title: Transcriptional effects of siRNA-mediated MAF and MAFB  knockdown on IVIg treatment and TLR7 activation of M-CSF-derived macrophages

city: Madrid

first: Angeles

last: Domínguez Soto

address: Ramiro de Maeztu

country: Spain

institute: CSIC

summary: Analysis of the role of MAF and MAFB on the transcriptional signature of TLR7-activated human M-CSF-dependent monocyte-derived macrophages.   Methods: Human Peripheral Blood Mononuclear Cells (PBMC) were isolated from buffy coats from donors over a Lymphoprep gradient according to standard procedures. Monocytes were purified from PBMC by magnetic cell sorting using anti-CD14 microbeads (>95% CD14+ cells). Monocytes from three independent donors (0.5 x 106 cells/ml, >95% CD14+ cells) were cultured  in RPMI 1640 supplemented with 10% fetal bovine serum (FBS) at 37°C in a humidified atmosphere with 5% CO2 and 21% O2 for 6 days in the presence of 1000 U/ml M-CSF, with cytokine addition every two days. Then, monocyte-derived macrophages were transfected with MAF and MAFB-specific siRNA or control siRNA, kept in culture for 24 hours, and then stimulated (or not) with IVIg (10mg/ml) and the TLR7 ligand CL264 (1 microgram/ml). After 4 and 12 hours, cells were lysed and RNA isolated for transcriptional analysis.

overall_design: mRNA profiles of human M-CSF-derived macrophages treated with IVIg and the TLR7 ligand CL264 after downregulation of MAF and MAFB expession

first: Miriam

last: Simón Fuentes

first: Ángeles

first: Miguel

last: Vega

first: Angel

last: Corbí


title: Hippo pathway component WWC1 is a key regulator of apoptosis and photosensitivity in lupus keratinocytes

status: Public on Jul 06 2023

city: Pittsburgh

first: Amr

last: Sawalha

state: PA

address: 4401 Penn Avenue

country: USA

institute: University of Pittsburgh

summary: Skin inflammation and photosensitivity are common manifestations of cutaneous and systemic lupus erythematosus (SLE), yet the underlying mechanisms are poorly understood. Non-lesional SLE skin exhibits increased UVB-driven cell death that persists in culture, supporting a potential role for epigenetic modifications to sustain this phenotype. We thus examined differential DNA methylation of non-lesional SLE vs. healthy control keratinocytes (KC) and identified Hippo signaling as the top significantly differentially methylated pathway, likely driven by hypomethylation of WWC1, a scaffold protein and Hippo pathway regulator. Analysis of non-lesional SLE skin biopsies and SLE keratinocytes in culture confirmed WWC1 overexpression that led to enhanced phosphorylation of YAP resulting in a pro-apoptotic transcriptional profile reflective of decreased YAP/TEAD transcriptional coactivation. Functional studies of UV-mediated apoptosis confirmed a regulatory role for YAP/TEAD interactions, and blockade of overactive Hippo signaling via a LATS1/2 inhibitor abrogated enhanced apoptosis in SLE KCs. Thus, our work identifies a novel mechanistic paradigm in SLE KCs in which aberrant UVB-apoptosis is driven by Hippo signaling via promotion of YAP phosphorylation and restriction of YAP coactivation of TEAD transcriptional activity. Hippo modulation may be a novel target for photosensitivity in SLE and CLE.

overall_design: The study cohort consisted of DNA methylation profiles of primary keratinocytes isolated from skin biopsies of six systemic lupus erythematosus patients with a history of cutaneous lupus erythematosus and six matched healthy controls at the University of Michigan Lupus Cohort. Participants were matched by age (±5 years), sex, and race/ethnicity.

middle: H

first: Patrick

last: Coit


title: Tissue-Engineered Disease Modeling of Lymphangioleiomyomatosis Exposes a Therapeutic Vulnerability to HDAC Inhibition

city: Ottawa

first: Theodore

last: Perkins

state: ON

address: 501 Smyth Rd.

department: Cellular and Molecular Medicine

country: Canada

institute: Ottawa Hospital Research Institute

type: Expression profiling by high throughput sequencing

summary:
Lymphangioleiomyomatosis (LAM) is a rare disease involving cystic lung
destruction by invasive LAM cells. These cells harbor loss-of-function
mutations in TSC2, conferring hyperactive mTORC1 signaling. Here, tissue
engineering tools are employed to model LAM and identify new therapeutic
candidates. Biomimetic hydrogel culture of LAM cells is found to recapitulate
the molecular and phenotypic characteristics of human disease more faithfully
than culture on plastic. A 3D drug screen is conducted, identifying histone
deacetylase (HDAC) inhibitors as anti-invasive agents that are also selectively
cytotoxic toward TSC2−/− cells. The anti-invasive effects of HDAC inhibitors
are independent of genotype, while selective cell death is mTORC1-dependent
and mediated by apoptosis. Genotype-selective cytotoxicity is seen exclusively
in hydrogel culture due to potentiated differential mTORC1 signaling, a
feature that is abrogated in cell culture on plastic. Importantly, HDAC
inhibitors block invasion and selectively eradicate LAM cells in vivo in
zebrafish xenografts. These findings demonstrate that tissue-engineered
disease modeling exposes a physiologically relevant therapeutic vulnerability
that would be otherwise missed by conventional culture on plastic. This work
substantiates HDAC inhibitors as possible therapeutic candidates for the
treatment of patients with LAM and requires further study.

overall_design: RNA profiling of WT and TSC2-/- teratoma-derived smooth muscle cells, on hydrogel and plastic, with or without rapamycin, two replicates each.

first: Adam

last: Pietrobon

first: William

middle: L

last: Stanford


title: Cdk4-E2F3 signals enhance skeletal muscle oxidative function and improve whole  body metabolism

city: Bethesda

first: WeiPing

last: Chen

state: MD

address: Bldg 8, Room 1A11, NIDDK/NIH

department: GCL

institute: NIDDK/NIH

summary: Skeletal muscle insulin resistance and β-cell dysfunction are signature features of type  2 diabetes (T2D) pathogenesis. We previously demonstrated a pivotal role for the cell  cycle kinase, Cdk4, in regulation of β-cell mass. Here, we demonstrate that Cdk4R/R  mice, which harbor constitutively active Cdk4 kinase, are resistant to obesity and  diabetes. The metabolic protection is associated with Cdk4 promoting the numbers and  regeneration potential of slow/oxidative muscle fibers, improved muscle mitochondrial  bioenergetics and elevated E2F3 and PGC-1α expression in muscle. In contrast,  muscle-specific E2F3 knockout mice exhibit poor exercise capacity and susceptibility  to obesity and diabetes. Exercise induces levels of Cdk4/E2F3/PGC-1α, while those  levels are suppressed in obesity. Also, levels of E2F3/PGC-1α negatively correlate with  adiposity, insulin resistance and lipid accumulation in human muscle biopsies. These  findings are supportive of an important role for Cdk4/E2F3 in muscle fiber type  development and metabolism with therapeutic potential for metabolic and muscular  diseases.

overall_design: Identification of genes expressed in Control vs. Mutant (Cdk4-E2F3) mice fed with two levels of fat (RD, HFD) with three replications per group.

first: Hariom

last: Yadav

first: Young

middle: J

last: Bahn

first: Oksana

last: Gavrilova

first: Danielle

last: Springer

first: Michele

middle: D

last: Allen

first: Brent

last: Abel

first: Ioannis

last: Papazoglou

first: Patricia

last: Zerfas

first: Weiping

first: Ronald

last: Ouwerkerk

first: Ahmed

middle: M

last: Gharib

first: Monica

last: Skarulis

first: Alexandra

middle: C

last: McPherron

first: Sushil

last: Rane


title: Changes in Physiology of Burley Tobacco Plants Genetically Engineered to Express a Functional NtEGY2 Gene

status: Public on Jul 05 2023

city: Raleigh

first: Ramsey

last: Lewis

state: NC

address: 101 Derieux PI

department: Crop and Soil Sciences Department

institute: North Carolina State University

summary: Nitrogen physiology is important in tobacco because of its role in generation of leaf yield and accumulation of nitrogen-containing alkaloids and that can react with nitrosating agents in the formation of carcinogenic tobacco specific nitrosamines. Cultivars of the burley tobacco market class are homozygous for deleterious alleles at the duplicate Yb1 and Yb2 loci which have previously been associated with decreased nitrogen use and utilization efficiency,; increased leaf nitrate, total nitrogen, and alkaloid levels,; and reduced yields. How mutant alleles at these two loci affect these traits is not well understood. Recent identification of the Yb1 and Yb2 genes enabled overexpression of the wild-type Yb1 allele in yb1yb1yb2yb2 plants to determine if observed unfavorable effects were due to linkage or pleiotropy, and to determine if overexpression could lead to beneficial modifications in any of these traits in transgenic plants relative to naturally-occurring wild-type genotypes. Yb1 overexpression was found to confer an agronomic benefit to yb1yb1yb2yb2 genotypes but no advantage to wild-type genotypes. RNA-Seq was used to carry out a comparative transcriptome analyses of genetically engineered and wild-type NILs to gain insight on metabolic pathways affecting carbon and nitrogen metabolism that might be altered as the result of genetic variability at the Yb1 and Yb2 loci. Results indicate that complex changes in the transcriptome of tobacco can be manifested by altered expression of Yb1.

