title: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. [scATAC-Seq]

city: Houston

first: Xiaoping

last: Su

state: Texas

address: 7300 Brompton St, Apt 5633

institute: MD Anderson Cancer Center

summary: Monotherapy with Menin inhibitor (MI), e.g., SNDX-5613, induces clinical remissions in patients with relapsed/refractory AML harboring MLL1-r or mtNPM1, but most patients either fail to respond or eventually relapse. Utilizing single cell RNA-Seq, ChiP-Seq, concordant perturbations in ATAC-Seq and RNA-Seq peaks, RPPA and CyTOF analyses, present pre-clinical studies elucidate gene-expression correlates of MI efficacy in AML cells harboring MLL1-r or mtNPM1. MI-mediated genome-wide, concordant, log2 fold-perturbations (up or down-regulation) in ATAC-Seq and RNA-Seq peaks were observed at the loci of MLL-FP target genes, with upregulation of mRNAs associated with AML differentiation. scRNA-Seq analysis of bone marrow aspirate (BMA) cells harboring MLL1-FP and FLT3 mutation revealed enrichment of gene-sets of TNFα, interferon α/γ, inflammatory response and apoptosis gene-sets, but negative enrichment of the gene-set of MYC targets. Notably, MI treatment reduced the number of cells expressing the stem/progenitor cell signature. A protein domain-focused CRISPR-Cas9 screen in MLL1-r AML cells identified targetable co-dependencies with MI treatment, including BRD4, EP300, MOZ and KDM1A. Consistent with this, in vitro co-treatment with MI and BET, MOZ, LSD1 or CBP/p300 inhibitor induced synergistic loss of viability of AML cells with MLL1-r or mtNPM1. Co-treatment with MI and BET or CBP/p300 inhibitor also exerted significantly superior in vivo efficacy in xenograft models of AML with MLL1-r. These findings highlight novel, MI-based combinations that could prevent escape of AML stem/progenitor cells following MI monotherapy and could potentially prevent therapy-refractory relapse of AML with MLL1-r or mtNPM1.

overall_design: Single cell ATAC Seq of an MLL-AF9 expressing AML treated with Menin inhibtor for 16 hours.

first: Warren

last: Fiskus

first: Kapil

middle: N

last: Bhalla


title: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. [bulk ATAC-Seq]

status: Public on Apr 19 2023

country: USA

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Paired end ATAC Seq of leukemia cell lines of an MLL-AF9 expressing AML treated with Menin inhibtor for 16 hours.


title: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. [scRNA-Seq]

type: Expression profiling by high throughput sequencing

overall_design: Single cell RNA Seq of an MLL-AF9 expressing AML treated with Menin inhibtor for 16 hours.


title: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1.

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

overall_design: Refer to individual Series


title: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. [bulk-RNA-Seq]

overall_design: Paired end RNA Seq of Leukemia cell lines of an MLL-AF9 expressing AML treated with Menin inhibtor for 16 hours.


title: Targeting of epigenetic co-dependencies enhances anti-AML efficacy of Menin inhibitor in AML with MLL1-r or mutant NPM1. [ChIP-Seq]

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for the histone modification H3K27Ac in MOLM13 cells.


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [11B_190325]

status: Public on Apr 20 2023

city: La Jolla

first: Joseph

middle: R

last: Ecker

state: CA

address: 10010 North Torrey Pines Road

department: Genomic Analysis Laboratory

institute: HHMI-Salk-Institute

type: Methylation profiling by high throughput sequencing

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

overall_design: Apply snmC-seq2 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (11B).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

middle: K

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

middle: G

last: Castanon

last: Nery

first: Peter

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: Jesse

last: Dixon

first: M

middle: M

last: Behrens


title: Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation [EPS_CL]

city: Blommenholm

first: Kari Bente

middle: Foss

last: Haug

address: Skogstien 28

department: Medical Biochemistry

country: Norway

institute: Oslo University Hospital

summary:
We have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of extracellular vesicles derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.
During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from 6 morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter.Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix microarray GeneChip TM Multispecies miRNA 4.0 and Flash Tag TM Biotin RNA labelling, Thermo Fisher), and selected microRNAs (miRs) validated by real time RT-qPCR. We found that human myotubes secrete both exosomes and MV. EPS treatment of the myotubes, clearly changed the protein content of both exosomes and MV, whereas the miR content was changed only in exosomes. We suggest that skeletal muscle derived EVs can contribute to circulatory EVs and mediate beneficial effects of exercise in metabolically active organs.

overall_design: Number of patients: 4. Each patient was their own control by comparing the RNA and protein-cargo before and after EPS. Cellular activation by EPS was detected by IL-6 analysis. Non template controls and spike ins control probe sets were included in the microarray analysis. The Affymetrix GeneChip Command Console sodtware was used for normalization, the Robust Multichip Analysis (RMA) alogoritm was applied for signal generation, and Partek R Genomics SuiteTM software for statistical analyis. Validation of microarray results was carried out by RT-qPCR of selected miRNAs.

first: Vigdis

last: Aas

first: Reidun

last: Øvstebø

first: Berit

middle: S

last: Brusletto

first: Trude

last: Aspelin

first: Anne-Marie

last: Trøseid

first: Saba

last: Qureshi

first: Desima

last: Eid

first: Ole

last: Olstad

first: Tuula

last: Nyman

first: Kari

middle: F


title: Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation [EPS_EXO]

summary:
We have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of extracellular vesicles derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.
During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from 6 morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter.Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix GeneChip Multispecies miRNA-4_0 Array microarray and Flash Tag TM Biotin RNA labelling, Thermo Fisher), and selected microRNAs (miRs) validated by real time RT-qPCR. We found that human myotubes secrete both exosomes and MV. EPS treatment of the myotubes, clearly changed the protein content of both exosomes and MV, whereas the miR content was changed only in exosomes. We suggest that skeletal muscle derived EVs can contribute to circulatory EVs and mediate beneficial effects of exercise in metabolically active organs.

overall_design: Number of patients: 3. Each patient was their own control by comparing the RNA and protein-cargo before and after EPS. Cellular activation by EPS was detected by IL-6 analysis. Non template controls and spike ins control probe sets were included in the microarray analysis. The Affymetrix GeneChip Command Console sodtware was used for normalization, the Robust Multichip Analysis (RMA) alogoritm was applied for signal generation, and Partek R Genomics SuiteTM software for statistical analyis. Validation of microarray results was carried out by RT-qPCR of selected miRNAs.

first: Anne


title: Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation [EPS_MV]

summary:
We have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of extracellular vesicles derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.
During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from 6 morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter.Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix GeneChip Multispecies miRNA-4_0 Array and Flash Tag TM Biotin RNA labelling, Thermo Fisher), and selected microRNAs (miRs) validated by real time RT-qPCR. We found that human myotubes secrete both exosomes and MV. EPS treatment of the myotubes, clearly changed the protein content of both exosomes and MV, whereas the miR content was changed only in exosomes. We suggest that skeletal muscle derived EVs can contribute to circulatory EVs and mediate beneficial effects of exercise in metabolically active organs.


title: Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation


title: STING-dependent interferon signatures restrict osteoclast differentiation and bone loss in mice

city: Boston

first: Shruti

last: Sharma

state: MA

address: 156 Harrison Ave

department: Immunology

institute: Tufts University

summary: Stimulator of Interferon Genes (STING) is a key mediator of type-I interferon (IFN-I) signaling in response to a variety of stimuli, but the contribution of STING to homeostatic processes is not fully characterized. Previous studies showed ligand activation of STING limits osteoclast differentiation in vitro through the induction of IFN and IFN-I Interferon Stimulated Genes (ISGs).  In a disease model (SAVI) driven by the V154M gain-of-function mutation in STING, fewer osteoclasts form from SAVI precursors in response to RANKL in an IFN-I-dependent manner. Due to the described role of STING-mediated regulation of osteoclastogenesis in activation settings, we sought to determine whether basal STING signaling contributes to bone homeostasis, an unexplored area. Using whole-body and myeloid-specific deficiency, we show that STING signaling prevents trabecular bone loss in mice over time and that myeloid-restricted STING activity is sufficient for this effect. STING-deficient osteoclast precursors differentiate with greater efficiency than wildtypes. RNA sequencing of wildtype and STING-deficient osteoclast precursor cells and differentiating osteoclasts reveals novel clusters of ISGs including a previously undescribed ISG set expressed in RANKL naïve precursors (tonic expression) and downregulated during differentiation. We identify a 50 gene tonic ISG signature that is STING-dependent and shapes osteoclast differentiation. From this list, we identify Interferon Stimulated Gene 15 (ISG15) as a tonic STING-regulated ISG that limits osteoclast formation.  Thus, STING is an important upstream regulator of tonic IFN-I signatures shaping the commitment to osteoclast fates, providing evidence for a nuanced and novel role for this pathway in bone homeostasis.

overall_design: Bulk RNA sequencing of murine bone marrow derived osteoclast precursors at baseline (d0) and following RANKL stimulation for 2, 3 and 4 days differentiated in vitro.  Samples are from either WT or STING-deficient bone marrow.  Samples were isolated from three mice per genotype (triplicates).

first: Albert

last: Tai

first: Susan

last: MacLauchlan


title: OBSCN restoration via OBSCN-AS1 long-noncoding RNA CRISPR-targeting suppresses metastasis in triple-negative breast cancer

city: Baltimore

first: Aikaterini

last: Kontrogianni-Konstantopoulos

state: MD

address: 108 N. Greene Street

institute: University of Maryland School of Medicine

summary:
While advances have been made in the detection and treatment of primary breast tumors, metastasis and recurrence have remained remain major challenges. Mounting evidence implicates OBSCN in breast tumorigenesis. Accordingly, low(er) OBSCN levels correlate with significantly reduced overall and relapse-free survival in breast cancer patients, while high(er) OBSCN levels correlate with increased patient responsiveness to anthracycline-chemotherapy. Restoration of OBSCN expression could therefore be of high pathophysiological relevance. Herein, we unravel mechanistic information involving the direct regulation of OBSCN via OBSCN-Antisense RNA 1 (OBSCN-AS1), a nuclear long-noncoding RNA gene. Remarkably, OBSCN restoration via OBSCN-AS1 targeting drastically suppresses cell migration and metastasis. Collectively, our study pinpoints the metastasis suppressor function of the OBSCN-AS1/OBSCN pair that may serve as prognostic biomarker and/or therapeutic target for metastatic breast cancer.
We then performed gene expression profiling analysis using RNA-seq data obtained from MDA-MB-231 EV vs sgAS2 and sgAS3 cells

