title: Genetic and monoclonal antibody blockade of GDF8 enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following ligament injury [quadricep]

status: Public on Dec 06 2023

city: Lexington

middle: Romano

last: Keeble

state: KY

address: 900 S Limestone st

institute: University of Kentucky

summary: Background: Musculoskeletal disorders contribute to a substantial proportion of disability among people worldwide. Anterior cruciate ligament (ACL) tears are among the most frequent knee injuries, and a majority of patients will go on to develop knee osteoarthritis within 10 years. Traditional rehabilitation following injury has limited success restoring muscle strength and mitigating the onset of posttraumatic knee osteoarthritis. Growth differentiation factor 8 (GDF8), or myostatin, is a myokine that has been implicated in the pathogenesis of musculoskeletal degeneration following ACL injury. This study investigated GDF8 levels in injured human skeletal muscle and serum and compared the efficacy of a humanized monoclonal GDF8 antibody against a placebo in a mouse model of injury-induced osteoarthritis (surgically induced ACL tear). Muscle GDF8 peaks rapidly following ACL injury, and early induction of GDF8 in skeletal muscle was predictive of atrophy, weakness and periarticular bone loss in patients six months following surgical ACL reconstruction. GDF8 antibody administration at the time of injury substantially reduced muscle atrophy, weakness and fibrosis in the mouse ACL injury model. GDF8 antibody treatment rescued the skeletal muscle and articular cartilage transcriptomic response to ACL injury and attenuated the severity of injury-induced knee osteoarthritis. Subcutaneous treatment with GDF8 antibody also diminished loss of periarticular bone microarchitecture. Genetic deletion of GDF8 neutralized musculoskeletal deficits in response to ACL injury. Our findings support an opportunity for rapid targeting of GDF8 to enhance functional musculoskeletal injury recovery and mitigate the development posttraumatic knee osteoarthritis, which could substantially reduce the disability burden associated with this injury.

overall_design: Comparative gene expression was assessed in mouse quadricep tissue in non-ACL injured (control) limbs and ACL-transected (injured) limbs at 7-days post-injury in both placebo-treated and anti-GDF8 antibody-treated mice

first: Camille

last: Brightwell

first: Christine

last: Latham

first: Nicholas

last: Thomas

first: Allison

last: Owen

first: Kelsey

middle: A

last: Reeves

first: Douglas

last: Long

first: Matthew

last: Patrick

first: Varag

last: Abed

first: Ramkumar

last: Annamalai

first: Cale

last: Jacobs

first: Caitlin

last: Conley

first: Gregory

middle: S

last: Hawk

first: Austin

last: Stone

first: Jean

middle: L

last: Fry

last: Thompson

first: Darren

last: Johnson

first: Brian

last: Noehren

first: Christopher


title: Effect of recombinant protein CXCL12 on patient-derived glioblastoma stem cells

status: Public on Dec 01 2023

city: Bronx

first: Jorge

middle: Eduardo

last: Fajardo

state: NY

address: 1300 Morris Park Avenue

department: Systems and Computational Biology

country: USA

institute: Albert Einstein College of Medicine

type: Expression profiling by high throughput sequencing

summary: To investigate the effect of recombinant CXCL12 on patient-derived glioblastoma stem cells, we treated GSCs with recombinant CXCL12 in cell culture media

overall_design: We then performed differential gene expression and functional analysis using data obtained from RNA-seq of glioblastoma stem cells treated with CXCL12 for 2 days

first: Yusuke

last: Suita

first: J

middle: E

first: Nikos

last: Tapinos


title: Non-canonical activation of IRE1α during Candida albicans infection enhances macrophage fungicidal activity

status: Public on Nov 13 2023

city: Ann Arbor

first: Teresa

last: O'Meara

state: MI

address: 1150 W. Medical Center Dr

department: Microbiology and Immunology

institute: University of Michigan

summary: Infection by intracellular pathogens can trigger activation of the IRE1α branch of the unfolded protein response (UPR), which then modulates innate immunity and infection outcomes during bacterial or viral infection. However, the mechanisms by which infection activates IRE1α have not been fully elucidated. While recognition of microbe-associated molecular patterns can activate IRE1α, it is unclear whether the canonical role of IRE1α in detecting misfolded proteins is required for its activation. Here, we report that Candida albicans infection of macrophages results in IRE1α activation through C-type lectin receptor signaling, reinforcing a role for IRE1α as a central regulator of host responses to infection by a broad range of pathogens. However, IRE1α activation was not preceded by protein misfolding in response to either C. albicans infection or lipopolysaccharide treatment, implicating a non-canonical mode of IRE1α activation after recognition of microbial patterns. Investigation of the phenotypic consequences of IRE1α activation in macrophage antimicrobial responses revealed that IRE1α activity enhances the fungicidal activity of macrophages. Macrophages lacking IRE1α activity displayed inefficient phagolysosomal fusion, enabling C. albicans to evade fungal killing and escape the phagosome. Together, these data provide mechanistic insight for the non-canonical activation of IRE1α during infection, and reveal central roles for IRE1α in macrophage antifungal responses.

overall_design: To compare Ire1 dependent transcriptional responses to Candida albicans, we infected WT or IRE1ΔR macrophages for 4 hours before extracting RNA and sequencing via paired end Illumina reads

first: Michael

last: McFadden


title: Genetic and monoclonal antibody blockade of GDF8 enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following ligament injury [cartilage]

first: Alexander

last: Keeble

overall_design: Comparative gene expression was assessed in mouse cartilage tissue in non-ACL injured (control) limbs and ACL-transected (injured) limbs at 7-days post-injury in both placebo-treated and anti-GDF8 antibody-treated mice (pooled cartilage samples from 4 mice per treatment)

first: Camille

middle: R

last: Brightwell

first: Christine

middle: M

last: Latham

first: Nicholas

middle: T

last: Thomas

first: Allison

last: Owen

first: Kelsey

last: Reeves

first: Douglas

last: Long

first: Matthew

middle: V

first: Katherine


title: Single nuclei RNA-seq profiles from medulloblastoma tumors with extensive nodularity [methylation array]

status: Public on Nov 15 2023

city: Heidelberg

first: Konstantin

last: Okonechnikov

state: Germany

address: Im Neuenheimer Feld 280

department: Pediatric Neurooncology

country: Germany

institute: German Cancer Research Center

type: Methylation profiling by high throughput sequencing

summary: Medulloblastoma with extensive nodularity (MBEN) are cerebellar tumors with two histologically distinct compartments and varying disease course.  We investigated this tumor class in detail with single cell transcriptome analysis confirmed with inter-nodular microdissected bulk profiles.

overall_design: Dataset represents methylation data from MBEN samples using Illumina HumanMethylation450 BeadChips or Illumina Infinium HumanMethylation850 BeadChips

first: David

last: Ghasemi


title: Single nuclei RNA-seq profiles from medulloblastoma tumors with extensive nodularity [bulk RNA-Seq]

status: Public on Oct 26 2023

summary: Medulloblastoma with extensive nodularity (MBEN) are cerebellar tumors with two histologically distinct compartments and varying disease course.  We invetiagated this tumor class in detail with single cell transcriptome analysis confirmed with inter-nodular microdissected bulk profiles.

overall_design:
Microdissection with subsequent RNA isolation was performed on FFPE-derived histological slides (nodular, inter-nodular) from 13 MBEN patients
NOTE FROM SUBMITTER: Due to patient rights reugalations in German Cancer Research Center the raw data reads are not allowed to be shared, therefore we provide only processed data.


title: Genetic and monoclonal antibody blockade of GDF8 enhances musculoskeletal recovery and mitigates posttraumatic osteoarthritis following ligament injury

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

overall_design: Refer to individual Series


title: Effect of ATM inhibition in primary endothelial cells

status: Public on Nov 01 2023

city: San Antonio

first: Henry

last: Miller

state: TX

address: 8403 Floyd Curl Drive

department: Cell Systems and Anatomy

institute: UT Health San Antonio

summary: Analysis of gene expresssion in HUVECs following ATM inhibition. The main objective of the study was to get insights about the metabolic pathways regulated by ATM in primary endothelial cells.Here we demonstrate that besides the DNA damage repair defect, metabolic dysregulation causes several of the phenotypes observed in AT patients. We discovered a new aspect of metabolic control by ATM, the control of cystine and arginine influx via the phosphorylation of CD98HC. Our data provide further insights into why NAC treatment and production of GSH is beneficial to AT patients aside from antioxidant effects and we propose a novel mechanistic link between these acute responses and disease manifestation.

overall_design: Total RNA-seq was performed in two different isolates of HUVECs and each condition run in triplicates. HUVECs were between passages 3-5. Cells were treated with either the drug delivery vehicle (DMSO) or ATM inhibitors (5uM KU60019 or 10uM KU55933) for 8 hours.

first: July

middle: C

last: Romero

middle: J

last: Bishop


title: Single nuclei RNA-seq profiles from medulloblastoma tumors with extensive nodularity

type: Methylation profiling by genome tiling array


title: Polyketide synthase-derived sphingolipids determine microbiota-mediated protection against pathogens inC. elegans

status: Public on Oct 14 2023

city: Kiel

first: Katja

last: Dierking

address: Am Botanischen Garten 9

department: Evolutionary Ecology and Genetics

institute: Kiel University

summary: Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematodeCaenorhabditis elegansand its microbiota isolatePseudomonas fluorescensMYb115 that is known to protect againstBacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids that are derived from an iterative type I polyketide synthase (PKS), thereby describing a noncanonical pathway of bacterial sphingolipid production. We provide evidence that MYb115-derived sphingolipids affectC. eleganstolerance to Bt infection by altering host sphingolipid metabolism. This work establishes sphingolipids as structural outputs of bacterial PKS and highlights the role of microbiota-derived sphingolipids in host protection against pathogens.

overall_design: N2 grown on either P. fluorescens MYb115 or P. fluorescens MYb115 ∆sgaAB, and then either infected with Bt247 or not infected; 3 biological replicates per treatment group

first: Lena

last: Peters

first: Barbara

last: Pees


title: Single nuclei RNA-seq profiles from medulloblastoma tumors with extensive nodularity [scRNA-Seq]

summary: Medulloblastoma with extensive nodularity (MBEN) are cerebellar tumors with two histologically distinct compartments and varying disease course.  We invetiagated this tumor class in detail with single cell transcriptome analysis.

