiltration (group H-d: GS>7, pN0, DoD), (vi) high risk survivors with lymph node infiltration (group H+s: GS>7, pN1), (vii) high risk non-survivors with lymph node infiltration (group H+d: GS>7, pN1, DoD). For high risk groups adjacent tumor-free prostate tissue samples were obtained (groups H+sf, H-sf, H+df, H+df). The control group contained patients with benign prostate hyperplasia (group C).
Information on the course of the disease, survival of the patients and the cause of death were obtained from the general practitioners or treating urologists or from records of the regional tumor registry. Clinicopathological parameters were obtained by routine histopathological examination of the surgical specimens. Serum levels of the prostate-specific antigen (PSA) were determined preoperatively (Abbott, Wiesbaden, Germany).
Frozen tissue samples were embedded in Tissue-Tek OCT-compound (Sakura Finetek GmbH, Staufen im Breisgau, Germany) and fixed on metal indenters by freezing. Cryo-sections were prepared using a cryo-microtome (Leica Biosystems, Nußloch, Germany) equipped with a microtome blade C35 cooled to -28 °C. For every tissue three stacks of consecutive cryo-sections (10 µm) were generated, each bordered/flanked by HE-stained cryo-sections (4 µm), which were evaluated by a pathologist with regard to tumor and stroma cell content. PCa tissue stacks had to be flanked on either side by sections containing at least 50 % tumor cells to be used for further analyses. Sections of the tissue stacks were immediately transferred to 1 ml Qiazol (Qiagen, Hilden, Germany) and stored at -80 °C until RNA isolation.

overall_design: Total RNA of RPE-derived freshly frozen tissue of 164 PCa and 39 BPH patients was assessed for gene expression profiling by custom microarrays, including the 48 samples analyzed previously by RNA-seq.

first: Gustavo

middle: B

last: Baretton

first: Sophie

last: Bartsch

first: Catharina

last: Bertram

first: Conny

last: Blumert

first: Tilo

last: Buschmann

first: Sabina

last: Christ

first: Kati

last: Erdmann

first: Maik

last: Friedrich

first: Michael

last: Froehner

first: Susanne

last: Fuessel

first: Joerg

last: Hackermueller

first: Friedemann

last: Horn

first: Markus

last: Kreuz

first: Dennis

last: Loeffler

last: Muders

first: Dominik

last: Otto

first: Sven-Holger

last: Puppel

last: Rade

last: Specht

first: Marieta

middle: I

last: Toma

first: Karolin

last: Wiedemann

first: Manfred

last: Wirth


title: Evaluation of the physiological effects of a biotechnologically produced oyster mushroom in the liver of obese Zucker rats by transcriptomics

status: Public on Jun 06 2020

city: Gießen

first: Robert

last: Ringseis

address: Heinrich-Buff-Ring 26-32

department: Institute of Animal Nutrition and Nutrition Physiology

country: Germany

institute: JLU Gießen

summary: The hypothesis was tested that biotechnologically produced Pleurotus sajor-caju (PSC) influences metabolic health of obese Zucker rats. To test this, obese Zucker rats were randomly assigned to 2 groups of 12 rats each with similar body weights (BW) and fed diets either without (OC) or with 5 % PSC (OPSC) for 4 weeks and hepatic transcript profiling was performed.  Transcriptomics of the liver revealed a total of 580 transcripts differentially expressed between OPSC and OC.

overall_design: For microarray analysis, n = 6 RNA samples each of the group OC and group OPSC were used for hybridization to the Affymetrix Rat Gene 2.0 ST array.

first: Garima

last: Maheshwari

first: Denise

middle: K

last: Gessner

first: Klaus

last: Eder


title: RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia [KARPAS-45 AI-10-104 RNA-seq]

status: Public on Jun 05 2020

city: Ghent

first: Filip

last: Matthijssens

state: België

address: Corneel Heymanslaan 10

department: Biomolecular Medicine

country: Belgium

institute: Ghent University

type: Expression profiling by high throughput sequencing

summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy with a high incidence of relapse. Here we show that Runt-related transcription factor 2, RUNX2 is upregulated in high-risk T-ALL with KMT2A rearrangements (KMT2A-R) or immature phenotype. In KMT2A-R cells, we identified RUNX2 as a direct target of the KMT2A chimeras, while it reciprocally binds the KMT2A promoter, establishing a regulatory feed-forward mechanism. Notably, RUNX2 is required for survival in immature and KMT2A-R T-ALL in vitro and in vivo. We report a direct transcriptional regulation of CXCR4 signaling by RUNX2, which thereby promotes cell migration and adhesion. Functionally, RUNX2 impacts T-ALL cell homing and exacerbates T-ALL progression to medullary and extramedullary sites. We demonstrate that RUNX2 enables these energy-demanding processes by increasing metabolic activity in T-ALL cells through positive regulation of both glycolysis and oxidative phosphorylation. Concurrently, RUNX2 upregulation results in increased mitochondrial dynamics and biogenesis in T-ALL cells. As a proof of concept, immature and KMT2A-R T-ALL cells are vulnerable to pharmacological targeting of the interaction of RUNX2 with its co-factor CBFβ. In conclusion, we identify RUNX2 a dependency factor in immature and KMT2A-R T-ALL that regulates cell metabolism and disease progression

overall_design: Examination of transcriptional changes upon in KARPAS-45 upon 24 hours treatment with 20 µM of the pan-RUNX inhibitor AI-10-104.

first: Pieter

last: Van Vlierberghe


title: Ets1 confers context-dependent activation of Notch signaling in T-cell leukemia

status: Public on Jul 07 2020

city: Ann Arbor

first: Mark

middle: Yat-fung

last: Chiang

state: MI

address: 109 Zina Pitcher Place

department: Internal Medicine/Heme-onc

country: USA

institute: University of Michigan

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Expression data of whole kidneys from fetuses subjected to chronix hypoxia or caloric restriction vs controls

status: Public on Jun 30 2020

city: Bern

first: Stefan

last: Rudloff

state: BE

address: Freiburgstrasse 15

department: Department for BioMedical Research

country: Switzerland

institute: University of Bern and University Hospital

summary:
Reduced oxygen availability during embryogenesis leads to intra-uterine growth restriction (IUGR), increasing the risk for hypertension, cardiovascular and chronic kidney disease (CKD) in adults. Although this association has long been recognized, underlying mechanisms still require extensive research.
We set up a robust murine model of fetal hypoxia-induced IUGR and characterize its short and long-term consequences, using the kidney as a readout. Developing hypoxic kidneys show an induction of liver-specific genes.

overall_design: Total RNA was isolated from male hypoxic (Hy1, Hy2, Hy3), normoxic (No1, No2, No3) and caloric control (Cc1, Cc2, Cc3) E18.5 kidneys, processed and hybridized to Affymetrix Mouse Gene 1.0 ST arrays

first: Mathilde

last: Janot

first: Uyen

last: Huynh-Do


title: Identification of genes associated with biosynthesis of unsaturated fatty acid and oil accumulation in herbaceous peony 'Hangshao' (Paeonia lactiflora 'Hangshao') seeds based on transcriptome analysis

status: Public on Jun 04 2020

city: Yangzhou

first: Jiasong

last: Meng

address: 48 east wenhui road

department: College of horticulture and  plant protection

country: China

institute: Yangzhou University

summary: High-throughput RNA sequencing were performed to identify a large number of mRNAs in developmental herbaceous peony seeds at different periods to provide useful information for elucidating the molecular mechanism of the lipid biosynthesis and fatty acid accumulation for herbaceous peony 'Hangshao'.

overall_design: RNA sequencing in Paeonia lactiflora (‘Hangshao’) seeds

first: Jun

last: Tao


title: RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia [KARPAS-45 RUNX2 shRNA knockdown RNA-seq]

overall_design: Examination of transcriptional changes upon  RUNX2 shRNA mediated knockdown  in the T-ALL cell line KARPAS-45. KARPAS-45 cells were transduced with shRUNX2-1 (TRCN 0000013653), shRUNX2-2 (TRCN 0000013655) or scrambled control (plko-shc002) and sampled 48 hours and 72 hours later. Data obtained from control was compared to pooled data from both RUNX2 specific hairpins for 5 independent experiments


title: The chromatin landscape modified by Zbtb18 in activated B cells

status: Public on Sep 01 2020

city: Oxford

first: Irina

last: Udalova

state: Oxfordshire

address: The Kennedy Institute of Rheumatology, Roosevelt Drive, Headington

department: NDORMS

country: United Kingdom

institute: Kennedy Institute

summary: The differentiation of plasma cell is prescisely controlled by the key transcriptional program as well as epigenetic changes. Recently, we have identified, one zinc finger protein, Zbtb18, as a new regulator for B cell differentiation process. To investigate the molecular mechanisms of Zbtb18 during B cell differentiation program we employed the assay for transposase (Tn5) -accessible chromatin followed by deep sequencing (ATAC-Seq) in the sorted Control and Zbtb18 over-expressing B cells (B220+ CD138-) before and after anti-CD40 and IL-4 stimulation. Mice primary B cells were retrovially transduced  with either control vector with RFP repoter or Zbtb18 with GFP repoter, and both were primed 2 days on the 40LB stroma cells before mixed 1:1 and then stimulated with anti-CD40 (10ug/ml) and IL-4 (10ng/ml) for 2 days. Activated B cells, B220+ CD138-, were sorted by BD AriaIII and followed by ATAC-seq protocol (Nat Methods. 2017 Oct;14(10):959-962).

overall_design: ATAC-seq in control and Zbtb18 over-expressing B cells, stimulated with anti-CD40 and IL-4 for 2 days (n=3) or unstimulated (n=2)

first: Bin

last: Xie

first: Tariq

middle: E

last: Khoyratty

first: Tal

last: Arnon


title: RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia [RUNX2 ChIP-seq]

overall_design: Examination of RUNX2 genomewide binding and H3K27acetylation in two T-ALL cell lines


title: RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia [KMT2A-MLLT1_ Runx2 ko RNA-seq]

overall_design: Examination of transcriptional changes upon in Runx2fl/fl;CreER T2tg mouse bone marrow progenitor compared to cells that were transformed in vitro by KMT2A-MLLT1 retroviral transduction. In vitro transformation of mouse progenitor cells was performed on lineage depleted (Runx2fl/fl CreErt2tg/+) BM cells that were transduced with KMT2A-MLLT1-eGFP expressing retrovirus. To achieve complete Runx2 knockout, cells were treated with 400 nM 4-hydroxytamoxifen (4-OHT) for 24 hours.


title: RNA-seq on MCF10A-YAP cells (overexpressed constrictively activated YAP in MCF10A cells) transduced with sgRNAs vectors targeting TRAM2 gene

status: Public on Jun 01 2020

city: amsterdam

first: LI

last: LI

address: hamontstraat, 378

country: Netherlands

institute: NKI

summary: We performed a CRISPR-based functional genetic screen targeting TEAD4 binding motif  located within the YAP-bound enhancers. The screen identified a novel enhancer regulating TRAM2. We observed TRAM2 overexpression can induce EMT as YAP does. Then, we performed the RNA-seq to measure the transcription changes upon TRAM2-KOs in MCF10A-YAP cells

overall_design: We have three conditions including empty vector control, TRAM2-overexpression, YAP-over expression, for each sample, we have three biological  replicates

first: Li

last: Li

first: Alejandro

middle: P

last: Ugalde

first: Reuven

last: Agami


title: RNA-seq on MCF10A cells overexpressed with empty control vectors, TRAM2 and activated-YAP

summary: We performed a CRISPR-based functional genetic screen targeting TEAD4 binding motif  located within the YAP-bound enhancers. The screen identified a novel enhancer regulating TRAM2. We observed TRAM2 overexpression can induce EMT as YAP does. Then, we performed the RNA-seq to measure the transcription changes upon TRAM2 and YAP overexpression


title: The early T4 protein, MotB, compacts host DNA and disrupts H-NS dependent repression.

