title: Targeting NEK2 impairs oncogenesis and radioresistance via inhibiting the Wnt1/β-catenin signaling pathway in cervical cancer

status: Public on Apr 30 2021

city: Wuhan

first: Yulan

last: Zeng

state: Hubei

address: No.1277 Jiefang Rd, Jianghan District

department: Tongji Medical College

country: China

institute: Huazhong University of Science and Technology

type: Expression profiling by high throughput sequencing

summary: We report that NEK2 protein level is overexpressed and correlated with the tumor stage and lymph node metastasis in cervical cancer. Furthermore, we provided evidence that NEK2-depleted cervical cancer cells exhibit impaired oncogenesis and enhanced radiosensitivity. Using RNA sequencing, we identify Wnt1 as a key downstream effector of NEK2. Knockdown of NEK2 downregulates the mRNA and protein levels of Wnt1, thereby inhibiting the activation of the Wnt/β-catenin signaling pathway. More importantly, the observed consequences induced by NEK2 depletion in cervical cancer cells can be partially rescued by Wnt1 overexpression. Taken together, these results demonstrate that NEK2 activates the Wnt/β-catenin signaling pathway via Wnt1 to drive oncogenesis and radioresistance in cervical cancer, indicating that NEK2 may be a promising target for the radiosensitization of cervical cancer.

overall_design: In our study, we demonstrate that NEK2 protein levels are significantly upregulated and that elevated expression of NEK2 is correlated with the tumor stage and lymph node metastasis in cervical cancer. Furthermore, we identify Wnt1, a member of the Wnt family, as a key downstream effector of NEK2. Importantly, we show that NEK2 depletion impairs cervical cancer progression and radioresistance in a Wnt1-dependent manner, indicating that NEK2 may be a promising target for cervical cancer radiotherapy.

first: Shuangbing

last: Xu

first: Tie


title: Global Gene Expression Changes in Cholangiocytes Treated with P300 inhibitor SGC-CBP30 (10 μM; Selleckchem, #S7256)

city: Rochester

first: Aditya

last: Bhagwate

state: MN

address: 200 1st Street SW

country: USA

institute: Mayo Clinic

summary: Histone modification is a critical epigenetic regulatory mechanism that is under-explored in cholestatic liver disease. Lysine 27 on histone 3 (H3K27) is a key regulatory residue that can be acetylated by the histone acetyltransferase (HAT) p300, which acts as a transcriptional coactivator.

overall_design: Cholangiocyte cell line, HiBEC,  were treated with DMSO or SGC-CBP30 (10uM)  to look at the gene expression changes due to pharmacological inhibition of P300

first: NidhiJalan-Sakrikar

middle: A

last: Navarro-Corcuera

first: Robert

middle: C

last: Huebert


title: Distinct DNA methylomes of moso bamboo in the phase transition from vegetative to reproductive growth

city: Guangzhou

first: zeyu

last: zhang

state: Guangzhou

address: Kaiyuan streat 190

department: South China Institute for Stem Cell Biology and Regenerative Medicine

institute: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences

type: Methylation profiling by high throughput sequencing

summary: In mammals, it is well known that DNA methylation has important roles during aging. However, age-related DNA methylation changes during phase transitions largely remain unclear in plants. Moso bamboo needs a very long time to transition from vegetative to floral phase. To comprehensively investigate the influence of DNA methylation on aging, we present here a distinctive single-base-resolution DNA methylation profile using both high-throughput bisulfite sequencing (BS-Seq) and single-molecule nanopore-based DNA sequencing, which covers the long period of vegetative growth and transition to flowering of moso bamboo’s development. We discovered that CHH methylation gradually accumulated from vegetative to reproductive growth in a time-dependent fashion. Importantly, DMR (differential DNA methylation) correlating with chronological aging occurred preferentially at both transcription start sites (TSS) and transcription termination sites (TTS). Genes with CG methylation changes showed enrichment of gene ontology (GO) categories in ‘vegetative to reproductive phase transition of meristem’. In addition, In combination with mRNA sequencing (RNA-Seq) revealed that DNA methylation in promoter, intron, and exon has different roles in regulating gene expression. Finally, circular RNA sequencing (circRNA-Seq) revealed that flanking introns of circRNAs show hypermethylation. Further analysis revealed that these flanking introns were enriched in LTR-retrotransponsons. Together, observations in this study provide insights about dynamic DNA methylation and circRNAs landscape with chronological ages, which paves the way to further study the impact of epigenetic factors on flowering in moso bamboo.

overall_design: In this study we used Oxford Nanopore Technologies (ONT)  to directly identify 5mC by detection of electrical current signals for  three week leaf and flower leaf, respectively.

first: Zeyu

last: Zhang

first: Lianfeng

last: Gu


title: Defining a role for GPCR/cAMP/Creb signaling in HFSC activation

city: Los Angeles

first: William

last: Lowry

state: CA

address: 621 Charles Young Drive

department: MCDB

institute: UCLA

summary: Our study demonstrates direct evidence that canonical cAMP/Creb signaling through adrenergic receptors can regulate HFSC activation and the hair cycle. This intracellular signaling circuit connects to downstrean glycolytic metabolism processes which have been previously shown to stimulate HSFC activation.

overall_design: Total mouse epidermis was topically treated with either forskolin or cAMP three times over a span of 5 days to characterize the downstream mechanisms by which Creb can influence the acceleration of the hair cycle

first: Matilde

last: Miranda

first: Itzetl

last: Avila

first: Jasmine

last: Esparza

first: Yulia

last: Shwartz

first: Ya-Chieh

last: Hsu

first: Rebecca

last: Berdeaux

middle: E


title: RNA sequencing reveals enhanced photosynthetic activity in Brassica napus treated with Pseudomonas chlororaphis PA23

city: Winnipeg

first: Ayooluwa

last: Bolaji

address: 50 Sifton Road

department: Biological Sciences

country: Canada

institute: University of Manitoba

summary: Purpose: high-throughput sequencing was utilized to study gene expression pattern in b. Napus and PA23 bacteria interaction

overall_design: plant mRNA was harvested at 24 hours and 7 days post treatment with PA23

first: Joey

last: Wan

first: Mark

last: Belmonte


title: Role of Cop1 on transcriptional output in 4T1 mouse triple negative breast cancer cells

city: Boston

first: Xiaoqing

last: Wang

state: MA

address: 450 Brookline Ave

institute: Dana Farber Cancer Institute

summary: Cop1 regulates stability of transcription factors. We determined the role of Cop1 in the regulation of Cebpd transciptional output. We generated 4T1breast cancer cells with CRISPR/Cas9 mediated Cop1 (gene symbol RFWD2) knockout. We treated control sgRosa26 and sgCop1 cells with vehicle or IFNgamma (20ng/ml) for 24 hours and isolated RNA for sequencing.

overall_design: Examination of transcriptome in Cop1 intact and Cop1 loss 4T1 breast cancer cells in response to IFNgamma.

first: Binbin

first: Shengqing


title: Exposure to non-esterified fatty acids results in short- and long-term changes in the ovarian environment and granulosa cells

city: Utrecht

first: Maria

middle: Belen

last: Rabaglino

address: Yalelaan 7

department: Population Health Science

country: Netherlands

institute: Utrecht University

summary: Determine the differences (if any) of 8 day culture in a high NEFA environment on bovine ovarian tissue compared with a control environment.

overall_design: Ovarian cortical strips were isolated from abattoir-derived bovine ovaries. Natural follicles were removed & remaining cortical strips were randomly assigned into one of two groups: control tissue medium (CON) and high NEFA with a combination of free fatty acids Palmitic Acid (PA), Stearic Acid (SA), & Oleic Acid (OA)

first: Gabriela

middle: H

last: Pedroza

first: Lawrence

last: Lanzon

middle: B

first: Wendy

last: Walker

first: Payam

last: Vahmani

first: Anna

last: Denicol


title: Illumina Infinium HumanMethylationEPIC array after SGI-110 treatment in rhabodmyosarcoma cell lines

first: Katherine

middle: K

last: Slemmons

address: 4650 Sunset Blvd

department: Hematology/Oncology

institute: Children's Hospital Los Angeles

summary: Genome wide methylation microarray was performed on two RD and Rh30 rhabdomyosarcoma cell lines treated with 0.5µM of the dna methyltrasferase inhibitor SGI-110 for 5 days or DMSO control.

overall_design: Genomic DNA was collected from rhabdomyosarcoma cell lines after 5 days of treatment with the dna methyltrasferase inhibitor SGI-110 in biological triplicate. Bisulfite converted DNA was run on the Illumina Infinium HumanMethylationEPIC array. Drug treate

first: Lee

middle: J

last: Helman


title: CDK5 activates Hippo signaling to confer resistance to radiotherapy via upregulating TAZ in lung cancer

first: Yulan

last: Zeng

summary: Tumor resistance to radiotherapy is a therapeutic challenge in the treatment of patients with lung cancer. Cyclin-dependent kinase 5 (CDK5) has been proposed to participate in cell proliferation, migration and invasion; drug resistance; and immune evasion. However, the functions and regulatory mechanisms of CDK5 in lung cancer radioresistance have not been investigated.SiRNAs and ShRNAs were used to knock down CDK5 in A549 and H1299 cells. The effects of CDK5 depletion on the tumorigenic behaviors of non-small cell lung cancer (NSCLC) cells were evaluated in vitro and in vivo. Gene expression was examined by RNA-seq and quantitative real-time PCR.

overall_design: Human lung cancer cell line ( A549) were purchased from the American Type Culture Collection (ATCC) and cultured in  RPMI-1640 supplemented with 10% fetal bovine serum (FBS) and 1% penicillin/streptomycin and incubated at 37°C with 5% CO2. Cells transfected with Scramble or CDK5-targeting siRNAs were harvested after 48 h. TRIzol reagent (Takara) was used to extract total RNA. RNA sequencing was conducted with an BGIseq500 platform (BGI-Shenzhen, China). Genes were considered to be significantly differentially expressed by the transcript fragments per kilobase million (FPKM) values if they satisfied the cutoff threshold criteria of a fold change of > 2.0 and a false discovery rate of < 5%.

first: Shuangbing

last: Xu

first: Tie


title: Distinct transcriptional profiles of Leptospira borgpetersenii serovar Hardjo strains JB197 and HB203 cultured at different temperatures

status: Public on Apr 28 2021

city: Columbia

first: Sathesh

last: Sivasankaran

state: MO

address: Bond Life Sciences Center Suite 106, 1201 Rollins Street

institute: University of Missouri

summary: Leptospirosis is a global zoonotic, neglected tropical disease. Interestingly, a high level of species specificity (both bacteria and host) plays a major role in the severity of disease presentation which can vary from asymptomatic to multi-organ failure. Pathogenic Leptospira colonize the kidneys of infected individuals and are shed in urine into the environment where they can survive until they are contracted by another host. This study looks at two strains of L. borgpetersenii, HB203 and JB197 which are genetically very similar, and identical by serotyping as serovar Hardjo, yet HB203 causes a chronic infection in the hamster while JB197 causes organ failure and mortality. To better characterize bacterial factors causing different disease outcomes, we examined the gene expression profile of these strains in the context of temperatures that would reflect natural Leptospira life cycles (environmentally similar 29oC and 37oC which is more indicative of host environment). We found vast differences in gene expression both between the strains and within strains between temperatures. Characterization of the transcriptome of L. borgpetersenii serovar Hardjo strains JB197 and HB203 provides insights into factors that can determine acute versus chronic disease in the hamster model of infection. Additionally, these studies highlight strain to strain variability within the same species, and serovar, at different growth temperatures, which needs to be considered when serovars are selected and propagated for use as bacterin vaccines used to immunize domestic animal species.