overall_design:
Cohort of MBEN tumors was processed with 10X Genomics 3' V2 and Smart-Seq V2.5 protocols in order to obtain single nuclei profiles
***Submitter declares that the raw sequence data cannot be provided, including through controlled access databases, due to novel patient information security regulations in German Cancer Research Center***


title: Spatial single cell RNA profiles from medulloblastoma tumors with extensive nodularity

overall_design: Cohort of MBEN tumors was processed with Resolve Bioscience protocol in order to obtain spatial single cell profiles


title: Schwann cells regulate brown adipose tissue innervation and remodeling through MEK/ERK signaling axis

status: Public on Oct 15 2023

city: Guang zhou

first: ming'qiang

last: lai

address: Sha Tai Road 1023

country: China

institute: Southern Medical University

summary: Brown Adipose Tissue (BAT) is driven by neural innervation for thermogenesis and represents a potential therapeutic target for human obesity. However, the regulation mechanisms of BAT's neural innervation are still unclear. In this study, we validate the terminal regulation mechanism of BAT's neural innervation in which Schwann cells (SCs) control the neural innervation and remodeling of BAT by regulating the distribution of nerve endings. We found that specific ablation of Olfm4 in brown adipocytes instigates an abnormal dedifferentiation and atrophy of mature SCs, which is mediated by the activation of the MEK/ERK signaling axis. This atrophy results in a decrease in the distribution of myelinated sensory and unmyelinated sympathetic nerve endings, leading to a reduction in BAT's neural innervation and thermogenic impairment. Consequently, mice exhibit heightened sensitivity to cold and diet-induced obesity. Notably, the application of a MEK/ERK inhibitor reverses this abnormal dedifferentiation of SCs, rescuing these phenotypes. In addition, our study describes the profound remodeling process that SCs undergo in response to temperature changes, wherein SCs experience reversible dedifferentiation in response to thermal neutrality or mild cold exposure, thus modulating the remodeling of the BAT neural network. Importantly, inhibition of MEK/ERK blocks this dedifferentiation of SCs, reversing thermal neutrality-induced BAT remodeling, thereby reinforcing the central role of SCs in the complex cellular response during temperature-induced BAT remodeling. In conclusion, our study confirms the crucial regulatory role of SCs in the neural innervation and remodeling process of BAT, offering novel insights for the activation of BAT to treat obesity.

overall_design: To study the function of OLFM4 in BAT, we crossed Olfm4 flox/flox mice with Ucp1-Cre mice to construct brown adipocyte-specific knockout mice (Ucp1-Cre; Olfm4 flox/flox, Olfm4CKO) for Olfm4To investigate the effect of Olfm4 ablation on BAT, we employed RNA sequencing (RNA-Seq) to analyze the interscapular BAT (iBAT) of Olfm4CKO and Ctrl mice.


title: Characterization of microRNA profiles in the mammary gland tissue of dairy goats at the late lactation, dry period and late gestation stages

status: Public on Oct 01 2023

city: Alaer

first: Rong

last: Xuan

state: Xinjiang Uyghur Autonomous Region

address: No. 1487 Tarim Avenue

institute: Tarim University

type: Non-coding RNA profiling by high throughput sequencing

summary: The mammary gland redeveloped to the pre-pregnancy state during involution, which shows that the mammary cells have the characteristics of remodeling. The rapidity and degree of mammary gland involution are different between mice and dairy livestock (dairy cows and dairy goats). However, the molecular genetic mechanism of miRNA in involution and remodeling of goat mammary gland has not yet been clarified. Therefore, this study carried out the RNA-sequencing of nonlactating mammary gland tissue of dairy goats in order to reveal the transcriptome characteristics of miRNA in nonlactating mammary tissues and clarify the molecular genetic mechanism of miRNA in mammary cell involution and remodeling.

overall_design: This research used nine healthy, disease-free Laoshan dairy goats raised at the Qingdao Aote goat breeding farm (Qingdao, Shandong, China). The goats were provided with the farm’s standard feeding and management environment. All goats were of third parity, and their average age was four years. Mammary gland tissues were collected during late lactation (LL) (n = 3, 240 d postpartum), the dry period (DP) (n = 3, 300 d postpartum), and late gestation (LG) (n = 3, 140 d after mating). And high-throughput transcriptome sequencing was conducted on these samples.

first: Tianle

last: Chao

first: Jianmin

last: Wang

first: Yilin

last: Zhao


title: β-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice

status: Public on Sep 30 2023

first: Hisashi

last: Sawada

address: 741 South Limestone BBSRB B251

summary: The purpose of this study was to determine whether lysyl oxidase inhibition using β-aminopropionitrile (BAPN) induced region-specific aortopathies in mice. The effects of BAPN were first characterized with regard to dose, strain, age, and sex. Subsequently, BAPN was administered to young male C57BL/6J mice. BAPN-induced aortic rupture predominantly occured or originated in the descending thoracic aorta. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while relatively sporadic in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissection with false lumen formation, macrophage infiltration, collagen deposition, and remodeling of the media and adventitia. Cells surrounding the false lumen were predominantly positive for α-smooth muscle actin. To investigate the molecular basis of the regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration prior to the appearance of overt pathology. BAPN compromised contractile properties in both regions equivalently, while RNA sequencing demonstrated that BAPN altered transcriptomes related to extracellular matrix and cell division differentially between the two regions. In conclusion, BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in young mice.

overall_design: Comparative gene expression analysis of RNA-seq data for ascending and descending aortas of C57BL/6J mice administered with either water or BAPN for 1 week.


title: MYD88 dimerization controls the proliferative, invasive, and pro-inflammatory responses of synovial fibroblasts from rheumatoid arthritis patients

status: Public on Sep 27 2023

city: Atlanta

first: Sergio

last: Ramirez-Perez

state: Georgia

address: 615 Michael St NE

department: Orthopaedics

institute: Emory University

summary:
Purpose: We analyzed RNA-seq from rheumatoid arthritis synovial fibroblats and osteoarthritis syniovial fibroblast patients. Our goal was to evaluate the gene expression signatures after treatment with the MyD88 dimerization onhibitor ST2825 and identify its therapeutic potential.
Methods: We analyzed bulk RNA-seq from RA synovial fibroblasts in diferent conditions: Untreated, ST2825-treated, LPS-treated, LPS+ST2825-treated. Aditionally, we analyzed bulk RNA-seq from OA synovial fibroblatss as a control. Collection of RNA was performed after 24 h of treatment and samples were sequenced to determine transcriptional changes and regulated processes.
Results: paired-end reads were mapped to the homo sapiens GRCh37 genome assembly. RNA levels were normalized by RPKM and student's t-test.
Conclusion: The aggressiveness of the RA SFs, in terms of their proliferation, invasiveness, and increased expression of pain and inflammation mediators was decreased by ST2825. Our data strongly suggest that targeting MyD88 dimerization could mitigate joint inflammation in RA SFs.

overall_design: Identification of the potential effect of the MyD88 dimerisation inhibitor ST2825 on pathogenic expression signatures to modulate joint inflammatory processes in RA patients.

first: Pallavi

last: Bhattaram


title: Unique territorial and sub-chromosomal organization revealed in the holocentric moth Bombyx mori [Hi-C embryo]

status: Public on Sep 17 2023

city: Paris

first: Héloïse

last: Muller

address: 26 rue d'Ulm

country: France

institute: Institut Curie

summary: Genome organization in diverse eukaryotes follows conserved principles including the formation of chromosome territories (CT), chromatin compartments, and TADs. Here, we describe the 3D architecture of holocentric chromosomes in the silkworm Bombyx mori. At the genome-wide scale, B. mori chromosomes are highly territorial lacking any visible trans contact pattern. At the chromosomal scale, B. mori chromosomes segregate into three chromatin compartments: an active A and an inactive B as described in other eukaryotes, and a third type, X, with a unique contact pattern. Compartment X is strongly enriched for short-range interactions and depleted of long-range interactions, hosts a specific combination of genetic and epigenetic features and localizes towards the periphery of CT. Biophysical simulations reveal the necessity of the combined effects of affinity-based compartmentalization and activity-based loop extrusion to lead to the unique interaction patterns observed. Our analyses contribute to our understanding how chromosomes fold highlighting the evolutionary plasticity of 3D genome organization.

overall_design: Hi-C and ChIP-seq and RNA-seq data from Bombyx mori p50 reference strain embryos post-diapause. ChIP-seq experimments are all performed in duplicates. Hi-C have been done at several embryonic time points: 2h, 24h and 48h after dipause release and on adults heads. RNA-seq has been perfomred at 24h after diapause release

first: Ines

last: Drinnenberg

first: José

last: Gil Jr


title: Unique territorial and sub-chromosomal organization revealed in the holocentric moth Bombyx mori

type: Genome binding/occupancy profiling by high throughput sequencing


title: Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets

status: Public on Aug 09 2023

city: Cleveland

first: Shanshan

last: Zhang

state: OH

address: 10900 Euclid Avenue

department: Department of Genome and Genetics

institute: Case Western Reserve University


title: Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming [ATAC-Seq]

status: Public on Aug 05 2023

city: Beijing

first: Wenxue

address: Yiheyuan Road

institute: Peking University

summary: The increased stiffness of the extracellular matrix is a key driver of liver fibrosis. The activated hepatic stellate cell (HSC) is the major producer of extracellular matrix (ECM) components. While little is known about the epigenomic changes that underlie the fibrogenic impact of  ECM mechanics. In this study, we utilized a reliable in vitro system to mimic liver cirrhosis and integrated multi-omics analysis, which includes time-series RNA-seq and ATAC-seq as well as histone modification Cut&Tag, with imaging and biochemical essays to study the mechanism underlying the biomechanics function on fibrotic phenotype. We found that cells cultured in stiff matrix displayed more accessible chromatin sites, consisting of amount regions became accessible before stable fibrotic phenotype. We defined these regions as primed chromatin that chromatin accessibility foreshadows changes in gene expression. This kind of chromatin enriched in cytoskeleton organization and responding to mechanical stimulus biological process. Here, we depicted the AP-1 transcription factor family as being responsible for driving the construction of primed chromatin. Among AP-1 transcription factors, we confirmed JUN was critical to reconstruct chromatin accessibility to promote fibrogenic genotype. In addition, we described ERK contribute to the activation of JUN resulting in its binding on chromatin. Our results profiled a dynamic landscape of chromatin accessibility and defined the primed chromatin that contribute to fibrosis during responding to stiff matrix. We identified that AP-1 was capable of reorganizing the chromatin accessibility in mechanotransduction.

overall_design: ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) analysis of LX-2 cell line cultured in stiff with or without the expresison of JUN-AA. ATAC-seq analysis of LX-2 cell line cultured in soft with or without the expression of JUN-EE.

first: Weihong

last: Yuan


title: The differential microRNA profile between male and hermaphrodite gonads

status: Public on Aug 03 2023

city: Milwaukee

first: Allison

last: Abbott

state: WI

address: 1428 W. Clybourn St.

department: Biological Sciences

institute: Marquette University

summary: microRNAs are a group of small RNAs that regulate target gene expression post transcriptionally. The roles of microRNAs in regulating sperm production and function have been implicated by previous studies. In clinical studies, samples from patient with defective sperm production or function have been shown to display a different microRNA expression profile. Disruption of microRNA biogenesis is shown to result in sperm production or function defects in previous studies. However, the roles of individual microRNAs are largely unknown. Here, we aim to identify microRNAs that are enriched in male germlines of C. elegans, and study their potential roles in regulating sperm production or function.

overall_design: Gonads were isolated from N2 wild-type adult males and hermaphrodites for sequencing. Sequencing data identified microRNAs that are expressed in the gonads and further comparison between male and hermaphrodite microRNA sequencing reads revealed male gonad-enriched microRNAs which may have potential roles in regulating sperm production and function.

