title: Genome-wide maps of R-loops in Drosophila embryogenesis and cultured cells

city: Nashville

first: Jared

last: Nordman

state: TN

address: 465 21st Ave S

department: Biological Sciences

institute: Vanderbilt University

summary: We report the genome localization of R-loops in early and late-stage embryos relative to Drosophila cultured cells. We demonstrate that proper absolute R-loop levels chage during embryogenesis and that resolution of R-loops is critical for embryonic development. R-loop mapping by strand-specific DRIP-seq revealed that R-loop localization is plastic across development, both in the genes which form R-loops and where they localize relative to gene bodies. Importantly, these changes are not driven by changes in the transcriptional program. Rather, negative GC skew and absolute changes in AT skew are associated with R-loop formation in Drosophila. Furthermore, we demonstrate that while some chromatin binding proteins and histone modification such as H3K27me3 are associated with R-loops throughout development, other chromatin factors associated with R-loops in a developmental specific manner.

overall_design: Examination of R-loops via ssDRIPseq in 2-3 hour embryos, 14-16 hour embryos, and S2 cultured cells.

first: Alexander

last: Munden


title: Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia [ChIP-seq]

status: Public on Jun 21 2022

city: Suita

first: Masaki

last: Nomura

state: Osaka

address: 2-2, Yamadaoka

department: Department of Cancer Pathology

country: Japan

institute: Graduate School of Medicine, The University of Osaka

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Detailed genomic and epigenomic analyses of MECOM (the MDS1 and EVI1 complex locus) have revealed that inversion or translocation of chromosome 3 at MECOM drive inv(3)/t(3;3) myeloid leukemias and revealed MECOM germline mutations in patients with MECOM-associated bone marrow failure syndromes. Here we identify a novel, previously unannotated oncogenic RNA-splicing derived isoform of EVI1 which is frequently present in inv(3)/t(3;3) AML and directly contributes to leukemic transformation. Expression of this EVI1 splice variant enhanced the self-renewal of hematopoietic stem cells and introduction of mutant SF3B1 in mice bearing the humanized inv(3)(q21;26) allele hastened leukemogenesis in vivo. These data provide a mechanistic basis for the frequent co-occurrence of SF3B1 mutations as well as new insights into the pathogenesis of myeloid leukemias harboring inv(3)/t(3;3).

overall_design: One day before sample preparation, 293T cells were transfected with pMIGII_3xHA, pMIGII_3xHA-EVI1-WT, or pMIGII_3xHA-EVI1+18 retroviral vector. Detailed protocols for sample preparation were described at: doi.org/10.1016/j.xpro.2021.100404.

first: Atsushi

last: Tanaka

first: Akihiko

last: Yokoyama

first: Akinori

last: Kanai

first: Daichi

last: Inoue


title: Oo-site: A dashboard to visualize gene expression during Drosophila oogenesis reveals meiotic entry is regulated post-transcriptionally

city: Albany

first: Prashanth

last: Rangan

state: NY

address: 1400 Washington

country: USA

institute: RNA Institute

type: Expression profiling by high throughput sequencing

summary: Determining how stem cell differentiation is controlled has important implications for understanding the etiology of degenerative disease and designing regenerative therapies. In vivo analyses of stem cell model systems have revealed regulatory paradigms for stem cell self-renewal and differentiation. The germarium of the female Drosophila gonad, which houses both germline and somatic stem cells, is one such model system. Bulk mRNA sequencing (RNA-seq), single cell (sc) RNA-seq, and bulk translation efficiency of mRNAs is available for stem cells and their differentiating progeny within the Drosophila germarium. However, visualizing those data is hampered by lack of a tool to spatially map gene expression and translational data in the germarium. Here, we have developed Oo-site (https://www.ranganlab.com/Oo-site), a tool for visualizing bulk- and scRNA-seq and translational efficiency data during different stages of germline differentiation, that makes these data accessible to non-bioinformaticians. Using this tool, we recapitulated previously reported expression patterns of developmentally regulated genes and discovered that meiotic genes, such as those that regulate the synaptonemal complex, are regulated at the level of translation.

overall_design: polysome-seq of duplicate samples of ovaries from germline bam RNAi; hs-bam to determine cyst expression

first: Elliot

middle: T

last: Martin

first: Kahini

last: Sarkar

first: Alicia

last: McCarthy


title: Dysregulation of gene expression in SCGB3A2 Knock-out mouse

city: Bethesda

first: Shioko

last: Kimura

state: MD

address: 9000 Rockville Pike

department: CCR

institute: NIH

summary: Gene expression in lung tissues were evallulated in SCGB3A2 knock-out mice.

overall_design: lung mRNA profiles of wild type (WT) and SCGB3A2 Knock out mice

first: Lei

last: Xu

first: Jieqiong

last: Dai

first: Maxwell

middle: P

last: Lee


title: Aberrant EVI1 splicing contributes to EVI1-rearranged leukemia [K562_RNA-seq]

overall_design: K562 cells were transduced with retroviral supernatant from GP2-293 cells transfected with pMYs-IG_empty vector, pMYs-IG_3xHA-EVI1-WT, or pMYs-IG_3xHA-EVI1+18 by using polybrene. Three days after infection, GFP-positive cells were selected by fluorescence activated cell sorting (FACS) method and cultured for sample preparation.


title: Anti-inflammatory clearance of amyloid beta by a chimeric Gas6 fusion protein

city: Daejeon

first: Hyuncheol

last: Jung

address: Daehakro 291

country: South Korea

institute: KAIST

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Protein Kinase 2 (CK2) Controls CD8+ T-cell Effector and Memory Function during Infection

city: New York

first: Wei

last: Yang

address: Belfer Research Building,Room 760B,413 E. 69th Street

department: Department of Medicine

institute: Weill Cornell Medicine

summary: Protein kinase 2 (CK2) is a serine/threonine kinase composed of two catalytic subunits (CK2α and/or CK2α') and two regulatory subunits (CK2β). CK2 has been shown to promote cancer progression by regulating the NF-κB, PI3K/AKT/mTOR, JAK/STAT and HIF-1α pathways, and also plays a critical role for immune cell development and function. However, the potential involvement of CK2 in CD8+ T-cell function has not explored. Here, we demonstrate that CK2 protein levels and kinase activity are enhanced upon CD8+ T-cell activation. CK2α deficiency results in impaired CD8+ T-cell activation and proliferation upon TCR stimulation. Furthermore, CK2α is involved in CD8+ T-cell metabolic reprogramming during activation through regulating the AKT/mTOR signaling pathway. Lastly, using a Listeria monocytogenes infection model, we demonstrate that CK2α is required for CD8+ T-cell expansion, maintenance and effector function in both primary and memory immune responses. Taken together, our study implicates CK2 as an important regulator of CD8+ T-cell activation and differentiation both in vitro and in vivo.

overall_design: OT-I CK2αfl/fl and OT-I CK2α-/- CD8+ T-cells were sorted from the spleen at day 7 post infection. Total RNA was extracted from FACS-sorted CD8+ T-cells using the miRNeasy Mini Kit (Qiagen, Venlo, Netherlands) according to the manufacturer’s protocols and submitted to GENEWIZ (South Plainfield, NJ) for RNA sequencing (RNA-seq) and bioinformatics analysis.

first: Hongwei

last: Qin

first: Etty

middle: N

last: Benveniste


title: High-throughput RNA sequencing analysis of mouse peritoneal cells from wild type and Lactoferrin knockout mouse during Lipopolysaccharide(LPS) stimulation

city: Changsha

first: Jian

last: Ma

state: Hunan

address: 110  Xiangya  Road

department: Cancer  Research Institute

country: China

institute: Central South University

summary:
Purpose: The goal of this study is using  RNA sequencing analysis to evaluate the role of lactoferrin in the LPS-induced acute inflammation in mouse
Methods: 4 hs after intraperitoneal injection with LPS(4mg/kg) or equal volume PBS , the peritoneal cells were isolated from the peritoneal lavage fluid from wild type and lactoferrin knockout mice (n=3 for each group) . Then the cell RNA was sequenced by the HiSeq 2500 high-throughput sequencing service (Oebiotech, Shanghai, China). Data were extracted and normalized according to the manufacturer’s standard protocol.
Results: Log-fold changes of up- or down-regulated mRNAs between the control and experiment group were selected with a significance threshold of p<0.05.
Conclusions: Our study describes the mRNA expression profile changes of  peritoneal cells from wild type and lactoferrin knockout mice  during LPS-induced acute inflammation

overall_design: The peritoneal cells were isolated from the wild type and lactoferrin mice, and cellular RNA was used for RNA-sequencing to show the gene expression profile change induced by lactoferrin deﬁciency during  LPS-induced acute inflammation

first: Can

last: Liu


title: ADAP-STAT1 module maintains platelet homeostasis via restraint of macrophage phagocytic in ITP

city: Suzhou

first: Hebin

address: 199 Renai Road

department: Institutes of Biology and Medical Sciences

institute: Soochow University

summary: Heightened platelet phagocytosis by macrophages accompanied with an increase in IFN-γ is often attributed to the etiology of immune thrombocytopenia (ITP), an autoimmune disease characterized by low platelet counts. While deletion of the hematopoietic cell adaptor protein ADAP predisposes to ITP in mice, the mechanisms that underlie the functional role of ADAP during ITP remains largely unknown. Here we report that ADAP restrains platelet clearance by macrophages via modulation of STAT1-FcγR signaling axis. We show that under-expression of ADAP in splenic macrophage was associated with low platelet counts in patients with ITP. Further, macrophages from Adap−/− mice had an elevated phagocytosis capacity and exhibited upregulated pro-inflammatory signaling, and the thrombocytopenia in Adap−/− mice was mitigated in vivo by depletion of macrophages. Mechanically, ADAP interacted and competed with STAT1 binding to importin a5, a nuclear shuttling receptor for activated STAT1. While having no effect on STAT1 tyrosine phosphorylation, loss of ADAP increased the assembly of STAT1-importin a5 complex and facilitated STAT1 nuclear entry, leading to a selective enhancement of transcription of FcγRI/IV in macrophages. Moreover, pharmacological inhibition of STAT1 or disruption of STAT1-importin a5 interaction relieved the thrombocytopenia in Adap−/− mice. Thus, our findings reveal a critical role for ADAP as an intracellular immune checkpoint for shaping macrophage phagocytic ability in homeostatic maintenance of platelets.

overall_design: RNA profiles of splenic macrophages from wild-type and Adap-KO mice

first: Yiwei

last: Xiong

first: Lifeng

last: Zhang

first: Xiaodong


title: Innate immune role of Rnd1 during H5N1 infection

city: Bhopal

first: Himanshu

last: Kumar

state: MADHYA PRADESH

address: Indore bypass road

country: India

institute: IISER Bhopal

summary: Intracellular and cell surface molecules are an essential part of the innate immune system. We describe a novel cellular defense mechanism based upon a membrane-associated protein RND1. RND1 belongs to the Rho GTPase family, but unlike other members, it is constitutively active. We show that RND1 is induced by pro-inflammatory cytokines during viral and bacterial infections and provides protection against these pathogens through two distinct mechanisms.