status: Public on Jun 11 2020

city: Bethesda

first: Jennifer

middle: Patterson

last: West

state: Md

address: 8 Center Drive

department: Laboratory of Cell and Molecular Biology

institute: NIDDK

summary:
Purpose: We investigated the effect of the T4 MotB protein on E. coli gene expression
Method: BL21(DE3) E. coli containing either pNW129 or pNW129-MotB were grown to early log phase (OD600 ~ 0.3)  then induced with 0.2% arabinose for 20 minutes. Cells were then harvested and total RNA was isolated. The cDNA library was prepared using a modified RNATagSeq workflow as previously described (Shishkin, A.A. et al. 2015 Nat Methods). Optimum fragmentation of the total RNA samples in this library was determined to be 3 min at 94C in FastAP buffer (Thermo Fischer Scientific).  The cDNA Library was run on a Bioanalyzer using the Agilent High Sensitivity DNA Kit to evaluate the quality of the library.  The concentration of the cDNA library was determined by qPCR using the KAPA Library Quantification Kit (Kapa Biosystems, Wilmington, MA, USA) and CFX96 Real-Time PCR Detection System (Bio-Rad, Hercules, CA, USA). Sequencing was performed by the NIDDK Genomics Core facility using a MiSeq system with the single-end 50 bp Sequencing Kit (Illumina, San Diego, CA, USA). RNA-seq data was processed as previously described using E. coli B str. DE3 (NC_012971.2) as the reference genome.  Differential expression between conditions was represented as a fold change, and genes with both a fold change ≥2 and adjusted p value ≤ 0.05 were considered significant.
Results: RNA-seq data revealed that the expression of genes encoded in the cryptic prograge Lambda DE3 as well as an additional 29 of E. coli genes were significantly increased after motB expression.
Conclusion: T4 MotB is a DNA binding protein that compacts host DNA and disrupts H-NS dependent repression.

overall_design: To determine the effect of the T4 MotB protein on E. coli  gene expression, RNAseq was performed for BL21 (DE3) E. coli  producing T4 MotB for 20 minutes.

last: Patterson-West

first: Bokyung

last: Son

first: Meng-Lun

last: Hsieh

first: Emilios

last: Dimitriadis

first: Revathy

last: Ramachandran

first: James

middle: R

last: Iben

first: Leslie

last: Knipling

first: Chin-Hsien

last: Tai

first: Deborah

middle: M

last: Hinton


title: XPO4 negatively regulates immune activation in the cpr5 mutant

status: Public on Jun 15 2020

city: Berkeley

first: Yangnan

last: Gu

state: CA

address: 371 Koshland Hall

department: Plant and Microbial Biology

institute: University of California at Berkeley

summary:
Purpose: To understand the severe phenotype caused by the genetic interaction between CPR5 and XPO4, we performed the whole genome transcriptome analysis on 10-day-old seedlings of WT, xpo4, cpr5, and xpo4cpr5.
Conclusions: XPO4 is a critical negative regulator of plant immunity, which is required to prevent an otherwise catastrophic induction of immune and cell death responses in the cpr5 mutant.

overall_design: mRNA profiles of 10-day-old seedlings of wild type (Col-0), xpo4, cpr5, and xpo4cpr5 mutants were generated by deep sequencing, in triplicate, using Illumina HiSeq PE-150.

first: Feifei

last: Xu


title: Low KLF11 Determines the CSC–like Identity in Sarcoma via restraining YAP transactivity

status: Public on Jun 25 2020

city: Nanjing

first: Le

last: Qu

address: 305 East Zhongshan Road

institute: Jinling Hospital, Clinical School of Medical College, Nanjing University

relation:
SuperSeries of: GSE133309
SuperSeries of: GSE133310
SuperSeries of: GSE133311


title: Gene expression profiling of chondrodysplasia mutants and isogenic controls during hypertrophic induction from iPSCs

status: Public on May 20 2020

city: Kyoto

first: Junya

last: Toguchida

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

country: Japan

institute: Center for iPS Cell Research and Application

summary:
In order to better understand chondrodysplasia disease mechanisms, we induced hypertrophic chondrocytes from chondrodysplasia-specific iPSCs and analyzed their gene expression profile.
This dataset includes the expression data obtained from iPSC-derived cartilage pellets on day 56 of hypertrophic induction. Three COL10A1 mutants and two MATN3 mutants were compared to their isogenic controls to determine the effects of each mutation on the unfolded protein response.

overall_design: A total of 27 samples (5 mutants and 4 isogenic controls, each with 3 biological replicates) were analyzed.

first: Yann

last: Pretemer


title: Genome-wide maps of CoRest-C, Rpd3, and CBP binding and nuclear RNA-seq in Drosophila mushroom body

status: Public on May 16 2020

city: Sai Kung

first: Yukinori

last: Hirano

address: Clear water bay

department: LIFS

country: Hong Kong

institute: The Hong Kong University of Science and Technology

summary:
Purpose: In Drosophila, we determined that neural activity-dependent transcription is controlled by CBP, Rpd3, and CoRest-C. To investigate the dynamics of those binding to the chromatin, and the relationship with activity-dependent transcription, we conducted the ChIP-seq assay for the three proteins, and nuclear RNA-seq analysis in mushroom body in Drosophila, either in naive state or after optogenetic activation.
Methods: The nuclei of mushroom body were collected by immunoprecipitation-based method (Hirano Y., et al, 2016, Nature Communications, also see extraction protocol below). The chromatin prepared from the collected mushroom body was used for ChIP-seq with antibody for CBP, Rpd3 or CoRest-C. For CBP and Rpd3, antibody was raised against the endogenous proteins. For CoRest-C, which was tagged by myc, anti-myc antibody was used. In nuclear RNA-seq, mRNA was purified from the mushroom body nuclei with oligo dT magnetic beads, and used to prepare library. After deep sequencing in triplicate using illumine Hiseq X, the adaptors were trimmed via Trimommatic, followed by mapping to the Drosophila reference genome, dm6 from UCSC using STAR. The reads with low mapping quality below 8 and the non-primary mapped reads were eliminated. MACS was used for peak calling in ChIP-seq on Strand NGS software, using a default setting except for the following parameters; 10-4 as a P-value cutoff, and 3 as a enrichment factor. The binding sites were determined when the peaks were overlapped in at least 2 out of 3 biological replicates, using the optogenetically activated samples. For RNA-seq, the filtered reads were analyzed with HTSeq-count to obtain numbers of the reads mapped on exons, which was further analyzed on R using DESeq2
Results: Using an optimized data analysis workflow, we mapped about 9-18 million reads for ChIP-seq, and 30-40 million reads for nuclear RNA-seq to Drosophila reference genome, dm6  In ChIP-seq, binding of all proteins was enriched nearby the transcriptional start site (TSS). The binding sites determined were 1,237 for CoRest-C, 2,717 for Rpd3, and 6,684 for CBP. Importantly, among CoRest-C binding sites, overlapping sites of CoRest-C and CBP were 1,038/1,237 (83.9%), those of CoRest-C and Rpd3 were 789/1,237 (63.8%), and those of CoRest-C, Rpd3, and CBP were 704/1,237 (56.9%), suggesting that these three proteins colocalize on the specific genomic regions In nuclear RNA-seq, we found that upregulation of gene expression is robust at 10-min after 5-min optogenetic activation. The genes showing significant difference were 2,702 at this time point, in which 1,582 genes showed increase, and the rest showed decrease in the expression. Among the 1,582 increased genes, 1,055 genes were bound by CBP, supporting the idea that CBP is an important factor in activity-dependent transcription. Furthermore, 338 was bound by CoRest-C, 254 of which showed colocalization with CBP and Rpd3.
Conclusions: Our study represents the first detailed analysis of activity-dependent transcription in mushroom body in Drosophila, with biologic replicates, generated by ChIP-seq and RNA-seq technology. We found the rapid response of transcription after optogenetic activation, and its colocalization with CBP, Rpd3 and CoRest-C binding sites. These data strongly support the idea that these three proteins control activity-dependent transcription.

overall_design: Examination of 3 different proteins (CBP, Rpd3, and CoRest-C) and nuclear RNA-seq in mushroom body nuclei from WT Drosophila


title: Role of PDK1 in Skeletal Muscle Hypertrophy Induced by Exercise Load

status: Public on May 14 2020

city: Kobe

first: Naoki

last: Kuramoto

state: Hyogo

address: 7-5-1 Kusunoki-cho, Chuo-ku

department: Division of Diabetes and Endocrinology, Department of Internal Medicine

institute: Kobe University Graduate School of Medicine

summary:
Skeletal muscle mass is an important determinant of whole-body glucose disposal. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3'-phosphoinositide–dependent kinase 1 (PDK1), a key component of the phosphatidylinositol 3-kinase (PI3K) signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of exercise load–induced muscle hypertrophy.
Whereas exercise load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by exercise load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of protein synthesis via the S6K-S6 axis.

overall_design: Total RNA was extracted from plantaris muscle of wild-type or mutant mice at 10 days after synergistic muscle ablation and was subjected to hybridization with the use of an Affymetrix Mouse Gene 2.0 ST Array (Affymetrix, Santa Clara, CA).

first: Wataru

last: Ogawa

last: Kurmoto


title: Robust Hi-C maps of enhancer-promoter interactions reveal the function of non-coding genome in neural development and diseases

status: Public on Jun 26 2020

city: Cleveland

first: Xiaoxiao

last: Liu

state: Ohio

address: 10900 Euclid Ave

department: Genetics and Genomes Sciences

institute: Case Western Reserve University

summary: Despite recent progress in mammalian 3D genome studies, it remains experimentally and computationally challenging to identify chromatin interactions genome-wide. Here we developed a highly efficient “easy Hi-C” (eHi-C) protocol that generates high-yield libraries with 0.1 million cells. After rigorous bias-correction with a significantly improved Hi-C analysis pipeline, we can directly recognize the dynamic long- and short-range chromatin loops from contact heatmaps. We compared 10 ultra-deep Hi-C or eHi-C datasets (billion- read scale) from human tissue- or cell types focusing on brain and neurogenesis. We found that H3K9me3 marks a 3D genome compartmental barrier for induced pluripotency. Dynamic chromatin loops, but not genome compartments, are hallmarks of neuronal differentiation and neuron-related diseases. Interestingly, we observed many neuron-specific enhancer-promoter looping clusters spanning Mb-scale neighborhoods, supporting a phase-separation model leading to enhancer aggregation during brain development. Taken together, our 3D genome analyses shed light on the regulation of brain development and complex neuronal diseases.