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MDA-MB-231 empty-vector (EV) cells compared to OBSCN/OBSCN-AS1 overexpressing (sgAS2 and sgAS3) cells


title: A tumor microenvironment-driven network regulated by STAT3 and p65 controls the enrichment of cancer stem cells in human HR+/HER2- breast cancer cells

city: Tel Aviv

first: Metsada

last: Pasmanik-Chor

address: Ramat Aviv

department: Biology

country: Israel

institute: Tel Aviv University

summary: The high incidence of the HR+/HER2- breast cancer subtype is a major public health concern, leading us to explore the way three arms of the tumor microenvironment (TME) – hormonal, inflammatory and growth-stimulating – affect tumor progression in this disease. Our past findings indicate that such a joint “TME Stimulation” induces pro-metastatic traits in HR+/HER2- cells, primarily enrichment of cancer stem cells (CSCs), playing key roles in metastasis in vivo. Here, we reveal unexpected roles for STAT3 in this setting, serving as negative regulator that limits CSC enrichment while promoting cancer cell abilities to exploit the immune/inflammatory system in their favor. Moreover, our data provide evidence to novel roles for the strong pro-inflammatory transcription factor p65, whose activities could compensate for complete loss of STAT3 and recapitulate its ability to limit CSC enrichment. These findings call for in depth studies on STAT3 and p65 roles in regulating TME activities in malignant diseases.

overall_design: following RNAseq analyses of TME-stimulated CSCs and Non-CSCs, we found that TME Stimulation has given rise to increased activation of S727-STAT3, Y705-STAT3, STAT1 and p65. Experiments with the STAT3 inhibitor stattic indicated that Y705-STAT3 activation served as negative regulator of CSC enrichment and epithelial-to-mesenchymal transition (EMT), while inducing CXCL8 and PD-L1 expression. In contrast, complete knock-out of STAT3 by siSTAT3 had no effect on any of these cancer cell functions.

first: Hagar

last: Ben-Yaakov

first: Tsipi

last: Meshel

last: Pasmanik Chor

first: Cindy

last: Körner

first: Adit

last: Ben-Baruch


title: Maternal patterns of inheritance alter transcript expression in eggs

city: Raleigh

first: Nathan

last: Harry

state: North Carolina

address: 112 Derieux Place

institute: North Carolina State University

summary: Background: Modifications to early development can lead to evolutionary diversification. The early stages of development are under maternal control, as mothers produce eggs loaded with nutrients, proteins and mRNAs that direct early embryogenesis. Maternally provided mRNAs are the only expressed genes in initial stages of development and are tightly regulated. Differences in maternal mRNA provisioning could lead to phenotypic changes in embryogenesis and ultimately evolutionary changes in development. However, the extent that maternal mRNA expression in eggs can vary is unknown for most developmental models. Here, we use a species with dimorphic development— where females make eggs and larvae of different sizes and life-history modes—to investigate the extent of variation in maternal mRNA provisioning to the egg.  Results: We find that there is significant variation in gene expression across eggs of different development modes, and that there are both qualitative and quantitative differences in mRNA expression. We separate parental effects from allelic effects, and find that both mechanisms contribute to mRNA expression differences. We also find that offspring of intraspecific crosses differentially provision their eggs based on the parental cross direction (a parental effect), which has not been previously demonstrated in reproductive traits like oogenesis.   Conclusion: We find that maternally controlled initiation of development is functionally distinct between eggs of different sizes and maternal genotypes. Both allele-specific effects and parent-of-origin effects contribute to gene expression differences in eggs. The latter indicates an intergenerational effect where a parent’s genotype can affect gene expression in an egg made by the next generation.

overall_design: RNAseq of mature oocytes from females of the developmentally dimorphic species Streblospio benedicti. Oocytes were excised by razor and washed extensively to ensure single tissue samples. Seven replicate libraries of each morphotypes oocytes are included. Five replicate libraries for both reciprocal cross directions between morphotypes are included.

first: Christina

last: Zakas


title: INTAC endonuclease and phosphatase modules have distinct roles in transcription (TT-Seq)

city: Shanghai

first: Linna

last: Peng

address: Dong'an Road

country: China

institute: Fudan University

summary:
Gene expression in metazoans is controlled by promoter-proximal pausing of RNA polymerase II, which can undergo productive elongation or early termination. Integrator-PP2A (INTAC) plays a crucial role in determining the fate of paused polymerases, but the underlying mechanisms remain unclear. Here we establish a rapid degradation system to dissect the direct functions of INTAC RNA endonuclease and phosphatase modules. We find that both catalytic modules function at most if not all active promoters and enhancers, yet differentially affect polymerase fate. The endonuclease module induces early termination, with its disruption leading to accumulation of non-competent polymerases and downregulation of highly expressed genes, while competent polymerases accumulate at lowly expressed genes and non- coding elements, leading to their upregulation. The phosphatase module primarily prevents the release of paused polymerases and limits transcriptional activation, especially for highly paused genes. Thus both INTAC’s catalytic modules have unexpectedly general yet distinct roles in dynamic transcriptional control.
We performed PRO-seq, ChIP-seq, or TT-seq to investigate the role of INTAC in regulating transcription.

overall_design: In this study, samples for each condition were collected in biological duplicates. Cells were treated with dTAG13 for 0, 1, or 3 hours, the corresponding control cells were treated for the same duration with vehicle only (DMSO) at the same vol/vol dilution.

first: Shibin

last: Hu

first: Aixia

last: Song

first: Fei

middle: X

last: Chen


title: INTAC endonuclease and phosphatase modules have distinct roles in transcription (PRO-Seq)


title: Li-Fraumeni Syndrome-associated dimer-forming mutant p53 promotes transactivation-independent mitochondrial cell death

city: New York

first: Joshua

last: Choe

state: NY

address: 816 Fairchild Center, MC 2422

department: Department of Biological Sciences

institute: Columbia University


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [11C_190530]

first: Joseph

last: Ecker

overall_design: Apply snmC-seq2 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (11C).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

last: Castanon

last: Nery

first: Peter

last: Berube

first: Huaming

first: Michael

last: Nunn

first: Jesse

last: Dixon

first: M

last: Behrens


title: Arabidopsis HOT3/eIF5B1 constrains rRNA RNAi by facilitating 18S rRNA maturation during translation initiation (miRNA-Seq)

first: Chenjiang

last: You

state: Shanghai

address: 2005 Songhu Rd

type: Non-coding RNA profiling by high throughput sequencing

summary: Ribosome biogenesis is essential for protein synthesis in gene expression. Yeast eIF5B has been shown biochemically to facilitate 18S rRNA 3’ end maturation during late-40S ribosomal subunit assembly and gate the transition from translation initiation to elongation. But the effects of eIF5B have not been studied at the genome-wide level in any organism, and 18S rRNA 3’ end maturation is poorly understood in plants. Arabidopsis HOT3/eIF5B1 was found to promote development and heat-stress acclimation by translational regulation, but its molecular function remained unknown. Here, we show that HOT3 is a late-stage ribosome biogenesis factor that facilitates 18S rRNA 3’ end processing and is a translation initiation factor that globally impacts the transition from initiation to elongation. By developing and implementing 18S-ENDseq, we revealed previously unknown events in 18S rRNA 3’ end maturation or metabolism. We quantitatively defined new processing hotspots and identified adenylation as the prevalent non-templated RNA modification at the 3’ ends of pre-18S rRNAs. Aberrant 18S rRNA maturation in hot3 further activated RNAi to generate RDR1- and DCL2/4-dependent risiRNAs mainly from a 3’ portion of 18S rRNA. We further showed that risiRNAs in hot3 were predominantly localized in ribosome-free fractions not responsible for the 18S rRNA maturation or translation initiation defects in hot3. Our study uncovered the molecular function of HOT3/eIF5B1 in 18S rRNA maturation at the late-40S assembly stage and revealed the regulatory crosstalk among ribosome biogenesis, mRNA translation initiation, and siRNA biogenesis in plants.

overall_design: Comparative sRNA expression profiling analysis of small RNA-seq data for 18-day-old seedlings of WT, hot3-2, hot3-3 and HOT-EYFP/hot3-2

first: Runlai

last: Hang

first: Xuemei


title: Arabidopsis HOT3/eIF5B1 constrains rRNA RNAi by facilitating 18S rRNA maturation during translation initiation (RNA-Seq)

overall_design: Comparative gene expression profiling analysis of RNA-seq data for 18-day-old seedlings of WT, hot3-2, and hot3-3

last: Chen


title: INTAC endonuclease and phosphatase modules have distinct roles in transcription (ChP-Seq)

first: Linna

last: Peng

overall_design: In this study, samples for each condition were collected in biological duplicates. Cells were treated with dTAG13 for 3 hours, the corresponding control cells were treated for the same duration with vehicle only (DMSO) at the same vol/vol dilution.