overall_design: To analyze the role of Rnd1 during influenza virus infection, Rnd1 was knocked down using Rnd1 specific siRNA in A549 cells. 24 hours after transfection cells were infected with H5N1 high pahtogenicity influenza virus in serum free DMEM for 1 hour. Cells were harvested and total RNA was isolated using TRIzol 24 hours of infection.

first: Akhilesh

first: Ashish


title: Anti-inflammatory clearance of amyloid beta by a chimeric Gas6 fusion protein [RNA-Seq]

summary: To report the effects of Fc or TAM receptors mediated Aβ phagocytosis on inflammatory responses in vivo

overall_design: We performed bulk RNA seqeuncing using Axl overexpressed THP-1 cells after 1-hour incubation with FITC-labelled beads (5.7μm) and E2 antibody or ⍺FITC-Gas6 (E).

first: Seongjoon

last: Lim

first: Kyung

middle: H

last: Han

first: Won-Suk

last: Chung

first: Chan

last: Kim


title: BNT162b2 vaccination enhances interferon-JAK-STAT-regulated antiviral programs in COVID-19 patients infected with the SARS-CoV-2 Beta variant

first: Hye Kyung

address: 8 CENTER DR RM 107

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

institute: National Institutes of Health (NIH)

summary: SARS-CoV-2 infection activates interferon-controlled signaling pathways and elicits a wide spectrum of immune responses and clinical manifestations in human patients. Here, we investigate the impact of prior vaccination on the innate immune response of hospitalized COVID-19 patients infected with the SARS-CoV-2 Beta variant through RNA sequencing of peripheral blood immune cells. Four patients had received the first dose of BNT162b2 about 11 days prior to the onset of COVID-19 symptoms and five patients were unvaccinated. Patients had received dexamethasone treatment. Immune transcriptomes were obtained at days 7-13, 20-32 and 42-60 after first symptomology. RNA-seq reveals an enhanced JAK-STAT-mediated immune transcriptome response at day 10 in vaccinated patients as compared to unvaccinated ones. This increase subsides by day 35. Expression of the gene encoding the antiviral protein oligoadenylate synthetase (OAS) 1, which is inversely correlated with disease severity, and other key antiviral proteins increases in the vaccinated group. We also investigate the immune transcriptome in naïve individuals receiving their first dose of BNT162b2 and identify a gene signature shared with the vaccinated COVID-19 patients. Our study demonstrates that RNA-seq can be used to monitor molecular immune responses elicited by the BNT162b2 vaccine, both in naïve individuals and in COVID-19 patients, and it provides a biomarker-based approach to systems vaccinology.

overall_design: RNA-seq were performed with peripheral blood mononuclear cells (PBMCs) of 9 COVID-19 patients infected by varient B.1.351of SARS-CoV-2 virus.

first: Ludwig

last: Knabl


title: Delamination of trophoblast-like syncytia from the amniotic ectodermal analogue in human primed embryonic stem cell-based differentiation model.

city: Kyoto

first: Masatoshi

last: Ohgushi

address: 53 Shogoin Kawahara-cho, Sakyo-ku

department: Instutute for Frontier Life and Medical Sciences

institute: Kyoto University


title: Cyclophilin D promotes disease tolerance to influenza A virus infection by licensing NK cell development and function

city: Chicago

first: Luis

middle: B

last: Barreiro

address: 900 E 57th Street

institute: University of Chicago

summary: An effective immune response to influenza A virus (IAV) requires two arms: host resistance, which restricts viral replication, and disease tolerance that limits tissue damage caused by the immune response to IAV. Interestingly, fatal influenza infections are more often associated with dysregulated inflammation, rather than an inability to control viral replication, highlighting the importance of mechanisms involved in disease tolerance to IAV. Here, we show that cyclophilin D (CypD), a mitochondrial protein known to regulate cell death and cytokine production, protects against IAV infection through disease tolerance. Mice deficient in CypD (CypD-/-) exhibit enhanced susceptibility to IAV infection, despite comparable myeloid immune responses and intact antiviral immunity. Instead, CypD-/- susceptibility was due to pulmonary tissue damage, caused by a lack of the cytokine IL-22 that protects the lung epithelium. We found the necessary source of IL-22 following IAV infection to be conventional natural killer (NK) cells that failed to reach the airways of infected CypD-deficient mice, as a result of dysregulated lymphopoiesis in the bone marrow. Importantly, following infection, a single administration of recombinant IL-22 in the airways abrogated pulmonary damage and rescued CypD-/- mice. Thus, the CypD/IL-22/NK cell axis is critical in immunity to IAV by promoting disease tolerance, limiting lung tissue damage and maintaining pulmonary function.

overall_design: RNA expression profiles of control (uninfected) and influenza-infected purified splenic natural killer (NK) cells from wild type (WT) and CypD knockout mice

first: Jeffrey

last: Downey

first: Haley

middle: E

last: Randolph

first: Erwan

last: Pernet

first: Kim

middle: A

last: Tran

first: Shabaana

last: Khader

last: Barriero

first: Maziar

last: Divangahi


title: Irf8 deficiency induces functional, transcriptional and epigenetic reprogramming of cDC1 into the cDC2 lineage

city: Lund

first: Jonas

last: Ungerback

address: Klinikgatan 26

department: Division of Molecular Hematology

country: Sweden

institute: Lund University

summary: Conventional dendritic cells (cDC) consist of two functionally and phenotypically distinct subsets, cDC1 and cDC2, whose development is dependent on distinct sets of transcription factors. Interferon regulatory factor 8 (IRF8) is required at multiple stages of cDC1 development, but its role in mature cDC1 remains unclear. Here we used XCR1-cre to delete Irf8 in committed cDC1 and demonstrate that Irf8 is required for maintaining the identify of cDC1 but not their survival. In the absence of Irf8, committed cDC1 (“ex-cDC1”) acquired the transcriptional, functional and chromatin accessibility properties of cDC2. This conversion was independent on Irf4 and was associated with decreased accessibility in putative IRF8, Batf3 and composite AP-1-IRF (AICE) binding elements, together with increased accessibility of cDC2 associated transcription factor binding elements. Thus, IRF8 expression by committed cDC1 is required for preventing their conversion into cDC2.

overall_design: Bulk RNA-seq and ATAC-seq was used to compare murine conventional dendritic cells sorted from mesenteric lymph nodes (MLN) in steady state from conditional knockout strains lacking IRF4 and/or IRF8 transcription factors.

first: Telma

last: Lanca

last: Ungerbäck

first: Julien

last: Vandamme

first: William

last: Agace


title: Anti-inflammatory clearance of amyloid beta by a chimeric Gas6 fusion protein [scRNA-Seq]

first: Hyuncheol

last: Jung

summary: To report the effects of Aducanumab or ⍺Aβ-Gas6 mediated Aβ phagocytosis on inflammatory responses in vivo

overall_design: We performed Single cell RNA seqeuncing using cells collected from the 8 m-old 5xFAD mouse hippocampus injected with LV-control, LV-Aducanumab, and LV-⍺Aβ-Gas6.

first: Se

middle: Y

last: Lee

first: Seongjoon

last: Lim

last: Chung


title: Delamination of trophoblast-like syncytia from the amniotic ectodermal analogue in human primed embryonic stem cell-based differentiation model [RNA-seq]

last: Ohgushi

summary: Human embryonic stem cells were converted into GATA3-expressing extraembryonic cells (GATA3+ ExE cells) when they were exposed to chemical inhibitors for ACTIVIN/NODAL (A83-01, 1uM) and FGF signaling (PD03714, 100nM). We refer here to this inhibitor-induced differentiation method as an 'AP' protocol. To understand the transcriptome dynamics during AP-induced differentiation, we performed timecourse profiling of genome-wide gene expression by RNA sequencing.

overall_design: To understand transcriptome dynamicts during trophoblast-like differentiation, GATA3 reporter human ESCs were exposed to AP for 0-8 days.


title: Semaphorin activates Hippo signaling to control cell growth

city: La Jolla

first: Yunjiang

last: Qiu

state: CA

address: 9500 Gilman Drive

institute: University of California, San Diego

summary: Semaphorins play critical roles in the tumorigenesis of various organs. Originally identified as neuronal axonal guidance molecules and developmental regulators of the nervous and the vascular systems, class 3 Semaphorins (SEMA3s) act through their receptors Plexin As (PLXNAs) and co-receptors Neuropilins (NRPs) to control various processes such as axon growth cone directionality, cell cycle, and angiogenesis. Deletion or silencing of SEMA3B and SEMA3F genes has been observed in lung cancer, metastatic breast cancer, renal carcinoma, and many other malignancies; however, the downstream effectors of SEMA3 in tumorigenesis are still unclear. Here we show that the Hippo pathway is a key mediator of SEMA3’s tumor suppressive function. SEMA3 activates the Hippo pathway to control gene expression and inhibit cell growth. Restoration of SEMA3B expression in lung cancer cells that harbor SEMA3B deletion or silencing suppressed anchorage-independent growth and xenograft formation in a Hippo pathway-dependent manner. Mechanistically, PLXNA promotes the interaction and activation of p190RhoGAPs (ARHGAP5 and ARHGAP35) by the RND GTPase. Activated ARHGAP5/35 in turn act through RhoA and the Hippo kinase cascade to phosphorylate and inactivate YAP and TAZ, the transcriptional co-activators and key effectors of the Hippo pathway. Cancer-associated mutations of RND or ARHGAP5/35 compromised cellular responses to SEMA3, as indicated by YAP phosphorylation and cell growth inhibition. Our study defines a new role of the Hippo pathway in SEMA3 signaling as well as a mechanism for the tumor suppressive function of Semaphorins.

overall_design: The overall goal is to examine expression changes in response to class 3 Semaphorins (SEMA3s). mRNA profiles of wild type (WT), LATS1/2 dKO (KO) upon SEMA3s treatment for U87-MG cells were generated using deep sequencing with three biological replicates.

first: Zhipeng

last: Meng


title: Single cell profiling of total murine lung cells

city: Helsinki

first: Andrey

last: Anisimov

address: Haartmaninkatu 8

department: Faculty of medicine

country: Finland

institute: University of Helsinki

summary: This dataset was generated using adult (11 weeks) wild-type mice as a part of multiorgan profiling project. The samples were analyzed using the Chromium Single-cell 3'RNA-sequencing system.

overall_design: Mouse lungs were dissociated to single cells by protease digestion

first: Kari

last: Alitalo


title: Genomic profiling of SSCs (spermatogonial stem cells) transplanted recipients (SSCTR), premature ovarian failure (POF) and wild-type (WT) control ovaries.

city: Shanghai

first: Ji

last: Wu

address: No.800, Dongchuan Road, Minhang District

institute: Shanghai Jiao Tong University

summary: Through comparing the global expression profiles of SSCTR, POF and WT using cDNA microarrays, the differences among the SSCTR, POF and WT will be revealed, especially about the molecular mechanisms induced transdifferentiation.

overall_design: Total RNAs were isolated from ovaries, including cell transplanted recipients (SSCTR), premature ovarian failure (POF) and wild-type (WT), and gene expression signature was detected by microarray.

