title: MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [France3]

first: François

last: Ghiringhelli

overall_design: This advanced non-small cell lung cancer (NSCLC) cohort comprises patients treated with anti-PD1 therapy in first or second line as monotherapy at the Centre Georges-François Leclerc in Dijon (France #3), and is composed of 35 patients. Tumors were collected at diagnosis, stored, and used with the written informed consent of the patients and RNAseq data was generated in our NGS core facility. Raw data were pseudo-aligned and gene counts were quantified using the kallisto software. Clinical data were collected by Prof. F. Ghiringhelli.

first: Emeric

last: Limagne

first: Lisa

last: Nuttin

first: Marion

last: Thibaudin

first: Elise

last: Jacquin

first: Romain

last: Aucagne

first: Marjorie

last: Bon

first: Solène

last: Revy

first: Robby

last: Barnestein

last: Ballot

first: Caroline

last: Truntzer

first: Valentin

last: Derangère

first: Jean-David

last: Fumet

first: Charlène

last: Latour

first: Cédric

last: Rébé

last: Bellaye


title: SARS-CoV-2 infection-induced human B cells

status: Public on Nov 19 2021

city: New York

first: Patrick

last: Wilson

state: NY

address: 413 E. 69th Street

department: gale and Ira Drukier Institute for Children's Health

country: USA

institute: Weill Cornell Medicine

type: Expression profiling by high throughput sequencing

summary: This study was designed to capture the single cell transcriptome and BCR sequence of B cells that were bait sorted using oligo-tagged viral antigens.

overall_design: Human B cells (viable/CD19+/antigen-PE+ or viable/CD19+/antigen-APC+) were bait sorted after initial magnetic enrichment and used in downstream sequencing.

middle: C

first: Haley

middle: L

last: Dugan

first: Christopher

middle: T

last: Stamper

first: Siriruk

last: Changrob

first: Nick

middle: W

last: Asby

first: Steven

middle: A

last: Erickson

first: Lei

last: Li


title: Genome-wide association studies identify novel genetic loci for epigenetic age acceleration among survivors of childhood cancer

status: Public on Mar 09 2022

city: Memphis

first: Zhaoming

last: Wang

state: TN

address: 262 Danny Thomas Place

department: Epidemiology & Cancer Control

institute: St. Jude Children's Research Hospital

type: Methylation profiling by genome tiling array

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

overall_design: Refer to individual Series


title: Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure

status: Public on Nov 03 2021

city: Barcelona

first: Ferran

last: Aguilar Parera

state: BARCELONA

address: Avinguda Diagonal 477, 11th floor, EF CLIF

country: Spain

institute: EF-CLIF

summary: Background&aims: Patients with acute decompensation (AD) of cirrhosis progressing to acute-on-chronic liver failure (ACLF) present a systemic hyperinflammatory response associated with increased circulating levels of small-molecule metabolites. To investigate whether these alterations reflect inadequate cell energy output, we assessed mitochondrial morphology and central metabolic pathways with emphasis on the tricarboxylic acid (TCA) cycle in peripheral leukocytes from AD patients with and without ACLF. Methods: The study included samples from AD patients (102 without and 126 with ACLF) along with 41 healthy subjects. Leukocyte mitochondria ultrastructure was visualized by transmission electron microscopy and cytosolic and mitochondrial metabolic fluxes were determined by assessing NADH/FADH 2 production from various substrates. Plasma GDF15 and FGF21 were determined by Luminex and acylcarnitines by LC-MS/MS. Gene expression was analyzed by RNA-seq and PCR-based glucose metabolism profiler array. Results: Mitochondrial ultrastructure in patients with advanced cirrhosis was distinguished by cristae rarefication and swelling. The number of mitochondria per leukocyte was higher in patients, accompanied by a reduction in their size. Increased FGF21 and C:6- and C:8-carnitines predicted mortality whereas GDF15 strongly correlated with a gene set signature related to leukocyte activation. Metabolic flux analyses revealed increased energy production in mononuclear leukocytes from patients with preferential involvement of extra-mitochondrial pathways, supported by upregulated expression of genes encoding enzymes of the glycolytic and pentose phosphate pathways. In ACLF patients, mitochondrial function analysis uncovered two break-points in the TCA cycle at the isocitrate dehydrogenase and succinate dehydrogenase level, which were bridged by anaplerotic reactions involving glutaminolysis and nucleoside metabolism. Conclusions: Our findings provide evidence at the cellular, organelle and biochemical levels that severe mitochondrial dysfunction governs immunometabolism in leukocytes from patients with AD cirrhosis and ACLF.

overall_design: RNA-seq transcriptomics in ACLF(n=8), AD(n=5) and Healthy volunteers (n=5)

first: I

last: Zhang

first: A

last: Curto

first: J

last: Clària


title: Molecular characterization of chronic liver disease dynamics: from liver fibrosis to acute-on-chronic liver failure

status: Public on Sep 11 2021

first: Juanjo

last: Lozano

address: C/ Rosselló 153

department: Plataforma de Bioinformatica

institute: CIBEREHD

summary: BACKGROUND: The molecular mechanisms driving the progression from early chronic liver disease (eCLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Thus, the aim of this work is to develop a network-based approach to investigate molecular pathways driving progression from eCLD to ACLF. We created 9 liver-specific biological networks capturing key pathophysiological processes potentially related to CLD. We used these networks as framework to perform gene set enrichment analyses(GSEA) and create dynamic profiles of disease progression.  RESULTS: Principal component analyses revealed that samples clustered according to the disease stage. GSEA analyses of the defined processes showed an up-regulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between CC and DC, while ACLF showed acute expression changes in all the defined liver-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated to ACLF onset. Functional analyses showed that ascending profiles were associated to inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the up-regulation of 4 genes of the ascending profile CXCL-6, KRT-18, SPINK-1, and ITGA2, and validated our findings on an independent patient’s cohort.  CONCLUSION: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis processes. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting thus the hypothesis that ACLF should be considered a distinct entity.

overall_design: Transcriptome analysis on liver biopsies from patients at different liver disease stages, including 5 fibrosis(eCLD), 8 compensated cirrhosis, 12 decompensated cirrhosis, 8 ACLF, and 6 control healthy livers was performed.

last: Graupera

first: L

last: Isus

middle: J

first: P

last: Sancho-Bru

last: Ginès

last: Aloy


title: Gene expression patterns in blood during human anaphylaxis, trauma, and sepsis

status: Public on Sep 12 2021

city: Subiaco

first: Anthony

last: Bosco

state: WA

address: 100 Roberts Road

country: Australia

institute: Telethon Kids Institute

summary:
Gene expression was profiled in peripheral blood samples collected from patients during anaphylaxis, trauma, or sepsis, and from healthy controls.
Patients were recruited from three Australian emergency departments (ED) between March 2011 and June 2013. Samples were collected at ED arrival (T0), 1 hour later (T1), and 3 hours post arrival (T2).

overall_design: The study design consisted of four disease phenotypes (anaphylaxis, sepsis, trauma, healthy controls) and up to 3 time points. Healthy controls were matched to patients within each study.

first: Erika

last: Bosio

first: Simon

last: Brown


title: A unique adipocyte progenitor population that promotes age-related adiposity

status: Public on Dec 02 2021

city: Los angeles

first: Gaoyan

state: CA

address: 1929 beloit ave, apt315

institute: UCLA

summary: The average fat (adipose tissue) mass in adults increases dramatically with age, and older people often suffer from visceral obesity and related adverse metabolic disorders. Unfortunately, how aging leads to adipose accumulation is poorly understood. It is known that fat cell (adipocyte) turnover is very low in young mice, similar to that in young humans. Single-cell RNA sequencing analyses reveal that aging globally remodels APCs. Herein, we identify a novel, age-specific committed APC population as CP-A cells, existing both in mice and humans, with a global activation of proliferation and adipogenesis pathways. CP-A cells display high proliferation and adipogenesis activity, both in vivo and in vitro. M1 macrophages may regulate the remodeling of APCs and the generation of CP-A cells during aging.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: single cell RNA sequencing profiles of Lin- stromal vascular fraction (SVF) cells and CD45+ immune cells from 2.5-month-old or 12-month-old C57BL/6J male mice epididymal white adipose tissue or Lin- SVFs from human peri-pancreatic adipose tissue.

first: Guan

first: Qiong

first: Xia

last: Yang


title: ChIP-seq of H3K27acethylation of human aortic endothelial cells (HAECs) treated with Cobalt chloride (CoCl2)

status: Public on Nov 18 2021

city: Tokyo

first: Naoko

last: Hattori

address: 5-1-1 Tsukiji, Chuo-ku

department: Research Institute

country: Japan

institute: National Cancer Center

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodeling, and hypoxia is known to induce EndMT and involved in cardiovascular disease development. Cobalt chloride (CoCl2), a chemical inducer of hypoxia-inducible factor-1 (HIF-1) could influence cellular function and its differentiation. However, exact molecular mechanism how stabilization of HIF-1 by cobalt chloride in human primary ECs affects cellular behavior and EndMT process is largely unknown. In this study, we performed ChIP-seq for H3K27ac in human aortic endothelial cells (HAECs) treated with CoCl2

overall_design: H3K27ac profiles of HAECs were generated by ChIP-sequencing using Illumina HiSeqX.

first: Yoshito

last: Yamashiro

first: Yu-Yu

last: Liu


title: Double-strand GFP RNA injection reveals no off-target effect in Nasonia vitripennis

status: Public on Dec 21 2021

city: Wageningen

first: Julien

last: Rougeot

address: Droevendaalsesteeg 1

department: Plant Science Group

country: Netherlands

institute: Wageningen University and Research (Netherlands)

summary: The aim of this experiment is to assess the off-target effect of RNAi in Nasonia vitripennis at transcriptome level by comparing the effect of a non-specific RNAi against GFP together with water or not injected controls.

overall_design: RNAseq of dsGFP RNA, water-injected, or non-injected controls each in triplicates.

first: Yidong

last: Wang

first: Eveline

last: Verhulst


title: Single nuclei RNAseq of rat area postrema and nucleus tractus solitarius

status: Public on Sep 09 2021

city: Philadelphia

first: Benjamin

middle: C.

last: Reiner

state: PA

address: 125 S 31st St

institute: University of Pennsylvania

summary: We performed single-nuclei RNAseq of Sprague Dawley rat area postrema and nucleus tractus solitarius brain samples to identify cellular subtypes.

