title: Increased Apoptosis and aberrant apoptosis signaling pathways of CD4+CD25+FOXP3+ regulatory T cells in patients with systemic lupus erythematosus

city: Guangzhou

first: Mingfang

last: Li

address: 2 Lujing Road

institute: Dermatology Hospital, Southern Medical University

summary: Background: Systemic Lupus Erythematosus (SLE) is a prototype of autoimmune disease. Decreased cell numbers and suppressive defects of naturally occurring CD4+CD25+FOXP3+ regulatory T cells (Tregs) play an important role in the breakdown of SLE immune tolenrance. We have peviously observed significantly increased apoptosis of peripheral blood CD4+ T cells in SLE patients. Our objective here was to detect the apoptosis of Tregs in SLE patients to see if it could contribute to reduced suppressive activity of Tregs, and further elucidate the genes and signaling pathways which trigger the apoptosis in these cells. Methods and findings: The cell number and apoptosis rates of Tregs was respectively evaluated in SLE patients and normal controls (NCs) by FACS. The suppressive activity of Tregs was measured by coculture with CD4+CD25-CD127dim/- T cells. The relationship of abnormal Tregs apoptosis with clinical parameters was analyzed by Pearson correlation analysis. Gene expression profiles of unstimulated Tregs from active SLE patients and NCs were generated by microarray analysis. Differential genes expression was verified by real time-PCR. We found that the Tregs from SLE patients showed a significantly reduced number, elevated apoptosis rates and impared suppressive capacity compared to NCs. The increased apoptosis of Tregs was negatively correlated with the total number of Tregs and positively correlated with disease activities. Gene expression profiles of unstimulated Tregs from recent-onset SLE subjects reveal a cellular response that could make the cells sensitive to apoptosis, partially due to the stress responses, DNA-damaging and cytokine stimulation. This global picture of pathway-specific expression signatures is a step further into dissecting Tregs defects in the pathogenesis of SLE.

overall_design:
3 recent-onset and untreated female SLE patients whose disease activity were all considered severe and 3 age-, gender-, and ethnically matched healthy female subjects were selected to perform microarray analysis. 20ml peripheral blood was freshly extracted, CD4+CD25+CD127dim Tregs cells were isolated by immunomagnetic beads. Mixed Tregs of 3 normal controls  as one normal sample for gene expression profile detection.
As for the normal control samples, we extracted the peripheral blood of three healthy subjects, separated the peripheral blood Tregs of them respectively, and then mixed the three Tregs together as one normal control sample for microarray detection.

last: Luo


title: Chronic stress targets mitochondrial respiratory efficiency in the skeletal muscle of C57BL/6 mice [Methylome Dataset]

status: Public on Apr 03 2023

city: Duesseldorf

first: Birgit

last: Knebel

address: Auf'm Hennekamp 65

department: Cinical Biochemistry and Pathobiochemistry

country: Germany

institute: German Diabetes Center

type: Methylation profiling by high throughput sequencing

summary: Chronic stress can result in dysregulation of the cellular metabolism leading to severe disorders including depression, posttraumatic stress disorder but also the metabolic syndrome and type 2 diabetes. We aimed to determine the acute and adaptive effect of stress on energy metabolism in muscle tissue as the main determinant of whole-body energy expenditure. C57Bl6 mice under 15 days of chronic variable stress (Cvs) showed decreased lean mass despite increased energy intake. This was accompanied by reduced energy expenditure (EE) with a concomitant shift in substrate utilization depending on the circadian rhythm. The combination of omics approaches excluded stress effects on transcription and methylation processes in gastrocnemius muscle. Nevertheless, Cvs interfered with altered proteome composition in mitochondria on metabolic components, whilst OXPHOS and structural relevant components were unaltered. Functionally, Cvs resulted in impaired complex independent mitochondrial electron flow and reduced coupling efficiency that correlate for oxidative phosphorylation (state 3) of complex I to diurnal energy expenditure (EE) and for maximal uncoupled respiration (state 3u) of complex II to reduced diurnal and nocturnal EE. Bioenergetics assessment of mitochondria revealed higher optimal thermodynamic efficiencies (ƞ-opt) in Cvs muscle. Conclusion: These results show, that the Cvs reduced mitochondria respiration is associate with low rate of total EE, but does not primary affect transcription and genome methylation in muscle. However, the counter regulation by increased efficiency of complex II may be the driving force in to pave the way to longitudinal metabolic changes as basis of stress memory to muscle physiological adaptation.

overall_design: C57/Bl6 male mice were stressed with our Cvs protocol as previously described (doi:https://doi.org/10.1016/j.molmet.2018.06.012), or left untreated (Ctrl). Transcriptome analyses (MTA array, Affymetrix) was performed in Ctrl and Cvs gastrocmnemius muscle biopsies of each condition. Mice were phenotyped for body composition, serum analyses, methylome,  mitochondrial proteome and mitochondrial function and thermodymamic efficency immediately after stress to determine CVS dependant molecular alterations im metabolic regulation.

first: Aleksandra

last: Nikolic

first: Pia

last: Fahlbusch

first: Joerg

last: Kotzka


title: tRNA-seq of Arabidopsis leaves during pattern-triggered immunity

status: Public on Apr 02 2023

city: Durham

first: Paul

last: Zwack

state: NC

address: Campus Box 90338

country: USA

institute: Duke University

type: Non-coding RNA profiling by high throughput sequencing

summary: During pattern-triggered immunity (PTI), the first line of active defense against infection in plants, the translatome undergoes rapid reprogamming. To understand how defense proteins are selectively translated, we conducted a genetic screen for regulators of PTI using a translational reporter. We identified a mutant of RNA helicase 12 (RH12) showing compromised reporter translation and pathogen resistance. RH12 is a homolog of yeast DEAD-box Helicase Homolog 1, which targets mRNAs with low codon optimality for decay. Therefore, we sequenced the Arabidopsis tRNAome to determine codon optimality during PTI. We discovered a PTI-associated reduction in overall codon optimality of the transcriptome, and found that the decay of transcripts with reduced optimality is mediated by interaction with RH12. Our results demonstrate the first example of codon optimality-associated decay as part of an adaptive response in which the dynamics of both the tRNAome and the transcriptome facilitate rapid changes in translational output during PTI.

overall_design: profiling of tRNA from 3 reps of mock and elf18 treated samples

middle: J

first: Xinnian

last: Dong


title: Embryonic stem cell-derived brainstem and spinal astrocyte-like cells develop a neurotoxic phenotype in vitro following clinically relevant pro-inflammatory stimulation

city: Stockholm

first: Caroline

last: Lindblad

address: BioClinicum J5:20

country: Sweden

institute: Karolinska Institutet

type: Expression profiling by high throughput sequencing

summary: Traumatic axonal injury (TAI) in the brainstem carries a particularly poor prognosis. Although the role of neuroinflammation in this process is incompletely characterized, astrogliosis has been shown to coincide with TAI. Moreover, astrogliotic forebrain astrocytes were recently shown to confer a toxic effect on neurons. We sought to assess if ventral brainstem- or rostroventral spinal astrocytes exert similar effects on motor neurons in vitro. We derived brainstem/rostroventral spinal astrocyte-like cells (ES-astrocytes) and motor neurons using directed differentiation of embryonic stem cells (ES). ES-astrocyte identity was assessed using RNA-sequencing, immunocytochemistry, and comparison with primary subventricular zone-astrocytes. We activated the ES-astrocytes using the neurotoxicity-eliciting cytokines interleukin- (IL-) 1α and tumor necrosis factor-(TNF-)α. In co-cultures with reactive ES-astrocytes and motor neurons, we demonstrated neurotoxic ES-astrocyte activity, similarly to what has previously been shown for other central nervous system (CNS) regions. When exposed to IL-1β and IL-6, two neuroinflammatory cytokines found in the cerebrospinal fluid and serum proteome following severe traumatic brain injury (TBI), ES-astrocytes exerted similar effects on motor neurons. This demonstrates that ventral brainstem and rostroventral spinal cord astrocytes can exert neurotoxic effects in vitro. This highlights the importance of neuroinflammation as a secondary injury mechanism following neurotrauma, and presents a possible treatment avenue to improve neuronal survival in particularly vulnerable CNS regions following TAI.

overall_design: N = 40 unique samples from either astrocyte (n= 20) or motor neuron cultures (n = 20) dispersed across n = 5 treatments (including negative control) with n = 4 biological replicates per treatment.

first: Susanne

last: Neumann


title: Impact of polymicrobial infection on fitness of Streptococcus gordonii in vivo

city: Louisville

first: Richard

last: Lamont

state: Kentucky

address: 501 S. Preston St

department: Oral Immunology and Infectious Diseases

institute: University of Louisville

summary: Tn-Seq was used to identify S. gordonii genes that confer fitness during cooperative growth with P. gingivalis in a murine abscess model.

overall_design: After generating a saturating Streptococcus gordonii transposon library using EZ-Tn5 based transposon mutagenesis, this library was inoculated either alone (Sg) or in conjunction with Porphyromonas gingivalis (PgSg) subcutaneously into BALB/cJ mice. Bacteria recovered from developed abscesses were inoculated and cultured in vitro anaerobically until turbid and genomic DNA was isolated. Genomic DNA was also isolated from the S. gordonii transposon library (Input) and was not used to infect mice and used as a control.

first: Satya

middle: D

last: Pandey

first: John

last: Perpich

first: Kendall

middle: S

last: Stocke

first: Margaret

middle: M

last: Vickerman


title: Malignant Peripheral Nerve Sheath Tumors are Comprised of Two Epigenetic Subgroups with Distinct Molecular Landscapes, Outcomes and Therapeutic Targets: snRNA Seq Samples

city: Toronto

first: Jeff

last: Liu

state: Ontario

address: 101 College Street, RM 4-601

department: Princess Margaret Cancer Center

country: Canada

institute: University Health Network

summary: We focused on studying the methylation signature of the spectrum of PNSTs to develop a methylome-based classification of these common tumors. We studied the genome-wide DNA methylation patterns using the Illumina MethylationEPIC array and classified the samples into 5 subgroups. Gene Expression comparing the subgroups were performed using single nuclear RNA Seq

overall_design: Single nuclear RNA profiling analysis for different methylation subgroups of PNSTs.

first: Suganth

last: Suppiah

middle: C

first: Gelareh

last: Zadeh


title: Effects of FLT3/ACVR dual targeting using TP-0184 on three FLT3 mutated cell lines of human acute myeloid leukemia (AML)

status: Public on Apr 01 2023

city: Houston

first: Zheng

last: Yin

state: TX

address: 6565 Fannin St, MC: F6-300

department: Systems Medicine and Bioengineering

institute: Houston Methodist Cancer Center

summary: We developed a novel ACVR1 inhibitor, TP-0184, which selectively caused growth arrest in FLT3-mutated AML cell lines, and we aim to investigate the molecular mechanisms mediating such effects

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MV4-11, MOLM-13 and MOLM-14 cell lines (all FLT3-mutated AML cell lines) after vs. before treatment of TP-0184 at 200nM for 48h, with triplicated samples for each cell line in each condition.

first: Anudishi

last: Tyagi

first: Venkata

last: Lokesh Battula


title: Small RNA-seq of small extracellular vesicles secreted by Zika virus (ZIKV)-infected JEG-3 trophoblast cells

city: Guro-gu

first: Jae Kyung

last: Lee

state: Seoul

address: 148 Gurodong-ro

country: South Korea

institute: Korea University

summary: Comparison of microRNA profiles of small extracellular vesicles isolated from mock- vs. ZIKV-infected JEG-3 cells.