first: Rui

last: Shi


title: HER3 targeting augments the efficacy of panobinostat in claudin-low triple-negative breast cancer cells

city: new orleans

first: Hui

last: Lyu

state: LA

address: 1700 Tulane Ave

institute: LSU

summary: Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used to test the in vivo antitumor activity of panobinostat alone or its combinations with gefitinib, an EGFR-tyrosine kinase inhibitor (TKI). Panobinostat potently inhibited proliferation and induced apoptosis in all TNBC cells tested. However, in CL TNBC cells, this HDAC inhibitor markedly enhanced expression of HER3, which interacted with EGFR to activate both receptors and Akt signaling pathways. Combinations of panobinostat and gefitinib synergistically suppressed CL TNBC cell proliferation and promoted apoptosis in vitro and in vivo. Upregulation of HER3 compromises the efficacy of panobinostat in CL TNBC. Inactivation of HER3 combined with panobinostat represents a practical approach to combat CL TNBC.

overall_design: The RNA sequence raw data in this study pertains to TNBC cell line MDA-MB231 and focuses on investigating adaptive gene expression changes upon treatment with panobinostat. The raw data files are in BAM format and are identified with sample labels (e.g., S1, S2) and corresponding experimental conditions (e.g., MDA231_P0, MDA231_P50). Each experimental condition was independently repeated three times. The data was generated using the Illumina HiSeq platform utilizing sequencing-by-synthesis technology.


title: DENND1A Desensitizes Granulosa Cells to FSH by Arresting Intracellular FSHR Transportation

city: Jinan

first: Rusong

last: Zhao

state: Shandong

address: 44 Wenhua xi Road

department: Center for Reproductive Medicine

country: China

institute: Shandong University

summary: Genome-wide association studies (GWAS) have identified polycystic ovary syndrome (PCOS)-associated loci, including DENND1A encoding a clathrin-binding protein involved in vesicle transport as a guanine nucleotide exchange factor. The effect of DENND1A on reproduction and whether it participates in follicle development disorder and androgen synthesis in PCOS remain unknown. Here, we demonstrated that DENND1A expression increased in ovarian granulosa cells (GCs) of PCOS patients and was positively correlated with serum testosterone concentration. We constructed a systemic transgenic Dennd1a mouse (TG mouse) model, which showed subfertility, irregular estrous cycles, and increased production of testosterone after PMSG stimulation. Moreover, TG mice showed hyporesponsiveness to PMSG with smaller ovary size and less well-developed follicles. Intracellular follicle-stimulating hormone receptor (FSHR) transport was disturbed by overexpression of Dennd1a, which promoted FSHR internalization and inhibited its recycling. Our findings revealed the reproductive function of DENND1A and the underlying mechanisms, which provided new insights into the PCOS pathogenesis and contributing to drug design for PCOS treatment.

overall_design: In our study it was shown that a markedly FSH insensitivity is responsible for low fertility in Dennd1a transgenic mouse compared to wild type mouse. Ovaries from 3 animals of the wild type and transgenic mouse were respectively collected at the injection of 44 hours of PMSG and processed for mRNA-seq analysis.

first: Yunde

last: Dou

first: Han

first: Shigang


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [7F, 7G, 7H, 7J]

city: La Jolla

first: Joseph

middle: R

last: Ecker

state: CA

address: 10010 North Torrey Pines Road

department: Genomic Analysis Laboratory

institute: HHMI-Salk-Institute

type: Methylation profiling by high throughput sequencing

summary: Illustrating the cellular architecture of the mammalian brain is critical to understanding its diverse functions and complex animal behaviors. With support from NIMH and NINDS as part of the BRAIN Initiative Cell Census Network (BICCN), the Center for Epigenomics of the Mouse Brain Atlas (CEMBA) applied single nucleus methylation sequencing in 117 brain funtional regions across the whole adult male P56 C57BL/6J mouse brain. In each major brain regions, we identified distinct cell clusters and formed them in a hierarchical taxonomy. These clusters include known primary brain cell types and possible sub-types. We use these data to identify the epigenomic characteristics and to define specific regulatory elements for each cell cluster. We integrate the single cell methylome with single cell gene expression and chromatin accessibility profiles from the same brain region to further identify potential enhancers and their corresponding genes for several neuronal cell types. By brain region spacial comparisons, we found spatial specificity among excitatory neuronal clusters within the same cortical layer. We identify brain-region-specific transcription factors that may regulate cortical region development of excitatory neurons. These data define the landscape of cell type and spatial heterogeneity in the mouse brain and the underlining regulatory epigenomic basis.

overall_design: Apply snmC-seq2 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (7F_200728, 7G_190702, 7G_190709, 7H_200820, 7H_200827, 7J_200305).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

middle: K

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

middle: G

last: Castanon

last: Nery

first: Peter

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: Jesse

last: Dixon

first: M

last: Behrens


title: Transcriptional circuits that regulate early T cell precursor acute leukemia (RNA-seq)

city: New York

first: Bettina

last: Nadorp

state: NY

address: 500 1st Ave

department: Medicine/Pathology

institute: NYU Langone Health

summary: The discovery of early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) was based on expression of stem cell genes that are characteristic of mouse ETP cells, the most primitive multipotent cells in the thymus. Using complementary mouse and human genetic models and genome-wide expression and chromatin profiling integrated with 3D chromatin mapping, we show that the PIAS-like coactivator ZMIZ1 promotes immature T-ALL proliferation by recruiting the transcription factor MYB in feedforward circuits to cooperatively induce MYCN, MEF2C, and BCL2, which were recently associated with the high-risk bone marrow progenitor (BMP-like) subset.

overall_design: Primary samples and prototypical cell lines of T cell acute lymphoblastic leukemia (T-ALL) and early T cell precursor leukemia (ETP-ALL) were collected and analyzed

first: Francesco

last: Boccalatte

first: Javier

last: Rodriguez-Hernaez

first: Giovanni

last: Gambi

first: Ioannis

last: Aifantis

first: Aristotelis

last: Tsirigos


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [18A, 18B, 6E, 6F]

first: Joseph

last: Ecker

overall_design: Apply snmC-seq2 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (18A_210107, 18A_210610, 18A_210617, 18B_210422, 18B_210429, 6E_190718, 6E_190723, 6F_200723).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

last: Lucero


title: Gene expression profile of macrophages of monocytic origin and Kupffer cells under conditions of co-cultivation with Ito cells, endotheliocytes of sinusoidal capillaries of the liver and HGF.

city: Moscow

first: Polina

last: Vishnyakova

address: Oparina 4

country: Russia

institute: National Medical Research Center for Obstetrics, Gynecology and Perinatology

summary:
The aim of the work was to study the expression profile of Kupffer cells and macrophages of monocytic origin under conditions of co-cultivation with Ito cells, endotheliocytes of sinusoidal capillaries of the liver and HGF. To test the hypothesis that it is the microenvironment that forms the specific phenotype of resident organ macrophages.
We used microarrays for comparison of Kupffer cells and  macrophages of monocytic origin gene expression on different time periods of cocultivation with Ito cells, endotheliocytes of sinusoidal capillaries of the liver and HGF.

overall_design: Kupffer cells were obtained by magnetic sorting from the liver of Balbc male mice by the F4/80 antigen, and monocytes from the blood of the same mice by the CD115 marker. Next, the cells were preliminarily cultured for a 1 day with MCSF. Next, monocytic macrophages and Kupffer cells were co-cultivated for 1 or 3 days with Ito cells or sinusoidal endotheliocytes or HGF. Macrophages of monocytic origin or Kupffer cells that continued to be cultivated for 1 or 3 days in a medium containing MCSF served as controls. At the end of the required period, RNA was extracted from the cells, which was used for transcriptome analysis.

first: Maria

last: Kuznetsova


title: Transcriptome analysis reveals that auxin promotes strigolactone-induced adventitious root growth in the hypocotyl of melon seedlings

city: Baoding

first: li

middle: jing

last: rui

address: lekainan Street

institute: HeBei Agricultural University

summary: Strigolactone (SL) and auxin are two important phytohormones involved in plant root development, but whether they show synergistic or mutual promotion effects during adventitious root (AR) formation has not been adequately explored.

