title: The Role of Sphingosine 1 Phosphate Receptor 2 Signaling in Chronic Glucocorticoid Exposure Induced Hepatic Steatosis and Hypertriglyceridemia

city: Berkeley

first: Jen-Chywan

address: 315 Morgan Hall, UC Berkeley

department: Nutritional Sciences & Toxicology

institute: UC Berkeley

summary: Glucocorticoids (GC) are potent anti-inflammatory agents that are frequently used to treat inflammatory diseases. Chronic glucocorticoid treatment, however, causes unwanted adverse effects such as hypertriglyceridemia and hepatic steatosis. Hepatic sphingosine-1-phosphate receptor 2 knockdown in mice reduced chronic GC treatment induced triglyceride accumulation in the liver and plasma. Chronic glucocorticoid treatment increased the recruitment of sterol regulatory element-binding protein 1c (Srebp1c) to the sterol regulatory element of mouse fatty acid synthase (Fasn) gene. This response was attenuated in hepatic S1PR2 knockdown mice. Chronic glucocorticoid treatment also increased the recruitment of carbohydrate response element binding protein (ChREBP) to the carbohydrate response elements (ChOREs) of lipogenic and glycolytic genes such as pyruvate kinase L/R (Pklr) and malic enzyme 1 (Me1) in mice liver. This response was also reduced in hepatic S1PR2 knockdown mice. Reducing hepatic ChREBP expression reduced the expression of Pklr, Me1 and Fasn. However, long-term glucocorticoid induced triglyceride accumulation in the liver and the plasma were not affected whereas the hepatic lactate levels were decreased. Thus, ChREBP plays a major role in chronic glucocorticoid induced glycolysis whereas its role in hypertriglyceridemia and hepatic steatosis was modest. Overall, this study demonstrated that hepatic S1PR2 signaling is involved in chronic glucocorticoid exposure activated Srebp1c and ChREBP, which promote lipogenesis and glycolysis, respectively.

overall_design: To establish the role of S1PR2 in chronic Dexamethasone (a synthetic glucocorticoid) treatment, we used AAV8 to knockdown S1PR2 in a liver-specific manner. We performed RNA sequencing in mouse liver to identify differentially expressed genes between control and S1PR2 knockdown mice treated with or without Dexamethasone

first: Maggie

last: Chang


title: Transient dietary intervention induces healthy adipose tissue expansion and metabolically healthy obesity in mice

status: Public on Jul 23 2025

city: Nagoya

first: Eri

last: Wada

state: Aichi

address: Furo-cho, Chikusa-ku

department: Research Institute of Environmental Medicine

country: Japan

institute: Nagoya University

type: Expression profiling by high throughput sequencing

summary: As obesity progresses, dynamic tissue remodeling of adipose tissue occurs over time, i.e., adipocyte hypertrophy, chronic inflammation, and interstitial fibrosis. Some obese individuals exhibit healthy adipose tissue expansion, characterized by modest inflammation and fibrosis despite adipocyte hypertrophy, resulting in “Metabolically Healthy Obesity (MHO)”.  Our research has revealed that MHO can be induced by temporary weight loss during the development of obesity.

overall_design: We fed high-fat fed (HFD) or standard diet (SD) to eight-week-old male C57BL/6J mice to establish a Weight Cycling (WC) protocol. The WC group was fed HFD for 8 weeks, followed by SD for 2 weeks for weight loss, then HFD again for an additional 6 weeks.The control group was fed HFD continuously for 14 weeks from 10 weeks of age. We collected  epididymal adipose tissue samples from the mice.

first: Miyako

last: Tanaka

first: Tomoo

last: Ogi

first: Takayoshi

last: Suganami


title: The paradoxical significance of CD39+CD8+ T cells in clear cell renal cell carcinoma [scRNA-seq]