first: Huacheng

last: Luo


title: Genome-wide AR and H3K27Ac binding profiles in DSRCT cells, xenograft and PDX mouse tumors

city: Houston

first: Mahinur

last: Mattohti

state: TX

address: 6670 Bertner Ave

department: Surgery

institute: Houston Methodist Research Institute

summary: DSRCT is an aggressive, often fatal, sarcoma subtype that usually present in post-pubertal adolescents and young adults. Though the pathognomonic EWSR1-WT1 fusion protein is responsible for tumorigenesis, the androgen receptor (AR) has been suggested as a key contributor to tumor survival and growth. Reverse-phase protein lysate arrays (RPPA) were used to identify new drug targets in DSRCT not present in Ewing sarcoma, a close molecular cousin that shares an EWSR1 N-terminus chimeric partner. Among the 151 proteins analyzed, the AR protein was the most differentially expressed protein, which led to follow-on studies to investigate its role in DSRCT survival and growth in cell lines, xenografts, and patient-derived tumor explants (PDXs), which retain the best fidelity to their human tumor counterparts. Modern-day 2nd-generation AR antagonists were tested for preclinical antitumor activity, in addition to novel AR-directed antisense oligonucleotides that rapidly suppress post-transcriptional activity. Our research demonstrates an important role for the AR in promoting tumor growth and survival in preclinical DSRCT models. Given the widespread availability of safe, orally administered FDA-approved agents used for prostate cancer, such as abiraterone or enzalutamide that potently block AR steroidogenesis or intracellular AR signaling, one could quickly evaluate their effect in DSRCT in phase 2 trials.

overall_design: Examination of AR and H3K27Ac binding in DHT stimulated or unstimulated DSRCT cell lines, xenograft and PDX mouse tumors

first: Mayinuer

last: Maitituoheti

first: Kunal

last: Rai

first: Joseph

last: Ludwig


title: Adult type Maturation of Human Induced Pluripotent Stem Cells Derived Cardiomyocytes

city: Farmington

first: Yasir

last: Suhail

state: Connecticut

address: 263 Farmington Avenue

department: BME

institute: UCHC

summary: Cardiac tissue constructs from human induced pluripotent stem cells (hiPSCs) have been  heralded for their possibilities to serve as disease models, utilized in drug screening and cardiac  regeneration. That potential remains to be realized because human iPSC derived cardiomyocytes  (hiPSC-CMs) are immature, and do not reflect the characteristics of adult human myocytes. Here,  we present a method to accelerate hiPSC-CM maturation by maintaining them on a substrate,  Cardiac Mimetic Matrix (CMM), which mimics the adult human heart matrix ligand chemistry  and submicron ultrastructure.

overall_design: 3 replicates each of human induced pluripotent stem cells, were differentiated and matured in 3 different conditions: 30 days maturation (d30), 60 days prolonged maturation (d60), and maturation on our Cardiomimetic Matrix (CMM). A total of 9 samples were seqeunced.

first: Kshitiz

last: Gupta


title: Reinforcement of DNA methylation in CHH context through RNA-directed DNA methylation ensures sexual reproduction in rice [BS-Seq]

city: Nanjing

first: Lili

last: Wang

address: Weigang No.1

institute: Nanjing Agricultural University

type: Methylation profiling by high throughput sequencing

summary: DNA methylation is an important epigenetic mark that regulates the expression of genes and transposons. RNA-directed DNA methylation (RdDM) is the main molecular pathway responsible for de novo DNA methylation in plants. Although the mechanism of RdDM has been well understood in Arabidopsis, mutations in RdDM genes cause no visible developmental defects in Arabidopsis. Here, we isolated and cloned Five Elements Mountain 1 (FEM1), which encodes RNA-dependent RNA polymerase 2 in rice. Mutation in OsRDR2 abolished the accumulation of 24-nt small interfering RNAs, and consequently substantially decreased genome-wide CHH methylation levels. Moreover, male and female reproductive development was disturbed, which led to the sterility of osrdr2 mutants. We discovered that OsRDR2-dependent DNA methylation likely regulates the expression of multiple key genes involved in stamen development and meiosis. In wild-type (WT) plants but not in osrdr2 mutants, genome-wide CHH DNA methylation levels were greater in panicles, stamens, and pistils than in seedlings. The global increase of methylation in reproductive organs of the WT was mainly explained by the enhancement of RdDM activity including OsRDR2 activity. Our results, which revealed a global increase in DNA methylation through enhancement of RdDM activity in reproductive organs, demonstrate the crucial role of OsRDR2 in the sexual reproduction of rice.

overall_design: whole genome wide DNA methylation data by bisulphite sequencing

first: Dong-Lei

last: Yang


title: Reinforcement of DNA methylation in CHH context through  RNA-directed DNA methylation ensures sexual reproduction in rice

type: Non-coding RNA profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Transcriptome analysis of myeloid cells after acute myocardial infarction (AMI) in C57BL/6N wild-type mice.

status: Public on Jun 20 2022

city: Hannover

first: Marc

middle: R.

last: Reboll

state: NDS

address: Carl-Neuberg-Str. 1

department: Molecular and Translational Cardiology, Department of Cardiology and Angiology

country: Germany

institute: Hannover Medical School

summary: Three days after AMI, myeloid cells were isolated from spleen and left ventricle and used in transcriptome analyses.

overall_design: Three spleens and 3 infarcted left ventricles were individually analyzed.

middle: R

first: Kai

middle: C

last: Wollert


title: Reinforcement of DNA methylation in CHH context through  RNA-directed DNA methylation ensures sexual reproduction in rice [sRNA-Seq]

overall_design: small RNA sequencing data


title: Over-expression of GUSB leads to primary resistance of anti-PD1 therapy in hepatocellular carcinoma

first: Xiangyi

last: Kong

address: Hanzhong road

institute: The First Affiliated Hospital of Nanjing Medical University

summary: Treatment with immunotherapy, particularly immune checkpoint blockade, can lead to benefit in the clinical setting. However, many preclinical and clinical studies suggest that resistance to anti-PD1 treatment frequently occurs, resulting in tumor relapse and treatment failure in cancer including hepatocellular carcinoma (HCC) patients. In  this  study ,10 HCC patients were treated with anti-PD1, and the biopsy samples before treatment were used for 289 nanostring panel RNA sequencing to compare responding and non-responding tumors to find possible pretreatment biomarkers or targets of the anti-PD1 therapy response

overall_design: In this study ,10 HCC patients were treated with anti-PD1 therapy. To found possible pretreatment biomarkers or targets of anti-PD1 treatment response, pre-treated biopsy samples of these patients were used for 289 nanostring panel RNA sequencing to compare responding and non-responding tumors

first: Weiwei

last: Tang


title: Promoter Capture-C analysis of Hepatocyte-like cells

city: Philadelphia

first: Christopher

last: Brown

state: PA

address: CRB, 415 Curie Bouevard

institute: University of Pennsylvania

summary: The goal of this study is to identify chromatin interactions in hepatocyte-like cells

overall_design: Methods: hepatocyte-like cells (HLC) were produced by differentiating three biological replicates of iPSCs (which in turn were generated from peripheral blood mononuclear cells using a previously published protocol (Pashos et al 2017.) 10 million cells were used for promoter Capture-C library generation. Custom capture baits were designed using an Agilent SureSelect library design targeting both ends of DpnII restriction fragments encompassing promoters (including alternative promoters) of all human coding genes, noncoding RNA, antisense RNA, snRNA, miRNA, snoRNA, and lincRNA transcripts, totaling 36,691 RNA baited fragments shows the custom bait map boundaries in hg19 coordinates). Each library was then sequenced on an Illumina NovaSeq. HiCUP was used to process the raw FastQ files into loop calls; we then used CHiCAGO to define significant looping interactions; a default score of 5 was defined as significant.

first: Struan

last: Grant


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

city: Frederiksberg C

first: Andrew

last: Williams

state: --- Select One ---

address: Dyrlægevej 100

country: Denmark

institute: University of Copenhagen

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

overall_design: RNA was obtained from the lungs of 11 pigs infected with A. suum and 12 uninfected pigs. Within each infection group, pigs were fed either a control diet or the control diet supplemented with 1 % PAC derived from grape seed


title: Enzymatic treatment using trypsin and cold-active protease for C2C12 myoblasts

city: Fukuoka

first: Yasuyuki

last: Ohkawa

address: 3-1-1 Maidashi

institute: Medical Institute of Bioregulation

summary: We have comprehensively profiled the time-series changes in gene expression dependent on enzymatic treatment using trypsin, and attempted to elucidate the global changes suppressed by treatment with cold active protease in a low-temperature environment.

overall_design: We performed BRB-seq for C2C12 cells after enzymatic treatment.

first: Atsuko

last: Miyawaki-Kuwakado

first: Qianmei

last: Wu

first: Kosuke

last: Tomimatsu

first: Akihito

last: Harada


title: Epigenetic mechanism and survival prognosis analysis of serum exosomes from ovarian cancer patients based on sequencing technology and Bioinformatics

city: Urumqi

first: xia

last: li

address: 567Shangde North Road

department: Department of Histology and Embryology ,School of Basic Medical Sciences

institute: Xinjiang Medical University

summary:
Background: This study aimed to screen the signaling axis of epigenetic modification in serum exosomes of ovarian cancer patients based on sequencing technology and raw signal analysis, perform an in-depth study of the potential mechanism of action of ovarian cancer, predict potential therapeutic targets and perform a survival prognosis analysis of potential targets
Methods: Serum exosomes from three ovarian cancer patients were selected as the experimental group, and serum exosomes from three uterine fibroid patients were selected as the control group. The whole transcriptomes of serum exosomes were used to obtain differentially expressed lncRNAs and mRNAs in ovarian cancer. The miRcode database and miRNA target gene prediction website were used to predict the target genes. Cytoscape software was used to draw a ceRNA network model of epigenetic modification of ovarian cancer serum exosomes, and R language was used for GO and KEGG enrichment analyses of the target genes. Finally, the TCGA website was used to download clinical and expression data related to ovarian cancer, and the common potential target genes obtained in the previous period were analyzed for survival.
Results: A total of 117 differentially expressed lncRNAs and 513 differentially expressed mRNAs (P < 0.05, |log2 FC|≥ 1.0) were obtained by combining sequencing data and raw signal analysis, and 841 predicted target genes were reciprocally mapped by combining the miRcode database and the miRNA target gene prediction website, resulting in 11 potential target genes related to ovarian cancer (FGFR3, BMPR1B, TRIM29, FBN2, PAPPA, CCDC58, IGSF3, FBXO10, GPAM, HOXA10, LHFPL4). Survival prognosis analysis of the above 11 target genes revealed that the survival curve was statistically significant (P < 0.05) for HOXA10-only genes but not for the other genes. Through enrichment analysis, we found that the above target genes were mainly involved in biological processes such as regulation of transmembrane receptor protein kinase activity, structural molecule activity with elasticity, transforming growth factor-activated receptor activity, and GABA receptor binding, and were mainly enriched in metabolism pathways regulating stem cell pluripotency, bladder cancer, glycerolipid metabolism, central carbon metabolism of cancer, and resistance to EGFR tyrosine kinase inhibitors.
Conclusions: The serum exosomal DIO3OS-hsa-miR-27a-3p-HOXA10 epigenetic modification signaling axis affects ovarian cancer development and disease survival prognosis by targeting transcriptional dysregulation pathways in cancer.