overall_design: In this study, we investigated the mechanisms of GR24 (synthetic SL)and indole-3-acetic acid (IAA; a type of auxin) in the formation of ARs using melon as the study material

first: Jingrui

last: Li

first: Mi

last: Fan

first: Qinqin

last: Zhang

first: Guiyun

last: Lu

first: Xiaolei

last: Wu

first: Binbin

last: Gong

first: Yubo

last: Wang

first: Ying

first: Hongbo

last: Gao


title: A structured evaluation of cryopreservation in generating single cell transcriptomic from cerebrospinal fluid

first: Philip

last: De Jager

department: Neurology

institute: Columbia University Medical Center

summary: Recent advances in single-cell transcriptomics now allow characterization of CSF cells at an unprecedented scale and precision. With the availability of different single cell technologies with which to characterize CSF cells, there is a need for a simple yet robust protocol to cryopreserve CSF cells. In this study, we report a reliable cryopreservation protocol adapted for CSF cells that facilitates the characterization of these rare, fragile cells in moderate to large scale studies. To establish this protocol, excess CSF was collected following diagnostic lumbar punctures in twenty-one patients at two independent sites, and CSF cells were isolated. Each cell sample was split into two fractions for single cell analysis using one of two possible chemistries: 3’ sc-RNA-Sequencing or 5’sc-RNA-Sequencing. One cell fraction was processed fresh while the second sample was cryopreserved and profiled at a later time after thawing. B and T cell receptor sequencing were performed in a subset of samples. Our comparison of fresh and cryopreserved data from the same individuals demonstrates highly efficient recovery of all known CSF cell types. The proportion of all cell types was similar between the fresh and the cryopreserved cells processed, and cellular transcriptomes were not significantly different. Results were comparable at both performance sites and with different single cell sequencing chemistries. Cryopreservation also did not affect recovery of T and B cell clonotype diversity. Hence, our cryopreservation protocol for CSF cells provides an important alternative to fresh processing of fragile CSF cells which is also resource-intensive: cryopreservation enables the involvement of research sites with limited capacity for experimental manipulation and reduces technical variation by enabling batch processing and pooling of samples. sequencing (scRNA-seq) to analyze the diversity of GCs in the intestine.

overall_design: Using sc-RNA-Seq we analyzed 44 individual CSF-cell samples from a total of 21 patients affected by other neuroimmunological diseases, migraine and others. Each sample was split into two fractions, one fresh and one fraction was cryopreserved and further thawed prior analysis, except for two CSF samples that were split into 3 fractions (2 fresh and 1 cryopreserved).

first: Hanane

last: Touil

first: Tina

last: Roostaei

first: Daniela

last: Calini

first: Claudiu

last: Diaconu

first: Samantha

last: Epstein

first: Catarina

last: Raposo

first: Kaho

last: Onomichi

first: Kiran

middle: T

last: Thakur

first: Licinio

last: Craveiro

first: Ilaria

last: Callegari

first: Julien

last: Bryois

first: Claire

middle: S

last: Riley

first: Vilas

last: Menon

first: Tobias

last: Derfuss

first: Dheeraj

last: Malhotra


title: The NAC transcription factors SNAP1/2/3/4 are central regulators mediating high nitrogen responses in mature nodules of soybean

city: Guangzhou

first: Xin

last: Wang

address: waihuanxi road

institute: Guangzhou University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Legumes can utilize atmospheric nitrogen via symbiotic nitrogen fixation, but this process is inhibited by high soil inorganic nitrogen. So far, how high nitrogen inhibits N2 fixation in mature nodules is still poorly understood. Here we construct a co-expression network in soybean nodule and find that a dynamic and reversible transcriptional network underlies the high N inhibition of N2 fixation. Intriguingly, several NAC transcription factors (TFs), designated as Soybean Nitrogen Associated NAPs (SNAPs), are amongst the most connected hub TFs. The nodules of snap1/2/3/4 quadruple mutants show less sensitivity to the high N inhibition of nitrogenase activity and acceleration of senescence. Integrative analysis shows that these SNAP TFs largely influence the high N transcriptional response through direct regulation of a subnetwork of senescence-associated genes and transcriptional regulators. We propose that the SNAP-mediated transcriptional network may trigger nodule senescence in response to high N.

overall_design: Chromatin immunoprecipitation sequencing (ChIP-seq) for four SNAP genes with soybean root nodule tissues.

first: Yuefeng

last: Guan

first: Peitao

last: Lü


title: Circadian rhythm does not affect the miRNA cargo of bovine raw milk extracellular vesicles

city: Zurich

first: Maria

middle: Desemparats

last: Saenz-de-Juano

address: Universitatstrasse 2

country: Switzerland

institute: ETH Zurich

type: Non-coding RNA profiling by high throughput sequencing

summary: Extracellular vesicles (EVs) and their microRNA (miRNA) cargo have been suggested as potential biomarkers for mammary gland health in cattle. However, milk is a dynamic fluid, and its biologically active components, including miRNAs, could be subject to changes throughout the day. The current study aimed to evaluate the circadian fluctuation of milk EVs miRNA cargo to assess the feasibility of milk EVs as future biomarkers for mammary gland health management. Milk from four healthy dairy cows was collected manually from one quarter during four consecutive days in the two daily milking sessions in the morning and the afternoon. The SCC was determined, and the milk EVs were isolated from skimmed milk. The presence of EVs was confirmed by transmission electron microscopy (TEM), tunable resistive pulse sensing (TRPS), and western blot (WB). Small RNA libraries were produced from 10 ng of extracted RNA and sequenced in two lanes of a HiSeq2500. The heterogeneity and integrity of EVs and the protein EV markers CD9, CD81, and TSG101 were confirmed by TEM and WB. The sequencing revealed that despite daily fluctuation in other milk components, like the somatic cells during milking sessions, the miRNA cargo abundance in milk EVs stayed constant. Our results show that the miRNA cargo of milk EVs is very stable regardless of the hour of the day, supporting their potential use as diagnostic markers for mammary gland health.

overall_design: 28 samples: 14 Morning, 14 Evening

first: Giulia

last: Silvestrelli

first: Susanne

middle: E

last: Ulbrich


title: A novel type of monocytic leukemia stem cell revealed by the clinical use of venetoclax-based therapy

city: Aurora

first: Austin

last: Gillen

state: CO

address: 12801 East 17th Avenue

institute: University of Colorado Anschutz Medical Campus

summary: Acute Myeloid Leukemia (AML) is a heterogeneous disease on both inter- and intra-patient levels. In many patients, relapse is driven by a relatively small pool of Leukemia Stem Cells (LSCs) that are able to resist therapeutic perturbation and drive proliferation of the malignant AML blast pool. Due to the low frequency of LSCs and high degree of heterogeneity between and within patients, inspecting these specimens at the single cell level is critical to identifying the true relapse driving cells and tailoring therapies towards these cells.

overall_design: We performed CITE-seq on primary AML patient specimens derived from either peripheral blood or bone marrow to capture single cell transcriptomics and surface protein expression.

first: Shanshan

last: Pei

first: Craig

last: Jordan


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool41_h1930001_BNST_a

first: Joseph

last: Ecker

summary: Illustrating the cellular architecture of the human brain is critical to understanding its diverse functions and complex animal behaviors. Single nucleus methylation sequencing was applied to regions of human brains. we identified distinct cell clusters and formed them in a hierarchical taxonomy. These clusters include known primary brain cell types and possible sub-types. We use these data to identify the epigenomic characteristics and to define specific regulatory elements for each cell cluster.

overall_design: Apply snmC-seq3 to brain regions to identify epigenomic landcape of the adult human brains

first: Wei

last: Tian

first: Anna

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon

last: Nery

first: Huaming

last: Chen


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling  - pool46_h1930001_CBL


title: Examining the potential protective effect of Vasaka tea extract on lung cells exposted to Pine wood smoke

city: Salt Lake City

first: Christopher

last: Reilly

state: Utah

address: 30 South 2000 E Skaggs Rm 201

institute: University of Utah

summary: This study tested the hypothesis that a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus expression. Wood/biomass smoke is a common pneumotoxic air pollutant that activates transient receptor potential ankyrin 1 (TRPA1) and causes endoplasmic reticulum (ER) stress and AEC damage. This stimulates epidermal growth factor receptor and mucin 5AC (MUC5AC) production by AECs. Mucus normally protects the airways, but excessive MUC5AC production can obstruct airflow and cause respiratory distress. Vasaka tea pre- and co-treatment dose-dependently inhibited MUC5AC mRNA induction in cells treated with wood smoke particles. This correlated with TRPA1 inhibition, an attenuation of ER stress, and AEC damage/death, among other effects. Induction of mRNA for Anterior Gradient 2 (AGR2), an ER chaperone/disulfide isomerase required for MUC5AC production, and TRP vanilloid-3 (TRPV3), a gene that suppresses ER stress and wood smoke particle-induced cell death, were also attenuated. Variable inhibition of TRPA1, ER stress, and MUC5AC mRNA induction was observed using selected chemicals identified in Vasaka tea including vasicine, vasicinone, apigenin, 9-oxoODE, and 9,10-EpOME. 9,10-EpOME and apigenin were the most cytoprotective and mucosuppressive.  Cytochrome P450 1A1 mRNA was also induced by Vasaka tea and wood smoke particles. Inhibition of CYP1A1 enhanced ER stress and MUC5AC mRNA expression, suggesting a role in producing protective oxylipins in stressed cells. The results provide mechanistic insights and support for the purported benefits of Vasaka tea in treating lung inflammatory conditions, raising the possibility of further development as a preventative therapy.

