title: Mechanisms of Th17 and Treg cell dysregulation in oral mucosal inflammation during HIV disease

status: Public on May 11 2021

city: Cleveland

first: Pushpa

last: Pandiyan

state: OH

address: 2124, Cornell Road

institute: Case Western Reserve University

summary:
Purpose: The goal of this study is to compare the transcriptomic profiles of healthy individuals and HIV+ patients on therapy
Methods: Cells were pelleted from gingival mucosa. mRNA profiles were generated by Next-gen sequencing using the Illumina platform.
Results: Comprehensive transcriptome data that showed underlying changes in the oral mucosal immune system of HIV+ patients on therapy. The transcriptome data of the pooled healthy controls are presented here.
Conclusions: Our study represents the analysis of oral gingival transcriptomes. We conclude that RNA-seq based transcriptome characterization would expedite genetic network analyses and permit the dissection of complex biological functional alterations during chronic viral infections such as HIV infection.

overall_design: Oral mucosal gingival cell mRNA profiles ex vivo of control (healthy) and HIV+ patients on therapy (HIV + cART)


title: Muscle Stem Cell Response to Perturbations of the Neuromuscular Junction Are Attenuated With Aging

status: Public on May 06 2021

city: Ann Arbor

first: Carlos

middle: Andres

last: Aguilar

state: MI

address: 2200 Bonisteel Blvd

department: Biomedical Engineering

country: USA

institute: University of Michigan

type: Expression profiling by high throughput sequencing

summary: During aging and neuromuscular diseases, there is a progressive loss of skeletal muscle volume and function, which is often associated with denervation and a loss of muscle stem cells (MuSCs). A relationship between MuSCs and innervation has not been established however. Herein, we administered neuromuscular trauma to a MuSC lineage tracing model and observed a subset of MuSCs specifically engraft in a position proximal to the neuromuscular junction (NMJ). In aging and in a model of neuromuscular degeneration (Sod1-/-), this localized engraftment behavior was reduced. Genetic rescue of motor neurons in Sod1-/- mice reestablished integrity of the NMJ and partially restored MuSC ability to engraft into NMJ proximal positions. Using single cell RNA-sequencing of MuSCs, we demonstrate that a subset of MuSCs are molecularly distinguishable from MuSCs responding to myofiber injury. These data reveal unique features of MuSCs that respond to synaptic perturbations caused by aging and other stressors.

overall_design: C57BL/6J wild-type female mice were obtained from Charles River Breeding Laboratories, the National Institute on Aging, or from a breeding colony at the University of Michigan (UM). All mice were fed normal chow ad libitum and housed on a 12:12 hour light-dark cycle under UM veterinary staff supervision. All procedures were approved by the University Committee on the Use and Care of Animals at UM and were in accordance with the U.S. National Institute of Health (NIH). Young female mice (4-6 months) and aged female mice (20-24 months) were randomly assigned to one of five groups: uninjured, day 3, and day 7 injured (n=4 per group). To induce skeletal muscle injury, mice were first anesthetized with 2% isoflurane and administered a 1.2% barium chloride (BaCl2) solution injected intramuscularly into several points of the tibialis anterior and gastrocnemius muscles for a total of 80 µL per hindlimb.

first: Jacqueline

last: Larouche

first: Mahir

last: Mohiuddin

first: Jeongmoon

middle: J

last: Choi

first: Peter

last: Ulintz

first: Paula

middle: M

last: Fraczek

first: Sarah

last: Kurpiers

first: Jesus

last: Castor-Macias

first: Wenxuan

last: Liu

first: Robert

middle: L

last: Hastings

first: Lemuel

middle: A

last: Brown

first: James

middle: F

last: Markworth

first: Kanishka

last: De Silva

first: Benjamin

middle: D

last: Levi

first: Sofia

last: Merajver

first: Gregorio

last: Valdez

first: Joe

middle: V

last: Chakkalakal

first: Young

last: Jang

first: Susan

last: Brooks


title: Liver transcriptome analysis comparing gene expression between Esr1 knockout mice and wild type littermates

status: Public on May 18 2021

city: Montreal

first: Anna

middle: K.

last: Naumova

state: Quebec

address: 2155 rue Guy

department: Departments of Obstetrics and Gynecology and Human Genetics

country: Canada

institute: McGill University

summary: The overall purpose of the study is to understand the origin of the different DNA methylation patterns in mice with different sex phenotypes. Specifically, we look at the roles of three factors associated with sex hormone signaling, including estrogen receptor alpha (ESR1), during development in mouse liver. In order to do that, we compare the transcriptomes of male and female B6N(Cg)-Esr1^tm4.2Ksk/J mice (ESR1 KO) mice and wild type (WT) control littermates, and identify differentially expressed genes. Those genes will then be compared to the differential methylation data obtained using pyrosequenceing.

overall_design: rRNA depleted RNA-seq libraries were prepared from RNA extracted from the livers of 8-week old Male and Female ESR1 KO and WT mice.

first: Najla

last: AlOgayil

first: Klara

last: Bauermeister

first: Jose

middle: H

last: Galvez

first: Varun

middle: S

last: Venkatesh

first: Qinwei

middle: K

last: Zhuang

first: Matthew

last: Chang

first: Rachel

last: Davey

first: Jeffrey

last: Zajac

first: Kinuyo

last: Ida

first: Akihide

last: Kamiya

first: Teruko

last: Taketo

first: Guillaume

last: Bourque


title: Single-cell RNA-seq analysis in TBI mgll KO mice

status: Public on Jun 22 2021

city: San Antonio

first: Chu

last: Chen

state: Texas

address: 7703 Floyd Curl Dr

department: Cellular and Integrative Physiology

institute: UT Health San Antonio

summary: Using 10x Genomics' single-cell RNA-seq (scRNA-seq) technology, we profiled expression of genes in cell type-specific MAGL knockout mice that received TBI. We found that there are differences in expression of genes between WT, tKO, nKO, and aKO mice in sham or TBI.

overall_design: Profile expression of genes in MAGL KO mice that received TBI.

first: Chen

last: Chu


title: Single Cell RNA sequencing (DropSeq) of esophageal adenocarcinoma and matched normal samples

city: Southampton

first: Tim

last: Underwood

address: Somers Cancer Research Building, General Hospital

department: Cancer Sciences

country: United Kingdom

institute: University of Southampton

summary: Cancer grows within the complex ecosystem of the tumor microenvironment (TME) which can define responses to treatment. Esophageal adenocarcinoma (EAC) is typically resistant to cytotoxic therapies and immunotherapies have gained little traction against this disease.  We used single cell RNA sequencing to identify the key constituents of the TME in EAC in a cohort of 22 patients. We found differences within and between individual patients in cancer cells and also in the stromal and immune cell populations. We found a subtype of cancer-associated fibroblasts, the myofibroblastic CAFs (myoCAFs), acting as TME interaction hubs to drive the hallmarks of cancer. Finally, we demonstrated the efficacy of repurposed PDE5 inhibitors in targeting myoCAFs in near-patient models of the disease.

overall_design:
EAC tumor and normal tissue samples were obtained from patients from a single centre.
To isolate single cells for droplet-based sequencing (Drop-seq) tumor material obtained by 8mm biopsy punch from the epicenter of the tumor on the luminal surface (or at the proximal esophageal resection margin >5cm from tumor to obtain normal tissue), was enzymatically dissociated using a protocol optimized to recover all of the broad cell categories in the TME. Following the Drop-seq procedure, approximately 1,000 single-cell transcriptomes per sample were selected for sequencing using Illumina NextSeq 500. In total, after filtering for feature cut-offs (number of genes, % mitochondrial content, dissociation induced artefacts. STAR Methods), we retained 16,328 cells and 28,620 genes for downstream analysis. In total 10,250 cells were from tumors and 6,078 cells were from normal esophagus.

first: Robert

last: Walker

first: Jack

last: Harrington

last: Parker

first: Annette

last: Hayden

first: Mat

last: Rose-Zerelli


title: Role of beta-actin in mouse embryonic fibroblasts (MEFs)

status: Public on May 01 2021

city: Abu Dhabi

first: Piergiorgio

last: Percipalle

state: Abu Dhabi

address: Saadiyat Campus, Abu Dhabi

department: Biology Department, Science Division

country: United Arab Emirates

institute: New York University Abu Dhabi

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: RNA-sequencing data of  intestinal tissue of pigs infected with parasites and adminstered proanthocyanidins (PAC)

status: Public on May 08 2021

city: Frederiksberg C

first: Andrew

last: Williams

state: --- Select One ---

address: Dyrlægevej 100

country: Denmark

institute: University of Copenhagen

summary: We show here the transcriptional response in the  intestine of pigs infected or not with Ascaris suum, fed either a control pr a PAC-enriched diet

overall_design: RNA was obtained from the jejunum of 12 pigs infected with A. suum and 12 uninfected pigs. Within each infection group, pigs were fed either a control diet or the control diet supplemented with 1 % PAC derived from grape seed

middle: R


title: Hi-C sequencing analysis of wild-type, β-actin knockout and β-actin hetereozygous mouse embryonic fibroblasts

summary: β-actin is a crucial component of several chromatin remodeling complexes which control chromatin structure and accessibility. The mammalian Brahma-associated factor (BAF) is one such complex that plays essential roles in development and differentiation by regulating the chromatin state of critical genes and opposing the repressive activity of polycomb repressive complexes. While previous work has shown that β-actin loss can lead to extensive changes in gene expression and heterochromatin organization, it is not known if changes in β-actin levels can directly influence chromatin remodeling activities of BAF and polycomb proteins. Here we conduct a comprehensive genomic analysis of β-actin knockout mouse embryonic fibroblasts (MEFs) using ATAC-Seq, HiC-seq, RNA-Seq and ChIP-Seq of various epigenetic marks. We demonstrate that β-actin levels can affect the complex interplay between chromatin remodelers such as BAF/BRG1 and EZH2 in a dosage-dependent manner. Our results show that changes in β-actin levels and associated chromatin remodeling activities can not only impact local chromatin accessibility but also induce reversable changes in 3D genome architecture. Our findings support a novel role for β-actin levels in shaping the chromatin landscape during development and differentiation.

overall_design: Hi-C sequencing was performed for 12 samples (6 different genotypes with two biological replicates each)

first: Syed

last: Mahmood

first: Xin

last: Xie

first: Nadine

last: ElSaid

first: Kristin

middle: C

last: Gunsalus


title: ATAC-seq in shControl Huh7 and shARID1A Huh7 cells without or with rapamycin treatment

status: Public on Apr 01 2021

city: Guangzhou

first: Shanshan

last: Zhang

address: 651 Dongfeng Road East

country: China

institute: Sun Yat-sen University Cancer Center

summary: mTORC1 is a conserved central controller of cell growth, which is commonly activated in hepatocellular carcinoma (HCC), driving liver tumorigenesis. In addition to its established cytoplasmic functions, mTORC1 is found in the nucleus where it regulates transcription by all three major RNA polymerases. However, precisely how mTORC1 controls gene expression remains poorly understood. Herein we show that mTORC1 interacts with the BAF SWI/SNF complex and regulates genome-wide chromatin remodeling through ARID1A. Mechanically, mTORC1 stimulates ubiquitination and proteasomal degradation of ARID1A protein through SCF ubiquitin ligase. mTORC1-ARID1A axis promotes chromatin remodeling and expression of YAP target genes, thereby enhancing oncogenic growth in vitro and in vivo. These findings reveal a novel nuclear mTORC1 function and the underlying mechanism that controls oncogenic chromatin remodeling to promote hepatocarcinogenesis.