overall_design: miRNA-seq

first: Ok

last: Shin

first: Jae

middle: K


title: Malignant Peripheral Nerve Sheath Tumors are Comprised of Two Epigenetic Subgroups with Distinct Molecular Landscapes, Outcomes and Therapeutic Targets: Methylation Samples

summary: We focused on studying the methylation signature of the spectrum of PNSTs to develop a methylome-based classification of these common tumors. We studied the genome-wide DNA methylation patterns using the Illumina MethylationEPIC array

overall_design: A cohort (n = 108) representing the full spectrum of PNSTs were analyzed by MethylationEPIC for identifying subgroups of MPNST


title: Identification of a DAMP receptor and its cognate peptide ligand in sweet potato (Ipomoea batatas)

city: Jena

first: Axel

last: Mithöfer

state: Thuringia

address: Hans-Knöll-Straße 8

department: Plant Defense Physiology

institute: Max-Planck-Institute for Chemical Ecology

summary:
We identified a leucine-rich repeat receptor kinase (IbLRR-RK1) that is induced upon wounding and herbivory, and related to peptide-elicitor receptors (PEPRs) from tomato and Arabidopsis. We also identified a gene encoding a precursor protein comprising a peptide ligand (IbPep1) for IbLRR-RK1.
RNAseq of I. batatas reveals differentially expressed genes (DEGs) upon IbPep1 and IbHypSysIV treatment

overall_design: Comparative gene expression profiling analysis of RNA-seq data for I. batatas leaves treated with water, IbHypSysIV or IbPep1

first: Hsueh-Han

last: Lu

first: Anja

last: Meents

first: Judith

last: Fliegmann

first: Ming-Jing

last: Hwang

first: Ching-Shu

last: Suen

first: Georg

last: Felix

first: Kai-Wun

last: Yeh


title: The enhancer landscape predetermines the skeletal regeneration capacity of stromal cells [ATAC-seq]

city: Berlin

first: Julia

last: Polansky

address: Augustenburger Platz 1

institute: Charité - Universitätsmedizin Berlin

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Mesenchymal stromal cells (MSCs) derived from bone marrow (BM) have stronger potential for endochondral ossification compared to white adipose tissue (WAT)-MSCs, umbilical cord (UC)-MSCs, and skin fibroblasts (FB). We assessed uniquely accessible enhancers facilitating bone regeneration potential.

overall_design: ATAC-seq data was generated from 2-3 replicates of BM-, WAT-, UC-MSC, and FB.

first: Sarah

last: Hochmann

first: Kristy

last: Ou

first: Rodolphe

last: Poupardin

first: Salaheddine

last: Ali

first: Sven

last: Geissler

first: Dirk

last: Strunk


title: Transcriptome profiles in zmp mutants

city: Riverside

first: Brandon

last: Le

state: CA

address: 3401 Watkins Drive

department: Institute for Integrative Genome Biology

institute: University of California, Riverside

summary: We profiled the small RNA-ome, transcriptome, DNA methylome, and chromatin association to the study the molecular and biological functions of ZMP in Arabidopsis.

overall_design: Three biological replicates per genotype were obtained for this study

middle: H

first: Yuan

last: Wang

first: Xuemei

last: Chen


title: Conferring Flocculation Phenotype to Pichia pastoris Improves D-lactic Acid Production and Tolerance

city: Khlong Luang

first: Wuttichai

last: Mhuantong

state: Pathum Thani

address: National Center for Genetic Engineering and Biotechnology (BIOTEC)

country: Thailand

institute: BIOTEC

summary: D-lactic acid is a three-carbon organic acid with a chiral structure and can improve the thermostability of polylactic acid. Microorganisms such as the methylotrophic yeast Pichia pastoris, which lack the natural ability to produce or accumulate high amounts of D-lactic acid, have been engineered to produce it in high titers. However, tolerance to D-lactic acid remains a challenge. In this study, we demonstrate that cell flocculation improves tolerance to D-lactic acid and leads to increased D-lactic acid production in Pichia pastoris. By incorporating a flocculation gene from Saccharomyces cerevisiae (ScFLO1) into P. pastoris KM71, we created a strain (KM71-ScFlo1) that demonstrated up to a 1.6-fold improvement in specific growth rate at high D-lactic acid concentrations. Furthermore, integrating a D-lactate dehydrogenase gene from Leuconostoc pseudomesenteroides (LpDLDH) into KM71-ScFlo1 resulted in an engineered strain (KM71-ScFlo1-LpDLDH) that can produce D-lactic acid at a titer of 5.12  0.35 g/L in 48 hours , a 2.6-fold improvement over the control strain lacking ScFLO1 expression. Transcriptomics analysis of this strain provided insights into the mechanism of increased tolerance to D-lactic acid including the upregulations of genes involved in lactate transport and iron metabolism. Overall, our work represents an advancement in the efficient microbial production of D-lactic acid by manipulating yeast flocculation.

overall_design: The engineered strains were pre-cultured in 5-mL aliquots of MGYH medium overnight and used to inoculate 10 mL of MGYH medium in 50 mL Corning tubes to achieve an initial optical density of 0.05 at 600 nm (OD600). The cultures were grown at 30 °C and 250 rpm in an orbital shaking incubator. When the strains reached the mid-exponential phase (approximately 21 hours), a 2-mL aliquot of each culture was collected and centrifuged for 5 minutes at 3000 x g.

first: Sae-tang

last: Kittapong

first: Bumrungtham

last: Pornsiri

first: Mhuangtong

last: Wuttichai

first: Champreda

last: Verawat

first: Tanapongpipat

last: Sutipa

first: Zhao

last: Xin

first: Liu

first: Runguphan

last: Weerawat


title: Deubiquitinase OTUD6A in macrophages promotes intestinal inflammation and colitis via deubiquitination of NLRP3

city: Wenzhou

first: guang

last: liang

state: Wenzhou

address: Wenzhou medical university of  higher education park  chashan town

department: School of Pharmaceutical Sciences

country: China

institute: Wenzhou Medical University

summary: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which has been shown to increase the incidence of colorectal cancer. Recent studies have highlighted the role of ubiquitination, a post-translational modification, in the occurrence and development of colonic inflammation. Ovarian tumor deubiquitinase 6A (OTUD6A) is a deubiquitinating enzyme, which regulates cell proliferation and tumorigenesis. In this study, we investigated the expression and role of OTUD6A in IBD. Wide-type or Otud6a-/- mice were used to develop dextran sodium sulfate (DSS)- or 2,6,4-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, as well as azoxymethane (AOM)/DSS-induced colitis-associated cancer model. Bone marrow-derived macrophages (BMDMs) were isolated from wild-type and Otud6a-/- mice to dissect molecular mechanisms. Our data show that OTUD6A deficiency attenuated DSS or TNBS-induced colitis, as well as AOM/DSS-induced colitis-related colon cancer in vivo. Bone marrow transplantation experiments further revealed that OTUD6A in myeloid cells was responsible for exacerbation of DSS-induced colitis. Mechanistically, OTUD6A directly bound to NACHT domain of NLRP3 inflammasome and selectively cleaved K48-linked polyubiquitin chains from NLRP3 at K430 and K689 to enhance the stability of NLRP3, leading to increased IL-1β level and inflammation. Taken together, our research identifies a new function of OTUD6A in the pathogenesis of colitis by promoting NLRP3 inflammasome activation, suggesting that OTUD6A could be a potential target for the treatment of IBD.

overall_design: Otud6a-/- and WT BMDMs of four groups (WT_CTRL,WT_LPS,KO_CTRL,KO-LPS) were collected in TRIzol reagent. Three biological replicates were performed for each group. RNA-seq analysis was performed at Hangzhou Lc-Bio Technologies Co.,Ltd, China. Paired-end sequencing was performed using the Illumina Novaseq 6000 (California, United States).

first: Xin

last: Liu

first: Guang

last: Liang


title: ZMP, NRPD1 and histone chromatin profiles

overall_design: Two biological replicates per genotype were obtained for this study


title: Stub1 acetylation by CBP/p300 attenuates chronic hypoxia-induced pulmonary hypertension by suppressing HIF-2α transcriptional activity

city: Milwaukee

first: Adeleye

middle: J.

last: Afolayan

state: Wisconsin

address: 8701 Watertown Plank Rd., PD278, CRI TBRC, Rm C3278

institute: Medical College of Wisconsin

summary: Chronic hypoxia induces pulmonary vascular remodeling and pulmonary hypertension (PH). While it is established that transcription factors, hypoxia-inducible factors (HIF-1α/HIF-2α) activate gene programs that drive hypoxia-induced PH, the mechanism of HIF-1/2 activation is less clear. Here, we report that carboxylterminus of Hsp70-interacting protein (CHIP or Stub1) modulates HIF-1α and HIF-2α transcription rather than reducing their stability. Knocking-down Stub1 reduced hypoxic activation of HIF-1α mRNA, protein, and activity while enhancing hypoxic induction of HIF-2α mRNA, protein, and target genes in pulmonary vascular cells. Mechanistically, CBP/p300-mediated acetylation of lysine (K287) inactivates the ubiquitin ligase activity of Stub1 and triggers its translocation from the cytoplasm into the nucleus. There, it recognizes the HIF promoter and hypoxia response elements (HREs) in target genes. Expression of Stub1-K287Q mutant (mimicking acetylation) enhanced hypoxia-induced HIF-1α expression, while acetyl-deficient Stub1-K287R mutant had the opposite effect on HIF-α but enhanced hypoxia-induced HIF-2α transcriptional activity. Endothelial-Stub1 transgenic mice tolerated chronic hypoxia better, had less pulmonary vascular remodeling, reduced pulmonary vascular resistance, and greater cardioprotection. Thus, Stub1 nuclear translocation enhances hypoxic induction of HIF-1α activity while suppressing deleterious effects of HIF-2α. These observations indicate that nuclear-Stub1 synergizes with HIF-1α to promote transcriptional responses and antagonizes HIF2α-driven PH in chronic hypoxia.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Examination of the effect of nuclear localization or exclusion of STUB1 protein on downstream gene expression.

first: Paul

last: Sidlowski


title: Spatiotemporally Deciphering the Unknown Role of Persistent HPV Infection in Precancer to Cervical Cancer Progression: Integrating Single-Cell RNA-Sequencing Landscape and Spatial Transcriptomics Atlas [Spatial Transcriptomics]

city: Shanghai

first: Chenyan

last: Guo

address: 419 Fangxie Road, Shanghai, China

institute: Fudan University Obstetrics and Gynecology Hospital

summary: The mechanism underlying the cervical carcinogenesis mediated by persistent HPV infection remains elusive. Here we pioneeringly deciphered both temporal transition and spatial distribution of the cellular subsets during the disease progression from normal cervix, precancer lesions to cervical cancer by integrating scRNA-seq with ST. We not only identified three ‘HPV-related epithelial clusters’ unique to normal, HSIL and cervical cancer respectively, but also discovered node genes which potentially determined the disease progression. Moreover, we observed a gradual transition of multiple immune cells from positive immune response to dysregulation and exhaustion, to an immune-suppressive microenvironment during the malignant program. Besides, the cellular interaction analysis further verified a ‘homeostasis-balance-malignancy’ change within cervix microenvironment during disease escalation. Together, these findings not only deciphered mysterious persistent HPV infection spatiotemporally from the process of precancer to cervical cancer but also provided unprecedented possibilities for accurate diagnosis, precise treatment and prognosis evaluation for precancer and cervical cancer.