overall_design: This study examines gene expression changes in HBEC-3KT cells after a 24 hr treatment with (n=3) vehicle, pine, vasaka, or Pine + Vasaka.

first: Cassandra

last: Rice

first: Tosifa

last: Memon

first: Philip

last: Moos


title: Down Syndrome Airway Epithelium Bulk RNA-seq Analysis

first: Andrew

last: Goodspeed

address: 12801 E 17th Ave, Mail Stop 8303

summary: Bulk RNA-seq Analysis of In Vitro-Differentiated Murine Tracheal Epithelial Cells from Wild-type and Dp(16)1/Yey Mice When Unchallenged and After Influenza A Virus Infection

overall_design: Exploratory analysis of differentially expressed genes in mTECs from a murine Down syndrome model (Dp16) vs. wild-type control with and without infection with influenza A virus

first: Samantha

middle: N

last: Thomas

first: James

last: Costello

first: Kambez

last: Benam


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool44_h1930002_SEP


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool43_h1930002_CaB


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool47_h1930002_TH-TL


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c44_h1930004_FI

overall_design: Apply snm3C-seq to brain regions to identify epigenomic landcape of the adult human brains

first: Jingtian

last: Zhou


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c50_h1930004_MTG

last: Ecker


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool42_h1930001_CaB

last: Tian


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c46_h1930004_NAC

last: Bartlett


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool3_h1930002_CBV

last: Liu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling  - pool45_h1930001_SI

last: Altshul


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c43_h1930004_LEC

last: Gomez Castanon


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c49_h1930004_GPe

last: Nery


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c51_h1930004_SEP

last: Chen


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool16_h1930001_A1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c45_h1930004_A46


title: Epigenetic landscape of Human Brains by Single Nucleus Methylation Sequencing - pool3_h1930001_CBV


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool19_h1930002_A44-A45


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool9_h1930001_FI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool40_h1930001_TH-TL


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool18_h1930002_A1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c48_h1930004_A24


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool17_h1930001_A44-A45


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool48_h1930002_BNST


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c47_h1930004_Pir


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool13_h1930002_FI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c42_h1930004_CMN


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool12_h1930002_V1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool0_h1930002_CBV


title: Epigenetic landscape of Human Brains by Single Nucleus Methylation Sequencing - pool0_h1930001_CBV


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool35_h1930002_NAC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool34_h1930001_NAC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool33_h1930002_A19


title: Differential gene expression of adenoid cystic carcinoma of the lacrimal gland compared to normal lacrimal gland

city: Miami

first: Daniel

last: Pelaez

state: FL

address: 1638 NW 10th Ave, Room 804

department: Ophthalmology

institute: University of Miami

summary: To identify the transcriptomic signature of adenoid cystic carcinoma of the lacrimal gland (LGACC), we performed RNA sequencing on LGACC tumor samples and normal lacrimal gland samples.

overall_design: mRNA sequencing of tissue samples, LGACC tumor and normal lacrimal gland

first: Acadia

last: Moeyersoms


title: Arginine methylation of C/EBP⍺ controls the speed of immune cell transdifferentiation (ChIP-Seq)

city: Barcelona

first: Thomas

last: Graf

address: Carrer del Dr. Aiguader, 88

institute: Center for Genomic Regulation

summary: C/EBPα is a potent inducer of lymphoid to myeloid cell transdifferentiation. Here we describe that Carm1 methylates arginine 35 in the transactivation domain of C/EBPα, modulating the factor’s activity. Inhibition of methylation or mutation of R35 dramatically enhances the capacity of C/EBPα to induce a B cell-to-macrophage conversion through accelerated chromatin remodeling and subsequent upregulation of myeloid genes and downregulation of B cell genes. This phenomenon is mediated by an increased interaction of unmethylated C/EBPα with the bi-lineage transcription factor PU.1, resulting in the accelerated relocation of PU.1 from B cell to myeloid gene regulatory elements and thus enhancing chromatin remodeling. Our data suggests that C/EBPα effectively converts PU.1 from a B cell to a myeloid regulator through a ‘stealing’ process, and that methylation of C/EBPα by Carm1 modulates this interaction. We propose that individual cells display a pool of methylated and unmethylated C/EBPα, and the proportion of the two molecular forms determines the velocity of cell fate conversion.

overall_design: Study of C/EBPa and PU.1 binding in B cells induced for 3 hours with C/EBPa WT or mutant (R35A)

first: Guillem

last: Garcia

first: Elisabeth

last: Kowenz-Leutz

first: Tian

middle: V

first: Antonios

last: Klonizakis

first: Jonathan

last: Lerner

first: Luisa

last: de Andrés-Aguayo

first: Clara

last: Berenguer

first: Marcos

last: Plana-Carmona

first: Maria

last: Vila-Casadesús

first: Romain

last: Bulteau

first: Mirko

last: Francesconi

first: Sandra

last: Peiró

first: Kenneth

last: Zaret

first: Achim

last: Leutz


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool32_h1930001_A19

first: Joseph

last: Ecker

first: Wei

last: Tian

first: Anna

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon

last: Nery

first: Huaming

last: Chen


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [XRN2-dTAG_POINT-seq]

city: Exeter

first: Steven

last: West

state: Devon

address: Stocker Rd

department: Living Systems Institute

country: United Kingdom

institute: University of Exeter

summary: There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex.ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function. They facilitateZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction.ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs.  We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions.We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.

overall_design: Comparative gene expression and meta analysis of chromatin RNA by polymerase intact nascent transcript (POINT-Seq) for HCT116 XRN2-dTAG degron (with or without KD)

first: Chris

last: Estell

first: Lee

last: Davidson

first: Steve


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool29_h1930002_Pir


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [PNUTS_U1_AMO]

overall_design: Comparative gene expression and meta analysis of nuclear RNA-Seq for HCT116 PNUTS-AID degron cells electroporated with control or U1 antisense morpholino oligonucleotide (AMO) (plus or minus PNUTS KD).


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [PNUTS_ChIP-seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for PNUTS occupancy in HCT116 cells.


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool31_h1930002_LEC


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [ARS2_POINT-Seq]

overall_design: Comparative gene expression and meta analysis of chromatin RNA by polymerase intact nascent transcript (POINT-Seq) for HCT116 ARS2 dTAGv1 degron (with or without KD)


title: 10X single-cell RNA-seq profiling of T cells from the pancreas, pancreatic lymph nodes, and blood of NOD mice with spontaneous or anti-PD-1-induced Type 1 Diabetes

city: Boston

first: Jenna

middle: Lynn

last: Collier

state: Massachusetts

address: 77 Avenue Louis Pasteur

department: Immunology

institute: Harvard University

summary: Immune-related adverse events (irAEs) are a notable complication of PD-1 cancer immunotherapy. A better understanding of how these iatrogenic diseases compare to naturally arising autoimmune diseases is needed for treatment and monitoring of irAEs. We identified differences in anti-PD-1-induced Type 1 Diabetes (T1D) and spontaneous T1D in non-obese diabetic (NOD) mice by performing single-cell RNA-seq and TCR-seq on T cells from the pancreas, pancreas-draining lymph node (pLN), and blood of mice with PD-1-induced T1D or spontaneous T1D. In the pancreas, anti-PD-1 resulted in expansion of terminally-exhausted/effector-like CD8+ T cells, an increase in T-bethi CD4+FoxP3- T cells, and a decrease in memory CD4+FoxP3- and CD8+ T cells in contrast to spontaneous T1D. Notably, anti-PD-1 caused increased TCR sharing between the pancreas and the periphery. Moreover, T cells in the blood of anti-PD-1-treated mice expressed markers that differed from spontaneous T1D, suggesting that the blood may provide a window to monitor irAEs rather than relying exclusively on the autoimmune target organ.

overall_design:
10X 5' single cell RNASeq and paired TCR sequencing was performed on sorted TCR-beta+CD11A+ T cells from the pancreas, pancreatic lymph nodes, and peripheral blood of NOD mice. Samples from individual mice were labeled using hashtag antibodies and detected using CITE-seq. Using the TCR sequence as a molecular barcode, we identified matching T cell clones between the pancreatic lymph node, blood and pancreas, and characterized the matching versus non-matching T cell populations within a tissue compartment and between tissue compartments.
Please note that processed data files generated from both *FB* and *GEX* raw data are linked to the corresponding *GEX* sample records.