overall_design: We performed the 10x Genomics 3' gene expression assay (v3.1) on nuclei isolated from frozen Sprague Dawley rat area postrema and nucleus tractus solitarius combined brain punches. At the onset of the dark cycle, rats (n=4, ~400 g) were injected with saline (i.p.). After six hours, rats were deeply anesthetized with a triple cocktail of ketamine, xylazine and acepromazine (180 mg/kg, 5.4 mg/kg and 1.28 mg/kg, respectively; i.p.) in the middle of the dark phase. Brains were removed and snap-frozen in dry ice-cold hexane. Three adjacent micro-punch samples (each ~1 cubic mm) containing the AP and left and right NTS were collected from coronally-prepared brains on a cryostat, pooled together, and stored at -80°C until further processing. Nuclei were isolated by differential centrifugation and microfluidically captured using the 10x Genomics Chromium controller. Sequencing libraries were constructed and sequenced on an Illumina NovaSeq 6000.

first: Richard

last: Crist

first: Matthew

middle: R

last: Hayes

first: Bart

last: De Jonghe

first: Tito

last: Borner


title: Organ-differential Regulation of Vascular Development by DEAD-box Helicase 24

status: Public on Oct 08 2021

city: Zhuhai

first: Fangbin

last: Chen

state: Guangdong

address: Meihua East Road No.52

country: China

institute: Sun Yat-sen University

summary: The goal of this study is to understand the molecular mechanisms by which DDX24 regulates vascular development in an organ-specific manner. To this end, we performed RNA sequencing on HUVECs and HCMECs transfected with either DDX24 siRNA or control siRNA and compared the expression levels of genes involved in angiogenesis

overall_design: mRNA profiles were generated from HUVECs and HCMECs transfected with either DDX24 or control siRNA. Total RNA was extracted from collected cells, and cDNA libraries were constructed for sequencing. Samples were prepared in duplicate and sequenced using the Illumina NovaSeq 6000 platform

first: Zhaohua

last: Deng

first: Hong

last: Shan

first: Huanhuan

last: He


title: Aging, inflammation and DNA damage in the somatic testicular niche with idiopathic germ cell aplasia

status: Public on Aug 04 2021

city: Milan

first: Anna Sofia

last: Tascini

address: Via Olgettina, 60

department: Center for Omics Science

country: Italy

institute: IRCCS, Ospedale San Raffaele

summary: Germ cell aplasia represents the most severe form of male infertility, and is associated with increased risk of early onset age-related chronic diseases and higher risk of death. Here we investigated the transcriptional landscape of 3880 somatic cells clustered in Sertoli, peritubular Myoid, Leydig, endothelial, stromal, T cells and macrophages from 3 human testis with idiopathic germ cell aplasia. Deregulated somatic pathways were associated with over-expression of paternally imprinted genes in immature Leydig cells, extracellular matrix composition and organization, hormonal milieu, chronic pro-inflammatory environments and early ageing, which were validated with an external cohort of 44 men with idiopathic germ cell aplasia compared to 102 age-matched fertile men. These 7 transcriptomic datasets unveil new insights into the germ cell aplasia, and prompts new thinking to better understand the pathogenesis of the idiopathic disease and the associated clinical manifestations of early ageing process.

overall_design: Droplet-based scRNAseq on freshly isolated human testis paranchyma from three men with idiopathic non-obstructive azoospermia and one man with obstructive azoospermia

first: Massimo

last: Alfano


title: RNA-Seq to identify NMUR-1-regulated genes in C. elegans defense against pathogen infection

status: Public on Feb 28 2022

city: Spokane

first: Yiyong

address: 412 E Spokane Falls Blvd

institute: Washington State University

summary: To gain molecular insights on how NMUR-1 regulates C. elegans defense against pathogen infection, we used RNA-Seq to profile gene expression in nmur-1(ok1387) animals relative to wild-type animals with or without E. faecalis or S. enterica infection.  We found that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens.

overall_design: Five replicates of six groups of RNA samples (nmur-1(ok1387) and wild-type animals with or without exposure to E. faecalis or S. enterica) were sequenced.  Gene expression was compared between groups to identify NMUR-1-regulated genes under uninfection or infection conditions.

first: Phillip

last: Wibisono

first: Jingru

last: Sun


title: Combinatorial analyis of translation dynamics reveals eIF2 dependence of translation initiation at near-cognate codons

status: Public on Jul 01 2021

city: Higashi-ku, Fukuoka

first: Kazuya

last: Ichihara

address: 3-1-1, Maidashi

institute: Kyushu University

summary: Although ribosome-profiling and translation initiation sequencing (TI-seq) analyses have identified many noncanonical initiation codons, the precise detection of translation initiation sites (TISs) remains a challenge, mainly because of experimental artifacts of such analyses. Here we describe a new method, TISCA (TIS detection by translation Complex Analysis), for the accurate identification of TISs. TISCA proved to be more reliable for TIS detection compared with existing tools, and it identified a substantial number of near-cognate codons in Kozak-like sequence contexts. Analysis of proteomics data revealed the presence of methionine at the NH2-terminus of most proteins derived from near-cognate initiation codons. Although eukaryotic initiation factor 2 (eIF2), eIF2A, and eIF2D have previously been shown to contribute to translation initiation at near-cognate codons, we found that most noncanonical initiation events are dependent on eIF2, consistent with the initial amino acid being methionine. Comprehensive identification of TISs by TISCA should facilitate characterization of the mechanism of noncanonical initiation.

first: K

first: A

last: Matsumoto

last: Nakayama


title: MEK inhibition overcomes chemoimmunotherapy resistance by inducing CXCL10 in cancer cells [LLC1]

status: Public on Dec 08 2021

city: DIJON

first: François

last: Ghiringhelli

address: 1 rue du Professeur Marion

country: France

institute: UMR INSERM 1231

summary: Chemotherapy with anti PD-1/PD-L1 mAb has become the standard of care for patients with metastatic non-small cell lung cancer (NSCLC). Using lung tumor models, where pemetrexed-platinum chemotherapy (PEM/CDDP) remains unable to synergize with immune checkpoint inhibitors (ICI), we linked failure of this treatment with its inability to induce CXCL10 expression and CD8+ T cell recruitment. Using drug screening, we showed that combining a MEK inhibitor (MEKi) with PEM/CDDP triggers CXCL10 secretion by cancer cells and CD8+ T cell recruitment, and restores ICI efficacy. PEM/CDDP plus MEKi promotes optineurin (OPTN)-dependent mitophagy, resulting in CXCL10 production in a mitochondrial DNA and TLR9-dependent manner. TLR9 or autophagy/mitophagy processes genetic inactivation of abort the antitumor efficacy of PEM/CDDP plus MEKi/anti PD-L1 therapy. In human NSCLC, high OPTN, TLR9 and CXCL10 expression is associated with better response to ICI. Our results underline the role of TLR9 and OPTN-dependent mitophagy in enhancing chemoimmunotherapy efficacy.

overall_design: All conditions are in triplicat and analyszed at two times after treatment (6 (T6) and 24hrs (T24)). Control LLC1 cells (NT) were treated only with 0,1% DMSO. CP cells were treated with cisplatin (2.5µM) and pemetrexed (2.5 µM). T cells were treated with trametinib (MEK inhibiteur, 10 nM). TCP cells were treated with both cisplatin, pemetrexed and trametinib. Total RNA from tumor cells was extracted with TriReagent (Fisher Scientific), RNA Sequencing was performed by the GenomEast platform, a member of the “France Génomique” consortium (ANR-10-INBS- 0009). Differential expression analysis was performed with the DESeq2 R package (Love et al., 2014). LLC1 cells treated with trametinib, PEM/CDDP or PEM/CDDP plus trametinib were compared to each other and to the control group. Raw p-values associated with each gene were adjusted using Bonferroni correction, as advised. For each comparison, genes with an-adjusted p-value < 0.10 were selected as differential.

first: Emeric

last: Limagne

first: Lisa

last: Nuttin

first: Marion

last: Thibaudin

first: Elise

last: Jacquin

first: Romain

last: Aucagne

first: Marjorie

last: Bon

first: Solène

last: Revy

first: Robby

last: Barnestein

last: Ballot

first: Caroline

last: Truntzer

first: Valentin

last: Derangère

first: Jean-David

last: Fumet

first: Charlène

last: Latour

first: Cédric

last: Rébé

first: Pierre-Simon

last: Bellaye

first: Coureche-Guillaume

last: Kaderbhaï

first: Aodrenn

last: Spill

first: Bertrand

last: Collin

first: Mary

middle: B

last: Callanan

first: Aurélie

last: Lagrange

first: Laure

last: Favier

first: Bruno

last: Coudert

first: Laurent

last: Arnould

first: Sylvain

last: Ladoire

last: Routy

first: Philippe

last: Joubert


title: Gingival transcriptomics phases of periodontitis lesions in nonhuman primate model

status: Public on Jul 22 2021

city: Lexington

first: kuey

middle: Chu

last: Chen

state: KENTUCKY

address: 800 Rose Street, UK Med Ctr

department: Pharmacology and Nutritional Sciences

institute: University of Kentucky

summary:
We used a nonhuman primate (NHP) model of ligature-induced periodontitis to identify gingival transcriptome changes associated with aging during the phases of periodontitis lesions (initiation, progression, and resolution).
Four age groups of nonhuman primate were studied: Young (<3 years of age); Adolescent (3 to 7 years), Adult (12 to 15 years), and Aged (17-23 years)

overall_design: Gingival tissues from healthy nonhuman primates were obtained at baseline (BL) before ligation, 2 weeks and 1 month (initiation), 3 months (progression) after placing ligatures, as well as two months after removing the ligatures (5M-resolution) for RNA extraction and hybridization on Affymetrix microarrays.

first: Octavio

last: Gonzalez

first: Jeffrey

last: Ebersole


title: Single cell RNA sequencing of polarized cystic fibrosis (CF) and non-CF human airway cell cultures following transduction of primary basal cells with lentivirus

status: Public on Aug 31 2021

city: Iowa City

first: Alejandro

middle: A.

last: Pezzulo

state: Iowa

address: 6316 Pappajohn Biomedical Discovery Building

department: Department of Internal Medicine

institute: Universty of Iowa

summary: The goal of this study was to compare cell composition, gene expression, and transduction efficiency of different epithelial cell types following transduction with lentiviruses containing either green fluorescent protein (GFP) or the human CFTR gene.

overall_design: Primary basal cells were collected from CF and non-CF lung donors, transduced with a lentivirus and polarized, prepared for single cell sequencing via 10X Genomics Chromium controller, and sequenced on Illumina HiSeq4000 and NovaSeq6000

first: Ashley

last: Cooney

first: Andrew

last: Thurman

first: Paul

last: McCray Jr.