overall_design:
3D genome structure mapping in human neurogenesis (from human induced pluripiotent stem cells to neural progenitor cells to neuron cells) using a newly designed easy Hi-C method
----------------------------------
GSM1267196: anchor_2_anchor.loop.H1.txt.gz
GSM1267197: anchor_2_anchor.loop.H1.txt.gz
GSM1055800: anchor_2_anchor.loop.IMR90.txt.gz
GSM1055801: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154021: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154022: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154023: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154024: anchor_2_anchor.loop.IMR90.txt.gz
GSM1055802: anchor_2_anchor.loop.IMR90.txt.gz
GSM1055803: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154025: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154026: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154027: anchor_2_anchor.loop.IMR90.txt.gz
GSM1154028: anchor_2_anchor.loop.IMR90.txt.gz
GSM1181867: anchor_2_anchor.loop.GM12878.txt.gz
GSM1181868: anchor_2_anchor.loop.GM12878.txt.gz
GSM1551583: anchor_2_anchor.loop.GM12878.txt.gz
GSM1551584: anchor_2_anchor.loop.GM12878.txt.gz
GSM1551586: anchor_2_anchor.loop.GM12878.txt.gz
GSM1608505: anchor_2_anchor.loop.GM12878.txt.gz
GSM2054564: anchor_2_anchor.loop.CP.txt.gz
GSM2054565: anchor_2_anchor.loop.CP.txt.gz
GSM2054566: anchor_2_anchor.loop.CP.txt.gz
GSM2054567: anchor_2_anchor.loop.GZ.txt.gz
GSM2054568: anchor_2_anchor.loop.GZ.txt.gz
GSM2054569: anchor_2_anchor.loop.GZ.txt.gz

first: Leina

last: Lu

first: Wei-Kai

last: Huang

first: Yan

last: Li

first: Fulai

last: Jin

first: Guoli

last: Ming


title: RUNX2 is a dependency factor in immature and KMT2A-rearranged T-cell acute lymphoblastic leukemia

first: Filip

last: Matthijssens

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: RNA sequencing of mouse myotubes C2C12 along with treatment of S2-013 conditioned media with and without resveratrol

status: Public on May 10 2020

city: Omaha

first: Pankaj

last: Singh

state: Nebraska

address: 505 S 45th St

department: Eppley

institute: University of Nebraska Medical Center

summary: RNA was sequenced from differentiated C2C12 mouse myotubes that were treated with S2-013 conditioned media with or without resveratrol in comparison to control media

overall_design: C2C12 mouse myotubes were differentiated and treated with control media or 24 hour conditioned media from S2-013 cells with or without supplementation with 50 µM of resveratrol for 24 hours

first: Aneesha

last: Dasgupta

first: Ryan

middle: J

last: King

first: Surendra

last: Shukla


title: CTCF is dispensable for cell fate conversion but facilitates acute cellular responses [ATAC-seq]

status: Public on May 06 2020

city: Barcelona

first: Maria

last: Vila-Casadesús

state: Barcelona

address: Carrer del Dr. Aiguader, 88

country: Spain

institute: CRG

summary: Studies of genome topology, chromatin state and gene expression dynamic during human B cell to macrophage transdifferentiation with and without CTCF

overall_design: Chromatin accessible site profiling during  human B cell to macrophage transdifferentiation using ATAC-seq

first: Gregoire

last: Stik

last: Vila-Casadesus

first: Thomas

last: Graf


title: Integrated omics analysis reveals the norisoprenoid responses in Vitis vinifera L. cv. Cabernet Sauvignon berries to abscisic acid and synthetic auxin

status: Public on May 12 2020

city: Beijing

first: Lei

last: He

address: No. 17 Tsinghua east road

institute: China Agricultural University

summary: The abscisic acid (ABA) increase and auxin decline are both indicators of ripening initiation in grape berry, and norisoprenoid accumulation also start at around the onset of ripening. To investigate the transcriptional and posttranscriptional regulation of the ABA and synthetic auxin 1-naphthaleneacetic acid (NAA) on norisoprenoid production, we performed time series GC-MS and RNA-seq analyses on Cabernet Sauvignon grape berries from pre-veraison to ripening. Higher levels of free norisoprenoids were found in ABA-treated mature berries in two consecutive seasons, and both free and total norisoprenoids were significantly increased by NAA in one season. The expression pattern of known norisoprenoid-associated genes in all samples and the up-regulation of specific alternative splicing isoforms of VviDXS and VviCRTISO in NAA-treated berries were predicted to contribute to it. Combined weighted gene co-expression network analysis (WGCNA) and promoter motif prediction analysis suggested that GATA26 and GATA28 could be potential regulators of norisoprenoid accumulation. Finally, the network analysis uncovered the interaction between previously identified switch genes, hormone-related genes and norisoprenoid-associated genes.

overall_design: Twelve grape berry sample groups were used for RNA sequencing in this study, consisting of ABA1000, NAA100 and the control at the E-L 34, E-L 35 E-L 36 and E-L 38 stages, respectively.

first: Zhi-Yuan

last: Ren

first: Xiao-Ping

last: Tang

first: Qiu-Hong

last: Pan


title: CTCF is dispensable for cell fate conversion but facilitates acute cellular responses

overall_design: Refer to individual Series


title: Transcriptome analysis of QPRT silencing in breast cancer cells

city: Taipei

first: Shih-Ping

last: Cheng

address: 92, Chung-Shan North Road, Section 2

department: Department of Surgery

country: Taiwan

institute: MacKay Memorial Hospital

summary: We identified quinolinate phosphoribosyltransferase (QPRT) as a prognostic factor in breast cancer. Transcription profiling analysis was performed in breast cancer cells transfected with control or QPRT shRNA.

overall_design: QPRT expression was depleted in BT-20 and MDA-MB-468 human breast cancer cells by shRNA interference. Total RNA was extracted following QPRT knockdown and submitted to RNA sequencing.

first: Yuan-Ching

last: Chang


title: Hallmarks of basidiomycete soft- and white-rot in wood-decay -omics data of Armillaria [AROC18]

status: Public on May 04 2020

city: Szeged

first: Laszlo

middle: G.

last: Nagy

state: Csongrad

address: Temesvari krt 62

department: Institute of Biochemistry, Synthetic and Systems Biology Unit

country: Hungary

institute: Biological Research Centre, Hungarian Academy of Sciences

summary: The genus Armillaria spp. (Fungi, Basidiomycota) includes devastating pathogens of temperate forests and saprotrophs that decay wood. Pathogenic and saprotrophic Armillaria species can efficiently colonize and decay woody substrates, however, mechanisms of wood penetration and colonization are poorly known. We assayed the colonization and decay of autoclaved spruce roots using the conifer-specialists Armillaria ostoyae and A. cepistipes using transcriptomic and proteomic data. Transcript and protein levels were altered more extensively in the saprotrophic A. cepistipes than in the pathogenic A. ostoyae and in invasive mycelia of both species compared to their rhizomorphs. Diverse suites of carbohydrate-active enzyme genes (CAZymes), in particular pectinolytic ones and expansins, were upregulated in both species, whereas ligninolytic genes were mostly downregulated. Our gene expression data, together with previous comparative genomic and decay-chemistry analyses suggest that wood decay by Armillaria differs from that of typical white rot fungi and shows features resembling soft rot. We propose that Armillaria species have modified the ancestral white rot machinery so that it allows for selective ligninolysis based on environmental conditions and/or host types.

overall_design: Tissue samples from pathogenic and saprotropic Armillaria species colonizing spurce root were collected and profiled. Each group has 2-3 replicates.

first: Neha

last: Sahu

first: Zsolt

last: Merenyi

first: Balazs

last: Balint

first: Brigitta

last: Kiss

first: Gyorgy

last: Sipos

first: Rebecca

last: Owens

middle: G


title: Effects of various causes, such as aging, smoking, and epithelial damage, on the global gene expression profiles of the mouse nasal mucosa and olfactory bulb

status: Public on May 28 2020

city: Chiba

first: Shigeyuki

last: Shichino

address: 2641, Yamasaki, Noda-shi

department: Department of Molecular regulation of Inflammatory and Immune Diseases

institute: Tokyo University of Science

summary: The olfactory system is a part of the mammalian central nervous system and is characterized by neurogenesis and replacement of degenerated neurons. Clinically, it has been reported that the various causes including aging, smoking, and epithelial damage have a high incidence of olfactory impairment. However, the molecular mechanisms underlying these causes-associated defect of olfaction have yet been unclear. To elucidate this problem, we performed micoarray analysis against mouse nasal mucosa and olfactory bulb and compared the transcriptome of them among groups.

overall_design: Gene expression of nasal mucosa and olfactory bulb from young-adult (8 weeks of age) and aged (16 months of age) male C57BL/6 mice was measured as follows; young and aged control groups, young and aged smoking groups (days 1, 7, 14, 28, 42 after 20 times of smoking), young and aged damaged groups (days 7 and 14 after epithelial damage), young and aged smoking and damaged group (days 7 and 14 after epithelial damage).　Each total RNA sample pooled from 5 biological replicates (two experimental replicate) was analyzed using microarray.

first: Rumi

last: Ueha

first: Satoshi

first: Kenji

last: Kondo

first: Shu

last: Kikuta

first: Hironobu

last: Nishijima

first: Francis

last: HW Shand

first: Kouji

last: Matsushima

first: Tatsuya

last: Yamasoba


title: Whole genome non-coding RNA profiling of the developing hippocampus of the Down syndrome mouse model Dp16(1)Yey

status: Public on May 31 2020

city: Guangzhou

first: Xiaoling

last: Jiang

state: Guangdong

address: 9 Jinsui Road, Tianhe District

department: Department of Genetics and Endocrinology

institute: Guangzhou Women and Children's Medical Center

type: Non-coding RNA profiling by high throughput sequencing

summary: In this study we performed a systematic analysis of the non-coding RNA (ncRNA) transcriptomes of the Down Syndrome (DS) developing hippocampus using the DS mouse model Dp16(1)Yey. DS, caused by the trisomy of chromosome 21 (HSA21) is the most frequent human chromosomal disorder. Hippocampal-dependent learning and memory impairment is one of the most significant deficits of DS. ncRNAs: microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) have been increasingly revealed to be participating in various biological activities, especially in the brain development and neuronal functions. This study provides a map of the dysregulated lncRNAs and circRNAs in the DS developing hippocampus for the first time.

overall_design: Hippocampi were isolated from the postnatal day 7 Dp16(1)Yey pups and their wild-type littermates. Three hippocampi with the same genotype were pooled together. The non-coding RNA profilings of the DS mutant Dp16(1)Yey were compared with the ones of wild-type.