overall_design: Female serum exosomes, ovarian cancer group and ovarian normal control group

first: Xia

last: Li

first: He

last: Huang

first: Yurong

first: Chunju

last: Xu


title: Exosomal-microRNA transcriptome profiling of Parental and CSC-like MDA-MB-231 cells in response to cisplatin treatment [NanoString]

city: Semenyih

first: May Zie

last: Koh

state: Selangor

address: Jalan Broga

department: Faculty of Sciences and Engineering

country: Malaysia

institute: University of Nottingham Malaysia

summary: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype that promotes higher risk of metastasis and cancer reoccurrence, subsequently reduces survival rate of cancer patients. Cisplatin is one of the potential anticancer drugs for treating TNBC. However, occurrence of cisplatin resistance still remains as one of the challenges to fully eradicate TNBC. Since presence of cancer stem cells (CSCs) often known as one of the contributors of drug resistance, investigation has been conducted, suggesting sorted CSC-like subpopulation to be more resistant to cisplatin as compared to parental cells, alongside with higher self-renewability. On the other hand, plethora evidences showed the transmission of exosomal-miRNAs are capable of promoting drug resistance in breast cancers. In this study, we aim to elucidate the differential expression of exosomal-microRNAs profile and reveal the potential target genes in correlation to cisplatin resistance associated with CSC-like subpopulation by using TNBC cell line (MDA-MB-231). Utilizing next generation sequencing and Nanostring techniques, cisplatin-induced dysregulation of exosomal-miRNAs were evaluated in maximal for CSC-like subpopulation as compared to parental cells. Intriguingly, cisplatin induced a relatively oncogenic exosomal-miRNAs profile derived from treated CSC-like subpopulation as compared to treated parental cells, which may correlate to enhancement of drug resistance and maintenance of CSCs. Among the detected exosomal-miRNA profile in treated CSC-like subpopulation, unique clusters of miRNAs namely miR-221-3p, miR-196a-5p, miR-17-5p and miR-126-3p were predicted to target on six genes (ATXN1, LATS1, GSK3β, ITGA6, JAG1 and MYC), aligned with previous finding which demonstrated dysregulation of these genes in treated CSC-like subpopulation. Our results highlight the potential correlation of exosomal-miRNAs and their target genes as well as novel perspectives of the corresponding pathways that may be essential to contribute to the attenuated cytotoxicity of cisplatin in CSC-like subpopulation.

overall_design: The small RNA in exosomes of parental and CSC-like MDA-MB-231, before and after cisplatin treatment were analyzed by multiplexed NanoString nCounter miRNA expression assay (Human v3 miRNA panel)

first: May

middle: Z

first: Wan

last: Ho

first: Swee

middle: K

last: Yeap


title: Exosomal-microRNA transcriptome profiling of Parental and CSC-like MDA-MB-231 cells in response to cisplatin treatment

overall_design: The small RNA in exosomes of parental and sorted CSC-like MDA-MB-231, before and after cisplatin treatment were analyzed by Next Gen RNA Sequencing

first: Koh

last: Zie

first: Ho

last: Yong

first: Yeap

last: Keong


overall_design: The small RNA in exosomes of parental and CSC-like MDA-MB-231, before and after cisplatin treatment were analyzed by Next Gen RNA Sequencing and Nanostring


title: Transcriptome sequencing of triple-matched samples of gastric cancer patients with ovarian metastasis

first: Shenglin

address: 270 Dongan

institute: Fudan University

summary: Our aim was to decipher the underlying molecular mechanism of synchronous ovarian metastasis of gastric cancer. We hereby conducted transcriptome sequencing of triple-matched samples including normal gastric mucosa, primary gastric cancer and ovarian metastatic tumors from 3 individual patients with the application of Illumina sequencing platform with 150-bp paired-end. Follow-up analyses not only identified differentially expressed genes between different sample sets (a threshold of fold change >2 and adjusted P value <0.05) but also uncovered significantly enriched signaling pathways of individual type. To sum up, our comparative transcriptomic analyses of triple-matched fresh samples stored in liquid nitrogen profiled the molecular expression and revealed functionally enriched pathways underlying the ovarian metastasis of gastric cancer.

overall_design: Transcriptomic profiling of triple-matched primary gastric cancer, normal mucosae and ovarian metastasis with the application of deep sequencing via Illumina Hiseq.

first: Jianpeng

last: Gao

first: Dazhi


title: HDAC3 Inhibition Causes the Impairment in Development of Neocortical VIP Interneurons via dysregulation of Notch Signaling and Autism-like Behaviors

city: Isehara

first: Takatoshi

last: Iijima

state: Kanagawa

address: 143 Shimokasuya

department: School of Medicine

institute: Tokai University

summary: Autism spectrum disorders (ASDs) are a neurodevelopmental disorder characterized by impairments in social interactions and stereotyped behaviors. While ASD has a strong genetic background, environmental factors including toxins, pesticides, infection and drugs are also known to confer autism susceptibility, likely by inducing epigenetic changes. Exposure to Valproic acid (VPA), a drug for epilepsy and bipolar disorders, during pregnancy is highly associated with the risk of ASD children. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Since VPA is an inhibitor of histone deacethytransferase (HDAC) activity, it thought to cause ASD with epigenetic modification. However, the core mechanism by which prenatal VPA exposure causes onset of ASD is still not fully uncovered.  Here we revealed that prenatal VPA exposure strongly influences development of vasoactive intestinal peptide (VIP) - positive neurons, a subtype of cortical GABAergic interneurons. The number of VIP+ interneurons was severely reduced in somatosensory area of VPA-exposed ASD animals. We then found that the reduction in VIP+ interneurons is caused by the inhibition of HDAC3 activity upon prenatal VPA exposure. Importantly, prenatal HDAC3 inhibition caused not only the selective reduction in VIP+ interneurons but also the ASD-like behaviors in mice. We then demonstrated that the HDAC3 inhibition aberrantly activates Notch signaling, which influences the cell fate determination of VIP+ interneuron progenitors in caudal ganglionic eminence. Thus, this study uncovers the mechanism by which specific HDAC inhibition during development influences a specific type of GABAergic interneurons in the ASD model. The findings provide a novel insight into the understanding of ASD pathophysiology.

overall_design: To explore the whole aspect of prenatal VPA exposure on neural development, we screened the gene alteration in the in vitro VPA model that mimics in utero VPA exposure by transcriptomic analyses.

first: Yoko

last: Hanno-Iijima

first: Moe

last: Nakanishi

first: Masami

last: Tanaka

first: Masayuki

first: Chisa

last: Okada

first: Goichi

last: Miyoshi

first: Toru

last: Takumi


title: Changes in gene expression in SMCHD1 knockout clones of HCT116

city: Tallahassee

first: Sunny

last: Das

state: FL

address: 319 Stadium Drive

department: Biological Science

institute: Florida State University

summary: Development of effective therapies for complex Mendelian disorders such as Facioscapulohumeral muscular dystrophy necessitates a clear understanding of the pathology of this disease. The inappropriate expression of DUX4-fl is believed to be responsible for the disease phenotype. We sought to understand the role of SMCHD1, an epigenetic modifier of the D4Z4 array, in DUX4-fl expression, by a TALEN mediated knockout of the gene in a model cell line HCT116. Analysis of SMCHD1 and DNMT knockouts of HCT116, along with patient cell lines highlighted the importance of epigenetic determinants of the disease and revealed a novel DUX4 isoform. We show that while SMCHD1 loss sensitizes cells to DUX4 expression by increasing transcription of unspliced product from D4Z4, splicing of the transcripts to generate disease associated DUX4-fl can only be induced by CpG hypomethylation and loss of heterochromatic histone marker H3K9me3. Additionally, telomere shortening has an effect similar to SMCHD1 loss, suggesting involvement of a telomere position effect in maintaining DUX4 repression. In light of our observations, we have developed a model for expression of DUX4-fl through a simultaneous loss of heterochromatin at D4Z4 and at the telomere, otherwise maintained by SMCHD1 that acts as a bridge between these two regions.

overall_design: Samples include three replicate miroarray hybridizations of the parental cells (HCT116) and three replicates from three independent SMCHD1 knock-out clones (40, 41 and 43)

first: S

first: B

last: Chadwick


title: RNA-seq of Fasciola hepatica eggs during the maturation process elucidate the role of proteolytic enzymes

city: Brno

first: Jiri

last: Vorel

address: Kotlarska 267/2

department: Department of Botany and Zoology

country: Czech Republic

institute: Masaryk University

summary: Fasciola hepatica represents a socioeconomically important species of parasitic fluke which causes significant economic losses in the livestock industry. During an indirect life cycle, immature eggs are passed out of the host in the stool and embyonate in the external environment until the release of miracidium which invades a freshwater snail - intermediate host. By utilization of RNA-seq technique (Illumina NextSeq 500), differentially expressed genes were analysed in F. hepatica eggs during the maturation process in three time points: 0 days (freshly laid eggs by adult F. hepatica individuals) and after incubation for 5 and 10 days.

overall_design: Examination of 3 egg samples of different ages (0, 5, 10 days), 3 replicates per sample.


title: YAP/TAZ activity in stromal cells prevents ageing by controlling cGAS/STING

city: Padova

first: Silvio

last: Bicciato

address: via U. Bassi 59/b

department: Molecular Medicine

country: Italy

institute: University of Padova


title: cAMP-MicroRNA-203-IFNγ Network Regulates Subcutaneous White Fat Browning and Glucose Tolerance

city: Singapore

first: Lei

last: Sun

address: 8 College Road

country: Singapore

institute: Duke-NUS

summary: To determine the function of miR-203 in white fat browning upon cold exposure, we injected miR-203 inhibitors and negative control into inguinal white adipose tissue, followed by cold exposure (4oC) for 24 hours. Total RNA were harvested for RNA-seq.

overall_design: RNAs from 3 individual animals were pooled as one sample. Two samples were generated for the control and inhibitor conditions. Totally, 4 samples were collected and analyzed.

first: Yen

last: Lim


title: Genome-wide DNA methylation analysis using MethylCap-seq in canine high-grade B-cell lymphoma

city: Taipei

first: Chen-Si

last: Lin

address: No. 1, Sec. 4, Roosevelt Road

department: Department of Veterinary Medicine

country: Taiwan

institute: Nationwide Taiwan University

summary: In the present study, MethylCap-seq was used to characterize the genome-wide DNA methylation patterns in canine high-grade B-cell lymphoma (cHGBL). Canine methylated DNA fragments were captured and the MEDIUM-HIGH and LOW fraction of methylated DNA was obtained based on variation in CpG methylation density. In the MEDIUM-HIGH and LOW fraction, 2,144 and 1,987 cHGBL-specific hypermethylated genes, respectively, were identified. Functional analysis highlighted pathways strongly related to oncogenesis. The relevant signaling pathways associated with neuronal system were also revealed. In addition, 14 genes were hypermethylated in all the cHGBL cases but not in the healthy dogs. These genes might be potential signatures for tracing cHGBL. Further, the distinct methylation pattern of cHGBL showed a concordance with the clinical outcome, suggesting that aberrant epigenetic changes may influence tumor behavior. In summary, our study characterized genome-wide DNA methylation patterns using MethylCap-seq in cHGBL; the findings suggest that specific DNA hypermethylation holds promise for dissecting tumorigenesis and uncovering biomarkers for monitoring the progression of cHGBL.