first: Shibin

last: Hu

first: Aixia

last: Song

first: Fei


title: Arabidopsis HOT3/eIF5B1 constrains rRNA RNAi by facilitating 18S rRNA maturation during translation initiation


title: Arabidopsis HOT3/eIF5B1 constrains rRNA RNAi by facilitating 18S rRNA maturation during translation initiation (Ribo-Seq)

overall_design: Comparative translation profiling analysis of Ribo-seq data for inflorescence  of WT, hot3-2, hot3-3 and HOT-EYFP/hot3-2


title: Cellular Senescence and Disrupted Proteostasis induced by Myotube Atrophy are Prevented with Low Dose Metformin and Leucine Cocktail

city: Salt Lake City

first: Micah

middle: J

last: Drummond

state: Utah

address: 520 Wakara Way

department: Physical Therapy and Athletic Training

institute: The University of Utah

summary: Skeletal muscle atrophy is dictated by the balance between protein synthesis and protein breakdown, known as proteostasis. With advanced age, muscle atrophy contributes to development of co-morbidities, loss of strength and independence, and all-cause mortality. Aging also coincides with the accumulation of senescent cells within skeletal muscle that produce inflammatory products, known as the senescence associated secretory phenotype. Previously, we found that a metformin + leucine (MET+LEU) combination treatment had synergistic effects in aged mice to improve skeletal muscle structure and function during disuse atrophy. Therefore, the objective of this study was to determine the mechanisms by which MET+LEU exhibits muscle atrophy protection in vitro and if this occurs through cellular senescence. C2C12 myoblasts differentiated into myotubes were used to determine MET+LEU mechanisms during serum-deprivation (SD) atrophy. Single myofibers were isolated from aged (22-23 mo) C57Bl6/J mice, and human primary myoblasts were extracted from a healthy older adult donor. 25 + 125 µM MET+LEU treatment increased differentiation of myotubes and prevented SD induced atrophy. Low concentration (0.1 + 0.5 µM) MET+LEU had unique effects to prevent myotube atrophy and cause transcriptional reprogramming compared to individual therapies. SD increased inflammatory and cellular senescence pathways that was reversed with MET+LEU treatment. SD resulted in dysregulated proteostasis that was rescued with MET+LEU, and proteasome inhibition with MG-132 also rescued myotube atrophy. Cellular senescence transcriptional pathways and markers increased by SD were reversed with MET+LEU treatment, and dasatinib + quercetin (D+Q) senolytic treatment prevented myotube atrophy similar to MET+LEU. In aged myofibers, MET+LEU prevented SD atrophy, and in human primary myotubes MET+LEU prevented reductions in myonuclei fusion. These data provide evidence that MET+LEU has muscle cell intrinsic properties to prevent atrophy by reversing senescence and improving proteostasis

overall_design: Comparative gene expression profiling analysis of RNA-seq data for mature C2C12 skeletal muscle cells (myotubes) with 6 replicates per group

first: Jonathan

last: Petrocelli

first: Chris

last: Stubben


title: Arabidopsis HOT3/eIF5B1 constrains rRNA RNAi by facilitating 18S rRNA maturation during translation initiation (18S END-Seq)

overall_design: Qualification and quantitation analysis of 18S rRNA 3' end for 18-day-old seedlings of WT, hot3-2, hot3-2 dcl2-1 dcl4-2, and dcl2-1 dcl4-2


title: Expression data from Botryococcus terribilis ethanol extract (BTEE)-treated RAW264 cells

city: Tsukuba

first: Farhana

last: Ferdousi

state: Ibaraki

address: Tennodai 1-1-1

country: Japan

institute: University of Tsukuba

summary:
Gene expression profiling reveals anti-inflammatory effects of BTEE on lipopolysaccharide (LPS)-induced murine RAW264 cells
We evaluated the pretreatment effect of BTEE on LPS-induced inflammation in RAW264 cells. Pretreatment with BTEE could significantly attenuate nitric oxide (NO) production and LPS-induced release of inflammatory mediators in RAW264 cells.

overall_design: RNA was extracted using Isogen (Nippon Gene Co. Ltd., Toyama, Japan). The integrity of RNA was quantified using NanoDrop 2000 spectrophotometer (Thermo Scientific, Wilmington, DE, USA). Clariom S assay system (Thermo Fisher, Japan) was used on duplicate RNA samples of each group. In accordance with the user manual, complementary DNA (cDNA) for microarray was generated using the GeneChip WT Plus Reagent kit (Thermo Fisher Science, Japan). Samples were hybridized using Clariom S GeneChip microarray kit (Thermo Fisher Science, Japan). After washing and staining, images were captured, and then CEL data were generated using the GeneChip Scanner 3000 (Thermo Fisher Science, Japan). The raw CEL data were normalized using the transcriptome analysis console (TAC) software ver.4.0.1 following the SST-robust multichip average (SST-RMA) algorithm (Thermo Fisher Scientific, Japan).

first: Seri

last: Yamamoto


title: Transcriptomes of UFMylation gene knockdown in human breast cancer cell

city: Dongguan

first: Zhou

last: Junzhi

state: Guangdong

address: Xincheng Road 1#, Songshan Lake

institute: Guangdong Medicine University

summary: To investagate the gene expression profiling of dysUFMylation in breast cancer, we constructed UFL1 and UFM1 konckouted-MDA-MB-231 using CRISPR-Cas9 and couducted RNA-seq. mRNAs were isolated and purified using RNeasy Plus Mini Kit (Qiagen). Samples were prepared from three biological replicates.

overall_design: Total RNA transcriptomes of UFL1 or UFM1 KO MDA-MB-231 cells  were profiled by RNA-seq.

first: JUNZHI

last: ZHOU

first: YONGKANG

last: ZOU


title: Functional and morphological renal changes in a Göttingen Minipig model of obesity-related and diabetic nephropathy

city: Frederiksberg C

first: Lisbeth Høier

last: Olsen

address: Ridebanevej 9

department: Veterinary and Animal Sciences

country: Denmark

institute: University of Copenhagen

summary:
Male Göttingen Minipigs were divided into 4 groups: SD (standard diet, n=8), FFC (FFC diet, n=16), FFC-DIA (FFC diet + diabetes, n=14), FFC-DIA+S (FFC diet with extra salt + diabetes, n=14). Blood and urine biomarkers, glomerular filtration rate (GFR), blood pressure and resistive index (RI) were evaluated after 6-7 months (T1) and 12-13 months (T2). Histology, electron microscopy and gene expression (excluding FFC-DIA+S) were evaluated at T2.
Göttingen Minipigs fed FFC diet displayed some of the characteristic features of human ORG. Presence of diabetes on top of FFC diet, lead to changes resembling the early phases of human DN.

overall_design: qPCR gene expression profiling. Kidney tissue from 28 Göttingen Minipig.

first: Camilla

middle: A

last: Kristensen

first: Susanna

last: Cirera

first: Berit

last: Christoffersen

first: Lisbeth

middle: H

first: Rikke

last: Lindgaard

last: Kirk

first: Birgitte

last: Viuff

first: Peter

last: Kvist

first: Henrik

middle: D

last: Pedersen

first: Trine

middle: P

last: Ludvigsen

first: Tine

last: Skovgaard

first: Johannes

last: Fels

first: Liselotte

middle: B

last: Christiansen

first: Torben

last: Martinussen


title: The effect of accumulation of a Cit1 mutant that lacks presequence in Saccharomyces cerevisiae

city: Nagoya

first: Kunio

last: Nakatsukasa

state: Aichi

address: Yamanohata 1, Mizuho-cho, Mizuho-ku

institute: Nagoya City University

summary: Deficiencies in mitochondrial protein import are associated with a number of diseases. However, although non-imported mitochondrial proteins are at great risk of aggregation, it remains largely unclear how their accumulation causes cell dysfunction. In this study, we found that citrate synthase (Cit1) mutant that lacks the N-terminal mitochondrial targeting sequence, which we call here NdeltaCit1, is localized in the cytosol and is targeted for proteasomal degradation by the ubiquitin ligase SCFUcc1. Intriguingly, NdeltaCit1 is soluble in the cytosol and exhibits enzymatic activity. To analyze the cellular consequence of the accumulation of NdeltaCit1, we created a NdeltaCit1 mutant that escapes SCFUcc1-mediated degradation (NdeltaCit1-DS/AA). We also created a mutant that lacks the catalytic activity (NdeltaCit1-DS/AA-H/G). We performed an RNA sequence analysis and compared the gene expression profile of wild-type cells expressing NdeltaCit1-DS/AA or NdeltaCit1-DS/AA-H/G under the control of the GAL1 promoter.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for cells expressing NdeltaCit1-DS/AA or NdeltaCit1-DS/AA-H/G.


title: Transcriptomic Profiling of Extracellular Vesicles Secreted by Fetal Neural Stem Cells Following Chronic Alcohol Exposure

city: Bryan

first: Rajesh

last: Miranda

address: 8447 Riverside Parkway

institute: Texas A&M University

summary:
To profile the transcriptome of samples by “sample type (EV vs. Cell)”, “sex (Female vs. Male)”, and “treatment (0 vs. 120 vs 320 mg / dL)”.
We performed gene expression profiling analysis using data obtained from RNA-seq of 18 EV samples and 18 cell samples in different treatment groups and sex.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for C57BL/6J murine fetal neural stem cells and their extracellular vesicles.

first: D

last: Chung

first: M

last: Pinson

first: A

last: Mahnke

first: N

last: Salem

last: Lai

last: Collins

middle: E

last: Hillhouse

first: R

middle: C


title: MORF2 is a key effector of plastidial retrograde signaling for stress response and plant morphogenesis beyond RNA editing

city: Athens

first: Zhihua

last: Hua

state: Ohio

address: 22 Richland Ave

department: Department of Environmental and Plant Biology

institute: Ohio University

summary: Multiple Organellar RNA Editing Factor 2 (MORF2) was previously discovered to be involved in chloroplast RNA editing.  However, the albino and unviable phenotype of the T-DNA insertion mutants, morf2-1 and morf2-2, seems to be inconsistent with many other viable chloroplast RNA editing mutants, suggesting that MORF2 has other biological functions beyond RNA editing.

overall_design:
To discover new biological functions of MORF2, we applied a novel inducible Clustered Regularly Interspaced Short Palindromic Repeat interference (iCRISPRi) approach to quantitatively monitor early transcriptome changes upon the gradient reduction of MORF2 by RNA-Seq analysis.
P1-12 is an Arabidopsis transgenic line in a Col-0 background transformed with a dCas9-KRAB transcription repressor driven by a Dexamethasone (Dex)-inducible promoter and a sgRNA gene containing a protospacer specific to -2 to +18 nt of the transcription start site of MORF2.  Upon 0.025 microM and 0.25 microM Dex treatment, dCas9-KRAB expression is induced at different levels resulting in a gradient suppression of MORF2 in P1-12.
KRAB indicates the Arabidopsis transgenic line in a Col-0 background only transformed with a dCas9-KRAB transcription repressor driven by a Dex-inducible promoter.