overall_design: L. borgpetersenii serovar Hardjo strains JB197 and HB203 were isolated from the kidneys of experimentally infected hamsters and maintained at 29°C and 37°C. RNAseq revealed distinct gene expression profiles; 440 genes were differentially expressed (DE) between JB197 and HB203 at 29°C, and 179 genes were DE between strains at 37°C. Comparison of JB197 cultured at 29oC and 37oC identified 135 DE genes while 41 genes were DE in HB203 with those same culture conditions. The consistent DE of ligB, which encodes the outer membrane virulence factor LigB, was validated by immunoblotting and 2D-DIGE. Differential expression of lipopolysaccharide was also observed between JB197 and HB203.

first: Ellie

last: Puts

first: Luis

middle: V

last: Fernandes

first: Brian

last: Brunelle

first: John

middle: D

last: Lippolis

first: David

middle: P

last: Alt

first: Darrell

middle: O

last: Bayles

first: Richard

middle: L

last: Hornsby

first: Jarlath

last: Nally


title: MicroRNA expression differences in blood-derived CD19+ B cells of methotrexate treated rheumatoid arthritis patients

city: Oslo

first: Fatima

last: Heinicke

address: Kirkeveien 166

department: Department of Medical Genetics

country: Norway

institute: Oslo University Hospital

type: Non-coding RNA profiling by high throughput sequencing

summary: The aims of the study were to assess the global miRNA repertoire of peripheral blood CD19+ B cells, by high throughput sequencing, and to uncover miRNA expression differences between RA patients (newly-diagnosed and methotrexate treated) and healthy controls.

overall_design: Newly-diagnosed rheumatoid arthritis patients (n=10), methotrexate treated rheumatoid arthritis patients (n=18), healthy controls (n=9),

first: Benedicte

last: Lie


title: RNA sequencing of mice primary Hepatic Stellate Cells  with Exosomes from pancreatic cancer cells

city: Shanghai

first: Ya

last: Gao

state: China

address: zhizaoju road

institute: Shanghai 9th People’s Hospital Schoolof Medicine ShanghaiJia

summary: Pancreatic ductal adenocarcinoma (PDAC) shows a remarkable predilection for liver metastasis. Prooncogenic secretome delivering and trafficking via exosomes is crucial for pre-metastatic microenvironment formation and metastasis. This study aims to explore the underlying molecular mechanisms of how PDAC derived exosomes (Pex) modulate the microenvironments of future sites of metastasis.So we dicided using Hepatic Stellate Cells  to see their transcriptomes changing after Pex addition.

overall_design: Examination of Mice primary Hepatic Stellate Cells RNA sequencing comparing the  PDAC derived exosomes (adding Panc02/KPC derived exosomes) addition group with the control group (adding Exosomes from Primary mice pancreatic duct epithelial cells).

first: Zhibo

last: Xie

first: Chiakang

last: Ho

first: Yifan

last: Zhang


title: Genome-wide maps of chromatin state in LUAD and normal tissues

city: Chengdu

first: Tingting

last: Song

address: The Incubation Building, Tianfu Life Science and Technology Park, 38 Keyuan South Road, Chengdu City, Sichuan Province.

institute: 四川大学华西医院

summary: We report the application of Hi-C technology for high-throughput profiling of LUAD and normal tissues. By obtaining over three billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of LUAD. We found the main conversion type of compartment is A→B in tumor tissues, 216 tumor-specific TADs and 41 distinct enhancer-promoter loops in tumor tissue. And these chromatin structure variations are mainly on chromosome 3. We also found 5 most important genes (SYT16, NCEH1, NXPE3, MB21D2, and DZIP1L), which were detected in both A→B compartment, TADs and chromatin loops.

overall_design: Examination of LUAD and paired normal tissues of 2 patients

first: Li


city: fuzhou

first: Lianfeng

last: Gu

address: No.15 Shangxiadian Road, Cangshan District, Fuzhou City, Fujian Province, China

institute: Fujian Agriculture and Forestry University

summary: Bamboo represents the only major lineage of grasses that is native to forests and is one of the most important non-timber forest products in the world. Moso bamboo is a large woody bamboo that has ecological, economic and cultural value in Asia and accounts for ~70% of the total bamboo growth area (Peng et al., 2013). In the aspect of epigenetics of Moso bamboo,the total genomic DNA methylation rates in Moso bamboo at different chronological ages were significantly different (Yuan et al., 2014). Those show that the  flowering of Moso bamboo are closely related to epigenetic modification. However, DNA methylation in single base resolution has never been reported in moso bamboo. In this study, leaves from three-week bamboo, one-year bamboo, flower in next year bamboo, flowering bamboo and Flower florets was used for bisulfite sequencing (BS-seq), and RNA-Seq. Genome-wide methylation profile and gene expression analysis were constructed to reveal the factors to regualte the phase transition from vegetative to reproductive growth in moso bamboo.

overall_design: In this study, leaves from three-week bamboo, one-year bamboo, flower in next year bamboo, flowering bamboo and Flower florets was used for bisulfite sequencing (BS-seq) which covered the phase transition from vegetative to reproductive growth in moso bamboo.

first: Zeyu


title: Distinct transcriptomes and DNA methylomes of moso bamboo in the phase transition from vegetative to reproductive growth

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

overall_design: Refer to individual Series


title: Whole Blood Targeted Bisulfite Sequencing Validates Differential Methylation in C6orf10 gene of Patients with Rheumatoid Arthritis

first: Vidyanand

last: Anaparti

state: MB

address: 715 McDermot Avenue

summary: Targeted bisulphite pyrosequencing of the major histocompatibility complex (MHC) region was performed using CATCH-Seq kits on whole blood DNA isolated from healthy controls and patients with rheumatoid arthritis. Data analysis showed 74 unique and differentially methylated loci (DMLs) in the MHC region of RA patients compared to healthy controls. Further, differentially methylated CpGs in C6orf10 gene were negatively associated with preclinical RA risk factors.

overall_design: Whole blood DNA was isolated from 17 healthy controls and 17 RA patients. All the study participants were recruited from Indigenous North American Communities (Cree, Ojibway and Ojicree) in Central Canada.

first: Prasoon

last: Agarwal

first: Irene

last: Smolik

first: Neeloffer

last: Mookherjee

first: Hani

middle: S

last: El-Gabalawy


title: Assembly of a spatial circuit of T-bet-expressing lymphocytes is required for antiviral humoral immunity

city: New York

first: Michail

last: Schizas

address: 1275 York ave

institute: Memorial sloan Kettering

summary: Effective antiviral immunity requires generation of T and B lymphocytes expressing transcription factor T-bet, a regulator of type 1 inflammatory responses. Using T-bet expression as an endogenous marker for cells participating in a type 1 response, we report coordinated interactions of T-bet-expressing T and B lymphocytes based on their dynamic co-localization at T cell zone and B follicle boundary (T-B boundary) and germinal centers (GC) within the draining lymph node during lung influenza infection. We demonstrate that the assembly of this circuit takes place in distinct anatomical niches, guided by CXCR3, which enables positioning of TH1 cells at the T-B boundary. The encounter of B and TH1 cells at T-B boundary enables IFN produced by the latter to induce IgG2c class switching. Within GCs, T-bet+ TFH cells represent a specialized stable sub-lineage required for GC growth, but dispensable for IgG2c class switching. Our studies show that during respiratory viral infection, T-bet-expressing T and B lymphocytes form a circuit assembled in a spatio-temporally controlled manner that acts as a functional unit enabling a robust and coherent humoral response tailored for optimal antiviral immunity.

overall_design: Cells from mediastinal lymph nodes were isolated from Tbx21tdTomato-T2Acre, Bcl6-YFP, Foxp3Thy1.1 reporter mice 14 days after influenza infection. Populations were FACS-sorted on an Aria II cell sorter (BD Bioscience). TH1 cells were defined as Thy1.1-RFP+YFP-; T-bet+TFH cells defined as Thy1.1-RFP+YFP+; and T-bet-TFH cells defined as Thy1.1-RFP-YFP+. Three replicates of each cell subset were generated. Cells were resuspended in Trizol™. RNA was extracted from Trizol™ and prepared for sequencing by the Integrated Genomics Core at Memorial Sloan Kettering Cancer Center. 10-30 million 50bp paired-end reads were acquired on an Illumina HiSeq 4000.

first: Alejandra

last: Mendoza

first: William

middle: T

last: Yewdell

first: Beatrice

last: Hoyos

first: Regina

last: Bou-Puerto

first: Anthony

last: Michaels

first: Chrysothemis

last: Brown

first: Jayanta

last: Chaudhuri

first: Alexander

middle: Y

last: Rudensky


title: RNAseq of rhabdomyosarcoma cells after treatment with SGI-110 and/or Dasatinib

first: Katherine

last: Slemmons

summary: Patients with metastatic or recurrent rhabdomyosarcoma, the most common childhood soft tissue sarcoma, continue to do poorly and new treatments are needed. In this study we evaluated a novel combination therapy using a dna methyltransferase inhibitor, SGI-110, and the SRC family kinase inhibitor, Dasatinib. To understand the transcriptional changes that occur after treatment with SGI-110 with and without Dasatinib we performed RNAseq on two human RMS cell lines (Rh30 and RD) after 5 days of drug treatment.

overall_design: RNAseq was performed on Rh30 and RD human rhabdomyosarcoma cell lines treated with 0.5µM SGI-110, Dasatinib, or combination for 5 days in biological triplicates.

first: Lee

last: Helman


title: NKG2A educates uterine NK cells to optimise pregnancy outcomes in humans and mice

status: Public on Apr 29 2021

city: Cambridge

first: Norman

last: Shreeve

address: Rosie Hospital, Dept. of Obstetrics & Gynaecology, Robinson Way

department: O&G

country: United Kingdom

institute: Univerisity of Cambridge

summary: We report abnormal pregnancy outcomes in mice lacking NKG2A, including altered placental transcription. In humans, we find HLAB-21T snp to be associated with an increased risk of pre-eclampsia.

overall_design: We compared placental mRNA expression at E15.5 in genetically-matched fetuses who were closest to their litter mean weight, from Klrc1-/- and C57BL/6 dams. Samples were run in 2 batches, with a SAVANT correction for batch effect.

first: Francesco

last: Colucci


title: Pan-cancer analysis of IFI6 and its tumor promotor effects in esophageal squamous cell carcinoma

city: Jiangyin

first: Pengfei

last: Liu

state: Jiangsu province

address: NO. 163 Shoushan Road

institute: Jiangsu Jiangyin People's Hospital

summary: IFI6 is one of the ISG family, which is considered to play an important role in signal transduction pathway and immune response. However, there are few reports on IFI6, and only a few studies have reported that IFI6 may play a role in the occurrence and development of some tumors. We downloaded normal tissue and tumor tissue information from GTEx, TCGA and CCLE, and used survival analysis to study the relationship between IFI6 expression and OS, DSS, etc. We found that IFI6 was expressed in a variety of tumors, and the expression of individual tumors such as LUAD was very high. In addition, we also studied the relationship between IFI6 and immune cell infiltration enrichment, tumor immune microenvironment, methylation and so on. Furthermore, the high expression level of IFI6 was verified in esophageal squamous cell carcinoma (ESCC). In ESCC cells, IFI6 overexpression significantly promoted cell proliferation and growth, and inhibited cell apoptosis. In the lncRNA sequencing analysis, we found that IFI6 could regulate the expression of multiple genes, including HNRNPC, PEMT, INTS7, and several pathways, such as  VEGF signaling pathway, and PPAR signaling pathway. Our study provides new insights into the role of IFI6 in pan-cancer. IFI6 may represent a novel target for the treatment of esophageal squamous cell carcinoma.