first: Lu

last: Lu

first: Abbott

last: Allison


title: SOX9-positive pituitary stem cells differ according to their position in the gland and maintenance of their progeny depends on context.

status: Public on Oct 12 2023

city: London

first: Probir

last: Chakravarty

address: 1 Midland Road

country: United Kingdom

institute: Francis Crick Institute

summary: Pituitary stem cells are heterogeneous and differentiate more than formerly thought but maintenance of their progeny is selective.

overall_design: Single cell RNAseq analyses of FACSorted Sox9iresGFP pituitary cells.

first: Karine

last: Rizzoti

first: Robin

last: Lovell-Badge


title: A functional interaction between hepatic Estrogen Receptor-a and PNPLA3 p.I148M variant drives fatty liver diseases susceptibility in women

status: Public on Sep 20 2023

city: Milan

first: Luca

middle: Vittorio Carlo

last: Valenti

address: via Francesco Sforza 35

department: Transfusion Medicine and Haematology

country: Italy

institute: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

summary: Fatty liver disease (FLD) caused by metabolic dysfunction is the leading cause of liver disease, and the prevalence is rising, especially in women. Although during reproductive age women are protected against FLD, for still unknown and understudied reasons some develop rapidly progressive disease at menopause. Patatin-like phospholipase domain containing 3 (PNPLA3) p.I148M variant accounts for the largest fraction of inherited FLD variability. Hepatic gene expression profile of 125 obese individuals stratified by sex and PNPLA3 genotype revealed higher PNPLA3 mRNA levels in women carrying PNPLA3 p.I148M variant. Furthermore, we showed that there is an estrogen receptor-alpha (ERα) binding site within the PNPLA3 enhancer sequence, suggesting a specific multiplicative interaction between female sex and PNPLA3 p.I148M in determining FLD.

overall_design: Hepatic transcriptome of 125 obese individuals who underwent percutaneous liver biopsy performed during bariatric surgery.

first: Alessandro

last: Cherubini

first: Guido

last: Baselli

first: Elia

last: Casirati

first: Stefano

last: Romeo

first: Paola

last: Dongiovanni


title: Accelerated Epigenetic Aging and DNA Methylation Alterations in Berardinelli-Seip Congenital Lipodystrophy

status: Public on Aug 08 2023

city: Doha

first: Georges

last: Nemer

address: Education City

country: Qatar

institute: Hamad Bin Khalifa university

summary: Genome wide DNA methylation profiling of Congenital Lipodystrophy type 2 patients, mutation carriers , and healthy control samples .The Infinium MethylationEPIC Kit was used to measure genome-wide DNA methylation across > 868,000 CpG sites.

overall_design: Bisulfite converted DNA hybridized to the Infinium MethylationEPIC BeadChip.

first: Nady

last: El Hajj


title: Integrated copy number and transcriptomic profiling reveal novel oncogenic drivers and clinically significant biomarkers in adenoid cystic carcinoma [Affymetrix]

status: Public on Aug 02 2023

city: Gothenburg

first: Mattias

last: Andersson

address: Medicinaregatan 1F

department: Sahlgrenska Cancer Center

country: Sweden

institute: University of Gothenburg

summary: This experiment investigates global gene expression in adenoid cystic carcinoma (30) and normal salivary gland tissue (7).

overall_design: A total of 37 samples are analyzed of which 7 are control samples.

first: Marta

last: Persson

middle: K

first: Per-Erik

last: Sahlin

first: Yoshitsugu

last: Mitani

first: Renata

last: Ferrarotto

first: Adel

last: El-Naggar

first: Göran

last: Stenman


title: Integrated copy number and transcriptomic profiling reveal novel oncogenic drivers and clinically significant biomarkers in adenoid cystic carcinoma

type: Genome variation profiling by genome tiling array


title: Global mapping of RNA-chromatin contacts reveals a proximity-dominated connectivity model for ncRNA-gene interactions

city: Stanford

first: Aaron

middle: F

last: Straight

state: CA

address: 279 Campus Drive, B409A

department: Biochemistry

institute: Stanford University

summary: Non-coding RNAs (ncRNAs) are transcribed throughout the genome and provide regulatory inputs to gene expression through their interaction with chromatin. Yet, the genomic targets and functions of most ncRNAs are unknown. Here we use chromatin-associated RNA sequencing (ChAR-seq) to map the global network of ncRNA interactions with chromatin in human embryonic stem cells, and the dynamic changes in interactions during differentiation into definitive endoderm. We uncover general principles governing the organization of the RNA-chromatin interactome, demonstrating that nearly all ncRNAs exclusively interact with genes in close three-dimensional proximity to their locus, and provide a model predicting the interactome. We uncover RNAs that interact with many loci across the genome, and unveil thousands of unannotated RNAs that dynamically interact with chromatin. By relating the dynamics of the interactome to changes in gene expression, we demonstrate that activation or repression of individual genes is unlikely to be controlled by a single ncRNA.

overall_design: To map chromatin interacting RNAs during cell differentiation we performed ChAR-seq on human ES cells and after differentiation into definitive endoderm (DE). We generated two datasets for each cell state. We also performed RNA-seq in quadruplicate on these samples to characterize changes in transcriptional output.

first: Charles

last: Limouse

first: Owen

last: Smith

first: David

last: Jukam

first: Kelsey

last: Fryer

first: William

last: Greenleaf


title: CEBP-β and PLK1 as Potential Mediators of the Breast Cancer/Obesity Crosstalk: ‘in vitro’ and ‘in silico’ approaches inside a spiderweb interaction network

status: Public on Jul 19 2023

city: Caserta

first: Gilda

last: Cobellis

address: Viale Abramo Lincoln

institute: University of Campania "Luigi Vanvitelli"

summary: Here, we report a transcriptomics analysis on MCF-7 breast cancer cells exposed to adipocyte conditioned medium (CM) and focus on the functional relevance that CM-affected pathways and processes and related biomarkers may have in breast cancer response to obesity.

overall_design: Comparative transcriptomic profile between MCF-7 cells untreated or treated with conditioned medium derived from 3T3L1 mature adipocytes.

first: Ines

last: Barone

first: Stefania

last: Catalano

first: Cinzia

last: Giordano


title: Long-read transcriptome sequencing reveals expression characteristics of osteosarcoma

city: Changsha

first: Lin

last: Qi

address: 139 Renmin Road

institute: The Second Xiangya Hospital, Central South University

summary: Osteosarcoma is the most common primary bone cancer in children, adolescents and young adults. It is a rare cancer type. To comprehensively reveal the transcriptomic characteristics of osteosarcoma, we performed Oxford Nanopore Technologies (ONT) long-read RNA-Seq of tumor and adjacent normal tissues from 23 patients with osteosarcoma.

overall_design: To comprehensively reveal the transcriptomic characteristics of osteosarcoma, 23 osteosarcoma samples and 13 paired normal adjacent tissue samples were analyzed using ONT long-read RNA sequencing

first: Zhihong

last: Li

first: Chao

last: Tu

first: Wenchao

last: Zhang


title: Single cell multi-omics analysis deconstructs diabetes-associated β-cell heterogeneity in human islets(scATACSeq)

first: Shanshan

summary: The functional heterogeneity of β-cells is important for metabolism and diseases, but the nature and mechanism of such variation at molecular level remain elusive. Here we explore this question by comparing both single cell RNA-seq and single cell ATAC-seq maps of healthy and type II diabetic (T2D) human islets. We dissect the T2D-associated single cell trajectory and identified signature genes and enhancers in β-cells. We also map the 3D genome of both α- and β-cells with low-input eHi-C approach to unravel the cell type-specific gene regulatory circuits. Strikingly, more than one third of the T2D signature genes show significant intra-donor heterogeneity at single cell level; these genes are functionally distinct from other signature genes that are largely invariant among cells from the same individual but differentially expressed between donors, suggesting different roles in T2D pathogenesis. Importantly, we identified consistent intra-donor variations at both transcriptomic and epigenomic levels, which strongly support the heterogenous β-cell states and transcription programs. Finally, we construct the disease-signature regulatory networks and pinpointed HNF1A as one of the top transcription factors governing T2D-associated β-cell heterogeneity. Taken together, we provide the first multi-omic characterization of β-cell heterogeneity and reveals its connection to T2D.

overall_design:
scATAC-seq for Human Pancreatic islet from 11 individuals respectively. Including 7 Healthy donor and 4 Type II diabetes patient donor.

The records have been updated with the files containing barcode information on Oct 13, 2023.

first: Chen

last: Weng

first: Anniya

last: Gu

first: Fulai

last: Jin

first: Yan


title: WT distal colon RNA-seq

status: Public on Aug 01 2023

city: Boston

first: Roni

last: Nowarski

state: MA

address: 60 Fenwood Rd

institute: Brigham and Women's Hospital

summary: To perform RNA-seq of distal colon tissue from WT mouse obtained from Jackson Laboratories

overall_design: Distal colon from 8 week WT mouse was rinsed in PBS and flash-frozen in liquid nitrogen for RNA extraction.

first: Kisha

middle: N

last: Sivanathan

first: Aditya

last: Misra


title: Integrated copy number and transcriptomic profiling reveal novel oncogenic drivers and clinically significant biomarkers in adenoid cystic carcinoma [Agilent]

first: Mattias

last: Andersson

summary: We analyzed 100 patient samples by high-resolution arrayCGH to study genomic imbalances in ACC.

overall_design: High-resolution aCGH (4x180K and 244K) on fresh frozen and paraffin embedded tissue from 100 well-characterized ACCs.

first: Marta

last: Persson

first: Per-Erik

last: Sahlin

first: Yoshitsugu

last: Mitani

first: Margaret

last: Brandwein-Weber

first: Henry

last: Frierson Jr

first: Christopher

last: Moskaluk

first: Isabel

last: Fonseca

first: Renata

last: Ferrarotto

first: Thomas

last: Loening

first: Adel

last: El-Naggar

first: Göran

last: Stenman


title: Gene expression profiling of mouse liver after a ketogenic diet (KD)

status: Public on Jul 29 2023

city: Wuhan

first: xinhe

last: XinheHuang

state: Hubei

address: Hust

country: Singapore

institute: Huazhong University of Science and Technology

summary: To understand how KD regulates gene expression, the gene expression profiles of livers from mice fed a control (Ctrl) or KD are compared using RNA-seq

overall_design: Six biological replicates oflivers from mice fed Ctrl or KD

first: Junhong

last: Qin

first: Xinhe

last: Huang


title: Transcriptomic exploration of SSR42 and its impact on Staphylococcus aureus virulence

status: Public on Jul 25 2023

city: Tampa

first: Lindsey

last: Shaw

state: FL

address: 4202 E Fowler Avenue

department: CMMB

institute: University of South Florida

summary: Perhaps the most pivotal feature contributing to Staphylococcus aureus pathogenicity is the production of a wealth of virulence factors such as secreted toxins, adhesive proteins, and factors that aid in host immune evasion. The abundance and activity of these factors is tightly regulated by a multitude of effectors, including two-component systems, alternative sigma factors, DNA binding transcription factors, and regulatory RNAs. SSR42 is a ~1,200-nt long regulatory RNA that has been previously shown to be highly stable and abundant in stationary phase growth. To explore the role of SSR42 within the S. aureus cell, we created a full deletion mutant for this gene and performed RNA sequencing analysis after 15h of growth. Following standardized bacterial growth and sample processing, total bacterial RNA was isolated utilizing the Qiagen RNeasy mini kit and contaminating DNA was removed by treatment with Ambion DNA-free kit. Total RNA was enriched for mRNA using MicrobExpress kit and Illumina RiboZero rRNA removal kit for Gram-positive bacteria. Library construction was performed using the TruSeq Stranded mRNA Kit from Illumina, and RNA was sequenced using an Illumina Nextseq 550. When compared to wild-type, the SSR42 mutant exhibited profound changes in its transcriptomic landscape, suggesting that SSR42 has myriad regulatory targets across niches of function.