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [11B_190314]

first: Joseph

last: Ecker

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

overall_design: Apply snmC-seq2 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (11B).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

last: Castanon

last: Nery

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: Jesse

last: Dixon

last: Behrens


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [11A_191114]

overall_design: Apply snmC-seq2 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (11A).

first: Peter


title: Gene expression profile of FFPE samples collected with translational purposes from the MITO16/MaNGO-OV2 clinical trial

city: Milan

first: Loris

last: De Cecco

address: via Venezian 1

country: Italy

institute: IRCSS Istituto Nazionale Tumori

summary: MITO16/MaNGO-OV2 (NCT01706120) is a multicenter, phase IV, single arm trial for advanced stage IIIB-IV or recurrent, previously untreated, ovarian cancer patients receiving carboplatin, paclitaxel plus bevacizumab for six 3-weekly cycles followed by bevacizumab single agent until progression or unacceptable toxicity up to a maximum of 22 total cycles. The trial that was specifically designed with a translational primary endpoint to explore if selected clinical and biological factors could identify ovarian cancer patients with better prognosis in terms of progression free survival and overall survival after combined first-line treatment with chemotherapy plus Bevacizumab. The translational study, designed together with the clinical trial, the translational study implicated the collection of patients’ tissue (formalin-fixed paraffin-embedded – FFPE) and blood samples. Gene expression profile was among the molecular analyses proposed on FFPE samples.

overall_design: After pathological revision, two 1 mm-cores of FFPE tissues cores were selected to represent at least a percentage >70% of tumor cells, no significant signs of necrosis and to avoid excessive presence of stromal tissue for RNA extraction. RNA from 195 patients of MITO16/MaNGO-OV2 trial was isolated using Qiagen RNeasy FFPE kit (Qiagen, Hilden, Germany) and quality checked. RNA concentration was assessed by the Nanodrop 2000 UV-Vis Spectrophotometer. Sample purity was assessed by 260/280 and 260/230 ratios and the recorded values ranged from 1.9-2.2. Gene expression profiling was performed using the GeneChip WT Pico kit (Affymetrix, Thermo Fisher Scientific) following the guidelines for FFPE material. EGFR status: M0,negative; MM,100%membrane expression; M,≤ 30%.


title: EMD37 triggers endoplasmic reticulum stress in cancer cells

city: Cairo

first: Amal Kamal

last: Abdel-Aziz

address: African Union Organization St. Abbassia,

department: Pharmacology and Toxicology

country: Egypt

institute: Ain Shams University

summary: Targeting endoplasmic reticulum (ER) stress presents a promising strategy in cancer therapy. We have previously reported that a series of 1,2,4-oxadiazole derivatives induces the degradation of epidermal growth factor receptor and c-Met which are implicated in tumorigenesis. Based on our previous SAR studies, herein, we synthesized EMD37, a novel 1,2,4-oxadiazole derivative, and systematically investigated its anticancer activity.

overall_design: Genome-wide transcriptome profiling of cancer cells treated with EMD37

first: Amal

first: Saverio

last: Minucci


title: Gene expression alteration in rat primary TNF-α-induced chondrocytes and the treatment of Nanofat lysate

city: Hangzhou

first: Yanzhi

last: Ge

address: 548 Binwen Road, Binjiang District

institute: Zhejiang Chinese Medical University

summary:
In order to overcome the defect of Nanofat, we developed Nanofat lysate (NFL) by repeated freeze-thawing lysis preparation on Nanofat. During the preparation, cell membranes of Nanofat cells were ruptured and the cellular contents were released. Thus, NFL may have storage stability in low temperature.
Therefore, to investigate the effects of the stimulation of TNF-α on primary chondrocytes and the effect of NFL, we can speculate that unique genetic profiles in vitro might exist with different interventions.

overall_design: Primary chondrocytes were isolated from 180-220g male Sprague-Dawley rats, and were subject to 10 ng/ml TNF-α for 6h (TNF-α group) and 10ng/ml TNF-α for 6h followed by NFL for another 24h (TNF-α+NFL group). RNA was extracted directly from the intervened chondrocytes.


title: Claudin-4–adhesion signaling drives breast cancer metabolism and progression via liver X receptor β

city: Fukushima

first: Hideki

last: Chiba

address: 1 Hikarigaoka

institute: Fukushima Medical University

summary: Cell adhesion molecules exhibit the signaling abilities to control a variety of physiological and pathological processes; however, the underlying molecular basis remains poorly defined. Here, we demonstrate that the claudin-4 (CLDN4)-adhesion signaling accelerates breast cancer metabolism and progression via the nuclear receptor LXRb (liver X receptor b). Knockout and rescue experiments revealed that the CLDN4 signaling targets S432 in LXRb, leading to enhanced cell proliferation and tumor growth in breast cancer cells. In addition, RT-qPCR analysis showed the CLDN4-regulated genes are classified into at least six groups by distinct LXRb- and LXRbS432-dependence. Collectively, our results provide a link between cell adhesion and nuclear receptor signalings to coordinate cancer metabolism and advancement.

overall_design: RNA-seq analysis was performed using wild-type and CLDN4-knockout breast cancer cell lines (T47D and MCF7).

first: Yuko

last: Murakami

first: Kotaro

last: Sugimoto

first: Makoto

last: Kobayashi

first: Kazunoshin

last: Tachibana

first: Manabu

last: Kojima

first: Tadashi

last: Nomizu

last: Hashimoto

first: Shigehira

last: Saji

first: Toru

last: Ohtake


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [11A_191107]

city: La Jolla

first: Joseph

last: Ecker

address: 10010 North Torrey Pines Road

institute: HHMI-Salk-Institute

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

last: Castanon

last: Nery

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: M


title: An essential role for the Ino80 chromatin remodeling complex in regulation of gene expression during cellular quiescence

city: Stockholm

first: Anastasios

middle: Erik

last: Damdimopoulos

state: Huddinge

address: Hälsovägen 7c

department: Department of Biosciences and Nutrition

country: Sweden

institute: Karolinska Institute

summary: Cellular quiescence is an important physiological state both in unicellular and multicellular eukaryotes. Quiescent cells are halted for proliferation and stop the cell cycle at the G0 stage. Using fission yeast as a model organism, we have previously found that several subunits of a conserved chromatin remodeling complex, Ino80C (INOsitol requiring nucleosome remodeling factor), are required for survival in quiescence. Here, we demonstrate that Ino80C has a key function in regulation of gene expression in G0 cells. We show that null mutants for two Ino80C subunits Arp42 and Iec1, a null mutant for histone variant H2A.Z, and a null mutant for the Inositol kinase Asp1 have very similar phenotypes in quiescence. These mutants show reduced transcription genome-wide, and specifically fail to activate 149 quiescence genes, of which many are localized to the subtelomeric regions. Based on these observations and previous findings, we propose a model in which Ino80C, modulated by Inositol kinase activity, is required to remove H2A.Z, especially in subtelomeric regions in order to reorganize the chromosome structure and activate genes required to survive in quiescence.

overall_design: There are in total 72 samples. There are wild type (smt0) and five different mutant (hht2, pht1, iec1, asp1, arp42) samples in triplicate at four time points (T0, T1D, T1W, T2W) of nitrogen starvation.

first: Yasaman

last: Zahedi

first: Karl

last: Ekwall


title: Effects of Assisted Reproductive Technology on Gene Expression in Heart and Spleen tissues of Adult Offspring

city: Zhengzhou

first: Lei

last: Zhang

state: Henan

address: No. 7, Weiwu Road

department: Reproductive Medicine Center

institute: Henan Provincial People’s Hospital

summary: Assisted reproductive technology (ART) is an important part of reproductive medicine that comprises superovulation, in vitro fertilization (IVF), in vitro culture of embryos, cryopreservation and embryo transfer. Because it occurs in the sensitive period of gametogenesis and early embryonic development, its possible health effects on the offspring have received widespread attention in recent years. Relevant studies, though, are limited to postnatal follow-up and blood sample analysis. In this study, a mouse model was used to explore the effect of ART on gene expression in the organs of the off-spring using next-generation sequencing. The results showed that it caused abnormal expression in 1060 and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and cardiovascular system development is also enriched. STRING analysis identified Ccl2, Ptgs2, Rock1, MAPK14, Agt, Wnt5a as core interaction factors. DEGs in the spleen are significantly enriched in anti-infection and im-mune responses and in the hematopoiesis-related pathway "hematopoietic cell lineage", which includes the core factors Fos, Jun and Il1r2. Then, we explored the effects of ART on epigenetic modifiers and imprinted genes. The results showed that 42 heart genes and 5 spleen genes were abnormally expressed, most of which were related to histone modification and chromatin remodeling. Imprinted genes are very important for normal fetal and individual growth and development. It was found that the expression of imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the heart of ART offspring, and the DNA methylation levels of Igf2 and Mest imprinting control regions (ICRs) increased abnormally. Therefore, we con-cluded that, in the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring, causing potentially adverse effects on organ function. The results of this study can provide a reference for evaluating the safety of human ART and helping improve the clinical system.

overall_design: Comparison of gene expression in offspring organs between control and ART

first: Huanhuan

first: Cuilian

first: Li

last: Meng


title: RNA-seq analysis of TOX2 knockdown in in human natural killer/T Cell Lymphoma NKYS cell line

city: Singapore

first: Tuan Zea

last: Tan

address: 14 Medical Drive, #11-01, Singapore

department: Cancer Science Institute Singapore

country: Singapore

institute: National University of Singapore

summary: RNA-Seq was performed in human natural killer/T Cell Lymphoma cell line NKYS ells treated with TOX2-shRNA1, -shRNA2 or with scrambel shRNA. Total RNA was extracted using RNeasy mini kit (Qiagen). The decreased TOX2 expression was confirmed by RT-PCR. The RNA library construction and RNA-sequencing services were provided by Novogene Singapore.

overall_design: Total RNA of NKYS sh-Scramble and TOX2 knockdown cells were analyzed.