overall_design: Examination 12 TE-1 cell samples, involving 3 cases of IFI6 overexpressed (OE) TE-1 cell samples , 3 cases of non-specific control (NC)-OE, 3 cases of sh-IFI6 and 3 cases of sh-NC. Analyse the genes and pathways that affected by different expression level of IFI6.

first: Liu

last: Pengfei

first: Zhang

last: Shuyu

first: Gao

last: Yi


title: Distinct transcriptome of moso bamboo in the phase transition from vegetative to reproductive growth

first: Lianfeng

last: Gu

overall_design: In this study, leaves from three-week bamboo, one-year bamboo, flower in next year bamboo, flowering bamboo and flower florets was used for RNA sequencing (RNA-seq) which covered the phase transition from vegetative to reproductive growth in moso bamboo.

first: Zeyu

last: Zhang


title: Chronic GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese insulin resistant mice

city: Indianapolis

first: Kyle

last: Haas

state: IN

address: 893 Delaware St

institute: Eli Lilly and Company

summary: Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor agonist, has been shown to deliver enhanced glycemic control and superior weight loss compared to a selective GLP-1 receptor (GLP-1R) agonist in patients with type 2 diabetes mellitus. However, the mechanism by which tirzepatide improves efficacy and how GIP receptor (GIPR) agonism contributes to the therapy is not fully understood. Here, hyperinsulinemic-euglycemic clamp studies were used to show that tirzepatide is a highly effective insulin sensitizer, improving insulin sensitivity in obese mice to a greater extent than GLP-1R agonism. To determine if GIPR agonism contributes to the insulin sensitization, we compared the effect of tirzepatide in obese wild-type and Glp-1r null mice. In the absence of GLP-1R induced weight loss, tirzepatide improved systemic insulin sensitivity by enhancing glucose disposal in WAT. To corroborate these results, chronic treatment with a long-acting GIPR agonist (LAGIPRA) was also found to enhance insulin sensitivity by increasing insulin stimulated glucose uptake in WAT. Interestingly, the effect of tirzepatide and LAGIPRA on insulin sensitivity was associated with reduced branched chain amino and keto acids in the circulation. Whole-body insulin sensitization was associated with pronounced upregulation of genes associated with the catabolism of glucose, lipid and BCAAs in brown adipose tissue. Together, our studies show that tirzepatide improved insulin sensitivity in a weight-dependent and -independent manner. These results highlight how GIPR agonism contributes to the therapeutic profile of dual GIP and GLP-1 receptor agonism, offering mechanistic insights into the clinical efficacy of tirzepatide.

overall_design: 24 total samples. Treatments include Vehicle, LAGIPRA, TZP, PairFed groups. N = 6 for each treatment group.

first: Ricardo

last: Samms

first: Michael

last: Christe

first: Kyla

last: Collins

first: Valentina

last: Pirro

first: Brian

last: Droz

first: Adrienne

last: Holland

first: Jessica

last: Friedrich

first: Samantha

last: Wojnicki

first: Debra

last: Konkol

first: Richard

last: Cosgrove

first: Ellen

last: Furber

first: Xiaoping

last: Ruan

first: Libbey

last: O'Farrell

first: Anne

middle: M

last: Rodgers

first: Mridula

last: Dogra

first: Jill

last: Willency

first: Yanzhu

last: Lin

first: Liyun

last: Ding

first: Christine

last: Cheng

first: Over

last: Cabrera

first: Daniel

last: Briere

first: Jorge

last: Alsina-Fernandez

first: Ruth

last: Gimeno

first: Julie

last: Moyers

first: Tamer

last: Coskun

first: Matthew

last: Coghlan

middle: W

last: Sloop

first: William

last: Roell


title: Upregulation of PGC-1α in Neurons Protects Against Experimental Autoimmune Encephalomyelitis

city: tianjin

first: chun

last: dang

address: Tianjin Anshan Road

institute: Tianjin Medical University General Hospital

summary:
Background/Aims:Increasing evidence have associated mitochondrial dysfunction and reactive oxygen species (ROS) generation to neuron loss in multiple sclerosis (MS). PGC-1α regulates mitochondrial biogenesis and respiration and plays a pivotal role in modulating ROS levels. Here, we investigated the potential function of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) in the mammalian MS disease model, EAE experimental autoimmune encephalomyelitis (EAE).
Methods:We used WT mice to evaluate the change of PGC during the course of EAE. The transgenic mice with neuron-specific overexpression of PGC-1α was applied to explore how PGC1 in neuron affects EAE outcome. A neuronal cell line of lentivirus transfection leading to PGC-1α markedly increased was applied to verify the protective effects of PGC1 in neurons. RNA-seq was employed to explore the potential target genes and signaling pathways.
Results: We observed that PGC-1α were decreased at 13d, continuously decreased at 20d, then mildly increased at 30d in wild-type (WT) EAE mice, which is accompanied with alterations of mitochondrial antioxidants SOD2, Prx3, Trx2 and UCP4,5. Our study revealed that PGC-1αf/f Eno2-Cre mice improved EAE clinical symptoms, ameliorated inflammation and demyelination in spinal cords, increased mitochondrial antioxidants SOD2, Prx3, Trx2 and UCPs, reduced the production of ROS and inhibited the apoptotic pathways. In addition, PGC-1αf/f Eno2-Cre mice showed decreased apoptotic neurons compared with the WT EAE mice. In vitro, overexpressing PGC-1α by lentivirus transfection revealed similar results with that of in vivo by using NSC-34 cells treated with 1mg/ml lipopolysaccharide (LPS). Furthermore, RNA-seq analysis showed that apoptotic processes were significantly enriched in the top 10 significant GO terms of differentially expressed (DE) gene and apotosis pathway was significantly enriched in KEGG pathway analysis.
Conclusion: Taken together, our findings indicate that upregulation of neuronal PGC-1α protected neuron apotosis in EAE and in vitro.

overall_design: NSC-34 cells RNA profiles of  test and control samples were generated by deep sequencing, using Illumina HiSeq 4000.

first: Chun

last: Dang

first: Bin

last: Han

first: Qian

last: Li

first: Ranran

first: Junwei

last: Hao


first: Charlotte

last: Summers

address: Box 157, Cambridge Biomedical Campus

department: Department of Medicine

institute: University of Cambridge

summary: We report the characterisation of the transcriptional changes associated with neutrophil hypersegmentation in primary human cells. We established a model of hypersegmentation by exposing healthy peripheral blood neutrophils to the angiotensin converting enzyme inhibitor (ACEi) captopril. Laser capture microdissection (LCM) was then adapted to isolate a population of hypersegmented neutrophils. Transcriptomic analysis of microdissected hypersegmented neutrophils was undertaken using RNA sequencing. This study reveals the transcriptomic signature of hypersegmented neutrophils, with five genes differentially expressed and modulated pathways including histone modification, protein-DNA complex assembly and antimicrobial humoral response.

overall_design: Transcriptomic analysis of hypersegmented human neutrophils.

first: Eléonore

last: Fox


title: The prevalence of human cytomegalovirus in colorectal cancer and viral gene expression profiles

city: Wenzhou

first: yuesheng

last: zhu

state: Zhejiang

address: Lucheng District

department: Department of Gastroenterology

institute: Second Affiliated Hospital, Wenzhou Medical University

summary: Five HCMV (+) CRC tissues detected by PCR were selected for RNA-seq. GEPs were pre-processed by Cutadapter and FastQC to remove jointed reads and low-quality reads. Tophat (v.2.0.0) was used to compare the sequences with Homo sapiens and HCMV genomes. The GEPs of HCMV was determined by Integrated Genomics Viewer (IGV) and Partek® Genomics Suite™ (version 6.5 beta, Partek Inc., St. Louis, MO, USA).

overall_design: HCMV gene expression profiles in 5 CRC tissues by transcriptome-sequencing.

first: Zhengzai

last: Cai

first: Lele

last: Ye

first: Yuesheng

last: Zhu

first: Xiangyang

last: Xue

first: Shanli


title: High-throughput sequencing analysis of mRNA and lncRNA in intestinal epithelial cells of wild-type mice, germ-free mice and wild-type mice infected with S. Typhimurium

first: Yunhuan

last: Gao

address: Wei Jin Road No. 94

department: School of Medicine

institute: Nankai University

summary: At the epigenetic level, lncRNAs play important roles in cell differentiation and function. We identified novel long-stranded non-coding RNA (GM1082) in intestinal epithelial cells.We used high-throughput sequencing to detail the global programme of gene expression and identified distinct classes of up or down regulated genes in intestinal epithelial cells of wild-type mice, germ-free mice and wild-type mice infected with S. Typhimurium.

overall_design: Intestinal epithelial cells were isolated by incubating in HBSS containing 2 mM EDTA for 30 min and shaking.

first: Ya

last: Wang


title: High-throughput sequencing analysis of mRNA in wild-type,GM1082-/- and lnc57Rik-/- mouse bone marrow-derived macrophages

summary: At the epigenetic level, lncRNAs play important roles in cell differentiation and function. We identified novel long-stranded non-coding RNA (GM1082) in BMDMs, which may play an important role in macrophage differentiation and function.We used high-throughput sequencing to detail the global programme of gene expression and identified distinct classes of up or down regulated genes in GM1082-/- and lnc57Rik-/-BMDMs.

overall_design: Bone marrow cells from wild-type,GM1082-/- and lnc57Rik-/- mice were cultured in 10% FBS medium containing M-CSF (20 ng/ml) for 6 days to generate BMDMs, and total RNA was extracted for high-throughput sequencing.


title: 16s rDNA-sequencing of gut microbiota in Temozolomide-treated glioma mice

city: Wuhan

first: Zhi-Qiang

state: Hubie

address: No.169 Donghu road

department: neurosurgery

institute: Zhongnan Hospital of Wuhan university

summary:
Purpose: Gut microbiota is associated with the progression of brain tumor. However, the alterations in the gut microbiota during glioma growth and temozolomide (TMZ) therapy remains to be understood.
Methods: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered by gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses.
Results: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased at the earlier stage of glioma development (T1), and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase and then a subsequent decrease. Twenty genera altered following TMZ treatment. The enrichment of Akkermansia and Bifidobacterium was observed only at the early stage following TMZ treatment (T2), but not at the later stage (T3). Additionally, the decrease of Anaerotruncus was slighter in TMZ group at T3 comparing to the vehicle group. The abundance of Intestinimonas increased constantly during the progression of glioma, but was unaffected by TMZ.
Conclusions: Glioma development and progression resulted in altered gut microbiota. TMZ reversed the decrease of Anaerotruncus in glioma at T3, and increased the abundance of Bifidobacterium with no influence on the increase of Intestinimonas. Short-term and long-term effects of TMZ treatment on the bacterial communities may be differential. This study will improve understanding the role of gut microbiota in glioma, and help develop gut microbiota as a potential therapeutic target.