overall_design: S. aureus RNA was extracted to compare global gene expression of two samples: HOU wildtype and HOU SSR42 deletion mutant. HOU wildtype serves as the parental control strain. Each sample was generated by pooling three independent biological replicate RNA preps.

first: Brooke

last: Tomlinson

first: Mary-Elizabeth

last: Jobson


title: Characterization of a human regulatory T cell-like cell line, MT-2, in the presence or absence of FOXP3

status: Public on Sep 21 2023

city: Chapel Hill

first: Jason

middle: Robert

last: Mock

state: NC

address: 125 Mason Farm Road

institute: University of North Carolina

summary: These studies profiled the transcriptional differences in a human regulatory T cell-like cell line, MT-2, when FOXP3 a master transcriptional regulatory element was present or absence. In the FOXP3 null MT-2 cell line FOXP3 express had been deleted by CRISPR-Cas9.  RNA was prepared for bulk RNA-seq from 4 replicates for each cell line.  In the absence of FOXP3 in the MT-2 cell line there were 1251 differential expressed genes. These differentially expressed gene results indicate that hte loss of FOXP3 in MT-2 cells results in altered transcripts and pathways often associated with regultory T cell activity or phenotypes.

overall_design: Wild type MT-2 or a MT-2 where FOXP3 has been deleted by CRISPR-Cas9 were grown for 3 days in vitro. Cell lystates for bulk RNA-seq were obtained and used to determine difference in gene transcription between the two cell lines.

first: Morgan

last: McCullough

first: Miriya

last: Tune

first: Hong

last: Dang


title: Molecular fingerprints for bone marrow cells, acute lymphoblastic leukemia [bulk RNA-seq]

status: Public on Jul 04 2023

city: Munich

first: Carolin

last: Prexler

address: Kölner Platz 1, Haus 11

department: School of Medicine and Health, Department of Pediatrics

institute: Technical University of Munich, TUM University Hospital

summary: The overall goal of this study was to characterize bone marrow cells based on their transcriptome. This submission includes preleukemic samples (B-cell acute lymphoblastic leukemia) from 6 mice. This project has received funding from ERA perMed JTC2018 under the title „Genomics-based tools for personalized treatment to reduce chemotherapy burden in paediatric cancer” (Acronym “GEPARD”)

overall_design: Bulk RNA-seq samples were generated from murine bone marrow using the 10X Genomics Chromium platform and protocols. Bone marrow cells were collected and sorted from wildtype and PAX5 heterozygous mice.

first: Julia

last: Hauer

first: Franziska

last: Auer


title: Molecular fingerprints for bone marrow cells, acute lymphoblastic leukemia [scRNA-seq]

summary: The overall goal of this study was to characterize bone marrow cells based on their transcriptome, surface protein expression and BCR-VDJ-profile for accurate identification of clinically relevant cell states. This submission includes B-cell acute lymphoblastic (pre-)leukemia samples from mice. This project has received funding from ERA perMed JTC2018 under the title „Genomics-based tools for personalized treatment to reduce chemotherapy burden in paediatric cancer” (Acronym “GEPARD”)

overall_design: CITE-seq (scRNA-seq) and scVDJ-seq samples were generated from murine bone marrow cells using the 10X Genomics Chromium platform and protocols. Bone marrow cells (different B cell populations) were collected and sorted from wildtype and PAX5 heterozygous mice. Cells were stained with specific hashtag antibodies to label mice or B cell populations. Single cell suspensions were loaded and processed for sequencing.


title: Combined CDK4/6 and ERK1/2 inhibition enhances anti-tumor activity in NF1-associated plexiform neurofibroma

status: Public on Jun 26 2023

city: Indianapolis

first: Steven

last: Rhodes

state: IN

address: 1044 W. Walnut St.; Bldg R4, Rm 325

institute: Indiana University

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

overall_design: Refer to individual Series


title: Immune cell distribution properties of the murine abdominal aortic aneurysm and normal aortas at single cell resolution

status: Public on Jul 18 2023

city: Hangzhou

first: Zhejun

last: Cai

state: Zhejiang

address: 88 Jiefang Road

department: Department of Cardiology, The Second Affiliated Hospital

institute: Zhejiang University School of Medicine

summary: Inflammation is still a crucial factor in the development of abdominal aortic aneurysm (AAA). The CD45+ cell population of elastase-induced murine AAA was deconstructed at the single-cell level using the single-cell RNA (scRNA) transcriptomic technique.

overall_design: We isolated each group of immune cells and subdivided them into multiple subgroups, enumerated the remarkable differentially expressed genes, investigated the developmental pathways of immune cells, and demonstrated their interactions.


title: Molecular fingerprints for bone marrow cells, acute lymphoblastic leukemia


title: Secukinumab versus guselkumab in the complete treatment of ustekinumab‑resistant psoriatic plaques: ARROW

status: Public on Jun 21 2023

city: New York

first: James

last: Krueger

address: 1230 York Avenue

department: Center for Clinical and Translational Science

institute: The Rockefeller University

summary: To investigate the clinical and molecular effects of direct IL-17A versus selective IL-23 inhibition in patients with anti-IL-12/23 refractory psoriatic plaques.

overall_design:
A 16-week, randomized, open-label, parallel-group, phase 2a multicenter study (ARROW) was conducted in patients presenting with ≥1 active psoriatic plaque (total clinical score [TCS] ≥6) at screening despite adequate treatment with ustekinumab (label dose ≥24 weeks) and with a Psoriasis Area Severity Index (PASI) score 1–10. Patients were randomized 1:1 to receive secukinumab 300 mg (n=20) or guselkumab 100 mg (n=20).

Descriptions:
BL = Baseline
W16 = 16 weeks of treatment
NL = non-lesional skin
LS = lesional skin

first: Sandra

last: Garcet


title: Overexpression of the receptor-like kinase BIR1 gene causes SOBIR1- and EDS1-dependent cell death phenotypes in Arabidopsis

status: Public on Jun 15 2023

city: Lausanne

first: Irene

last: Guzmán-Benito

state: Vaud

address: Biophore, UNIL-SORGE

department: DBMV

country: Switzerland

institute: UNIL

summary: In order to understand the downstream biological processes and pathways associated to BIR1 induction, we conducted a global transcriptome RNA-Seq assay in Arabidopsis wild-type (WT) and transgenic plants with a dexamethasone (DEX)  inducible BIR1-mCherry transgene (ine 9, L9).

overall_design: Comparative gene expression profiling of RNA-seq data from Arabidopsis thaliana WT and L9 plants. Samples were collected at 4 and 12 days of daily treatment with DEX to induce the BIR1 expression. Mock-treated plants (water) ere used as controls.

first: César

last: Llave


title: Mouse model of Heptablastoma

status: Public on Jun 09 2023

city: Memphis

first: Xiang

last: Chen

state: TN

address: 262 Danny Thomas Place

department: Computational Biology

institute: St.Jude Children's Research Hospital

summary: Lack of relevant animal models and cell lines hampers the understanding of hepatoblastoma and identification of therapeutic targets. We report a  hepatoblastoma murine model that faithfully recapitulates the pathological features of mixed fetal and embryonic hepatoblastoma, with transcriptomics resembling the high-risk gene signatures of human disease

overall_design: Tumor was analyzed from Hepatocellular model at single cell RNA sequencing. The ScRNAseq was performed using 10X genomics -Single cell gene expression kit.

first: Jie

last: Fang

first: Shivendra

last: Singh

first: Sivaraman

last: Natarajan

first: Jun

last: Yang


title: Combined CDK4/6 and ERK1/2 inhibition enhances anti-tumor activity in NF1-associated plexiform neurofibroma [trigeminal nerve]

summary:
Purpose: Plexiform neurofibromas (PNF) are peripheral nerve sheath tumors that cause significant morbidity in persons with neurofibromatosis type 1 (NF1), yet treatment options remain limited. To identify novel therapeutic targets for PNF, we applied an integrated multi-omics approach to quantitatively profile kinome activation in a mouse model that has predicted therapeutic responses in clinical trials for NF1-associated PNF with high fidelity.
Experimental Design: Utilizing RNA sequencing combined with chemical proteomic profiling of the functionally enriched kinome using multiplexed inhibitor beads coupled with mass spectrometry, we identified molecular signatures predictive of response to CDK4/6 and RAS/MAPK pathway inhibition in PNF. Informed by these results, we evaluated the effectivity of the CDK4/6 inhibitor, abemaciclib, and the ERK1/2 inhibitor (LY3214996) alone and in combination to reduce PNF tumor burden in Nf1flox/flox;PostnCre mice.
Results: Converging signatures of CDK4/6 and RAS/MAPK pathway activation were identified within the transcriptome and kinome that were conserved in both murine and human PNF. We observed robust synergism of the CDK4/6 inhibitor, abemaciclib, in combination with the ERK1/2 inhibitor (LY3214996) in primary Nf1-/- Schwann cell cultures. Consistent with these findings, the combination of abemaciclib (CDK4/6i) and LY3214996 (ERK1/2i) synergized to suppress molecular signatures of MAPK activation and exhibited enhanced anti-tumor activity in Nf1flox/flox;PostnCre mice in vivo.
Conclusion: These findings provide rationale for the clinical translation of CDK4/6 inhibitors alone and in combination with therapies targeting the RAS/MAPK pathway for the treatment of PNF and other peripheral nerve sheath tumors in persons with NF1.