first: Jianbiao

last: Zhou

first: Sabrina

last: Toh

first: Kalpnaa

last: Balan

first: Tze

first: Jing

last: Lim

first: Sinan

last: Xiong

first: Yunlu

last: Jia

first: Siok-Bian

last: Ng

first: Takaomi

last: Sanda

first: Wee-Joo

last: Chng


title: Loss of Ezh2 function reshapes DNA replication initiation landscape

city: birmingham

first: ildem

last: akerman

address: BR Tower, 3rd Floor, Room 333, Edgbaston,

department: IMSR

country: United Kingdom

institute: University of Birmingham

summary: DNA replication initiation is made possible by the assembly of pre- replication complexes (Pre-RCs) at genomic locations called DNA replication initiation sites (origins) during G1-phase.  Although there are no conserved characteristics of metazoan origins on which Pre-RCs form, previous findings suggest that origins are strongly associated with open, active chromatin regions of the genome such as promoters, enhancers, and active histone marks. However, over a third of transcriptionally silent genes associate with DNA replication initiation activity in mESC cells, and most of these genes are bound and repressed by the Polycomb repressive complex 2 (PRC2) through the repressive H3K27me3 mark. This is the strongest observed association of an epigenetic regulator element with replication origin activity. Thus, I wished to ask whether Polycomb-mediated gene repression plays a direct role in the recruitment of DNA replication origins activity to silent genes. I comprehensively characterized the consequences of PRC2 catalytic activity (EZH2 subunit) depletion on the activity of DNA replication origins in mESC through a genome-wide evaluation. My findings suggest that absence of EZH2 results in increased DNA replication initiation activity at EZH2-bound sites. Interestingly, the increase in DNA replication initiation activity does not correlate with transcriptional de-repression or acquisition of the activating marks H3K4me3 and H3K27ac but loss of the repressive H3K27me3 mark leading to increased accessibility of chromatin.

overall_design: Chip-seq, SNSseq and RNA-seq analysis from WT or EZH2 knockout mouse embryonic stem cells

first: Nerea

last: Murrugarren Garrido

first: Paulina

last: Prorok

first: Marcelo

last: Mechali

first: Ildem

last: Akerman


title: HPV integration generates cellular super enhancer and functions as ecDNA to regulate genome-wide transcription

city: Guangzhou

first: yuyan

last: wang

address: Zhongshan 2nd Road, Yuexiu

institute: The First Affiliated Hospital, Sun Yat-sen University

summary: Human papillomavirus (HPV) integration is a critical step in cervical cancer development, while the oncogenic mechanism in genome-wide transcriptional level is still poorly understood. In this study, we employed integrative analysis on multi-omics data of cervical cancer cell lines. Through HPV integration detection, super enhancer (SE) identification, SE-associated gene expression and extrachromosomal DNA (ecDNA) investigation, we aimed to explore the genome-wide transcriptional influence of HPV integration. We identified 5 high-ranking cellular super enhancers generated by HPV integration (the HPV breakpoint induced cellular super enhancers, BP-cSE), leading to intra-chromosomal and inter-chromosomal regulations of chromosomal genes. The pathway analysis showed the dysregulated chromosomal genes were correlated to cervical cancer associated pathways. Importantly, we demonstrated that BP-cSE existed in the HPV-host ecDNA, explaining above transcription alterations. Our results suggest that HPV integration generates cellular super enhancers and functions as ecDNA to regulate unconstraint transcription, expanding the tumorigenic mechanism of HPV integration and providing insights of developing new diagnostic and therapeutic strategies.

overall_design: We employed integrative analysis on multi-omics data of cervical cancer cell lines. We performed WGS, WGBS, HiC, H3K27ac and H3K4me3 ChIP-seq, RNA-seq in 4 HPV-positive cell lines (CaSki, S12, all omics; SiHa, HeLa, except WGS), two EBV-positive cell lines (Raji, except WGBS; C666-1, except WGS and WGBS), and three non-virus cell lines (C33A, all omics; HEK293T, except WGBS and H3K4me3 ChIP-seq; HaCaT, only WGS). In addition, Raji were performed EBV virus capture sequencing and 10 normal cervical tissue from the patients were performed RNA-seq. We employed rolling-circle amplification in HeLa and S12 by long-reads sequencing, corrected by short-reads, to validate the ecDNA.

first: Rui

last: Tian

first: Zheying

last: Huang

first: Lifang

last: Li

first: Jingping

last: Yuan

first: Qinghua

last: Zhang

first: Lirong

first: Bin

last: Lang

first: Yongfeng

last: Hong

first: Chaoyue

last: Zhong

first: Xun

first: Zifeng

last: Cui

first: Zhuang

last: Jin

first: Jiashuo

last: Liu

first: Zhaoyue

first: Yuyan

last: Wang

first: Ye

last: Chen

first: Zheng

last: Hu


title: Function-first proteomic strategies for chemical probe discovery in human cells

city: South San Francisco

first: Simon

last: Hogg

state: California

address: 1000 Gateway Boulevard

department: Oncology Discovery Research

institute: AbbVie

summary: Transcriptional consequences of Pladienolide B, WX-02-23, and WX-02-43 treatment in 22Rv1 cells by RNA-sequencing

overall_design:
Treatment of 22Rv1 cells treated in biological triplicate with Pladienolide B, WX-02-23 (1ÂµM and 5ÂµM, respectively), WX-02-43, or DMSO vehicle control for 8 hours prior to RNA-sequencing.

Treatment of 22Rv1 cells treated in biological triplicate with KB02 or KB05 (200 µM) for 1 hour followed by 2 hour recovery in fresh media prior to gene expression profiling by RNA-sequencing (RNA-seq).

first: Jarrett

middle: R

last: Remsberg

first: Benjamin

last: Cravatt


title: Ten-hour time-restricted eating improves glycaemic control and alters transcriptomic profile in adipose tissue in men at increased risk of type 2 diabetes

city: San Diego

first: April

middle: Elizabeth

last: Williams

address: 10010 N Torrey Pines Rd

department: IGC

institute: Salk Institute for Biological Studies

summary: Time restricted eating  (TRE) is a simple intervention that has beneficial effects on glucose control in individuals with obesity, who are at high risk of metabolic diseases. TRE altered transcriptomic profile of adipose tissue but series sampling studies are need to evaluate the diurnal changes of gene expression.

overall_design: In a single-arm, within-subject trial, 15 men (aged 62.9 ± 4 years, waist circumference 113 ± 4 cm) with no history of diabetes were enrolled and instructed to eat their regular diets within a contiguous 10-hour time frame each day for 8 weeks. The timing of food intake was tracked via a photograph-based application. After 2-weeks of baseline monitoring period and 8-weeks of TRE, participants were provided with a 3-day lead-in diet before they underwent a 35-hour metabolic ward stay, during which all food intake was strictly controlled within 14-hours (pre) or 10-hours (post). Identical standardized meal tolerance tests were performed at breakfast and dinner (52% carbohydrate, 33% fat, 15% protein). Transcriptional profiles in subcutaneous adipose tissue were measured in by RNA-sequencing (n=11).This study was designed to examine the effects of eight weeks of TRE (10-hours per day) on the glucose area under the curve (AUC) and appetite regulation at breakfast and dinner, and gene expression in adipose tissue in men with obesity.

first: John

last: Au

first: Siobhan

last: Banks

first: Leonie

middle: K

last: Heilbronn

first: Amy

middle: T

last: Hutchison

first: Hiep

last: Le

first: Bo

first: Emily

middle: N

last: Manoogian

first: Leanne

last: Nguyen

first: Satchidananda

last: Panda

first: Xiao

last: Teong

first: Campbell

last: Thompson

first: Gary

last: Wittert

first: Crystal

middle: L

last: Yates

first: Lijun

last: Zhao


title: Genome-wide DNA methylation analysis in early-stage colorectal cancer

first: Huichuan

last: Yu

address: 26 Yuancun Erheng Road

institute: Sun Yat-sen University

summary: The current risk stratification system defined by clinicopathological features do not accurately identify the risk of disease recurrence in patients with stage I-II colorectal cancer (CRC). We aimed to investigate whether the CpG sites from newly established genome-wide methylation profiles could serve as biomarkers to improve prognosis prediction.

overall_design: In this retrospective cohort study, we profiled genome-wide DNA methylation using Infinium MethylationEPIC array in tumor and adjacent normal samples from 23 recurrent and 22 recurrence-free CRC patients to identify new candidate methylation markers for disease recurrence risk.

first: Jianping

last: Wang

first: William

middle: M

last: Grady

first: Yanxin

last: Luo


title: In vitro effects of equine autologous conditioned serum and autologous equine serum on inflamed chondrocyte pellets

city: Uppsala

first: Maria

last: Löfgren

department: Department of Biomedical Sciences and Veterinary Public Health

institute: Swedish University of Agricultural Sciences

summary: The aim of the study was to investigate the effects of autologous equine serum (AES) incubated for 24 h  and autologous conditioned serum (ACS) on inflamed equine chondrocyte pellets in vitro.

overall_design: Inflammation was induced in vitro in 3-D pellet cultures of chondrocytes using recombinant equine IL-1β (5ng/ml). The pellet cultures were treated with culture media as unstimulated controls,  IL-1β or IL-1β and one of the following treatments: AES, AES 24h and ACS. Chondrocyte pellets were harvested after 2 and 48 hours and total RNA was isolated. The effects were evaluated using GeneChip® Equine Gene 1.0 ST Array (Affymetrix Inc.).

first: Stina

last: Ekman

first: Josefine

last: Ekholm

first: Mona

last: Engström

first: Cathrine

last: Fjordbakk

first: Emilia

last: Svala

first: Karin

last: Holm Forsström

first: Anders

last: Lindahl

first: Eva

last: Skiöldebrand


title: Adrenal stress response is an essential host response against lethal T cell activation

city: Cincinnati

first: Lei

middle: Frank

last: Huang

address: 2600 Clifton Ave

institute: Uiversity of Cincinnati

summary: Cytokine release syndrome (CRS) is a major cause of death in lethal T cell activation and presents a significant barrier for CAR-T immunotherapy or allogenic hematopoietic cell transplantation. We reported here that adrenal stress response, defined by a 5-10-fold increase in induced glucocorticoid (iGC) production, is an essential host response against lethal T cell activation. We identified scavenger receptor BI (SR-BI), a HDL receptor, as a key regulator for iGC production. Using SR-BI null mice as an adrenal stress response deficiency model, we demonstrated that adrenal stress response protects anti-CD3 induced death through keeping CRS under control and relative adrenal insufficiency (RAI) – lacking adrenal stress response, is a risk factor.

overall_design: To understand how induced glucocorticoid (iGC) regulates CRS in lethal T cell activation, we conducted single cell RNA sequencing analysis of splenocytes from SR-BI+/+ and SR-BI-/- mice at 20h post anti-CD3 challenge.