first: Kristen

last: Pauken

first: Arlene

last: Sharpe


title: Phase Separation Modulates DNA Guanine Quadruplex Formation in vitro and in cells

city: Riverside

first: Yinsheng

last: Wang

address: 501 Big Springs Rd.

institute: UCR

summary: In the presence of monovalent alkali metal ions, G-rich DNA sequences containing four runs of contiguous guanines can fold into G-quadruplex (G4) structures. Recent studies showed that these structures are located in critical regions of the human genome and assume important functions in many essential DNA metabolic processes, including replication, transcription and repair. However, not all potential G4-forming sequences are actually folded into G4 structures in cells, where G4 structures are known to be dynamic and modulated by G4-binding proteins as well as helicases. It remains unclear whether there are other factors influencing the formation and stability of G4 structures in cells. Herein, we showed that DNA G4s can undergo phase separation in vitro. In addition, immunofluorescence microscopy and ChIP-Seq experiments with the use of BG4, a G4 structure-specific antibody, revealed that disruption of phase separation in cells could result in global destabilization of G4 structures. Together, our work revealed phase separation as a new determinant in regulating the formation and stability of G4 structures in human cells.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) of G4s using BG4 antibody with untreated and 1,6-hexanediol treated U2OS cells.

first: Zi

last: Gao

first: Jun

last: Yuan

first: Xiaomei

last: He

first: Handing


title: Combined CRISPR and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression [gRNA]

city: TAMPA

first: Liang

address: 14059 Riveredge Drove

institute: Moffitt Cancer Center

summary:
Introduction Genome-wide association studies along with expression quantitative trait loci (eQTL) have identified hundreds of single nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PrCa). Although these genetic associations to PrCa have been widely reported, functional characterization of these risk loci remains challenging.    Methods To screen for regulatory SNPs, we designed a library containing 9133 guide RNAs (gRNAs) to target 2,166 candidate SNP sites implicated in PrCa. We performed negative screening in dCas9-KRAB stable prostate cell lines and applied the RIGOR program to identify the essential SNPs for cell proliferation. We further characterized the regulatory role of a selected single nucleotide polymorphim (SNP, rs60464856) using luciferase reporter assay, ChIP-qPCR, and xCas9 base editing in prostate cells. Finally, we investigated the biological impact of the SNP-regulated gene RUVBL1 on cell proliferation and tumor growth via gene knockdown using in vitro and in vivo assays.    Results From interference of 2,166 candidate SNPs via CRISPR interference screening, the RIGOR program identified 117 SNPs that could regulate genes to promote growth advantage in prostate cancer cell lines. Compared to unselected SNPs, the 117 candidates tended to reside near 5 kb flanking the transcription start sites (p = 0.01). To characterize the regulatory role of these SNPs, we selected one SNP (rs60464856) for detailed analysis. This SNP was covered by multiple gRNAs significantly depleted in the screening (FDR<0.05). Pooled SNP association analysis in the PRACTICAL cohort showed significantly higher PrCa risk for the G allele (pvalue=1.2E-16). eQTL analysis showed that the G allele is associated with an increased expression of RUVBL1 in multiple datasets. To further validate the CRISPR interference effect, we transfected a gRNA targeting the rs60464856 site in the dCas9 stable cell lines and observed significant inhibition of the RUVBL1 expression. We also applied the xCas9 adenine base editor to convert the rs60464856 A into G allele and observed an increased RUVBL1 expression in subclones carrying the rs60464856 G allele in prostate cell lines. To test if any protein showed allele-specific binding at rs60464856, we used SILAC-based DNA pull-down proteomics and observed that cohesin subunits (including SMC3) preferred the A allele. ChIP qPCR assays showed significant enrichment of CTCF and SMC3 signals at the rs60464856 site with preferential binding to the A allele. To evaluate the potential role of this locus in maintaining long-range chromatin structure, we analyzed a HiC dataset and found that the rs60464856 locus enriched consistent chromatin interactions in prostate cell lines. To determine the potential role of the rs60464856 target gene, we knocked down the RUVBL1 via shRNA and observed significant proliferation inhibition in prostate cell lines. We also tested PC3 cells with RUVBL1 knockdown in nude mice xenografts and observed reduced tumorigenesis. Gene set enrichment analysis showed that RUVBL1 expression was associated with the enrichment of cell cycle related pathways in both cell line and TCGA prostate cancer cohorts. Lastly, we showed that an increased RUVBL1 expression and its relevant pathway activation were associated with poor survival.    Conclusion We applied the CRISPR interference screening at selected prostate cancer risk loci and identified over a hundred regulatory SNPs essential for prostate cell proliferation. Further analysis confirmed the important role of rs60464856 and its target gene RUVBL1 in prostate cell growth and tumorigenesis.
To discover proliferative essential SNP loci, we used CRISPRi screening technology and DNA-seq to determine those functional candidate from previously published eQTL variants

sample_organism:
Homo sapiens
Expression vector lentiGuide-Puro

overall_design: Guide RNA (gRNA) read count were compared between screening ending and start in two replicates with RIGER program. Differential gene expression analysis were performed to compare the RUVBL1 induced changes

first: Yijun

last: Tian

first: Dandan

last: Dong

first: Lang

last: Wu

first: Jong

last: Park

first: Gong-Hong

last: Wei


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool30_h1930001_LEC

first: Joseph

last: Ecker

first: Wei

first: Anna

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon

last: Nery

first: Huaming


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c41_h1930004_AMY

first: Jingtian

last: Zhou

last: Chen


title: Combined CRISPR and proteomics screening reveal a cohesin-CTCF-bound allele contributing to increased expression of RUVBL1 and prostate cancer progression [RNA]

last: Wang

summary:
Introduction Genome-wide association studies along with expression quantitative trait loci (eQTL) have identified hundreds of single nucleotide polymorphisms (SNPs) and their target genes in prostate cancer (PrCa). Although these genetic associations to PrCa have been widely reported, functional characterization of these risk loci remains challenging.    Methods To screen for regulatory SNPs, we designed a library containing 9133 guide RNAs (gRNAs) to target 2,166 candidate SNP sites implicated in PrCa. We performed negative screening in dCas9-KRAB stable prostate cell lines and applied the RIGOR program to identify the essential SNPs for cell proliferation. We further characterized the regulatory role of a selected single nucleotide polymorphim (SNP, rs60464856) using luciferase reporter assay, ChIP-qPCR, and xCas9 base editing in prostate cells. Finally, we investigated the biological impact of the SNP-regulated gene RUVBL1 on cell proliferation and tumor growth via gene knockdown using in vitro and in vivo assays.    Results From interference of 2,166 candidate SNPs via CRISPR interference screening, the RIGOR program identified 117 SNPs that could regulate genes to promote growth advantage in prostate cancer cell lines. Compared to unselected SNPs, the 117 candidates tended to reside near 5 kb flanking the transcription start sites (p = 0.01). To characterize the regulatory role of these SNPs, we selected one SNP (rs60464856) for detailed analysis. This SNP was covered by multiple gRNAs significantly depleted in the screening (FDR<0.05). Pooled SNP association analysis in the PRACTICAL cohort showed significantly higher PrCa risk for the G allele (pvalue=1.2E-16). eQTL analysis showed that the G allele is associated with an increased expression of RUVBL1 in multiple datasets. To further validate the CRISPR interference effect, we transfected a gRNA targeting the rs60464856 site in the dCas9 stable cell lines and observed significant inhibition of the RUVBL1 expression. We also applied the xCas9 adenine base editor to convert the rs60464856 A into G allele and observed an increased RUVBL1 expression in subclones carrying the rs60464856 G allele in prostate cell lines. To test if any protein showed allele-specific binding at rs60464856, we used SILAC-based DNA pull-down proteomics and observed that cohesin subunits (including SMC3) preferred the A allele. ChIP qPCR assays showed significant enrichment of CTCF and SMC3 signals at the rs60464856 site with preferential binding to the A allele. To evaluate the potential role of this locus in maintaining long-range chromatin structure, we analyzed a HiC dataset and found that the rs60464856 locus enriched consistent chromatin interactions in prostate cell lines. To determine the potential role of the rs60464856 target gene, we knocked down the RUVBL1 via shRNA and observed significant proliferation inhibition in prostate cell lines. We also tested PC3 cells with RUVBL1 knockdown in nude mice xenografts and observed reduced tumorigenesis. Gene set enrichment analysis showed that RUVBL1 expression was associated with the enrichment of cell cycle related pathways in both cell line and TCGA prostate cancer cohorts. Lastly, we showed that an increased RUVBL1 expression and its relevant pathway activation were associated with poor survival.    Conclusion We applied the CRISPR interference screening at selected prostate cancer risk loci and identified over a hundred regulatory SNPs essential for prostate cell proliferation. Further analysis confirmed the important role of rs60464856 and its target gene RUVBL1 in prostate cell growth and tumorigenesis.
To validate one of our candidate, we knocked down RUVBL1 gene in BPH1 and PC3 cell lines and observed the transcriptome alterations with RNA-seq