overall_design: Nine cervical tissue samples of different disease stages from normal, HPV-infected, precancer to cancer were collected from colposcopy examination and analyzed using scRNAseq and spatial transcriptomics .


title: Core binding factor fusion downregulation of ADAR2 RNA editing contributes to acute myeloid leukaemia (AML) leukemogenesis

city: Singapore

first: Henry

last: Yang

address: 28 Medical Drive

country: Singapore

institute: Cancer Science Institute of Singapore

summary: Adenosine to inosine (A-to-I) RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes ADAR1 and ADAR2, has been shown to contribute to multiple cancers. However, other than chronic myeloid leukemia (CML) blast crisis, relatively little is known about its role in other types of hematological malignancies. Here, we found that ADAR2, but not ADAR1 and ADAR3, was specifically downregulated in the core binding factor (CBF) AML with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was repressed by the RUNX1-ETO AE9a fusion protein in a dominant negative manner. Further functional studies confirmed that ADAR2 could suppress leukemogenesis specifically in t(8;21) and inv16 AML cells dependent on its RNA editing capability. Expression of two exemplary ADAR2-regulated RNA editing targets COPA and COG3 inhibited clonogenic growth of human t(8;21) AML cells. Our findings support a hitherto unappreciated mechanism leading to ADAR2 dysregulation in CBF AML and highlight the functional relevance of loss of ADAR2-mediated RNA editing to CBF AML.

overall_design: investigate RNA expression and RNA editing in Kasmui1 cells

first: Mingrui

first: Tim

last: Chan

first: Qiling

last: Zhou

first: Omer

last: An

first: Ying

last: Li

first: Yangyang

last: Song

first: Zi

last: Tan

first: Vanessa

last: Ng

first: Philomina

last: Peramangalam

first: Zhi

middle: Q

first: Xinang

last: Cao

first: Eisaku

last: Iwanaga

first: Masao

last: Matsuoka

first: Melissa

last: Ooi

first: Wei

middle: Y

last: Jen

first: Liang

middle: P

last: Koh

first: Esther

first: Lip

first: Yufen

last: Goh

first: Wilson

first: Bryan

middle: T

first: Chan

last: Chun

last: Fullwood

first: Wee

last: Chng

first: Motomi

last: Osato

first: John

middle: A

last: Pulikkan

first: Leilei

first: Daniel

middle: G

last: Tenen


title: Plant and aphid vector manipulation by a persistent plant virus

city: Strasbourg

first: Veronique

last: Ziegler-Graff

address: rue du general Zimmer

department: INSB

country: France

institute: CNRS

summary: Plant viruses rely on both host plant and vectors for a successful infection. This study investigated the global transcriptomic changes in Arabidopsis thaliana that were simultaneously exposed to both a plant virus (turnip yellows virus, polerovirus genus and Solemoviridae family) and its aphid vector (Myzus persicae). Some of these modifications in gene expression may promote in a timely manner viral transmission and dispersion.

overall_design: RNA seq method was used to analyze the effect of the virus on plants infested or not by aphids (Myzus persicae)

first: Célia

last: Krieger

first: David

last: Halter

first: Véronique

last: Brault

first: Valérie

last: Cognat


title: Ex Vivo Expansion of Phenotypic and Transcriptomic Chronic Myeloid Leukemia Stem Cells

city: Boston

first: Mahmoud

middle: Adel

last: Bassal

state: Massachusetts

address: 3 Blackfan Circle

department: Hematology and Oncology

institute: Beth Israel Deaconess Medical Center

summary: Despite decades of research, standard therapies remain ineffective for most leukemias, pushing toward an essential unmet need for targeted drug screens. Moreover, preclinical drug testing is an important consideration for success of clinical trials without affecting non-transformed stem cells. Using the transgenic chronic myeloid leukemia (CML) mouse model, we determine that leukemic stem cells (LSCs) are transcriptionally heterogenous with a preexistent drug-insensitive signature. To test targeting of potentially important pathways, we establish ex vivo expanded LSCs that have long-term engraftment and give rise to multilineage hematopoiesis. Expanded LSCs share transcriptomic signatures with primary LSCs including enrichment in Wnt, JAK-STAT, MAPK, mTOR and transforming growth factor b signaling pathways. Drug testing on expanded LSCs show that transforming growth factor b and Wnt inhibitors had significant effects on the viability of LSCs, but not leukemia-exposed healthy HSCs. This platform allows testing of multiple drugs at the same time to identify vulnerabilities of LSCs.

overall_design: Comparing drug-sensitive and resistant CML leukemic cells and murine stem progenitor cells

first: S

middle: B

last: Patel

first: V

last: Kuznetsova

middle: R

last: Matkins

first: A

last: Franceski

first: M

first: R

last: Welner


title: Targeting ATP12A, a non-gastric proton pump alpha subunit, for idiopathic pulmonary fibrosis treatment

city: GRAND RAPIDS

first: Xiaopeng

last: Li

state: MI

address: 400 Monroe Ave NW

department: Pediatrics & Human Development

institute: Michigan State University

summary: Idiopathic Pulmonary Fibrosis (IPF) is a pathological condition of unknown etiology which results from injury to the lung and an ensuing fibrotic response that leads to thickening of the alveolar walls and obliteration of the alveolar space. The pathogenesis is not clear and there are currently no effective therapies for IPF. Small airway disease and mucus accumulation are prominent features in IPF lungs, similar to Cystic Fibrosis (CF) lung disease. The ATP12A gene encodes the alpha-subunit of the non-gastric H+, K+-ATPase, which functions to acidify the airway surface fluid and impairs mucociliary transport function in cystic fibrosis patients. We hypothesize that the ATP12A protein may play a role in the pathogenesis of IPF. Our studies demonstrate that ATP12A protein is overexpressed in distal small airways from IPF patient lungs compared to normal human lungs. In addition, overexpression of the ATP12A protein in mouse lungs worsened the bleomycin (BLEO)-induced experimental pulmonary fibrosis. This was prevented by a potassium-competitive proton pump blocker, vonoprazan (VON). This data supports the concept that the ATP12A protein plays an important role in the pathogenesis of lung fibrosis. Inhibition of the ATP12A protein has the potential as a novel therapeutic strategy in IPF.

overall_design: Differential gene expression analysis of RNA-seq data for mouse lung tissue with bleomycin-induced lung fibrosis

first: Mohamed

last: Abdelgied

first: Katie

last: Uhl

first: Tara

middle: E

last: Jager

first: Shreya

last: Paithankar

first: Bin

last: Chen


title: Effect of nociceptive neuropeptides on dendritic cells

first: Ulrich

last: von Andrian

state: MA

address: 77 Ave Louis Pasteur

department: Immunology

institute: Harvard Medical School

summary: We compared the effects of nociceptive neuropeptides and nociceptors on DCs by means of coculture of Flt3L-induced bone marrow-derived DCs and primary mouse nociceptors.

overall_design: Day 9 Flt3L-induced bone marrow with nociceptors or alone in the presence of CGRP and SP neuropeptides. DC subsets were FACS-sorted and sequenced

first: Urich

first: Pavel

last: Hanč


title: Role of Girdin in LPS-induced macrophage polarization

city: LA JOLLA

first: Sahar

last: Taheri

state: California

address: 9500 GILMAN DR.

institute: UCSD

overall_design: GIV depleted RAW cells (ShGIV) and control RAW cells were treated with LPS (100ng/ml) for 5h

first: Debashis

last: Sahoo

first: Soumita

last: Das

first: Pradipta

last: Ghosh


title: CTLA-4 blockade induces tumor pyroptosis via CD8+ T cells in head and neck squamous cell carcinoma

city: wuhan

first: wang

last: shuo

state: HuBei

address: 237 Luoyu Road

institute: Wuhan University

summary: Immune checkpoint blockade (ICB) therapy has demonstrated promising clinical results in oncology and is currently one of the most sought-after immunotherapies for tumors. However, there are a number of issues with ICB therapy, including low response rates and a lack of effective efficacy predictors. Gasdermin-mediated pyroptosis is a typical form of inflammatory death mode, but it is unclear whether ICB treatment can trigger its occurrence or whether gasdermin expression has any effect on the response rate to ICB treatment. Herein, we discovered that high expression of gasdermin protein was associated with a favorable tumor immune microenvironment and a favorable prognosis in head and neck squamous cell carcinoma (HNSCC), and taking advantage of the mouse HNSCC cell line 4MOSC1 (responsive to CTLA-4 blockade) and 4MOSC2 (resistant to CTLA-4 blockade) orthotopic models, we also demonstrated that CTLA-4 blockade treatment induced gasdermin-mediated pyroptosis of tumor cells and that the expression of gasdermin was positively associated with the effectiveness of CTLA-4 blocking treatment. Mechanistically, through RNA sequencing, flow cytometry, ELISA, Western blotting and RT-PCR, we discovered that CTLA-4 blockade activated CD8+ T cells in the tumor and increased the levels of the cytokines TNF-α and IFN-γ in the tumor microenvironment, and that TNF-α and IFN-γ synergistically activated the STAT1/IRF1 axis, inducing tumor cell pyroptosis and the release of large amounts of inflammatory substances and chemokines such as CXCL10.

overall_design: 4MOSC1-Control as control group: 3, 4MOSC1-TNF-α+IFN-γ (stimulation with TNF-α and IFN-γ) group: 3

first: Shuo

last: Wang

first: Zhi-Zhong

last: Wu

first: Su-Wen

last: Zhu

first: Shu-Cheng

last: Wan

first: Meng-Jie

last: Zhang

first: Bo-Xin

first: Qi-Chao

last: Yang

first: Yao

last: Xiao

first: Hao

first: Liang

last: Mao

first: Zhi-Yong

first: J

last: Gutkind

first: Zhi-Jun

last: Sun


title: Investigation of prodromal features in metabolic syndrome based on transcriptome analysis

city: DaeJeon

first: Hee Jeong

last: Jin

address: 672 Yuseong-daero

department: Korean Medicine (KM) Data Division

institute: Korea Institute of Oriental Medicine

summary: The goals of this study are to investigate the molecular mechanism of three groups, consist of normal, preMetS, MetS group.

overall_design: A total of 100 subjects were classified as 33 normal, 42 Pre-Mets, and 25 MetS enrolled in this study.

first: Hee-Jeong

first: Sang-Min

last: Park

first: Siwoo

last: Lee


title: Association of NUP153 on genomic DNA in TE5 cells [ChIP-seq]

city: kanazawa city

first: Masaharu

last: Hazawa

state: Ishikawa

address: Kakuma-machi

country: Japan

institute: Kanazawa University

summary: To understand the regulatory regions of genomic DNA by nuclear pore, the genomic region associated by NUP153, one of nuclear pore protein, was determined by Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) .

overall_design: ChIP-seq for endogenous NUP153 in TE5 cells.


title: Single-cell chromatin accessible state of paired primary and liver metastasis colorectal cancer cells from PDX cells derived mouse model

city: ANN ARBOR

first: Shasha

last: Li

address: 1109 Maiden Ln, ct apt 104

institute: University of Michigan

summary: Chromatin regulatory networks that maintain differentiated cell states are frequently dysregulated in and thus contribute to cancer metastasis. Here, we reveal the dynamic transitions of regulatory states of colorectal cancer (CRC) cells during metastasizing to liver by profiling single-cell chromatin accessibility of paired primary and metastatic CRC tumors in mouse. We discover CRC subclones, which are characterized by losing chromatin accessibility around colon-tissue specific genes and gain that around liver-specific genes,including transcription factors in FOXA family and HNF family we discovered in our previous study, might partially mimic types of liver cells across the liver development.  A particular subclone with stem-like state, which is highly enriched in metastases but not primary tumors , clearly shows poor prognosis.