first: Patrick

last: Sinn


title: A cis-acting mechanism mediates trancriptional memory at Polycomb target genes in mammals [ChIP-Seq]

status: Public on Aug 19 2021

city: Paris

first: Daniel

last: Holoch

state: Cedex 05

address: 26 rue d'Ulm

department: Genetics and Developmental Biology Unit

institute: Institut Curie, Centre de Recherche

summary: Epigenetic inheritance of gene expression states enables a single genome to maintain distinct cellular identities. How histone modifications contribute to this process remains unclear. Using global chromatin perturbations and local, time-controlled modulation of transcription, we establish the existence of epigenetic memory of transcriptional activation for genes that can be silenced by the Polycomb group. This property emerges during cell differentiation and allows genes to be stably switched following a transient transcriptional stimulus. This transcriptional memory state at Polycomb targets operates in cis; however, rather than relying solely on read-and-write propagation of histone modifications, the memory is also linked to the strength of activating input opposing Polycomb proteins and therefore varies with the cellular context. Our data and computational simulations suggest a model whereby transcriptional memory arises from double-negative feedback between Polycomb-mediated silencing and active transcription. Epigenetic memory at Polycomb targets thus depends not only on histone modifications but also on the gene-regulatory network and underlying identity of a cell.

overall_design:
H3K27me3 enrichment profiles (CUT&RUN-seq) of mouse neural progenitor cells in untreated (2 replicates), PRC2-inhibitor-treated (2 replicates) and PRC2-inhibitor-washout (2 replicates) conditions (6 samples).
H3K27me3 enrichment profiles (ChIP-seq) of immortalized mouse embryonic fibroblast line A (= C2) in wild-type (2 replicates), Ezh2 KO (2 replicates) and Ezh2 rescue (2 replicates) conditions (6 samples).
H3K27me3 enrichment profiles (ChIP-seq) of immortalized mouse embryonic fibroblast line B (= C26) in wild-type (2 replicates), Ezh2 KO (2 replicates), Ezh2 rescue (2 replicates) conditions (6 samples).
Input sample for ChIP-seq of immortalized mouse embryonic fibroblast line A (= C2) (1 sample).
RNA polymerase II enrichment profiles (ChIP-seq) of immortalized mouse embryonic fibroblast line A (= C2) in Ezh2 KO (2 replicates) (2 samples).
H3K4me3 enrichment profiles (ChIP-seq) of immortalized mouse embryonic fibroblast line A (= C2) in Ezh2 KO (2 replicates) (2 samples).
H3K36me3 enrichment profiles (ChIP-seq) of immortalized mouse embryonic fibroblast line A (= C2) in Ezh2 KO (2 replicates) (2 samples).

UPDATE: [Feb-05-2026] The titles, source names, and characteristics of Samples GSM4434061-GSM4434064 were corrected. The bigWig files were reassociated with the GSM records accordingly, but the names and contents of the bigWig files did not change. The raw data associated with each GSM record did not change.

first: Michel

last: Wassef

first: Cecilia

last: Lövkvist

first: Dina

last: Zielinski

first: Setareh

last: Aflaki

first: Bérangère

last: Lombard

first: Tiphaine

last: Héry

first: Damarys

last: Loew

first: Martin

last: Howard

first: Raphaël

last: Margueron


title: Identification of EMT and EMT/Cilium-dependent gene expression signatures + Identification of breast tumors of the claudin-low molecular subtype among triple-negative breast cancers

status: Public on Oct 05 2021

city: Cambridge

first: Charles

middle: Arthur

last: Whittaker

state: MA

institute: Koch Institute

summary: The goal of the first gene expression analysis reported here (Samples 1-16) was to establish gene expression signatures associated to activation of an Epithelial-Mesenchymal Transition (EMT) and primary ciliogenesis, in immortalized and non-transformed (HMLE) or transformed (HMLER) human mammary epithelial cells, respectively. The goal of the second gene expression analysis (Samples 17-83) was to determine the molecular subtypes of human breast cancers of a triple-negative breast cancer (TNBC) biobank.

overall_design:
Samples 1-16: Epithelial-like (shCTL, CTL) and Mesenchymal-like (shEcad, Snail) HMLE and HMLER cells non-treated or treated with DMSO or Ciliobrevin A were analyzed.
Samples 17-83: Triple-negative breast tumors (17-78) and control luminal breast tumors (79-83) were analyzed.

first: Vincent

last: Guen

first: Molly

middle: M

last: Wilson

first: Matthieu

last: Le Gallo

first: Jacqueline

last: Lees


title: CPD-seq map of UV damage formation in isolated human genomic DNA

status: Public on Aug 27 2021

city: Pullman

first: John

middle: J.

last: Wyrick

address: Biotechnology Life Sciences 241

department: School of Molecular Biosciences

summary: UV-induced CPDs were mapped in isolated human genomic DNA following 80J/m2 of UVC irradiation

overall_design: UV-induced cyclobutane pyrimidine dimers (CPDs) were mapped across the genome of isolated genomic DNA from human NHF1 cells that was irradiated in vitro with UV dose of 80 J/m2 of UVC light.

first: Peng

last: Mao


title: A single-cell and spatially resolved atlas of human breast cancers

status: Public on Jun 24 2021

city: Darlinghurst

first: Alexander

last: Swarbrick

state: NSW

address: 384 Victoria Street

institute: Garvan Institute of Medical Research

summary: This study presents a single cell and spatially resolved transcriptomics analysis of human breast cancers. We develop a single cell method of intrinsic subtype classification (scSubtype) to reveal recurrent neoplastic cell heterogeneity. Immunophenotyping using CITE-Seq provides high-resolution immune profiles, including novel PD-L1/PD-L2+ macrophage populations associated with clinical outcome. Mesenchymal cells displayed diverse functions and cell surface protein expression through differentiation within 3 major lineages. Stromal-immune niches were spatially organized in tumors, offering insights into anti-tumor immune regulation. Using single cell signatures, we deconvoluted large breast cancer cohorts to stratify them into nine clusters, termed ‘ecotypes’, with unique cellular compositions and clinical outcomes. This study provides a comprehensive transcriptional atlas of the cellular architecture of breast cancer.

overall_design:
We performed scRNA-Seq (Chromium, 10X Genomics) on 26 primary tumors from three major clinical subtypes of breast cancer, including 11 ER+, 5 HER2+ and 10 TNBC. We also performed bulk RNA-Seq on a total of 24 of these matched samples.
***Raw Data Disclaimer: Raw human data files are deposited to the EGA (EGAS00001005173) to adhere to ethics.***

first: Sunny

last: Wu

first: Ghamdan

last: Al-Eryani

first: Daniel

last: Roden


title: Effect of lactational high fat diet and metformin on mid-lactation murine mammary gland gene expression

status: Public on Jun 04 2021

city: Ann Arbor

first: Dave

last: Bridges

state: MI

address: 1415 Washington Heights

department: Nutritional Sciences

institute: University of Michigan

summary: Maternal health and diet can have important consequences for offspring nutrition and metabolic health. Signals are communicated from the mother to the infant during lactation through milk via macronutrients, hormones and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring beginning to wean. We found that lactational HFD increased maternal adipose tissue, mammary gland adipocytes, and altered milk lipid composition causing a higher amount of n-6 long chain fatty acids and lower n-3. Offspring of HFD dams were heavier with more body fat during suckling. Metformin exposure decreased maternal glucose and several amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to recuse from the effects of a maternal HFD during lactation.

overall_design: n=4 per group from 4 groups

first: Hannah

last: Hafner

first: Noura

last: El Habbal

first: Brigid

last: Gregg


title: Cisplatin-induced decrease of mRNA length reveals functional and translated intronic-polyadenylation isoforms in the annotated 5’-untranslated region of genes

status: Public on Jul 28 2021

city: Orsay

first: Céline

middle: M.

last: Labbé

address: Rue Henri Becquerel

institute: Institut Curie

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

overall_design: Refer to individual Series


title: Cellular crosstalk regulates the aqueous humor outflow pathway and provides new targets for glaucoma therapies

status: Public on Aug 06 2021

city: Chicago

first: Benjamin

last: Thomson

state: IL

address: 303 E Superior St. SQ8-500

department: Feinberg Cardiovascular and Renal Research Institute

institute: Northwestern University Feinberg School of Medicine

summary: Angiopoietin-1 signaling is essential for development of Schlemm's canal, a large lymphatic-like endothelial vessel in the iridocorneal angle. Single cell RNA sequencing is a powerful tool allowing for examination of the specific transcriptome of each cell type within a tissue. Here, we used single cell RNA sequencing to examin the structures of the mouse iridocorneal angle, using loss of Schlemm's canal in neural-crest specific Angpt1 knockout mice to aid in identification of Schlemm's canal endothelial cells. This dataset provides a resource for analysis of trabecular meshwork / Schlemm's canal crosstalk and the role(s) of Angpt1 in formation of the iridocorneal angle.

overall_design: The 10x Genomics Chromium platform was used to obtain single cell transcriptomes from iridocorneal angle region of 6 week old wild-type and neural crest-specific Angpt1 knockout mice.

first: Pan

last: Liu

first: Tuncer

last: Onay

first: Jing

last: Du

first: Stuart

last: Tompson

first: Terri

last: Young

last: Jin

first: Susan

middle: E

last: Quaggin


title: Venn diagram of PARP1-ChIP, TET1-ChIP and MeDIP in bone marrow-derived human mesenchymal stem cell

status: Public on Jun 25 2021

city: Taichung City

first: Chun-Te

last: Ho

address: 7F, No. 6, Xueshi Rd., North Dist.

department: Integrative Stem Cell Center

country: Taiwan

institute: China Medical University Hospital

type: Methylation profiling by high throughput sequencing

summary: Venn diagram showing overlap in binding sites. Genomic regions from MeDIP analysis (Late > Early) were compared for PARP1 ChIP-seq analysis (Early > Late) and TET1 ChIP-seq analysis (Early > Late). Numbers indicate the number of overlapping genes or regions.

overall_design: PARP1-ChIP-Seq, TET1-ChIP-Seq and MeDIP-Seq of bone marrow-derived mesenchymal stem cells with 2 biological replicates

first: Shih-Chieh

last: Hung


title: Single-cell transcriptomic analysis of 36 hpf Zebrafish etv2 and jam2b positive cells

status: Public on Jul 13 2021

city: Tampa

first: Sanjeeva

middle: Sudhakar

last: Metikala

state: FL

address: 560 Channelside Dr

department: Pathology and Cell Biology

institute: University of South Florida

summary: We performed single-cell RNAseq analysis of FACs sorted etv2 and jam2b psoitive cells from etv2Gt(2A-Venus) ; jam2bGt(2A-Gal4);UAS:NTR-mCherry zebrafish embryos at 36 hpf using 10x Genomics' Chromium platform.   18 distinct cell populations were identified including vascular endothelial cells and LPM cells.