overall_design: shControl Huh7 and shARID1A Huh7 cells without or with 100nM rapamycin treatment for 6 hours


title: Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis

status: Public on Mar 05 2021

city: Tampere

first: Dario

last: Greco

address: Arvo ylpön Katu 34

department: Faculty of Medicine and Health Technology

country: Finland

institute: Tampere University

type:
Expression profiling by array
Methylation profiling by array


title: DRM2 mediates CHH DNA methylation via a substrate deformation mechanism

city: St Louis

first: Xuehua

last: Zhong

state: MO

address: One Brookings Drive

department: Biology

institute: Washington University in St. Louis

type: Methylation profiling by high throughput sequencing

summary: This study investigated the structural basis for DRM2 mediated CHH methylation in Arabidopsis thaliana

overall_design: Whole-genome bisulfite sequencing of DRM2 mutants to determine sequences flanking methylated cytosines and genome wide proportions of different methylation contexts

first: Sarah

last: Leichter


title: Inhibition of xCT Suppresses Melanoma progress

status: Public on Feb 11 2021

city: Changsha

first: Nian

last: Liu

state: Hunan

address: Xiangya road 87#

department: Department of Dermatology

institute: Xiangya Hospital, Central South University

summary: Tumor cells increase glutamate release through the cystine/glutamate transporter xCT to balance oxidative homeostasis in tumor cells and promote tumor progression.  Here, we demonstrated that although inhibition of xCT either by pharmacological inhibitor (sulfasalazine, SAS), approved by FDA for inflammatory diseases, or genetic knockdown induced ROS-related death in melanoma cells. Taken together, our results reveal that inhibition of xCT by SAS is a promising therapeutic strategy for melanoma.

overall_design: mRNA profiles of 3 replicated vehicle and 3 replicated 500μm SAS-treated B16F10 melanoma cells for 24 hours

last: liu

first: JiangLin

first: Mingzhu

last: Yin

first: Hong

first: Xu

first: Jiaoduan

last: Li

first: Bei

last: Yan

first: Yeye

last: Guo

first: Jianda

last: Zhou

first: Juan

last: Tao

first: Shuo

last: Hu

first: Xiang

last: Chen

first: Cong

last: Peng


title: The global downregulation of protein synthesis observed during hepatogenic maturation is associated with a decrease in TOP mRNA translation

status: Public on Apr 23 2021

city: Leuven

first: Marino

last: Caruso

address: Herestraat 49

department: Oncology

country: Belgium

institute: KULeuven

summary: Translational regulation is of paramount importance for proteome remodeling during stem cell differentiation both at the global and transcript-specific level. In this study, we characterized translational remodeling during hepatogenic differentiation of induced pluripotent stem cells (iPSCs) by polysome profiling. We demonstrate that protein synthesis increases during the initial exit from pluripotency, but is then globally repressed during later steps of hepatogenic maturation. This global downregulation of translation is accompanied by a decrease in the protein abundance of components of the translation machinery, which involves a global reduction in translational efficiency of terminal oligopyrimidine tract (TOP) mRNA encoding translation-related factors. Despite global translational repression during hepatogenic differentiation, key hepatogenic genes remain efficiently translated, and the translation of several transcripts involved in hepato-specific functions and metabolic maturation are even induced. We conclude that, during hepatogenic differentiation, a global decrease in protein synthesis is accompanied by a specific translational rewiring towards hepato-specific transcripts.

overall_design: Rna-sequencing analysis of cytoplasmic and high-polysome RNA (polysome profiling) from control hiPSCs and in vitro differentiating hiPSCs toward hepatogenic progeny


title: RNA-seq in shControl Huh7 and shARID1A Huh7 cells without or with rapamycin treatment

first: Shanshan


title: shControl Huh7 and shARID1A Huh7 cells without or with rapamycin treatment


title: Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [expression]

first: Dario

summary: Multi-omics approach to characterize the dynamic dose-dependent (DDD) molecular alterations in a model of human macrophages was used to highlight key-genes altered due to rCNT exposure. Results emphasize short and long term changes in gene regulation, that further suggest fibrotic responses, previously reported in in vivo animal model.

overall_design: The gene expression profiles of THP-1 macrophages exposed to three concentrations (5, 10 or 20 µg/mL) of rigid multi-walled carbon and untreated controls were profiled at 24, 48 and 72 hours. Each group was performed as triplicates.

first: L

last: Saarimaki

first: P

last: Kinaret

first: A

last: Federico

first: G

last: del Giudice

last: Scala

last: Serra

first: D


title: mRNA-Seq of male and female embyos of the honeybee (Apis mellifera)

status: Public on Jan 01 2021

city: Düsseldorf

first: Oksana

last: Netschitailo

address: Universitätsstraße 1

department: Evolutionary Genetics

country: Germany

institute: Heinrich-Heine University

summary: Transcriptional profiling of male and female honeybee embryos 10-15 h, 25-40 h, 55-70 h after egg laying was performed by RNA-SEQ. The sex specific expressed and spliced genes were examined comparing male and female embryos.

overall_design: Examination of mRNA profiles of male and female embryos 10-15 h, 25-40 h, 55-70 h after egg laying.

first: Martin

last: Beye


title: Transcriptome analysis of Caco-2 Cells upon deoxynivalenol and its acetylated exposure

status: Public on Jan 07 2021

city: Wuhan

first: Gong

last: zhiyong

address: Xuefunan Road 68

institute: Wuhan Polytechnic University

summary: Deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON) and 15-acetyldeoxynivalenol (15-ADON) are type B trichothecenes and are major pollutants in food and feed products. Although the toxicity of DON has been well documented, the information of toxicity of its acetylated derivative remains incomplete. To acquire more detailed insight in 3-ADON and 15-ADON, Caco-2 cells under 0.5 µM DON, 3-ADON and 15-ADON treatment for 24 h were subjected to RNA-seq analysis. In the present study, 2656, 3132 and 2425 differentially expressed genes (DEGs) were selected respectively and were enriched utilizing KEGG and GO database. The upregulation of ataxia-telangiectasia mutated kinase (ATM), WEE1 homolog 2 (WEE2) and downregulation of proliferating cell nuclear antigen (PCNA), minichromosome maintenance (MCMs), cyclin dependent kinase (CDKs), E2Fs indicate that the three toxins induced DNA damage, inhibition of DNA replication and cell cycle arrest in Caco-2 cells. Apart from these, the upregulation of sestrin (SENEs) and NEIL1 implied that the reason of DNA damage may attribute to oxidative stress. Our study provides an insight in the toxic mechanism of 3-ADON and 15-ADON.

overall_design: Transcriptome analysis of Caco-2 Cells: untreated, treated with DON for 24 h, 3-ADON for 24h, or 15-ADON for 24h

first: Xiaoyao

last: Yin

first: Yuyun

last: He

first: Jingjing

last: Dong

first: Qing

last: Yang


title: Comparative transcriptomics of epithelial cells grown under static and microfluidic gut-on-chip conditions and benchmarked against human in vivo intestinal cells

status: Public on Feb 08 2021

city: Wageningen

first: Guido

last: Hooiveld

address: HELIX, Stippeneng 4

department: Div. Human Nutrition & Health

country: Netherlands

institute: Wageningen University

summary: Gut-on-chip devices enable exposure of cells to a continuous flow of culture medium, inducing shear stresses and could thus better recapitulate the in vivo human intestinal environment in an in vitro epithelial model compared to static culture methods. We aimed to study if dynamic culture conditions affect the gene expression of Caco-2 cells cultured statically or dynamically in a gut-on-chip device and how these gene expression patterns compared to that of intestinal segments in vivo. For this we applied whole genome transcriptomics. Dynamic culture conditions led to a total of 5927 differentially expressed genes (3280 upregulated and 2647 downregulated genes) compared to static culture conditions. Gene set enrichment analysis revealed upregulated pathways associated with the immune system, signal transduction and cell growth and death, and downregulated pathways associated with drug metabolism, compound digestion and absorption under dynamic culture conditions. Comparison of the in vitro gene expression data with transcriptome profiles of human in vivo duodenum, jejunum, ileum and colon tissue samples showed similarities in gene expression profiles with intestinal segments. It is concluded that both the static and the dynamic gut-on-chip model are suitable to study human intestinal epithelial responses as an alternative for animal models.

overall_design: Microarray analysis was performed on Caco-2 cells cultured statically or in a gut-on-chip device for 21 days.

first: Kornphimol

last: Kulthong

first: Meike

last: van der Zande

first: Hans

last: Bouwmeester


title: Contribution of resident and circulating precursors to tumor-infiltrating CD8+ T cell populations in lung cancer [scRNA-Seq]

status: Public on Jan 29 2021

city: Paris

first: Paul

last: Gueguen

address: 26 rue D'Ulm

department: Inserm U932

country: France

institute: Institut Curie

summary:
Purpose: The goal of this study is to delineate the processes of CD8+ T cell differentiation in primary NSCLC by integrating transcriptomic and tcr profiles.
Methods: A combination of single cell RNA and TCR sequencing (scRNA-seq and scTCR- seq) was used, in tumors, normal tissues adjacent to the tumor (juxta-tumor), and circulating blood derived from 11 patients with untreated, primary NSCLC.
Results: We show that precursor, memory-like CD8+ TILs include 2 main populations: one is also present in the blood (circulating precursors); the other is also present in juxta-tumor tissue and bears markers of memory resident T cells (resident precursors). Both precursor subtypes differentiate into a main population of terminal effectors through a similar “transitional” stage. Terminal effectors are not observed in blood or juxta-tumor tissue, are more clonally expanded, and express signatures of exhaustion. A significant proportion of transitional and terminal effectors also express cell cycle signatures and Ki67, suggesting that clonal expansion occurs in situ is part of the terminal differentiation process.

overall_design: 11 patients with early-stage, untreated NSCLC

first: Christina

last: Metoikidou


title: Mapping nucleolus-associated chromatin interactions by nucleolus-Hi-C reveals repression network

status: Public on Feb 01 2021

city: Beijing

first: Howard

last: MENG

state: Beijing

address: No.5 Yiheyuan Road Haidian District

department: School of Life Sciences

institute: Peking University

summary: Nucleolus plays a key role in organizing global nuclear structure and facilitating gene regulation, but the three dimensional information within the nucleolus associated chromatins are still unknown, so here we development the Nucleolus Hi-C (NHi-C) experimental technique, which combines the nucleolus isolation with Hi-C experiment, and study the interactions within and surrounding nucleolus in human cells with a high resolution. With NHi-C experiment, we report how the nucleolus-associated chromatin regions interact at genome scale, and how these interactions organize the repressive nucleus architecture.