first: Zhaowei

last: Cai

first: Zhilan

last: Xiao

first: Huazhen

last: Liu

first: Li


title: Neurodevelopmental Defects and Neurodegenerative Phenotypes in Human Brain Organoids Carrying Parkinson Disease-Linked DNAJC6 Mutations

status: Public on May 27 2020

city: Seoul

first: wahyu

last: handoko

address: 222 Wangsimni-ro, Seongdong-gu, Seoul

department: Department of Biochemistry and Molecular Biology

country: South Korea

institute: Hanyang University

summary: In this study, human isogenic model of juvenile onset PD caused by DNAJC6 mutation were made. Human ESCs edited using CRISPR-Cas9 to make deleterious DNAJC6 mutation was induced to human midbrain like organoid (hMLO) for studying the mechanism of DNAJC6 deleterious mutation in causing PD

overall_design: mRNA profile from 3D organoid Culture of Wildtype and Mutant DNAJC6 midbrain-like Organoid at DIV0, DIV 4, DIV 15, and DIV 30

first: Sang-Hun

last: Lee

first: Seung-Jae

first: Noviana

last: Wulansari

first: Wahyu

last: Darsono


title: Hallmarks of basidiomycete soft- and white-rot in wood-decay -omics data of Armillaria [ARCE]

first: Laszlo

last: Nagy

first: Neha

last: Sahu

first: Zsolt

last: Merenyi

first: Balazs

last: Balint

first: Brigitta

last: Kiss

first: Gyorgy

last: Sipos

first: Rebecca

last: Owens


title: Long-term transcriptional memory in rice plants submitted to salt shock

status: Public on Apr 28 2020

city: Rio de Janeiro

first: Luis

middle: Willian

last: Pacheco Arge

state: Rio de Janeiro

address: Av. Carlos Chagas Filho, 373

department: Genetica

country: Brazil

institute: UFRJ

summary:
Purpose: Soil salinity is one of the main environmental factors that negatively influences yield, especially for sensitive crops such as rice. Studies report that a disturbing event can prepare the plant for a subsequent event through memory acquisition, involving physiological and molecular processes. Therefore, genes that provide altered responses in subsequent events define a category known as "memory genes." In this work, the RNA-Sequencing (RNA-Seq) technique was used to analyse the transcriptional profile of rice plants subjected to different salt shock events and to characterise genes associated with long-term memory.
Methods: The mRNA of rice plants cv. Ligeirinho was generated using deep sequencing, in duplicate, using Illumina Hi-Seq 2500, for the following treatments:I) control (C): plants received irrigation with water and nutrient solution throughout the experiment; II) vegetative (SV), plants were exposed to saline shock only at the vegetative stage; III) reproductive (SR) plants were exposed to saline shock only at the reproductive stage; and IV) vegetative + productive (SV+R), plants were exposed to saline shock at the vegetative stage (first shock event) and at the reproductive stage (recurrent event). The sequence reads that passed quality filters were analyzed at the transcript level using this method: Mapping using STAR and identification of differentially expressed genes (DEGs) was performed with the edgeR (false discovery rates - FDRs of <0.05). RT–qPCR validation was performed using SYBR Green assays.
Results: Plants subjected to recurrent salt shock showed differences in differentially expressed genes (DEGs). Additionally, the mammalian target of rapamycin (mTOR) pathways, and carbohydrate and amino acid associated pathways were altered under all conditions. Memory genes can be classified according to their responses during the first event (+ or –) and the second shock event (+ or –), being possible to observe a larger number of transcripts for groups [+/–] and [–/+], genes characterised as "revised response."
Conclusions: This is the first long-term transcriptional memory study in rice plants under salt shock, providing new insights into the process of plant memory acquisition.

overall_design: mRNA profiles of rice plants subjected to salt shock at different stages of development (V4 and R0-R1)  were generated by deep sequencing, in duplicate, using Illumina Hi-seq 2500.

first: Amaral

middle: N

last: Marcelo

first: Arge

last: Luís Willian


title: RNA-Seq of wild type and miR-574 knockout mouse hearts at baseline

status: Public on Apr 23 2020

city: Rochester

first: Peng

last: Yao

state: NY

address: 601 Elmwood Avenue, Box CVRI

department: Medicine

institute: Univeristy of Rochester Medical Center

summary:
Purpose: The target mRNAs of miR-574 in mouse heart are unknown. The goal of this study is to use next generation sequencing (NGS) RNA-seq followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) methods to identify the downstream target genes that are directly regulated by miR-574 in murine hearts at the mRNA level.
Results: Using a well established data analysis workflow from the Genomic Research Center from University of Rochester Medical Center,  we analyzed RNA-seq data. We have identified novel genes that are regulated by miR-574 via miRNA-induced silencing complex (miRISC). We defined differentially regulated genes (either upregulated or downregulated) with statistical significance in total RNA expression change (p value <0.05 for differential expressed genes). We identified 34 upregulated genes involved in the small molecule metabolism and the mitochondrial function, and 49 downregulated genes in the electron transport chain (ETC) complex, oxidative phosphorylation, and tricarboxylic acid cycle.
Conclusions: Among 34 upregulated genes, eight genes contain the predicted target seed sequence of miR-574-5p and Fam210a (family with sequence similarity 210 member A) is the only upregulated gene that contains the target seed sequence of both the guide strand miR-574-5p and the passenger strand miR-574-3p. We confirmed that FAM210A was the downstream target of both miR-574-5p and miR-574-3p in vivo and in vitro. Based on our results, we conclude that miR-574 downregulates a limited number of mitochondrial function related genes including FAM210A in mouse hearts at baseline.

overall_design: We extracted totoal RNA from three pairs of fresh P60 heart tissues from WT and miR-574 KO mice (under C57BL6/J genetic background) at baseline. The total RNA samples were subjected to next generation RNA deep sequencing (RNA-Seq). All the extracted RNA samples were treated with DNase I to remove potential genomic DNA followed by purification using phenol:chloroform:isoamyl alcohol for RNA-Seq. Raw reads were generated from the Illumina HiSeq2500 sequencer in the Genomic Core from Case Western Reserve University.

first: Jiangbin

last: Wu

first: Kadiam

middle: C

last: Venkata Subbaiah

first: Feng

last: Jiang

first: Omar

last: Hadaya

first: Amy

last: Mohan

first: Tingting

last: Yang

first: Kevin

last: Welle

first: Sina

last: Ghaemmaghami

first: Wai

middle: H

last: Wilson Tang

first: Eric

last: Small

first: Chen

last: Yan


title: CTCF is dispensable for cell fate conversion but facilitates acute cellular responses [ChIP-seq]

first: Maria

last: Vila-Casadesús

overall_design: CTCF binding site profiling during  human B cell to macrophage transdifferentiation with and without CTCF using ChIP-seq

first: Gregoire

last: Stik

last: Vila-Casadesus

first: Thomas

last: Graf


title: Hippo signaling coordinates cellular quiescence with terminal maturation in iNKT cell development and fate decisions

status: Public on Apr 07 2020

city: Memphis

first: Hongbo

last: Chi

state: TN

address: 262 Danny Thomas Place

department: Immunology

institute: St Jude Children's Research Hospital

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


title: CTCF is dispensable for cell fate conversion but facilitates acute cellular responses [RNA-Seq]

overall_design: Genome expression profiling during  human B cell to macrophage transdifferentiation with and without CTCF using RNA-seq


title: CTCF is dispensable for cell fate conversion but facilitates acute cellular responses [Hi-C]

overall_design: Genome topology profiling during  human B cell to macrophage transdifferentiation with and without CTCF using insitu HiC

middle: V

last: Casadesus


title: miR-200b/200a/429 cluster prevents metastasis and induces dormancy in murine claudin-low mammary tumor cells

status: Public on May 08 2020

city: Guelph

first: Roger

last: Moorehead

address: 50 Stone Rd E

department: Biomedical Sciences

country: Canada

institute: University of Guelph


title: RUNX1-EVI1 disrupts lineage determination and the cell cycle by interfering with RUNX1 and EVI1 driven gene regulatory networks [ChIP-seq]

status: Public on Apr 17 2020

city: Birmingham

first: Peter

last: Keane

address: Vincent Drive

department: Institute for Cancer and Genomic Sciences

institute: University of Birmingham

summary: Hematological malignancies are characterised by a block in differentiation, which is in many cases caused by recurrent mutations affecting the activity of hematopoietic transcription factors. RUNX1-EVI1 is a fusion protein formed by the t(3;21) translocation linking two transcription factors required for normal hematopoiesis. RUNX1-EVI1 is found in myelodysplastic syndrome, secondary acute myeloid leukemia, and blast crisis of chronic myeloid leukemia; with clinical outcomes being worse than in patients with RUNX1-ETO, RUNX1 or EVI1 mutations alone. As RUNX1-EVI1 is usually found as a secondary mutation, the molecular mechanisms underlying how RUNX1-EVI1 alone contributes to poor prognosis are not well understood. To address this question, we induced expression of RUNX1-EVI1 at the onset of hematopoiesis and in progenitor cells derived from an embryonic stem cell differentiation model. Induction resulted in disruption of the RUNX1-dependent endothelial-hematopoietic transition, blocked the cell cycle and undermined cell fate decisions in multipotent hematopoietic progenitor cells. Integrative analyses of gene expression with the chromatin and transcription factor binding landscape demonstrated that RUNX1-EVI1 binding caused the re-distribution of endogenous RUNX1 within the genome and interfered with both RUNX1 and EVI1 regulated gene expression programs. In summary, RUNX1-EVI1 expression alone leads to extensive epigenetic reprogramming which is incompatible with healthy blood production and thus is only compatible with a pre-transformed cellular context.

overall_design: ChIP-seq targeting RUNX1 and RUNX1-EVI1 in hematopoietic progenitor cells expressing a doxycycline inducible RUNX1-EVI1 construct.

first: Sophie

last: Kellaway

first: Ella

last: Kennett

first: Constanze

last: Bonifer


title: Transcription profiling of monocytes from patients with active and inactive systemic juvenile idiopathic arthritis.

status: Public on Mar 27 2020

city: Cincinnati

first: Grant

last: Schulert

state: OH

address: 3333 Burnet Ave

department: Pediatrics

institute: Cincinnati Children's Hospital

summary: Systemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening episode of hyperinflammation driven by IFN-γ. Monocytes in SJIA display IFNγ-hyperresponsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte polarization phenotypes including features of interferon response. Bulk RNA-seq of purified monocytes was performed on healthy controls as well as patients with inactive SJIA (satisfy Wallace criteria for clinically inactive disease), active SJIA, new-onset SJIA (NOS), and macrophage activation syndrome (2016 MAS Classification Criteria). We observed marked transcriptional changes in patients with elevated ferritin levels. We also identified substantial overlap with multiple polarization states but little evidence of IFN-induced signature.

overall_design: Monocyes from control (n=11), active (n=16), and inactive (n=10) SJIA.

middle: S

first: Alex

last: Pickering

first: Thuy

last: Do

first: Sanjeev

last: Dhakal

first: Ndate

last: Fall

first: Mario

last: Medvedovic

first: Nathan

last: Salomonis

first: Sherry

last: Thornton

first: Alexei

middle: A

last: Grom


title: RUNX1-EVI1 disrupts lineage determination and the cell cycle by interfering with RUNX1 and EVI1 driven gene regulatory networks


title: Gene expression profiles in solid and cystic central nervous system hemangioblastomas

status: Public on Apr 15 2020

city: Chengdu

first: Qian

last: Bu

address: No.24 South Section 1, Yihuan Road

department: Department of food and Technology

institute: Sichuan University

summary:
OBJECTIVE: Due to the common occurrence of peritumoral cysts throughout the central nervous system tumors, hemangioblastomas (HBs) provide a model of cyst to further study the molecular mechanisms of peritumoral cyst formation.
METHODS: We conducted an integrated lipidomics and transcriptomics analysis on solid and cyst HB samples, to elucidate the changes in lipid profile and the expression levels of genes associated with lipid metabolism in the cyst formation.
RESULTS: Transcriptomic analysis revealed differentially expressed genes between the solid and cystic HBs. The lipidomic analysis further showed a significant reduction in the abundance of triacylglycerol, ceramide, lysophosphatidylcholine, and lysophosphatidylethanolamine, and an increase in phosphatidylcholine and phosphatidylethanolamine in the cystic group. Besides, bioinformatics analysis revealed altered lipid biosynthesis, glycerophospholipid metabolism and phospholipase activity in the cyst HBs.
CONCLUSION: Our findings indicate that aberrant lipid metabolism is a causative factor of cyst formation in HBs, and provide novel insights into the role of lipid metabolism in HBs.