overall_design: 16s rDNA-sequencing was performed on 48 samples to detect gut microbiota change during glioma progression and the effect of Temozolomide  on gut microbiota in glioma mice.

first: Xiao-Chong

first: Bang-Sheng

last: Wu

first: Yi

last: Jiang

first: Jie

first: Ze-Fen

first: Chao

last: Ma

first: Yi-Rong

last: Yao

first: Xiao-Qing

last: Jin


title: Transcriptome analysis of the effect of far-red light on hypocotyl elongation of pumpkin

city: Yangling

first: zhenchao

last: yang

address: China

institute: Northwest A&F University

summary: The mechanism of hypocotyl elongation in pumpkin mediate by end of day far red  was analyzed by transcriptome analysis

overall_design: One treatment and one control were designed, with three replicates per group

first: Zhenchao

last: Yang

first: Yongjun

first: Qi

last: liu


title: matchSCore: Matching Single-Cell Phenotypes Across Tools and Experiments

city: Barcelona

first: Gustavo

last: Rodriguez-Esteban

state: Catalonia

address: C. Baldiri Reixac, 4; Barcelona Science Park

department: Development

country: Spain

institute: Centro Nacional de Análisis Genómico

summary: Single-cell transcriptomics allows the identification of cellular types, subtypes and states through cell clustering. In this process, similar cells are grouped before determining co-expressed marker genes for phenotype inference. The performance of computational tools is directly associated to their marker identification accuracy, but the lack of an optimal solution challenges a systematic method comparison. Moreover, phenotypes from different studies are challenging to integrate, due to varying resolution, methodology and experimental design. In this work we introduce matchSCore (https://github.com/elimereu/matchSCore), a measure to fastly match cell populations across tools, experiments and technologies. We compared 14 computational methods and evaluated their accuracy in clustering and gene marker identification in simulated data sets. Further, we used matchSCore to project cell type identities across mouse or human cell atlas projects. Despite originated from different technologies, cell populations could be matched across datasets, allowing the assignment of clusters to reference maps and their annotation.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: We produced single-cell transcriptome profiles for pancreas and bladder tissue and projected our and publically available cell clusters onto a human or mouse organ reference atlas, respectively.

first: Holger

last: Heyn

last: Rodríguez-Esteban


title: Understanding the impact of integration copy number and genome location on heterologous gene expression in Rhodosporidium toruloides

city: Emeryville

first: John

last: Gladden

address: 5885 Hollis Street

institute: Agile BioFoundry

summary: Transcriptome sequencing to understand the impact of integration copy number and genome location on heterologous gene expression in R. toruloides

overall_design: Transcriptomics of wild type and four bisabolene producing R. toruloides strains (BIS18, BIS14, BIS3, and GB2) at 18 and 48 hours of growth in SD + 2% glucose

first: Mary

last: Bao Tran-Gymfi

first: Junko

last: Yaegashi

first: Joonhoon

last: Kim


title: A lncRNA HAR1B has a potential as a predictive marker for pazopanib therapy in patients with sarcoma

city: Sendai

first: Hideharu

last: Yamada

state: Miyagi

address: 4-1 Seiryocyo, Aobaku,

department: Department of Clinical Oncology

country: Japan

institute: Institute of Development, Aging and Cancer, Tohoku University

summary: Bone and soft tissue sarcomas are rare and highly heterogeneous mesenchymal malignancies. Their rarity makes it difficult to acquire clinical data of patients with specific histological subtypes of sarcoma from large clinical trials. The diagnoses and treatment of sarcomas need to be further developed. We show that a long non-coding RNA (lncRNA) HAR1B may serve as predictive biomarkers for pazopanib treatment in bone and soft tissue sarcomas. Multiplex real-time reverse transcription polymerase chain reaction and microarray analyses revealed that HAR1B and HOTAIR were differentially expressed in pazopanib-sensitive cells and responders. We further clarified this mechanism by showing that siRNA-knockdown of HAR1B led to an increased resistance to pazopanib in sarcoma cell lines. Gene expression profiles related to pazopanib sensitivity included cellular molecular pathways, including genes involved in von-Willebrand factor-related signaling. Our study demonstrates that lncRNA HAR1B expression affects cellular sensitivity to pazopanib in sarcoma cell lines and in patients with sarcoma.

overall_design: We collected 16 different bone and soft tissue sarcoma cell lines (cell lines) consisting of various tissue types. MTT assays using pazopanib against these cell lines were conducted to classify the cell lines into pazopanib effective (pazopanib-sensitive group) and ineffective (pazopanib-resistant group). The expression profiles of 90 lncRNAs known to be associated with cancer and stem cells in these cell lines were analyzed by multiplex qPCR to extract lncRNAs with differential expression between the two groups.  23 Tissues from patients with bone and soft tissue sarcoma who had been previously treated with pazopanib (patient tissues) were classified into two groups based on the therapeutic effect of pazopanib (responder group (R) and non-responder group (NR)). Patient tissues were subjected to comprehensive expression analysis by microarray targeting lncRNA as well as mRNA, and lncRNAs differentially expressed between the two groups were extracted. Among the lncRNAs also targeted in cell lines, candidate lncRNAs with similar expression differences also in patient tissues were extracted. Comprehensive gene and lncRNA expression analysis was also conducted in the cell lines using the same microarrays. Combined with the results from patient tissues, gene ontology (GO) analysis, and functional cluster analysis of genes and lncRNAs that showed common expression trends between pazopanib effective group and pazopanib ineffective group were performed. We examined which genes and lncRNAs were differentially expressed in the pazopanib-effective group in both cell lines and patient tissues.

first: Masanobu

last: Takahashi

first: Munenori

last: Watanuki

first: Mika

last: Watanabe

first: Sakura

last: Hiraide

first: Ken

last: Saijo

first: Keigo

last: Komine

first: Chikashi

last: Ishioka


title: Nrf2 overexpression rescues RPE morphology  in mouse models of retinitis pigmentosa [CD1-p40_analysis]

city: Boston

middle: N

last: Hutchinson

state: Massachusetts

address: 201 Wachusett Street

institute: Diamond Age Data Science

summary: Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in CD1 wild type mice

overall_design: Used AAV with an RPE-specific (Best1) promoter to isolate the contribution of Nrf2 overexpression to the RPE of CD1 mice at age p40.

first: David

last: Wu

last: Piper


title: Dual RNA-seq transcriptome analysis of chicken macrophage-like cells (HD11) infected in vitro with Eimeria tenella

city: Utrecht

first: Arnar Kari

last: Sigurdarson Sandholt

address: Yalelaan 2

department: IRAS

institute: Utrecht University

summary: In order to elucidate the infection mechanisms of Eimeria tenella and the chicken immune response, chicken macrophage cell cultures of cell line HD-11 were infected with Eimeria tenella strain Hougton sporozoites. Samples were taken at 0, 2, 4, 12, 24, 48 and 72 hours post-infection and, purified and mRNA sequenced. A dual-RNA seq analysis was carried out, comparing the expression of infected chicken macrophages with uninfected ones at the same time points post-infection and comparing E. tenella samples during the infection with a sample of pure sporozoites. The results show a variety of response signals in the chicken, both previously known and unknown, as well as a clear role for different sets of SAG and MIC proteins for sporozoites and merozoites of E. tenella

sample_organism:
Eimeria tenella
Gallus gallus

platform_organism:
Eimeria tenella
Gallus gallus

overall_design: mRNA profiles of chicken macrophage cells, both uninfected and infected with Eimeria tenella sporozoites

first: Arnar-Kári

last: Sigurðarson Sandholt

first: Feifei

last: Xu

first: Robert

last: Söderlund

first: Anna

last: Lundén

first: Karin

last: Troell

first: Staffan

middle: G

last: Svärd

first: Eva

last: Wattrang


title: Fibroblast Gata4 and Gata6 promote myocardial adaptation to pressure overload by enhancing cardiac angiogenesis

city: Mannheim

first: Joerg

last: Heineke

state: Baden Wuttemberg

address: Ludolf-Krehl-Str. 7-11

department: – Department of Cardiovascular Research (HKF)

country: Germany

institute: Medizinische Fakultät Mannheim

summary: Here, we show that adult cardiac fibroblasts express the cardiomyocyte transcription factors GATA-4 and GATA-6 to promote adaptive remodeling in pressure overload induced cardiac hypertrophy. Using a mouse model with specific single or double deletion of Gata4 and Gata6 in stress activated fibroblasts, we found a reduced myocardial capillarization in mice with Gata4/6 double deletion following pressure overload, while single deletion of Gata4 or Gata6 had no effect. Importantly, we confirmed the reduced angiogenic response using an in vitro co-culture system with Gata4/6 deleted cardiac fibroblast and endothelial cells. A comprehensive RNA-sequencing analysis revealed an upregulation of anti-angiogenic genes upon Gata4/6 deletion in fibroblasts, and siRNA mediated downregulation of these genes restored endothelial cell growth. In conclusion, we identified a novel role for the cardiac transcription factors GATA4 and GATA6 in heart fibroblasts, where both proteins act in concert to promote myocardial capillarization and heart function by directing intercellular crosstalk.

overall_design: Total of 15 samples were analyzed with 3 replicates in each group

first: Gesine

last: Dittrich

first: Julio

last: Cordero


title: Nrf2 overexpression rescues RPE morphology  in mouse models of retinitis pigmentosa [rd1-p40_analysis]

first: John

summary: Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in the PDEb (rd1) model of retinal degeneration

overall_design: Used AAV with an RPE-specific (Best1) promoter to isolate the contribution of Nrf2 overexpression to the rescue of the RPE  in the PDEb (rd1) model of retinal degeneration at age p40.

first: Mary


title: Nrf2 overexpression rescues RPE morphology  in mouse models of retinitis pigmentosa [rd1-p20_analysis]

overall_design: Used AAV with an RPE-specific (Best1) promoter to isolate the contribution of Nrf2 overexpression to the rescue of the RPE  in the PDEb (rd1) model of retinal degeneration at age p20.


title: FoxP1 is sufficient and required for skeletal muscle wasting

first: Boston University

last: Microarray and Sequencing Resource

address: 72 East Concord Street, E631

department: Microarray and Sequencing Resource

institute: Boston University

summary:
Skeletal muscle wasting is a devastating consequence of cancer that affects up to 80% of cancer patients and associates with reduced survival. Herein we identified the transcriptional repressor protein, Forkhead box P1 (FoxP1), as a downstream target gene of FoxO1 whose skeletal muscle expression is elevated in multiple models of cancer cachexia and in patients with cancer who exhibit cachexia. Through generation of inducible skeletal muscle-specific FoxP1 over-expressing (FoxP1iSkmTg/Tg) mice, we demonstrate that FoxP1 upregulation is sufficient to induce features of cachexia, including body and skeletal muscle wasting characterized by reduced muscle fiber cross-sectional area of type IIX/B muscle fibers. Muscles from FoxP1iSkmTg/Tg mice also showed significant muscle damage and myopathy characterized by the accumulation of p62 and cellular material-filled vesicles, the presence of centrally nucleated myofibers, and were significantly weaker than controls. In the context of cancer cachexia, blocking FoxP1 upregulation prevented the cancer-induced repression of target genes critical to muscle structural integrity and repair, including Myocyte enhancer factor 2c (Mef2c), improved muscle ultrastructure and significantly attenuated muscle fiber atrophy. We further show that the muscle wasting phenotype induced by FoxP1 required the activity of histone deacetylase (HDAC) proteins, which are well-established to cooperate with FoxP1 to mediate gene repression, and which were necessary for FoxP1-dependent repression of Mef2c. In summary, we identify FoxP1 as a negative transcriptional regulator of skeletal muscle mass and function, whose up-regulation mediates cancer-induced muscle wasting.
We used microarrays to investigate the genome-wide transcriptional networks regulated by the FoxO1 and FoxP1 transcription factors in skeletal muscle of tumor-bearing mice.