title: PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [RNA-seq]

status: Public on Apr 18 2023

city: Shanghai

first: Jun

last: Deng

address: No. 25, Lane 2200, Xietu Road, Xuhui District

institute: Renji Hospital, Shanghai Jiao Tong University School of Medicine

summary:
PD-1+CD8+ T cells are exhausted in infection and cancer, their roles in lupus nephritis (LN) are largely unknown.
PD-1+CD8+ and PD-1-CD8+ cells from spleens of NZB/W F1 mice were sorted for RNA-seq.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PD-1+CD8+ and PD-1-CD8+ cells from spleens of NZB/W F1 mice.

last: Shen


title: PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis [scRNA-seq, scTCR-seq]

summary: To dissect whether PD-1+CD8+ T cells are exhausted in lupus nephritis, scRNA-seq were performed to define the heterogeneous and pathologic subset.

overall_design: Splenic and kidney-infiltrating PD-1+CD8+ T cells were sorted for scRNA and scTCR sequencing.


title: Alterations in serum extracellular vesicle miRNAs in a mouse model of adipose tissue regeneration

city: Bunkyo-ku

first: yoshihiro

last: niitsu

state: Tokyo

address: 1-5-45 Yushima

institute: Tokyo medical and dental univercity

summary:
To investigate changes in serum extracellular vesicle miRNAs during adipose tissue regeneration, we created tamoxifen-inducible adipocyte-specific insulin receptor knockout (iFIRKO) mice.
We then performed comprehensive miRNA analysis on the serum extracellular vesicles of iFIRKO and control mice.

overall_design: Comprehensive analysis of miRNA-seq data from the serum extracellular vesicles of iFIRKO and control mice.

first: Yoshihiro

last: Niitsu

first: Chikara

last: Komiya

first: Tetsuya

last: Yamada


title: PD-1-PD-L1 Axis Activation Suppresses CD8+ T Cells and Improves Nephritis.

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

overall_design: Refer to individual Series


title: Identification and characterization of new pancreatic cancer stem cells marker

city: beijing

first: Yanhong

last: Wang

address: Dong dan san tiao No.5

institute: Institute of Basic Medical Sciences Chinese Academy of Medical Sciences，School of Basic Medicine Peking Union Medical College

summary: To identify gene transcripts that were responsible for the stemness formation in pancreatic cancer cells, spheroid PANC1 and BXPC3 cells from primary sphere formation were enriched and then used for RNA-seq analysis. A gemcitabine-resistant SW1990 cell line was also established and used for RNA-seq analysis. In order to ensure the data quality, raw reads were preprocessed by removing low quality sequences, dejunction contamination(Trimmomatic), A/T/G/C Content Distribution(RSeQC), rRNA removal(bowtie2), etc to obtain high quality sequences (clean reads) and all subsequent analyses were based on clean reads. Clean Data was aligned to the reference genome by HISAT, and gene expression quantification was done via software FeatureCounts. DESseq2 package in the R software was introduced to analysis differentially expressed genes between comparisons using read counts estimated by FeatureCounts. Genes with adjusted pvalue< 0.05 and |log2(Fold Change) | > 1 were defined as differentially expressed genes. Totally, we identified 108 DEGs whose expression changes were almost similar in all the data sets.

overall_design: Identification of DEGs between wilt type (WT) and spheroid-forming (Sphere) pancreatic cancer cells (BXBP3, PANC1), and  between wilt type (WT) and gemcitabine-resistant (GR) SW1990 cell line.


title: RNA-seq analysis after siRNA-METTL16 treatment in PANC-1 cells

city: Chongqing

first: Fuming

last: Xie

address: Yuzhong District Yixueyuan Road 1#

institute: Chongqing Medical University

summary: RNA-seq analysis was performed in PDAC patient-derived cell line PANC-1 (NC and METTL16-silenced) to analyze the expression of RNA levels after loss of METTL16.

overall_design: PANC-1 cells were transfected with siRNA of METTL16 and control siRNA. Total RNA was extracted from the samples using the TRIzol method. The total RNA extracted from the samples was tested by a NanoDrop 2000 and denaturing gel electrophoresis. RNA Sequencing Analysis were performed after the sample quality control.

first: Yao

last: Zheng

first: Songsong

last: Liu

first: Huaizhi


title: Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice

city: Baltimore

first: Akrit

last: Sodhi

state: Maryland

address: 1800 Orleans St

department: Ophthalmology

institute: John Hopkins University

summary: Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that vitreous levels of angiogenic proteins regulated by hypoxia-inducible factor (HIF)-1 and -2 (HIFs) remain elevated in diabetic eyes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs we normalized the expression of multiple vasoactive mediators – including VEGF – in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF-inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

overall_design: Transcriptional analysis of retinal tissue of OIR mice at P17 following treatment with a single intraocular injection with DMSO (vehicle; OIR) or the HIF-inhibitor 32-134D (70 ng/µl; OIR+32-134D) at P12 compared with non-OIR (control) mice at P17.

first: Jing

last: Zhang

first: Deepti

last: Sharma

first: Aumreetam

last: Dinabandhu

first: Jaron

last: Sanchez

first: Brooks

last: Puchner Applewhite

first: Kathleen

last: Jee

first: Monika

last: Deshpande

first: Miguel

last: Flores-Bellver

first: Ming-Wen

last: Hu

first: Chuanyu

last: Guo

first: Shaima

last: Salman

first: Yousang

last: Hwang

first: Nicole

last: Anders

first: Michelle

last: Rudek

first: Jiang

last: Qian

first: Maria

middle: V

last: Canto-Soler

first: Gregg

last: Semenza

first: Silvia

last: Montaner


title: Intrinsic TGF-b Signaling Attenuates Proximal Tubule Mitochondrial Injury and Inflammation in Chronic Kidney Disease

city: Zurich

first: Genome

last: Informatics

address: Winterthurerstrasse 190

department: Functional Genomics Center Zurich (FGCZ)

country: Switzerland

institute: ETH ZURICH / University of Zurich

summary:
To investigate how TGF-b affects proximal tubule cell metabolism and response to injury, we generated conditional immortalized mouse PT cells and deleted the TGF-beta Receptor II in vitro using adeno-cre
We then performed gene expression profiling analysis using data obtained from RNA-seq of WT cells (PT cre-) and KO cells (PTcrex2) treated or not with H2O2 in serum free media (4 conditions in total)

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PT cre- and PT crex2 at baseline and under stress condition (H2O2 and serum free media)

first: Stellor

last: Nlandu Khodo

first: Ge

last: Tan

first: Peter

last: Leary

first: Hubert

last: Rehrauer


title: Patient-derived iPSCs faithfully represent the genetic diversity and cellular architecture of human acute myeloid leukemia

city: New York

first: Nataly

last: Cruz

address: 1470 Madison Ave

institute: Mount Sinai

summary: The reprogramming of human acute myeloid leukemia (AML) cells into induced pluripotent stem cell (iPSC) lines could provide new faithful genetic models of AML, but is currently hindered by low success rates and uncertainty about whether iPSC-derived cells resemble their primary counterparts. Here we developed a reprogramming method tailored to cancer cells, with which we generated iPSCs from 15 patients representing all major genetic groups of AML. These AML-iPSCs retain genetic fidelity and produce transplantable hematopoietic cells with hallmark phenotypic leukemic features. Critically, single-cell transcriptomics reveal that, upon xenotransplantation, iPSC-derived leukemias faithfully mimic the primary patient-matched xenografts. Transplantation of iPSC-derived leukemias capturing a clone and subclone from the same patient allowed us to isolate the contribution of a FLT3-ITD mutation to the AML phenotype. The results and resources reported here can transform basic and preclinical cancer research of AML and other human cancers.

overall_design: Single-cell RNA-sequencing was performed with the Chromium 10x Genomics 3' protocol (v3.0) on cryopreserved primary AML patient PBMCs, iPSC-HSPCs from day 11 (AML-9.9 and AML-47.1) or day 17 (AML-4.10) of differentiation and hCD45+ cells from primary and iPSC-derived xenografts sorted using Magnetic Activated Cell Sorting.

last: Cruz-Rodriguez

first: Saul

last: Carcamo

first: Dan

last: Hasson

first: Eirini

last: Papapetrou


title: Rational designs of Cas12a nuclease with the improved targeting specificity at both the proximal and distal region from the PAM

status: Public on Apr 17 2023

city: Wuhan

first: chen

last: peng

address: College of Life Sciences, Wuhan University

department: College of Life Sciences

institute: Wuhan University

summary: Our findings provide a novel version of AsCas12a variant with low off-target effects, especially capable of dealing with the high off-targeting at the distal region from the PAM.

overall_design: we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand

first: Lei

last: Yin


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [10J_210121]

city: La Jolla

first: Joseph

last: Ecker

address: 10010 North Torrey Pines Road

department: Genomic Analysis Laboratory

institute: HHMI-Salk-Institute

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

overall_design: Apply snmC-seq3 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (10J).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

middle: G

last: Castanon

last: Nery

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: Jesse

last: Dixon

first: M

last: Behrens


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [10J_210114]

first: Peter


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [10H_210121]

overall_design: Apply snmC-seq3 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (10H).


title: Effects of acute loss of mature adipocytes in adipose tissue on the liver

first: yoshihiro

last: niitsu

summary:
To investigate the effects of acute loss of mature adipocytes in adipose tissue on the liver, we created tamoxifen-inducible adipocyte-specific insulin receptor knockout (iFIRKO) mice.
We then performed comprehensive gene expression analysis on the liver of iFIRKO and control mice.

overall_design: Comprehensive gene expression analysis of RNA-seq data from the liver of iFIRKO and control mice.

first: Yoshihiro

last: Niitsu

first: Chikara

last: Komiya

first: Tetsuya

last: Yamada


title: Transcriptomic profile of CTDP1 knockdown in MDA-MB-231 cells

city: Omaha

first: Nicholas

last: Woods

state: Nebraska

institute: Univeristy of Nebraska Medical Cent

summary: MDA-MB-231 cells with transfected lentivirus carrying shRNA (shScr, shCTDP1-#1 and shCTDP1-#2) and selected with puromycin. 1000 and 616 genes were found commonly up- and down-regulated in both shCTDP1-#1 and #2.