overall_design: 3 cystic and 3 solid central nervous system hemangioblastomas


title: Vitamin D regulates MerTK-dependent phagocytosis in human myeloid cells

status: Public on Apr 21 2020

city: Montreal

first: Jo

middle: Anne

last: Stratton

state: Quebec

address: 3801 University street

department: Neurology and Neurosurgery

institute: McGill University

summary: Vitamin D deficiency is a major environmental risk factor for the development of multiple sclerosis (MS).  The major circulating metabolite of vitamin D (25OHD) is converted to the active form (calcitriol) by the hydroxylase enzyme CYP27B1. In MS lesions the tyrosine kinase MerTK expressed by microglia and macrophages regulates phagocytosis of myelin debris and apoptotic cells that can accumulate and inhibit tissue repair and remyelination. We show that calcitriol downregulates MerTK mRNA and protein expression in primary adult human microglia and monocyte-derived macrophages, thereby inhibiting myelin phagocytosis and apoptotic cell clearance. Proinflammatory myeloid cells express high levels of CYP27B1 compared to homeostatic (TGFb-treated) myeloid cells. Only proinflammatory cells in the presence of TNF-a generate calcitriol from 25OHD, resulting in repression of MerTK expression and function. The selective production of calcitriol in proinflammatory myeloid cells leading to downregulation of MerTK-mediated phagocytosis has the potential to reduce the risk for auto-antigen presentation while retaining the phagocytic ability of homeostatic myeloid cells, thereby contributing to inflammation reduction and enhanced tissue repair.

overall_design: Primary human microglia and primary human monocyte-derived-macrophages were differentiated into their CNS homeostatic phenotype (M-CSF+TGFβ) and proinflammatory phenotype (GM-CSF) over 6 days in the presence of 100nM calcitriol. Control populations were differentiated in the absence of calcitriol. 500000 cells were seeded in each condition. Experiment samples consist of three (3) biological replicates.

first: Jelani

last: Clarke

first: Moein

last: Yaqubi

first: Naomi

last: Futhey

first: Sara

last: Sadaghat

first: Caroline

last: Baufeld

first: Manon

last: Blain

first: Sergio

last: Baranzini

first: Oleg

last: Butovsky

first: Jack

last: Antel

first: John

last: White

first: Luke

last: Healy


title: Expression analysis of Synechocystis sp. PCC 6803 nblD mutant in nitrogen starvation and normal condition in contrast to wild type

status: Public on Apr 29 2020

city: Freiburg

first: Vanessa

last: Krauspe

address: Schänzlestraße 1

institute: Uni Freiburg

summary: Small proteins are an underinvestigated class of gene products in all domains of life. Here we describe the role of NsiR6/NblD, a cysteine-rich 66 amino acid small protein in the acclimation response of cyanobacteria to nitrogen starvation. Phycobilisomes, the macromolecular pigment-protein complexes for photosynthetic light harvesting, are rapidly degraded upon shift to low nitrogen. Deletion of nblD in Synechocystis sp. strain PCC 6803 prevents this degradation, indicated by the non-bleaching (nbl) phenotype. Complementation by a plasmid-localized gene copy fully restored the phenotype of the wild type, while overexpression of NblD under nitrogen-replete conditions did not lead to any phenotypical effect, different from the unrelated proteolysis adaptors NblA1 and NblA2, which can trigger phycobilisome degradation ectopically. However, transcriptome analysis revealed that nitrogen starvation induced nblA1/2 transcription in the ΔnblD strain, which excluded the possibility that the nbl phenotype was due to a possible NblD function as transcriptional co-regulator. In contrast, fractionation experiments indicated the presence of NblD in the phycobilisome fraction and pull-down experiments with NblD containing a triple FLAG tag identified the α and β phycocyanin subunits as the only two co-purifying proteins. Homologs of NblD exist in all cyanobacteria that use phycobilisomes but not in the genera Prochlorococcus and Acaryochloris which use alternative light-harvesting mechanisms. These data suggest that NblD plays a crucial role in the coordinated dismantling of phycobilisomes when nitrogen becomes limiting. We performed a microarray, to examine the global expression pattern of wild type and ∆nblD isolated RNA after 0h and 3h past induction of nitrogen depletion (-N) to detect potential differences in the nitrogen acclimation process.

overall_design: Cultures were starved for nitrogen (-N) for 0 h (negative control), 3 h, 6 h and 24 h to induce nsiR6 nblD expression. After harvesting the culture by filtering through hydrophilic polyethersulfone filters (Pall Supor®-800, 0.8 μm) and immersion in PGTX (Pinto et al., 2009), samples were snap frozen in liquid nitrogen. RNA isolation was performed like stated before (Hein et al., 2013).  For microarray analysis, the same procedure was used like described in before (Hernández-Prieto et al., 2012) using 5 µg of total RNA at time points 0 h and 3 h –N, for the array 500 ng Cy3-labeled RNA was applied. The microarray included a duplicate for each sample.

first: Matthias

last: Fahrner

first: Philipp

last: Spät

first: Boris

last: Macek

first: Claudia

last: Steglich

first: Oliver

last: Schilling

first: Wolfgang

last: Hess


title: Hallmarks of basidiomycete soft- and white-rot in wood-decay -omics data of Armillaria

first: Laszlo

last: Nagy

sample_organism:
Armillaria cepistipes
Armillaria ostoyae


title: Nutrient sensing controlling gut motility in the stomachless fish ballan wrasse (Labrus berggylta)

status: Public on Apr 01 2020

city: Bergen

first: Kai

middle: Kristoffer

last: Lie

state: Hordaland

address: Pobox 2029 Nordnes

department: Feed Safety

country: Norway

institute: Institute of Marine research

summary: Ex vivo intestines from 15-20 g ballan wrass (Labrus bergylta) were administered a bolus (lipid, protein, inert matter or empty control) before being mounted in oxygenated physiological buffer inside a glass vial. The intestinal motility patterns were documented with time lapse imaging for 14 hours. The images were used to construct spatio-temporal maps for gut motility analysis; i.e. to determine the speed, amplitude, frequency, travelled distance, direction, and initiation site of waves of muscle contractions. The experiments were repeated for RNA sampling and deep seq analysis. Gene expression analysis showed that intestines administered intact lipids clustered closer to the empty intestines compared to those given hydrolyzed lipids.

overall_design: Four different treatments were included in this study; Lipid (Hydrolyzed lipids), Protein (hydrolyzed casein), cellulose and Empty (n = 6). The diets were prepared to explore the effects of nutrient sensing on intestinal motility of ballan wrasse in vitro. Eviscerated ballan wrasse intestines containing the different “diets” were put in to a ringer’s solution for 60 min incubation before tissue sampling and downstream RNA extraction.

first: Hoang

middle: T

last: Le

middle: K

first: Angela

last: Ros

first: Ivar

last: Rønnestad

first: Øystein

last: Sæle


title: Small RNAseq for B16F1 cells exposed to BrdU or L-Tyr

status: Public on Mar 19 2020

city: Bogotá

first: LUIS

middle: ALBERTO

last: GOMEZ

state: Boogotá

address: El Dorado avenue 51-20

department: Dirección de Investigación Científica y Tecnológica

country: Colombia

institute: Instituto Nacional de Salud

summary:
Purpose: to evaluate changes in the expression of microRNAs, which contribute to explain a phenotype of differential pigmentation and reduction of proliferation, in B16F1 melanoma cells exposed to analogue of tymidine BrdU or aminoacid L-Tyr
Methods: Small RNAseq evaluation of the expression profiles of miRNAs in B16F1 melanoma cells exposed to BrdU (0.25 μg / mL) and L-Tyr (5 mM) for 72 h, as well as the expression by RT-qPCR of some molecular targets related with melanogenesis, cell cycle and senescence and construction of network models of regulation and co-expression of microRNAs.
Results: It was confirmed that stimulation or melanogenic repression with L-Tyr or BrdU, respectively, generates changes in melanin concentration, reduction in proliferation and changes in expression of microRNAs 470-3p, 470-5p, 30d-5p , 129-5p, 148b-3p, 27b-3p and 211-5p, which presented patterns of coordinated co-expression, related to melanogenesis through their putative targets MITF, Tyr and Tyrp1 and control of cell cycle and senescence: Cyclin D1, Cdk2, Cdk4 and p21.
Conclusion: This work improves our understanding of the events of melanogenesis, cell cycle control, and senescence mediated by the coordinated expression of miRNAs and helps to develop new approaches to a molecular biology of melanoma that operates in network

overall_design: The extraction of total RNA, used as input material for small-RNAseq, was performed from three independent replicates of B16F1 cells exposed or not to L-Tyr or BrdU

first: Luis

last: Gómez

first: Hernan

last: Rivera

first: Esther

last: Muñoz


title: Transcriptional profiling of laser captured intestinal tissue from the planarian Schmidtea mediterranea

status: Public on Mar 20 2020

city: Oklahoma

first: David

last: Forsthoefel

state: OK

address: 825 NE 13th St

department: Genes and Human Disease Research Program

institute: Oklahoma Medical Research Foundation

summary: Proper function and repair of the digestive system are vital to most animals. Deciphering the mechanisms involved in these processes requires an atlas of gene expression and cell types. Here, we applied laser-capture microdissection (LCM) and RNA-seq to characterize the intestinal transcriptome of Schmidtea mediterranea, a planarian flatworm that can regenerate all organs, including the gut. We identified hundreds of genes with intestinal expression undetected by previous approaches. Systematic analyses revealed extensive conservation of digestive physiology and cell types with other animals, including humans. Furthermore, spatial LCM enabled us to uncover previously unappreciated regionalization of gene expression in the planarian intestine along the medio-lateral axis, especially among intestinal goblet cells. Finally, we identified two intestine-enriched transcription factors that specifically regulate regeneration (hedgehog signaling effector gli-1) or maintenance (RREB2) of goblet cells. Altogether, this work provides resources for further investigation of mechanisms involved in gastrointestinal function, repair and regeneration.

overall_design: Methacarn-fixed planarians were cryosectioned, then medial intestine, lateral intestine, and non-intestinal tissue were collected using laser capture microdissection. Tissue was captured from 10-20 sections from a single animal and pooled for each biological replicate. The experiment was performed in quadruplicate, resulting in 12 samples total (4 medial intestine, 4 lateral intestine, and 4 non-intestine). RNA was extracted using the Arcturus PicoPure RNA Isolation Kit, followed by library generation and RNA-Seq.

first: Nicholas

middle: I

last: Cejda

first: Umair

middle: W

last: Khan

first: Phillip

last: Newmark


title: Rosmarinic acid changes the hippocampal transcriptome in 3 × Tg mice.