overall_design: Tibialis anterior muscles of 10-week old male mice were directly injected with AAV9 vectors encoding scrambled-shRNA, FoxO1-shRNA or FoxP1-shRNA. Two weeks later mice were subcutaneously inoculated with either C26 cells into both flanks (C26 groups), or PBS (Sham group). Muscle tissues from all mice were subsequently harvested at tumor endpoint (26 days post-C26 inoculation) for RNA extraction and RT-qPCR for confirmation of successful knockdown of FoxO1 or FoxP1 in groups receiving AAV9-FoxO1-shRNA or AAV9-FoxP1-shRNA vectors.  Equal amounts of RNA were subsequently pooled from muscle tissue from three animals per group, followed by hybridization on Affymetrix microarrays.

first: Sarah

last: Judge

first: Andrew

first: Daria

last: Neyroud

first: Rachel

last: Nosacka


title: Nrf2 overexpression rescues RPE morphology  in mouse models of retinitis pigmentosa

last: Hutchinson

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

overall_design: Refer to individual Series


title: Neutralization of IL-2 enables tissue PD-L1 to effectively prevent acute GVHD while preserving strong GVL activity

city: Duarte

first: Xiwei

last: Wu

address: 1500 E. Duarte Rd.

department: Computational and Quantitative Medicine

institute: City of Hope National Medical Center


title: Single cell RNA sequening Analysis of T cell genomic change in the HCT recipients given Tacrolimus or anti-IL-2 treatment

summary: Purpose:  The goals of this study are to compare T cell genomic change with Tacrolimus or anti-IL-2 treatment

overall_design: Compare T cell genomic difference  in spleen of the HCT recipients with Tacrolimus or anti-IL-2 treatment

first: Qingxiao

last: Song

first: Defu

last: Zeng


title: Distinct Immune-microenvironment Construction Diversely Responded to Induction Immunotherapy among Multiple Primary Lung Adenocarcinoma

city: Guangzhou

first: Chao

last: Zhang

address: Zhongshan Er Road

department: Thoracic Oncology

institute: Guangdong Lung Cancer Institute

summary: We performed an integrated multi-omics analysis including single-cell RNA sequencing in one multiple lung nodules patient treated with pembrolizumab. We found that responded nodule showed notably higher infiltrating macrophages and lymphocytes through mIHC. Much higher genomic somatic copy number variants events were observed in two non-responded nodules. scRNA highlighted HLA-related gene down-regulation in both non-responded nodules indicating one of its immune evasion mechanisms. Moreover, significantly high proportion of Tissue resident memory T cells were found in responded nodule which has been validated to be both predictive and prognostic signature among multiple cancer types through external datasets. As for macrophages, MDSC-like subtype was predominantly observed in responded nodule while TAM-like subtype mainly in other two non-responded nodules. Through TCGA-LUAD cohort, MDSC-like macrophages showed inferior prognostic value compared to TAM-like macrophages suggesting a potential resistant mechanism along with increased responded immune infiltration. This study provides an in-depth multi-omics analysis on firstly reported multiple primary lung adenocarcinoma receiving immunotherapy and describes potential early immune signals responding to immunotherapy, as well as impaired antigen-presenting process in sub-solid nodules which may attribute to primary resistant of immunotherapy.

overall_design: Three surgically resected lung adenocarcinoma treated in freshly digested single cell suspension were set for single cell RNA sequencing.

first: Wen-zhao

last: Zhong


title: Expression profiles and potential functions of long non-coding RNAs and mRNAs in autoimmune pulmonary alveolar proteinosis patients

city: Beijing

first: Jinghua

last: Yang

address: 32 North Third Ring Road West, Haidian District, Beijing

institute: Beijing Zhiyun data technology co. LTD

type:
Expression profiling by array
Non-coding RNA profiling by array

summary: Autoimmune pulmonary alveolar proteinosis (APAP) is a rare lung disease which may be closely associated with autoantibody. However, there is little known about the function of long non-coding RNAs (lncRNAs) in APAP.To further investigate the role of lncRNAs in APAP, we screened the differential expression profiles of lncRNAs and mRNAs in peripheral blood samples between five APAP patients and five matched healthy controls. We analyzed the regulatory networks of lncRNA-mRNA and lncRNA-miRNA-mRNA via bioinformatics methods. This study identified differentially expressed (DE) lncRNAs and their potential corresponding mRNAs to provide a basis for the study of APAP pathogenesis.

overall_design: Expression profiling was performed on the peripheral blood samples to identify differentially expressed (DE) lncRNAs and mRNAs in 5 APAP patients and 5 healthy volunteers. Twenty DE lncRNAs and mRNAs were validated by quantitative real-time PCR (qRT-PCR). A coding-non-coding gene co-expression (CNC) network and competing endogenous RNA (ceRNA) network were constructed to reveal the core genes in APAP. Gene Oncology (GO) and KEGG enrichment analysis were performed.

first: Yanl-Li

first: Wen-Shuai

last: Xu

first: Ruo-Lan

last: Xiang

first: Kai-Feng

first: Xin-Llun

last: Tian


title: Transcriptome profiling of tumors from Kenyan triple negative breast cancer (TNBC) patients.

city: Birmingham

first: Sooryanarayana

last: Varambally

state: Alabama

address: 1824 6th Avenue S

department: Pathology

institute: University of Alabama

summary: Triple negative breast cancer is an aggressive phenotypic breast cancer characterized by ER negative, PR negative and Her2 negative immunohistochemistry status. We embarked on a study to explore the transcriptome of Kenyan TNBC patients and identify potential biomarkers specific to Kenyan population. The transcriptome sequencing of tumors from Kenyan TNBC patients and comparisons with African American and Caucasian TNBC transcriptomes revealed several interesting targets and dysregulated pathways.

overall_design: Total RNA was extracted from FFPE (Formalin-Fixed Paraffin-Embedded) sections from each of 15 Kenyan TNBC patients. RNA-seq experiment was performed to study RNA level expression profiles of protein-coding and non-coding genes. The transcriptome sequencing profile of Kenyan TNBC patients is compared with that of African American and Caucasian TNBC patients (obtained from University of Alabama at Birmingham [UAB]) and genes with Kenyan TNBC specific expression were identified.  Insilico validations using TCGA breast invasive carcinoma dataset further aided in identification of potential biomarkers.

first: Mansoor

last: Saleh

first: Upender

last: Manne

last: Varamabally

first: Darshan

last: Chandrashekar

first: Shahin

last: Sayed

first: Asim

last: Jamal

first: Peter

last: Bird

first: Hyung-Gyoon

last: Kim


title: Nrf2 overexpression rescues RPE morphology  in mouse models of retinitis pigmentosa [rd1-p20_p40_analysis]

first: John

last: Hutchinson

summary: Contribution of Nrf2 overexpression to the rescue of the RPE and/or photoreceptors in the PDEb (rd1 and rd10) model of retinal degeneration

overall_design: Used AAV with an RPE-specific (Best1) promoter to isolate the contribution of Nrf2 overexpression to the rescue of the RPE  in the PDEb (rd1 and rd10) model of retinal degeneration at age p20 and p40.

first: David

last: Wu

first: Mary

last: Piper


title: Transcriptome profiling of tumors from Caucasian and African American triple negative breast cancer (TNBC) patients.

summary: Triple negative breast cancer is an aggressive phenotypic breast cancer characterized by ER negative, PR negative and Her2 negative immunohistochemistry status. We embarked on a study to explore the transcriptome of African American and Caucasian TNBC patients and identify race specific biomarkers.

overall_design: Total RNA was extracted from FFPE (Formalin-Fixed Paraffin-Embedded) sections from each TNBC patients. RNA-seq experiment was performed to study RNA level expression profiles of protein-coding and non-coding genes. The transcriptome sequencing profile of African American and Caucasian TNBC patients were compared to identify race specific TNBC biomarkers.

first: Clayton

last: Yates


title: Vascular Aging in the Invertebrate Chordate, Botryllus schlosseri

city: Santa Barbara

first: Delany

last: Rodriguez

address: Biological Science Building  RM1201 University of California Santa Barbara

department: Molecular Cellular and Developmental Biology

institute: University of California Santa Barbara

summary: Ageing causes a progressive deterioration of the structure and function of vascular cells that results in a decline of vascular functionality. Impaired functionality of vascular cells is a key factor that triggers several age-related vascular diseases. Most of our understanding of this process comes from in vitro studies. Further understanding of the mechanism underlying vascular aging in vivo are needed to get new insights into the pathobiology of age-associated vascular diseases. Here we use a combination of transcriptomics, immunostaining, and in vivo pharmacological and regeneration assays coupled with the extracorporeal vasculature of the invertebrate chordate Botryllus schlosseri  (which is large, transparent, accessible and easy to manipulate) and show that we can study morphological, transcriptional and functional age-associated changes of vascular cells that are similar to those of mammalian vascular cells from tissue culture and fixed vascular cells. We showed that age-associated changes in the cytoskeleton and the ECM reshape vascular cells into flatten and elongated form and heavily accumulate Collagen, rendering the vessels into more rigid and less responsive to pharmacological insults. These changes did not alter the regeneration potential of aged blood vessels and newly regenerated vascular cells retained the same aged phenotype. Furthermore, we found that a subset of blood circulating hemocytes showed reduced proliferation while increasing apoptosis in aged animals.

overall_design: mRNA profiles of 3 generations of Botryllus schlosseri colonies (each in triplicates) using illumina deep sequencing and analyzed for differential expression between the youngest and the oldest age. We used the following genotypes: SB825_g1 (3 years old), SB825_g2(F1 from SB825_g1 genotype 2 years old), SB825_g3 (F1 from SB825_g2 genotype 4 months old);SMG_g1 (3 years old), SMG_g2(F1 from SMG_g1 genotype 2 years old), SMG_g3 (F1 from SMG_g2 genotype 4 months old); SMH_g1 (3 years old), SMH_g2(F1 from SMH_g1 genotype 2 years old), SMH_g3 (F1 from SMH_g2 genotype 4 months old)

first: Daryl

middle: A

last: Taketa

first: Roopa

last: Madhu

first: Susannah

last: Kassmer

first: Dinah

last: Loerke

first: Megan

last: Valentine

first: Anthony

last: De Tomaso


title: Gene expression profiles from heart, lung and liver samples of total body irradiated minipigs

status: Public on Apr 27 2021

city: Northbrook

first: Michael

last: Falduto

state: IL

address: 1808 Janke, Unit M

institute: GenUs BioSystems, Inc.

summary: The present work identified gene expression changes in response to total body irradiation (TBI) in heart, lungs, and liver tissue in Gottingen minipigs. Animals were exposed to 1.7 Gy, 1.9 Gy, 2.1 Gy and 2.3 Gy of TBI and were followed for 45 days. Organ samples were collected at the end of 45 days or sooner if the animal displayed morbidity necessitating euthanasia. RNA was extracted and gene expression profiling studied using Agilent arrays.