overall_design:
RNAseq of trigeminal nerve from Nf1 flox/flox PostnCre - (WT) and PostnCre+ (Nf1) mice
12 experimental samples

middle: D

middle: P

last: Angus


title: RNA expression profile (RNA-Seq) in mouse colonic tumors expressing endogenous K-Ras-WT, K-Ras-G12D, or K-RAS-G12D/K104Q

status: Public on Jun 01 2023

first: Bing

last: Shui

address: 360 Longwood Ave

department: Cancer Biology

institute: Dana-Farber Cancer Institute

summary: Ras proteins are GTPases that regulate a wide range of cellular processes. The activity of Ras is dependent on its nucleotide-binding status, which is modulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs). Previously, we demonstrated that mutation of lysine 104 to glutamine (K104Q) attenuates the transforming capacity of oncogenic K-Ras by interrupting GEF induced nucleotide exchange. To assess the effect of this mutation in vivo, we used CRISPR/Cas9 to generate mouse models carrying the K104Q point mutation in wild-type and conditional K- RasLSL-G12D alleles. Homozygous animals for K104Q were viable, fertile, and arose at Mendelian frequency, indicating that K104Q is not a complete loss of function mutation. Consistent with our previous findings from in vitro studies, however, the oncogenic activity of K-RasG12D was significantly attenuated by mutation at K104. These data demonstrate that lysine at position 104 is critical for the full oncogenic activity of mutant K-Ras and suggest that modification at K104, for example acetylation, may also regulate its activity. Using biochemical and structural analysis, we found that the G12D and K104Q mutations cooperate to suppress GEF-mediated nucleotide exchange, explaining the preferential effect of K104Q on oncogenic K-Ras. Furthermore, we found that K104 site forms allosteric network with three residues (M72, R73 and G75) on 2 helix at switch II. Intriguingly, point mutation at glutamine 75 to alanine (G75A) showed strong negative regulatory effect on K-RasG12D. Collectively, modulating these sites may provide a unique therapeutic approach in cancer expressing mutant K-Ras.

overall_design: RNA-Seq of colonic tumor from three mouse models, Fabp-Cre/+ (Control), Fabp-Cre/+; K-Ras-G12D/+ (Experimental), and Fabp-Cre/+; K-Ras-G12D-K104Q/+ (Experimental). Colonic tumor from the control model expressed K-Ras-WT. Colonic tumor from the experimental model expressed oncogenic K-Ras-G12D or K-Ras-G12D-K104Q/+.

first: Moon

middle: H

first: Kevin

last: Haigis


title: Single-Cell Multi-Omics Identifies Chronic Inflammation as a Driver of TP53 mutant Leukaemic Evolution

status: Public on May 10 2023

city: Oxford

first: Sean

last: Wen

address: Headley Way

institute: University of Oxford

summary: TP53 is the most commonly mutated gene in human cancer, typically occurring in association with complex cytogenetics and dismal outcomes. Understanding the genetic and non-genetic determinants of TP53- mutation driven clonal evolution and subsequent transformation is a crucial step towards the design of rational therapeutic strategies. Here, we carry out allelic resolution single-cell multi-omic analysis of haematopoietic stem/progenitor cells (HSPC) from patients with a myeloproliferative neoplasm who transform to TP53- mutant secondary acute myeloid leukaemia (AML), a tractable model of TP53 -mutant cancer evolution.

overall_design: We performed TARGETseq (genotyping and mRNA-sequencing from the same cell) to enable integrated mutational and gene expression analysis.

first: Alba

last: Rodriguez-Meira

first: Wei

first: Adam

last: Mead


title: Long-range genomic contacts and spatiotemporal chromatin landscape of human histone gene clusters at Histone Locus Bodies during the cell cycle in breast cancer

city: Burlington

first: Joseph

last: Boyd

state: Vermont

address: University of Vermont

department: Biomedical and Health Sciences

institute: University of Vermont


title: Matrix stiffness regulate fibrotic phenotype through AP-1 contributing to chromatin accessibility dynamic [RNA-seq]

status: Public on May 01 2023

city: Beijing

first: Wenxue

last: Zhao

address: Yiheyuan Road

institute: Peking University

summary: The increased stiffness of the extracellular matrix is a key driver of liver fibrosis. The activated hepatic stellate cell (HSC) is the major producer of extracellular matrix (ECM) components. While little is known about the epigenomic changes that underlie the fibrogenic impact of  ECM mechanics. In this study, we utilized a reliable in vitro system to mimic liver cirrhosis and integrated multi-omics analysis, which includes time-series RNA-seq and ATAC-seq as well as histone modification Cut&Tag, with imaging and biochemical essays to study the mechanism underlying the biomechanics function on fibrotic phenotype. We found that cells cultured in stiff matrix displayed more accessible chromatin sites, consisting of amount regions became accessible before stable fibrotic phenotype. We defined these regions as primed chromatin that chromatin accessibility foreshadows changes in gene expression. This kind of chromatin enriched in cytoskeleton organization and responding to mechanical stimulus biological process. Here, we depicted the AP-1 transcription factor family as being responsible for driving the construction of primed chromatin. Among AP-1 transcription factors, we confirmed JUN was critical to reconstruct chromatin accessibility to promote fibrogenic genotype. In addition, we described ERK contribute to the activation of JUN resulting in its binding on chromatin. Our results profiled a dynamic landscape of chromatin accessibility and defined the primed chromatin that contribute to fibrosis during responding to stiff matrix. We identified that AP-1 was capable of reorganizing the chromatin accessibility in mechanotransduction.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for LX-2 cell line cultured in stiff or soft matrix for 2 or 4 days.

first: Weihong

last: Yuan


title: Matrix stiffness regulate fibrotic phenotype through AP-1 contributing to chromatin accessibility dynamic [Cut&Tag]

overall_design: CUT&Tag (Cleavage Under Targets and Tagmentation) analysis targetting p-Jun and the histone modifications H3K4me3, H3K27me3 and H3K27ac3 for LX-2 cell line cultured in stiff or soft matrix for 2 days.


title: Matrix stiffness regulate fibrotic phenotype through AP-1 contributing to chromatin accessibility dynamic [ATAC-seq]

overall_design: ATAC-seq (Assay for Transposase-Accessible Chromatin with high throughput sequencing) analysis of LX-2 cell line cultured in stiff or soft matrix for 2 or 4 days.


title: Matrix stiffness modulates fibrogenesis in hepatic stellate cells through AP-1-induced chromatin priming


title: transcriptome alteration of cultured HN6 cancer stem cells

status: Public on Mar 15 2023

first: Ling-fei

last: Jia

address: 22 Zhongguancun Avenue South, Haidian District

institute: Peking University School and Hospital of Stomatology

summary: To investigate the  difference of lncrna in HN6 cancer stem cells(CSCs) compared with non-CSCs

overall_design: We performed RNA-Seq in HN6 ALDH1 high cells and HN6 ALDH1 low cells  isolated by flow cytometry based on ALDEFLUOR analysis.

first: Lingfei


title: RNA-seq data for tumor and adjacent non-tumor tissues from hepatocellular carcinoma patients with anti-PD-1 therapy

city: Nanjing

first: Binghua

last: Li

state: Jiangsu

address: Zhongshan road 321, Nanjing, Jiangsu, China

department: Department of Hepatobiliary Surgery

institute: the Affiliated Drum Tower Hospital, Medical School of Nanjing University

summary: Immune checkpoint inhibitors elicit durable antitumor effects in multiple cancers, yet not all patients respond. Here, we aimed to develop and validate a molecular classification of  hepatocellular carcinoma (HCC) patients based on 42 fatty acid degradation genes and demonstrate its predictive ability in the clinical response of anti-PD1 therapy in HCC patients. We studied global mRNA expression profiles from 41 primary tumor tissues and 25 nontumor tissues derived from 41 HCC patients. 17 patients received anti-PD1 therapy and were available with clinical response. 63 samples were also sent for lipidomics analysis. Methods for the study included gene expression analysis, consensus clustering analysis, pathway enrichment analysis, and Single-Sample Gene Set Enrichment Analysis (ssGSEA). This study identified and validated a novel molecular classification based on fatty acid degradation that predicts clinical response to anti-PD-1 therapy in hepatocellular carcinoma.

overall_design: In total, 69 samples from hepatocellular carcinoma tumors and adjacent non-tumor liver tissue have been obtained from 44 patients who underwent radical resection between January 2019 and June 2021 in Nanjing Drum Tower Hospital. Three samples didn’t pass the quality control for RNA-seq and 6 samples didn’t pass the quality control for lipidomics analysis due to tissue degradation or limited tissue amount, thus being ruled out from the study. Seventeen patients received anti-PD1 therapy and were available with clinical response. The study was approved by the Research Ethics Committee of Drum Tower hospital, and written informed consent was obtained from each patient. Each sample was assigned a new research ID, and the patient’s name or medical record number used during hospitalization was de-identified.

first: Yunzheng

first: Beicheng

last: Sun

first: Decai

last: Yu


title: Bulk RNA seq of sorted C. elegans neurons

status: Public on Apr 06 2023

city: New Haven

first: Marc

last: Hammarlund

state: Connecticut

address: 295 Congress Ave

department: Genetics

institute: Yale University

summary: Bulk RNA seq of FACS isolated C. elegans neurons, with pan-neuronal reference, and sorted viable cell reference samples. Collected for comparison to single cell sequencing data

overall_design: Cell type specific C. elegans neuronal samples were obtained via FACS for comparison to each other, and to pan-neuronal and all cell references. Sample names describe the cell type targeted (ASG, AVE, AWA, etc…), Rab3 indicates samples targeted with a Pan-Neuronal Marker for direct comparison to each individual cell type. Ref samples were obtained by dissociating and FACS isolation using only stains to sepatate living and dead cells and thus represents an "all cell" reference.

first: Alec

last: Barrett

first: Rebecca

last: McWhirter

first: Seth

last: Taylor

first: Alexis

last: Weinreb

first: David

last: Miller III


title: RNA-sequencing analysis of Drosophila Hpo overexpression and knockdown in larval fat tissue

status: Public on Apr 28 2023

city: Daejeon

first: Kyu-Sun

last: Lee

address: 125 Gwahak-ro

country: South Korea

institute: KRIBB

summary: To find the lipolysis-related function of Hpo, RNA-sequencing analysis was processed using Hpo-induced larval fat tissue.

overall_design: 3 samples for Dcg-Gal4/+ control larval fat tissue and Dcg>Hpo, Dcg>Hpo RNAi larval fat tissue


title: Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation [RNA-Seq]

status: Public on Jan 23 2023

city: San Francisco

first: Robert

last: Blelloch

address: 35 Medical Center Way

institute: UCSF

summary: Enhancers are essential in defining cell fates through the control of cell type specific gene expression. Enhancer activation is a multi-step process involving chromatin remodelers and modifiers. One of these steps is monomethylation of histone H3 lysine 4 (H3K4m1) by MLL3 (KMT2C) and MLL4 (KMT2D) is thought to be critical for enhancer activation and cognate gene expression including through the recruitment of acetyltransferases targeting H3K27. Here we test this model by evaluating the impact of MLL3/4 loss on chromatin states and gene expression during early embryonic stem cell (ESC) differentiation. We find that MLL3/4 activity is required at most if not all sites that normally gain or lose H3K4m1, but infrequently at sites that remain unchanged during this transition. This requirement extends to H3K27 acetylation (H3K27a) at most transitional sites. Unexpectedly, many sites gain H3K27a independent of MLL3/4 or H3K4m1 including enhancers regulating key factors in early differentiation. Furthermore, despite the failure to gain active histone marks at thousands of enhancers, transcriptional activation of nearby genes is largely unaffected, thus uncoupling enhancer regulation from transcription during this transition. These data challenge current models of enhancer activation and imply distinct mechanisms between stable and dynamically changing enhancers. Moreover, the data suggest limited roles for enhancers in transcriptional regulation in early ESC differentiation. Collectively, our study highlights gaps in knowledge about the steps and epistatic relationships of enzymes necessary for enhancer activation and cognate gene transcription.