overall_design: in situ  Hi-C and Nucleolus Hi-C data in human cells to detect the 3D genome information, the detailed information about all files uploaded to GEO for this study are explained in "DataFiles.README"

first: Tingting

last: Li

first: Haowei

last: Meng

first: Cheng


title: Single-cell transcriptomic landscape reveals the differences in cell differentiation and immune microenvironment of papillary thyroid carcinoma between male and female patients

status: Public on Dec 31 2020

first: chen

middle: wei

last: fen

address: 4F, Building 1, Standard Property Unit 3, International Biotech Island

institute: Forevergen

summary:
Objective: Papillary thyroid carcinoma (PTC) is the main pathological type of thyroid carcinoma (TC), whose incidence and prognosis are related to the gender of patients. We focused on the differences of cell clusters and immune microenvironment induced by gender in PTC.
Methods: We collected tissues from nodular goiter, male PTC patients and female PTC patients respectively, performed single-cell RNA sequencing (scRNA-seq) based on BD Rhapsody and characterized the first single-cell transcriptomic landscape of PTC involving gender. The differential cell clusters and their genes profile were identified in male- and female- PTC, analyzed by multi-resolution network. Finally, we analyzed the interaction of fibroblasts, endothelial cells with malignant epithelial cells, and the difference of immune infiltration of B lymphocytes and T lymphocytes driven by gender.
Results: Malignant epithelial cells were divided into two distinct subsets in male PTC patients and female PTC patients, with significant difference involving gene mutation, gene profile and cell differentiation. In the interaction between fibroblasts, endothelial cells and malignant epithelial cells, members of human leukocyte antigen and their receptors were considered as typical in female PTC patients, while TGFB1 and its receptors in male PTC patients. Both B cells and T cells were significantly different between male- and female PTC patients, involving cell clusters, cell differentiation and dominant genes set.
Conclusions: Our research indicated the detailed differences of cell clusters and immune microenvironment in PTC driven by gender, and provided an insight to further understand the impact of gender on PTC at single-cell level.

overall_design: Single cell RNA sequencing of  PTC tissue from 14 patients (3 for nodular goiter, 7 for female PTC patients, 4 for male PTC patients).

first: Miaoguan

last: Peng

first: Guohong

last: Wei

first: Yunjian

last: Zhang

first: Hai

first: Yingrong

last: Lai

first: Yan

last: Guo

first: Yuxin

last: Chen

first: Liehua

last: Liu

first: Haipeng

last: Xiao

first: Hongyu

last: Guan

first: Yanbing


title: Temporal transcriptome in Pou5f3 and Sox19b mutant zebrafish embryos

status: Public on Mar 03 2021

city: Freiburg

first: Daria

last: Onichtchouk

address: Hauptstrasse 1

institute: University of Freiburg

summary: We applied time-series SE50bp RNA-seq with 35M reads per sample in wild-type, MZsox19b, MZspg, and double MZspgsox19b mutants in zebrafish embryos to understand the role of Pou5f3 and Sox19b during zebrafish zygotic genome activation. In total we sequenced 4 biological replicates (rep1-4) for WT time curve and 2 biological replicates (rep1-2) for each mutant. WT rep5 are technical replicates for WT rep1, while MZsox19b rep3 and MZspg rep3 are techical replicates for MZsox19b rep1 and MZspg rep1, respectively.

overall_design: temporal transcripts changes to record zygotic genome activation in zebrafish early development

first: Meijiang

last: Gao


title: Cell Surface Protein mRNAs Show Differential Transcription in Pyramidal and Fast-Spiking Cells as Revealed by Single-Cell Sequencing

status: Public on Dec 22 2020

city: Philadelphia

first: Junhyong

last: Kim

state: PA

address: 433 S University Avenue

institute: University of Pennsylvania

summary: We performed physiological recording and single cell RNAseq on mouse prefrontal cortical pyramidal and fast-spiking interneurons in the live brain slice preparation. One of the goals was to identify potential gene targets whose function might be disrupted in schizophrenia.

overall_design: Brain slices from mouse brain were acutely cultured, individual neurons recorded from and the RNA isolated from these same neurons for RNAseq analysis. The RNA was amplified with the aRNA procedure.

first: Lilla

last: Ravasz

first: Katalin

last: Kékesi

first: Dániel

last: Mittli

first: Mihail

middle: I

last: Todorov

first: Zsolt

last: Borhegyi

first: Mária

last: Ercsey-Ravasz

first: Botond

last: Tyukodi

first: Jinhui

last: Wang

first: Tamás

last: Bártfai

first: James

last: Eberwine

first: Gábor

last: Juhász


title: Single cell RNA sequencing redefines the mesenchymal cell landscape of mouse endometrium [single cell RNA-seq]

status: Public on Nov 16 2020

city: Edinburgh

first: Philippa

middle: TK

last: Saunders

address: 47 Little France Crescent

department: College of Medicine and Veterinary Medicine

institute: The University of Edinburgh

summary: We profile the transcriptomes of over 5,000 mouse single cells, yielding molecular definitions for mesenchymal cell types present in heathy cycling mouse uterus. We uncover novel heterogeneity within the Pdgfrb+ mesenchymal cell compartment of the mouse uterus, defining five subpopulations including two closely related Cspg4+ pericytes/vascular smooth muscle cells and three Pdgfra+Cd34+ subpopulations of fibroblasts.Our work dissects cellular heterogeneity within the mouse uterine mesenchyme providing a platform to understand the roles of these cell populations in uterine physiology and disease and for comparisons between mesenchymal cells in endometirum and other adult tissue which are prone to fibrosis.

overall_design: We present single-cell transcriptomic data on mesenchymal cells isolated from the uteri of 4 healthy cycling mice.

first: Phoebe

last: Kirkwood

first: Douglas

last: Gibson

first: Jamie

last: Smith

first: John

last: Wilson-Kanamori

first: Olympia

last: Kelepouri

first: Arantza

middle: E

last: Zufiaurre

first: Ross

last: Dobie

first: Neil

last: Henderson

middle: T


title: Core transcription regulatory circuitry orchestrates stratified epithelial homeostasis (RNA-seq)

status: Public on Dec 07 2020

city: Bengbu

first: Mingsen

last: Li

state: Anhui

address: No. 2600, Donghai Avenue, Bengbu City, Anhui Province

department: Interdisciplinary Eye Research Institute (EYE-X Institute)

institute: Bengbu Medical University

summary: Adult stem cell identity, plasticity, and homeostasis are precisely orchestrated by lineage-restricted epigenetic and transcriptional regulatory networks. Here, by integrating super-enhancer and chromatin accessibility landscapes, we delineate core transcription regulatory circuitries (CRCs) of limbal stem/progenitor cells (LSCs) and find that RUNX1 and SMAD3 are required for maintenance of the corneal epithelial identity and homeostasis.  RUNX1 or SMAD3 depletion inhibits PAX6 and induces LSCs to differentiate into epidermal-like type. RUNX1, PAX6 and SMAD3 (RPS) interact with each other and synergistically establish a CRC to govern the lineage-specific cis-regulatory atlas. Moreover, RUNX1 shapes LSC chromatin architecture via modulating H3K27ac deposition. Disturbance of RPS cooperation results in cell identity switching and dysfunction of the corneal epithelium, which is strongly linked to various human corneal diseases. Our work highlights CRC TF cooperativity for the establishment of stem cell identity and lineage commitment, and provides comprehensive regulatory principles for human stratified epithelial homeostasis and pathogenesis.

overall_design: RNA-seq for wildtype LSCs and skin epithelial stem cells (SESCs). RNA-seq for scrambled shRNA- and shRUNX1-treated LSCs.  RNA-seq for scrambled shRNA- and shSMAD3-treated LSCs.


title: Core transcription regulatory circuitry orchestrates stratified epithelial homeostasis (ChIP-seq, ATAC-seq)

overall_design: ChIP-seq for H3K27ac, H3K4me1, H3K4me3,  H3K27me3, RUNX1, PAX6, and SMAD3  in LSCs.  Chromatin accessibility profile of LSCs were generated by ATAC-seq


title: Core transcription regulatory circuitry orchestrates stratified epithelial homeostasis

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

overall_design: Refer to individual Series


title: Sub-lethal stimulation of ferroptosis leads to trophoblast dysfunction

status: Public on Sep 27 2020

city: Pittsburgh

first: Ofer

last: beharier

address: 204 Craft Ave

institute: MWRI

summary: Ferroptosis is a recently identified program of regulated cell death, defined by excessive accumulation of hydroperoxy-arachidonoyl (C20:4)- or adrenoyl (C22:4)- phosphatidyl-ethanolamine (OOH-PE). The selenium-dependent glutathione peroxidase 4 (GPX4) inhibits ferroptosis, converting unstable ferroptotic lipid hydroperoxides to non-toxic lipid alcohols. The effect of GPX4 ablation is divergent among cells and tissues, suggesting that additional regulators may guard trophoblasts against ferroptosis. While placental oxidative stress and lipotoxicity are hallmarks of placental dysfunction, the possible role of ferroptosis in placental function has not been hitherto investigated. Here we found that placental dysfunction is associated with ferroptosis, and that inhibition of GPX4 causes trophoblast injury and ferroptosis in vitro and in vivo during mouse pregnancy. Importantly, we uncover a role for the phospholipase PLA2G6 (PNPLA9, iPLA2beta), known to metabolizes OOH-PE to lyso-PE and oxidized fatty acid, in mitigating ferroptosis induced by GPX4 inhibition in vitro or by hypoxia-reoxygenation injury in vivo. Together, we identified ferroptosis in the human and mouse placenta, and established a novel role for PLA2G6 in attenuating trophoblastic ferroptosis. Our data provide mechanistic insights to the ill-defined entity of placental lipotoxicity, and may inspire new therapeutic strategies that target PLA2G6 as a means to modulate ferroptosis in placental and non-placental tissue.

overall_design: RNAseq of BeWo cells constantly expressing shControl or shGPX4 following ferrostatin-1 withdrawal

last: Beharier

first: Tianjiao

last: Chu

first: Yoel

last: Sadovsky


title: Single-cell characterization of transcriptomic heterogeneity in human tonsillar B-cell subsets

status: Public on Oct 21 2020

city: Durham

first: Micah

last: Luftig

state: NC

address: 213 Research Dr, DUMC Box 3054

department: Molecular Genetics and Microbiology

institute: Duke University School of Medicine

summary: BFL-1 is an understudied anti-apoptotic protein that is upregulated in melanoma, certain forms of leukemias and lymphomas, and Epstein-Barr virus (EBV)-immortalized lymphoblastoid cell lines (LCLs). We have previously shown that BFL-1 is upregulated in LCLs through a viral-mediated chromatin conformation. However, BFL-1 is also highly expressed in uninfected B cells undergoing maturation in the germinal center. We therefore sought to determine the non-viral mechanisms underlying BFL-1 upregulation in B cells. Here, we characterized the chromatin landscape of maturing B cell subsets found in human tonsillar lymphoid tissue. While chromatin accessibility at the BFL-1 locus increases as naïve B cells enter the germinal center reaction, we found that BFL-1 expression during the transition from dark zone to light zone correlates with a significant increase in three-dimensional chromatin association between upstream enhancer regions and the BFL-1 transcriptional start site (TSS). Interestingly, both LCLs and germinal center light zone B cells shared similar chromatin architectures at the BFL-1 TSS, suggesting a conserved mechanism underlying BFL-1 upregulation. Increased BFL-1 in LCLs also protects against FasL and TRAIL-activated extrinsic apoptosis. In addition to BFL-1 expression, LCLs and germinal center light zone B cells share similar patterns of gene expression, suggesting strong evidence that EBV infection phenocopies various aspects of the germinal center reaction. From this, we infer that EBV-infected B cells co-opts strategies from germinal center light zone B cells to upregulate BFL-1 and enhance their survival in establishing long-lived latent infection.

overall_design: Characterization of two human tonsils for heterogeneity in individual cell RNA levels. The gene expression profiles were used to identify cell subsets and also then to compare differential gene expression between these subsets. The purpose in the context of this study was primarily to corroborate the relationship between BFL-1 expression and the transition from dark zone to light zone of the germinal center. Furthermore, these samples provide biological references for phenotypes that arise in de novo B cell infection.