overall_design: Six animals per dose group were used in the study. Three sham irradiated animals served as control. Microarrays were performed in two batches. First batch included sham controls, 1.7Gy, 2.1Gy and 2.3Gy samples while second batch included same sham animals and 1.9Gy animals

first: Sunita

last: Chopra

first: Maria

last: Moroni

first: Shannon

middle: E

last: Martello

first: Michelle

last: Bylicky

first: Jared

last: May

first: Bernadette

last: Hritzo

first: Laurel

last: MacMillan

first: C

last: Coleman

first: Molykutty

last: Aryankalayil


title: Next Generation Sequencing Facilitates Quantitative Analysis of IL-2-STAT5 pathway change in the WT or PD-L1-/- HCT recipients with or without anti-IL-2 treatment

first: Xiwei

last: Wu

summary: Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare STAT5 pathway change with or without neutralization of IL-2

overall_design: Examination IL-2-STAT5 pathway on CD8+ T or CD4+ T cells in spleen and gut of the HCT recipients with or without anti-IL-2 treatment

first: Qingxiao

last: Song

first: Defu

last: Zeng


title: MYB ChIP-Seq of K562 cells

city: Oslo

first: Roza Berhanu

last: Lemma

address: Blindernveien 31

department: Department of Biosciences

institute: University of Oslo

type: Genome binding/occupancy profiling by high throughput sequencing

summary: We analyzed genome-wide chromatin binding of the transcription factor c-Myb using ChIP-Seq. K-562 cell lines stably expressing N-termianl 3xTY tagged Myb (pEFneo-3xTY-Myb) and control cell lines expressing the tag (pEFneo-3xTY) were used.

overall_design: K-562 cells stably expressing pEFneo-3xTY-Myb and pooled control cell lines expressing pEFneo-TY were crosslinked followed by nuclei isolation and sonication. Sonicated chromatin was immunoprecipitated with a mouse monoclonal anti-TY1 antibody followed by elution of immnoprecipitated chromatin into two fractions. Pooled fractions were subjected to DNA purification using 'ChIP DNA clean concentrator KIT' (Zymo research #D5205). Libraries were prepared using ThruPLEXⓇ low-input sample-prep method. 75 bp single-end reads were generated from three biological replicates using the Illumina NextSeq 500 sequencer.

first: Odd

last: Gabrielsen

first: Marit

last: Ledsaak

first: Roza

middle: B


title: Fragmentation of apolipoprotein E4 is required for differential expression of inflammation and activation related genes in microglia cells

city: Boise

first: James

middle: David

last: Beck

state: ID

address: 1910 University Drive

department: Biology

institute: Boise State University

summary: This study assessed the effects of the full-length ApoE4 protein on modulating the transcriptome of BV2 microglial cells and comparing to a previous report looking at an amino-terminal fragment of ApoE4 (residues 1-151). The results indicated that full-length ApoE4 had a very small effect on gene expression compared to the fragment.  Only 48 differentially expressed genes (DEGs) were identified (p<0.05, and greater than 2-fold change). A gene ontology analysis of these DEGs indicated that they are not involved in inflammatory and activation processes, in contrast to the genes upregulated by the E4-fragment. In addition, genes that showed a negative fold-change upon FL-E4 treatment typically showed a strong positive fold-change upon treatment with the fragment (Pearson’s r=-0.7). Taken together, these results support the hypothesis that a key step in the conversion of microglia to an activated phenotype is proteolytic cleavage of FL-ApoE4. Therefore, the neutralization of this amino-terminal fragment of ApoE4, specifically, may serve as an important therapeutic strategy in the treatment of AD.

overall_design: Total RNA-sequencing was performed to assess transcriptional changes that occurred in BV2 microglial cells following treatment with human full-length ApoE4

first: Troy

last: Rohn

first: Jim

first: Eric

last: Hayden


title: Vitis riparia bud transcriptome in response to long and short photoperiod.

city: Brookings

first: Anne

last: Fennell

state: South Dakota

address: North Campus Drive

department: Department of Plant Science

institute: South Dakota State University

summary: The transition of axillary grapevine buds from paradormancy to endodormancy is an important mechanism for winter survival. Maintenance of paradormancy and transition to endodormancy may be synchronized by factors including phytohormones, genes, transcription factors and other molecular regulators. In the present study we used age matched buds from vines subjected to 28 days of short day (SD; 13h) treatment or continued long day (LD; 15h) photoperiod for high throughput transcriptome profiling.

overall_design: Three biological replicates of LD and SD bud RNA were sequenced and analysed.

first: Shuchi

last: Smita


title: Epithelial Hypoxia-Inducible Factor 2α Facilitates the Progression of Colon Tumors through Recruiting Neutrophils

city: Ann Arbor

first: Justin

last: Colacino

state: MI

address: 6651 SPH1, 1415 Washington Heights

department: Environmental Health Sciences

institute: University of Michigan

summary: Inflammation is a significant risk factor for colon cancer. Recent work has demonstrated essential roles for several infiltrating immune populations in the metaplastic progression following inflammation. Hypoxia and stabilization of hypoxia-inducible factors (HIFs) are hallmark features of inflammation and solid tumors. Previously, we demonstrated an important role for tumor epithelial HIF-2α in colon tumors; however, the function of epithelial HIF-2α as a critical link in the progression of inflammation to cancer has not been elucidated. In colitis-associated colon cancer models, epithelial HIF-2α was essential in tumor growth. Concurrently, epithelial disruption of HIF-2α significantly decreased neutrophils in the colon tumor microenvironment. Intestinal epithelial HIF-2α-overexpressing mice demonstrated that neutrophil recruitment was a direct response to increased epithelial HIF-2α signaling. High-throughput RNA sequencing (RNA-seq) analysis of HIF-2α-overexpressing mice in conjunction with data mining from the Cancer Genome Atlas showed that the neutrophil chemokine CXCL1 gene was highly upregulated in colon tumor epithelium in a HIF-2α-dependent manner. Using selective peptide inhibitors of the CXCL1-CXCR2 signaling axis identified HIF-2α-dependent neutrophil recruitment as an essential mechanism to increase colon carcinogenesis. These studies demonstrate that HIF-2α is a novel regulator of neutrophil recruitment to colon tumors and that it is essential in shaping the protumorigenic inflammatory microenvironment in colon cancer.

overall_design: Comparing gene expression profiles of colon tissues from Hif2a (+/+; n=9) and Hif2a (LSL; n=9) mice

first: Yatrik

last: Shah


title: RNA sequencing of mesenteric lymph node ILC2s  from non-treated mice

city: New York

first: Gregory

last: Putzel

state: NY

address: 430 East 29th Street

department: Microbiology

institute: NYU Langone Health

summary: Transcriptomes of ILC2s sorted as KLRG1+CD127+CD90+Lin-CD45+ cells from mesenteric lymph nodes of non-treated mice were analyzed.  The mice were part of the experiments described in PMID: 29496881 and were sequenced together with samples submitted in GSE108884.

overall_design: ILC2s were sorted from the mesenteric lymph nodes of three naïve mice.

first: Saya

last: Moriyama

first: Anne-Laure

last: Flamar

first: David

last: Artis


title: Role of Cebpd on transcriptional output in 4T1 mouse triple negative breast cancer cells

first: Xiaoqing

last: Wang

state: MA

address: 450 Brookline Ave

institute: Dana Farber Cancer Institute

summary: Cebpd is a transcription factor regulating cytokines. We determined the role of Cebpd in the regulation of transciptional output. We generated 4T1 breast cancer cells with CRISPR/Cas9 mediated Cebpd knockout. We treated control sgRosa26 and sgCebpd cells with vehicle or IFNgamma (20ng/ml) for 24 hours and isolated RNA for sequencing.

overall_design: Examination of transcriptome in Cebpd intact and Cebpd loss 4T1 breast cancer cells in response to IFNgamma.

first: Collin

last: Tokhein

first: Shengqing

last: Gu

first: Binbin


title: Transcriptional dysregulation in developing trigeminal sensory neurons in the LgDel mouse model of DiGeorge 22q11.2 deletion syndrome.

city: Roanoke

first: Thomas

last: Maynard

state: VA

address: 2 Riverside Circle

institute: Virginia Tech Carilion/FBRI

summary:
Purpose: The cellular composition of the trigeminal ganglion is altered in the mouse model of 22q11.2 deletion syndrome (the LgDel mouse). The goal of this study is to use RNA-seq to identify transcriptional differences in the embryonic day 10.5 trigeminal ganglion that prefigure changes in mature cell identity in this cranial nerve ganglion.
Methods: Trigeminal ganglion mRNA profiles of E10.5 trigeminal ganglia from WT and LgDel mice were generated by deep sequencing.  Ganglia samples were prepared as pools of at least 6 ganglia each, from at least 3 embryos.  5 biological replicates of LgDel and WT pools were sequenced.  Paired-end libraries were constructed according to the Illumina protocol for the HiSeq2000 platform. Each pooled CNgV RNA sample, defined as a single biological replicate, was fragmented prior to cDNA conversion to ensure transcript coverage. WT (n = 5 replicates) and LgDel (n = 5 replicates) were subjected to sequencing (~100 million paired-end reads/replicate, 100 bp read length) on the Illumina HiSeq2000 platform. Quality-filtered reads were aligned against the mouse reference genome (GRCm38/mm10) using HISAT2 (v.2.1.0). These alignments were indexed using SAMtools (v.1.4) and aligned reads assembled into transcripts using Cufflinks (v.2.2.1) (58). Differential expression analysis was performed using Cufflinks.  Validation of key transcriptional differences was performed by SYBR Green qPCR.
Results: For WT RNA-Seq, 111–123 million paired-end reads were generated after QC filtering, and 97.3–97.9% of the reads aligned to the mouse genome reference sequence. For LgDel RNA-Seq, 77–137 million paired-end reads were generated after QC filtering, and 94.3–97.8% of the reads aligned to the mouse genome reference sequence. LgDel versus wild-type (WT) CNgV transcriptomes differ significantly at E10.5 just after the ganglion has coalesced. Some changes parallel altered proportions of cranial placode versus cranial neural crest-derived CNgV cells. Others are consistent with a shift in anterior–posterior patterning associated with divergent LgDel cranial nerve differentiation. The most robust quantitative distinction, however, is statistically verifiable increased variability of expression levels for most of the over 17 000 genes expressed in common in LgDel versus WT CNgV.
Conclusions: Quantitative expression changes of functionally relevant genes and increased stochastic variation across the entire CNgV transcriptome at the onset of CN V differentiation prefigure subsequent disruption of cranial nerve differentiation and oropharyngeal function in LgDel mice.

overall_design: RNA-seq analysis of trigeminal nucleus in LgDel mouse

first: Anelia

last: Horvath

last: Bernot

first: Beverly

last: Karpinski

first: Qianqian

last: Zheng

first: Liam

last: Spurr

first: Jacqueline

last: Olender

first: Claire

last: Fraser

first: Anthony-S

last: LaMantia

first: Norman

middle: H

last: Lee


title: Dual BTK/SYK inhibition with CG-806 disrupts B-cell receptor and Bcl-2 signaling networks in mantle cell lymphoma

city: Portland

first: Alexey

last: Danilov

state: Oregon

address: 3681 SW Sam Jackson Rd

department: Knight Cancer Institute

institute: Oregon Health and Science University

summary: We show the impacts of the BTK/SYK inhibitor CG806 on RNA-seq gene expression in mice xenografted with Mantle Cell Lymphoma

overall_design: Examination of MCL tumor xenografts in mice either treated with a control or CG-806

first: Nur

last: Bruss

middle: V


title: P0NeuronData and e12p5-wc-neuron

city: La Jolla

first: Samuel

last: Pfaff

state: CA

address: 10010 N Torrey Pines Rd

institute: Salk Institute for Biological Studies

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

overall_design: Refer to individual Series


title: E12.5 spinal cord scRNA-seq [e12p5-wc-neuron]

summary: Cells along the entire spinal cord were isolated from two E12.5 embryos from two litters and were subjected to scRNA-seq as separate samples. These datasets were merged posthoc.