overall_design: Transgenic etv2Gt(2A-Venus) fish were crossed to jam2bGt(2A-Gal4);UAS:NTR-mCherry fish. Whole embryos at 36 hpf were then dissociated into a single-cell suspension by cold protease tissue dissociation protocol. Cells expressing Venus only, mCherry only, and both (Venus and mCherry) were sorted using a BD/FACSAria II flow cytometer cell sorter. After sorting, cells expressing both Venus and mCherry were equally divided and added into the Venus only and mCherry only populations manually. Barcoding of cells and and cDNA library construction was carried out using 10X Genomics' Chromium platform.

first: Suman

last: Gurung

first: Saulius

last: Sumanas


title: Bone marrow-derived human mesenchymal stem cell RNA-Seq Heat map

summary: TET1-KD or PARP1-KD highly correlate with late MSC in RNA seq Heat map.

overall_design: RNA-Seq of bone marrow-derived mesenchymal stem cells with 2 biological replicates


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: Deconvoluting ACS1 retrograde signaling networks that regulate leaf development

status: Public on Jun 02 2021

city: Davis

first: Blake

last: Meyers

address: 451 Health Sciences Dr.

department: UC Davis Genome Center

institute: University of California - Davis

summary: Signals originating within plastids modulate organelle differentiation by transcriptionally regulating nuclear-encoded genes. These retrograde signals are also integral regulators of plant development, including leaf morphology. The clb5 mutant displays severe leaf morphology defects due to Apocarotenoid Signal 1 (ACS1) accumulation in the developmentally arrested plastid. Transcriptomic analysis of clb5 validates ACS1 as a true retrograde signal impacting expression of hundreds of nuclear genes, including suppression of most genes encoding plastid ribosomal proteins.

overall_design: Examination of Arabidopsis mutant leaves and cotyledons; three replicates of six genotypes or stages were analyzed by RNA-seq.

first: Lina

last: Escobar-Tovar

first: Julio

last: Sierra

first: Arihel

last: Hernández-Muñoz

first: Sandra

last: Mathioni

first: Elizabeth

last: Cordoba

first: Ryan

middle: P

last: McQuinn

middle: C

first: Barry

last: Pogson

first: Patricia

last: León


title: Immune transcriptomes of highly exposed SARS-CoV-2 asymptomatic seropositive versus seronegative individuals from the Ischgl community

status: Public on May 01 2021

city: Bethesda

first: Hye Kyung

last: Lee

state: MD

address: 8 CENTER DR RM 107

department: National Institute of Diabetes and Digestive and Kidney (NIDDK)

institute: National Institutes of Health (NIH)

summary: SARS-CoV-2 infection ranges from asymptomatic to severe with lingering symptomatology in some. This prompted investigation of whether or not asymptomatic disease results in measurable immune activation post-infection. Immune activation following asymptomatic SARS-CoV-2 infection was characterized through a comparative investigation of the immune cell transcriptomes from 43 asymptomatic seropositive and 52 highly exposed seronegative individuals from the same community four to six weeks following a superspreading event. Few of the 95 individuals had underlying health issues. One seropositive individual reported Cystic Fibrosis and one individual reported Incontinentia pigmenti. No evidence of immune activation was found in asymptomatic seropositive individuals with the exception of the Cystic Fibrosis patient. There were no statistically significant differences in immune transcriptomes between asymptomatic seropositive and highly exposed seronegative individuals. Four positive controls, mildly symptomatic seropositive individuals whose blood was examined three weeks following infection, showed immune activation. Negative controls were four seronegative individuals from neighboring communities without COVID19. All individuals remained in their usual state of health through a five-month follow-up after sample collection. In summary, whole blood transcriptomes identified individual immune profiles within a community population and showed that asymptomatic infection within a super-spreading event was not associated with enduring immunological activation.

overall_design: RNA-seq were performed with peripheral blood mononuclear cells (PBMCs) of 43 asymptomatic COVID-19 patients (A_sample#), 52 highliy exposed seronegative subjects (B_sample#), 5 healthy controls (C_sample#), 4 non-Ischgl COVID-19 patients with mild symtoms (D_sample#) and 4 highly exposed seronegative non-Ischgl subjects (E_sample#).

first: Ludwig

last: Knabl


title: RNA Sequencing Facilitates Quantitative Analysis of differentially expressed genes after Twist1 knockout in mouse bone marrow stromal cells

status: Public on May 26 2021

city: TianJin

first: Xiao Tong

last: Ma

state: TianJin

address: Blood hospital, 288 Nanjing Road

department: Institute of Hematology & Blood Diseases Hospital

institute: Chinese Academy of Medical Sciences

summary:
Purpose: The goals of this study are to determine possible  downstream targets of Twist1  in bone marrow stromal cells  with or without Twist1 knockout.
Methods: gene expression profiling with or without Twist1 knockout in bone marrow stromal cells  were generated by deep sequencing, using Illumina Hiseq.The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks. qRT–PCR validation was performed using  SYBR Green assays.
Conclusions: Notch signaling were activated after Twist1 knockout.

overall_design: mRNA profiles of stromal cells   with or without Twist1 knockout were generated by deep sequencing using Illumina Hiseq.

first: Xiaotong

first: Xiaoyan

last: Liu


title: Adult rat ventral tegmental area single-nucleus RNA-seq dataset for "An atlas of transcriptionally defined cell populations in the rat ventral tegmental area"

status: Public on Mar 31 2021

city: Birmingham

first: Jeremy

middle: Jason

last: Day

state: AL

address: 1825 University Blvd

department: Neurobiology

institute: UAB

summary: This dataset contains single-nucleus RNA sequencing results from adult rat brain (ventral tegmenal area, or VTA). The goal of this experiment was to define the transcriptional landscapes of distinct cell types in the VTA. Single-cell sequencing was carried out with nuclei suspensions (sorted using flow cytometry) using the 10X Genomics Chromium single cell sequencing platform.

overall_design: This experiment contains 4 biological samples, each of which combined tissue collected from 3 animals of the same sex. Samples were adult rat VTA microdissections isolated from male and female rats. Tissue was lysed to allow for nuclei collection via centrifugation. FACS-sorted nuclei were subject to 10X Genomics GEM generation and barcoding, GEM-RT cleanup and cDNA amplication, and library construction using a Chromium Single Cell 3ʹ Reagent Kit (v3 chemistry). Libraries underwent directional, paired-end PolyA+ RNA-seq on an Illumina Next-seq 500. Each sample has multiple raw fastq files, corresponding to different sequencing lanes (e.g., L001, L002, etc) and different reads (e.g., R1, R2). Additional index files are also provided for each sample and each lane (I1).

first: Robert

last: Phillps

first: Jennifer

last: Tuscher

first: Samantha

middle: L

last: Black

first: Lara

last: Ianov


title: A cis-acting mechanism mediates trancriptional memory at Polycomb target genes in mammals

first: Daniel

last: Holoch


title: Single-cell RNA-sequencing of mouse islets exposed to proinflammatory cytokines

status: Public on Apr 15 2021

first: Weiguo

last: Cui

address: 303 E Chicago Ave

department: Pathology

institute: Northwestern University

summary: Exposure to proinflammatory cytokines is believed to contribute to pancreatic β-cells during diabetes development.  While some cytokine-mediated changes in islet gene expression are known, the heterogeneity of the response is not well-understood. Following 6 hour treatment with interleukin-1 beta (IL-1β) and interferon-gamma (IFN-γ) alone or together, mouse islets were subjected to single-cell RNA-sequencing (scRNA-seq). Inducible nitric oxide synthase (iNOS) mRNA (Nos2), antiviral genes, and immune-associated genes were induced in a subset of β-cells in response to both cytokines, while IL-1β alone activated only antiviral genes. Subsets of α- and δ-cells expressed Nos2 and exhibited similar gene expression changes as β-cells, including induction of antiviral genes and repression of identity genes. Finally, cytokine-responsiveness was inversely correlated with expression of genes encoding heat shock proteins. Our findings show that all endocrine cell types respond to cytokines, IL-1β induces the expression of protective genes in β-cells, and cellular stress gene expression is associated with an inhibition in cytokine signaling.

overall_design: Four samples of murine islets (no cytokine treatment, IL-1B only, IFNg only, IL-1B and IFNg exposure for 6 hours) were prepared using 10x Genomics Chromium platform

first: John

last: Corbett

last: Stancill


title: Extensive Sub-RPE Complement Deposition in a Nonhuman Primate Model of Early Stage Diabetic Retinopathy

city: Stockholm

first: Jiawei

last: Zhong

address: Blickagången 16, Flemingsberg

department: Department of Medicine, Huddinge

country: Sweden

institute: Karolinska Institutet

summary:
Purpose: This study aims to reveal retinal abnormities in a spontaneous diabetic nonhuman primate (NHP) model and explore the mechanism of featured injuries.
Methods: Twenty-eight cynomolgus monkeys were identified to suffer from spontaneous Type 2 diabetes from a colony of more than eight hundred aged monkeys and twenty-six age-matched ones were used as controls. Their blood biochemistry profiles were determined and the retinal changes were examined by multimodal imaging, hematoxylin-eosin (H&E) staining and immunofluorescence. Retinal pigment epithelium (RPE) cells were isolated and determined by RNA-sequencing  and computational analyses.
Results: Diabetic monkeys were characterized by early vascular and neural damage in the retina and dyslipidemia. The typical acellular capillaries and pericyte ghost were found in the diabetic retina, which also exhibited reduced retinal nerve fiber layer (RNFL) thickness compared to the controls. Of note, distinct sub-RPE drusenoid lesions were extensively observed in these diabetic monkeys and complements deposition including C3 and C5b-9 were accumulated in these lesions. The RNA-seq data of RPE cells showed complement activation, AGE/RAGE activation and 18 inflammatory response at the setting of diabetes. Consistently, the plasma levels of C3 and C4 were also increased in the diabetic monkeys.
Conclusions: The spontaneous Type 2 diabetic cynomolgus monkeys featured with early-stage retinopathy including not only typical vascular and neural damage, but also a distinct sub-RPE deposition. The complement activation and metabolic stress of RPE cells in response to hyperglycemia might contribute to the deposition, revealing an unrecognized role of RPE cells in the early-stage pathological process of diabetic  retinopathy (DR).

overall_design: RPE cells were collected from 3 diabetic and 3 control subjects using an ophthalmic spatula. Total RNA was purified using a TRIzol (Thermo Fisher Scientific) in accordance with the manufacturer’s protocol. The RNA sample quality was confirmed by the Agilent 2100 Bioanalyzer (Agilent Technologies). Libraries were constructed using the TruSeq RNA-Seq kit (Illumina) following the manufacturer’s instructions. After evaluating the quality by Agilent 2100 Bioanalyzer, libraries were pooled and sequenced on Illumina Hiseq X10.