first: Joanne

last: Dai

first: Gregory

last: Crawford

first: Lingyun

last: Song

first: Elliott

last: SoRelle


title: Interleukin-18 and cytotoxic impairment are independent and synergistic causes virus-induced hyperinflammation in mice

status: Public on Nov 12 2020

city: St. Louis

first: Emily

last: Landy

state: Missouri

address: 425 S. Euclid Ave

summary: To determine the effects of excess IL-18 on virus-induced immunopathology, we infected Il18-transgenic (Il18tg) mice with Lymphocytic Choriomeningitis Virus (LCMV, Armstrong). LCMV infection is self-limited in wild-type (WT) mice, but Prf1-/- mice develop prolonged viremia and fatal HLH. LCMV-infected Il18-transgenic (Il18tg) mice developed cachexia and hyperinflammation comparable to Prf1-/- mice, albeit with minimal mortality.  We use RNA-sequencing to identify differences in the transcriptome of GP33 - specific CD8 T cells from these mice in comparison to a wild type mouse under the same conditions. We saw expression of Ifng was elevated about 4-fold in both Prf1-/- and Il18tg mice. Genes specifically upregulated in Il18tg CD8 T-cells included Csf2, Il1rl1, and Il12rb2. We also saw differences between Prf1-/- and WT/Il18tg CD8 T-cells that included Klrg1 and transcripts associated with CD8 T-cell exhaustion, including the inhibitory receptors Lag3, Havcr2, and Tigit, and the transcription factors Tox and Prdm1. These data support that IL-18 as a potent, independent, and modifiable driver of life-threatening innate and adaptive hyperinflammation, and support the rationale for an IL-18-driven subclass of hyperinflammation.

overall_design: FACS sorted GP33 Tetramer+ CD8 T lymphocytes from day 8 post LCMV-Armstrong infection in Prf1-/-, Il18tg, and C57BL/6 mice

first: Paul

last: Tsoukas

last: Rapp

first: Scott

last: Canna


title: Obesity in cardiac surgery patients

status: Public on Oct 20 2020

city: Leicester

first: Marcin

last: Wozniak

address: Leicester

institute: University of Leicester

summary: We report on the application of RNA sequencing to study expression changes in cardiac surgery patients of different obesity categories.

overall_design: Patients attending surgery were recruited as part of a clinical trial. Total RNA was obtained from myocardial tissue (specifically atrial biopsies), sequenced and analyzed. Comparison of gene expression was made among obese, normal-weight and overweight groups as well as comorbidity and other patient characteristics

first: Adewale

last: Adebayo

first: Gavin

last: Murphy


title: Swarming sample vs non-swarming sample

status: Public on Sep 19 2020

city: Shanghai

first: Sibao

last: Wang

address: 300 Feng Lin Road

department: CAS Center for Excellence in Molecular Plant Science/ Institute of Plant Physiology and Ecology

institute: Chinese Academy of Sciences

summary:
Transcriptional profiling of mosquito head comparing control non-swarming mosquito with swarming mosquito.
Screen the genes associated with swarming.

sample_organism:
Anopheles gambiae
Anopheles coluzzii

overall_design: Two-condition experiment, non-swarming mosquitoes vs. swarming mosquitoes. Biological replicates: 3 non-swarming replicates, 3 swarming replicates.


title: Loss of Setd2 promote Kras-induced acinar-to-ductal metaplasia and epitheliamesenchymal transition during pancreatic carcinogenesis

status: Public on Aug 02 2020

first: Ningning

last: Niu

address: 160 Pu Jian Road, Shanghai

department: Clinical Stem Cell Research Center

institute: Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital

summary: TCGA(PAAD) public database and PDAC tissue array with SETD2/H3K36me3 staining was used to investigate the clinical relevance of SETD2 in PDAC. Furthermore, to define the role of SETD2 in the carcinogenesis of PDAC, we crossed conditional Setd2 knockout mice (PdxcreSetd2flox/flox) together with with KrasG12D mice. Moreover, to examine the role of SETD2 after ductal metaplasia, Crisp/cas9 was used to deplete Setd2 in PDAC cells. RNA-seq and H3K36me3 Chip-seq were performed to uncover the mechanism.

overall_design: RNA-seq and H3K36me3 Chip-seq were performed in mouse acinar cell and KPC1199 cell line.

first: Jing

last: Xue


title: Zfp281 functions as a barrier in embryonic stem cells to extraembryonic endoderm stem cells differentiation [RNA-seq]

status: Public on Aug 19 2020

city: New York

first: Jianlong

state: New York

department: Department of Medicine

institute: Columbia University Irving Medical Center

summary: Cell-fate decisions and lineage commitment in early embryonic development are governed by comprehensive gene-regulatory programs. However, the molecular details leading to initial segregation of different lineages remain unclear. In the second cell-fate decision, epiblast (EPI) and primitive endoderm (PrE) lineages are formed from the pluripotent inner cell mass (ICM) cells at blastocyst stage. Here, we demonstrated that the pluripotency transcription factor Zfp281 is a barrier in embryonic stem cells (ESCs) to PrE lineage differentiation. Zfp281 is expressed in extraembryonic endoderm cells (XENs), the ex vivo derivatives of PrE. But knockdown of Zfp281 doesn’t affect either maintenance or expression of the PrE master regulators in XENs. Using an in vitro differentiation protocol, we revealed that knockout of Zfp281 significantly increased the efficiency of ESC to XEN derivation. Using a Zfp281 rescue line for the knockout cells, we further confirmed that effects of elevated efficiency of XEN derivation is specifically due to loss of Zfp281. Mechanistically, we revealed that Zfp281 interacts with components in the polycomb repressive complex 2 (PRC2), and recruits PRC2 to promoters of PrE master regulators GATA4 and GATA6 for transcriptional and epigenetic repression. Taken together, our results demonstrated a novel role of Zfp281 in second cell-fate decision in embryonic stem cell differentiation.

overall_design: RNA sequencing analysis was performed in WT and Zfp281KO ESCs, XENs, and intermediate cells during ESC-to-XEN differentiation

first: Xin

last: Huang


title: Fragile X Mental Retardation Protein Regulates R-loop Formation and Prevents Global Chromosome Fragility

status: Public on Sep 13 2020

city: Syracuse

first: Wenyi

last: Feng

state: NY

address: 750 East Adams Street

department: Biochemistry and Molecular Biology

institute: SUNY Upstate Medical University

summary: We adapted a previously published method, Break-seq, which was developed in the model organism Saccharomyces cerevisiae to mammalian cells and mapped DNA double strand breaks (DSBs) genome-wide.

overall_design: EBV transformed lymphocytes derived from a normal individual(GM06990) and a Fragile X individual (GM03200) were grown in RPMI1640, supplemented with GlutaMAX, 15% heat-inactivated FBS, 100 IU/ml penicillin and 100 ug/ml streptomycin.  At a density of 0.4-0.5x10E6 cells/ml, cells were treated with solvent (DMSO, 0.02%), 0.03 micromolar aphidicolin (APH), 0.3 micromolar APH, or nothing at all.  APH was dissolved in 0.02% DMSO at both concentrations.  After 24 h treatment, cells were harvested for Break-seq analysis.  Three independent sets of experiments were performed, wherein Set A and B are technical replicates from the same experiment and Set D and E are biological replicates.  Each strain/treatment combination has at least two indepent experiments.

first: Arijita

last: Chakraborty


title: 3D Genome of macaque fetal brain reveals evolutionary innovations during primate corticogenesis

status: Public on Dec 15 2020

first: Yuting

last: Liu

address: Haidian District, Beijing Summer Palace Road No. 5

department: School of Life Science

summary: Elucidating the regulatory mechanisms of human brain evolution is essential to understanding human cognition and mental disorders. We generated multi-omics profiles and constructed a high-resolution map of 3D genome architecture of rhesus macaque during corticogenesis. By comparing the 3D genomes of human, macaque and mouse brains, we identified many human-specific chromatin structure changes, including 499 topologically associating domains (TADs) and 1,266 chromatin loops. The human-specific loops are significantly enriched in enhancer-enhancer interactions and the regulated genes show human-specific expression changes in the subplate, a transient zone of the developing brain critical for neural circuit formation and plasticity. Notably, many human-specific sequence changes are located in the human-specific TAD boundaries and loop anchors, which may lead to the formation of new transcription factor binding sites and chromatin structures in human. Collectively, the presented data highlight the value of comparative 3D genome analyses in dissecting the regulatory mechanisms of brain development and evolution.

overall_design:
Hi-C, RNA-seq, ChIP-seq and DNase-seq in macaque cortical development

NOTE:
The GSM4974109-GSM4974114 processed data .hic files were replaced and the CP_cis_allValidPairs.hic, GZ_cis_allValidPairs.hic were added on Oct 25, 2022 as the previous files were incomplete.

The GSM4974109-GSM4974114 raw data have been updated with additional/technical replicate runs on Feb 20, 2023.

last: Luo

first: Dachang

last: Dang

first: Ting

last: Hu

first: Yingping

last: Hou

first: Xiaoyu

last: Meng

first: Fengyun

last: Zhang

first: Tingting

last: Li

first: Can

first: Min

first: Haixu

last: Wu

first: Qiushuo

last: Shen

first: Yan

first: Xuerui

last: Zeng

first: Xiechao

last: He

first: Lanzhen

last: Yan

first: Shihua

first: Cheng

first: Bing

last: Su


title: Reduction in Gene Expression Noise by Targeted Decondensation of Gene Loci

status: Public on Sep 04 2020

city: Newark

first: Ryan

last: Dikdan

state: NJ

address: 225 Warren St

department: Dept. of Medicine

institute: NJMS

summary: ATAC-seq was done on various cell lines generated from HeLa cells. The cell lines contained dCas9 constructs conjugated to the histone acetyltransferase p300, as well as a similar system with multiple p300 fragments present, per dCas9 enzyme utilizing SunTag.

overall_design: Analysis of chormatin accessbility of HeLa cells using ATAC-seq

first: Sanjay

last: Tyagi


title: Thousands of novel unannotated proteins expand the MHC I immunopeptidome in cancer

status: Public on Aug 01 2020

city: Cambridge

first: Tamara

last: Ouspenskaia

state: Massachusetts

address: 415 Main St

institute: Broad Institute

summary:
Tumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of the genome. Motivated by the recent discovery of translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized that cancer-associated processes could generate nuORFs that can serve as a new source of tumor antigens that harbor somatic mutations or show tumor-specific expression.
To identify cancer-specific nuORFs, we generated Ribo-seq profiles for 29 malignant and healthy samples. These included primary normal and chronic lymphocytic leukemia (CLL) B cells, patient-derived primary glioblastoma (GBM) and melanoma cell cultures, primary healthy melanocytes, as well as established colon carcinoma and melanoma cell lines. These also included B721.221 cells, the parental cell line previously used to generate 92 single HLA allele-expressing lines from which we collected mono-allelic MHC I immunopeptidome data.
We developed a hierarchical approach to identify translated novel unannotated open reading frames that leverages the large amount of Ribo-seq data we have generated in order to uncover lowly expressed nuORFs, while also preserving tissue specificity. We  constructed a database of novel unannotated ORFs (nuORFdb) and used it to analyze mass spectrometry datasets of MHC I-bound peptides, where we detected peptides from 3,555 nuORFs. Additionally, we used nuORFdb to identify cancer-specific nuORFs, as well as nuORFs harboring cancer-specific somatic variants as potential sources of neoantigens in cancer.
*This repository contains data from the publicly available cell lines used in this study, including B721.221 cells, A375 cells, HCT116 cells and primary healthy melanocytes (Thermo C0025C). The data pertaining to primary patient samples that are part of this study is deposited in dbGaP.