overall_design: Characterization of E12.5 spinal cord neurons

first: Neal

last: Amin

first: Marito

last: Hayashi

first: Peter

last: Osseward


title: Conserved genetic signatures parcellate cardinal spinal neuron classes into local and projection subsets [P0NeuronData]

summary:
We uncovered orderly genetic tiers that sequentially divide groups of neurons by their motor- sensory, local-long range, and excitatory-inhibitory features. The genetic signatures defining neuronal projections were tied to neuronal birthdate and conserved across cardinal classes. The intersection of cardinal class with projection markers provides a unifying taxonomic solution for systematically identifying distinct functional subsets.
In order to minimize technical and biological variabilities, timed-matings were set up to obtain both Vglut2:Cre; tdTomato and Vgat:Cre ;tdTomato neonates at postnatal day 0 on the experiment day. Sex of the animals were visually inspected and verified by genotyping (40). Lumbar segments were dissected from Vglut2; tdTomato (2 female and 1 male) and Vgat; tdTomato (2 female and 1 male) in aCSF. Cell dissociation was conducted using Papain following the manufacturer’s instruction (Worthington Biochemical) with 5% Trehalose, 50uM APV, and 800uM KA added during the dissociation process (41). Via FACS (FACSDIVA, BD), 30,000 Vglut2; tdTomato cells and 30,000 Vgat;tdTomato cells were sequentially collected into 500ul of FACS buffer (DMEM w/o Phenol Red; 1mM EDTA; 25mM Hepes pH7.0; 5% FBS). Cell suspension was centrifuged at 300 rcf for 2 minutes, and supernatant was removed leaving 60 ul of FACS buffer and cell pellet. The cells were resuspended, and 33.4 ul of the resuspended cells (~30,000 cells) were loaded onto the 10X Chromium Controller using Chromium Single Cell 3’ v2 reagents.

overall_design: Vglut2:Cre; tdTomato+ and Vgat:Cre ;tdTomato+ P0 spinal neurons


title: Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses in autoimmune disorders

city: Dundee

first: Stephan

last: Wilmes

address: Dow Street

department: School of Life Sciences

institute: University of Dundee

summary: High levels of inflammation are often present in autoimmune diseases and can impact the functioning of the immune system. Specifically, how surrounding inflammation affects cytokine responses has not been extensively studied. We use IL-6 and IL-27, two cytokines playing opposite roles in inflammation, to ask how cytokines adapt to the inflammatory environment. We show that IL-27 induces a more sustained STAT1 phosphorylation than IL-6, with the two cytokines inducing comparable levels of STAT3 phosphorylation. Mathematical and statistical modelling of IL-6 and IL-27 signaling identify STAT1 (or STAT3) binding dynamics to GP130 (or IL-27R) as the main parameter contributing to sustained pSTAT1 by IL-27. Mutation of Tyr613 on IL-27R decreased IL-27-induced STAT1 phosphorylation by 80%, with limited effect on STAT3 phosphorylation. The strong receptor/STAT coupling by IL-27 led to the induction of a unique gene expression program by this cytokine, which required sustained STAT1 phosphorylation and IRF1 expression and was enriched in classical Interferon Stimulated Genes. Interestingly, the STAT/receptor coupling exhibited by IL-6/IL-27 was altered in Crohn’s disease and SLE patients. IL-6/IL-27 induced a more potent STAT1 activation in SLE patients than in healthy controls, which can be explained by the higher STAT1 expression in these patients. Partial inhibition of JAK activation by sub-saturating doses of Tofacitinib lowered the levels of STAT1 activation by IL-6, representing a new strategy to treat auto-immune disorders where cytokine responses are dysregulated.

overall_design: Human Th-1 cells were stimulated under 7 conditions each; control (unstimualted), IL-27 1h, IL-27 6h, IL-27 24h, HypIL-6 1h, HypIL-6 6h, HypIL-6 24h. Each condition has three biolocial replicates (human donors). IL-27 was used at 2nM and HypIL-6 was used at 10nM

first: Polly-Anne

last: Jeffrey

first: Jonathan

last: Martinez-Fabregas

first: Maximillian

last: Hafer

first: Paul

middle: K

last: Fyfe

first: Elizabeth

last: Pohler

first: Silvia

last: Gaggero

first: Martín

last: López-García

first: Suman

last: Mitra

first: Jacob

last: Piehler

first: Carmen

last: Molina-París

first: Ignacio

last: Moraga


title: Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer

status: Public on Apr 26 2021

city: Philadelphia

first: Christopher

last: McNair

state: PA

address: 833 Chestnut Street Ste 1140

department: Medical Oncology

institute: Thomas Jefferson University


title: Rescue of advanced Pompe disease in mice with hepatic expression of secretable acid α-glucosidase

city: Madrid

first: Manuel

middle: J

last: Gomez

state: Madrid

address: Melchor Fernández Almagro, 3

institute: CNIC

summary: Pompe disease is a neuromuscular disorder caused by mutations in the gene encoding for the lysosomal enzyme acid α-glucosidase (GAA). GAA converts lysosomal glycogen to glucose, and its deficiency leads to pathologic glycogen accumulation. Enzyme replacement therapy (ERT) is the only available treatment for Pompe disease at the moment with several shortcomings. We have shown that liver expression of secGAA has better therapeutic efficacy than non-engineered GAA after long-term treatment of four months old Gaa-/- mice with low vector doses. Based on those results, we have treated severely affected nine months old Gaa-/- mice with the AAV-secGAA vector and followed the animals for nine months thereafter. At the end of the study, AAV-treated Gaa-/- mice showed complete rescue of the Pompe phenotype. Transcriptomic profiling of skeletal muscle highlighted mitochondrial bioenergetics defects, supported by electron microscopy, western blotting and biochemical findings, which were partially corrected after AAV treatment. Together, these results provide insight into the reversibility of advanced Pompe disease in the Gaa-/- mouse model via liver gene transfer of secGAA.

overall_design: Transcriptomic analysis comparing the gene expression profile in quadriceps muscle from WT and GAA KO mice, with that of GAA KO mice treated with secGAA.

first: U

last: Cagin

first: F

last: Mingozzi


title: Distinct metabolic perturbations associated with pediatric Plasmodium falciparum malaria during Intra-erythrocytic development stage

city: Abu dhabi

first: Youssef

last: Idaghdour

state: Abu dhabi

address: Saadiyat Marina District

country: United Arab Emirates

institute: NYUAD

summary: The goal of this study was to interrogate the impact of metabolic perturbations during P. falciparum infection on the host immune response in a cohort of West African children sampled and profiled before and during infection. Here, we use integrative metabolomics-transcriptomic approach to the investigate potential immunomodulatory effects of serum metabolites during the blood stage of infection.

overall_design: 72 peripheral blood mRNA profiles of 36 children between the ages of (2-12) sampled and profiled before and during P. falciparum infection.

first: Abdrabou

last: Wael

first: Diawara

last: Aïssatou

first: Dieng

last: Mame Massar

first: Idaghdour

last: Youssef


title: Comparison of the RB loss-induced transcrptiome in hormone-therapy sensitive and castration-resistant prostate cancer [RNA-seq]

summary: These studies examine the biological networks altered after RB loss across prostate cancer progression.

overall_design: Transcriptome alterations in resposne to RB loss after AR stimulation were assessed in early (LNCaP-shCon and LNCaP-shRB) and late (C42-shCon and C42-shRB) stage disease models

first: Karen

last: Knudsen

first: Amy

middle: C

last: Mandigo


title: RNA-SEQ analysis of CD4+ T cells in presence or absence of Ikaros.

city: Illkirch

first: Tao

last: YE

address: 1 rue Laurent Fries

country: France

institute: IGBMC (CNRS/INSERM/UDS)

summary: We found by microarray analysis that Ikaros is critical to limit the expression of several pro-inflammatory genes during Th17 cell polarization. To unravel the role of Ikaros in the expression of pro-inflammatory genes without Th17 polarizing cytokines, we performed an RNA-seq analysis in naive CD4+ T cells and  CD4+ T cells activated with anti-CD3+anti-CD28 antibodies (Th0 condition), from WT (Ikaros f/f CD4-Cre-) and Ikaros TKO mice (Ikaros f/f CD4-Cre+).

overall_design: RNA-seq of naive and activated CD4+ T cells in WT and Ikaros TKO mice.

first: Chiara

last: Bernardi

last: Ye

first: Susan

last: Chan

first: Philippe

last: Kastner

first: Céline

last: Charvet


title: CD4+ T cells in presence or absence of Ikaros


title: Transcriptomic profiling of three-dimensional cholangiocyte spheroids long-term exposed to repetitive Clonorchis sinensis excretory-secretory products

city: Seoul

first: Jung-Woong

last: Kim

address: 84 Heuksuk-ro Dongjak-ku

department: Life Science

country: South Korea

institute: Chung-Ang University

summary: Microarray and RNA-Seq analysis revealed that ESP-treated cholangiocyte H69 spheroids displayed global changes in gene expression compared to untreated spheroids. In ESP-treated H69 spheroids, 185 and 63 probes were found to be significantly upregulated and downregulated, respectively, corresponding to 209 genes (p < 0.01, fold change > 2).

overall_design: Six untreated and treated Samples

first: Junyeong

last: Yi

first: Jinhong

last: Park

first: Ji

last: Jeong

first: Jinho

first: Jihee

last: Won

first: Seok

last: Chung

first: Tong-Soo

first: Jhang

last: Pak


title: Transcriptional network analysis of osmotic and ionic responses in Arabidopsis

city: Wuhan

first: Zhulong

state: Hubei Province

address: No. 1, Shizishan St, Nanhu

department: College of Horticulture and Forestry Sciences

institute: Huazhong Agricultural University

summary: Salt and PEG tolerances of 70 Arabidopsis accessions were screened. Five commonly used Arabidopsis accessions （C24, Col, Ler, SHA, Ws） were selected for further analysis. The results showed that SHA and C24 were relatively tolerant, while Ler and Ws were relatively susceptible to both salt and PEG stress. Transcriptomic analysis revealed that 4105 to 8782 genes exhibited significant expression level changes among five accessions in the presence and absence of stress treatments. The function of these genes were involved in stress response, ROS and metabolic pathways. The detailed networks affected by salt and osmotic stresses were dissected.

overall_design: Salt stress (100mM NaCl), osmotic stress (-1.2 MPa PEG) and control treatments were applied on 10-day-old plants for 4 days. Two biological reps and 5 Arabidopsis accessions were used in this study. In total 30 Agilent microarrays were hybridized with Cyanine-3 (Cy3) labeled probe.