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

status: Public on May 06 2021

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.

last: Walker

first: Jack

last: Harrington

first: Rachel

last: Parker

first: Annette

last: Hayden

first: Mat

last: Rose-Zerelli


title: Patient-derived glioblastoma stem cells transcriptome regulation by CD109

status: Public on Mar 24 2021

city: Helsinki

first: Vadim

last: Le Joncour

state: Uusimaa

address: Haartmaninkatu 8

department: Research Programs Unit

country: Finland

institute: University of Helsinki

summary: Glioma stem cells (GSCs) drive propagation and therapeutic resistance of glioblastomas, the most aggressive diffuse brain tumor. However, the molecular mechanisms that maintain the stemness and promote therapy resistance remain poorly understood. Here we study CD109 – STAT3 axis as crucial for the maintenance of stemness and tumorigenicity of GSCs and as a mediator of chemoresistance. Mechanistically, CD109 physically interacts with glycoprotein 130 (GP130) to promote activation of the IL-6/STAT3 pathway in GSCs. Genetic depletion of CD109 abolished the stemness and self-renewal of GSCs and impaired tumorigenicity. Loss of stemness was accompanied with a phenotypic shift of GSCs to more differentiated astrocytic-like cells. Importantly, genetic or pharmacologic targeting of CD109 – STAT3 axis sensitized the GSCs to chemotherapy suggesting that targeting CD109 – STAT3 axis has potential to overcome therapy resistance in glioblastoma.

overall_design: Profiling of patient-derived glioblastoma stem cells according to the phenotypic subtypes identified by Neftel et al., 2019 (PMID 31327527) and investigation of the impact of CD109 silencing on the phenotypic states of Mesenchymal and Neuronal Precursor cells.

first: Pirjo

last: Laakkonen

first: Pauliina

last: Filppu

first: Jayendrakishore

middle: T

last: Ramanathan

first: Juho

last: Väänänen

first: Martyn

last: James


title: Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

status: Public on May 08 2021

city: Stanford

first: Aaron

middle: James

last: Wilk

state: California

address: 300 Pasteur Dr Bldg S131, Grant

institute: Stanford University

summary: Our understanding of protective vs. pathologic immune responses to SARS-CoV-2, the virus that causes Coronavirus disease 2019 (COVID-19), is limited by inadequate profiling of patients at the extremes of the disease severity spectrum. Here, we performed multi-omic single-cell immune profiling of 64 COVID-19 patients across the full range of disease severity, from outpatients with mild disease to fatal cases. Our transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including prominent hyperactivation signatures in neutrophils and monocytes with anti-inflammatory features. We also leverage epigenomic analysis to identify loss of accessibility at NF-kB binding sites within pro-inflammatory cytokine gene loci as a potential mechanism for the striking lack of cytokine production observed in monocytes in severe and fatal COVID-19. We further demonstrate that emergency myelopoiesis is a prominent feature of fatal COVID-19. Collectively, our results reveal disease severity-associated immune phenotypes in COVID-19 and identify pathogenesis-associated pathways that are potential targets for therapeutic intervention.

overall_design: Single-cell RNA and single-cell ATAC sequencing of peripheral blood mononuclear cells (PBMCs) from 8 samples from COVID-19 patients and 6 healthy controls.

middle: J

first: Ben

last: Parks

first: William

last: Greenleaf

first: Catherine

middle: A

last: Blish


title: Mapping the regulatory landscape of auditory hair cells from single cell multi-omics data

status: Public on Mar 11 2021

first: Joerg

last: Waldhaus

address: Medical Sciences I Building, Rm. 5315A, 1150 West Medical Center Drive

department: Department of Otolaryngology–Head and Neck Surgery, Kresge Hearing Research Institute

summary: Auditory hair cells transduce sound to the brain and in mammals these cells reside together with supporting cells in the sensory epithelium of the cochlea, called the organ of Corti. To establish the organ’s delicate function during development and differentiation, spatiotemporal gene expression is strictly controlled by chromatin accessibility and cell type specific transcription factors, jointly representing the regulatory landscape. Bulk-sequencing technology and cellular heterogeneity obscured investigations on the interplay between transcription factors and chromatin accessibility in inner ear development. To study the formation of the regulatory landscape in hair cells, we collected single-cell chromatin accessibility profiles accompanied by single-cell RNA data from genetically labeled murine hair cells and supporting cells after birth.

overall_design: Examination of transcriptional and chromatin accessibility profiles in the organ of Corti with apical and basal compartment separately at P2

first: Shuze

last: Wang

first: Mary

last: Lee

first: Scott

last: Jones


title: The expression of circRNA in rheumatic valvular heart disease (RVHD) and healthy controls plasma samples

status: Public on Mar 16 2021

city: Ningbo

first: Linwen

last: Zhu

address: 57 Xingning Road, Yinzhou District

institute: Ningbo Medical Treatment Center Lihuili Hospital

summary: To determine the circRNA expression profile in RVHD and healthy controls plasma samples, we uesed circRNA microArray analysis form Arraystar to examine the expression of circRNAs in RVHD and healthy controls plasma samples.

overall_design: RVHD and healthy controls plasma samples were distributed into two experimental groups: RVHD plasma group and healthy controls plasma group, then perform circRNAs chips by Arraystar Human circRNAs chip (Arraystar)

first: Guofeng

last: Shao


title: Inflammatory gene expression profiling in peripheral blood from patients with Alzheimer’s disease reveals key pathways and hub genes with potential diagnostic utility

status: Public on Mar 13 2021

city: Thuwal

first: Antonio

last: Adamo

state: Makkah

address: Thuwal 23955-6900 KAUST

department: iological, Environmental Sciences and Engineering

country: Saudi Arabia

institute: King Abdullah University of Science and Technology

summary: Late-onset Alzheimer disease (LOAD) is the most common neurodegenerative disorder worldwide. Recent studies have shown that differential expression in genes (DEG) related to inflammatory response may result associated with disease onset and progression. This study aimed to explore the molecular pathogenesis of LOAD-related inflammation through next-generation sequencing, to assess RNA expression profiles in Alzheimer's disease patients and healthy controls.

overall_design: RNA was isolated from whole blood from 5 LOAD cases and 10 controls (all female. Mean age 76.3±3.5). The amplicon sequencing approach using 20812 probes sets specific to human mRNA was applied to assess gene expression profiles, and functional annotation was performed.

first: Kelly

middle: Y

last: Cardona-Londoño

first: J

last: Medina-Salcedo

last: Orrego-Cardozo

first: Francia

last: Restrepo de Mejía

first: Xabier

last: Elcoroaristizabal Martín

first: Carlos

last: Naranjo-Galvis


title: Correlation between immune lymphoid cells and plasmacytoid DCs in colon cancer

city: Changchun

first: Jing

last: Wu

state: Jilin

address: 519 Dongminzhu Ave

institute: 1st Hospital of Jilin University

summary:
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to use RNA-seq to compare ILC3s and pDCs gene expression in colon cancer.
Results: Using an optimized data analysis workflow, More than >60  million clean reads were obtained from each sample group after elimination of low-quality reads. A total of 14,943 in ILC3s and 10,840 in pDCs DEGs were found up-regulated and 4,213 in ILC3s and 11,549 DEGs in pDC s down-regulated on comparison of ILC3s and pDCs from tumor samples and controls samples transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. Approximately 10% of the transcripts showed differential expression between the WT and Nrl−/− retina, with a fold change ≥1.5 and p value <0.05. Altered expression of 25 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Data analysis with BWA and TopHat workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling.
Conclusion: These findings highlighting the important roles of ILC3s and pDCs in the processes of tumor progression and inhibition in colon cancer promote the development of new strategies for inducing antitumor immune responses in metastatic and recurrent colon cancer.

overall_design: Methods: ILC3s and pDCs mRNA profiles of tumor sample and those of control were generated by deep sequencing, using Hiseq Xten.The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks.

first: Jingtao

last: Chen


title: The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis [ncRNA-seq]

status: Public on Mar 01 2021

city: La Jolla

first: Julie

middle: Ann

last: Law

state: CA

address: 10010 North Torrey Pines Rd

department: PLANT MOLECULAR AND CELLULAR BIOLOGY LABORATORY

institute: The Salk Institute for Biological Studies

type: Non-coding RNA profiling by high throughput sequencing

summary: DNA methylation alters the epigenetic landscape of the genome, plays critical roles in regulating gene expression, and ensures transposon silencing. As evidenced by the numerous defects associated with aberrant DNA methylation landscapes, establishing proper tissue-specific methylation patterns is critical. Yet, how such differences arise remains a largely open question in both plants and animals. Here we demonstrate that four CLASSY proteins (CLSY1-4), which are differentially expressed during plant development, play major roles in controlling tissue-specific DNA methylation patterns. Depending on the tissue, the genetic requirements for specific CLSYs differ significantly and on a global scale, certain clsy mutants are sufficient to largely shift the epigenetic landscape between tissues. Together, these findings not only reveal substantial epigenetic diversity between tissues, but assign these changes to specific CLSY proteins, revealing how locus-specific targeting combined with tissue-specific expression enables the CLSYs to generate epigenetic diversity during plant development.

overall_design: smRNA-seq libraries were sequenced.

first: Ming

last: Zhou


title: The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis [ChIP-seq]

overall_design: 3 ChIP-seq libraries were sequenced.


title: The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis

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

overall_design: Refer to individual Series


title: The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis [RNA-seq]

overall_design: 84 RNA-seq libraries were sequenced.