status: Public on Mar 18 2020

city: Yayoi, Bunkyo

first: Shoko

last: Kobayashi

state: Tokyo

institute: Univ. of Tokyo

summary:
Rosmarinic acid (RA), has been regarded as a capable component of preventing AD since it suppresses aggregation of amyloid β (Aβ). Despite the understanding of the association of Aβ suppression with RA, little is known
regarding the effect of RA on tau phosphorylation and cognitive dysfunction. Therefore, we investigated the influence of RA on the hippocampal transcriptome, and elucidated the mechanism by which RA prevents AD.

overall_design: In order to clarify the effect of RA, the gene expression of the hippocampus of male 3 × Tg mice who ingested RA for 8 months was compared with non-ingested mice of the same age.

first: So

last: Yamamoto

first: Moeko

last: Shinohara

first: Tsuyoshi

last: Hamaguchi

first: Masahito

last: Yamada


title: RUNX1-EVI1 disrupts lineage determination and the cell cycle by interfering with RUNX1 and EVI1 driven gene regulatory networks [RNA-seq]

first: Peter

last: Keane

overall_design: RNA-seq (2 biological replicates) of hemogenic endothelial and hematopoietic progenitor cells expressing a doxycycline inducible RUNX1-EVI1 construct.

first: Sophie

last: Kellaway

first: Ella

last: Kennett

first: Constanze

last: Bonifer


title: RNA editing enzyme APOBEC3A promotes pro-inflammatory (M1) macrophage polarization

status: Public on Mar 13 2020

city: BUFFALO

first: Eduardo

last: Cortes

address: ELM AND CARLTON STREETS

department: Biostatistics and Bioinformatics

institute: ROSWELL PARK CANCER INSTITUTE

summary: Macrophages acquire a pro-inflammatory M1 phenotype in response to microbial products or pro-inflammatory cytokines through incompletely understood molecular mechanisms. We recently described the induction of APOBEC3A-mediated cellular site-specific cytosine-to-uracil (C>U) RNA editing during M1 macrophage polarization. However, the functional significance of this RNA editing is unknown. Here, we find that cellular RNA editing by APOBEC3A can also be induced by influenza or Maraba virus infections in normal macrophages, and by interferons in tumor-associated macrophages. Gene knockdown and RNA Seq analyses show that APOBEC3A induces C>U RNA editing (range 7%-88%) of 209 exonic or UTR sites in 203 genes during M1 polarization of monocyte-derived macrophages. The highest level of deleterious protein-recoding C>U RNA editing is observed in THOC5, which encodes a key nuclear protein implicated in the export of mRNAs during M-CSF driven macrophage differentiation. Knockdown of APOBEC3A in M1 macrophages reduces pro-inflammatory IL6, IL23A, and IL12B gene expression, CD80 and CD86 surface protein expression, and TNF-α, IL-1β and IL-6 cytokine secretion, and increases glycolysis and glycolytic capacity. These results demonstrate that APOBEC3A cytidine deaminase plays an important role in transcriptomic and functional polarization of pro-inflammatory M1 macrophages.

overall_design: 9 RNAseq samples; 3M0, 3 A3A-KD and 3 Scrambled

first: Emad

last: Alqassim

first: Shraddha

last: Sharma

first: Anm

last: Kahn

first: Tiffany

last: Emmons

last: Gomez

first: Kelly

middle: L

last: Singel

first: Jaron

last: Mark

first: Kirsten

middle: B

last: Moysich

first: Jianmin

last: Wang

first: Kunle

last: Odunsi

first: Brahm

last: Segal

first: Bora

middle: E

last: Baysal


title: RUNX1-EVI1 disrupts lineage determination and the cell cycle by interfering with RUNX1 and EVI1 driven gene regulatory networks [DNaseI-seq]

last: Keane

overall_design: DNaseI-seq of hemogenic endothelial and hematopoietic progenitor cells expressing a doxycycline inducible RUNX1-EVI1 construct.


title: Adults with Systemic Lupus Exhibit Distinct Molecular Phenotypes Associated with Clinical Disease Activity

status: Public on Mar 16 2020

city: Oklahoma City

first: Judith

middle: A.

last: James

state: Oklahoma

address: 825 NE 13th Street

department: Arthritis and Clinical Immunology

summary: Background: The clinical and pathologic diversity of systemic lupus erythematosus (SLE) has hindered diagnosis, management, and treatment development. This study clustered adult SLE patients through comprehensive molecular phenotyping to improve distinctions with prognostic and therapeutic relevance.   Methods: Plasma, serum, and RNA were collected from 198 adult SLE patients. Disease activity was scored by modified SELENA-SLEDAI. Twenty-nine co-expression module scores were calculated from microarray gene-expression data. Plasma soluble mediators (n=23) and autoantibodies (n=13) were assessed by multiplex bead-based assays and ELISAs. Phenotypic patient clusters were identified by machine learning combining K-means clustering and random forest analysis of co-expression module scores and soluble mediators. Findings: SLEDAI scores correlated strongly with interferon module scores, more modestly with plasma cell and select cell cycle modules, and with circulating IFNα, IL21, IL1α, IL17A, IP10, and MIG levels. Co-expression modules and soluble mediators differentiated seven clusters of SLE patients with unique molecular phenotypes. Inflammation and interferon modules were elevated in Clusters 1 (moderately) and 4 (strongly), with decreased T cell modules in Cluster 4. The other clusters differed in monocyte, neutrophil, plasmablast, B cell, and T cell modules. Clusters 1 and 4 had higher SLEDAI scores, and more frequent anti-dsDNA, low complement, and renal activity. These features were also prominent in Cluster 3, which lacked the interferon and inflammation signatures. Arthritis and rashes were common in all clusters.  Interpretation: Molecular profiles can distinguish SLE subsets. Prospective longitudinal studies of these profiles may help to improve prognostic evaluation, clinical trial design, and precision medicine approaches.

overall_design: Total RNA was isolated and purified from PaxGene tubes from 48 healthy controls and 100 SLE patients with both lower (mSELENA-SLEDAI < 4) (n=50) and higher (mSELENA-SLEDAI ≥4) (n=48) disease activity timepoints. Study groups included controls, SLE patients with either one disease activity timepoint (low) or (high), or both high and low disease activity timepoints (high/low).

first: Joel

middle: M

last: Guthridge


title: The serine hydroxymethyltransferase-2 (SHMT2) initiates lymphoma development through epigenetic tumor suppressor silencing

city: New York

first: Matt

last: Teater

address: 445 E 69th St

institute: Weill Cornell Medical College

type: Methylation profiling by high throughput sequencing

summary: Cancer cells are thought to adapt their metabolic activities to support growth and proliferation. However, increased activity of metabolic enzymes is not usually considered an initiating event in the malignant process. Here we show that the enzyme serine hydroxymethyltransferase-2 (SHMT2) is sufficient to initiate lymphoma development through a surprising epigenetic mechanism. This is relevant because SHMT2 localizes to the most frequent region of copy number gains Chr12q14.1 in lymphoma and other cancers. Physiologically, SHMT2 catalyzes the conversion of serine to glycine which yields activated methyl groups in the form of S-adenosyl methionine (SAM). A modest increase in the enzyme’s physiological function is both sufficient and required for lymphoma development. SHMT2 acts as a tumor initiator by inducing changes in DNA and histone methylation patterns. In particular, we observe promoter silencing of previously uncharacterized tumor suppressor genes that are also mutational targets in lymphoma, such as the scaffold protein SASH1 and the tyrosine phosphatase PTPRM. Together, our findings reveal that amplification of the wild type SHMT2 enzyme initiates lymphoma development through epigenetic tumor suppressor silencing.

overall_design: RNAseq, ChIPseq, and ERRBS data for B220+ cells transfected with VavPBcl2;vector or VavPBcl2;SHMT2 tumors.

first: Sara

last: Parsa

first: Hans-Guido

last: Wendel


title: Transcriptional analyses to decipher iron homeostasis in the pathogenic yeast Candida glabrata.

status: Public on Mar 31 2020

city: ORSAY

first: Thomas

last: Denecker

address: Bâtiments 400 - UFR des Sciences - Université Paris-Sud - 15, rue Georges Clémenceau

department: Genome Biology

country: France

summary: Microarray experiments were performed to reveal the key genes involved in iron homeostasis in the pathogenic yeast Candida glabrata.

overall_design: Microarray technology was used to compared gene expression levels to ferrous iron (Fe2+) deficient and overload conditions, at 30°C and 37°C.

first: Youfang

last: Zhou Li

first: Cécile

last: Fairhead

first: Karine

last: Budin

first: Jean-Michel

last: Camadro

first: Monique

last: Bolotin-Fukuhara

first: Adela

last: Angoulvant

first: Gaëlle

last: Lelandais


title: Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development [RRBS]

status: Public on Mar 11 2020

city: Copenhagen

first: Ali

last: Altintas

address: Blegdamsvej 3B

department: NNF Center for Basic Metabolic Research

country: Denmark

institute: Copenhagen University

summary: Aim: Innate circadian rhythms are critical for optimal tissue-specific functions, including skeletal muscle, a major insulin-sensitive tissue responsible for glucose homeostasis. We determined whether transcriptional oscillations are associated with CpG methylation changes in skeletal muscle. Materials & methods: We performed rhythmicity analysis on the transcriptome and CpG methylome of circadian synchronized myotubes. Results: We identified several transcripts and CpG-sites displaying oscillatory behavior, which were enriched with GO terms related to metabolism and development. Oscillating CpG methylation was associated with rhythmic expression of 31 transcripts. Conclusion: Although circadian oscillations may be regulated by rhythmic DNA methylation, strong rhythmic associations between transcriptome and CpG methylation were not identified. This resource constitutes a transcriptomic/epigenomic atlas of skeletal muscle and regulation of circadian rhythms.

overall_design: Time course in triplicate of C2C12 cells in 6h time intervals from 12h til 60h after synchronization by serum shock.

last: Altıntaş

first: Rhianna

middle: C

last: Laker

first: Christian

last: Garde

first: Romain

last: Barrès

first: Juleen

middle: R

last: Zierath


title: Transcriptomic and epigenomics atlas of myotubes reveals insight into the circadian control of metabolism and development

overall_design: Refer to individual Series


title: Single-cell analysis reveals regulation of germline stem cell fate in the human parasite Schistosoma mansoni

status: Public on Mar 28 2020

city: Stanford

first: Yuan

last: Xue

state: CA

address: 318 Campus Drive

country: USA

institute: Stanford University

summary: Schistosomes are parasitic flatworms that cause one of the most prevalent infectious diseases from which millions of people are currently suffering. Here, we construct a cell type atlas of juvenile schistosomes to capture germline stem cells (GSCs) in the course of de novo gonadal development.

overall_design: We sequenced all body cells in juvenile schistosomes using Smart-seq2 protocol, resulting in a total of 10,945 single-cell transcriptomes sequenced. 7,657 of the sequenced cells passed the initial quality control and were analyzed downstream. The processed tsv files contain all cells, including cells that were filtered in the downstream analysis.

first: Pengyang

last: Li

first: Stephen

last: Quake

first: Bo

last: Wang


title: Effects of combined tamoxifen and short-term starvation on the gene expression profile of hormone receptor-positive breast cancer cells

city: Trieste

first: Silvano

last: Piazza

address: localita' Padriciano 99

country: Italy

institute: ICGEB

summary: Periodic fasting or modified fasting hold promise as strategies to enhance the activity of cancer treatments. We aimed at defining whether culture conditions that mimic the metabolic effects of fasting (1% serum and 0.5 g/L glucose) have an impact on the effects of tamoxifen, a broadly used selective estrogen receptor modulator, on the gene expression profile of MCF7 cells, a hormone receptor+ breast cancer cell line.