overall_design: DNA methylation profiles of 5 cHGBL clinical cases and 3 healthy controls were generated by deep sequencing using Illumina Novaseq.

first: Chia-Hsin

last: Hsu

first: Wei-Chi

last: Wang


title: Lack of electron acceptors contributes to redox stress and growth arrest in asparagine-starved sarcoma cells

city: Freiburg

first: Geoffroy

last: Andrieux

address: Breisacherstr 153

institute: University clinics Freiburg

summary: Adequate availability of the non-essential amino acid asparagine is necessary to support growth and survival of sarcoma cells. The three top pathways enriched among transcripts upregulated in asparagine-depleted cells included ribosome, aminoacyl tRNA biosynthesis and oxidative phosphorylation.

overall_design: Transcriptional changes in asparagine-depleted mouse sarcoma cells compared to control mouse sarcoma cells were evaluated by RNA-Seq.

first: Christoph

last: Bauer

first: Melanie

last: Boerries

first: Simone

last: Hettmer


title: Identification of ocular regulatory functions of core histone variant H3.2

status: Public on Jun 19 2022

city: Munich

first: sharmilee

last: vetrivel

state: Bayern

address: ziemssenstraße 1, DG

institute: Ludwig Maximilian University of Munich (Universität München)

summary:
Transgene line containing the histone gene fused to GFP was established and characterized at genomic, transcriptional and protein level. The GFP tag was then used for ChIP Seq analysis of the DNA sequences bound by H3.2. The analysis revealed interesting ocular specific targets including Ephrin family genes. Altered incorporation of H3.2 was found in the mutant, specifically around the ligand Efna5 and the receptor Ephb2. The effect of this altered incorporation on Ephrin signaling was further analyzed by QPCR and immunohistochemistry.
Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for GFP (sc-9996)

overall_design: Sharmilee,Vetrivel

first: Florian

last: Giesert


title: Methylation of HBP1 by PRMT1 inhibits its tumor-suppressive function through regulating   2 GSN-mediated actin cytoskeleton remodeling

city: beijing

first: ZHANG

last: Tongjia

address: xueyuan Road 38

institute: peking university

summary: HBP1 is a sequence-specific transcription factor which acts as a tumor inhibitor. HBP1  exerts tumor-suppressive function through regulating the expression of many genes during cell  metabolism and cell cycle process. Posttranslational modification of HBP1 is crucial for its  function. In this study, we found that HBP1 was methylated at R378 by PRMT1, which decreased 16 HBP1 protein stability by promoting its ubiquitination and proteasome-mediated degradation.  PRMT1-mediated methylation of HBP1 could alleviate the repressive effects of HBP1 on tumor  metastasis and growth through regulation of GSN expression. GSN was identified as a novel  target gene of HBP1. Methylation of HBP1 promoted actin cytoskeleton remodeling and tumor  progression by downregulating GSN levels. The methylated HBP1-GSN axis was also associated  with the clinical outcomes of cancer patients. Targeting methylated HBP1-GSN axis may provide a  therapeutic strategy for cancer. Significance: This investigation elucidated the mechanism of how methylation of HBP1 at R378  inhibits its tumor-suppressive function and promotes actin cytoskeleton remodeling, thus  providing the strategy for targeting HBP1 during cancer treatment.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Hela cells(WT HBP1) and its mut derivatives (HBP1 R378A).

first: Jiyin

first: Ruixiang

last: Yang

first: Yuning

last: Cheng

first: Yue

last: Zhou

first: Tongjia

last: Zhang

first: Shujie

first: Hui

last: Li

first: Wei

last: Jiang

first: Xiaowei


title: A Physcomitrella protein acts in spermatogenesis and sporophyte abortion

first: Volker

middle: Michael

last: Lüth

address: Schänzlestr. 1

institute: University of Freiburg

summary: Functional targeting of PpPINC gene in Physcomitrella, researching it's role during gametangia and sporophyte development.

overall_design: Collection of mature gametangia, day 18 of sporophyte induction, per sample 8 antheridia (male) or 8 archegonia (female) were collected  from wild type and PpPINC mutant plant (pinC#29) on three different occasions.

middle: M

last: Lueth

first: Christine

last: Rempfer


title: The effect of metals on human prostaspheres derived from an immortalized human prostate epithelial cell line RWPE-1 cells

city: Cincinnati

first: Mario

last: Medvedovic

state: OH

address: 3223 Eden Av. ML 56

department: Department of Environmental Health

institute: University of Cincinnati

summary: Adverse health effects of metal contamination in our municipal waters is of an alarming concern. The molecular mechanisms that underlie effects of metals on prostate carcinogenesis is understudied. We demonstrated that levels of six metals were higher in the urinary samples collected from prostate cancer patients when compared to non-prostate cancer patients. We previously reported that environmental agents targeted human prostate epithelial stem progenitor cells and increased prostate cancer risk. Our study will reveal the molecular pathways underlying metal-induced transformation of human prostate epithelial stem progenitor cells.

overall_design: Prostate epithelial stem progenitor cells that were enriched as prostaspheres from an immortalized human prostate epithelial cell line RWPE-1 cells on ultra-low attachment matrices were treated with 1 μM lead chloride, 5 μM sodium arsenite, 1 μM copper (II) sulfate, 1 μM titanium oxide, 10 μM chromium (VI) sulfate, or 1 μM cadmium chloride for seven days . Human prostaspheres with no metal treatment was used as negative control.

first: Ana

last: Cheong

first: Pheruza

last: Tarapore

first: Bin

last: Ouyang

first: Xiang

first: Jacek

last: Biesiada

first: Yuet-Kin

last: Leung

first: Shuk-Mei

last: Ho


title: Lactobacillus brevis strains UCCLBBS124 and UCCLBBS449, control (MRS broth) vs. stress condition (5 % EtOH, pH4 or 30 ppm iso-a-acids)

city: Cork

first: Marine

last: Feyereisen

state: Cork

address: Western raod

country: Ireland

institute: Univeristy College Cork

summary: Transcriptional profiling of Lactobacillus brevis UCCLBBS124 and UCCLBBS449 comparing control strain grown in MRS broth with strains growing in different stress conditons (5 % EtOH, pH4 or 30 ppm iso-a-acids).This study aimed to evaluate how certain Lb. brevis isolates are adapted so as to allow them to survive and grow in beer.

overall_design: DNA-microarrays containing oligonucleotide primers combining shared and unique genes of the 2648 and 2719 annotated genes on the genome of Lb. brevis UCCLBBS124 and UCCLBBS449, respectively, were designed by and obtained from Agilent Technologies (Palo Alto, Ca., USA). Three diffrerent experiments: MRS broth vs. MRS broth 5% EtOh, MRS broth vs. MRS broth pH4, MRS broth vs. MRS broth 30 ppm iso-a-acids for each of the two Lb. brevis strains UCCLBBS124 and UCCLBBS449


title: Expression data from rats post injured tendons 1 week

status: Public on Jun 18 2022

city: Beijing

first: 唐

last: 伟评

address: 2 Anzhen Rd, Chaoyang District,

institute: Beijing Institute of Heart Lung and Blood Vessel Diseases

summary:
DNA methylation is involved in many biological activities, such as gene transcription, gene structure stabilization, cell differentiation and foreign body metabolism. Methylation often plays a role in gene silencing in gene regulated transcription. However, the role of DNA methylation of lncRNA in tendon repair is rarely reported.
All rats were randomly undertaken control surgery or injured tendons.Tendons were harvested 1 weeks following injured tendons and performed to further analysis.

overall_design: For microarray profiling, the rats tendons total RNA was harvested using TRIzol reagent (Invitrogen, Carlsbad, Canada) and purified using RNeasy Mini Kit (Qiagen, Hilden, Germany) according to the manufacturer’s protocol. The amount and quality of RNA were determined using UV-Vis Spectrophotometer (Thermo, NanoDrop 2000, USA) at the absorbance of 260 nm. The mRNA expression profiling was measured using Affymetrix ClariomTM D mouse Array (Affymetrix GeneChip, Santa Clara CA, USA), which contains 65957 gene-level probe sets.

first: Haibo

last: Zhao

first: Tengbo

last: Yu


title: Active DNA demethylation regulates MAMP-triggered immunity in Arabidopsis

city: Wuhan

first: mengling

last: Huang

state: Hubei

address: shizisan

department: College of Plant Science and Technology

institute: Huazhong Agricultural Universityhuazong

summary: We found that active DNA demethylation is required for MAMP-triggered immunity to bacteria pathogen. Triple mutant plants deficient in ROS1, DML2, and DML3 (RDD) exhibited compromised immune responses such as induction of immune genes .

overall_design: RNA-seq analysis was performed with 10-day-old seedlings or 4-week-old plants of WT, rdd with or without 100 nM flg22 treatment for 1 h, 3 h, 24 h, and priming . Three independent repeats were performed for RNA-seq analysis. DNA methylation profiles of 10-day-old seedlings of WT, rdd with or without 100 nM flg22 treatment for 1 h, 6 h, 12 h. Three independent repeats were performed for Whole-Genome Bisulfite analysis. Three independent repeats were performed for Whole-Genome Bisulfite analysis.  For adult-plants, 4-week-old plants were hand-inoculated with H2O  or 100 nM flg22 for 24 h. Two independent repeats were performed for Whole-Genome Bisulfite analysis.

first: Mengling

first: Ying

last: Zhang

last: Wang

first: Jiatao

last: Xie

first: Jiasen

last: Cheng

first: Yanping

last: Fu

first: Daohong

first: Libo

last: Shan

first: Ping

last: He

first: Xiao

first: Bo


title: The novel circle-RNA ZNF208 regulates the proliferation of cervical cancer fibroblasts through a ceRNA network

city: Nanjing

first: Wei

last: Sun

state: Jiangsu

address: Nanjing, Jiangsu, China

institute: Jiangsu People's Hospital

summary: Cervical cancer is one of the major cancers that threaten the health of women. CircRNA is an important factor in the regulation of cancer development and progression. The role of circRNA in cervical cancer is less well studied. The aim of this study was to explore the mechanism of circRNA effects on cervical cancer using circRNA-seq technology to study the expression profile data of 9 pairs of primary cervical cancer and paracancerous tissues.

overall_design: The clinical samples were added into TRizol reagent (Life Technologies) and the total RNA was extracted using the total RNA extraction kit (Tiangen, China) from each sample per the manufacturer’s instructions.Then, whole transcriptome libraries were constructed using the TruSeq Ribo Profile Library Prep Kit (Illumina, United States) per the manufacturer’s protocol. Briefly, 10 mg of total RNA was depleted of rRNA with an Illumina RiboZero Gold kit and purified for end repair and 5’-adaptor ligations. Next, reverse transcription was performed with random primers containing 3’ adaptor sequences and randomized hexamers.   Finally, cDNA fragments of 250–400 bp were purified and amplified by 15–20 cycles of PCR. The libraries were subjected to 150 nt paired-end sequencing with an Illumina Hiseq4000 system (BGI, China). At least 45 million read pairs were generated for each library, and adapters were removed with VAHTSTM DNA Clean reads to obtain clean reads.


title: RNA profile in TRIM24-C52/55A knockin mouse liver

first: Chen

last: Shuai

address: Xuefu Road 12

institute: Nanjing University

summary: RNA profiling was performed in the liver of TRIM24-C52/55A knockin mice fed the high fat diet to identify key downstream targets of TRIM24.