overall_design: Comparative gene expression analysis of four different cell lines in two different cuture conditions with three biological replicates cultured, collected, and prepared independently

first: Ryan

last: Boileau


title: Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation [CUT&TAG]

summary: Enhancers are essential in defining cell fates through the control of cell type specific gene expression. Enhancer activation is a multi-step process involving chromatin remodelers and histone modifiers. One of these steps is monomethylation of H3K4 (H3K4me1) by MLL3 (KMT2C) and MLL4 (KMT2D). MLL3/4 are thought to be critical for enhancer activation and cognate gene expression including through the recruitment of acetyltransferases for H3K27. Here we test this model by evaluating the impact of MLL3/4 loss on chromatin and transcription during early embryonic stem cell differentiation. We find that MLL3/4 activity is required at most if not all sites that gain or lose H3K4me1, but is largely dispensable at sites that remain stably methylated during this transition. This requirement extends to H3K27 acetylation (H3K27ac) at most transitional sites. Unexpectedly, many sites gain H3K27ac independent of MLL3/4 or H3K4me1 including enhancers regulating key factors in early differentiation. Furthermore, despite the failure to gain active histone marks at thousands of enhancers, transcriptional activation of nearby genes is largely unaffected, thus uncoupling the regulation of chromatin state from transcriptional changes during this transition. These data challenge current models of enhancer activation and imply distinct mechanisms between stable and dynamically changing enhancers. Moreover, the data suggest limited roles for many enhancers in transcriptional regulation in early ESC differentiation. Collectively, our study highlights gaps in knowledge about the steps and epistatic relationships of enzymes necessary for enhancer activation and cognate gene transcription.

overall_design: CUT&TAG for H3K27a with WT and DKO cells in two different cuture conditions and two biological replicates cultured, collected, and prepared independently.


title: Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation

overall_design: Refer to individual Series


title: Glioblastoma remodeling of neural circuits in the human brain decreases survival

status: Public on Jan 20 2023

first: Abrar

last: Choudhury

state: California

institute: University of California, San Francisco

summary: Gliomas synaptically integrate into neural circuits. Prior work has demonstrated bidirectional interactions between neurons and glioma cells, with neuronal activity driving glioma growth and gliomas increasing neuronal excitability. In this study we sought to determine how glioma-induced neuronal changes influence neural circuits underlying cognition and whether these interactions influence patient survival. Using intracranial brain recordings during lexical retrieval language tasks in awake humans together with site-specific tumor tissue biopsies and cell biology experiments, we found that gliomas remodel functional neural circuitry such that task-relevant neural responses activate tumor-infiltrated cortex well beyond the cortical regions normally recruited in the healthy brain. Site-directed biopsies from regions within the tumor that exhibit high functional connectivity between the tumor and the rest of the brain are enriched for a glioblastoma subpopulation that exhibits a distinct synaptogenic and neuronotrophic phenotype. Tumor cells from functionally connected regions secrete the synaptogenic factor thrombospondin-1, which contributes to the differential neuron-glioma interactions observed in functionally connected tumor regions compared to tumor regions with less functional connectivity. Pharmacological inhibition of thrombospondin-1 through the FDA-approved drug, gabapentin decreases glioblastoma proliferation. The degree of functional connectivity between glioblastoma and the normal brain negatively impacts both patient survival and language task performance. These data demonstrate that high-grade gliomas functionally remodel neural circuits in the human brain, which both promotes tumor progression and impairs cognition.

overall_design: This SuperSeries is composed of the SubSeries listed below. Please refer to individual Series.


title: Genomic characterization of DICER1-associated neoplasms uncovers novel molecular classes

status: Public on Feb 08 2023

city: Heidelberg

first: Daniel

last: Schrimpf

address: Im Neuenheimer Feld 224

department: Neuropathology

institute: University Hospital Heidelberg, Intitute of Pathology

summary: DNA methylation data of a novel group of mesenchymal tumors with DICER1 alteration which includes two novel classes designated “low-grade mesenchymal tumor with DICER1 alteration” (LGMT DICER1) and “high-grade sarcoma with DICER1 alteration” (HGS DICER1), as well as the recently described class of primary intracranial sarcoma, DICER1-mutant (PIS DICER1)

overall_design: Methylation data from tumor samples

first: Felix

last: Kommoss


title: Spatial multi-omics reveals vulnerabilities of radial glia-like cancer-initiating cells within distinct ecosystems of pediatric and adult malignant gliomas

status: Public on Jan 17 2023

city: Chengdu

first: Yuan

last: Wang

state: Sichuan

address: No.17 People's South Road

institute: Sichuan university

summary: We collected five DMG, five GBM (including two secondary GBM), and one peritumor samples from eleven patients requiring surgical resection. To establish an atlas for spatially-resolved gene expression, we performed short-read  spatial transcriptomic sequencing  on the tissue sections using the 10x Visium platform.

overall_design: Here, we established a spatial atlas of H3K27M-DMG and GBM through short read spatial transcriptomics to reveal the niche-specific distribution and vulnerability of stem-like cells in H3K27M-DMG and GBM

first: Zongyao

last: Huang

first: Yanming

last: Ren

first: Lingling

last: Zhou

first: Peng

last: Xiao

first: Junwei

last: Song

first: Lu

last: Chen

first: Yan

last: Ju

first: Yuekang

last: Zhang


title: Long-range genomic contacts and spatiotemporal chromatin landscape of human histone gene clusters at Histone Locus Bodies during the cell cycle in breast cancer [ChIP-seq]

first: Joseph

last: Boyd

summary: Cell cycle controlled mechanistic remodeling of chromatin architecture at HLBs as non-membranous phase-separated nuclear domains represents a novel dimension to regulation of cell proliferation. Therefore, we sought to resolve a gap in our understanding of how 3D higher-order genomic organization supports the activation of multiple clustered histone genes. Our findings are consistent model that the HINFP/NPAT complex controls the formation and dynamic remodeling of higher-order genomic organization of histone gene clusters at HLBs in early to late G1 phase to support production of histone mRNAs in S phase. that the two principal histone gene regulators HINFP and NPAT are located at anchor-points for chromatin loops reflecting their obligatory functions in remodeling the spatiotemporal genomic organization at HLBs during the G1 phase to accommodate histone gene expression in S phase.

overall_design: ChIP-seq for 5 histone modifications in 4 BRCA cell lines with 2+ replicates and matched inputs.

first: Gary

last: Stein

first: Prachi

last: Ghule

first: Seth

last: Frietze


title: Oral cancer metastatic gene expression profiling: Identification of novel potential biomarker

status: Public on Feb 01 2023

city: Changsha

first: Zaiye

last: Li

state: Hunan

address: Xiangya load 87. Changsha, China

institute: Xiangya hospital of Central South University

summary: The survival rate of Oral squamous cell carcinoma has been around 50% for several decades because of cancer metastasis. Aberrant long nonconding RNAs (lncRNAs) have been demonstrated to play a crucial role in carcinogenesis and tumor development of OSCC. However, the potential mechanism of metastasis of OSCC remains unclear. In this study, We screened 487 differentially expressed mRNAs (DEmRNAs) and 1507 differentially expressed lncRNAs (DElncRNAs) between OSCC with and without metastasis to construct their interaction network in cis and trans way.

overall_design: The next generation sequencing was perform on Illumina Hiseq 2500 platform. Totally, 10 samples including 5 T1-T2 patients with cervical lymph node (LN) metastasis and 5 T3-T4 patients without cervical LN metastasis were included.A total of 487 differentially expressed mRNAs (DEmRNAs) (319 up-regulated and 168 down-regulated) and 1507 differentially expressed lncRNAs (DElncRNAs) (971 up-regulated and 536 down-regulated) were identified in RNA-seq data. Subsequently, RT-qPCR was used to varify the accuracy of RNA-seq result.

first: C

last: Jiang

first: Z

first: N

first: Y

last: Yuan

first: J

first: L

last: Wu


title: Single cell sequencing of peripheral blood mononuclear cells and spleenocytes from 4 polytraumatized patients with splenectomy

status: Public on Jan 13 2023

city: Brisbane City

first: Namrata

last: Bhattacharya

state: Queensland

address: 2 George St

country: Australia

institute: Queensland University of Technology

summary: Our understanding of role of immune cells in the different immune compartments is incomplete. Here, we investigate the heterogeneity of immune celltypes in splenocytes, in contrast with already well-characterized PBMCs.

overall_design: We performed scRNA sequencing to understand the function of immune celltypes in the heterogeneous PBMC and spleen cells population. We combined this technology to CITE-sequencing to obtain measurement at the protein and transcriptome level and to HASH-sequencing in order to measure these data simultaneously in PBMC and spleen.

first: Jeremie

last: Poschmann

first: Debarka

last: Sengupta


title: Antiandrogen treatment induces mitochondrial oxidative phosphorylation to promote castration resistance in prostate cancer

status: Public on Jan 15 2023

city: Shanghai

first: Zehua

last: Ma

address: Pujian road 160

institute: Shanghai Jiaotong university

summary: Tumor recurrence and therapy resistance are generally accompanied by alterations in cellular metabolism. However, the mechanism by which metabolic conversion occurs and contributes to castration-resistant prostate cancer (CRPC) remains unclear. Here, we demonstrate that androgen receptor signaling inhibitors (ARSI)-induced mitochondrial oxidative phosphorylation (OXPHOS) is critical for CRPC development. Our findings indicate that prostate cancer cells exhibit increased mitochondrial OXPHOS following ARSI treatment; however, there is no significant change in glycolytic activity. Importantly, this metabolic conversion relies on increased glucose and glutamine utilization. Mechanistically, ARSI treatment induces oxidative stress, resulting in AMPK/PGC-1α-dependent metabolic conversion. High mitochondrial OXPHOS in turn renders prostate cancer cells resistant to ARSI. Pharmacological inhibition of mitochondrial OXPHOS shows promising treatment efficacy for CRPC and synergizes with ARSI to inhibit CRPC growth. Collectively, we demonstrate the metabolic plasticity of prostate cancer cells following ARSI treatment, identifying mitochondrial OXPHOS as a metabolic target for CRPC treatment.

overall_design: 1 CSPC sample and 3 CRPC samples; LNCaP-WT and LNCaP-ENZR cells

first: Kai

first: Chenggong

last: Luo

first: Heng

first: Tengda

last: Wang

first: Yong

last: Ban

first: Xuan

last: Liu

first: Lingyue

last: An

first: Guangheng


title: Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation [ATAC-SEq]

first: Robert

last: Blelloch

overall_design: ATAC-seq with WT cells in two different cuture conditions and two biological replicates cultured, collected, and prepared independently.