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c38_h1930004_Pu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c39_h1930004_CaB


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c34_h1930001_NAC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c36_h1930001_A24


title: Generation and functional analysis of defective viral genomes during SARS-CoV-2 infection

city: Rochester

first: Raven

middle: M.

last: Osborn

address: 601 Elmwood Ave

department: Microbiology

institute: University of Rochester School of Medicine and Dentistry

summary: In this study, we elucidated defective viral genome generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from RNA-seq datasets of in vitro infections and autopsy lung tissues of COVID-19 patients.

overall_design: Gene expression profiling analysis of RNA-seq data of primary lung epithelial cells from donors of different age groups cultured on air-liquid interface for 4-5 weeks before infected with SARS-CoV-2.  Samples were collected at 2-3 timepoints post infection.

first: Christopher

last: Anderson

first: Nora

last: Gilliam

first: Terry

first: Sizhen

last: Li

first: Simone

last: Spaudau

last: Huang

first: David

last: Matthews

first: Stephen

last: Dewhurst

first: Juilee

last: Thakar

first: Yan

last: Sun

first: Thomas

last: Mariani


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c33_h1930002_SEP

first: Joseph

last: Ecker

first: Wei

last: Tian

first: Anna

last: Bartlett

last: Altshul


title: The m6A-enriched lncRNA LINC00839 promotes tumor progression by binding TAF15 and activate AOC1 transcription in nasopharyngeal carcinoma [ChIP-Seq]

first: Wei-Hong

last: Zheng

state: Guangdong

address: Dongfeng East Road 651

institute: Sun Yat-sen University Cancer Center

summary: Dysregulations of long non-coding RNAs (lncRNA) contribute to tumorigenesis by modulating specific cancer-related pathways, but the roles of m6A-enriched lncRNAs and underlying mechanisms remain elusive in nasopharyngeal carcinoma (NPC). Here, we reanalyzed the previous genome-wide analysis of lncRNA profile, and discerned that an oncogenic m6A-enriched lncRNA, LINC00839, which was substantially upregulated in NPC and correlated with poor clinical prognosis, promoted NPC growth and metastasis in vitro and in vivo. Mechanistically, LINC00839 interacted directly with transcription factor, TATA-box binding protein associated factor (TAF15), and coordinated its recruitment to promoter region of amine oxidase copper-containing 1 (AOC1), thereby activating AOC1 transcription in trans. Ectopic expression of AOC1 partially rescued the inhibitory effect of downregulation of LINC00839 in NPC. Furthermore, silencing vir like m6A methyltransferase associated (VIRMA) and insulin-like growth factor 2 mRNA-binding proteins 1 (IGF2BP1) were found to attenuate the expression level and RNA stability of LINC00839 in an m6A-dependent manner. This study unveils a novel oncogenic VIRMA/IGF2BP1–LINC00839–TAF15–AOC1 axis, and highlights significance and prognostic value of LINC00839 in NPC carcinogenesis.

overall_design: We reanalyzed the previous genome-wide analysis of lncRNA profile. The in vitro and in vivo functions of LINC00839 were confirmed by CCK8, colony formation, transwell migration and invasion assays, and animal experiments. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (CHIP) were conducted to investigate the downstream gene modulated by LINC00839. Methylated RIP (MeRIP) and RNA stability assays were performed to clarify the N6-methyladenosine (m6A)-modified status and attenuated rates of LINC00839.

first: Zhi-Qing

last: Long

first: Deng-Hui

last: Wei

first: Li

last: Lin


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c35_h1930002_NAC

address: 10010 North Torrey Pines Road

institute: HHMI-Salk-Institute

first: Jingtian

last: Zhou

first: Jordan

first: Rosa

last: Gomez Castanon

last: Nery

first: Huaming

last: Chen


title: The m6A-enriched lncRNA LINC00839 promotes tumor progression by binding TAF15 and activate AOC1 transcription in nasopharyngeal carcinoma [RNA-seq]


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c25_h1930002_CMN


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [PNUTS_POINT-seq]

first: Steven

last: West

overall_design: Comparative gene expression and meta analysis of chromatin RNA by polymerase intact nascent transcript (POINT-Seq) for HCT116 PNUTS-AID degron (with or without KD)

first: Chris

last: Estell

first: Lee

last: Davidson

first: Steve


title: Spatial transcriptomics of adenoid cystic carcinoma of the lacrimal gland

first: Daniel

last: Pelaez

summary: We performed spatial transcriptomics of a tumor section from a patient post-treatment with adenoid cystic carcinoma of the lacrimal gland.

overall_design: LGACC tissue was embedded in paraffin at the time of excision. The FFPE block was sliced at 10 µm and placed on 10x Genomics Visium slide for spatial transcriptomic pipeline.

first: Acadia

middle: H

last: Moeyersoms


title: The m6A-enriched lncRNA LINC00839 promotes tumor progression by binding TAF15 and activate AOC1 transcription in nasopharyngeal carcinoma

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

overall_design: Refer to individual Series


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c28_h1930001_A24

first: Joseph

last: Ecker


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c24_h1930001_CMN

first: Wei

last: Tian


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool28_h1930001_Pir

overall_design: Apply snmC-seq3 to brain regions to identify epigenomic landcape of the adult human brains

first: Anna

last: Bartlett

first: Hanqing

last: Liu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c21_h1930002_Pu

last: Altshul


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c22_h1930001_AMY


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c32_h1930001_SEP


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c23_h1930002_AMY


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c40_h1930004_SI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c10_h1930002_FI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c27_h1930002_Pir


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c26_h1930001_Pir


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c31_h1930002_GPe


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c37_h1930004_BNST


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c29_h1930002_A24


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c30_h1930001_GPe


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c10_h1930001_FI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c19_h1930002_CaB


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c17_h1930001_LEC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c15_h1930001_BNST


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c-unsorted_h1930002_M1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c7_h1930002_A46


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c14_h1930002_SI

last: GomezCastanon


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c18_h1930001_CaB


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c8_h1930001_MTG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c11_h1930002_FI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c20_h1930001_Pu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c12_h1930004_V1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c13_h1930001_SI


title: Inhibition of γ-glutamyl transpeptidase suppresses LPS induced asthma exacerbation in a mouse model

city: Zhengzhou

first: cancan

last: zhang

state: henan

address: 100 Science Road

institute: Zhengzhou university

summary:
To investigate the role of γ-glutamyltranspeptidase in severe asthma, we established an OVA/ LPS-induced asthma model.  Inflammation analysis and second-generation sequencing
revealed the mechanism by which inhibition of γ-glutamyltranspeptidase inhibited LPS-induced asthma exacerbation in mice.

overall_design:
In order to study the effect of GGsTop on asthma, we set up control group (PBS), asthma group (OL), and experimental group (OLG), and isolated trachea for transcriptomic sequencing.
Gene expression profiling was performed on RNA-seq data.

first: Cancan

last: Zhang


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool115_h1930004_SEP

last: Castanon


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c3_h1930002_V1C

overall_design: Apply snm3C-seq to brain regions to identify epigenomic landcape of the adult human brains

last: Zhou

last: Gomez Castanon


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c-unsorted_h1930001_M1C

last: Nery

last: Chen


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool8_h1930001_V1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c9_h1930002_MTG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool113_h1930004_Sub


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c-presorted_h1930001_M1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool111_h1930004_LEC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c2_h1930001_V1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool116_h1930004_V1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c-presorted_h1930002_M1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool135_h1930004_MD-Re


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c6_h1930001_A46


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool112_h1930004_GPe


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool114_h1930004_BNST


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool110_h1930004_Pro


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool134_h1930004_BL-La


title: RNA-seq analysis of canine soft tissue sarcomas.

city: Fort Collins

first: Sunetra

last: Das

address: 300 W Drake Rd

department: Clinical Sciences

institute: Colorado State University

summary: To investigate and delineate differences in the transcriptomic profiles of canine soft tissue sarcoma types, we ran RNAseq on 29 tumor samples.

overall_design: We ran gene expression profiling analysis, hierarchical clustering, and differential expression between in silico clusters, using data obtained from RNA-seq.