title: Cellular plasticity balances the metabolic and proliferation dynamics of a regenerating liver

status: Public on Feb 01 2021

city: Urbana

first: Sushant

last: Bangru

state: Illinois

address: 600 S Mathews Avenue

department: Biochemistry

institute: University of Illinois, Urbana-Champaign

summary: The adult liver has exceptional ability to regenerate, but how it sustains normal metabolic activities during regeneration remains unclear. Here, we use partial hepatectomy (PHx) in tandem with single-cell transcriptomics to track cellular transitions and heterogeneities of ~22,000 liver cells through the initiation, progression, and termination phases of mouse liver regeneration. Our results reveal that following PHx, a subset of hepatocytes transiently reactivates an early-postnatal-like gene expression program to proliferate, while a distinct population of metabolically hyperactive cells appears to compensate for any temporary deficits in liver function. Importantly, through combined analysis of gene regulatory networks and cell- cell interaction maps, we find that regenerating hepatocytes redeploy key developmental gene regulons, which are guided by extensive ligand–receptor mediated signaling events between hepatocytes and non-parenchymal cells. Altogether, our study offers a detailed blueprint of the intercellular crosstalk and cellular reprogramming that balances the metabolic and proliferation requirements of a regenerating liver.

overall_design: Mice underwent 2/3rd partial hepatectomy, and after surgery at the set times liver cells were isolated using the 2 step perfusion protocol. And then cells were passed through the 10x processing pipeline.

first: Ullas

middle: V

last: Chembazhi

first: Auinash

last: Kalsotra


title: Information Content Differentiates Enhancers From Silencers in Mouse Photoreceptors

status: Public on Jan 30 2021

city: St. Louis

first: Michael

middle: Aaron

last: White

state: MO

address: 4515 McKinley Ave, Campus Box 8510

department: Genetics

institute: Washington University School of Medicine

summary: Enhancers and silencers often depend on the same transcription factors (TFs) and are imperfectly distinguished from each other by genomic assays of TF binding or chromatin state. To identify sequence features that define enhancers and silencers, we assayed massively parallel reporter libraries of genomic sequences targeted by the photoreceptor TF CRX and found instances of enhancer, silencer, or no activity. Both enhancers and silencers contain more TF motifs than inactive sequences, but enhancers contain motifs from a more diverse collection of TFs. We developed a measure of information content that describes the number and diversity of motifs in a sequence and found that, while both enhancers and silencers depend on CRX motifs, enhancers have higher information content. Our results indicate that enhancers contain motifs for a diverse but degenerate collection of TFs, while silencers depend on a smaller and less diverse collection of TFs.

sample_organism:
Escherichia coli
Mus musculus

platform_organism:
Escherichia coli
Mus musculus

overall_design: Massively Parallel Reporter Assays of CRX-targeted cis-regulatory sequences in mouse retinas. Each unique sequence is tagged with 3 unique 9 bp barcodes. Each library also includes a basal control (basal promoter only) tagged with 18 unique 9 bp barcodes. Libraries contain genomic sequences centered on CRX motifs and versions of the same sequences with all CRX motifs abolished by point mutation. Libraries were cloned upstream of the Rho promoter or a minimal Polylinker. Libraries were electroporated into retinas dissected from P0 CD-1 mice. Retinas were harvested at P8. Barcode cDNA and the original DNA plasmids were sequenced. Three replicates per experiment.

first: Ryan

middle: Z

last: Friedman

first: David

last: Granas

first: Connie

last: Myers

first: Joseph

last: Corbo

first: Barak

last: Cohen


title: Single-Cell RNA-Seq Analysis of cells from human urine

status: Public on Jan 25 2021

city: Shanghai

first: Wei

last: Zuo

state: Shanghai

address: No. 500 Zhennan Road, Putuo District, Shanghai

institute: University

summary: Urine passes through the entire kidney and urinary tract system starting from the glomerulus and ending to the urethra. Cells in the kidney and urinary tract could be exfoliated from the epithelium into the urine, while leukocyte could infiltrate from the local tissue into the urine, which makes the urine a useful subject for clinical evaluation of relevant diseases. We performed scRNA-seq on voided urine samples. 50–100 mL middle stream urine samples were collected from 12 Chinese healthy adults and combined for droplet-based single-cell RNA sequencing after flow cytometric sorting of live cells. We presented the first single-cell atlas of adult human urine and identified multiple previously unrecognized cell types. Based on our scRNA-seq analysis data, a SOX9+ cell population was identified in adult human urine which we speculated to have progenitor potential.

overall_design: For scRNA-seq analysis, urine samples were collected from healthy adult volunteers. Midstream of voided urine specimen was collected for each donor. Samples were centrifuged immediately at the speed of 390 ×g and combined for droplet-based single-cell RNA sequencing after flow cytometric sorting of live cells.

first: Daniel

middle: W

last: Henry


title: RNA-seq of liver after SHAM or CLP with and without dexamethasone treatment [24hrs]

city: Gent

first: Steven

last: Timmermans

address: Technologiepark 71

country: Belgium

institute: VIB-UGent

summary: Study of the occurrence of glucocorticoid resistance after CLP induced sepsis in mice

overall_design: Examination of changes in gene expression in livers of C57BL/6J mice after CLP or SHAM operation followed after 24 with an injection of PBS or DEX, with organ isolation 2h post-injection. A total 4 groups with 3 biological replicates/group were sequenced for a total of 12 samples

first: Jolien

last: Vandewalle

first: Ville

last: Paakinaho

first: Lies

last: Vancraeynest

first: Liza

last: Dewyse

first: Lise

last: Van Wyngene

first: Kelly

last: Van Looveren

first: Tineke

last: Vanderhaeghen

first: Charlotte

last: Wallaeys

first: Melanie

last: Eggermont

first: Sylviane

last: Dewaele

first: Leo

last: van Grunsven

first: Mieke

last: Dewerchin

first: Peter

last: Carmeliet

first: Karolien

last: De Bosscher

first: Johan

last: Van de Voorde

first: Jorma

last: Palvimo

first: Claude

last: Libert


title: RNA-seq of liver after SHAM or CLP with and without dexamethasone treatment

first: Steven

last: Timmermans

overall_design: Examination of changes in gene expression in livers of C57BL/6J mice after CLP or SHAM operation followed after 6 with an injection of PBS or DEX, with organ isoloation 2h post-injection. A total 4 groups with 3 biological replicates/group were sequenced for a total of 12 samples

first: Jolien

last: Vandewalle

last: de Voorde


title: RNA-seq study on mouse bone marrow HSPC cells isolated from Arid2 conditional knockout and control mice.

status: Public on Jan 08 2021

city: Milwaukee

last: Zhu

state: WI

address: 8733 W Watertown Plank Rd

institute: Versiti Blood Research Institute Milwaukee

summary: We isolated lineage negative, cKit+, Sca1+ hematopoietic stem and progenitor cells from mouse bone marrow from Arid2fl/fl:MxCre+ (knockout) and MxCre+ (control) mice. Mice were injected with pIpC 6 weeks prior to isolation of LSK cells. Total RNA was isolated followed by mRNA selection. cDNA libraries were generated and NextGen Sequencing was performed.

overall_design: We performed RNA-seq in mouse LSK cells (lineage negative, cKit+, Sca1+) isolated from Arid2fl/fl:MxCre+ (knockout) and MxCre+ (control) mice 6 weeks post pIpC injection.

first: Robert

last: Burns

first: Shikan

last: Zheng

first: Theresa

last: Bluemn


title: Validation of Baboon Pluripotent Cells as a Model for Translational Stem Cell Research [RNA-Seq]

status: Public on Jan 21 2021

city: Yiwu

first: keren

last: cheng

state: Zhejiang

address: 1575 chouzhou bei road

department: School of Medicine

institute: Zhejiang University

summary: To investigate the extent of similarity in epigenetic programming among human, baboon and mouse PSCs, we examined genome-wide patterns of four chromatin modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac) and DNA methylation in baboon iPSC and ESCs. We show that baboon pluripotent cells (PSCs) recapitulate key molecular features of human PSCs with much greater accuracy than that found in PSCs from non-primate species. Specifically, baboon and human PSCs exhibit significantly greater conservation of gene expression patterns, higher sequence and structural homology among pluripotency factors, more equivalent genome-wide patterns of histone and DNA methylation modifications, and similar maintenance of bivalent programming of developmental genes than that found between human and non-primate PSCs.

overall_design: The gene expression profiles of baboon iPSC and ESC.

first: Keren

last: Cheng

first: Megan

last: Mahlke

first: John

middle: R

last: McCarrey


title: Validation of Baboon Pluripotent Cells as a Model for Translational Stem Cell Research


title: Persistent Variations of Blood DNA Methylation Associated with Treatment Exposures and Risk for Cardiometabolic Outcomes in Childhood Cancer Survivors

status: Public on Mar 19 2021

city: Memphis

first: Zhaoming

last: Wang

state: TN

address: 262 Danny Thomas Place

department: Epidemiology & Cancer Control

institute: St. Jude Children's Research Hospital

summary:
Background: It is well-established that cancer treatment substantially increases risk of long-term adverse health outcomes among childhood cancer survivors. However, there is limited research on the underlying mechanisms. To elucidate the pathophysiology and a possible causal pathway from treatment exposures to cardiometabolic conditions, we conducted epigenome-wide association studies (EWAS) to identify DNA methylation (DNAm) sites associated with cancer treatment exposures and examined whether treatment-associated DNAm sites mediate associations between specific treatments and cardiometabolic conditions.
Methods: We included 2,052 survivors (median age 33.7 years) of European ancestry from the St. Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Cumulative doses of chemotherapy and region-specific radiation were abstracted from medical records. Seven cardiometabolic conditions were clinically assessed. DNAm profile was measured using MethylationEPIC BeadChip with blood-derived DNA.
Results: By performing multiple treatment-specific EWAS, we identified 935 5’-cytosine-phosphate-guanine-3′ (CpG) sites mapped to 538 genes/regions associated with one or more cancer treatments at epigenome-wide significance level (P<9×10-8). Among the treatment-associated CpGs, 8 were associated with obesity, 63 with hypercholesterolemia, and 17 with hypertriglyceridemia (False-Discovery-Rate-Adjusted P<0.05). We observed substantial mediation by methylation at four independent CpGs (cg06963130, cg21922478, cg22976567, cg07403981) for association between abdominal field radiotherapy (abdominal-RT) and risk of hypercholesterolemia (70.3%) and by methylation at three CpGs (cg19634849, cg13552692, cg09853238) for association between abdominal-RT and hypertriglyceridemia (54.6%). In addition, three CpGs (cg26572901, cg12715065, cg21163477) partially mediated the association between brain-RT and obesity with 32.9% mediation effect and two CpGs mediated the association between corticosteroids and obesity (cg22351187, 14.2%) and between brain-RT and hypertriglyceridemia (cg13360224, 10.5%). Notably, several mediator CpGs reside in the proximity of well-established dyslipidemia genes: cg21922478 (ITGA1) and cg22976567 (LMNA).
Conclusions: In childhood cancer survivors, cancer treatment exposures are associated with DNAm patterns present decades following the exposure. Treatment-associated DNAm sites may mediate the causal pathway from specific treatment exposures to certain cardiometabolic conditions, suggesting the utility of DNAm sites as risk predictors and potential mechanistic targets for future intervention studies.