first: Ryan

last: Boileau


title: Loss of MLL3/4 decouples enhancer H3K4 monomethylation, H3K27 acetylation, and gene activation [CUT&RUN]

overall_design: CUT&RUN of four different cell lines in two different cuture conditions with two biological replicates cultured, collected, and prepared independently for H3K4m1 and a negative IgG control. Includes CUT&RUN for MLL4 for WT and DKO formative cells with two biological replicates cultured, collected, and prepared independently.


title: Transcriptomic data of Escherichia coli K-12 control and antibiotic-treated cultures

status: Public on Jan 21 2023

city: Orenburg

first: Alexander

middle: S

last: Balkin

address: 11 Pionerskaya st.

country: Russia

institute: Institute for Cellular and Intracellular Symbiosis

summary: Sequencing reads of Escherichia coli K-12 control and antibiotic-treated cultures enriched (Cappable-Seq) and not enriched (Ultra directional) for the 5’ end of primary transcripts.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: Mapping of transcription start sites (TSS) of Escherichia coli K-12 treated with various antibiotics. Evaluation of the correlation between the transcriptional activity of TSS and gene expression.


title: Bulk RNA sequencing of high- and low-functional connectivity glioblastomas

first: Abrar

last: Choudhury

summary: We report RNA sequencing of 7 glioblastomas, which are used to interrogate the biologic differences between high- and low-functional connectivity regions of the tumors.

overall_design: mRNA profiles of 7 glioblastoma samples from 5 patients. 3 samples were from high-connectivity regions, 4 samples were from low-connectivity regions.

first: Shawn

middle: L

last: Hervey-Jumper

first: Saritha

last: Krishna


title: CITEseq of lymphocytes from pancreatic lymph nodes, mesenteric lymph nodes, and spleen from 17 Human Pancreas Analysis Program (HPAP) donors

status: Public on Jan 03 2023

city: Philadelphia

first: Vincent

state: PA

address: 402 Johnson Pavilion

department: Microbiology

institute: University of Pennsylvania

summary: Type 1 diabetes (T1D) is caused by the autoimmune destruction of insulin-producing pancreatic beta cells, leading to life-long dependence on exogenous insulin. Profiling immune cells that infiltrate islets would be invaluable to understanding how beta cell destruction occurs. However, human pancreatic samples demonstrating active infiltration and beta cell destruction are rare. Alternatively, peri-pancreatic lymph nodes (pLNs) or other secondary lymphoid organs may harbor immune cells which participate in memory responses that drive T1D autoimmunity. To study the immune response throughout T1D onset and disease, lymphocytes from pLNs, mesenteric lymph nodes (mesLNs), and the spleen were collected from human T1D, auto-antibody positive (AAb+), and normal donors (NDs) enrolled in the Human Pancreas Analysis Program (HPAP). Tissue immune cell identity, phenotype, and transcriptional status was analyzed using Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITEseq). Lymphocytes from 17 pLN, 9 mesLN, and 15 spleen samples spanning 7 ND, 5 AAb+, and 7 T1D donors were thawed and processed through the CITEseq pipeline. 5 donors per disease group had a paired pLN and spleen sample, with 3 of the 5 donors having a paired mesLN sample, allowing for cross-tissue immune status comparison spanning multiple stages of disease onset. The dataset provides one of the first and largest CITEseq datasets on human AAb+ and T1D samples publicly available.

overall_design: All samples are human secondary lymphoid tissue mononuclear cells  acquired through the Human Pancreas Analysis Program (HPAP). The samples are derived from thawed mononuclear cells purified from either pancreatic lymph nodes (pLN), mesenteric lymph nodes (mesLNs), or the spleen. Samples from 7 normal (ND), 5 auto-antibody positive (AAb+), and 7 type 1 diabetic (T1D) donors are included in the dataset. All donors have 1 pLN sample, while 5 donors per group have a paired spleen sample. 3 of the 5 donors per group also have a paired mesLN sample. There are 45 total samples.

first: Gregory

last: Golden

first: Michael

last: Betts


title: Single-cell RNA sequencing of high- and low-functional connectivity glioblastomas

summary: We report single-cell RNA sequencing of 13,731 cells from 6 glioblastoma samples, which are used to analyze the biologic heterogeneity across functional connectivity regions.

overall_design: A total of 6 tissue samples from 3 glioblastoma patients were analyzed. Each patient had 2 tissue samples from their glioblastoma analyzed, one from a high-functional connectivity region and one from a low-functional connectivity region.


title: RNA pull-down analysis of hsa_circ_0001400 in 293T cells

status: Public on Dec 19 2022

city: Bethesda

first: Joseph

last: Ziegelbauer

state: MD

address: 10 Center Dr. 6N110

institute: NIH / National Cancer Institute

summary: 293T cells are transfected with hsa_circ_0001400 expression plasmid vectors for 24 hours. Cells are then incuvated with Psoralen, exposed to long-wave UV for 10 minutes, and total RNA was extracted. Biotynilated DNA oligos sense (control) or antisense of circ_0001400 are added and circRNA-RNA complexes are enriched using streptavidin beads. RNA was cleaned and exposed to short-wave UV and subjected for RNA-Seq.

overall_design: Triplicates of 293T cells are pulled-down for circ_0001400 using antisense DNA probes or control.

first: Takanobu

last: Tagawa


title: Transcriptome analysis of KSHV infected HUVECs after gain- and loss-of-function of hsa_circ_0001400

summary: Human umbilical vein endothelial cells are treated either with siRNA or lentivirus to manipulate hsa_circ_0001400 transcript levels. Cells are then infected with KSHV (BAC16) at MOI of 1 for 3 days until total RNAs were collected for RNA-Seq.

overall_design: Triplicates of HUVEC are treated with siRNA (negative control or circ_0001400 specific) or lentivirus (circGFP control or circ_0001400).


title: Thorough investigation of genes responsive to brassinosteroid in Arabidopsis

status: Public on Dec 15 2022

city: Tsukuba

first: Nobutaka

last: Mitsuda

state: Ibaraki

address: Central 6 Higashi 1-1-1

department: Bioproduction Research Institute

country: Japan

institute: National Institute of Advanced Industrial Science and Technology

summary: Genes responsive to brassinosteroid were fully investigated using bil1-1D/bzr1-1D mutant which shows constitutive/enhanced response to brassinosteroid. Bil1-1D plants and wild type were treated with Brz (brasinazole) followed with brassinolide or DMSO, respectively.

overall_design: bil1-1D plants and wild type were treated with Brz (brasinazole) followed with brassinolide or DMSO, respectively.

first: Takeshi

last: Nakano


title: PRO-cap from HCT116 (ENCSR273JQN)

status: Public on Dec 04 2022

city: Stanford

first: ENCODE

last: DCC

state: CA

address: 300 Pasteur Dr

institute: ENCODE DCC

summary:
A run-on assay that precisely maps the transcription start sites genome-wide with high sensitivity and specificity in SUPT16H_U.

For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf


title: Molecular basis of TPE-OLD [RNA-seq]

status: Public on Jan 05 2023

city: Marseille

first: Frederique

last: Magdinier

address: 27 Bvd Jean Moulin, Aix-Marseille Université. Faculté de Médecine. Campus La Timone

institute: Aix-Marseille Université - Marseille Medical Genetics

summary: Among epigenetic modifiers, telomeres, represent attractive modulators of the genome  in part through position effects. Telomere Position Effect – Over Long Distances (TPE-OLD)  modulates genes expression by changes in telomeric-dependent long-distance loops, with a  reach of 10Mb from the telomeres. However, TPE-OLD remain poorly defined. We used cells  with controlled telomere length combined to a genome wide approach revealing its  transcriptome and methylome. We identified a common cis element that behaved as an  insulator/ enhancer. By using reporter assays integrating this element, we disclosed additional  trans partners further validated by in silico data. Exploiting our cellular model we observed the  depletion of one candidate (RBPJ) at TPE-OLD associated loci concomitant to telomere  shortening. Therefore, we conclude that TPE-OLD is orchestrated by Alu-like elements acting  as enhancers in association with RBPJ. We propose that TPE-OLD functions by the  coordinated action of newly evolved enhancers; an associated protein RBPJ and telomere  length to produce an adapted response to external stimuli (i.e., Aging)

overall_design: Transcriptomic analysis Of Myoblasts and Myotubes with short and long telomeres

first: Raphael

last: Chevalier

first: Jérôme

last: Robin

first: Frédérique


title: Molecular basis of TPE-OLD [methylation]

overall_design: DNA methylation analysis Of Myoblasts, Myotubes and Fibroblasts with short and long telomeres

first: Raphaël

first: Magdinier

last: Frédérique


title: PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking (ChIP-Seq)

status: Public on Nov 09 2022

city: Martinsried

first: Jürg

last: Müller

state: Bavaria

address: Am Klopferspitz

institute: Max Planck Institute of Biochemistry

summary: The Polycomb repression machinery in Drosophila comprises PRC1 that monoubiquitinates histone H2A at lysine 118 (H2Aub1) and PR-DUB, a major H2Aub1 deubiquitinase, but how H2Aub1 levels must be balanced for Polycomb repression remains enigmatic.  We show that H2Aub1 is enriched at Polycomb target genes in early embryos but depleted from these genes during developmental stages when PRC1 represses their transcription.  Accordingly, Polycomb targets remain repressed in H2Aub1-deficient animals.  In PR-DUB catalytic mutants, high-level H2Aub1 accumulation at Polycomb targets increases chromatin accessibility, consistent with disruption of chromatin fiber folding by H2Aub1 in vitro.  Consequently, PR-DUB mutants show defective Polycomb repression, while general transcription is largely unperturbed by the genome-wide, low-level H2Aub1 increase.  Changes in H2Aub1 levels alter H3K27 methylation-kinetics but PRC2 nevertheless generates canonical H3K27me3 domains in PRC1 or PR-DUB catalytic mutants.  PR-DUB therefore acts as a rheostat that removes excessive H2Aub1 that, though deposited by PRC1, antagonizes PRC1-mediated chromatin compaction.

overall_design: Analyses of ChIP-seq profiles generated from wild-type and mutant animals at different stages of the Drosophila development.