overall_design: MCF7 breast cancer cells were plated in 10 cm dishes in regular DMEM medium containing 10% FBS and 1.0 g/L glucose. 24 h later, the cell medium was removed and cells were incubated for 24h either in the same medium or in low-glucose (0.5 g/L) DMEM medium with 1 % FBS (short-term starvation conditions). 24h later, tamoxifen (5 uM) or vehicle were added to the culture medium. 24 h later, cells were used for RNA extraction and gene expression was assessed by Agilent gene expression microarrays.  Direct comparisons were performed in order to obtain differential gene expression gene lists.

first: Irene

last: Caffa

first: Chiara

last: Zucal

first: Vanessa

last: Spagnolo

first: Valter

middle: D

last: Longo

first: Alessandro

last: Provenzani

first: Alessio

last: Nencioni


title: The 11q13.5 immune disease risk locus contains a distal enhancer required for Treg-mediated suppression of gut inflammation [RNA-Seq]

status: Public on Mar 02 2020

city: Cambridge

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary: Much of the genetic variation underlying susceptibility to common autoimmune and allergic diseases is concentrated within protein non-coding regulatory elements termed enhancers{Enhancer; Hsniz}. It has been difficult to assign functions to a majority of enhancers that overlap immune disease-associated variants due to their distance from the genes they regulate, our lack of understanding of the cell types in which they operate and our inability to recapitulate the biology of immune-mediated diseases in vitro. Here, using syntenic analysis and CRISPR-based mutagenesis to model enhancer function in mice, we show that a prominent human autoimmune/allergic disease risk locus at 11q13.5 contains a distal enhancer commissioned in Foxp3+ regulatory T (Treg) cells and required for Treg-mediated resistance to gut inflammation. Highly conserved binding sites within the enhancer recruit the transcription factor STAT5 to mediate interleukin (IL)-2-driven expression of Lrrc32, encoding Glycoprotein A Repetitions Predominant (GARP). Whereas disruption of the Lrrc32 gene results in loss of embryonic viability, mice lacking the enhancer (hereinafter Lrrc32 +70k) are viable but lack GARP expression on Foxp3+ Treg cells which subsequently are unable to control gut inflammation. In human Treg cells disease-risk alleles at 11q13.5 reduce levels of histone acetylation and are associated with reduced levels of LRRC32 expression. These findings define a function for the 11q13.5 risk locus in Treg-mediated immunoregulation and provide evidence of a causal involvement of Treg cells in the pathophysiology of polymorphic immune-mediated diseases at the intersection of genetics and the environment.

overall_design: RNA-Seq profiles of Treg and T conv cells derived from LRRC32 +70Kb Enhancer KO and WT animals

first: Rabab

last: Nasrallah

first: Francis

last: Grant

first: Lara

last: Bossini-Castillo

first: Firas

last: Sadiyah

first: Dafni

last: Glinos

first: Teresa

last: Lozano

first: Panagiota

last: Vardaka

first: Carina

last: Nava

first: Hodaka

last: Fujii

first: Derya

last: Unutmaz

first: Enrico

last: Lugli

first: Suman

last: Mitra

first: Gosia

last: Trynka

first: Rahul

last: Roychoudhuri


title: The 11q13.5 immune disease risk locus contains a distal enhancer required for Treg-mediated suppression of gut inflammation

status: Public on Mar 01 2020

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


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

status: Public on Mar 06 2020

city: Shanghai

first: Xiao

last: Ge

address: No. 800 Dongchuan Road

country: China

institute: Shanghai JiaoTong University

summary: By CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find 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 in silico and genetic deletions in vivo revealed balanced promoter usage 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: To investigate the effects of CTCF sites on 3D chromatin conformation and insulation mechanisms, we inserted CTCF sites with different orientations into Pcdhalpha cluster. In addition, to pinpoint the effects to CTCF binding sequence, we mutated 5 bp of the binding site and inserted it into the same location as a control. After screening of the single-cell clones, we performed circular chromosome conformation capture experiments with enhancer or promoter as anchors in the CBS insertion and mutation single-cell clones.

first: Zhilian

last: Jia

first: Yonghu

last: Wu

first: Qiang


title: Assessment of gene expression changes in ex vivo-expanded human skin-derived ABCB5-selected mesenchymal stem cells during passaging

status: Public on Feb 21 2020

city: Hennigsdorf

first: Martina

last: Schad

address: Neuendorfstrasse 16b

country: Germany

institute: OakLabs GmbH

summary: To evaluate the potential impact of multiple passaging on the homogeneity of ex vivo-expanded, GMP-manufactured human skin-derived ABCB5+ mesenchymal stem cells, comparative gene expression profile analysis on cells from various passages was employed.

overall_design: Microarrays were performed on total RNA from cultured human dermal mesenchymal stem cells at four various passages (out of passages 7–16) per donor from eight donors.

first: Mark

last: Kluth


title: Dynamic and distinct transcriptional response of CD8+ cytotoxic T lymphocytes to tissue alarmins and adaptive cytokines

status: Public on Feb 27 2020

city: Groningen

first: Raul

last: Aguirre-Gamboa

address: Antonius Deusinglaan 1

department: Department of Genetics

country: Netherlands

institute: University of Groningen, University Medical Center Groningen

summary: The respective effects of tissue alarmins like interleukin (IL)-15 and interferon beta (IFNb), and cytokines like IL-21 on the intraepithelial cytotoxic T lymphocytes (IE-CTLs) that cause autoimmune-mediated tissue destruction, is poorly understood. Analysis of the dynamics of transcriptomic and epigenomic profiles in primary IE-CTLs showed massive and distinct temporal transcriptional changes upon induction by tissue alarmins IL-15 and IFNb, while the impact of IL-21 was limited. Only anti-viral pathways were induced in response to all the three stimuli. Interestingly, the dynamically differentially expressed genes (DEGs), in particular genes in involved in IFN pathways, are enriched in autoimmune diseases risk loci. Changes in gene expression were primarily independent of changes in H3K27ac, but were enriched in differentially expressed non-coding (nc) RNAs. Together these results provide new insights into molecular mechanisms that fuel the activation of tissue resident CTLs under conditions that mimic aspects of the inflammatory environment in patients with immune-mediated diseases

overall_design: RNASeq of IE-CTLs upon IFNb, IL15 and IL21 stimulations at 3h, 4h and 24h

first: Raúl

first: Maria

last: Zorro


title: Yeasts collectively extend the limits of habitable temperatures by secreting glutathione

status: Public on Mar 24 2020

city: Delft

first: Diederik

last: Laman Trip

address: Van der Maasweg 9

department: Bionanoscience

institute: Delft University of Technology

summary: The conventional view is that high temperatures cause microorganisms to replicate slowly or die. In this view, microorganisms autonomously combat heat-induced damage. However, microorganisms co-exist with each other, which raises the underexplored and timely question of whether microorganisms can cooperatively combat heat-induced damages at high temperatures. Here, we use the budding yeast Saccharomyces cerevisiae to show that cells can help each other and their future generations to survive and replicate at high temperatures. As a consequence, even at the same temperature, a yeast population can exponentially grow, never grow or grow after unpredictable durations (hours to days) of stasis, depending on its population density. Through the same mechanism, yeasts collectively delay and can eventually stop their approach to extinction, with higher population densities stopping faster. These features arise from yeasts secreting and extracellularly accumulating glutathione—a ubiquitous heat-damage-preventing antioxidant. We show that the secretion of glutathione, which eliminates harmful extracellular chemicals, is both necessary and sufficient for yeasts to collectively survive at high temperatures. A mathematical model, which is generally applicable to any cells that cooperatively replicate by secreting molecules, recapitulates all of these features. Our study demonstrates how organisms can cooperatively define and extend the boundaries of life-permitting temperatures.

overall_design: Transcriptome analysis of wild-type yeast at various temperatures, being 39.1C (3 biological replicates) and 40.5C (2 replicates) compared with a reference at 30.0C (3 replicates).

middle: S

first: Hyun

last: Youk


title: Synovial fibroblast positional identity controlled by inductive Notch signaling underlies pathologic damage in inflammatory arthritis

status: Public on Feb 14 2020

city: Boston

first: Ilya

last: Korsunsky

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Brigham and Women's Hospital

summary: Effect of Notch3 perturbation on healthy and arthritic mouse synovium.

overall_design: Mouse synovial tissues were dissected from knee joints. Pooled synovial tissue from 10 mice from each treatment group were enzymatically dissociated. Synovial cells were stained with LIVE/DEAD stain (ThermoFisher) and live synovial cells were isolated by flow cytometric sorting. 7,000 - 10,000 live synovial cells were then used for droplet-based single cell RNAseq (10X Genomics). Mice were either healthy or arthritic (serum transfer from K/BxN). Treatment conditions: isotype control vs anti-Notch3 mAB, wild type vs Notch3-/- knock out.

first: Kevin

last: Wei

first: Soumya

last: Raychaudhuri

first: Michael

last: Brenner


title: Investigation of de novo mutations in a schizophrenia case-parent trio by induced pluripotent stem cell based in vitro disease-modelling: Convergence of schizophrenia and autism-related cellular phenotypes

city: Budapest

first: János

middle: Miklós

last: Réthelyi

address: Balassa utca 6.

institute: Semmelweis University

summary:
Background
De novo mutations (DNMs) have been implicated in the etiology of schizophrenia (SZ), a chronic debilitating psychiatric disorder characterized by hallucinations, delusions, cognitive dysfunction, and decreased community functioning. Several DNMs have been identified by examining SZ cases and their unaffected parents; however, in most cases, the biological significance of these mutations remains elusive. To overcome this limitation, we have developed an approach of using induced pluripotent stem cell (iPSC) lines from each member of a SZ case-parent trio, in order to investigate the effects of DNMs in cellular progenies of interest, particularly in dentate gyrus neuronal progenitors.

Methods
We identified a male SZ patient characterized by early disease onset and negative symptoms, who is a carrier of 3 non-synonymous DNMs in genes LRRC7, KHSRP, and KIR2DL1. iPSC lines were generated from his and his parents’ peripheral blood mononuclear cells using Sendai virus-based reprogramming and differentiated into neuronal progenitor cells (NPCs) and hippocampal dentate gyrus granule cells. We used RNASeq to explore transcriptomic differences and calcium (Ca2+) imaging, cell proliferation, migration, oxidative stress, and mitochondrial assays to characterize the investigated NPC lines.

Results
NPCs derived from the SZ patient exhibited transcriptomic differences related to Wnt signaling, neuronal differentiation, axonal guidance and synaptic function, and decreased Ca2+ reactivity to glutamate. Moreover, we could observe increased cellular proliferation and alterations in mitochondrial quantity and morphology.

Conclusions
The approach of reprograming case-parent trios represents an opportunity for investigating the molecular effects of disease-causing mutations and comparing these in cell lines with reduced variation in genetic background. Our results are indicative of a partial overlap between schizophrenia and autism-related phenotypes in the investigated family.