last: Song

first: Chia-Wei

last: Hsu

first: Haitao

last: Pan

first: Yinan

first: Lifang

last: Hou

first: Jin-ah

last: Sim

first: Zhenghong

last: Li

first: Heather

last: Mulder

last: Easton

first: Emily

last: Walker

first: Geoffrey

last: Neale

first: Carmen

last: Wilson

first: Kirsten

middle: K

last: Ness

first: Kevin

last: Krull

first: Deo

last: Srivastava

first: Yutaka

last: Yasui

first: Jinghui

last: Zhang

first: Melissa

middle: M

last: Hudson

first: Leslie

last: Robison

first: I-Chan

last: Huang


title: H3K27Ac modification and gene expression in psoriasis

status: Public on Jan 01 2021

city: Shoham

first: jasmine

last: Jacob

state: -Select-

address: haChevel 33

country: Israel

institute: Sheba Medical Center at Tel HaShomer

summary: Applying ChIP-seq with anti-acetylation of lysine 27 on Histone 3 (H3K27Ac), we report high-throughput profiling of H3K27Ac in human skin biopsies taken from psoriasis patients, both from the lesion and from adjacent non-lesion skin, and from skin biopsies from healthy match volunteers, in term of age, gender, and the biopsies place in the body. From each group we had 4 samples.   On three samples of each group we performed mRNA array.  There is a clearly different H3K27 acetylation patterns in psoriatic skin compared to uninvolved or healthy volunteer skin. in many of the most over express genes in psoriasis lesion, there is enrichment of H3K27Ac. However, loss of acetylation on H3K27 is not part of the biochemical mechanism by which gene expression is decreased in psoriatic skin.  Finally, we show Many of the over express genes in psoriasis lesion, that also were enriched with H3K27Ac harbor a putative GRHL transcription factor binding site.

overall_design: mRNA array was applied on skin biopsies from psoriasis patients, both from the lesion and from adjacent non-lesion skin. in parallel to skin biopsies from healthy match volunteers.

first: Dror

last: Avni

first: Moamen

last: Masalha


title: Validation of Baboon Pluripotent Cells as a Model for Translational Stem Cell Research [MeDIP]

first: keren

last: cheng

overall_design: Examination of transcriptome, H3K4me3, H3K27ac, H3K9me3, H3K27me3 and DNA methylation in baboon iPSC and ESC.

first: Keren

last: Cheng

first: Megan

last: Mahlke

first: John

last: McCarrey


title: Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer [ATAC-seq]

status: Public on Dec 31 2020

city: New York

first: Hideo

last: Watanabe

state: NY

address: One Gustave L. Levy Place

department: Department of Medicine, Division of Pulmonary, Critical Care and Sleep Medicine

institute: Icahn School of Medicine at Mount Sinai

summary: Small cell lung cancer (SCLC) frequently harbors mutually exclusive genomic amplification of MYC family members. Therefore, it has been long suggested that they are functionally equivalent; however, more recently, their expression has been associated with specific neuroendocrine markers and distinct histopathology. Integrated transcriptomic and epigenomic analyses showed that c-Myc and L-Myc impart neuronal and non-neuroendocrine associated transcriptional programs, respectively, both associated with distinct SCLC lineage. Genetic replacement of c-Myc with L-Myc in c-Myc-SCLC induced a neuronal state but was insufficient to induce ASCL1 lineage. In contrast, c-Myc induced transition from ASCL1-SCLC to NeuroD1-SCLC characterized by distinct LCNEC-like histopathology. Collectively, we characterize an undescribed role of historically defined general oncogenes, c-Myc and L-Myc, for regulating lineage plasticity across molecular subtypes as well as histological subclasses.

overall_design:
Accessible chromatin and Myc accessible profile of six SCLC cell lines, NCI-H82 cells genetically engineered to overexpress L-Myc and ablate the expression of c-Myc with control and of NCI-H1963 genetically engineered cells to overexpress c-Myc with control.

***************************************************************
Raw files for human/patient samples are available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) phs004458.v1.p1 for controlled access to the personally identifiable sequence data.
***************************************************************

first: Ayushi

middle: S

last: Patel


title: Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer


title: The CLASSY family controls tissue-specific DNA methylation patterns in Arabidopsis [BiSulfite-seq]

first: Julie

last: Law

overall_design: 36 methylC-seq libraries were sequenced.

first: Ming

last: Zhou


title: Validation of Baboon Pluripotent Cells as a Model for Translational Stem Cell Research [ChIP-Seq]


title: miR-181a initiates and perpetuates oncogenic transformation through the regulation of innate immune signaling (genomic Variation dataset)

status: Public on Dec 01 2020

city: Ann Arbor

first: Analisa

last: DiFeo

state: Michigan

address: 1600 Huron Parkway

institute: UNIVERSITY OF MICHIGAN-ANN ARBOR

summary:
Genomic instability predisposes cells to malignant transformation, however the molecular mechanisms that allow for the propagation of cells with a high-degree of genomic instability remains unclear. Here we report that miR-181a is able to transform fallopian tube secretory epithelial cells- the precursor cell type for the majority of high-grade serous ovarian cancers- through the inhibition of RB1 and simultaneously drives a cell protective inhibition of the stimulator-of-interferon-genes (STING) in order to maintain a microenvironment conducive to the propagation of cells with a high-degree of genomic instability. We found that miR-181a inhibition of RB1 leads to profound nuclear defects, genomic instability, and nuclear rupture resulting in a persistence of genomic material in the cytoplasm. While normally, this persistence of genomic material in the cytoplasm induces interferon response through STING to drive cell death, miR-181a directly downregulates STING and prevents apoptosis. The most common mechanism by which oncogenic miRNAs promote tumorigenesis is through the direct inhibition of tumor suppressor genes, however our studies highlight a new mechanism of oncomiR transformation through the combination of tumor suppressor gene inhibition and abrogation of immune surveillance that initiates and propagates tumor cell survival. Importantly, we found that miR-181a induction in ovarian patient tumors is tightly associated with decreased IFNg response and downregulation of lymphocyte infiltration amd leukocyte fraction. To date, DNA oncoviruses are the only known inhibitors of STING that allow for cellular transformation thus, our findings are the first to identify a genetic factor, miR-181a, that can downregulate STING expression, suppress activation of the immunosurveillance machinery, and impair signaling in cancer cells creating a survival advantage. Our studies support the notion that the induction of STING-mediated signaling in cancer cells could lead directly to cancer cell death however these effects are abrogated by miR-181a. Given the recent interest in the development of STING agonists as a strategy to harness the immune system to treat cancer, this study introduces novel patient selective biomarker as well as potent therapeutic target for development of the most effective combination treatments.
Infinium CytoSNP-850K  v1.2 BeadChip (Illumina)  was performed to assess genomic variation

overall_design: 4 samples were processed in duplicate


title: Transcriptomic profiling of primed and naive primate pluripotent stem cells by RNA-sequencing

city: Lyon

first: Irene

last: Aksoy

address: 18 avenue du Doyen Lepine

institute: Stem Cell and Brain Research Institute

summary: Analysis of rhesus monkey ESC cells that have been reprogrammed to naïve pluripotency using 7 different protocols including, TL2i,  4i/L/b, E-NHSM, NHSM-v, t2iLGöY, LCDM (EPS), TL-CDK8/19i and compared to primed cells.

overall_design: Primed cells vs Naïve cells

first: Pierre

last: Savatier


title: Prototypical oncogene family Myc defines unappreciated distinct lineage states of small cell lung cancer [RNA-seq]

overall_design:
Transcriptomic profile of NCI-H82 cells genetically engineered to overexpress L-Myc and ablate the expression of c-Myc with control and of NCI-H1963 genetically engineered cells to overexpress c-Myc with control.

***************************************************************
Raw files for human/patient samples are available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) phs004458.v1.p1 for controlled access to the personally identifiable sequence data.
***************************************************************


title: Expression profile of the 22Rv1 cells overexpressing ABHD5

status: Public on Nov 19 2020

city: Detroit

first: Jian

last: Wang

state: MI

address: 6135 Woodward Ave

institute: Wayne State University School of Medicine

summary: ABHD5 is a crucial metabolic regulator of cancer cells. The goal of this study is to identify the regulation of gene expression by ABHD5 in prostate cancer cells using RNA-seq.

overall_design: We utilized a 22Rv1 cell line engineered to overexpress a doxycycline-inducible ABHD5 transgene stably. The cells were grown in the absence or presence of doxycycline for 48 h and then harvested for transcriptome profiling.

first: Guohua

last: Chen


title: SCL15 is a critical regulator for plant development, germination, seed dormancy and seed vigor in Arabidopsis thaliana

status: Public on Nov 04 2020

city: Saskatoon

first: Dwayne

last: Hegedus

state: SK

address: 107 Science Place

country: Canada

institute: Agriculture and Agri-Food Canada

summary: Seed maturation, dormancy and germination are distinct physiological processes. Transition from maturation to dormancy, and from dormancy into germination are not only critical developmental phases in the plant life cycle but are also important agricultural traits. These developmental processes and their phase transitions are fine determined and coordinately regulated by genetic makeup and environmental cues. SCARECROW-LIKE15 (SCL15) has been demonstrated to be essential for repressing the seed maturation programme in vegetative tissues (Gao et al., Nat Commun, 2015, 6:7243). Here we report that SCL15 is also important for seed dormancy maintenance, germination timing and seed vigor performance based on the effects of SCL15 mutation on plant germination, growth and reproduction when compared with wild type Arabidopsis and over-expression lines 35S:SCL15 and Napin:SCL15. Seed dormancy is enhanced by the mutation of SCL15 in a GA signaling dependent way, indicating that SCL15 plays a negative role for primary dormancy release. Seed germination is positively regulated by SCL15 through interaction with ABA, GA and auxin signaling. SCL15 acts as positive regulator of seed vigor and effect of SCL15 mRNA abundance on seed reserve accumulation and seed development during late embryogenesis may contribute to the seed vigor performance.

overall_design: We compared gene expression in three plant lines:  Wild type, Scl15 knockout, and Scl15 seed-specific overexpression.  For each line we sequenced 3 biological replicates.