overall_design: We used scATAC-seq to profile 3 paired primary and liver metastasis colorectal cancer cells of PDX cells derived mouse model.

first: Ming

first: Shuaishuai

last: Teng

first: Dong


title: The Sm Core Protein SmEb Regulates Salt Stress Responses Through Maintaining Proper Splicing of RCD1 Pre-mRNA in Arabidopsis

city: Hefei

first: Zhen

state: Anhui

address: 130 Changjiangxilu

institute: Anhui Agricultural University

summary:
Salt stress caused by soil salination inhibits plant growth and development that result in reduction of crop yield and threaten the food security. Several spliceosome components are considered to modify salt stress responses in plants. However, the molecular basis of spliceosome proteins adjustment to salt stress is still unclear. Here we report that an Sm core protein SmEb is required for salt tolerance in Arabidopsis. In addition, SmEb controls alternative splicing of hundreds of pre-mRNA to participate in plant response to salt stress. Our results further reveal that SmEb takes effect on maintain proper ratio of two RCD1 splicing variants to adjust to H2O2 accumulation under salt stress. Together, our findings uncover that proper alternative splicing of pre-mRNAs governed by the spliceosome component SmEb is essential for plant salt stress responses.
Salt stress caused by soil salination inhibits plant growth and development that result in reduction of crop yield and threaten the food security. Several spliceosome components are considered to modify salt stress responses in plants. However, the molecular basis of spliceosome proteins adjustment to salt stress is still unclear. Here we report that an Sm core protein SmEb is required for salt tolerance in Arabidopsis. In addition, SmEb controls alternative splicing of hundreds of pre-mRNA to participate in plant response to salt stress. Our results further reveal that SmEb takes effect on maintain proper ratio of two RCD1 splicing variants to adjust to H2O2 accumulation under salt stress. Together, our findings uncover that proper alternative splicing of pre-mRNAs governed by the spliceosome component SmEb is essential for plant salt stress responses.

overall_design: Twelve-day-old smeb-1, smeb-2, and Col-0 seedlings grown on 0.5× MS medium were treated with 200 mM NaCl for 0 or 6 h.

first: Jia

last: Pang


title: Comparation of the anti-CD19 CAR-T and the NMN treated anti-CD19 CAR-T

city: Beijing

first: Shuai

last: Tong

address: No.10 Yangfangdian Road

institute: Beijing Shijitan Hospitol

summary: Our study provides compelling support to an effective CAR-T cell anti-aging intervention using NMN, a key NAD+ intermediate. We found the clinical potential of NMN for CAR-T cell immunotherapy for human cancers, attributed to their central memory phenotype. The cells are more viable, proliferative, and long-lived in vivo. Furthermore, these CAR-T cells exerted great antitumor efficacy against tumors in human xenograft mouse models. Detailed molecular mechanisms responsible for the pleiotropic effects of NMN need to be investigated further. So RNA-seq was used to analyze the different gene expression of these CAR-T cells.

overall_design: Compare gene expression profiles for CAR-T cells and NMN-treated CAR-T cells.

last: Yu

first: Can

first: Yue

last: Bai

first: Zhijing

last: An

first: Chang

last: Xu

first: Fang

last: Wang

first: Yi

last: Hu

first: Qinghui

last: Zhuang

first: Xiaosong

last: Zhong


title: ATACseq of differentiating ATDC5 mouse prechondrocytes

city: Saskatoon

first: Christopher

middle: H.

last: Eskiw

state: SK

address: 51 Campus Drive

department: Food and Bioproduct Science

institute: University of Saskatchewan

summary: We report the application of ATACseq to differentiating ATDC5 cells with the aim of identifying how chromatin architecture is changing as these cells move from pre-chondrocytes to differentiated chondrocytes. Raw data was generated by sequencing using the Novaseq6000 with 50bp single end reads. Trimming to remove adapters or poor-quality reads was performed with no sequence below 30 nucleotides in length used in the analysis. We found that there were significant changes in chromatin accessibility at both days 3 and 10 of differentiation.  Using diffBind, differential peaks were identified at day 3 and 10. These peaks were further analyzed for enriched transcription factor binding sites and identified motifs for the RUNX family transcription factors as well as SOX9.

overall_design: ATACseq of ATDC5 cells at 3 time points of differentiation.

first: Brian

last: Eames

first: Patsy

last: Gomez


city: London

first: Matteo

last: Righi

state: London

address: The MediaWorks, 191 Wood Ln

country: United Kingdom

institute: Autolus Therapeutics

summary:
Engineering CAR T cells expressing specific chimeric cytokine receptors that signal independently from the presence of an exogenous cytokine can significantly impact cancer cellular therapy by improving
: i) trafficking and expansion of the adoptive cells therapy product post-infusion, ii) extended persistence of the modified T cells post tumour eradication.
Altogether, these features will allow lifelong tumour protection. Furthermore, the technology here illustrated holds the potential to reduce the dose required to reach therapeutic efficacy, greatly reducing the overall manufacturing cost.
Finally, the generalisability of the architecture described holds the potential to tailor a specific cytokine signal to a particular type of cell that the developed therapy is based upon.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for T cells treated with recombinat IL2, Constitutive Chimeric cytokine receptor delivering IL2 signal (FabIL2), or no treatment.

first: Yuchen

first: Isaac

last: Gannon

first: Saket

last: Srivastava

first: Evangelia

last: Kokalaki

first: Thomas

last: Grothier

first: Francesco

last: Nannini

last: Allen

first: James

last: Sillibourne

first: Simon

last: Thomas

first: Shaun

last: Cordoba

first: Martin

last: Pule


title: Hepatocyte mARC1 Promotes Fatty Liver Disease

city: Oxford

first: Robert

last: Kitchen

address: Novo Nordisk Ltd, Innovation Building, Roosevelt Drive

institute: Novo Nordisk

summary:
Background and Aims
Non-alcoholic fatty liver disease (NAFLD) has a prevalence of ~25% worldwide, with significant public health consequences yet has few effective treatments. Human genetics can help elucidate novel biology and identify targets of new therapeutics. Genetic variants in mitochondrial amidoxime reducing component 1 (MTARC1) have been associated with NAFLD and liver-related mortality, however, its pathophysiological role and the cell type(s) mediating these effects remain unclear. We aimed to investigate how MTARC1 exerts its effects on NAFLD by integrating human genetics with in vitro and in vivo studies of mARC1 knockdown.
Methods
Analyses including multi-trait colocalization and Mendelian randomization were used to assess the genetic associations of MTARC1. In addition, we established an in vitro long-term primary human hepatocyte model with metabolic readouts and used the Gubra GAN diet NASH mouse model treated with hepatocyte specific GalNAc-siRNA to understand the in vivo impacts of MTARC1.
Results
We show that genetic variants within the MTARC1 locus are associated with liver enzymes, liver fat, plasma lipids and body composition and these associations are due to the same causal variant (p.A165T, rs2642438 G>A), suggesting a shared mechanism. We demonstrated that increased MTARC1 mRNA had an adverse effect on these traits using Mendelian Randomization, implying therapeutic inhibition of mARC1 could be beneficial. In vitro mARC1 knockdown decreased lipid accumulation and increased triglyceride secretion and in vivo GalNAc-siRNA mediated knockdown of mARC1 lowered hepatic, but increased plasma triglycerides. We found alterations in pathways regulating lipid metabolism and decreased secretion of 3-hydroxybutyrate upon mARC1 knockdown in vitro and in vivo.
Conclusions
Collectively, our findings from human genetics, and in vitro and in vivo hepatocyte-specific mARC1 knockdown support the potential efficacy of hepatocyte-specific targeting of mARC1 for treatment of NAFLD.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for cultured primary human hepatocytes treated with MTARC1 siRNA under different media conditions.

first: Lara

last: Lewis

first: Lingyan

last: Chen

first: L

middle: S

last: Hameed

first: Cyrielle

last: Maroteau

first: Shilpa

last: Nagarajan

first: Jenny

last: Norlin

first: Charlotte

last: Daly

first: Sara

last: Hjuler

first: Rahul

last: Patel

first: Iwona

last: Szczerbinska

first: Eilidh

middle: J

last: Livingstone

first: Tom

middle: N

last: Durrant

first: Elisabeth

last: Wondimu

first: Soumik

last: BasuRay

first: Anandhakumar

last: Chandran

first: Wan

last: Lee

first: Sile

last: Hu

first: Barak

last: Gilboa

first: Megan

last: Grandi

first: Enrique

last: Toledo

first: Abdullah

last: Erikat

first: Leanne

last: Hodson

first: William

last: Haynes

first: Natalie

middle: W

last: Pursel

first: Ken

last: Coppieters

first: Jan

last: Fleckner

first: Joanna

last: Howson

first: Birgitte

last: Andersen

first: Maxwell

last: Ruby


title: Next Generation Sequencing of tomato germplasm for cold tolerance and yield studies

city: Gandarbal

first: Basharat

middle: Ahmad

last: Bhat

state: Kashmir

address: Shuhama

department: Animal Biotechnology

country: India

institute: Sher-e-Kashmir University of Agricultural Sciences and Technology

type: Genome variation profiling by high throughput sequencing

summary: Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goal of this study is genome wide association mapping for cold tolerance and yield studies in tomato (Solanum spp.) by phenotyping the genotypes under six diffrent temporal arrangments. Also for conducting quantitative reverse transcription polymerase chain reaction (qRT–PCR) assay of cold tolerant genes.

sample_organism:
Solanum lycopersicum
Solanum peruvianum
Solanum chilense
Solanum pimpinellifolium
Solanum habrochaites
Solanum lycopersicum var. cerasiforme

overall_design: 50 samples

first: Labiba

last: Riyaz Shah

first: Nazeer

last: Ahmed

first: Khursheed

last: Hussain

first: Khalid

middle: Z

last: Masoodi


title: Human OTULIN haploinsufficiency impairs cell-intrinsic immunity to staphylococcal α-toxin

city: New York

first: Yelena

last: Nemirovskaya

address: 1230 York Avenue

institute: Rockefeller University

summary: We performed single-cell RNA sequencing (scRNASeq) on cryopreserved peripheral blood mononuclear cells (PBMCs) of healthy controls and OTULIN haploinsufficient patients in order to clarify the perturbation, if any, of cellular phenotypes in various leukocyte subsets in vivo at basal state attributable to OTULIN haploinsufficiency.

overall_design: Single-cell RNA sequencing of healthy controls and OTULIN haploinsufficient patients

first: András

last: Spaan

first: Masato

last: Ogishi

first: Peng

last: Zhang


title: Genetic inhibition of CARD9 accelerates the development of experimental atherosclerosis through CD36 dependent-defective autophagy

city: Paris

first: Hafid

last: Ait-Oufella

address: 56, Rue Leblanc

institute: Inserm

summary: Macrophage-mediated innate immune responses contribute to the initiation, progression and complications of atherosclerosis. However, the underlying pathways linking activation of macrophages to atherosclerotic plaque develoment are still poorly understood. We hypothesized that activation of caspase recruitment-domain containing protein 9 (CARD9) plays a determinant role in pro-atherogenic responses in macrophages. Transcriptomic analysis of human monocytes isolated from CARD9-deficient patients confirmed the pathogenic signature identified in several murine models: increased production of pro-inflammatory cytokines, improved lipid uptake, higher cell death susceptibility and defective autophagy.