overall_design: The transcriptome of each of the knockdown (shScr, shCTDP1-#1 and shCTDP1-#2) were acquired in triplicate

first: Henry

last: Law


title: Time of day dependent regulation of exercise-induced transcription in the heart

city: Las Vegas

first: Graham

last: McGinnis

state: NV

address: 4505 S Maryland Pkwy

department: Kinesiology and Nutrition Sciences

institute: University of Nevada Las Vegas

summary: We sought to determine the global transcriptional response to exercise in the heart in a time-of-day dependent manner. To accomplish this, adult male mice (C57Bl/6, ~12 weeks of age) were habituated to treadmill exercise and exposed to a single bout of low-moderate intensity exercise (60 mintue, 10 m/min, 0% grade) at ZT0 (beginning of rest phase) or ZT12 (beginning of active phase). RNA was isolated from whole hearts harvested immediately after exercise (or from sedentary control mice) for RNA-Seq.

overall_design: We performed RNA-Seq on 4 biological groups; ZT0-Sed - Sedentary mice at the beginning of the rest phase, ZT0-Ex - Exercised mice at the beginning of the rest phase, ZT12-Sed - Sedentary mice at the beginning of the active phase, ZT12-Ex - Exercised mice at the beginning of the active phase.

first: Richard

last: Tillett


title: Next Generation Sequencing Analysis of SRSF1 flox/flox and SRSF1-KO pancreatic islet Transcriptome

city: 上海

first: WENJU

last: QIAN

state: 上海

address: 徐汇区岳阳路

institute: 上海中科院

summary: we report insulin secretion defects in SRSF1 Ins2-Cre mice, in which SRSF1 is ablated in pancreatic β cells.

overall_design: The control and SRSF1 Ins2-Cre gene in pancreatic β cells mRNA profiles were generated by deep sequencing, using illumina novaseq 6000

first: Wenju

last: Qian

first: Ying

last: Feng


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [10D_201210]

first: Joseph

last: Ecker

state: CA

overall_design: Apply snmC-seq3 to 117 brain functional regions to identify epigenomic landcape of the adult mouse brain, this subseries consists of one single nucleus methylation sequencing experiment of brain region (10D).

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

last: Castanon

last: Nery


title: Somatic variants of MAP3K3 are sufficient to cause cerebral cavernous malformations

city: Beijing

first: Woo-ping

last: Ge

state: Beijing

address: 26 Shengming Kexue Yuan Rd

institute: Chinese Institute for Brain Research, Beijing

summary: To further explore the underlying molecular pathways altered by MAP3K3I441M in endothelial cells, the mouse endothelial cell line bEnd.3 was first infected with lentivirus-MAP3K3I441M (LV- MAP3K3I441M-P2A-EGFP; LV-EGFP was used as the control). Total RNA from these cells was then subjected to RNA sequencing.

overall_design: Comparative gene expression profiling analysis of RNA seq data. We performed gene profiling analysis of RNA seq data obtained from two groups of cells.Three samples from endothelial cells with lentivirus-MAP3K3I441M infection (Mut 1–3) and five control samples with lentivirus-EGFP infection (Ctrl 1–4).

first: Jian

last: Ren

first: Yazi

last: Huang

first: Yeqing

first: Daosheng

last: Ai

first: Tao

last: Hong


title: Biphasic expression of thyroid hormone receptor TRb1 in mammalian retina and anterior ocular tissues

city: Bethesda

first: Hong

state: MD

address: 9000 Rockville Pike

department: NIDDK

institute: NIH

summary:
Purpose: Using customized RNA-sequencing analyses to reveal notably different expression profiles of TRb1 and TRb2 in mouse retina.
Method and Results:  TRb2 peaks early whereas TRb1 peaks later during retinal maturation or during later differentiation. TRb1-knockout mice displayed only minor changes in opsin photopigment expression and normal electroretinogram responses, indicating that TRb2 and TRb1 are not functionally equivalent in cone differentiation. The biphasic expression patterns of TRb1 and TRb2 suggest versatile functions for thyroid hormone in retinal and non-neural ocular development.

overall_design: The specific expression of thyroid hormone receptor beta (Thrb) isoforms in retina tissue during development are profiled from RNA-seq data analysis.

first: Lily

last: Ng

first: Ye

first: Douglas

last: Forrest


title: AVA-ADR-001- a small molecular inhibitor of ADAR1 (Immuno-oncology target)

city: Bengaluru

first: Aditya

last: Kulkarni

state: Karnataka

address: Devarachikkanahalli Main Rd, Bommanahalli

country: India

institute: Aten Porus Lifesciences Pvt Ltd

summary:
To inhibitors for ADAR1 and a strong rationale for the development of ADAR1 p150 inhibitors for cancer immunotherapy
Here, we describe AVA-ADR-001, a potential first-in-class small molecule inhibitor of ADAR1 p150 targeting the Z alpha domain. AVA-ADR-001 binds specifically to the Z alpha domain of ADAR1 p150 as confirmed by fluorescence spectroscopy and showed significant interferon induction in THP1 macrophages, which have high ADAR1 p150 expression compared with monocytes. Proteomics and transcriptomics analysis revealed significant upregulation of interferon signaling upon treatment with AVA-ADR -001. Interestingly, activation of interferon signaling resulted in AVA-ADR-001 induced cell killing in ADAR1-independent cell lines. In addition, treatment with AVA-ADR -001 resulted in significant activation of PKR, which may explain the decreased cell proliferation. Finally, AVA-ADR-001 showed superior anti-tumor efficacy compared to anti-PD1 in an in vivo tumor efficacy study and has a moderately synergistic effect when combined. Overall, this study reveals that ADAR1 p150 inhibition by AVA-ADR-001 exerts a multipronged impact on anti-tumor efficacy mediated by immune cells, accumulation of interferons and activation of PKR, resulting in protein translation inhibition and cell proliferation arrest.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for A549 and HCT116 cells treated with AVA-ADR-001 for 24 h.

first: Avijit

last: Goswami

first: Barnali

last: Deb


title: Ribosome profiling of Aim29-knockout S.cerevisiae cells

city: Cambridge

first: Vladimir

last: Denic

state: MA

address: 52 Oxford St, Room 442

department: Molecular and Cellular Biology

institute: Harvard University

summary: The aim of this study was to gain insight into the ribosome occupancy on different genes and codons in AIM29 KO cells vs. wild-type cells

overall_design: Ribosome profiling in S. cerevisiae AIM29 KO vs. wild type cells

first: Anjali

last: Nelliat

first: Alexander

middle: J

last: McQuown

first: Dvir

last: Reif

first: Britnie

last: Santiago Membreno

first: Colin

last: Wu


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [10H_210114]

first: Joseph

last: Ecker

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

last: Castanon

last: Nery

first: Peter

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: Jesse

last: Dixon

first: M

last: Behrens


title: IsoDGR specific monoclonal antibody improves lung pathophysiology of PCMT1 knockout mice

city: Singapore

first: Pazhanichamy

last: Kalailingam

address: 60 Nanyang Drive

institute: NTU

summary:
At present work we have used PCMT1-/- (premature aging) and PCMT1+/- (aged) as the animal model to studies the role of isoDGR in the ageing and age associated disease in the pulmonary system
We  performed gene expression profiling analysis using data obtained from RNA-seq of Lung of PCMT1+/+, PCMT1+/- PCMT1-/- and PCMT1-/- +mAB at 5-6 weeks .

overall_design: Comparative gene expression profiling analysis of RNA-seq data for lung of PCMT1+/+, PCMT1+/-, PCMT1-/- and PCMT1-/- +mAB

first: Khalilatul

last: Hanisah

first: Mohd

last: Kahliab

first: Tian

last: Lu

first: SoFong

last: Cam Ngan

first: Benjamin

middle: S

last: Teck Lee

first: Bhargy

last: Sharma

first: Sint

last: Thida Bo

first: A

last: Richards

first: Dominique

last: de Kleijn

first: I

last: Hsin Su

first: Tiannan

last: Guo

first: Yonggui

last: Gao

first: Siu

last: Kwan Sze


title: Suppression of pyrrolidine ring biosynthesis and its effects on gene expression and subsequent accumulation of anatabine in leaves of Tobacco (N. tabacum L.)

city: Neuchâtel

first: Kacper

middle: Piotr

last: Kaminski

address: Rue Fleury 5

institute: Philip Morris International

summary: Background: Anatabine, although being one of four major tobacco alkaloids, is never accumulated in high quantity in any of the naturally occurring species from the Nicotiana genus. Previous studies therefore focused on transgenic approaches to synthetize anatabine, most notably by generating transgenic lines with suppressed putrescine methyltransferase (PMT) activity. This led to promising results, but the global gene expression of plants with such distinct metabolism has not been analyzed. In the current study, we describe how these plants respond to topping and the downstream effects on alkaloid biosynthesis. Results: The surge in anatabine accumulation in PMT transgenic lines after topping treatment and its effects on gene expression changes were analyzed. The results revealed increases in expression of isoflavone reductase-like (A622) and berberine bridge-like enzymes (BBLs) oxidoreductase genes, previously shown to be crucial for the final steps of nicotine biosynthesis. We also observed significantly higher methylputrescine oxidase (MPO) expression in all plants subjected to topping treatment. In order to investigate if MPO suppression would have the same effects as that of PMT, we generated transgenic plants. These plants with suppressed MPO expression showed an almost complete drop in leaf nicotine content, whereas leaf anatabine was observed to increase by a factor of ~1.6X. Conclusion: Our results are the first concrete evidence that suppression of MPO leads to decreased nicotine in favor of anatabine in tobacco roots and that this anatabine is successfully transported to tobacco leaves. Alkaloid transport in plants remains to be investigated to higher detail due to high variation of its efficiency among Nicotiana species and varieties of tobacco. Our research adds important step to better understand pyrrolidine ring biosynthesis and its effects on gene expression and subsequent accumulation of anatabine.

overall_design: Transgenic TN90 lines PMT1 (06TN2046), PMT2 (06TN2048) and PMT3 (06TN2052) together with TN90 control plants were sequenced in this experiment. Each genotype had 10 replicates, 5 replicates in 2 conditions: untopped and topped.