first: Dawn

last: Duval


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c5_h1930002_LEC

city: La Jolla

first: Jingtian

first: Jordan


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool132_h1930004_CA1R-CA2R-CA3R

first: Rosa

first: Huaming


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool133_h1930004_DGR-CA4Rpy


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool126_h1930004_CBL


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool130_h1930004_PN


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool128_h1930004_IC


title: Azide-containing amino acid modulation of cellular transcriptome and proteome composition – implications on click chemistry based secretome analysis

city: Mainz

first: Matthias

last: Klein

address: Langenbeckstrasse 1

department: Inst. for Immunology

country: Germany

institute: University Medical Center Mainz

summary: The analysis of the secretome provides important information on cellular communication and on the recruitment and behavior of cells in specific tissues. Especially in the context of tumors, knowledge on the composition of the secretome plays an important role for diagnosis and therapy. Mass spectrometry-based analysis of cell-conditioned media is widely used for the unbiased characterization of cancer secretomes in vitro. Azide-containing amino acid labeling in combination with click chemistry now facilitates this type of analysis without serum starvation. The modified amino acids, however, are less efficiently incorporated into newly synthesized proteins. Utilizing transcriptome and proteome analysis, we describe here in detail the effects of labeling cells with the methionine analog azidohomoalanin (AHA) on the modulation of gene expression and protein composition. We observe that 11% – 34% of the proteins detected in the secretome were affected by AHA labeling regarding their expression levels in the transcriptome and/or proteome. Performing gene ontology analyses, our results provide a detailed view on the AHA-based induction of cellular stress and apoptosis-related pathways and provide first insights on how this might affect the composition of the secretome on a global scale.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: To describe and understand the effects of AHA on the behaviour of cells in detail, we performed comparative transcriptome analyses of seven different tumor cells grown 20 h in AHA- or methionine-containing media and evaluated the gene expression profiles.

first: Danielle

last: Arnold-Schild

first: Friederike

last: Kirschner


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool129_h1930004_MD-Re

last: Ecker

summary: Illustrating the cellular architecture of the human brain is critical to understanding its diverse functions and complex animal behaviors. Single nucleus methylation sequencing was applied to regions of human brains. we identified distinct cell clusters and formed them in a hierarchical taxonomy. These clusters include known primary brain cell types and possible sub-types. We use these data to identify the epigenomic characteristics and to define specific regulatory elements for each cell cluster.

last: Tian


title: Assessing the impact of boldine on the gastrocnemius using multiomics profiling at 7 and 28 days post-complete spinal cord injury in young male mice [RRBS]

city: Birmingham

first: Luke

middle: Allen

last: Potter

state: Alabama

address: 901 19th St S

department: Pathology

institute: UAB

summary: Spinal cord injury (SCI) results in rapid muscle loss in the acute timeframe post-injury. The principal mechanisms of general muscle atrophy have been well-described but there is limited information available specific to SCI. Exogenous drug/small molecule interventions to slow muscle atrophy in severe-to-complete SCI have been relatively ineffective due to the unique combination in loss of central nervous system function due to the spinal lesion, systemic response to the trauma itself, and resultant paralysis. The wide-ranging physiologic response to SCI requires the search for novel therapeutic targets. Connexin hemichannels (CxHCs) allow non-selective passage of small molecules into and out of the cell. Boldine, a CxHC-inhibiting aporphine found in the boldo tree (Peumus boldus), has shown promising results in slowing muscle atrophy and preserving muscle function during endotoxemia-induced sepsis and dysferlinopathy. We administered 50 mg/kg/d of boldine to spinal cord transected mice beginning at day 3 post-injury. Tissue was collected at 7 and 28 d post-injury. Boldine treatment did not alter the loss of body or muscle mass. We then performed molecular analysis at three different levels on the gastrocnemius muscle. Metabolomic analysis revealed that boldine attenuated the SCI-induced changes in proline, phenylalanine, leucine, and isoleucine, as well as glucose, 7 d post-SCI in the gastrocnemius, but not at 28 d. RNA-sequencing further found that SCI resulted in the differential expression of 7,705 and 2,991 genes at 7 and 28 d compared to sham animals, with enrichment for pathways associated with ribosome biogenesis, translation and oxidative phosphorylation. Boldine altered the expression of 146 genes at 7 d and 110 genes at 28 d post-SCI. Additionally, DNA methylation analyses of reduced representation bisulfite sequencing highlighted distinct methylation patterns at both 7 and 28 d following SCI both with and without boldine, though most methylation changes did not associate with genes that were differentially expressed. Taken together, boldine is not an efficacious therapy to preserve body and muscle mass after complete SCI, though boldine was able to preserve or attenuate SCI-induced changes across the metabolome, transcriptome and methylome. Additional research is needed to determine if treatment could be modified or used in combination for long-term recovery or if boldine would be a more efficacious therapy in mild or moderate forms of injury.

overall_design: Comparative methylation coverage analysis of RRBS data from gastrocnemius tissue using Sham, SCI, and SCI-boldine mice.

middle: A

first: Zachary

last: Graham


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool127_h1930004_CBV

first: Joseph

last: Bartlett

last: Liu

last: Altshul


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - m3c16_h1930002_BNST

first: Wei


title: Assessing the impact of boldine on the gastrocnemius using multiomics profiling at 7 and 28 days post-complete spinal cord injury in young male mice


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool123_h1930004_Cla

first: Anna


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool120_h1930004_CMN

first: Hanqing


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool122_h1930004_NAC


title: Assessing the impact of boldine on the gastrocnemius using multiomics profiling at 7 and 28 days post-complete spinal cord injury in young male mice [RNAseq]

overall_design: Comparative gene expression analysis of RNA-seq data from gastrocnemius tissue using Sham, SCI, and SCI-boldine mice.


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool105_h1930004_Ig


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool109_h1930004_CaB


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool107_h1930004_Pir


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool108_h1930004_A44-A45


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool119_h1930004_Pu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool98_h1930004_IDG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool102_h1930004_MEC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool131_h1930004_Pul


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool125_h1930004_DGC-CA4Cpy


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool124_h1930004_CA1C-CA2C-CA3C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool100_h1930004_ITG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool96_h1930004_MTG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool93_h1930004_M1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool97_h1930004_A25


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool104_h1930004_A46


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool103_h1930004_FI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool121_h1930004_AMY


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool92_h1930004_A1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool106_h1930004_A38


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [ars2-zc3h4_double_degron]

first: Steven

last: West

summary: There are thousands of unstable non-coding (nc) RNAs in humans, but their transcriptional regulation is poorly characterized compared to protein-coding transcripts. We recently identified a restrictor complex containing ZC3H4 and WDR82, which terminates non-coding transcription. Here we show that the ncRNA termination factor, ARS2, and the nuclear exosome targeting complex (NEXT) are part of this complex.  ARS2/NEXT and WDR82 contact different parts of ZC3H4, which are required for its transcription regulatory function.  They facilitate ZC3H4-mediated termination by different mechanisms: ARS2 aids substrate targeting and WDR82 mediates RNA polymerase II interaction.  ZC3H4 and WDR82 predominantly affect antisense, unstable, and intragenic ncRNAs.  We provide an explanation for this by showing that U1 telescripting shields hundreds of protein-coding transcripts from their termination functions.  We have defined an expanded ZC3H4 restrictor complex, its principles of action, and how protein-coding transcripts evade it.

overall_design: Comparative gene expression and meta analysis of nuclear RNA-Seq for HCT116 dTAG-ARS2 ZC3H4-DHFR (ARS2, ZC3H4 and double KD) degron cells

first: Chris

last: Estell

first: Lee

last: Davidson

first: Steve


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool99_h1930004_A5-A7

last: Gomez Castanon

last: Nery


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool91_h1930004_S1C

last: Chen


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool101_h1930004_A24


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool118_h1930004_SI


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [chip-seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for RNA Polymerase (Pol) II, ZC3H4-HA and WDR82-GTF occupancy in ZC3H4-DHFR or WDR82-GFP HCT116 cells.


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool38_h1930001_Pu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool90_h1930002_CBL


title: Single-cell transcriptomics of cultured human amniotic fluid cells from the second trimester reveals their heterogeneity

first: Genome

last: Informatics

address: Winterthurerstrasse 190

department: Functional Genomics Center Zurich (FGCZ)

institute: ETH ZURICH / University of Zurich

summary: Amniotic fluid has been proposed as an easily available source of cells for numerous applications in regenerative medicine and tissue engineering. The use of amniotic fluid cells in biomedical applications necessitates their unequivocal characterization; however, the exact cellular composition of amniotic fluid and the precise tissue origins of these cells remain largely unclear. Using cells cultured from human amniotic fluid of the second trimester from a healthy fetus and fetuses with spina bifida aperta, we have performed single-cell RNA sequencing to characterize the tissue origin and marker expression of cultured amniotic fluid cells at the single-cell level. Our analysis identified nine different cell types of stromal, epithelial and immune cell phenotype, and from various fetal tissue origins, demonstrating the heterogeneity of the cultured amniotic fluid cell population at single-cell resolution. Further, our data question the presence of pluripotent stem cell populations in cultured AF, and provide a comprehensive list of markers for the characterization of its various progenitor and terminally differentiated cell types. Our study highlights the relevance of single-cell analysis approaches for the characterization of amniotic fluid cells in order to harness their full potential in biomedical research and clinical applications.