overall_design: RNA-seq analysis from circulating monocytes from CARD9 deficient patients (n=3) with those of controls.

first: Yujiao

first: Jean-Rémi

last: Lavillegrand

first: Coralie

last: Guérin

first: Marc

last: Diedisheim

first: Melanie

last: Migaud

first: Anne

last: Puel

first: Fanny

last: Lanternier

first: Jean-Laurent

last: Casanova

first: Clément

last: Cochain

first: Alma

last: Zernecke

first: Antoine-Emmanuel

last: Saliba

first: Jean-Sebastien

last: Silvestre

first: Alain

last: Tedgui

first: Ziad

last: Mallat

first: Soraya

last: Taleb

first: Cécile

last: Vindis

first: Stéphane

middle: M

last: Camus

first: Harry

last: Sokol


title: Immune mechanisms shape the clonal landscape during early progression of prostate cancer

city: stony brook

first: Fu

last: Luo

state: New York

address: 100 Nicholls Road

institute: Stony Brook University

summary: Understanding the role of the immune microenvironment in modulating intratumor heterogeneity is essential for effective cancer therapies. Here we show that two types of tumor clonal landscapes emerge during early progression of prostate cancer in genetically-engineered mouse models. Using lineage tracing and single-cell transcriptomics, we find that slowly progressing tumors contain a multiclonal landscape of relatively homogenous subpopulations within a well-organized tumor microenvironment, whereas more advanced and aggressive tumors contain competing dominant and minor clones accompanied by a disordered microenvironment. We demonstrate that the dominant/minor modality is associated with differential immunoediting, in which minor clones are marked by increased expression of  IFNγ-response genes and the T-cell activating chemokines Cxcl9 and Cxcl11. Furthermore, immunomodulation of the IFNγ pathway can rescue minor clones from elimination. These findings suggest new immunotherapy approaches to modulate clonal fitness and tumor progression in prostate cancer.

overall_design: Confetti+ cells from AP lobes of 4-weeks post-TAM Nkx3.1CreERT2/+; Ptenflox/flox; K-RasLSLG12D/+; R26r-Confetti (NPK) mice were collected via FACS. Dominant and minor clones were determined by the size of the larger patches per color. For bulk RNA-seq experiments,  dominant and minor cells were used for RNA isolation. For single cell RNA-seq experiments, dominant and minor cells were used for single-cell library construction via the 10x Genomics Chromium Single Cell 3′ Library & Gel Bead Kit v3 (10x Genomics).

first: Lara

middle: F

last: Tshering

first: Michael

last: Shen

first: Flaminia

last: Talos


title: XAP5 CIRCADIAN TIMEKEEPER regulates RNA splicing and the circadian clock by genetically separable pathways

city: DAVIS

first: Stacey

middle: L

last: Harmer

address: 1002 Green Hall, One Shields Ave.

department: Plant Biology

institute: UC Davis

summary:
Regulators of post-transcriptional events, such as pre-mRNA splicing factors, are involved in controlling the pace of the circadian clock. However, in most cases the underlying mechanisms remain unclear. Previously, we have identified XAP5 CIRCADIAN TIMEKEEPER (XCT) as an Arabidopsis thaliana circadian clock regulator with uncharacterized molecular functions.
To investigate a possible role for XCT in RNA splicing, we performed PacBio Isoform Sequencing (Iso-Seq) on wild-type Col-0, reduction-of-function allele xct-1, null allele xct-2, the complemented line xct-2 XCT and prl1-2 (a mutate with known defects in intron retention).
We then performed differential splicing analysis on the Iso-Seq data using JunctionSeq R package. Our results indicate that xct mutants have transcriptome-wide pre-mRNA splicing defects, predominantly aberrant 3’ splice site selection. Expression of a genomic copy of XCT fully rescues those splicing defects.

overall_design: Differential splicing analysis of PacBio Iso-Seq data for XCT- and othe splicing-factor-related alleles.

first: Hongtao

last: Zhang

first: Roderick

last: Kumimoto

first: Shajahan

last: Anver


title: Reciprocal regulation of phosphatidylcholine synthesis and H3K36 methylation programs metabolic adaptation II

city: Hangzhou

first: Zhu

last: Yibing

state: Zhe Jiang

address: Xihu

department: Life Of Science

institute: Zhejiang University

summary: Our findings demonstrated how phospholipid metabolism enabled metabolic transformation through an epigenetic modification, illuminating an underappreciated metabolic intersection for environmental adaptation in eukaryotic cells.

overall_design: Saccharomyces cerevisiae (CEN.PK) mRNA profiles of WT/set2Δ/cho2Δ/cho2set2Δ/opi1Δ/opi1set2Δ at 1h in SL (minimal culture condition) switching from YPL(rich culture condition)

first: Yibing

last: Zhu

first: Wen

last: Fang


title: Inductive genes upon aerial exposure to (+)-borneol in Arabidopsis

city: Shiga

first: Junji

last: Takabayashi

address: 2-509-3 Hirano, Otsu

department: Center for Ecological Research

institute: Kyoto University

summary: When aboveground parts of intact plants are exposed to volatile organic compounds emitted from neighboring con-/heterospecific plants that are artificially damaged or damaged by herbivores, the resistant responses are induced in the plants. Differential responses of plants to enantiomers of the same volatile compound have also been reported in Arabidopsis: the root became shorter when Arabidopsis seedlings are exposed to aerial borneol, and the dose-dependent root length reduction was significantly different between (+)- and (-)-borneol. We identified (+)-borneol dependent inductive genes in Arabidpsis in this transcriptome analysis.

overall_design: Expression profiling in Arabidopsis leaves treated by 25 mM (+) or (-) borneol for 24h was compared to mock control using single-color method with two or three biological replicates.

first: Kazunori

last: Okada


title: Effect of nociceptors on dendritic cells

city: Boston

first: Ulrich

last: von Andrian

address: 77 Ave Louis Pasteur

institute: Harvard Medical School

summary: We explored the effects of nociceptors on DC under various conditions by means of in vitro coculture of Flt3L-induced bone marrow-derived DCs and primary mouse nociceptors.

overall_design: Day 9 Flt3L-induced bone marrow DCs were cultured alone or with nociceptors and various stimuli overnight. DC subsets were FACS-sorted and sequenced

first: Urich

middle: H

first: Pavel

last: Hanč


title: Identification and expression pattern of mRNAs and lncRNAs in breast muscle during pigeon (Columba livia) development.

city: Chengdu

first: Yi

state: Sichuan

address: gongpin road #211

institute: Sichuan Agricultural University

summary: Hence, in order to investigate the gene expression profiles of skeletal muscle, we analyzed the four stages (1 day, 14 days, 28 days, and 2 years old) of breast muscle in White-King pigeon using transcriptome sequencing.

first: Xun

last: Wang


title: Transcriptome analysis in acute GI GVHD reveals a unique signature in children and shared biology with pediatric IBD

city: Cincinnati

first: Stella

last: Davies

state: OH

address: 3333 Burnet Ave

department: Cancer & Blood Disease Institute

institute: Cincinnati Children's Hospital

summary: We demonstrate a unique gene signature in acute GI GVHD with differential expression of genes which have been previously described as important in GVHD

overall_design: We performed transcriptomic analyses on freshly frozen (n=21) and paraffin embedded (n=35) gastrointestinal (GI)biopsies from children with and without acute GI graft versus host disease (GVHD) to study differential gene expressions

first: Pooja

last: Khandelwal

first: Dana

last: Lounder

first: Nathan

last: Luebbering


title: Multi-modal control of dendritic cell functions by nociceptors

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

overall_design: Refer to individual Series


title: mRNA expression profiles of 7 gastric cancer cell lines and primary cancer cells.

city: Tokyo

first: Masayuki

last: Komatsu

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

institute: National Cancer Center Research Institute

summary:
Molecular characterization of 7 peritoneally-metastatic gastric cancer cell lines and primary cancer cells established  from a patients’ ascites.
We performed comprehensive transcriptome analyses using microarrays of our established gastric cancer cell lines and primary cancer cells.

overall_design: 7 cancer cell lines and primary cancer cells

first: Fumiko

last: Chiwaki

first: Rie

last: Komatsuzaki

first: Hiroki

last: Sasaki


title: mRNA expression profiles of newly established 49 gastric cancer cell lines.

summary:
Establishment and molecular characterization of 49 peritoneally-metastatic gastric cancer cell lines from 18 patients’ ascites.
We performed comprehensive transcriptome analyses using microarrays of our established gastric cancer cell lines.

overall_design: 49 cancer cell lines


title: Small Intestinal Resident Eosinophils Maintain Gut Homeostasis Following Microbial Colonisation

city: Clayton

first: Nicholas

middle: C

last: Wong

state: Victoria

address: Wellington Road

department: Monash Bioinformatics Platform, Central Clinical School

country: Australia

institute: Monash University

summary: Intestinal homeostasis following postnatal microbial colonization requires the coordination of multiple processes, including the activation of immune cells, cell-cell communication, the controlled deposition of extracellular matrix, and epithelial cell turnover and differentiation. The intestine harbors the largest frequency of resident eosinophils of all homeostatic organs, yet the functional significance of eosinophil residence in the gut remains unclear. Eosinophils are equipped to both respond to, and modify, their local tissue environment and thus are able to regulate the adaption of tissues to environmental changes. We report a critical role for eosinophils in regulating villous structure, barrier integrity and motility in the small intestine. Notably, the microbiota was identified as a key driver of small intestinal eosinophil activation and function. Collectively our findings demonstrate a critical role for eosinophils in facilitating mutualistic interactions between host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.

overall_design: Whole Transcriptome Profiling of Bulk tissue from the proximal jejunum, devoid of epithelial cells (non-IEC fraction) or with epithelial cells, from BALB/c and dbl.GATA1 SPF mice housed in specific pathogen-free (SPF) environment for recolonisation. Up to six replicate mice were profiled from each study group

first: Kathleen

last: Shah

first: Nicola

last: Harris


title: Overexpression of the EMT modulator SNAI1 in HPC7 cells

city: Melbourne

first: Kevin

middle: Robert

last: Gillinder

address: 99 Commercial Road

department: Australian Centre for Blood Diseases

summary: Modulators of epithelial to mesenchymal transition (EMT) have recently emerged as novel players in the field of leukemia biology. The mechanisms by which EMT modulators contribute to leukemia pathogenesis, however, remain to be elucidated. Here we investigate the role SNAI1 - a key modulator of EMT – and its effect on chromatin state using ATAC-seq in hematopoietic cells (HPC7).

overall_design: A murine hematopoietic progenitor cell line, HPC7, were transduced with a retroviral vector encoding FLAG-tagged SNAI1. Cells were harvested to generate ATAC-seq libraries for Next-Generation Sequencing.

first: Catherine

last: Carmichael

first: Sona

last: Samuel

first: Helen

last: Mitchell

first: Andrew

last: Perkins

first: Jody

last: Haigh


title: Single-cell RNAseq of the mouse lung

city: San Francisco

first: Tien

last: Peng

state: CA

address: 513 Parnassus Ave, Health Sciences East 1350

department: Department of Pulmonary Medicine

institute: University of California San Francisco

summary: To define the hedgehog-interacting protein (Hhip) expression domain in adult mouse lung, we conduct single-cell RNAseq of the mouse lung using 10X scRNAseq technique.