overall_design: Deep sequencing of RNA in the liver of HFD-fed WT and TRIM24C52/55A mice

first: Shuai

last: Chen

first: Wen

last: Wei


title: CDDO drives transcriptomic and epigenetic reprogramming in response to TPA-induced JB6 cell neoplastic transformation [Methyl-seq]

city: Piscataway

first: Hsiao-Chen Dina

last: Kuo

address: 160 frelinghuysen road

department: Ernest Mario School of Pharmacy

institute: Rutgers University

summary: 12-O-tetradecanoylphorbol-13-acetate (TPA) promotes skin carcinogenesis. CDDO is a potential antioxidative and antiinflammatory agent to prevent the TPA-induced skin cell transformation at nanomolar scale. We characterized the transcriptome, CpG methylome, and pathway network of JB6 cells treated with TPA and TPA + CDDO using RNA sequencing, methyl sequencing, and QIAGEN Ingenuity Pathway Analysis.

overall_design: Samples of JB6 cells were used for extraction of DNA and RNA; DNA was enriched by Agilent SureSelect Kit then bisulfite converted methyl-seq was performed. RNA-seq was performed with routine strategy. This dataset contains data for the Methyl-seq only; Check the other SubSeries under this SuperSeries for RNA-seq data.

first: Renyi

last: Wu

first: Meinizi

last: Zheng

first: Davit

last: Sargsyan

first: Ah-Ng

last: Kong


title: CDDO drives transcriptomic and epigenetic reprogramming in response to TPA-induced JB6 cell neoplastic transformation

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

overall_design: Refer to individual Series


title: Transcription factor fluctuations underlie cell-to-cell variability in the Hedgehog response [bulk-RNAseq]

city: St. Louis

first: Barak

last: Cohen

state: Missouri

address: 4515 McKinley Ave

department: Genetics

institute: Washington University in St. Louis School of Medicine

summary: Stochastic differences among clonal cells can initiate cell fate decisions in development or cause cell-to-cell differences in the responses to drugs or extracellular ligands. We hypothesize that some of this phenotypic variability is caused by stochastic fluctuations in the activities of transcription factors. We tested this hypothesis in NIH3T3-CG cells using the response to Hedgehog signaling as a model cellular response. Here we present evidence for the existence of distinct fast and slow responding substates of NIH3T3-CG cells. These two substates have distinct expression profiles, and fluctuations in the activity of the Prrx1 transcription factor (TF) underlie some of the differences in expression and responsiveness between fast and slow cells. We speculate that similar variability in other TFs may underlie other phenotypic differences among genetically identical cells.

overall_design: NIH3T3-CG cells were transfected (Srebf2, Prrx1, Egr1, Jun and Snai1) and transduced (Prrx1) with different transcription factors. We collected cells that were transfected with the TF and a control plasmid and performed bulk RNA-sequencing on the two groups. For the transduced cells, we collected cells with Dox added and with no Dox added and performed bulk RNA-sequencing on the two groups.

first: Ramu

last: Avinash

first: Cohen

last: Barak


title: Paracrine-Mediated Rejuvenation of Aged Mesenchymal Stem Cells

city: New Haven

first: George

last: Hung

address: 300 George Street Room 741

institute: Yale University

summary: To examine underlying differences in gene expression between young and old MSCs  and the effects of exposure of old MSCs to media conditioned by young MSCs on gene expression  we performed RNA sequencing

overall_design: 6 replicates of 100 000 old MSCs were cultured separately  or in co-culture with young MSCs for 7 days using a 04 micron Transwell system in 6-well plates.

first: Andreas

last: Barth

first: Peter

middle: V

last: Johnston


title: CDDO drives transcriptomic and epigenetic reprogramming in response to TPA-induced JB6 cell neoplastic transformation [RNA-seq]

overall_design: Samples of JB6 cells were used for extraction of DNA and RNA; DNA was enriched by Agilent SureSelect Kit then bisulfite converted methyl-seq was performed. RNA-seq was performed with routine strategy. This dataset contains data for the RNA-seq only; Check the other SubSeries under this SuperSeries for Methyl-seq data.


title: The miRNA expression of exosome secreted by human urine-derived stem cells

city: zhengzhou

first: Li

last: Xudong

state: Henan

address: No. 1, Jianshe East Road, Erqi District

institute: The First Affiliated Hospital of Zhengzhou University

summary: We identify miRNA profiles from exosomes of human urine-derived stem cells (USCs).

overall_design: We hypothesized that miRNAs in the human urine-derived stem cells (USCs)-derived exosomes contributed to the vaginal epithelial cells through exosome transfer. MiRNA microarray analysis was performed on exosomes secreted by human USCs cells.

first: Qingkai

first: Yiyun

last: Xu


title: 4hpi - 6wpi Gene Expression in HCMV-Infected Primary Human Monocytes

city: Shreveport

first: Bailey

last: Mosher

state: LA

address: 1501 Kings Highway

department: Microbiology & Immunology

institute: Louisiana State University Health - Shreveport

summary: To investigate how HCMV alters monocyte gene expression over time, we collected RNA from HCMV-infected primary human monocytes (3 donors) from 4 hours to 6 weeks post infection and analyzed the differential gene expression by RNAseq.

overall_design: Primary human monocytes were mock-infected or HCMV-infected. RNA was collected at 4 hpi, 24 hpi, 2 wpi, 4 wpi, and 6 wpi. 3 replicates are included.

first: Jung

last: Kim

first: Akhalesh

last: Shakya

first: Donna

last: Collins-McMillen

first: Andrew

last: Yurochko


title: Gene Expression Data of Pancreatic Ductal Adenocarcinoma and Normal Tissue

city: Chongqing

first: Junfeng

last: Zhang

address: Gaotan Yanzheng Street, Shapingba District

institute: First Affiliated Hospital of Army Medical University

summary: We used Affymetrix HTA2.0 Array to identify the expression differences between 10 pancreatic ductal adenocarcinoma samples and 5 normal tissue samples.

overall_design: This experiment consists of 10 pancreatic ductal adenocarcinoma samples and 5 normal tissue samples. Gene expression was analyzed on Affymetrix HTA2.0 Array.

first: H

last: Wang

first: Songsong

last: Liu


title: The 3D architecture of the pepper genome and its relationship to function and evolution

status: Public on Jun 17 2022

city: Guangzhou

first: Juntao

state: Guangdong

address: Wushan Street

department: Collage of Horticulture

institute: South China Agricultural University

summary: The organization of chromatin into self-interacting domains is universal among eukaryotic genomes, though how and why they form varies considerably. Here we report a chromosome-scale reference genome assembly of pepper (Capsicum annuum) and explore its 3D organization through integrating high-resolution Hi-C maps with epigenomic, transcriptomic, and genetic variation data. Chromatin folding domains in pepper are as prominent as TADs in mammals but exhibit unique characteristics. They tend to coincide with heterochromatic regions enriched with retrotransposons and are frequently embedded in loops, which may correlate with transcription factories. Their boundaries are hotspots for chromosome rearrangements but are otherwise depleted for genetic variation. While chromatin conformation broadly affects transcription variance, it does not predict differential gene expression between tissues. Our results suggest that pepper genome organization is explained by a model of heterochromatin-driven folding promoted by transcription factories and that such spatial architecture is under structural and functional constraints.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for the histone modifications YZ-H3K27me3, YZ-H3K4me3 and YZ-H3K9me2 in Pepper leaves.

first: Yi

last: Liao

first: Zhangsheng

last: Zhu

first: Yuanlong

first: Jinfeng

last: Chen

first: Yongfeng

last: Zhou

first: Feng

first: Jianjun

last: Lei

first: Brandon

middle: S

last: Gaut

first: Bihao

last: Cao

first: JJ

last: Emersion

first: Changming


title: GPNMB confers risk for Parkinson’s disease through interaction with alpha-synuclein

city: Philadelphia

first: Alice

last: Chen-Plotkin

address: 150 Johnson Pavilion

department: Neurology

institute: University of Pennsylvania

summary: Many risk loci for Parkinson’s disease (PD) have been identified by genome-wide association studies (GWAS), but target genes and mechanisms remain largely unknown. We linked the GWAS-derived chromosome 7 locus (sentinel SNP rs199347) to GPNMB, through colocalization analyses of expression quantitative trait locus (eQTL) and PD risk signals, confirmed by allele-specific expression studies in human brain. In cells, Glycoprotein Nonmetastatic Melanoma Protein B protein (GPNMB) co-immunoprecipitated and co-localized with alpha-synuclein (aSyn). In induced pluripotent stem cell-derived neurons, loss of GPNMB resulted in loss of ability to internalize aSyn fibrils and develop aSyn pathology. In 781 PD and 59 control biosamples, GPNMB was elevated in PD plasma, associating with disease severity. Thus, GPNMB represents a PD risk gene, with potential for biomarker development and therapeutic targeting.

overall_design: Differential gene expression analysis of RNA-seq of iPSC neurons; WT iPSC neurons compared to heterozygous (Het) and homozygous (KO) loss of GPNMB on days 0 and 14 of differentiation. There were in total 30 RNA samples: 3 genotypes (WT, Het and KO) x 2 differentiation time (days 0 and 14) x 5 biological replicates.

first: Maria

last: Diaz-Ortiz

first: Yunji

last: Seo

first: Marijan

last: Posavi

first: Marc

last: Carceles Cordon

first: Elisia

last: Clark

first: Nimansha

last: Jain

first: Rakshita

last: Charan

first: Michael

middle: D

last: Gallagher

first: Travis

middle: L

last: Unger

first: Noor

last: Amari

first: R

middle: T

last: Skrinak

first: Roseanne

last: Davila-Rivera

first: Eliza

last: Brody

first: Noah

last: Han

first: Rebecca

last: Zack

first: Vivianna

last: Van Deerlin

first: Thomas

middle: F

last: Tropea

first: Kelvin

last: Luk

first: Edward

last: Lee

first: Daniel

last: Weintraub


title: A Novel Cytoskeletal Action of Xylosides

status: Public on Jun 16 2022

city: Bethesda

first: Herbert

last: Geller

state: MD

address: 9000 Rockville Pike

department: Cell and Developmental Biology

institute: NHLBI

summary: To investigate the concentration-dependent effects of xylosides on morphology and gene expression of Neuro2A cells

overall_design: Neuro2A cells were exposed to DMSO, 500 nM xyloside or 1 mM xyloside for 48 h.  We then performed gene expression profiling analysis using data obtained from RNA-seq of the 3 different conditions.

first: Caitlin

middle: P

last: Mencio


title: Human umbilical vein endothelial cells: Control vs. Uninfected Groups

city: Foshan

first: gong

last: meiling

address: Foshan university

institute: College of Life Sciences and Engineering

summary: Experiments compared uninfected ECV304 cells with ECV304 cells infected with HSV-2, and both were tested for differential genes by microarray with the goal of determining the effect of HSV-2 on gene expression in ECV304 cells.

overall_design:
Internal reference genes and positive and negative control genes are set on the chip. Each control gene was replicated 12 times

This series includes a dual-channel experiment displayed with each GSM representing a single channel, either Cy3 or Cy5.