middle: P

first: Lucien

last: Bovet

first: Aurore

last: Hilfiker

first: Helene

last: Laparra

first: Joanne

last: Schwaar

first: Nicolas

last: Sierro

first: Gerhard

last: Lang

first: Damien

last: De Palo

first: Philippe

middle: A

last: Guy

first: Csaba

last: Laszlo

first: Simon

last: Goepfert

first: Nikolai

last: Ivanov


title: Gene expression of C28/I2 cells in monolayer and spheroid culture

city: Shenzhen

first: Yan

last: WANG

address: 1068 Xueyuan Ave

institute: Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences

summary: Here we described the transcriptional differences of chondrocytes in monolayer and spheroid cultures.

sample_organism:
Homo sapiens
Mus musculus

overall_design: Transcriptional profiling was employed to test the expression profiles of C28/I2 cells in monolayer and spheroid cultures..

last: Wang

first: Qian

last: Xie

first: Jianhui

last: Liang


title: Time course transcriptomic analysis of cabbage (Brassica oleracea ssp. capitala L.) during vernalization

city: Anseong-si, Gyeonggi-do

first: Heewon

last: Moon

address: 4726,Seodong-daero, Daedeok-myeon

country: South Korea

institute: Chung-ang university

summary: We report here NGS RNA-seqencing datasets for three different vernalization time course of Brassica oleracea plants

overall_design: Three different veranlization treatment to B. oleracea whole plants: NV; non-vernalization under long day photoperiod (16h light/8h dark) for two weeks, V40; vernalization in refrigerator (4°C) under short day photoperiod (8h light/16h dark) for 40 days, AV; after 40days of cold exposure, the samples were returned back to a warm termperature under long day photoperiod (16h light/8h dark) for 7 days

first: Dong

middle: H

last: Kim


title: Next generation sequencing facilitates quantitative analysis of old and young mouse endothelial cells after injury

first: Bi-Sen

last: Ding

state: NY

address: York Avenue

institute: Weill Cornell

summary: The goal of this study is to determine the transcriptional difference between mouse endothelial cells after lung injury

overall_design: mRNA profilies of endothelial cells were generated by deep sequencing, in triplicate, using illumina's protocol.


title: Effect of depletion of OASIS on gene expression in primary cultured mouse astrocytes during DNA damage response.

city: Hiroshima

first: Atsushi

last: Saito

state: Hiroshima

address: 1-2-3 Kasumi, Minami-ku

institute: Hiroshima University

summary: To investigate the roles of OASIS/CREB3L1 in astrocytes during DNA damage response, we established OASIS wild type and deficient primary cultured mouse astrocytes treated with or without anti-cancer drug doxorubicin. We then performed gene expression profiling analysis using data obtained from RNA-seq of 4 different cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for OASIS wild type and deficient primary cultured mouse astrocytes and the cells treated with doxorubicin.


title: BET inhibition in ovarian cancer (i-BET858, i-BET151)

city: Cardiff

first: Marcos

last: Quintela

state: --- Select One ---

address: 52 Maindy Rd, Hadyn Ellis Building

department: European Cancer Stem Cell Research Institute

institute: Cardiff University

summary: Ovarian cancer cell line OVCAR-3 was treated with two different BET inhibitors for 4 and 24 hours.

overall_design: Total RNA was obtained from OVCAR-3 cells treated for 4h and 24h with i-BET858 and i-BET151 (1uM). DMSO treatments were used as controls.

first: David

middle: W

last: James


title: DNA Methylome and 3D Chromatin Landscape of Cell Types Across the Mouse Brain [10D_201203]

first: Joseph

middle: R

last: Ecker

first: Hanqing

last: Liu

first: Anna

last: Bartlett

first: Jacinta

last: Lucero

first: Julia

last: Osteen

first: Jordan

last: Altshul

first: Mia

last: Kenworthy

first: Rosa

last: Castanon

last: Nery

first: Peter

last: Berube

first: Huaming

last: Chen

first: Michael

last: Nunn

first: Jesse

last: Dixon

first: M

last: Behrens


title: An integrated network pharmacology and RNA-seq approach for exploring the vascular protection of neferine on attenuating Ang II-induced blood pressure elevation

status: Public on Apr 15 2023

city: Fuzhou

first: Jun

last: Peng

state: Fujian

address: 1 Qiuyang Road, Minhou Shangjie

department: Academy of Integrative Medicine

institute: Fujian University of Traditional Chinese Medicine

summary: The goals of this study is to compare the differently expressed genes in abdominal aorta tissues of Control and Ang II with or without neferine treatment. The  Ang II  (n=12) were randomly divided into 2 groups: Ang II , and  Ang II +  neferine (1 mg/kg/day) groups (n=6 for each group). Control groups (n=5) were set as control. Mouse in Control and Ang II groups were  intragastrically with double distilled water (dd H2O); while mice in  Ang II +  neferine (1 mg/kg/day) group were intragastrically with 1 mg/kg/day of  neferine for 6 weeks.  Then the abdominal aorta tissues were used to identify differentially expressed genes among different groups.

overall_design: RNA sequencing was performed with abdominal aorta of mice in 3 groups:Control(n=5), Ang II(n=6 )  ,  Ang II +  neferine(1 mg/kg/day,n=6) treated to identify the differently expressed genes and related pathway.

first: Aling

last: Shen

first: Xiuli

last: Zhang

first: Lingqi

first: Qihang

last: Ding


title: Small RNA-seq of MERS-CoV

city: Seoul

first: HEE

last: CHO

address: 50 YONSEI-RO, SEODAEMUN-GU

institute: Yonsei University

summary: MERS-CoV genome-derived small RNAs in Huh7 cells infected with a Korean isolate of MERS-CoV (KNIH002; Genbank accession no. KT029139.1)

overall_design: Small RNA-seq of MERS-CoV using total cellular RNAs recovered from KNIH002-infected Huh7 (n=2)

first: Minwoo

last: Kim

first: Hee

last: Cho

first: Jong-Won

last: Oh


title: IL-27 induces an IFN-like signature in murine macrophages

city: Frederick

first: Scott

last: Durum

address: Building 560, Room 31-71

department: CCR

institute: National Cancer Institute

summary: The effect of IL-27 stimulation of murine macrophages was investigated. RNA-seq was performed to evaluate the resulting gene expression.

overall_design: Comparative gene expression analysis of RNA-seq data between macrophages stimulated with IL-27 and untreated macrophages.

first: Caroline

last: Andrews

first: Maggie

last: Cam

first: Richard

last: Finney


title: Mouse resident lung eosinophils are dependent on IL-5

city: Tel Aviv

first: Guy

last: Shapira

address: Chaim Levanon 30

institute: Tel Aviv University

summary:
Purpose: we aimed to characterized eosinophils  in the murine model of asthma
Methods: Eosinophils were sorted from the lung of naïve and and HDM-induced asthma mice. There after RNA was extracted from the sorted eosinophils and subjected to RNAseq.
Results:we demonstrated that resident lung eosinophils require IL-5 for their survival and that the expression of Siglec-F, is regulated by IL-5 .
Conclusion: Our data  suggest that the distinct eosinophil populations in the asthmatic lung represent a continuum of activation states rather than distinct eosinophil subsets.

overall_design: RNAseq of sorted eosinophils from murine model of asthma


title: A specific protective mechanism against chloroplast photo-reactive oxygen species in phosphate-starved rice plants [RNA-seq]

city: Yangzhou

first: Mingnan

last: Qu

state: Jiangsu

address: Pazhou Dadao Rd, 17-19

institute: Yangzhou Univerisity

summary: Phosphorus (Pi) starvation prevents a good match between light energy absorption and photosynthetic carbon metabolism. Photosynthetic electron-transport chain switches to use molecular oxygen as an electron carrier, generating photo-reactive oxygen species (photo-ROS) in chloroplast. In rice (Oryza sativa), DEEP GREEN PANICLE1 (DGP1) is robustly up-regulated in response to Pi-deficiency stress. DGP1 decreases the DNA-binding activities of the photosynthetic activators GLK1/2 on the genes involved in chlorophyll biosynthesis, light harvesting and electron transport. This Pi-starvation-induced mechanism dampens electron transport rates (ETRI and ETRII) and alleviates the electron-excessive stress in mesophyll cells. Meanwhile, DGP1 hijacks glycolytic enzymes GAPC1/2/3, redirecting glucose metabolism toward pentose phosphate pathway with superfluous NADPH production. Phenotypically, light irradiation induces O2– accumulation in Pi-starved WT leaves, but was observably accelerated in dgp1 mutant and impaired in GAPCsRNAi line and glk1glk2 double mutant. Interestingly, overexpression of DGP1 in rice caused hyposensitivity to the ROS-inducers (catechin and methyl viologen) and dgp1 mutant shows a similar inhibitory growth with the WT plants. We conclude that DGP1 gene serves as a specific antagonizer against Pi-starvation-induced photo-ROS, which integrates light-absorbing and anti-oxidative systems by orchestrating transcriptional and metabolic regulations, respectively.

overall_design: We examined the transcriptional data in leaves of glk1glk2 and dgp1 mutants with their WT (DJ) plants under normal growth or low-Pi stress (10 µM KH2PO4).

first: Zhan

last: Xu


title: Effect of LLC1 tumor cell conditioned medium on RNA expression in mouse osteoblasts (MC3T3 cells)

city: Rochester

first: Xuewei

last: Wang

address: 200 1st street

institute: Mayo Clinic

summary: MC3T3 osteoblasts were grown in culture medium in the presence of 10 mM beta-glycerophosphate and and 100 micro g per mL of ascorbic acid and   25% LLC1 conditioned medium or vehicle for 7 days. Cells were lysed an RNA was isolated.

overall_design: The goal of the experiment was to determine the effect of LLC1 conditioned medium on MC3T3  cell RNA expression .  To this end, MC3T3 cells will grown in medium supporting mineralization.  Cells which treated with either LLC1 conditioned medium or vehicle for 7 days.  Cells were  collected, lysed an RNA was obtained for generation of libraries.

first: Rajiv

last: Kumar


title: 10x RNA Seq for Mouse Lung Tumorigenic Tissue

first: Hu

last: Li

address: 200 1st St SW

summary: We report the identification of senescent tissue resident macrophages in an oncogenic-Kras mouse model.

overall_design: Lung tissue of eight-week old ATTAC (control), Kras, and ATTAC;Kras mice all treated with AP treatment from birth.

first: Luis

last: Prieto

first: Baker

last: Darren