overall_design: Adult mouse lung epithelial and mesenchymal cells were sorted based on EpCAM+ and EpCAM-/CD45-/CD31-, respectively. Dead cells were excluded using DAPI negative selection. The sequencing sample were mixed with half epithelial cells and half mesenchymal cells.

first: Chaoqun

last: Wang


title: Plasma small extracellular vesicles microRNAs profile in advanced ovarian cancer

city: changsha

first: mu

last: Liu

address: No. 932, Lushan South Road, Yuelu District, Changsha City, Hunan Province

institute: Central South University

summary: No residual disease after debulking Surgery (R0 resection) is the most critical independent prognostic factor for advanced ovarian cancer (AOC). Therefore, it is of paramount importance to preoperative estimate the likelihood of R0 resection for choosing the best therapeutic strategy. Our study aimed to develop a non-invasive and reliable detection method for AOC patients with a high risk of residual disease. An integrated plasma small extracellular vesicles (sEVs) microRNA profiling was generated by RNA sequencing in AOC patients with no residual disease patients (R0) and residual disease(non-R0). We identified and validated a logistic model based on plasma sEVs miRNAs to predict residual disease in AOC patients.

overall_design: Plasma small extracellular vesicles microRNAs profile of advanced ovarian cancer patients with residual disease (non-R0=14) or no residual disease (R0=11)

first: Mu

first: Jie

last: Tang


title: Skeletal Muscle Transcriptomic Responses to Chronic Concurrent Exercise Training

first: Baubak

last: Shamim

state: VIC

address: Level 5, 215 Spring Street

department: Mary MacKillop Institute for Health Research

institute: Australian Catholic University

summary: Combining resistance and endurance exercises in a training regime (concurrent training) can impair improvements in muscle hypertrophy, strength, and power compared to resistance training alone. Here we aimed to characterize skeletal muscle transcriptomic changes following chronic concurrent training to determine whether contraction-induced gene expression may reveal molecular underpinnings explaining impaired adaptations. Eighteen young, healthy male participants underwent 12 weeks of resistance, endurance, or concurrent training. Maximal strength, aerobic capacity, and anaerobic power were assessed. Transcriptomics were performed on skeletal muscle biopsies obtained pre and post-intervention. Improvements to maximal anaerobic power are impaired with concurrent and endurance training. Gene expression related to plasma membrane structures was enriched while gene expression related to regulation of mRNA processing and protein degradation was suppressed with concurrent training. Considerable overlap of gene expression related to extracellular matrix remodeling was observed between concurrent and endurance training. Our results provide the first comprehensive comparison of unique and overlapping gene sets enriched following chronic resistance, endurance, and concurrent training, and reveals pathways that may have implications in relation to impaired adaptations when undertaking concurrent training.

overall_design: The study employed a parallel-groups design where participants were stratified according to lean body mass (LBM) and allocated to either a resistance only (RES), endurance only (END) or concurrent resistance and endurance exercise training (CET) group for 12 weeks. Measures of maximal strength, aerobic capacity, and anaerobic power, as well as body composition were performed pre- and post-intervention. Resting biopsies were obtained from the vastus lateralis muscle pre-intervention, after weeks 2 and 8 of exercise training, and post-intervention. For the duration of the intervention, all participants consumed a high-protein diet (2 g·kg-1·d-1). The study was approved by the Australian Catholic University Human Research Ethics Committee and was carried out in accordance with the latest revision of the Declaration of Helsinki. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617001229369).


title: Transcription Factor Network Reveals New Treatments for Prostate Cancer Docetaxel Drug Resistance

city: Ann Arbor

first: Evan

middle: T

last: Keller

address: 2800 Plymouth Rd

institute: University of Michigan

summary: Overcoming drug resistance is critical increasing the survival rate for prostate cancer (PCa).  In this study, we modeled docetaxel resistance using two PCa cell lines, DU145 and PC3.  We conducted both single cell and bulk RNA sequencing.  We constructed a transcription factor (TF) network for the docetaxel sensitive and resistant variants for all cell lines and sequencing methods resulting in 8 networks.  We identified shared edges and nodes that represent a shared TF network for PCa that modeled the changes after acquiring drug resistance.  Using this shared TF network, we identified drivers of the resistant phenotype.  Interestingly, the network constructed from the bulk sequencing dataset revealed different TF drivers of resistance compared with the network constructed from the single cells.  We validated the results constructed from the single cells to demonstrate the validity of the single cell sequenced TF network.  We targeted GABPA (only identified in the single cell constructed network) and successfully re-sensitized both cell lines to docetaxel treatment.  Additionally, we conducted connectivity map analysis to identify potential drugs that disrupt the resistant networks.  We identified trichostatin A as a potential combination treatment using the single cell sequenced network.  Combination treatment of trichostatin A and docetaxel, both in vitro and in vivo PCa models decreased tumor growth.  These results suggest by analyzing a population of resistant cells, identification of drivers and novel treatments is possible.

overall_design: RNA sequencing of DU145 and PC3 sensitive and docetaxel resistant cell lines

first: Patricia

last: Schnepp

first: Aqila

last: Ahmed

first: June

last: Escara-Wilke

first: Greg

last: Shelley

first: Atsushi

last: Mizokami


title: Exploring transcriptomic landscapes in red cell populations, in their extracellular vesicles and on single cell level

city: Helsinki

first: Jenni

last: Lahtela

address: Tukholmankatu 8

department: Institute for Molecular Medicine Finland FIMM

country: Finland

institute: University of Helsinki

summary: Circulating human red blood cells (RBCs) consist of mature erythrocytes, and immature reticulocytes. As being anucleated cells, RBCs lack typical, abundant transcriptomes but are known to contain low amounts of diverse long transcripts and microRNAs. The exact role and importance of these RNAs is, however, lacking. To study this further, we have explored the RNA content of RBCs as well as extracellular vesicles of RBCs using next generation sequencing (NGS). Furthermore, to understand the dynamics of the RBC transcriptome we performed single cell RNA sequencing on RBCs both from fresh blood and blood unit. Analysis of the single cell transcriptomes revealed that while the majority of the cells don’t have detectable RNA the remaining, approximately 10% of the cells fall into three sub-populations based on their RNA content. Overall decrease in the RNA quantity over the populations is observed. Qualitative changes include the differences in the hemoglobin (Hb) content of the cells, and the changes in the expression of ribosomal and mitochondrial genes. A previously unknown transcript of a long non-coding RNA, MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is the most enriched marker gene for one subpopulation of RBCs suggesting a role for MALAT1 in reticulocyte maturation. Enriched pathways in RBC transcriptome, such as autophagy, reflect the processes required for reticulocyte maturation to erythrocytes. RBC transcriptome  is transferred to extracellular vesicles (EVs) suggesting the vesiculation as the mechanism to remove the cellular contents at the final stages of erythrocyte maturation.

overall_design: Two human red blood cell samples were analysed. One leukoreduced red blood cell (RBC) unit sample and one fresh red blood extract sample. The data from these two samples was combined and analysed together.

first: Erja

last: Kerkelä

first: Antti

last: Larjo

first: Laura

last: Mäenpää

first: Pirkko

last: Mattila


title: Evolutionary dynamics of small RNA regulation through genomic hybridization in sugarcane

city: St. Louis

first: Blake

middle: C.

last: Meyers

state: MO

address: 975 N Warson Road

institute: Donald Danforth Plant Science Center

summary: The small RNAs and their targets were characterized in sugarcane wild species and cultivars. This was done by deep sequencing the small RNA populations and uncapped mRNAs of young leaves from mature plants.

sample_organism:
Saccharum robustum
Saccharum spontaneum
Saccharum hybrid cultivar
Saccharum barberi
Saccharum sinense
Saccharum hybrid cultivar SP70-1143
Saccharum hybrid cultivar RB867515

overall_design: Screening of the sRNA transcriptome of wild sugarcane species and cultivars

first: Clícia

last: Grativol

first: Tzuu-fen

last: Lee

first: Atul

last: Kakrana

first: Flávia

last: Thiebaut

first: Adriana

last: Hemerly

first: Paulo

last: Ferreira


title: Effect of depletion of NUP153 on gene expression in esophageal squamous cell carcinoma cell line TE5 cells [RNA-seq]

city: kanazawa city

first: Masaharu

last: Hazawa

address: Kakuma-machi

institute: Kanazawa University

summary: To investigate the function NUP153 in the regulation of cancer cell biology, we established TE5 cell lines in which NUP153 gene has been knocked down by shRNA.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for TE5 cells and its KD derivatives (shNUP153).


title: High-throughput sequencing and analysis of gene modification regulated by epigenetics modification in adult and old intracerebral hemorrhage rats. [RNA-Seq]

city: wuhan

first: dong

last: chen

state: Hubei

address: GaoXin 2nd Road

institute: ablife

summary: Here we performed in depth epigenome sequencing and analysis to study the mechanism of high mortality rate of ICH in rat brain. It reveals a systematical transcription activation of mRNA genes enriched in inflammation and immune responses. These genes are clustered to specific genomic loci and regulated by repressive and activation chromatin markers. We show that epigenetic reprogramming responding to ICH in old rat brains differs greatly from that in the adult.

overall_design: Examination of transcriptome genes in adult (13 mon old) and old (21 mon old) ipsilateral and contralateral brain tissues

first: Xiao-Yi

last: Xiong

first: Qing-Wu

last: Yang


title: Oral CBD treatment is associated to an anti-inflammatory gene expression signature in myeloid cells of people living with HIV

status: Public on Mar 31 2023

city: Gainesville

first: Simone

last: Marini

state: FLORIDA

address: 2004 Mowry road

institute: University of Florida

summary: HIV-related comorbidities appear to be related to chronic inflammation, a condition characterizing people living with HIV (PLWH). Prior work indicates that cannabidiol (CBD) might reduce inflammation; however, the genetics underpinning this effect are not well investigated. Our main objective is to detect gene expression alterations in human peripheral blood mononuclear cells (PBMCs) from PLWH after at least one month of CBD treatment.    We collected PBMCs from three HIV-positive subjects at baseline and after CBD treatment (at least 27 days) via single-cell RNA sequencing. We obtained a coherent signature, characterized by an anti-inflammatory activity, of differentially expressed genes in myeloid cells.    Our study shows how CBD is associated with alterations of gene expression in myeloid cells after CBD treatment.

overall_design: PBMCs from people living with HIV before and after CBD oil treatment were analyzed using scRNAseq.

first: Carla

last: Mavian


title: RNA Sequencing of liver samples of TERP-AUG, TERP-wt-AUG, TERP-del7 and TERP-del7-wt mice

city: Moscow

first: Leonid

last: Kats

address: Leninskye gory, 1, building 40

country: Russia

institute: Lomonosov Moscow State University

summary: We present RNA-Seq data for mice with mutated TERP (TERP-AUG and TERP-del7) and for mice from control groups (TERP-wt-AUG and TERP-del7-wt). TERP-AUG mutation leads to increased translation of TERP, and TERP-del7 mutation leads to the formation of nonfunctional TERP.

overall_design: Liver samples of 4 different groups of mice, namely: TERP-AUG, TERP-wt-AUG, TERP-del7 and TERP-del7-wt were obtained. cDNA libraries for RNA-Seq were constructed and sequenced, resulting in 16 RNA-Seq data sets.