first: Zhao

last: Haiquan

first: Gong

last: Meiling


title: Development of a physiological insulin resistance model in human stem cell-derived adipocytes

city: Cambridge

first: Max

last: Friesen

address: 455 Main St

institute: Whitehead Institute

summary: Adipocytes are key regulators of human metabolism, and their dysfunction in insulin signaling is central to metabolic diseases including type II diabetes mellitus (T2D). However, the progression of insulin resistance into T2D is still poorly understood. This limited understanding is due, in part, to the dearth of suitable models of insulin signaling in human adipocytes. Traditionally, adipocyte models fail to recapitulate in vivo insulin signaling, possibly due to exposure to supraphysiological nutrient and hormone conditions. We developed a protocol for hPSC-derived adipocytes that uses physiological nutrient conditions to produce a potent insulin response comparable to in vivo adipocytes. After systematic optimization, this protocol allows robust insulin-stimulated glucose uptake and transcriptional insulin response. Furthermore, exposure of sensitized adipocytes to physiological hyperinsulinemia dampens insulin-stimulated glucose uptake and dysregulates insulin-responsive transcription. Overall, our methodology provides a novel platform for the mechanistic study of insulin signaling and resistance using human pluripotent stem cell-derived adipocytes.

first: M

last: Inmaculada Barrasa

first: Rudolf

last: Jaenisch


title: Transcriptome of Knockdown Pspc1 in the MS1 pancreatic islet endothelial cell line

city: Taipei

first: Yuh-Shan

last: Jou

state: --- Select a state ---

address: No.128,Sec. 2, Academia Rd. Nankang

department: Institute of biomedical science

institute: Academia Sinica

summary: Specific knockout Pspc1 in mouse endothelial cells cause neonatal death with multiple defects related to vascular development. The transcriptome of Pspc1 knockdown in MS1 cells corresponded to the findings from  in-vivo model and reveal dampened signaling pathways.

overall_design: The mouse endothelial cell line MS1 was choosed to infect lentivirus with shRNA taregting to Pspc1 and LacZ(as control). The RNA profilings were compared, and the result were present by gene set enrichment analysis.

first: Chieh-Yu

last: Chang


title: Transcriptomic analysis of B-box containing protein (BBX4)-regulated genes in response to light

first: Xuncheng

last: Wang

address: 5 Yiheyuan Road

institute: Peiking University

summary: Global analysis of  genes regulated by BBX4 in response to light in Arabidopsis

overall_design: mRNA profiles of Arabidopsis Col and bbx4-1 mutant seedlings grown in constant red light for 4 days were combined respectively from three biological replicates for RNA sequencing.

first: Yueqin

last: Heng

first: Xing

middle: W

last: Deng

first: Dongqing

last: Xu


title: Reinforcement of DNA methylation in CHH context through RNA-directed DNA methylation ensures sexual reproduction in rice [RNA-seq]

first: Lili

address: Weigang No.1

institute: Nanjing Agricultural University

summary: DNA methylation is an important epigenetic mark that regulates the expression of genes and transposons. RNA-directed DNA methylation (RdDM) is the main molecular pathway responsible for de novo DNA methylation in plants. Although the mechanism of RdDM has been well understood in Arabidopsis, mutations in RdDM genes cause no visible developmental defects in Arabidopsis. Here, we isolated and cloned Five Elements Mountain 1 (FEM1), which encodes RNA-dependent RNA polymerase 2 in rice. Mutation in OsRDR2 abolished the accumulation of 24-nt small interfering RNAs, and consequently substantially decreased genome-wide CHH methylation levels. Moreover, male and female reproductive development was disturbed, which led to the sterility of osrdr2 mutants. We discovered that OsRDR2-dependent DNA methylation likely regulates the expression of multiple key genes involved in stamen development and meiosis. In wild-type (WT) plants but not in osrdr2 mutants, genome-wide CHH DNA methylation levels were greater in panicles, stamens, and pistils than in seedlings. The global increase of methylation in reproductive organs of the WT was mainly explained by the enhancement of RdDM activity including OsRDR2 activity. Our results, which revealed a global increase in DNA methylation through enhancement of RdDM activity in reproductive organs, demonstrate the crucial role of OsRDR2 in the sexual reproduction of rice.

overall_design: Total RNA sequencing data

first: Dong-Lei

last: Yang


title: In vivo loss of TET2 and TET2 results in aberrant differentiation and homeostasis in the small intestine

city: Heidelberg

first: Guenter

last: Raddatz

address: Im Neuenheimer Feld 580

institute: German Center for Cancer Research

summary: Although much research has been done on the diversity of the gut microbiome, little is known about how it influences intestinal homeostasis under normal and pathogenic conditions. Epigenetic mechanisms have recently been suggested to operate at the interface between the microbiota and the intestinal epithelium. We performed whole-genome bisulfite sequencing on conventionally raised and germ-free mice, and discovered that exposure to commensal microbiota induced localized DNA methylation changes at regulatory elements, which are TET2/3-dependent. This culminated in the activation of a set of ‘early sentinel’ response genes to maintain intestinal homeostasis. Furthermore, we demonstrated that exposure to the microbiota in dextran sodium sulfate-induced acute inflammation results in profound DNA methylation and chromatin accessibility changes at regulatory elements, leading to alterations in gene expression programs enriched in colitis- and colon-cancer-associated functions. Finally, by employing genetic interventions, we show that microbiota-induced epigenetic programming is necessary for proper intestinal homeostasis in vivo.

overall_design: Overall 6 colon crypts samples from eleven-weeks old mice were analyzed. Three of them correspond to WT mice (Tet2/3 fl/fl) and three correspond to Tert2/3-depleted mice (Tet2/3 fl/fl VillinCre).

first: F

last: Lyko

first: Y

last: Bergman


title: Locomotor ability and brain gene expression in Drosophila melanogaster exhibit non-monotonic dose-response to HFPO-DA

city: San Diego

first: Goran

last: Bozinovic

state: CA

address: 3030 Bunker Hill St

institute: Boz Life Science Research and Teaching Institute

summary: Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants known for their bio-accumulative properties and prevalence in water supplies and household products. Although legacy PFAS, such as perfluorooctanoic acid, are phased out in the U.S. due to public health concerns, a PFAS variant hexafluoropropylene oxide-dimer acid (HFPO-DA) is an emerging replacement. HFPO-DA is a potential neurotoxicant that has been shown to cause dopaminergic neurodegeneration. We investigated the bioaccumulative potential of HFPO-DA and its effects on lifespan, locomotor activity, and brain gene expression in female and male Drosophila melanogaster (fruit flies). Flies were collected less than 4 hours post-eclosion and exposed to 0, 10, 10^2, 10^3, or 10^4 mg/kg/day HFPO-DA. To measure the effect of HFPO-DA on lifespan, surviving flies from each exposure were recorded every 24 hours. Flies were subjected to a negative geotaxis assay at 3, 7, and 14 days of exposure to measure the effects of acute, sub-chronic, and chronic exposures on locomotor ability. To capture HFPO-DA-induced sexually dimorphic gene expression responses in the brain, we sequenced brain-specific mRNA from flies exposed for 3, 7, or 14 days. The Bioconcentration Factor was 0.031 for females, and 0.026 for males. Dose and median lifespan were negatively correlated in both female (R^2 adj = 0.77, p<0.0001) and male flies (R^2 adj = 0.77, p<0.0001). Log-rank Mantel-Cox tests and one-way ANOVAs revealed that median lifespan was reduced in females starting at 10 mg/kg/day and in males starting at 10^2 mg/kg/day (p< 0.01). Acute exposure at 10 mg/kg/day significantly decreased locomotor ability in females (p<0.0001) while acute exposures at 1 mg/kg/day decreased locomotor activity in males (p <0.0001). Among 7500 genes analyzed, pairwise gene expression comparison between controls and treatments identified 2496 differentially expressed genes. While HFPO-DA does not readily bioaccumulate in fruit fly bodies, high-dose exposures have sex-specific effects on lifespan, locomotor ability, and brain gene expression. LOAEL for median lifespan is 10 mg/kg/day in females, and 10^2 mg/kg/day in males. Both locomotor ability and brain gene expression exhibited non-conventional dose-response as seen in other endocrine disrupting chemical exposures.

overall_design: Gene expression profiling analysis of shallow RNA-seq data for D. melanogaster 3, 7, and 14 day exposures to hexafluoropropylene oxide dimer acid (HFPO-DA); three replicates of 24 experimental conditions (2 sex, 3 different dosages of HFPO-DA plus a control, 3 exposure durations) were generated, with each condition containing around 100 fly brains.

first: Jeanne

last: Vu

first: Flannery

last: McLamb

first: Sylvia

last: Gong

first: Zuying

last: Feng

first: Richard

last: Gersberg


title: Cyclin-dependent kinase 9 is a therapeutic target for anti-TNF resistant inflammatory bowel disease

city: London

first: Arnulf

last: Hertweck

address: Gower Street

department: UCL Cancer Institute

country: United Kingdom

institute: University College London

summary: The treatment of auto-inflammatory diseases is often limited by resistance to single cytokine blockade, primarily anti-TNF antibodies. This is a particularly important cause of treatment failure in inflammatory bowel disease (IBD). The transcription factor T-bet is a critical regulator of intestinal homeostasis and is genetically linked to mucosal inflammation by causal variation in its binding sites. However, transcription factors such as T-bet are difficult to target therapeutically. Using CDK9 inhibitors, we show that modulation of P-TEFb (cyclinT1/CDK9), a transcriptional elongation factor downstream of T-bet, potently represses genes responsible for pro-inflammatory signalling, and in particular genes regulated by T-bet. Remarkably, CDK9 inhibition targets genes that are highly expressed in anti-TNF resistant IBD and that predict non-response to anti-TNF therapy. Collectively, our findings reveal CDK9 as a potential target in anti-TNF resistant IBD, which has the potential for rapid translation to the clinic.

overall_design: poly-A+ RNA-Seq in human primary and secondary stimulated colonic CD4+ T cells from Crohn's disease and ulcerative colitis patients treated with NVP-2 or control

middle: G

last: Jenner

first: Omer

last: Omer

first: Graham

last: Lord


title: Annotation of estrogen-regulated enhancer RNAs [RNA-Seq]

city: Dallas

first: W. Lee

last: Kraus

state: TX

address: 5323 Harry Hines Blvd.

institute: UT Southwestern Medical Center

summary: To study the effects of BCAS2, an eRNA-interacting protein, depletion on estrogen-responsive genes.

overall_design: RNA-seq libraries from polyA-enriched fractions in MCF-7 treated with either DMSO or 6 hr 17-b-estradiol.

first: Tim

middle: Y

last: Hou

first: W


title: Gene expression profile at the single cell level of vagal ganglia neurons from P4 mice

city: Berlin

first: Carmen

last: Birchmeier

address: Robert-Roessle-Str. 10

institute: MDC

summary: Vagal neurons are an incredibly heterogeneous population of sensory neurons that are important for homeostasis. We used single cell RNA sequencing (scRNA-seq) to interrogate their molecular diversity shortly after birth.

overall_design: Vagal neurons from VGlut2Cre;R26-nGFP mice were isolated by fluorescence activated cell sorting (FACS) according to the presence of nuclear GFP at P4 and analyzed using scRNA-seq.