first: Jacques

last: Bonnet


title: Multiplatform Analysis of Primary and Metastatic Breast Tumors from the AURORA US Network identifies microenvironment and epigenetics differences as drivers of metastasis [RNA-Seq]

city: Pittsburgh

first: Uma

last: Chandran

address: 5150 Center Ave

department: BioMedical Informatics

institute: University of Pittsburgh

summary: Patients with metastatic breast cancer (MBC) typically have short survival times and their successful treatment represents one of the most challenging aspects of patient care. This poor prognostic behavior is in part due to molecular features including increased tumor cell clonal heterogeneity, multiple drug resistance mechanisms, and alterations of the tumor microenvironment. The AURORA US Metastasis Project was established with the goal to identify molecular features specifically associated with metastasis. We therefore collected and molecularly characterized specimens from 55 metastatic breast cancer (BC) patients representing 51 primary cancers and 102 metastases. The 153 unique tumors were assayed using RNAseq, tumor/germline DNA exomes and low pass whole genome sequencing, and global DNA methylation microarrays. We found intrinsic molecular subtype differences between primary tumors and their matched metastases to be rare in triple negative breast cancer (TNBC)/Basal-like subtype tumors. Conversely, tumor subtype changes were relatively frequent in estrogen receptor positive (ER+) cancers where ~30% of Luminal A cases switched to Luminal B or HER2-enriched (HER2E) subtypes. Clonal evolution studies identified changes in expression subtype coincident with DNA clonality shifts, especially involving HER2 amplification and/or the HER2E expression subtype. In contrast, we found remarkable conservation of cancer-associated DNA hypermethylation profiles within primary tumor-metastasis pairs. We further found evidence for ER-mediated downregulation of genes involved in cell-cell adhesion in metastases. Microenvironment differences varied according to tumor subtype where ER+/Luminal metastases had lower fibroblast and endothelial cell content, while TNBC/Basal-like metastases showed a dramatic decrease in B cells and T cells. In 17% of metastatic tumors, we identified DNA hypermethylation and/or focal DNA deletions near HLA-A that were associated with its significantly reduced expression, and with lower immune cell infiltrates. We also identified low immune cell features in brain and liver metastases when compared to other metastatic sites, even within the same patient. These findings have implications for the treatment of metastatic breast cancer patients with immune- and HER2-targeting therapies and suggest potential novel therapeutic avenues for the improvement of outcomes for some patients with MBC

overall_design:
Comparative gene expression profiling analysis of RNA-seq data of breast primary and matched metastatic tumors
NOTE FROM THE SUBMITTER: the raw files (BAMs) which will be submitted to dbGAP

first: Susana

last: Garcia-Recio

first: Toshinori

last: Hinoue

last: Wheeler

first: Benjamin

last: Kelly

first: Ana

last: Garrido-Castro

first: Tomas

last: Pascual

first: Aguirre

middle: A

last: De Cubas

first: Youli

last: Xia

first: Brooke

last: Felsheim

first: Marni

middle: B

last: McClure

first: Andrei

last: Rajkovic

first: Ezgi

last: Karaesmen

first: Markia

last: Smith

first: Cheng

last: Fan

first: Paula

middle: I

last: Gonzalez Ericsson

first: Melinda

middle: E

last: Sanders

first: Chad

last: Creighton

first: Jay

last: Bowen

first: Kristen

last: Leraas

first: Robyn

last: Burns

first: Sara

last: Coppens

first: Amy

last: Wheless

first: Salma

last: Rezk

last: Garrett

first: Joel

last: Parker

first: Kelly

last: Foy

first: Hui

last: Shen

first: Ben

last: Park

first: Ian

last: Krop

first: Carey

last: Anders

first: Julie

last: Gastier-Foster

first: Mothaffar

last: Rimawi

first: Rita

last: Nanda

first: Nancy

middle: U

last: Lin

first: Claudine

last: Isaacs

first: P

last: Kelly Marcom

first: Anna

last: Maria Storniolo


title: Multiplatform Analysis of Primary and Metastatic Breast Tumors from the AURORA US Network identifies microenvironment and epigenetics differences as drivers of metastasis

first: Uma

last: Chandran

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

overall_design: Refer to individual Series


title: Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome (RNA-Seq II)

status: Public on Oct 14 2022

city: Ramat Gan

first: Nissan

last: Yissachar

address: Bar-Ilan University

country: Israel

institute: Bar-Ilan University

summary: Changes in microbiome composition have been associated with a wide array of human diseases, turning the human microbiota into an attractive target for therapeutic intervention. Yet clinical translation of these findings requires the establishment of causative connections between specific microbial taxa and their functional impact on host tissues. Here, we infused gut organ cultures with longitudinal microbiota samples collected from therapy-naïve irritable bowel syndrome (IBS) patients under low-FODMAP (fermentable Oligo-, Di-, Mono-saccharides and Polyols) diet. We show that post-diet microbiota regulates intestinal expression of inflammatory and neuro-muscular gene-sets. Specifically, we identify Bifidobacterium adolescentis as a diet-sensitive pathobiont that alters tight junction integrity and disrupts gut barrier functions. Collectively, we present a unique pathway discovery approach for mechanistic dissection and identification of functional diet-host-microbiota modules. Our data support the hypothesis that the gut microbiota mediates the beneficial effects of low-FODMAP diet and reinforce the potential feasibility of microbiome based-therapies in IBS.

overall_design: For transcriptional profiling of B. adolescentis we infused  B. adolescentis  into the lumen of colon organ cultures for 2h, compared with tissues infused with sterile medium as an internal control. To characterize immediate-early gene expression, bulk RNA sequencing was performed on whole-tissue colon samples at 2h post-stimulation.

first: Hadar

last: Bootz-Maoz

first: Ayelet

last: Pearl

first: Ehud

last: Melzer

first: Stephen

last: Malnick

first: Efrat

last: Sharon

first: Yifat

last: Bennet

first: Rotem

last: Tsentsarevsky

first: Shlomi

last: Abuchatzera

first: Sivan

last: Amidror

first: Elana

last: Aretz

first: Shalhevet

last: Azriel

first: Chen

last: Gam Ze Letova

first: Maria

last: Naama

first: Irit

last: Shoval

first: Orly

last: Yaron

first: Sarit

last: Karako-Lampert

first: Shai

last: Bel


title: Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome

first: Nissan

last: Yissachar

sample_organism:
Mus musculus
human gut metagenome

platform_organism:
Mus musculus
human gut metagenome


title: circRNA microarray of the Epstein-Barr virus positive Burkitt's lymphoma cell line Akata

first: Joseph

middle: M

last: Ziegelbauer

summary: Epstein-Barr virus positive Burkitt's lymphoma cell line Akata (+) and it's EBV-depleted subclone Akata (-) were analyzed for human circRNA expression.

overall_design: Akata cell lines were incubated at stable condition. During log phase of growth, total RNAs were extracted and subjected tor Arraystar circRNA microarray v2.

first: Takanobu

last: Tagawa


title: Kaposi's sarcoma herpesvirus induces host circular RNAs and maintain latent infection


title: Structural adaptations of epidermal stem cells to mechanical stress

status: Public on Nov 10 2022

first: Brian

middle: C.

last: Capell

address: 421 Curie Boulevard Biomedical Research Building 1020 Biomedical Research Building 1020

department: Dermatology

summary: To elucidate the cellular mechanisms of keratinocytes in response to an acute mechanical force

overall_design:
p63CreER; Piezo1fl/fl ; R26-mTmG (Piezo1 cKO) mice were administered tamoxifen injections (3 times, 20ug/dose) at P45-P52 to activate cre recombination and delete Piezo1 gene expression in basal layer keratinocytes. Basal epidermal cells were isolated from Piezo1 cKO and control mouse back skin using flow sorting.

On Monday June 16, all processed and raw data files were replaced.

first: Sijia

last: Huang

first: Paola

last: Kuri

first: Jonathan

last: Zou

first: Maxwell

last: Marshall

first: Gabriella

last: Rice

first: Stephen

last: Prouty

first: Tzvete

last: Dentchev

first: Miriam

last: Doepner

first: Joel

last: Boerckel

middle: C

first: Todd

middle: W

last: Ridky

first: Pantelis

last: Rompolas


title: Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade [in vitro]

status: Public on Oct 09 2022

city: St Louis

first: David

last: DeNardo

email: varintra@wustl.edu, ddenardo@wustl.edu

address: 425 S Euclid Ave

institute: Washington University in St. Louis

summary: The effect of radiation therapy (RT) on tumor immunity in PDAC is not well understood. To better understand if RT can prime antigen-specific T cell responses, we analyzed human PDAC tissues and PDAC GEMMs. In both settings, we found little to support evidence of RT-induced T cell priming. Using in-vitro systems, we found tumor stromal components, including fibroblasts and collagen, synergize to both blunt RT efficacy and impair RT-induced interferon signaling. Focal Adhesion Kinase (FAK) inhibition rescued RT efficacy in-vitro and in-vivo, leading to tumor regression, T cell priming, and enhanced long-term survival in PDAC mouse models. Based on these data, we initiated a clinical trial of VS-6063 in combination with SBRT in PDAC patients (NCT04331041). Analysis of PDAC tissues from these patients showed stromal reprogramming mirroring our findings in GEMMs. Finally, the addition of checkpoint immunotherapy to RT and FAKi in animal models led to complete tumor regression and long-term survival.

overall_design: Examination of pancreatic cancer 3D organoid cell lines with different treatment conditions

middle: G

first: Varintra

last: Lander


title: Glis1 and oxaloacetate in nucleus pulposus stromal cell somatic reprogramming and survival

status: Public on Oct 28 2022

city: Potsdam

first: Petra

last: Kraus

state: NY

address: 8 Clarkson Avenue

department: Biology

country: Uruguay

institute: Clarkson University

summary: transcription factor Glis1 and metabolite oxaloacetic acid (OAA) could provide NP cells with survival tools for the harsh niche conditions in the IVD.

overall_design: We assessed adipose and IVD tissue-derived stromal cells through in vitro transcriptome analysis in 2D and 3D culture

first: Thomas

last: Lufkin


title: PR-DUB preserves Polycomb repression by preventing excessive accumulation of H2Aub1, an antagonist of nucleosome stacking

first: Jürg

last: Müller


title: Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome (RNA-Seq I)

first: Nissan

last: Yissachar

overall_design: Gut organ cultures were infused ex vivo with fecal samples collected from the first 3 patients that successfully completed the clinical phase (and exhibited positive clinical response), pre- and following 6 weeks of diet, at equivalent bacterial loads (107 CFUs/mL; Fig. S2A-B) (n=3 patients, pre- and post-diet, in duplicates, for a total of 12 samples).

first: Hadar

last: Bootz-Maoz

first: Ayelet

last: Pearl

first: Ehud

last: Melzer

last: Malnick

first: Efrat

last: Sharon

first: Yifat

last: Bennet

first: Rotem

last: Tsentsarevsky

first: Shlomi

last: Abuchatzera

first: Sivan

last: Amidror

first: Elana

last: Aretz

first: Shalhevet

last: Azriel

first: Chen

last: Gam Ze Letova

first: Maria

last: Naama

first: Irit

last: Shoval

first: Orly

last: Yaron

first: Sarit

last: Karako-Lampert

first: Shai

last: Bel


title: Diet-induced modifications to human microbiome reshape colonic homeostasis in irritable bowel syndrome (16S)

first: Nissan

last: Yissachar

overall_design: Gut microbiome composition was analyzed by 16S rRNA gene sequencing of IBS patients’ fecal samples collected at 0, 3 and 6 weeks under low-FODMAP diet.

last: Bootz-Maoz

first: Stephen


title: Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade [exp2]

first: David

last: DeNardo

overall_design: Examination of PDAC tissue biopsies through fine needle aspiration (FNA) from pre- and post-treatment patients treated with the combination of SBRT and FAK inhibitor

first: Varintra

last: Lander


title: Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade [scRNA seq data from mice]

overall_design: Examination of CD45+ and CAF-enriched FACS-sorted subsets in PDAC tissue from different treatment groups