overall_design: Ribo-seq of B721.221 cells expressing four different HLA alleles, A375 cells, HCT116 cells (cycloheximide pre-treated or not), primary healthy melanocytes (3 replicates). In order to get sufficient reads for analysis, B721.221_A0101, B1501, and B4402 libraries were sequenced twice, Hmel_rep1 and rep2 libraries were sequenced 3 times. The other libraries were sequenced once.

first: Aviv

last: Regev


title: The evolution of TF-regulatory network of core C4 metabolic pathway genes in the genus of Flaveria (high light)

status: Public on Jul 28 2020

city: shanghai

first: Ming

middle: Ju

last: Lu

state: shanghai

address: 320 Yueyang Road, Xuhui Area, Shanghai, China

department: Partner Institute for Computational Biology, Shanghai Institutes for Biologic Sciences, CAS

institute: Shanghai Institutes for Biological Sciences, CAS

summary: C4 photosynthesis was evolved from ancestral C3 photosynthesis by recruited pre-existed genes to perform new functions. Enzymes and transporters required for C4 metabolic pathway has been well documented, however, transcriptional factors (TFs) that regulate those C4 metabolic genes is poorly understood, in particular, how the TF regulatory network of C4 metabolic genes was re-wired, and the involved metabolic functions of those TFs along the evolution of C4 photosynthesis remained unknown. Here, by using RNA-Seq data from growth condition that reported to have effect on C4 photosynthesis, we constructed the TF regulatory network for four evolutionarily closely related species in the genus Flaveria, which represent different stages of the evolution of C4 photosynthesis, namely, C3, type I C3-C4, type II C3-C4 and C4. Our results show that four TFs are conserved along the evolution whose function either relate to stress response or light response. TFs regulating C4 core genes in C3 species involved in functions belong to RNA regulation and nitrogen metabolism, and that in both intermediate species and C4 species involved in photosynthesis and light responsiveness. Moreover, the TF-network of C4 core metabolic genes has the highest network density in type I C3-C4 species and C4 species when consider the fragment of TF-regulatory network that up-regulated under low CO2, suggesting that TFs regulating C4 genes were recruited to photosynthesis at type I C3-C4 both in involved functions and network density. Our results provide a valuable resource for studying molecular regulatory mechanisms underlying C4 metabolic process.

sample_organism:
Flaveria trinervia
Flaveria ramosissima
Flaveria robusta

overall_design: For high light experiment, plants were grown in the greenhouse in the Partner institute of computational biology, SIBS, CAS, with high light to be 1400 μmol m-2 s-1 and control to be 500 μmol m-2 s-1. The high light was achieved by given additive light from self-made light source. For all the experiments, plant were watered twice a week and fertilized weekly.

first: Ming-Ju

last: Lyu

first: Xin-Guang

last: Zhu


title: The evolution of TF-regulatory network of core C4 metabolic pathway genes in the genus of Flaveria [low CO2]

status: Public on Jul 27 2020

sample_organism:
Flaveria trinervia
Flaveria ramosissima
Flaveria robusta
Flaveria sonorensis

overall_design: For low CO2 experiment, plants were grown in growth chamber with light intensity to be 200 μmol m-2 s-1 and temperature to be 22oC, 16h/8h light/ dark duration, 70% humidity. The CO2 concentration of low CO2 condition 100 μmol m-2 s-1, and that for control is 380 μmol m-2 s-1.

middle: J

first: Xin

middle: G


title: The evolution of TF-regulatory network of core C4 metabolic pathway genes in the genus of Flaveria [low CO2 vs ctrl]

platform_organism:
Flaveria trinervia
Flaveria ramosissima
Flaveria robusta
Flaveria sonorensis

overall_design: For low CO2 experiment, Plants were grown in growth chamber with light intensity to be 200 μmol m-2 s-1 and temperature to be 22oC, 16h/8h light/ dark duration, 70% humidity. The CO2 concentration of low CO2 condition 100 μmol m-2 s-1, and that for control is 380 μmol m-2 s-1. Plants for ABA experiment were grown in green house of SIPPE, SIBS, CAS, the light intensity was controlled to be 500 μmol m-2 s-1, and temperature to be 25oC, 16h/8h light/ dark duration, 70% humidity. A concentration of 40 μM ABA dissolved in distill H2O was sprayed to mature leaf of one-month old plants, and the control was sprayed with distill H2O. Plants for high light experiment were grown in the greenhouse in the Partner institute of computational biology, SIBS, CAS, with high light to be 1400 μmol m-2 s-1 and control to be 500 μmol m-2 s-1. The high light was achieved by given additive light from self-made light source. For all the experiments, plant were watered twice a week and fertilized weekly.

middle: A


title: The evolution of TF-regulatory network of core C4 metabolic pathway genes in the genus of Flaveria (Low CO2)

sample_organism:
Flaveria ramosissima
Flaveria sonorensis

overall_design: For low CO2 experiment, Plants were grown in growth chamber with light intensity to be 200 μmol m-2 s-1 and temperature to be 22oC, 16h/8h light/ dark duration, 70% humidity. The CO2 concentration of low CO2 condition 100 μmol m-2 s-1. plant were watered twice a week and fertilized weekly.


title: The evolution of TF-regulatory network of core C4 metabolic pathway genes in the genus of Flaveria [ABA]

overall_design: For low CO2 experiment, Plants were grown in growth chamber with light intensity to be 200 μmol m-2 s-1 and temperature to be 22oC, 16h/8h light/ dark duration, 70% humidity. Plants for ABA experiment were grown in green house of SIPPE, SIBS, CAS, the light intensity was controlled to be 500 μmol m-2 s-1, and temperature to be 25oC, 16h/8h light/ dark duration, 70% humidity. A concentration of 40 μM ABA dissolved in distill H2O was sprayed to mature leaf of one-month old plants, and the control was sprayed with distill H2O. Plants for high light experiment were grown in the greenhouse in the Partner institute of computational biology, SIBS, CAS, with high light to be 1400 μmol m-2 s-1 and control to be 500 μmol m-2 s-1. The high light was achieved by given additive light from self-made light source. For all the experiments, plant were watered twice a week and fertilized weekly.


title: Differential contribution of p300 and CBP to regulatory elements in mESCs [ChIP-seq]

status: Public on Jul 16 2020

city: Dallas

first: Laura

last: Banaszynski

state: TEXAS

address: 5323 Harry Hines Blvd

department: Green Center for Reproductive Biology Sciences

institute: University of Texas Medical Center

summary: In this study we analyze the individual contribution of p300 and CBP to the H3K27ac landscape, chromatin accessibility, and transcription in mESC.

overall_design: Native ChIP analysis of H3K27ac and crosslink ChIP analysis of p53 in mouse embryonic stem cell lines (Ctl, p300 and CBP knock down). All inputs sequenced.

first: Sara

last: Martire


title: Differential contribution of p300 and CBP to regulatory elements in mESCs [ATAC-seq]

overall_design: ATAC-seq analysis in mouse embryonic stem cell lines (Ctl, p300 and CBP knock down).


title: Differential contribution of p300 and CBP to regulatory elements in mESCs

summary:
In this study we analyze the individual contribution of p300 and CBP to the H3K27ac landscape, chromatin accessibility, and transcription in mESC.

This SuperSeries is composed of the SubSeries listed below.

overall_design:
Native ChIP analysis of H3K27ac, crosslink ChIP analysis of p53, ATAC-seq analysis and RNA-Seq analysis in mouse embryonic stem cell lines (Ctl, p300 and CBP knock down). All inputs sequenced.

Refer to individual Series


title: Transcriptomic responses to a live-attenuated Francisella tularensis vaccine

status: Public on Jun 30 2020

city: Rockville

first: Johannes

last: Goll

state: MD

address: 401 N Washington St

department: Bioinformatics Service Group

institute: The Emmes Company

summary: Impact of live attenuated F. tularensis vaccine (DVC-LVS) on PBMC poly(A)-RNA expresssion in 10 subjects over time (Days 1, 2 ,7, and 14 post-vaccination) relative to pre-vaccination (Day 0).

overall_design:
PBMC aliquots from ten subjects, 5 time points per subject (pre-vaccination at Day 0, and post-vaccination at Days 1, 2, 7, 14) were assayed using RNA-Seq by two sequencing cores (Emory and St. Louis University).

>>> The submitter declares that the raw data cannot be made available via any mechanism due to patient privacy concerns. <<<

middle: B

first: Shuzhao

first: James

middle: L

last: Edwards

first: Steven

last: Bosinger

first: Travis

last: Jensen

first: Yating

last: Wang

first: William

middle: F

last: Hooper

first: Casey

last: Gelber

first: Katherine

last: Sanders

first: Evan

last: Anderson

first: Nadine

last: Rouphael

first: Muktha

last: Natrajan

first: Robert

last: Johnson

first: Patrick

last: Sanz

first: Daniel

last: Hoft

first: Mark

last: Mulligan


title: The evolution of TF-regulatory network of core C4 metabolic pathway genes in the genus of Flaveria

first: Ming

last: Lu

overall_design: Refer to individual Series


title: Differential contribution of p300 and CBP to regulatory elements in mESCs [RNA-seq]

first: Laura

last: Banaszynski

overall_design: RNA-Seq analysis in mouse embryonic stem cells (Ctl, p300 and CBP knock down).

first: Sara

last: Martire


title: A unique viral reservoir landscape associated with durable natural control of HIV-1 infection

status: Public on Jun 15 2020

first: Ce

last: Gao

state: MA

address: 400 Technology Square

institute: Ragon Institute of MGH, MIT and Harvard


title: A unique viral reservoir landscape associated with durable natural control of HIV-1 infection [ATAC-seq]

summary: Sustained, drug-free control of HIV-1 replication is naturally achieved in less than 0.5% of infected persons (“elite controllers”, ECs), despite the presence of a replication-competent viral reservoir. Such an ability to spontaneously maintain undetectable plasma viremia is a major objective of functional cure efforts, yet the characteristics of proviral reservoirs in ECs remain to be determined. Using single-genome, near full-length next-generation sequencing and chromosomal integration site analysis, we here show that proviral reservoirs of ECs frequently consist of oligoclonal to near monoclonal clusters of identical intact proviral sequences. In contrast to persons treated with long-term antiretroviral therapy, intact proviral species from ECs displayed highly distinct chromosomal integration sites in the human genome and were preferentially located in centromeric satellite DNA or in KRAB-ZNF genes on chromosome 19, both of which are associated with heterochromatin features. Moreover, integration sites of intact proviruses from ECs showed increased distance to host transcriptional start sites and accessible chromatin and were enriched for repressive chromatin marks. These data suggest that a distinct proviral reservoir configuration represents a structural correlate of natural viral control, and that quality rather than quantity of viral reservoirs can be an important distinguishing feature for a functional cure of HIV-1 infection. Moreover, failure to detect intact proviral sequences despite analyzing > 1.5 billion peripheral blood mononuclear cells in one EC raises the possibility that a sterilizing cure of HIV-1 infection, previously only observed following allogeneic hematopoietic stem cell transplantation, may be feasible in rare instances.

overall_design: We performed RNAseq and ATACseq on 5 subsets of CD4 T cells from Elite controller and ART-treated patient PBMC samples  to prolife transcriptome and chromatin accessiblity.