first: Ming-Jun

last: Gao

first: Cathy

last: Coutu


title: Efficient transcription-coupled chromatin accessibility mapping in situ

status: Public on Nov 13 2020

city: Seattle

first: Jorja

last: Henikoff

state: WA

address: 1100 Fairview AV N, A1-162

department: Basic Sciences

institute: Fred Hutchinson Cancer Research Center

summary: Chromatin accessibility mapping is a powerful approach to identify potential regulatory elements. In the popular ATAC-seq method, Tn5 transposase inserts sequencing adapters into accessible DNA (‘tagmentation’). CUT&Tag is a tagmentation-based epigenomic profiling method in which antibody tethering of Tn5 to a chromatin epitope of interest profiles specific chromatin features in small samples and single cells. Here we show that by simply modifying the tagmentation conditions for histone H3K4me2/3 CUT&Tag, antibody-tethered tagmentation of accessible DNA sites is redirected to produce accessible DNA maps that are indistinguishable from the best ATAC-seq maps. Thus, DNA accessibility maps can be produced in parallel with CUT&Tag maps of other epitopes with all steps from nuclei to amplified sequencing-ready libraries performed in single PCR tubes in the laboratory or on a home workbench. As H3K4 methylation is produced by transcription at promoters and enhancers, our method identifies transcription-coupled accessible regulatory sites.

overall_design: We used Cleavage under targets and Tagmentation (Cut-and-Tag), a chromatin profiling strategy in which antibody-targeted controlled integration of DNA sequencing adapters produces libraries for paired-end DNA sequencing.

first: Steven

first: Hatice

last: Kaya-Okur

first: Kami

last: Ahmad


title: Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders

status: Public on Nov 23 2020

city: Brisbane

first: Marta

middle: Filipa

last: Nabais

state: Queensland

address: 306 Carmody Rd, St. Lucia

department: Institute for Molecular Biosciences

institute: University of Queensland

summary: People with neurodegenerative disorders have diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) is a widely studied chemical modification to DNA, and increasing evidence suggests that DNAm alterations play an important role in neurodegenerative disorders. In this study we aimed to identify shared blood DNAm differences between 471-1,522 controls and people with Alzheimer’s disease (N = 161), amyotrophic lateral sclerosis (N = 3,032) and Parkinson’s disease (N = 1,132). We used a mixed-linear model method (MOMENT) that has been shown to account for the effect of (un)known confounders, to test for association of each DNAm site with each disorder. A fixed-effects meta-analysis of Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease results identified 12 differentially methylated positions passing a genome-wide significant threshold. Predicted immune cell-type proportions were disrupted across all neurodegenerative disorders, as well as schizophrenia and rheumatoid arthritis. Protein inflammatory markers were correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy ageing cohort. In contrast, they were not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights. We have identified shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.

overall_design:
161 Alzheimer's disease patients, 471 healthy individuals and 94 mild cognitive impairment patients, from the AIBL cohort (https://aibl.csiro.au/). All the other accession number from publicly available data used in this study have been properly cited in the accompanying manuscript.

For data access questions please contact Prof. Simon Laws at: s.laws@ecu.edu.au

middle: F

first: Simon

last: Laws

first: Naomi

last: Wray

first: Allan

last: McRae

first: Anjali

last: Henders

first: Leanne

last: Wallace


title: RNA-Seq analysis of melanoma cells, B16F10, in the presence of hypochlorous acid (HOCl)

status: Public on Dec 30 2020

city: Houston

first: David

last: Piwnica-Worms

state: TX

address: 1881 East Road, Unit 1907

department: Cancer Systems Imaging

institute: The University of Texas MD Anderson Cancer Center

summary: We evaluated the changes in the transcriptome of a melanoma cell line, B16F10, and spleen isolated murine T cells when in the presence of hypochlorous acid (HOCl) using RNA-sequencing technologies.

overall_design: mRNA profile changes comparing B16F10 cells without or in the presence of 600 uM HOCl and T cells without or in the presence of 600 uM HOCl

first: Tracy

last: Liu

first: Seth

last: Gammon


title: A novel patient stratification strategy to enhance the therapeutic efficacy of dasatinib in glioblastoma [Illumina]

status: Public on Oct 20 2020

city: Heidelberg

first: Obada

middle: Taleb

last: Alhalabi

address: Im Neuenheimer Feld 580 - TP3

department: Brain Tumor Translational Targets

country: Germany

institute: German Cancer Research Center DKFZ

summary: Abstract. Background: Glioblastoma is the most common primary malignancy of the central nervous system with dismal prognosis. Differential gene expression classifies IDH-wildtype glioblastoma into three subtypes: proneural, mesenchymal and classical. Dasatinib, an inhibitor of the proto-oncogene tyrosine-protein kinase SRC, is one of many therapeutics that, despite promising preclinical results, has failed to improve overall survival in glioblastoma patients in clinical trials. We examined whether glioblastoma subtypes differ in their response to dasatinib therapy and could hence be used for patient enrichment strategies in clinical trials. Methods: We carried out in silico analyses of the TCGA glioblastoma gene expression data and single-cell RNA-Seq data, in combination with in vitro experiments using glioblastoma stem-like cells (GSCs) derived from primary patient tumors with complimentary gene expression profiling and immunohistochemistry analyses of tumor samples. Results: Patients suffering from the mesenchymal subtype of glioblastoma showed higher SRC pathway activation based on gene expression profiling, and accordingly, mesenchymal cells were more sensitive to SRC inhibition by dasatinib compared to proneural and classical cells. Furthermore, SERPINH1, a heat-shock protein relevant in many cancer entities, was shown to highly correlate with dasatinib response and with the mesenchymal subtype. Notably, SRC phosphorylation status was not able to reliably predict response to dasatinib treatment. Conclusion: This work highlights the need for rational methods of patient selection for clinical trials, and retrospectively sheds light on a possible gene expression subtype-led patient stratification strategy that could have improved the outcome of SRC inhibition in patients and could have implications for future trials.

overall_design: No controls needed, simple gene expression profiling of in vitro cell line models

first: Violaine

last: Goidts


title: A novel patient stratification strategy to enhance the therapeutic efficacy of dasatinib in glioblastoma

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

overall_design: Refer to individual Series


title: The role of mesenchymal stromal cells (MSC) in the development of acute myeloid leukemia

status: Public on Aug 22 2020

city: Essen

first: Ludger

last: Klein-Hitpass

address: Virchowstr. 173

department: Universitaetsklinikum

institute: Institut fuer Zellbiologie

summary: Acute myeloid leukemia (AML) is a clonal disorder of hematopoietic stem cells with a poor prognosis. It has been reported in many tumors that mesenchymal stem/ stromal cells (MSCs) support the growth of the malignant cells. In this study we analyzed the interaction between MSCs and AML cells in patients and in murine models of human AML. We found that MSCs from AML patients or leukemic mice supported the growth of AML cells in vitro better than MSCs originating from healthy mice or control persons. Interestingly, MSCs from AML patients who achieved complete remission didn’t support the growth of leukemia cells  in vitro anymore.   Due to the difficulty to obtain sufficient human MSCs, we developed a novel method to immortalize human MSCs. Immortalized MSC cells derived from AML patients also supported the growth of human AML cells better than MSC cells derived from a healthy donor. Among others, AMSCs increased entering of leukemic cells into cell cycle and at the same time protected the leukemia cells against exogenous toxic events such as chemotherapy or irradiation. In vivo, we observed an increase in the number of MSCs in the bone marrow of leukemic mice compared to healthy mice. Microarray data of AMSCs show upregulation of epithelial mesenchymal trasition genes. The polarization of MSCs towards an AML-supporting state depends on upregulated expression of the transcription factor Growth factor independence 1 (Gfi1). Loss of Gfi1 abrogated the tumor-supporting state of AML-associated MSCs. In summary, we report that MSCs support the growth of AML cells in a Gfi1-dependent manner.

overall_design: 3 mice which are KP8201, KP8203 and KP8966, were transplanted with BM transduced with MLL-AF9 while 3 mice which are KP1820, KP8816 and TU1777, were transplanted with normal BM cells. When the mice became sick, they were killed and the MSCs from the crushed bones were sorted for RNA study.

first: Yahya

last: Al-Matary

first: Cyrus

last: Khandanpour

first: Lother

last: Vassan


title: RNA-seq across 27 developmental stages in Sus scrofa skeletal muscle

status: Public on Sep 01 2020

city: Shenzhen

first: Zhonglin

last: Tang

state: GuangDong

address: No.7, Pengfei road, Dapeng District

department: Agricultural Genome Institute at Shenzhen

institute: Chinese Academy of Agricultural Sciences

summary: To obtain an overview of the transcriptome landscape in developing pig skeletal muscle, 81 high-quality transcriptome libraries that covered 27 developmental stages (3 biological replicates per stage) in pig skeletal muscle were produced by strand-specific rRNA-depleted total RNA sequencing (RNA-seq). We generated  8.59 billion paired-end reads (150 bp × 2) covering 1.24 Tb of sequence for RNA-seq.

overall_design: RNA-seq profiles of Sus scrofa skeletal muscles that covered 27 developmental stages.


title: Whole-genome bisulfite sequencing across 27 developmental stages in Sus scrofa skeletal muscle

summary: To obtain an overview of the methylome landscape in the developing pig skeletal muscle, 81 high-quality whole-genome bisulfite sequencing(WGBS) libraries that covered 27 developmental stages (3 biological replicates per stage) from embryonic day 33 (E33) to postnatal day 180 (D180) were produced by whole-genome bisulfite sequencing.

overall_design: WGBS profiles of Sus scrofa skeletal muscles that covered 27 developmental stages.


title: 27 developmental stages in Sus scrofa skeletal muscle


title: Quantitative analysis of the splice variants expressed by the major hepatitis B virus genotypes

status: Public on Aug 20 2020

city: Dunedin

first: Christopher

middle: Michael

last: Brown

address: 710 Cumberland Street

country: New Zealand

institute: University of Otago

summary: RNA-seq of Huh7 cells transfected with replication competent clones of HBV genotypes A2, B2, C2, and D3.

overall_design: Total RNA samples were purified using RNeasy kit (Qiagen, Hilden, Germany). The libraries were prepared using TruSeq stranded Total RNA sample preparation kit with Ribo-Zero according to the manufacturer’s protocol and sequenced using HiSeq 2500 (Illumina, CA, USA), generating 125-bp paired-end reads.

first: Chun

last: Lim

first: Vitina

last: Sozzi

first: Peter

last: Revill

first: Chris