Limitations
Our study investigated only one family; therefore, the generalizability of findings is limited. We could not derive iPSCs from two other siblings to test for possible genetic effects in the family that are not driven by DNMs. The transcriptomic and functional assays were limited to the NPC stage, although these variables should also be investigated at the mature neuronal stage.

overall_design: IPSC lines were derived from 3 human subjects, resulting in 5 clones alltogether. RNASeq analysis was performed on a total of 18 human samples. All experiments were carried out at the NPC stage for the 5 cell lines in triplicates or quadriplicates. RNA was isolated at 3 or 4 different passages from each NPC line between p11-19.

first: Edit

last: Hathy

first: Nóra

last: Varga

first: Ágota

last: Apáti


title: Highly parallel quantification and compartment localization of transcription factors and nuclear proteins

status: Public on Feb 17 2020

city: SEATTLE

first: John

middle: A

last: Stamatoyannopoulos

state: WA

address: 2211 Elliott Avenue, 6th Floor

department: Genome Sciences

institute: Altius Institute / University of Washington

summary: Transcription factors and other chromatin-associated proteins are difficult to quantify comprehensively. Here we combine facile nuclear sub-fractionation with data-independent acquisition mass spectrometry to achieve rapid, sensitive, and highly-parallel quantification of the nuclear proteome in human cells. We apply this approach to quantify the response to acute degradation of BET bromodomains, revealing unexpected chromatin regulatory dynamics. The method is simple and enables systems-level study of previously inaccessible chromatin and genome regulators.

overall_design: Epigenomic characterization of K562 BET domains by CUT&RUN

first: Alex

middle: J

last: Federation

first: Richard

last: Sandstrom


title: Transcriptome profiling of inflorescence stem tissues from Arabidopsis thaliana series

status: Public on Feb 10 2020

city: Heidelberg

first: Thomas

last: Greb

address: Im Neuenheimer Feld 360

department: Centre for Organismal Studies

institute: Heidelberg University


title: Transcriptome profiling of inflorescence stem tissues from Arabidopsis thaliana series 1

summary: We report the Fluorescence Activated Nucleus Sorting (FANS)-based RNA sequencing for high resolution transcriptome profiling of the second internode of the Arabidopsis thaliana inflorescence stem. We compared GFP-positive nuclei and GFP negative nuclei from promoter reporter lines expressing Histone 4-GFP (NST3pro:H4-GFP, SMXL5pro:H4-GFP, APLpro:H4-GFP), and compared GFP positive nuclei from seven lines expressing Histone 4-GFP under the control of different tissue-specific promoters (NST3pro:H4-GFP, VND7pro:H4-GFP, PXYpro:H4-GFP, SMXL5pro:H4-GFP, APLpro:H4-GFP, SCRpro:H4-GFP, LTP1pro:H4-GFP).

overall_design: mRNA profiles of GFP-positive and GFP-negative nuclei from inflorescence stems of Arabidopsis thaliana NST3pro:H4-GFP, SMXL5pro:H4-GFP, APLpro:H4-GFP transgenic lines, respectively, were compared. In addition, mRNA profiles of GFP-positive nuclei from inflorescence stems of Arabidopsis thaliana of NST3pro:H4-GFP, VND7pro:H4-GFP, PXYpro:H4-GFP, SMXL5pro:H4-GFP, APLpro:H4-GFP, SCRpro:H4-GFP, LTP1pro:H4-GFP transgenic lines were also compared. 3 replicates for each sample were provided.

first: Dongbo

last: Shi

first: Virginie

last: Jouannet

first: Pablo

last: Sanchez


title: CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing) of paired diagnosis and relapse specimens from acute myeloid leukemia (AML) patients treated with venetoclax plus azacitidine

status: Public on Jan 24 2020

city: Aurora

first: Shanshan

last: Pei

state: CO

institute: University of Colorado

summary: To understand relapse mechanisms related to AML patients treated with venetoclax plus azacitidine therapy, we performed CITE-seq on paired diagnosis and relapse specimens from an AML patient treated with the therapy.

overall_design: An AML patient who achieved remission but ultimately relapsed from the venetoclax plus azacitidine therapy was chosen for this study. Cells were harvested from specimens at diagnosis and relapse stages of the patient's disease and subjected to CITE-seq analysis.

first: Austin

last: Gillen

first: Craig

last: Jordan


title: Depletion of erythropoietic miR-486-5p and miR-451a improves detectability of rare microRNAs in peripheral blood-derived small RNA sequencing libraries

status: Public on Jan 28 2020

city: Kiel

first: Simonas

last: Juzenas

address: Am Botanischen Garten 11

department: Institute of Clinical Molecular Biology

institute: Christian-Albrechts-University of Kiel

summary: Erythroid-specific miR-451a and miR-486-5p are two dominant microRNAs (miRNAs) in human peripheral blood-derived small RNA sequencing libraries. Their overabundance reduces diversity as well as complexity of libraries after PCR amplification and consequently causes negative effects such as inaccurate detectability and quantification of other low abundant miRNAs. Here we present a cost-effective and feasible hybridization-based method to deplete these two erythropoietic miRNAs from blood-derived RNA samples

overall_design: In order to test the efficiency of our blocking oligos targeting the erythropoietic miRNAs, for each replicate sample, we generated unblocked (standard) and blocked (modified) libraries using both TruSeq and NEXTflex protocols. With this design, we generated 8 paired libraries for TruSeq and 5 paired libraries for NEXTflex using whole blood total RNA as an input.

first: Georg

last: Hemmrich-Stanisak


title: Thioredoxin-1 (Trx1) maintains mitochondria function via mTOR signaling in the heart

status: Public on Jan 15 2020

city: Seoul

first: Jiyeon

last: Park

address: 222, Banpo-daero

department: Catholic Center for Precision Medicine Research

institute: The Catholic University of Korea

summary: To investigate the role of Trx1 in the heart, cardiomyocyte-specific Trx1 knockout mice were generated. RNA-sequencing was performed with RNA extracted from the heart.

overall_design: Cardiomyocyte specific Trx1 knockout mice were generated with  Myh6-Cre. Total RNA was extracted at 1 month of their age to conduct RNA-sequencing.  There are control (n=3) and test (n=3) samples.

first: Shin-ichi

last: Oka

first: Adave

last: Chin

first: Shohei

last: Ikeda

first: Wataru

last: Mizushima

first: Guersom

last: Ralda

first: Peiyong

last: Zha

first: Mingming

last: Tong

first: Jaemin

last: Byun

first: Fan

last: Tang

first: Yudai

last: Einaga

first: Chun-yang

last: Huang

first: Toshihide

last: Kashihara

first: Bin

last: Tian

first: Yoko

last: Hirabayashi

first: Junji

last: Yodoi

first: Junichi

last: Sadoshima


title: Two separate roles for the transcription coactivator SAGA and a set of genes redundantly regulated by TFIID and SAGA [ChEC-Seq]

status: Public on Jan 09 2020

city: Oklahoma City

first: Rafal

last: Donczew

address: 825 NE 13th St

department: Cell Cycle and Cancer Biology

institute: Oklahoma Medical Research Foundation

summary: Deletions within genes coding for subunits of the transcription coactivator SAGA caused strong genome-wide defects in transcription and SAGA-mediated chromatin modifications. In contrast, rapid SAGA depletion produced only modest transcription defects at 13% of protein-coding genes – genes that are generally more sensitive to rapid TFIID depletion. However, transcription of these “coactivator-redundant” genes is strongly affected by rapid depletion of both factors, showing the overlapping functions of TFIID and SAGA at this gene set. We suggest that this overlapping function is linked to TBP-DNA recruitment. The remaining 87% of expressed genes that we term “TFIID-dependent” are highly sensitive to rapid TFIID depletion and insensitive to rapid SAGA depletion. Genome-wide mapping of SAGA and TFIID found binding of both factors at many genes independent of gene class. DNA analysis suggests that the distinction between the gene classes is due to multiple components rather than any single regulatory factor or promoter sequence motif.

overall_design: A modified ChEC-seq method was used to map genome-wide binding of TFIID and SAGA. Experiments were done in four replicates (A,B,C,D).

first: Linda

last: Warfield

first: Derek

last: Pacheco

first: Ariel

last: Erijman

first: Steven

last: Hahn


title: EGR1 is a gatekeeper of inflammatory enhancers in human macrophages

status: Public on Jan 01 2020

city: London

first: Marco

last: Trizzino

state: UK

address: Imperial College Road

department: Life Sciences

country: United Kingdom

institute: Imperial College London

summary: We investigated the function of EGR1 in macrophage differentiation and activation. We generated EGR1 CHIP-seq and CUT-and-RUN data during GM-CSF induced macrophage differentiation, paired with ATAC-seq. We performed RNA-seq and CHIP-seq for H3K27ac in EGR1-depleted differentiated macrophages.  Finally we generated RNA-seq data in activated macrophages with EGR1 overexpression.

overall_design: Analysis of genome-wide activity of EGR1 in macrophage differentiation.

first: Avery

last: Zucco

first: Sandra

last: Deliard

first: Fang

last: Wang

first: Elisa

last: Barbieri

first: Sarah

last: Welsh

first: Filippo

last: Veglia

first: Dmitry

last: Gabrilovich

first: Alessandro

last: Gardini


title: Genome-wide maps of factors and gene expression in pre-B leukemic 697 line

city: Taipei

first: Wei-Yi

last: Chen

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

department: Institute of Biochemistry and Molecular Biology

institute: National Yang Ming Chiao Tung University

summary: E2A, a basic helix-loop-helix (bHLH) transcription factor, plays a crucial role in determining tissue-specific cell fate, including differentiation of B cell lineages. In 5% of childhood acute lymphoblastic leukemia (ALL), the t(1,19) chromosomal translocation specifically targets the E2A gene and produces an oncogenic E2A-PBX1 fusion protein. While previous studies have demonstrated oncogenic functions of E2A-PBX1 in cell and animal models, the E2A-PBX1-enforced cistrome, the E2A-PBX1 interactome, and related mechanisms underlying leukemogenesis remain unclear. Here, by unbiased genomic profiling approaches, we identify the direct target sites of E2A-PBX1 in t(1,19)-positive pre-B ALL cells and show that, compared to normal E2A, E2A-PBX1 preferentially binds to a subset of gene loci co-bound by RUNX1 and gene-activating machineries (p300, MED1, and H3K27 acetylation). Using biochemical analyses, we further document a direct interaction between E2A-PBX1 and RUNX1 and show that E2A-PBX1 binding to gene enhancers is dependent on RUNX1, but not the DNA-binding activity harbored within the PBX1 homeodomain of E2A-PBX1. Transcriptome analyses and cell transformation assays further establish a significant RUNX1 requirement for E2A-PBX1-mediated target gene activation and leukemogenesis. Notably, the RUNX1 locus itself is also directly activated by E2A-PBX1, indicating a multilayered interplay between E2A-PBX1 and RUNX1. Collectively, our study provides the first unbiased profiling of the E2A-PBX1 cistrome in pre-B ALL cells and reveals a previously unappreciated pathway in which E2A-PBX1 acts in concert with RUNX1 to enforce transcriptome alterations for the development of pre-B ALL.

overall_design: Genome-wide binding/occupancy profiling of E2A-PBX1, E2A, p300, RUNX1, H3K27ac, and MED1 by ChIP-seq and gene expression profiling by RNA-seq in 697 cells treated without or with indicated shRNAs

first: Wei-Chieh

last: Pi

first: Robert

last: Roeder