first: Chenyang

last: Jiang

first: Xiaodong

last: Lian

first: Xiaoming

last: Sun

first: Joshua

last: Chevalier

first: Kevin

last: Einkauf

first: Samantha

last: Chen

first: Jane

last: Blackmer

first: Stephane

last: Hua

first: Ben

last: Rhee

first: Michael

last: Peluso

first: Rebecca

last: Hoh

first: Lynn

last: Bertagnolli

first: Sarah

last: Sweet

first: Joseph

last: Varriale

first: Gregory

last: Laird

first: Erik

last: Serrao

first: Alan

last: Engelman

first: Mary

last: Carrington

last: Siliciano

first: Janet

first: Steven

last: Deeks

first: Bruce

last: Walker

first: Mathias

last: Lichterfeld


title: beta-cyclocitral-responsive genes in rice

status: Public on Jun 09 2020

city: miki

first: kenji

last: gomi

state: kagawa

country: Japan

institute: Kagawa University

summary: The plant volatilebeta-cyclocitral plays important roles in the regulation of defense responses in rice. To clarify the response to beta-cyclocitral in rice at gene expression level, we performed a microarray analysis using the Agilent Rice Oligo Microarray (44k, custom-made; Agilent Technologies, Redwood City, CA, USA). As a result, treatment of linalool caused high upregulation of many defense-related genes including pathogenesis-related (PR) genes in rice.

overall_design: An Agilent Rice Oligo Microarray (44k, custom-made; Agilent Technologies,　Redwood City, CA, USA) was used for the microarray analysis. Total RNA was extracted from leaf blades of five-leaf stage rice plants that had been treated with 10 μM beta-cyclocitral for 1 day. For each biological replicate, material from at least three rice plants was pooled to provide a single sample for RNA extraction. We performed 4 biological replicates for each treatment. All microarray procedures and data analyses were performed according to the manufacturer’s instructions. RNA integrity was checked using an Agilent 2100 Bioanalyzer (Agilent Technologies, Redwood City, CA, USA). Total RNA (100 ng) was labeled with Cy-3 using an Agilent Low Input Quick Amp Labeling Kit, One-Color (Agilent Technologies). Fluorescently labeled targets were hybridized to Agilent Rice Oligo Microarrays for 17 h at 65°C. After hybridization, following wash processes were performed according to the manufacturer’s instructions, and hybridized microarrays were scanned using an Agilent Microarray Scanner (G2565CA; Agilent Technologies). Feature extraction software (Agilent Feature Extraction; Agilent Technologies) was used to delineate and measure the signal intensity of each spot in the array, and to normalize intensities. The background was measured around each spot as local background, calculated by the Feature Extraction software. Statistical data extraction processes were performed according to the manufacturer’s instructions.

first: Kenji

last: Gomi

first: Shiduku

last: Taniguchi


title: A unique viral reservoir landscape associated with durable natural control of HIV-1 infection [RNA-seq]

first: Ce

last: Gao

first: Chenyang

last: Jiang

first: Xiaodong

last: Lian

first: Xiaoming

last: Sun

first: Joshua

last: Chevalier

first: Kevin

last: Einkauf

first: Samantha

last: Chen

first: Jane

last: Blackmer

first: Stephane

last: Hua

first: Ben

last: Rhee

first: Robert


title: The lncRNA expression profiles in hepatocellular carcinoma cell lines under sulfatide treatment

status: Public on May 25 2020

first: Qianqian

last: Cai

address: No.138, Yixueyuan Road

department: Department of biochemistry and molecular biology

institute: Fudan University

summary: Sulfatide significantly promoted hepatocellular carcinoma cells survival, proliferation and angiogenesis. To understand the molecular mechanisms of sulfatide, the transcriptional profiles of lncRNAs in human hepatocellular carcinoma cells SMMC-7721 was investigated with ArrayStar lncRNA microarray with sulfatide treatment. Galactose-cerebroside treatment served as the control.

overall_design: We analyzed the expression profiles of lncRNAs in human hepatocellular carcinoma cells SMMC-7721 with sulfatide treatment (three independent replicate samples named D1, D2, and D3), SMMC-7721 cells with Galactose-cerebroside treatment (three independent replicate samples named C1, C2, and C3). LncRNA expression profiles were evaluated by Arraystar Human LncRNA MicroArray v2.0.

first: Xingzhong

last: Wu


title: Transcriptional comparison of in vitro and in vivo generated human dendritic cells

status: Public on May 23 2020

city: London

first: Kristine

last: Vaivode

address: CIBCI, First Floor, New Hunt's House, Great Maze Pond

department: Centre for Inflammation Biology and Cancer Immunology

institute: King's College London

summary: Dendritic cells (DC) are antigen presenting cells controlling T cell activation. In human, the diversity, ontogeny and functional capabilities of DC subsets are not fully understood. Here, we identified circulating CD88-CD1c+CD163+ DC (termed as DC3) as an immediate precursor of inflammatory CD88-CD14+CD1c+CD163+FcεRI+ DC. DC3 develop via a specific pathway, independent from the cDC-restricted (CDP) and monocyte-restricted (cMoP) progenitors, and are activated by GM-CSF. As classical DC, but unlike monocytes, DC3 drove the activation of naïve T cells. In vitro, DC3 displayed a distinctive ability to prime CD8+ T cells expressing a tissue-homing signature and the epithelial homing alpha-E integrin (CD103) through transforming growth factor-b (TGF-β) signaling. In vivo, DC3 infiltrated luminal breast cancer primary tumors and DC3 infiltration correlated positively with CD8+CD103+CD69+ tissue-resident memory T cells. Altogether, these findings define DC3 as a lineage of inflammatory DC endowed with a strong potential to regulate tumor immunity.

overall_design: Blood monocytes, pDC, AS-DC, CD5+ DC2, CD5- DC2 and DC3 were isolated from healthy donor. Monocytes, DC2 and DC3 were stimulated by a TLR agonist coktail. Naive CD8+ T cells and CXCR3+CD103- and CXCR3+CD103- CD8+ T cells were sorted by flow cytometry at day 5 of in vitro coculture with blood DC3. All cell types were analyzed in triplicates with 200 to 1000 cells per subset.

first: Pierre

last: Bourdely

first: Giorgio

last: Anselmi

first: Rodrigo

middle: N

last: Ramos

first: Yoann

last: Missolo-Kousou

first: Sofia

last: Hidalgo

first: Jimena

last: Tosselo

first: Nicolas

last: Nunez

first: Wilfrid

last: Richer

first: Anne

last: Vincent-Salomon

first: Alka

last: Saxena

first: Kristie

last: Wood

first: Alvaro

last: Lladser

first: Eliane

last: Piaggio

first: Julie

last: Helft

last: Guermonprez


title: Pou5f3 and Sox19b select gene expression repertoire at zebrafish Zygotic Genome Activation

status: Public on May 07 2020

city: Freiburg

first: Daria

last: Onichtchouk

address: Hauptstrasse 1

institute: University of Freiburg

summary: In zebrafish embryos, the maternal  transcription factors (TFs) Pou5f3 and Sox19b activate the early zygotic gene expression. To evaluate the unique and common roles of Pou5f3 and Sox19b,   we examined the changes in H3K27ac and H3K4me3 chromatin modifications in the embryos mutant by each TF.

overall_design:
We performed ChIP-seq for H3K27ac and H3K4me3 chromatin modifications in  the wild-type  zebrafish embryos, embryos mutant by Pou5f3 transcription factor (MZspg), and embryos mutant by Sox19b transcription factor (MZsox19b). Experiments were performed at dome stage (4.3 hours post-fertilization (hpf)).

**Please note that processed data and data processing description has been updated on Feb 28, 2021.

first: Anna

last: Gebhard

first: Lenka

last: Buryan


title: Single-cell transcriptomic atlas of human donor muscle tissue

status: Public on Jun 02 2020

city: Ithaca

first: Andrea

last: De Micheli

address: 161 Weill Hall

department: Biomedical Engineering

institute: Cornell University

summary: The overall objective of the study was to survey the cellular and gene expression heterogeneity of human muscle tissue by single-cell RNA-sequencing.

overall_design: We report a series of single-cell transcriptomic datasets of human donor muscle tissue produced using the Chromium 10X technology.

first: Benjamin

middle: D

last: Cosgrove


title: A Single-cell Transcriptomic Atlas of Primate Pancreatic Islet Aging

status: Public on Jun 11 2020

first: Yuxuan

last: Zheng

address: 825 Zhangheng Rd.

summary: Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes. Endocrine cells age heterogeneously, complicating the effort to unravel the molecular drives underlying endocrine aging. To overcome these obstacles, we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys. Despite sex differences and increased single-cell level transcriptional variations, aged β-cells showed increased unfolded protein response (UPR) along with the accumulation of protein aggregates. We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling, comprising adaptive UPR during pancreatic aging. Notably, we found age-related β-cell-specific upregulation of HSP90B1, an ER-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at the single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis, suggesting an avenue for therapies to delay β-cell aging and prevent aging-related diabetes.

overall_design:
We collected ~5,000 single cells from the pancreas of 8 young and 8 aged monkeys and performed single-cell RNA-seq sequencing.
[Correspondences between file labels and monkey individuals]
CE01: YF1, CE07: YF2, CE08: YF3, CE14: YF4
CE04: YM1, CE05: YM2, CE06: YM3, CE15: YM4
CE09: OF1, CE10: OF2, CE13: OF3, CE16: OF4
CE03: OM1, CE11: OM2, CE12: OM3, CE17: OM4

first: Jingyi

last: Li

first: Pengze

last: Yan

first: Moshi

last: Song

first: Si

last: Wang

first: Liang

last: Sun

first: Zunpeng

last: Liu

first: Shuai

last: Ma

first: Piu

last: Chan

first: Qi

last: Zhou

first: Juan Carlos Izpisua

last: Belmonte

first: Weiqi

last: Zhang

first: Guang-Hui

first: Fuchou

last: Tang

first: Jing

last: Qu


title: Genetic ablation of maternal SoxB1 results in the delay of gastrulation gene regulatory program in zebrafish

first: Daria

last: Onichtchouk

summary:
Purpose: Find out the consequences of Sox19b binding to the nucleosome distribution after ZGA
Methods: MNase-seq of WT and MZsox19b mutant zebrafish embryos at dome stage, building up nucleosome occupancy profiles
Results:Maternal Sox19b is involved in the nucleosome displacement from HNARs at the zygotic genome activation.
Conclusions: Nucleosome clearance by maternal Sox19b is essential for proper onset and timing of gastrulation.

overall_design: Nucleosome occupancy profiles of dome staged wild type (WT) and MZsox19b zebrafish mutant were generated by MNase treatment followed by deep sequencing, using Illumina HiSeq 2500.

first: Meijiang

last: Gao

first: Marina

last: Veil


title: The serotonin neurotransmitter modulates virulence of enteric pathogens

status: Public on May 08 2020

first: Aman

last: Kumar

state: Texas

address: 5323 Harry Hines Blvd.

department: Microbiology

institute: UT Southwestern Medical Center

summary: RNA seq experiment was perfomed in the presence and absence of 10µM serotonin

overall_design: EHEC strain 86 24 was used for this study. WT EHEC were grown until late log phase in low gluocse DMEM in the presence and absence of 10µM serotonin. RNA was extracted from these samples. The experiment was conducted with three biological replicates.