first: Yanislav

last: Hrytseniuk

first: Dmitri

middle: A

last: Bykov

first: Artyom

last: Egorov

first: Olga

last: Averina

first: Viktoriia

last: Shliapina

first: Oleg

last: Permyakov

middle: O

last: Grigorieva

first: Nadezhda

last: Makarova

first: Petr

middle: V

last: Sergiev

first: Sergey

last: Dmitriev

first: Maria

middle: P

last: Rubtsova


title: Generation of ventralized thalamic organoids with inhibitory thalamic reticular nucleus

city: New Haven

first: In-Hyun

last: Park

state: CT

address: 10 AMISTAD ST # 201B

department: Genetics

institute: Yale University

summary: Single-cell RNA-seq was performed in SHH-treated thalamic organoids

overall_design: Human thalamic organoids (ThOs) resembling the dorsal thalamus by dual SMAD inhibition and insulin-driven caudalization coupled with thalamic patterning (MEK-ERK inhibition and BMP7 activation) from hESCs. The organoids were further guided into ventral identity with SHH treatment.

first: Bilal

last: Cakir

first: Ridvan

last: Kiral

first: Yoshiaki

last: Tanaka

first: Yangfei

last: Xiang


title: Gene expression changes in matched tumor and skin biospy in melanoma patients treated with atezolizumab

city: Durham

first: Rikhia

last: Chakraborty

state: North Carolina

address: 801 Capitola Drive, Suite 12

institute: Xilis, Inc.

summary: Immunotherapies, including immune checkpoint inhibitors (ICI), have revolutionized the treatment of many cancers, producing significant improvements in survival in patients with many different cancers. However, the intended anti-tumor effects also result in a unique form of autoimmunity, known as immune-related adverse events (irAEs), which have emerged as a limiting factor for many immunotherapies. Cutaneous irAEs (cirAEs), the most frequently occurring ICI–related toxicities, have been associated with improved efficacy and survival but, in their severe forms, require systemic steroids and have in cases led to premature ICI discontinuation and fatality. There is a need for both robust biomarkers and adequate models that effectively predict which patients who develop irAEs may have improved outcomes. Using a microfluidic droplet technology that generates "mini" patient-derived organoids called MicroOrganoSpheres (MOSTM), we successfully generated skin MOS from skin biopsy samples in both healthy skin and tumor-involved skin that sustain the original patient skin immune microenvironment over three weeks. Using this model, we assessed skin cell toxicity and cytokine release in response to ICI and targeted therapies. Clinical responses were largely consistent with the skin and tumor MOS assay readouts, indicating that MOS recapitulates the potential association between skin irAEs and efficacy. Matched pairs of patient melanoma and skin MOS showed good concordance with patient outcome indicating that MOS recapitulates the potential association between skin irAEs and efficacy. Enrichment of genes associated with atopic dermatitis, vitiligo, and psoriatic dermatitis were observed in MOS generated from skin of an ICI-sensitive patient compared to the MOS generated from skin of an ICI-resistant patient. These results indicated that the skin MOS platform can potentially predict the dermatological toxicity of ICI. As the MOS assay can be completed within 12 days after biopsy acquisition, this novel technology may enable personalized medicine approaches by prediction of cirAEs and efficacy for individual patients.

overall_design: MOS generated from matched skin and tumor tissue biopsies from 2 melanoma patients were treated with atezolizumab to determine correlation between treatment sensitivity and gene expression changes.

first: Katerina

last: Fagan-Solis

first: Jessica

last: DeVilla

first: Xiling

last: Shen


title: Effects of the bovine SLICK1 mutation in PRLR on sweat gland area and FOXA1 abundance and on global gene expression

city: GAINESVILLE

first: FAHONG

last: YU

state: FL

address: 2033 Mowry Rd

department: ICBR

institute: UNIVERSITY OF FLORIDA

summary: The SLICK1 mutation confers thermotolerance to cattle inheriting one or two copies of the gene. Results are unclear as to whether the mutation changes capacity of animals to undergo sweating during heat stress. Accordingly, differences in characteristics of sweat glands between slick and wildtype Holstein heifers was determined. There were no differences in the proportion of skin occupied by sweat glands but sweat glands from slick heifers had higher amounts of immunoreactive FOXA1 than wildtype heifers. FOXA1 is a transcription factor important for sweating.  While results do not support the idea that the SLICK1 mutation changes the abundance of sweat glands in skin, it did affect functional properties of sweat glands, as indicated by increased abundance of immunoreactive FOXA1.

overall_design: All animal procedures were approved by the University of Florida and University of California Davis Institutional Animal Care and Use Committees. Heifers were genotyped for the SLICK1 mutation in PRLR using either the CLARIFIDE Plus platform from Zoetis (Parsippany, NJ, USA) or ta KASP-PCR procedure previously described (Sosa et al., 2021). For the purposes of this paper, animals were referred to as SL-/- if they did not inherit a SLICK1 allele (i.e., were wild-type) and SL+/- if they were heterozygous for the SLICK1 allele. The objectives were to determine whether Holstein heifers heterozygous for the SLICK1 mutation (termed SL+/-) have a higher proportion of the dermis of the skin occupied by sweat glands than wildtype heifers without the mutation (termed SL-/-), evaluate whether amounts of immunoreactive FOXA1 in sweat glands differed between SL-/- and SL+/- heifers, and identify differences in skin transcriptome associated with inheritance of the SLICK1 allele.

first: F

last: Sosa

first: A

last: Carmickle

first: L

middle: J

last: Oliverira

first: M

last: Sagheer

last: Yu

middle: D

last: Altman

first: S

last: Dikmen

last: Denicol

first: C

last: Larson

first: T

last: Sonstegard

first: P

last: Hansen


title: Revealing the underlying regulatory mechanism of LINC00313 in Osimertinib-resistant NSCLC cells by ceRNA network analysis

city: Guangzhou

first: Liu

last: Huisheng

address: Wushan load

institute: South China University of Technology

summary: In this study, RNA-sequencing technology was employed to identify the differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) between H1975 and H1975OR. Based on the starbase 2.0 database, the potential targeting relationships between DE-lncRNAs and DE-mRNAs were predicted and identified to construct the ceRNA networks. Subsequently, functional and pathway enrichment analysis were carried for target DE-mRNAs to obtain functional pathways associated with Osimertinib resistance and potential drug resistance-related DE-mRNAs. Besides, the expression of LINC00313 and COL1A1 was validated by q-Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Finally, the activation of PI3K/Akt pathway was proved by immunohistochemistry staining.

overall_design: Osimertinib resistant H1975 cells (H1975OR); osimertinib-sensitive H1975 cells (H1975)

first: D

last: Ding

first: X

last: Xue

first: W

last: Liang

first: J

last: Zhong


title: A phase II study of guadecitabien combined with irinotecan vs regorafenib or TAS-102 in previously treated metastatic colorectal cancer patients

city: Baltimore

first: leslie

last: cope

state: MD

address: 550 N. Broadway

institute: leslie cope

type: Methylation profiling by genome tiling array

overall_design: Patients with metastatic CRC were randomized 2:1 to receive guadecitabine and irinotecan versus standard of care (regorafenib or TAS-102).  Pre- and post-methylation status were assessed on tumor biopsies (baseline compared to C2 between days 8-15) and peripheral blood drawn weekly x 6 weeks and at beginning of each subsesquent cycle.

first: Nilo

last: Azad

first: Leslie

last: Cope

first: Valerie

last: Lee

first: Rose

last: Parkinson

first: Marianna

last: Zahurak

first: Tamara

last: Lopez-Vidal


title: Epsilon Toxin-Producing Clostridium perfringens within the MS Gut Microbiome and Epsilon Toxin Function on Immune Privilege

city: New York

first: Timothy

last: Vartanian

state: NY

address: 1300 York Avenue

department: Brain and Mind Research Institute

institute: Weill Cornell Medical College, Cornell University

summary: Multiple Sclerosis (MS) is a complex disease of the CNS believed to require one or more environmental triggers and is characterized by episodic formation of inflammatory demyelinating lesions in the brain and spinal cord. Gut dysbiosis is a common feature in MS and here, using enhanced and quantitative PCR detection, we show that people with MS are more likely to harbor and have higher abundance of epsilon toxin (ETX)-producing strains of Clostridium perfringens within their gut microbiome compared to healthy controls (HC). MS patient-derived isolates produce functional ETX and have a genetic architecture typical of highly conjugative plasmids.  In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, we find that ETX can substitute for PTX in disease induction.  In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE results in multifocal demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the lesion distribution observed in MS. Transcriptional profiles from CNS endothelial cells reveal ETX-induced genes that are known to play a role in overcoming CNS immune privilege.  Together, these findings support ETX-producing strains of C. perfringens as biologically plausible pathogens in MS to trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

overall_design: Comparative gene expression profiling analysis of RNA-seq data of CNS endothelial cells treated with PBS, ETX (0.5 μg/kg b.w.), or PTX (5 μg/kg b.w).


title: Human myotube transcriptome response to intelectin

city: Stirling

first: Iain

last: Gallagher

address: Room 4B133 Cottrell Building, University of Stirling, Airthrey Road

department: Faculty of Health Sciences and Sport

institute: University of Stirling

summary: Human primary myoblasts were differentiated to myotubes and treated with 0, 10, 100, or 500ng/ml intelectin for 6 hours. Total RNA was extracted and profiled on Affymtrix Clariom D GeneChips reannotatwed to ENSG identifiers using the Brainarray V25 cdf.

overall_design: 3 separate primary human myoblast cell lines were purchased from Lonza. The myoblasts were expanded, differentiated to myotubes & treated with 0, 10, 100, or 500ng/ml recombinant intelectin for 6 hours. Total RNA was extracted and profiled on Affymetrix Clariom D GeneChips.

first: Robert

last: Paval


title: Investigation of small RNA biogenesis and turnover in the absence of the PRC2 associated protein Ded2p

city: Montpellier

first: Kazufumi

last: Mochizuki

address: 141 rue de la Cardonille

institute: Institute of Human Genetics, CNRS

summary: Heterochromatic histone H3 methylation at lysine 9 (H3K9me2/3) and lysine 27 (H3K27me3) is generally catalyzed by SUV39 and EZH family methyltransferases, respectively, and has distinct functions in most eukaryotes. In contrast, the ciliated protozoan Tetrahymena lacks the SUV39 enzyme, and the EZH enzyme Ezl1p is responsible for the deposition of both H3K9me3 and H3K27me3 during Piwi-directed DNA elimination. Understanding how both modifications are catalyzed by the EZH enzyme should shed light on the mechanism and the evolution of the division of labor between the two heterochromatic histone methyltransferase families in eukaryotes. Here, we show that loss of the novel protein Ded2p abolishes the accumulation of H3K9me3 but not H3K27me3 in Tetrahymena. The phenotypes of DED2 KO cells revealed that H3K27me3 is sufficient for promoting secondary small RNA biogenesis but not for suppressing TEs, assembling heterochromatin bodies and completing DNA elimination. Ded2p associates with Ezl1p through Rnf2p, a component of Tetrahymena Polycomb Repressive Complex 2 (PRC2) to promote the accumulation of H3K9me3. Our results indicate that there are functional distinctions between H3K9me3 and H3K27me3 in different steps of the DNA elimination process and the specificity of the methyltransferase activity of PRC2 can be modulated by its associated factor to catalyze H3K9me3.