overall_design: 1. Single cell RNA sequencing of cultured human amniotic fluid cells from the 2nd trimester

first: Athanasia

last: Dasargyri

first: Daymé

last: González Rodríguez

first: Hubert

last: Rehrauer

first: Ernst

last: Reichmann

first: Thomas

last: Biedermann

first: Ueli

last: Moehrlen


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool37_h1930002_GPe

last: Ecker

last: Tian

first: Jordan

first: Rosa

first: Huaming


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool95_h1930004_A19

first: Joseph

first: Wei

last: Bartlett

last: Liu


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool39_h1930002_Pu

first: Anna

first: Hanqing

last: Altshul


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [u1_amo]

first: Steven

last: West

overall_design: Comparative gene expression and meta analysis of nuclear RNA-Seq for HCT116 ZC3H4-DHFR degron cells electroporated with control or U1 antisense morpholino oligonucleotide (AMO) (plus or minus ZC3H4 KD).

first: Chris

last: Estell


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [point-seq]

overall_design: Comparative gene expression and meta analysis of chromatin RNA by polymerase intact nascent transcript (POINT-Seq) for HCT116 ZC3H4-DHFR degron and WDR82-mAID cells (with or without KD)

first: Lee

last: Davidson

first: Steve


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool36_h1930001_GPe

last: Gomez Castanon

last: Nery


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool94_h1930004_V2

last: Chen


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool58_h1930001_SEP


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool59_h1930001_DGC-CA4Cpy


title: ZC3H4, ARS2, and WDR82 coordinate non-coding transcriptional termination and are opposed by telescripting on protein-coding genes [zc3h4_rescue]

overall_design: Comparative meta analysis of nuclear RNA-seq from HCT116 ZC3H4-DHFR degron cells transfected with WT, delta82, deltaARMS or deltaZnF ZC3H4 deletion mutant plasmids.


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool57_h1930002_MEC


title: Arginine methylation of C/EBP⍺ controls the speed of immune cell transdifferentiation (ATAC-Seq)

last: Graf

summary: C/EBPα is a potent inducer of lymphoid to myeloid cell transdifferentiation. Here we describe that Carm1 methylates arginine 35 in the transactivation domain of C/EBPα, modulating the factor’s activity. Inhibition of methylation or mutation of R35 dramatically enhances the capacity of C/EBPα to induce a B cell-to-macrophage conversion through accelerated chromatin remodeling and subsequent upregulation of myeloid genes and downregulation of B cell genes. This phenomenon is mediated by an increased interaction of unmethylated C/EBPα with the bi-lineage transcription factor PU.1, resulting in the accelerated relocation of PU.1 from B cell to myeloid gene regulatory elements and thus enhancing chromatin remodeling. Our data suggests that C/EBPα effectively converts PU.1 from a B cell to a myeloid regulator through a ‘stealing’ process, and that methylation of C/EBPα by Carm1 modulates this interaction. We propose that individual cells display a pool of methylated and unmethylated C/EBPα, and the proportion of the two molecular forms determines the velocity of cell fate conversion.

overall_design: Study of chromatin accessibility changes of B cells induced with C/EBPa WT or mutant (R35A)

first: Guillem

last: Garcia

first: Elisabeth

last: Kowenz-Leutz

first: Tian

first: Antonios

last: Klonizakis

first: Jonathan

last: Lerner

first: Luisa

last: de Andrés-Aguayo

first: Clara

last: Berenguer

first: Marcos

last: Plana-Carmona

first: Maria

last: Vila-Casadesús

first: Romain

last: Bulteau

first: Mirko

last: Francesconi

first: Sandra

last: Peiró

first: Kenneth

last: Zaret

first: Achim

last: Leutz


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool56_h1930001_MEC

first: Joseph

last: Ecker

first: Wei

last: Tian

first: Anna

last: Bartlett

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon

first: Huaming


title: Arginine methylation of C/EBP⍺ controls the speed of immune cell transdifferentiation (RNA-Seq)

first: Thomas

last: Graf

overall_design: Study of gene expression changes from mRNA of B cells induced with C/EBPa WT or mutant (R35A)

first: Guillem

last: Garcia

first: Elisabeth

last: Kowenz-Leutz

first: Tian

first: Antonios

last: Klonizakis

first: Jonathan


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool54_h1930001_CMN

last: Nery

last: Chen


title: Arginine methylation of C/EBP⍺ controls the speed of immune cell transdifferentiation


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool55_h1930001_Pul


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool52_h1930002_MD-Re


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool51_h1930002_CMN


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool87_h1930001_CA1C-CA2C-CA3C-DGC-CA4C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool89_h1930002_ITG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool49_h1930002_SI


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool80_h1930002_Pul

last: Castanon


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool82_h1930002_Idg


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool86_h1930001_A25


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool78_h1930002_PN


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool50_h1930001_BM


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool173_h1930002_CA1C-CA2C-CA3C-DGC-CA4C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool79_h1930001_MD_Re


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool72_h1930002_CA1C-CA2C-CA3C-DGC-CA4C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool88_h1930002_A38


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool67_h1930001_CA1C-CA2C-CA3C-DGC-CA4C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool64_h1930002_IC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool84_h1930001_Idg


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool71_h1930002_Cla


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool81_h1930002_A25


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool65_h1930001_BL-La


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool53_h1930002_CEN


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool63_h1930002_CA1R-CA2R-CA3R

summary: Illustrating the cellular architecture of the human brain is critical to understanding its diverse functions and complex animal behaviors, Single nucleus methylation sequencing was applied to regions of human brains, we identified distinct cell clusters and formed them in a hierarchical taxonomy, These clusters include known primary brain cell types and possible sub-types, We use these data to identify the epigenomic characteristics and to define specific regulatory elements for each cell cluster,


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool74_h1930001_IC


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool85_h1930001_ITG


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool83_h1930001_A38


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool76_h1930002_BL-La


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool69_h1930002_Amy


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool60_h1930002_Sub


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool70_h1930001_Cla


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool66_h1930001_CA1R-CA2R-CA3R-DGR-CA4R


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool75_h1930001_CA1R-CA2R-CA3R-DGR-CA4R


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool77_h1930001_PN


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool61_h1930001_Sub


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool68_h1930001_Amy


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool22_h1930001_S1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool23_h1930002_S1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool26_h1930002_Pro


title: Targeting nuclear translocation of PKM2 activates HIF-2α mediated non-canonical regulation of PFKFB3 to inhibit breast cancer progression

city: Bhopal

first: Sanjeev

last: Shukla

state: Madhya Prades

address: Bhopal Bypass Road, Bhauri Bhopal 462 066 Madhya Pradesh, INDIA

department: Biological Sciences

country: India

institute: Indian Institute of Science Education and Research Bhopal

summary:
Analysis of transcriptome post hypoxia treatment in breast cancer cell line and its PKM2 knockout mutant
In order to explore the role of PKM2 in influencing global transcriptional alterations under hypoxia in breast cancer, we performed Human Transcriptome Array 2.0 with a breast cancer cell line and its PKM2 knockout mutant cell line.

overall_design: Breast cancer cell lines MCF7 its PKM2 knockout cell line were cultured in 1% O2 for giving hypoxia treatment. Post harvest, samples were analysed on Human Transcriptome Array 2.0 platform. Raw files generated were processed using Transcriptome Analysis Console tool.

first: Madhura

last: Pandkar

first: Srinivas

last: Mutnuru

first: Adarsh

last: Raveendran

first: Jharna

last: Mishra

first: Atul

last: Samaiya


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool24_h1930001_Ig

first: Joseph

last: Ecker

first: Wei

last: Tian

first: Anna

last: Bartlett


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool20_h1930001_A5-A7

first: Hanqing

last: Liu

first: Jordan

last: Altshul

first: Rosa

last: Gomez Castanon


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool27_h1930002_Ig

first: Huaming


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool4_h1930001_M1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool62_h1930002_DGR-CA4Rpy


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool5_h1930002_M1C


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool21_h1930002_A5-A7


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool25_h1930001_Pro


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool10_h1930001_A46


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool6_h1930001_V2


title: Mechanism of Taurochenodeoxycholic acid in U251

status: Public on Jul 04 2023

city: Hangzhou

first: Xue

middle: Xiu

last: Min

address: cangqian

institute: Hangzhou normal university

summary: Taurochenodeoxycholic acid can induce the changes of gene expression in U251 cells

overall_design: The cells were treated with 200μ Taurochenodeoxycholic acid in the experimental group and compared with the control group.


title: Epigenetic landscape of Human Brains by Single Nucleus DNA Methylation and Chromatin Conformation Profiling - pool1_h1930002_MTG

overall_design: Apply snmC-seq3 to brain regions to identify epigenomic landcape of the adult human brains