first: Vanessa

last: Sperandio


title: Comparative analysis of genome-wide DNA methylation identifies patterns that associate with conserved transcriptional programs in osteosarcoma

status: Public on May 01 2020

city: Minneapolis

first: Lauren

last: Mills

state: MN

address: 420 Delaware St SE

department: Department of Pediatrics

institute: University of Minnesota

summary: Osteosarcoma is an aggressive tumor of the bone that primarily affects young adults and adolescents. Osteosarcoma is characterized by genomic chaos and heterogeneity. While inactivation of tumor suppressor p53 TP53 is nearly universal other high frequency mutations or structural variations have not been identified. Despite this genomic heterogeneity, key conserved transcriptional programs associated with survival have been identified across human, canine and induced murine osteosarcoma. The epigenomic landscape, including DNA methylation, plays a key role in establishing transcriptional programs in all cell types.  The role of epigenetic dysregulation has been studied in a variety of cancers but has yet to be explored at scale in osteosarcoma. Here we examined genome-wide DNA methylation patterns in 24 human and 44 canine osteosarcoma samples identifying groups of highly correlated DNA methylation marks in human and canine osteosarcoma samples. We also link specific DNA methylation patterns to key transcriptional programs in both human and canine osteosarcoma. Building on previous work, we built a DNA methylation-based measure for the presence and abundance of various immune cell types in osteosarcoma. Finally, we determined that the underlying state of the tumor, and not changes in cell composition, were the main driver of differences in DNA methylation across the human and canine samples. Significance: This is the first large scale study of DNA methylation in osteosarcoma and lays the ground work for the exploration of DNA methylation programs that help establish conserved transcriptional programs in the context of different genomic landscapes.

sample_organism:
Homo sapiens
Canis lupus familiaris

platform_organism:
Homo sapiens
Canis lupus familiaris

overall_design: Targeted whole genome bisulfite sequencing of primary osteosarcoma tumors

first: Jaime

last: Modiano


title: Whole Genome Bisulfite sequencing: Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs

status: Public on Mar 18 2020

city: hackensack

first: Benjamin

last: Tycko

address: 40 prospect avenue

department: Epigenetics

institute: HUMC

summary: Background: Mapping of allele-specific DNA methylation (ASM) can be a post-GWAS strategy for localizing regulatory sequence polymorphisms (rSNPs). However, the advantages of this approach, and the mechanisms underlying ASM in normal and neoplastic cells, remain to be clarified.  Results: We performed whole genome methyl-seq on diverse normal cells and tissues and three types of cancers (multiple myeloma, lymphoma, glioblastoma multiforme). After excluding imprinting, the data pinpointed 15,114 high-confidence ASM differentially methylated regions (DMRs), of which 1,842 contained SNPs in strong linkage disequilibrium or coinciding with GWAS peaks. ASM frequencies were increased 5 to 9-fold in cancers vs. matched normal tissues, due to widespread allele-specific hypomethylation and focal allele-specific hypermethylation in poised chromatin. Cancers showed increased allele switching at ASM loci, but destructive SNPs in specific classes of CTCF and transcription factor (TF) binding motifs were similarly correlated with ASM in cancer and non-cancer. Rare somatic mutations in these same motif classes tracked with de novo ASM in the cancers. Allele-specific TF binding from ChIP-seq was enriched among ASM loci, but most ASM DMRs lacked such annotations, and some were found in otherwise uninformative “chromatin deserts”.   Conclusions: ASM is increased in cancers but occurs by a shared mechanism involving rSNPs in CTCF and TF binding sites in normal and neoplastic cells. Dense ASM mapping in normal plus cancer samples reveals candidate rSNPs that are difficult to find by other approaches. Together with GWAS data, these rSNPs can nominate specific transcriptional pathways in susceptibility to autoimmune, neuropsychiatric, and neoplastic diseases.

overall_design: For analyzing complete methylomes in 65 primary non-neoplastic and 16 primary neoplastic samples, plus the GM12878 LCL, WGBS was performed at the New York Genome Center (NYGC), MNG Genetics (MNG) and the Genomics Shared Resource of the Roswell Park Cancer Institute (RPCI). The NYGC used a modified Nextera transposase-based library approach. Briefly, genomic DNA was first tagmented using Nextera XT transposome and end repair was performed using 5mC. After bisulfite conversion, Illumina adapters and custom bisulfite converted adapters are attached by limited cycle PCR. Two separate libraries were prepared and pooled for each sample to limit the duplication rate and sequenced using Illumina X system (150 bp paired-end). WGBS performed at MNG used the Illumina TruSeq DNA Methylation Kit for library construction according to the manufacturer’s instructions and generated 150 bp paired end reads on an Illumina NovaSeq machine. WGBS performed at RPCI utilized the ACCEL-NGS Methyl-Seq DNA Library kit for library construction (Swift Biosciences) and generated 150 bp paired end reads on an Illumina NovaSeq. After trimming for low-quality bases (Phred score<30) and reads with a length <40 bp with TrimGalore, the reads were aligned to the human genome (GRCh37) using Bismark with paired end mode and default setting. Duplicate reads were removed using Picard tools and reads with more than 10% unconverted CHG or CHH cytosines were filtered out. SNP calling was performed with BisSNP using default settings, except for the maximum coverage filter set at 200 to encompass deep sequencing, and quality score recalibration. SNP calling was carried out using human genome GRCh37 and dbSNP147 as references. For ASM calling, we filtered out heterozygous SNPs with less than 5 reads per allele. In addition, SNP with multiple mapping positions were filtered out, as well as SNPs with more than one minor allele with allele frequency>0.05 and SNPs that deviated significantly from Hardy-Weinberg equilibrium based on exact tests corrected for multiple tests (FDR<0.05 by HardyWeinberg R package).  C/T and G/A SNPs were assessed after filtering out reads mapping to the C/T strand.   ASM calling was performed after separating the SNP-containing reads by allele. After Bismark methylation extractor is applied, CpG methylation calls by allele are retrieved using allele tagged read IDs. Paired reads with ambiguous SNP calling (i.e., called as REF allele on one paired end and ALT allele on the other) were discarded. For Nextera WGBS, due to the fill-in reaction using 5mC following DNA tagmentation which affects the 10 first base pairs (bp) on 5’ of read 2, methylation calling for Cs mapping to these bp were not considered. In addition, a slight methylation bias due to random priming and specific to each library kit was observed within the last 2 bp on 3’ of both paired ends for Nextera WGBS, within the first 10 bp on 5’ of both paired ends and the last 2 bp on 3’ of read 2 for TruSeq WGBS, and within the first 10 bp on 5’ of read 2 for ACCEL-NGS WGBS. Therefore, methylation calls in these windows were ignored.

first: Catherine

last: Do

first: Emmanuel

last: Dumont

first: Martha

last: Salas

first: Angelica

last: Castano

first: Huthayfa

last: Mujahed

first: Leonel

last: Maldonado

first: Arunjot

last: Singh

first: Govind

last: Bhagat

first: Soren

last: Lehman

first: Angela

middle: M

last: Christiano

first: Subha

last: Madhavan

first: Peter

last: Nagy

last: Green

first: Nicholas

last: Ilsey

first: Rena

last: Feinman

first: Cornelia

last: Trimble

first: Karen

last: Marder

first: Lawrence

last: Honig

last: Monk

first: Andre

last: Goy

first: Kar

last: Chow

first: Samuel

last: Goldlust

first: George

last: Kaptain

first: David

last: Siegel


title: Genome-wide targeted methyl-seq: Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs I

first: Benjamin

last: Tycko

summary:
Background: Mapping of allele-specific methylation (ASM) can be a post-GWAS strategy for localizing functional regulatory sequence polymorphisms (rSNPs). However, the unique advantages of this approach, and the mechanisms underlying ASM in normal and neoplastic cells, remain to be clarified.
Results: We performed sequence capture-based (25 samples, including 14 newly sequenced samples) and whole genome bisulfite sequencing (81 samples) on diverse normal human cells and tissues from multiple individuals, plus a group of cancers (multiple myeloma, lymphoma, and glioblastoma multiforme). After excluding imprinting, the data pinpointed 15,114 high-confidence ASM differentially methylated regions (DMRs), of which 1,842 contained SNPs in strong linkage disequilibrium or coinciding with GWAS peaks. ASM frequencies were increased 5 to 9-fold in cancers vs. matched normal tissues, due to widespread allele-specific hypomethylation and focal allele-specific hypermethylation in poised chromatin. Cancers showed increased allele switching at ASM loci, but destructive SNPs in specific classes of CTCF and transcription factor (TF) binding motifs were similarly correlated with ASM in cancer and non-cancer. Rare somatic mutations in these same motif classes tracked with de novo ASM in the cancers. Allele-specific TF binding from ChIP-seq was enriched among ASM loci, but most ASM DMRs lacked such annotations, and some were found in otherwise uninformative “chromatin deserts”.
Conclusions: ASM is increased in cancers but occurs by a shared mechanism involving rSNPs in CTCF and TF binding sites in normal and neoplastic cells. Dense ASM mapping in normal plus cancer samples reveals candidate rSNPs that are difficult to find by other approaches. Together with GWAS data, these rSNPs can nominate specific transcriptional pathways in susceptibility to autoimmune, neuropsychiatric, and neoplastic diseases.

overall_design: Agilent SureSelect methyl-seq DNA hybrid capture kit was used according to the manufacturer’s instructions. DNA was sheared to an average size of 200 bp and bisulfite converted with the EZ DNA methylation kit (Zymo). Paired end reads (100 bp, 150 or 250 bp) were generated at the Genomics Shared Resource of the Herbert Irving Comprehensive Cancer Center of Columbia University, with an Illumina HiSeq2500 sequencer. After trimming for low-quality bases (Phred score<30) and reads with a length <40 bp with TrimGalore, the reads were aligned to the human genome (GRCh37) using Bismark with paired end mode and default setting. Unpaired reads after trimming were aligned separately using single end-mode and the same settings. Duplicate reads were removed using Picard tools.

first: Catherine

last: Do

first: Emmanuel

last: Dumont

first: Martha

last: Salas

first: Angelica

last: Castano

first: Huthayfa

last: Mujahed

first: Leonel

last: Maldonado

last: Singh

last: Bhagat

middle: H


title: Whole genome bisulfite sequencing and Genome-wide targeted methyl-seq: Allele-specific DNA methylation is increased in cancers and its dense mapping in normal plus neoplastic cells increases the yield of disease-associated regulatory SNPs

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


title: Neutrophil extracellular traps activate IL-8 and IL-1 expression in human bronchial epithelia

status: Public on Apr 01 2020

city: Cincinnati

first: John

middle: M.

last: Snowball

state: OH

address: 3333 Burnet Ave

department: Pulmonary Research

institute: Cincinnati Childrens Hospital

summary: Human Broncial Epithilal cells (HBEs) exposed to NETs compared to HBEs exposed to PBS show  upregulatation of genes, most of which were related to IL-1 family members and GM-CSF.

overall_design: RNA sequencing  performed on primary HBEs from three healthy control subjects exposed to PBS or 5μg/ml human NETs isolated from three unrelated healthy donors for 18 hours.

first: Kristin

last: Hudock

middle: P

last: Clancy


title: Rational targeting of dynamic tumor subclones in relapsing human glioblastoma

status: Public on Feb 12 2020

city: Essen

first: Sied

last: Kebir

address: Hufelandstr. 55

institute: DKFZ-Division Translational Neurooncology at the West German Cancer Center (WTZ)

summary:
Glioblastoma therapy relies on the alkylating drug temozolomide (TMZ) administered to irradiated patients post-neurosurgery, which increases overall survival but cannot prevent fatal disease relapse. Using clinical samples and glioblastoma models, we here identify TMZ-driven enrichment of ALDH1A1+ tumor subclones acquiring AKT-dependent drug resistance en route to relapse.
We demonstrate that this recurrent phenotype switch is predictable and can be countered by a sequential rather than simultaneous combinatorial treatment approach.