first: Aristotelis

last: Misios

first: Elijah

last: Lowenstein


title: Effects of deletion of Arhgef15 gene in mouse sertoli cells  on spermatogenesis

city: Beijing

first: Feng

last: Chen

address: 2 Yuanmingyuan West Road, Haidian District, Beijing

institute: China Agricultural University

summary: Sertoli cells, which are the only somatic cells in the seminiferous tubules, facilitate the maintenance of testicular immune privilege through the formation of the blood-testis barrier (BTB) and the expression of immunoregulatory factors. Rho guanosine exchange factor 15 (ARHGEF15) is a member of guanosine exchange factors, which are involved in cell migration, cell polarity, and cell cycle progression via activation of Rho GTPases. This study investigated the functions of ARHGEF15 in Sertoli cells during spermatogenesis using Sertoli cell–specific Arhgef15 knockout mice. The results showed that Arhgef15 deficiency in Sertoli cells affected the localization of Sertoli cell nuclei, disrupted BTB integrity, and led to premature shedding of germ cells. In Arhgef15flox/flox/Amh-Cre+ mice, the ultrastructure of the round spermatids was impaired, accompanied by acrosome degeneration, acrosomal vesicle shedding, and atrophic nuclei. Consequently, the percentage of abnormal sperm in the Arhgef15flox/flox/Amh-Cre+ epididymis was markedly elevated. RNA-sequencing analysis revealed that most of the differentially expressed genes in Sertoli cells of Arhgef15flox/flox/Amh-Cre+ mice were related to immunity. Further study revealed that the sera of Arhgef15flox/flox/Amh-Cre+ mice showed immunoreactivity against testicular lysate of wild-type mice, indicating the production of antibodies against testicular autoantigens in Arhgef15flox/flox/Amh-Cre+ mice. In conclusion, the specific deletion of Arhgef15 in Sertoli cells leads to sperm abnormality, probably by disrupting the testicular immune homeostasis, in mice.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for the mouse of Sertoli-cell knockout Arhgef15 gene

first: Yingjie

last: Wu

first: Yinghe

last: Qin


title: IL-13Ra1-mediated signaling regulates ABC expansion and lupus pathogenesis

city: New York

first: HSS Genomics

last: Research Center

state: New York

address: 535 E 70th St

department: Research

institute: Hospital for Special Surgery

summary: ABCs are an emerging B cell subset that aberrantly expand in SLE. ABC generation and differentiation exhibit marked sexual dimorphism and TLR7 engagement is a key contributor to these sex differences. ABC generation is also controlled by IL-21 and its interplay with IFNg and IL-4. Here we investigated whether IL-13Ra1, an X-linked receptor that transmits IL-4/IL-13 signals, can regulate ABCs and lupus pathogenesis.

overall_design:
7 samples: 4 DKO, 3 IL13KO+DKO
contributor: HSS Genomics Research Center

first: Zhu

first: Danny

last: Castro

first: Sanjay

last: Gupta

first: Michela

last: Manni

first: Juan

last: Rivera-Correa

first: Rolf

last: Jessberger

first: Habib

last: Zaghuani

first: Eugenia

last: Giannopoulou

first: Tania

last: Pannelini

first: Alessandra

last: Pernis


title: Transcriptomic comparative analysis of different resistance to sheath blight in rice chromosome segment substitution lines

city: Nanchang

first: Haihui

last: Fu

address: 1101#, Zhimin Avenue，Nanchang, Jiangxi Province

institute: Jiangxi Agricultural University

summary: Purpose:The goals of this study are to compare NGS-derived  transcriptome profiling (RNA-seq) of  different resistance to sheath blight in rice chromosome segment substitution lines

overall_design: RNA-seq of three different resistance to sheath blight in rice chromosome segment substitution lines and Koshihikari  （one of parents）

first: Xiaotang

last: Sun

first: Haohua

last: He

first: Changlan

last: Zhu


title: Effects of NSUN6 deficiency by systematic transcriptomes and m5C profiles in mice across tissue

city: shenzhen

first: Liang

last: Fang

address: Shenzhen, Guangdong

department: Department of Biology

institute: Southern University of Science and Technology

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

overall_design: Refer to individual Series


title: Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches II

city: Boston

first: Megan

last: Sperry

state: MA

address: 3 Blackfan Circle

institute: Wyss Institute at Harvard University

summary: Current therapeutic strategies against bacterial infections focus on reduction of pathogen load using antibiotics; however, stimulation of host tolerance to infection in the presence of pathogens might offer an alternative approach. We used computational transcriptomics and Xenopus laevis embryos to discover infection response pathways, identify potential tolerance inducer drugs, and validate their ability to induce broad tolerance. Xenopus exhibits natural tolerance to Acinetobacter baumanii, Klebsiella pneumoniae, Staphylococcus aureus, and Streptococcus pneumoniae bacteria, whereas Aeromonas hydrophila and Pseudomonas aeruginosa produce lethal infections. Transcriptional profiling led to definition of a 20-gene signature that discriminates between tolerant and susceptible states, as well as identification of a more active tolerance response to gram negative compared to gram positive bacteria. Gene pathways associated with active tolerance in Xenopus, including some involved in metal ion binding and hypoxia, were found to be conserved across species, including mammals, and administration of a metal chelator (deferoxamine) or a HIF-1 agonist (1,4-DPCA) in embryos infected with lethal A. hydrophila increased survival despite high pathogen load. These data demonstrate the value of combining the Xenopus embryo infection model with computational multi-omics analyses for mechanistic discovery and drug repurposing to induce host tolerance to bacterial infections.

overall_design: Using embryos infected with A. hydrophila that are susceptible to infection, embryos were exposed to prophylaxis and/or post-infection treatment regimens of 40uM 1,4-DPCA. In the prophylactic treatment groups, we explored the effects of pretreating the pathogen or the Xenopus embryos separately to assess differential role of the drug on the overall disease tolerance response.

first: Richard

last: Novak

first: Michael

last: Levin

first: Donald

middle: E

last: Ingber


title: Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches I

overall_design: Xenopus were separately infected with six clinically-isolated bacterial pathogens, including gram negative (Acinetobacter baumanii, Klebsiella pneumoniae, Aeromonas hydrophila, and Pseudomonas aeruginosa) and gram positive (Staphylococcus aureus and Streptococcus pneumoniae) organisms. Gene expression was measured for embryos infected with each of the six types of bacteria both early after exposure (4 hours) and 1 day later (28 hours).


title: Effect of HGPP on MCD-diet NASH on gene expression during liver of C57BL/6 mice

city: Shanghai

first: Siran

last: Yue

address: CaiLun Road 1200,

institute: Shanghai University of traditional Chinese medicine

summary: Recent studies have revealed the pivotal role of gut microbiota in the precession of liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), have been extensively used applied in the treatment prevention of NASH, while the bioactive components and underlying mechanism remain unclear. The aim of this study was to investigate whether the polysaccharides of GP (GPP) has the protective effect on of NASH and to explore the potential mechanism underlying these effects. To investigate the function high dose of GPP(HGPP) in the regulation of hepatic gene expression, C57BL/6 male mice were fed with methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH, and administered daily oral gavage of the sodium carboxymethylcellulose (CMC-Na) for model group, HGPP for experimental group, compared with normal control methionine-choline-sufficient (MCS) group.

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq of liver samples from three groups of mice (including normal group: MCS-induced group, model group: MCD-induced group, experimental group: HGPP group).

first: Yiyun

last: Tan

first: Ruirui

last: Wang


title: Effects of NSUN6 deficiency by systematic transcriptomes and m5C profiles in mice across tissue [RNA-Seq]

summary: we constructed Nsun6-KO mouse, and observed that the wight and appearance of KO mice didn’t show abnormality. Through Bisulfite sequencing (BS-seq) in wild-type (WT) as well as KO mice and mRNA-seq, we identified high confident Nsun6-dependent m5C sites and performed the transcriptome analysis across five tissues.

overall_design: mouse tissue


title: Effects of NSUN6 deficiency by systematic transcriptomes and m5C profiles in mice across tissue [BS-Seq]

overall_design: mRNA-BisSeq


title: Annotation of estrogen-regulated enhancer RNAs [ChIP-Seq]

first: W. Lee

last: Kraus

summary: To study the effects of BCAS2, an eRNA-interacting protein, depletion on estrogen receptor alpha binding upon estrogen treatment.

overall_design: ChIP-seq libraries from MCF-7 treated with either DMSO or 45 min 17-b-estradiol.

first: Tim

last: Hou

first: W


title: White tea alleviates non-alcoholic fatty liver disease by regulating energy expenditure and lipid metabolism

city: Tianjin

first: Jiayuan

last: Chen

state: State...

address: Heping

institute: Tianjin Medical University

summary: Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.

overall_design: RNA-sequencing of liver tissues from mice treated with ND (normal diet), HFD (high fatty diet), HFD+WTE (high fatty diet + white tea extract)

last: Li


title: Decoding gene regulation in the mouse embryo using single-cell multi-omics

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary: During embryonic development, transcription-factor mediated remodelling of the epigenome is thought to precede changes in gene expression and prime cells for developmental trajectories. Yet, a comprehensive map of such epigenetic changes is lacking, as are the underlying gene regulatory networks. Here we generate a multi-omics atlas of mouse early organogenesis by simultaneously profiling gene expression and chromatin accessibility from tens of thousands of single cells. We develop a computational method to leverage the multi-modal readouts to predict transcription factor binding events in cis-regulatory elements, which we then use to infer gene regulatory networks that underpin lineage commitment events. Finally we show that these in silico transcription factor binding sites and gene regulatory networks can be used to predict the effect of transcription factor perturbation experiments. We demonstrate this by showing that Brachyury is essential for priming neuromesodermal progenitors into somitic mesoderm fate, which we then validate using embryonic Brachyury knockout.

overall_design: 11 samples taken from a time course of mouse embryonic development from E7.5 to E8.75. Includes 10 wildtype and 1 brachyury knockout. Processed using 10x Genomics Multiome kit to produce parallel snRNA-seq and snATAC-seq

first: Ricard

last: Argelaguet

last: Lohoff

first: Jingyu

first: Asif

last: Nakhuda

first: Deborah

last: Drage

first: Lars

last: Velten

first: Stephen

middle: J

last: Clark

first: Wolf

last: Reik


title: Role of yeast Nup60 lysine 467 acetylation  in regulation of transcription

city: Illkirch

first: Manuel

last: Mendoza

address: 1 rue Laurent Fries

country: France

institute: INSTITUTE OF GENETICS AND MOLECULAR AND CELLULAR BIOLOGY

summary:
Purpose: The experiment aimed to elucidate possible global effects of Nup60 K467 acetylation on transcription in S.cerevisiae.
Result: Neither acetyl-mimic nor deacetyl-mimic mutations in Nup60K467 cause major shifts in expression profile.

overall_design: In order to learn whether Nup60K467 acetylation plays a general role in transcription in budding yeasts we compared WT cells with cells expressing Nup60 with point acetyl mimic mutation (lysine 467 substituted with asparaginine, Nup60K467N) or a mutation mimicking constitutive deacetylation at this position (lysine 467 substituted with arginine, Nup60K467R). Each strain is present in 6 replicates.

first: Vasilisa

last: Pozharskaia


title: Enhancers of host immune tolerance to bacterial infection discovered using linked computational and experimental approaches

first: Megan

last: Sperry