title: Transcriptional profiling of human malignant mesethelioma cells that have constitutively treated with sialic acid binding lectin from Rana catesbeiana (cSBL)

city: Sendai

first: Takeo

last: Tatsuta

state: Miyagi

address: 4-4-1 Komatsushima, Aoba-ku,

department: Institute of Molecular Biomembrane and Glycobiology

institute: Tohoku Medical and Pharmaceutical University

summary: cSBL is a multifunctional protein that has lectin and ribonuclease activity, and show selective cytotoxicity against many kinds of cancer cells.For further understanding anti-tumor effects of cSBL, we treated cSBL-sensitive malignant mesothelioma H28 cells with cSBL consecutively, and established cSBL-resistant (cSR) cells. We have established 5 resistant clones and using two clones that show higher resistant rates, microarray analysis was performed to identify significant altered gene expression upon cSBL-sensitive and -cSR cell lines.

overall_design: The global gene expression analysis using parental (cSBL-sensitive) and cSBL-resistant malignant mesothelioma H28 cell lines.


title: Evidence of superior and inferior sinoatrial nodes in the mammalian heart [Rat]

city: Washington

first: Igor

last: Efimov

state: DC

address: 800 22nd St NW

department: Biomedical Engineering

institute: The George Washington University

summary: We report the application of RNA sequencing technology for high-throughput profiling of regionally separated sinoatrial nodal tissues from rat hearts. We find that both the superior and inferior regions of these sinoatrial nodal tissues (termed sSAN and iSAN, respectively) possess statistically comparable levels of cardiac ion channels, receptors, neural proteins, and transcription factors. This study provides new insights into regional molecular expression of pacemaking tissue in the right atria.

overall_design: Examination of 5 different tissue types from the rat heart.

first: Jaclyn

last: Brennan

first: Qing

last: Chen

first: Weiqun

last: Peng

middle: R


title: Myoepithelial cell perturbations in BRCA mutation carriers and in DCIS (ductal carcinoma in situ)

city: Houston

first: Haoqiang

last: Ying

state: Texas

address: 1515 Holcombe Blvd

institute: M. D. Anderson Cancer Center

summary: We describe the gene expression profiles and enhancer landscape of normal myoepithelial cells and perturbations of these in BRCA1 and BRCA2 mutation carriers and in DCIS. We identified a myoepithelial transcription regulatory network orchestrated by p63 and TCF7 and defined the genomic targets of these transcription factors by ChIP-seq. While the majority of myoepithelial cells co-express p63 and TCF7 in normal breast of healthy women, the frequency of these cells is significantly lower in BRCA1 mutation carriers and in DCIS. Downregulation of p63 in MCF10DCIS cells leads to loss of myoepithelial cells and invasive tumors, whereas overexpression of TCF7 enhances tumor growth. Our findings suggest that loss of normal myoepithelial cell function facilitates in situ to invasive carcinoma transition and it may also enhance tumor initiation in BRCA mutation carriers.

overall_design: Normal myoepithelial cells and perturbations of these in BRCA1 and BRCA2 mutation carriers and in DCIS

first: Lina

last: Ding

first: Ying

last: Su

first: Xintao

last: Qiu

first: Muhammad

last: Ekram

first: Sung

last: Huh

first: Noga

last: Bloushtain-Qimron

first: Nicholas

last: Harper

first: Bojana

last: Jovanovic

first: William

last: Hines

first: Xiaoyuan

last: Zi

first: Vanessa

middle: F

last: Merino

first: Sibgat

last: Choudhury

first: Gabrielle

last: Ethington

first: Laura

last: Panos

first: Michael

last: Grant

first: Gedge

middle: D

last: Rosson

first: Jason

last: Clark

last: Herlihy

first: Alfred

last: Au

first: Andrea

middle: L

last: Richardson

first: Pedram

last: Argani

first: E

middle: S

last: Hwang

first: Rong

last: Fan

first: D

last: Allred

first: Kristie

last: Bobolis

first: Celina

last: Kleer

first: Joanne

last: Blum

first: Henry

last: Long

first: Saraswati

last: Sukumar

first: So

first: Judy

last: Garber

first: Jun

last: Yao

first: Mina

last: Bissell

first: Kornelia

last: Polyak


title: Genome wide chromatin accessibility (ATAC-SEQ)  in the presence or absence of Ikaros in CD4+ T cells.

first: Tao

last: YE

summary: We found that Ikaros is critical to limit the expression of pro-inflammatory cytokines in TCR/CD28-activated CD4+ T cells. To understand if Ikaros could modify the chromatin accessibility in regions controling the expression of these pro-inflammatory genes, we examined the chromatin state in naive CD4+ T cells and CD4+ T cells activated with anti-CD3+anti-CD28 antibodies for 1 and 2 days, from WT (Ikaros f/f CD4-Cre-) and Ikaros TKO mice (Ikaros f/f CD4-Cre+), using the ATAC-seq approach.

overall_design: ATAC-seq of naive and activated CD4+ T cells in WT and Ikaros TKO mice.

first: Chiara

last: Bernardi

last: Ye

first: Susan

last: Chan

first: Philippe

last: Kastner

first: Céline

last: Charvet


title: Genome-wide binding of Ikaros in naive CD4+ T cells and Th0 at day1

summary: The aim of the project is to determine the binding sites of Ikaros in CD4+ T cells. To perform this, CD4 naive T cells (CD4 TN; d0) either rested or activated with anti-CD3+anti-CD28 Abs for 1 day (Th0 d1) were subjected to a ChIP using anti-Ikaros Ab followed by high throughput sequencing.

overall_design: Chip-seq of naive and activated CD4+ T cells in WT cells.


title: Transcriptome profiling of human pluripotent stem cell-derived cerebellar organoids reveals faster commitment under dynamic conditions

city: Lisboa

first: Leonilde

middle: Morais

last: Moreira

address: A. Rovisco Pais

department: Bioengineering

country: Portugal

institute: Instituto Superior Tecnico

summary: Human induced pluripotent stem cells (iPSCs) have great potential for disease modeling. However, generating iPSC-derived models to study brain diseases remains a challenge. In particular, the ability to recapitulate cerebellar development in vitro is still limited. We presented for the first time a reproducible and scalable production of cerebellar organoids by using the novel Vertical-Wheel single-use bioreactors, in which functional cerebellar neurons were obtained. Here, we evaluate the global gene expression profiles by RNA sequencing (RNA-seq) across cerebellar differentiation, demonstrating a faster cerebellar commitment in this novel dynamic differentiation protocol. Furthermore, transcriptomic profiles suggest a significant enrichment of extracellular matrix (ECM) in dynamic-derived cerebellar organoids, which can better mimic the neural microenvironment and support a consistent neuronal network. The presence of factors that favors angiogenesis onset was detected in dynamic condition, which can enhance functional maturation of cerebellar organoids. We anticipate that large-scale production of cerebellar organoids may help developing models for drug screening, toxicological tests and studying pathological pathways involved in cerebellar degeneration.

overall_design: Human induced pluripotent stem cells (iPSCs) were induced to aggregate and differentiate into cerebellar organoids using either static or dynamic protocols. RNA sequencing was used to evaluate the transcriptomic profile of iPSCs (day 0) and cerebellar organoids at different timepoints of differentiation (days 14 and 35) using static and dynamic conditions.

first: Teresa

middle: P

last: Silva

first: Rui

last: Sousa-Luís

first: Tiago

last: Fernades

first: Evguenia

last: Bekman

first: Carlos

last: Rodrigues

first: Sandra

last: Vaz

middle: M

first: Yas

last: Hashimura

first: Sunghoon

last: Jung

first: Brian

last: Lee

first: Maria

last: Carmo-Fonseca

first: Joaquim

last: Cabral


title: Increased cardiac fatty acid oxidation in a mouse model with decreased malonyl-CoA sensitivity of CPT1B

first: Sander

last: Houten

address: 1425 Madison Avenue, Box 1498

department: Genetics and Genomic Sciences

institute: Icahn School of Medicine at Mount Sinai

summary: Mitochondrial fatty acid oxidation (FAO) is an important energy provider for cardiac work and changes in cardiac substrate preference are associated with different heart diseases. Carnitine palmitoyltransferase 1B (CPT1B) is thought to perform the rate limiting enzyme step in FAO and is inhibited by malonyl-CoA. The role of CPT1B in cardiac metabolism has been addressed by inhibiting or decreasing CPT1B protein or after modulation of tissue malonyl-CoA metabolism. We assessed the role of CPT1B malonyl-CoA sensitivity in cardiac metabolism.

overall_design: 13 samples from heart (4 WT, 4WT/E3A and 5 E3A/E3A) were analyzed

first: Carmen

last: Argmann


title: Evidence of superior and inferior sinoatrial nodes in the mammalian heart [Human]

first: Igor

last: Efimov

summary: We report the application of RNA sequencing technology for high-throughput profiling of regionally separated sinoatrial nodal tissues from human hearts. We find that both the superior and inferior regions of these sinoatrial nodal tissues (termed sSAN and iSAN, respectively) possess statistically comparable levels of cardiac ion channels, receptors, neural proteins, and transcription factors. This study provides new insights into regional molecular expression of pacemaking tissue in the right atria.

overall_design: Examination of 4 different tissue types from the human heart.

first: Jaclyn

middle: A

last: Brennan

first: Qing

last: Chen

first: Weiqun

last: Peng


title: Evidence of superior and inferior sinoatrial nodes in the mammalian heart

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

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: Refer to individual Series


title: Comparison of the RB loss-induced E2F1 cistrome in hormone-therapy sensitive and castration-resistant prostate cancer [ChIP-seq]

first: Christopher

last: McNair

summary: These studies examine the consequence of RB loss on E2F1 function across prostate cancer progression.

overall_design: E2F1 cistrome alterations in resposne to RB loss after AR stimulation were assessed in early (LNCaP-shCon and LNCaP-shRB) and late (C42-shCon and C42-shRB) stage disease models

first: Karen

middle: E

last: Knudsen

first: Amy

last: Mandigo


title: ibrutinib resistance mantle cell lymphoma [ChIP-seq]

city: Tampa

first: Jianguo

last: Tao

state: Florida

address: 12902 Magnolia Dr

institute: Moffitt Cancer Center

summary: Ibrutinib, a bruton's tyrosine kinase inhibitor, was shown to have high response rates in mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. However, emergence of ibrutinib resistance (IR) and subsequent fatal progression is of significant clinical concern. By implementing genomics, chemical proteomics and drug screening, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the malignant phenotype of IR. Accordingly, IR MCL cells are vulnerable to inhibition of the transcriptional machinery and especially to inhibition of cyclin-dependent kinase 9 (CDK9). Thus, targeting transcriptional activation offers a novel strategy to prevent the emergence of IR and overcome IR via impeding IR-associated cellular signaling reprogramming in MCL. In addition, our ex-vivo microfluidic image-based functional drug screen can function not only as new technology platforms for predicting clinical therapeutic response but also, in conjunction with genomic profiling in primary MCL samples, identify the molecular vulnerabilities for drug resistance evolution, providing insight into the underlying IR mechanisms for MCL and other B-cell malignancies

overall_design: RNA sequencing to profile expression in paired parental and ibrutinib resistant mantle cell lymphoma cell lines as well as the differenctial changes by BRD4 and NVP2 treatment

first: Xiaohong

last: Zhao

first: Michelle

middle: Y

last: Wang

first: Paul

last: Park

first: Wei

last: Zhang


title: ibrutinib resistance mantle cell lymphoma [Pt_RNA]

overall_design: RNA sequencing to profile expression in primary mantel cell lymphoma patient samples as well as the differenctial changes by BRD4 inhibitor(INCB054329) and NVP2 treatment

first: Jing

last: Gao

first: Lawlor

last: Matthew


title: ibrutinib resistance mantle cell lymphoma [RNA-seq]