overall_design: Microarray gene expression was conducted on paired (treatment-naive and relapse) patient-derived and experimentally generated IDH wt glioblastoma samples.

first: Björn

last: Scheffler


title: CellOracle: Dissecting cell identity via network inference and in silico gene perturbation

status: Public on Feb 15 2020

city: St Louis

first: Samantha

last: Morris

address: Department of Developmental Biology, Washington University School of

institute: Washington University in St Louis

summary: Single cell RNA-sequencing analysis of zebrafish embryos with wild type and crispant sample.

sample_organism:
Danio rerio
Mus musculus

platform_organism:
Danio rerio
Mus musculus

overall_design: Single cell RNA-sequencing was performed on wild type zebrafish embryos or F0 perturbed embryos using CRISPR-Cas9 injection method.

first: Kenji

last: Kamimoto

first: Blerta

last: Stringa

first: Christy

last: Hoffmann

first: Lilianna

last: Solnica-Krezel


title: HDAC and NFκB antagonists synergistically inhibit growth and metastatic dissemination of MYC-driven medulloblastoma

status: Public on Dec 13 2019

city: Homburg (Saar)

first: Marc

last: Remke

state: Saarland

address: Kirrberger Straße 100, Gebäude 9

department: Pediatric Translational Oncology Lab

institute: Universitätsklinikum des Saarlandes

summary: Aberrant oncogenic activation of MYC drives tumorigenesis in the most aggressive subset of medulloblastoma, the most common malignant brain tumor in childhood. Metastatic dissemination at diagnosis and at recurrence is commonly observed in MYC-driven medulloblastomas. Since these tumors display remarkable resistance to standard multimodal therapeutic approaches, epigenetic modulators commonly altered in these tumors are highly promising targets for novel therapeutic approaches. Here, we report on a cross-entity, high-throughput epigenetic drug screen to evaluate therapeutic vulnerabilities in the most common malignant primary brain tumors. Specifically, we performed a primary screen including 78 epigenetic inhibitors and a secondary screen including 20 histone deacetylase inhibitors (HDACi) to compare response profiles in atypical teratoid/rhabdoid tumor (AT/RT, n=11), medulloblastoma (n=14), and glioblastoma (n=14). This unbiased approach revealed preferential activity of HDACi in MYC-driven medulloblastoma. Importantly, the class I selective HDACi CI-994 showed significant cell viability reduction mediated by induction of apoptosis in MYC-driven medulloblastoma, with little to no activity in non-MYC-driven medulloblastoma, AT/RT, and glioblastoma in vitro. Notably, CI-994 displayed antitumoral effects at the primary site and the metastatic compartment in two orthotopic mouse models of MYC-driven medulloblastoma. Furthermore, synergistic drug screening and RNA sequencing revealed NFκB pathway induction as a mechanism of resistance to CI-994 treatment. Taken together, our findings identified MYC pathway activation as a predictive biomarker for epigenetic treatment intervention in high-risk medulloblastoma and provide a preclinical rationale for further exploration of CI-994 combined with NFκB pathway inhibitors in the treatment of MYC-driven medulloblastoma.

overall_design: Cell lines were treated with CI-994 IC50 concentration or DMSO for 48 hours

first: Daniel

last: Picard

first: Viktoria

last: Marquardt


title: Single-cell transcriptomics of mesenchymal and endothelial cells during renal injury

status: Public on Feb 29 2020

city: Edinburgh

middle: Roger

last: Wilson-Kanamori

address: 47 Little France Crescent

department: Centre for Inflammation Research

institute: University of Edinburgh

summary: We profile the transcriptomes of ~2000 mouse single cells to better understand the mechanisms involved in kidney scarring

overall_design: Single-cell transcriptomic data (SS2) are presented from both healthy mice and following day 2 and day 10 unilateral ureteric obstruction (UUO).

first: Jamie

middle: R

last: Smith

first: Ross

last: Dobie

first: Neil

middle: C

last: Henderson


title: high-throughput sequencing analysis of NCD mice, HFD mice and db/db mice

status: Public on Nov 07 2019

city: nnajing

first: fangfang

last: zhang

address: 24 Tongjiaxiang, Nanjing, Jiangsu province, People's republic of China

institute: China Pharmaceutical University

type: Non-coding RNA profiling by high throughput sequencing

summary: The goals of this study are to compare obese model mice islet transcriptome profiling (RNA-seq) to analyze the different lnc RNAs

overall_design: normal or high-fed diet or db/db mice

first: Fang

last: Zhang


title: ATAC-seq studies to open chromatin acessible region of AD brain samples

status: Public on Oct 31 2019

city: Shanghai

first: Guofeng

last: Meng

address: Jinke 3528

institute: Shanghai University of Traditional Chinese Medicine

summary: We performed the ATAC-seq to brain tissue from prefrontal cortex region in 6 AD Postmortem samples and 6 control non-dementia postmortem samples.

overall_design: 6 AD sample and 6 normal samples


title: ChIP-seq studies to ATF4, OLIG2, THRA binding sites of AD brain samples

summary: We performed the Chip-seq to brain tissues from prefrontal cortex region in AD Postmortem samples and non-dementia control postmortem samples.

overall_design: The binding sites of three TFs were studied in 6 AD sample and 6 normal samples were studied, respectively. The used antibodies include: (1) ATF4, CTS,11815S (lot#4); (2) Olig2, RnD, AF2418 (lot#UPA0718031); (3) THRA, SantaCruz, SC-56873 ((lot#J1614)


title: Genome-wide histone modification profiling of inner cell mass and trophoectoderm of blastocyst stage bovine embryos by novel low input RAT-ChIP

status: Public on Nov 15 2019

city: Tartu

first: Tõnis

last: Org

address: Riia 23

department: Institute of Molecular and Cell Biology

country: Estonia

institute: University of Tartu

summary: Chromatin immunoprecipitation coupled with next-generation sequencing (ChIP-seq) has revolutionized our understanding of chromatin related biological processes. The method, however, requires thousands of cells and has therefore limited applications in situations where cell numbers are limited such as highly pure cell populations or early developmental stages of mammalian preimplantation embryo where only few hundred cells might be available. Numerous attempts have been made to reduce the number of cells needed for successful ChIP-seq experiment, however, the developed methods are often complex, laborious or not sensitive enough. Here we describe a new simple method called Restrictase Assisted Tagmentation Chromatin Immunoprecipitation (RAT-ChIP) that enables to obtain high quality genome-wide histone modification profiles from as few as 100 cells. The method is simple, cost-effective, takes one day to complete and can potentially be automated. We subsequently use the novel method to derive the first genome-wide maps of histone H3K4me3 and H3K27me3 modifications of inner cell mass (ICM) and trophoectoderm (TE) of bovine blastocyst stage embryos.

sample_organism:
Homo sapiens
Bos taurus

platform_organism:
Homo sapiens
Bos taurus

overall_design: Examination of  histone H3K4me3 and H3K27me3 modifications in K562, H1299 cell-lines and in inner cell mass and trophoectoderm of blastocyst stage bovine embryos

first: Kati

last: Hensen

first: Rita

last: Kreevan

first: Elina

last: Mark

first: Olav

last: Sarv

first: Reidar

last: Andreson

first: Ülle

last: Jaakmaa

first: Andres

last: Salumets

first: Ants

last: Kurg


title: Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [Bisulfite-Seq]

status: Public on Sep 19 2019

city: Cambridge

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary:
Background: Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on parent-of-origin, and is typically regulated by differential DNA methylation inherited from gametes.  Imprinting is pervasive in murine extra-embryonic lineages and, uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally-inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored.
Results: We identify imprinted regions in post-implantation epiblast and extra-embryonic ectoderm (ExE) by assaying allelic histone modifications (H3K4me3, H3K36me3, H3K27me3), gene expression and DNA methylation in reciprocal C57BL/6 and CAST hybrid embryos. We distinguish loci with DNA methylation- dependent (canonical) and independent (non-canonical) imprinting by assaying hybrid embryos with ablated maternally-inherited DNA methylation. We find that non-canonical imprints are localized to endogenous retrovirus-K (ERVK) long terminal repeats (LTRs), which act as imprinted promoters specifically in extra-embryonic lineages. Transcribed ERVK LTRs are CpG-rich and located in close proximity to gene promoters, and imprinting status is determined by their epigenetic patterning in the oocyte. Finally, we show that oocyte-derived H3K27me3 associates with non-canonical imprints is not maintained beyond pre-implantation development, and is replaced by secondary imprinted DNA methylation on the maternal allele in post-implantation ExE, while being completely silenced by bi-allelic DNA methylation in epiblast.
Conclusions: This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development, and identifies an integral role for ERVK LTR repetitive elements.

overall_design: To evaluate the allelic regulation of histone modifications in the embryo, we assayed H3K4me3, H3K36me3 and H3K27me3 using ultra low-input ChIP-seq (Hanna et al. 2018) and post-bisulfite adaptor tagging (PBAT) in reciprocal hybrid (C57BL6/Babr x CAST/Ei) embryonic day (E) 6.5 epiblast and extra-embryonic ectoderm (ExE).  We additionally profiled these epigenetic marks in E6.5 embryos derived from females with a double conditional knockout for Dnmt3a and Dnmt3b in oocytes (matDKO), driven by Zp3-cre.  Consequently, these matDKO embryos will inherit no maternal DNA methylation, but are able to sufficiently establish DNA methylation post-fertilisation.  Allelic gene expression was evaluated in E7.5 epiblast and ExE of all hybrid crosses.

first: Courtney

last: Hanna

first: Simon

last: Andrews

first: Wendy

last: Dean

first: Gavin

last: Kelsey


title: Transcriptome analysis of flowering variation under vernalization in two inbred lines of Chinese cabbage

status: Public on Oct 25 2019

city: Daejeon

first: Haemyeong

last: Jung

address: 125 Gwahak-ro, Yuseong-gu

department: Plant Systems Engineering Research Center

country: South Korea

institute: KRIBB

summary: We analyze the differentially expressed genes (DEGs) in RNA-seq data.

overall_design: After vernalization for a certain period of time, we observed the RNA-seq data.

first: Hye

middle: S

last: Cho


title: Transcriptional regulation loss disturbs the brain function and indicates detrimental clinical outcomes of Alzheimer's disease

first: Guofeng

last: Meng

overall_design: Refer to individual Series


title: Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [RNA-Seq]


title: Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues


title: Expression data from CAR knockout mouse E10.5 embryos

status: Public on Oct 15 2019

city: Berlin

first: Fritz

last: Rathjen

address: Robert-Roessle-str. 10

institute: Max-Delbrueck-Center

summary:
Gene expression analysis of whole heart samples obtained from CAR wild type and knockout mouse E10.5 embryos.
We used the microarray to detect any gene expression changes in the E10.5 embronic heart due to the global deletion of CAR.

overall_design: CAR wild type and knockout embryos were dissected and 3 hearts /sample were collected and RNA was isolated by Qiagen Rneasy MiniKit. Gene expression was analysed by Affymetric Microarray Kit, 5 samples per genotype were analysed.

first: Claudia

last: Matthaeus


title: Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues [ChIP-Seq]