overall_design: The primery biogenesis, homology-dependent degradation, and heterochromatin dependent secondary biogenesis of ~29-nt small RNA (scnRNA) were analyzed by sequencing 16-32-nt small RNAs at 3, 6 and 10 hours post-mixing of DED2 KO Tetrahymena thermophila strains

first: Tomoko

last: Noto


title: HTT regulates muscle differentiation in vitro.

city: Poznan

first: Marcin

last: Rucinski

address: Swiecicki 6

department: Histology and Embriology

country: Poland

institute: Poznan University of Medical Science

summary: Our study identified HTT as a key regulator of skeletal muscle differentiation in vitro.

overall_design: Huntingtin gene (HTT) has been knock down with pool of siRNAs and scramble siRNA library, which served as a negative control. In this study we used two murine cell lines: C2C12 cell line which were obtained from ATCC.

first: Mateusz

last: Sowinski

first: Witold

last: Szaflarski

first: Mark

last: Isalan

first: Michal

last: Mielcarek


title: Propagated circulating tumor cells uncover the role of NF-kB and COP1 in metastasis

city: Washington

first: Jerry

last: Xiao

state: DC

address: 3900 Reservoir Rd NW, PCS Bldg, Room GR10C

department: Tumor Biology

institute: Georgetown University

summary: Circulating tumor cells (CTCs), a population of cancer cells that represents the seeds of metastatic nodules, are a promising model system for studying metastasis. In this study, we perform NGS on cultured CTCs and corresponding CTC-derived xenografts for four different unique patients. Using RNA-sequencing and DNA-sequencing, we establish a prospective role for NF-kB signaling and COP1 muations in driving successful cancer metastasis.

overall_design: Samples were drawn from healthy donors and patient-specific whole blood (WB), cultured CTCs (CTCs), and CTC-derived xenograft primary tumors (CDX tumors) and corresponding tissues with macrometastatic nodules.

first: J

first: U

last: Sharma

first: A

last: Arab

first: S

last: Miglani

last: Bhalla

last: Suguru

first: R

last: Mukherji

first: M

middle: E

last: Lippman

first: P

middle: R

last: Pohlmann

last: Zeck

last: Marshal

first: BA

last: Weinberg

middle: W

last: He

middle: S

last: Noel

last: Schlegel

first: H

last: Goodarzi

last: Agarwal


title: CHIKV VLP Vaccination in Humans induced broadly neutralizing antibodies

first: Saravanan

last: Raju

address: 660 S Euclid Avenue

institute: Washington University in St. Louis

summary: VLP Vaccination in humans induced antigen-specific B cells with broad reactivity and protection in mouse models of infection

overall_design: Human PBMCs were enriched for non-naïve B cells and subject to single-cell sequencing with the 10x Genomics platform

first: Michael

last: Diamond


title: ΔNp63 controls stemness and inflammation in the adult epidermis

city: Stony Brook

first: Jinyu

last: Li

address: 101 Nicolls Rd

department: Cancer Center

institute: Stony Brook University

summary: The p63 transcription factor is critical for epidermis formation in embryonic development, but its role in the adult epidermis is barely investigated. Here we show that acute genetic ablation of ΔNp63, the main p63 isoform, in the adult epidermis disrupts keratinocyte proliferation and self-maintenance and, unexpectedly, triggers an inflammatory psoriasis-like condition. Mechanistically, single-cell RNA sequencing revealed down-regulation of the cell cycle genes, up-regulation of differentiation markers, and induction of several pro-inflammatory pathways in ΔNp63-ablated keratinocytes. Intriguingly, ΔNp63-ablated cells disappear three weeks post-ablation, at the expense of the remaining non-ablated cells. This was not associated with active cell death mechanisms, but rather with reduced stemness and self-maintenance capacity. Indeed, in vivo wound healing assay, a physiological readout of the epidermal stem cell function, was largely impaired in the ablated skin. We found that the Wnt signaling pathway (Wnt5a, Wnt10a, Fzd6, Fzd10) and Col17a1 are the likely ΔNp63 effectors responsible for keratinocyte proliferation and stemness, while AP1 factors are responsible for excessive differentiation, and Il-1a, Il-18, Il-24 and Il-36γ for the suppression of inflammation. These data implicate ΔNp63 as a critical node that coordinates balanced epidermal homeostasis and suppression of inflammation in the adult epidermis, upstream of known regulatory pathways.

overall_design: ScRNA-seq of control or ΔNp63 epidermis at 1 day and 1 week

first: Evguenia

middle: M

last: Alexandrova

first: Christopher

last: Eyermann


title: Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [methylation]

city: Madrid

first: GarciaCarbonero

last: Lab

state: Comunidad de Madrid

address: Av/ Córdoba s/n

department: Centro de Oncología Experimental

country: Spain

institute: Instituto de Investigación Hospital 12 de Octubre

summary:
Background: Neuroendocrine neoplasms (NENs) are mutationally quiet, and epigenetic mechanisms drive their development and progression. We aim to comprehensively characterize the microRNA (miRNA) profile of NENs, and explore downstream targets and their epigenetic modulation.
Material and Methods: In total, 84 cancer-related miRNAs were analyzed in 84 NEN samples from lung and gastroenteropancreatic GEP origin, and their prognostic value was evaluated by univariate and multivariate models. Transcriptomics (N=63) and methylomics (N=30) were performed to predict miRNA target genes, signaling pathways and regulatory CpG sites. Findings were validated in The Cancer Genome Atlas (TCGA) cohorts and in NEN cell lines.
Results: We identified a signature of eight miRNAs that stratified patients in three prognostic groups (5-year survival of 80%, 66% and 36%). Expression of the eight-miRNA gene signature correlated with 71 target genes involved in PI3K-Akt and TNFα-NF-kB signaling. Of these, 28 were associated with survival and validated in silico and in vitro. Finally, we identified five CpG sites involved in the epigenetic regulation of these eight miRNAs.
Conclusion: In brief, we identified an 8-miRNA signature able to predict survival of patients with GEP and lung NENs, and identified genes and regulatory mechanisms driving prognosis in NEN patient.

overall_design:
This study includes 85 paired tumor and non-tumor samples from 85 lung and GEP NEN patients. miRNAs profiling was performed in 84 patients, DNA methylation in 30 patients and RNA expressión in 63 patients.
This dataset includes the DNA methylation data.

first: Beatriz

last: Soldevilla

first: Alberto

last: Lens-Pardo

first: Paula

last: Espinosa-Olarte

first: Carlos

last: Carretero-Puche

first: Sonia

last: Molina-Pinelo

last: Robles

first: Marta

last: Benavent

first: Lourdes

last: Gomez-Izquierdo

last: Fierro-Fernández

first: Patricia

last: Morales-Burgo

last: Jimenez-Fonseca

last: Anton-Pascual

first: Yolanda

last: Rodríguez-Gil

first: Ana

last: Teijó-Quintants

first: Anna

last: La Salvia

last: Rubio-Cuesta

first: Maria

last: Riesco-Martinez

first: Rocio

last: Garcia-Carbonero


title: RNA expression in CCL19-treated CD4+ T cells

city: Research Triangle Park

first: Sara

last: Grimm

state: NC

address: 111 TW Alexander Dr

institute: NIEHS

summary: Transcriptome analysis of mouse naïve CD4+ T cells with or witout chemokine CCL19 treatment.

overall_design: Purified naïve CD4+ T cells (1 million) were cultured in 200 microlitter complete RPMI1640 with immorbilized anti-CD3 and -CD28 antibodies (coating at 1 microgram/mL) in 96 well plate in the presence or absence of recombinant mouse CCL19 for 6 hours. Cells were harvested, RNA was extracted, and cDNA libraries were generated. Comprehensve gene expression was analyzed by RNA sequencing.

first: Hideki

last: Nakano

first: Keiko

first: Donald

middle: N

last: Cook


title: Integrated miRNAs profiling, DNA methylation, and RNA expression in gastroenteropancreatic neuroendocrine neoplasias [mRNA]

first: GarciaCarbonero

last: Lab

overall_design:
This study includes 85 paired tumor and non-tumor samples from 85 lung and GEP NEN patients. miRNAs profiling was performed in 84 patients, DNA methylation in 30 patients and RNA expressión in 63 patients.
This dataset includes the RNA expression data.

first: Beatriz

last: Soldevilla

last: Lens-Pardo

last: Espinosa-Olarte

last: Carretero-Puche

last: Molina-Pinelo


title: Effect of drought stress on gene expression of maize leaves

city: Ithaca

first: yuan

last: jiang

address: 306 Tower Rd

institute: cornell university

summary: To investigate the different drought response between the different maize lines, we screened drought-tolerant line W9706 and drought-susceptible line B73 to compare the  transcriptome

overall_design: Comparative gene expression profiling analysis of RNA-seq data for W9706 and B73

first: yaping

last: yuan


title: Medulloblastoma associated DDX3X mutants restore malignant potential  of medulloblastoma cells decreased upon the loss of DDX3X expression

city: Navi Mumbai

first: Neelam

last: Shirsat

state: Maharashtra

address: Kharghar, Sector 21

department: Shirsat Lab

institute: Advanced Centre for Treatment, Research and Education in Cancer. Tata Memorial Centre

summary: DDX3X is an ATP-dependent RNA helicase. Missense mutations in DDX3X gene are known to occur in WNT, SHH subgroup medulloblastomas. The role of DDX3X in medulloblastoma biology was studied by downregulating its expression in a SHH subgroup Daoy medulloblastoma cell line. DDX3X knockdown resulted in considerable reduction in proliferation, clonogenic potential and anchorage-independent growth of the medulloblastoma cells. Transcriptome analysis was performed to delineate the molecular mechanism underlying reduction in the malignant potential of the medulloblastoma cells upon DDX3X knockdown. Exogenous expression of three DDX3X missense mutants in the DDX3X knockdown cells could restore the malignant potential of the medulloblastoma cells.

overall_design: The expression of DDX3X was downregulated in a doxycycline-inducible manner in Daoy medulloblastoma cell line using two independent shRNAs cloned in the lentiviral vector tet-pLKO-puro.  One shRNA targets the open reading frame while the other targets 3'-untranslated region (3'-UTR) of the DDX3X mRNA. Daoy cells stably expressing shRNA targeting 3'-UTR of the DDX3X mRNA, were stably transfected witha FLAG-tagged wild type DDX3X or mutant DDX3X cloned in the pCMV10-3xFlag vector. Total RNA was extracted from the parental, vector control, DDX3X shRNA expressing Daoy cells as well those expressing wild type or mutant DDX3X wherein expression of endogenous DDX3X was knocked down. Libraries were prepared using the polyA-enriched RNA fraction of the cells using the Illumina Truseq RNA library preparation kit and sequenced on the Illumina Hiseq 2500 or HiseqX platform.

first: Harish

last: Bharambe

first: Satishkumar

last: Singh


title: The transcriptomes of 22RV1 and PC3 cells with or without DDX52 interference

city: Shanghai

first: Wandong

last: Yu

state: China

address: No. 801, Heqing Road, Minhang District, Shanghai

institute: The Fifth People’s Hospital of Shanghai, Fudan University

summary: Total RNA was obtained from 22RV1 or PC3 cells with or without DDX52 interference to perform a High-throughput sequencing

overall_design: The prostate cancer cell line 22RV1 or PC3 expressing shRNA targeting DDX52 or a control sequence. The gene transcript expression profiles were generated by deep sequencing.

first: Guowei

last: Shi