city: Daejeon

first: YEO

last: JINHEE

address: 291 Daehak-ro

country: South Korea

institute: Korea Advanced Institute of Science and Technology

summary: CD39+CD8+ T cells are known as tumour antigen-specific cells among CD8+ tumour-infiltrating lymphocytes (TILs). However, CD39+CD8+ T cells also reportedly exhibit immunosuppressive activity in hypoxic tumour models. Here we investigated CD39+CD8+ TILs with regards to their molecular phenotypes, developmental mechanisms, functions, and prognostic significance in clear cell renal cell carcinoma (ccRCC), a VHL mutation-associated hypoxic tumour. Single-cell RNA and TCR analyses confirmed that CD39+CD8+ cells are a terminally exhausted subset of tumour-specific CD8+ TILs. CD39+CD8+ T-cell development was highly correlated with cAMP signals, and was directly induced by cAMP and TCR signallings. Analysis of an RCC cohort revealed a markedly elevated proportion of CD39+ cells among CD8+ TILs in ccRCC, compared to non-ccRCC. Moreover, the proportion of CD39+CD8+ TILs was associated with high tumour mutational burden and hypoxic features. Ex vivo functional assays revealed that CD39+CD8+ TILs exerted immunosuppressive activity on neighbouring CD8+ T cells via ectonucleotidase activity- and adenosine-dependent mechanisms. CD39+CD8+ TIL enrichment predicted poor prognosis of ccRCC patients, yet also predicted favourable treatment responses to anti-PD-1 therapy. This paradoxical prognostic significance in ccRCC is explained by the dual properties of CD39+CD8+ TILs: tumour antigen specificity and immunosuppressive activity.

overall_design: From single-cell suspensions of tumours and PBMCs, CCR7-CD45RA- and CCR7-CD45RA+ CD8+ T cells were sorted. Next, these cells were loaded onto the 10× Genomics Chromium Single Cell platform.

first: Eui-Cheol

last: Shin

first: Yong Joon

last: Lee

first: Seung Hyuck

last: Jeon

first: Jin Hee

last: Yeo

first: Sun-ju

last: Byeon


title: KDM6A downregulation promotes tumor-prone cytokines expression in cancer-associated fibroblasts by activating enhancers

city: Shanghai

first: Jun

last: Mi

address: 280 South Chongqing Rd.

department: Biochemistry & Molecular Cell Biology

country: China

institute: Shanghai Jiao Tong University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: This study reports that CAFs isolated from colon cancer tissue, TGF-β1-induced CAFs, or HCT116 co-cultured CAFs secrete more cytokines and growth factors represented by IGF1, ELN, and SFRP2. Mechanistic investigations demonstrate that aerobic glycolysis metabolites fumarate and succinate can induce the transcription of IGF1, ELN, and SFRP2 in CAFs, while α-ketoglutarate (α-KG) can antagonize the induction effect of fumarate and succinate. Moreover, the downregulation of KDM6A in CAFs is observed compared to quiescent fibroblasts (NAFs). Additionally, integrated analysis of ATAC sequencing and RNA sequencing revealed altered chromatin structure during fibroblast activation. CUT-tag sequencing and co-IP assays demonstrate that KDM6A is bound to WDR5, facilitating its association with the COMPASS complex and the polycomb repressive complex at the expected target loci. Depletion of KDM6A disrupts the homeostasis between polycomb and COMPASS complexes, leading to an increase in the expression of IGF1, ELN, and SFRP2. However, the inhibitor GSK-J4 specific for both KDM6A and KDM6B reduces IGF1 expression, indicating that KDM6B compensates for the demethylase function of KDM6A but cannot replace KDM6A to maintain the homeostasis of COMPASS and polycomb repressive complexes. These findings suggest a metabolism-related epigenetic mechanism for cytokine expression, where reduced KDM6A levels enhance the tumor-promoting effect of CAFs. This may provide insights into why colon cancer is more prevalent in men than in women since KDM6A is an X-chromosome-associated gene.

overall_design: A specific antibody against KDM6B or a counterpart IgG were used for chromatin A specific antibody against KDM6B or its counterpart IgG was utilized for chromatin immunoprecipitation on the chromatin of fibroblasts following fragmentation by ultrasound. KDM6A was knocked down in fibroblasts isolated from human skin.

first: Jieying

last: Zhang

first: Suoyu

last: Xiang

first: Dan

last: Liu

first: Xiaomeng

last: Pei


title: AS1842856: A dual FOXO1-GSK3 inhibitor for targeting B-ALL-specific molecular vulnerabilities

city: Ulm

first: Alexey

last: Ushmorov

address: Albert-Einstein-Allee 11

department: Institute of Physiological Chemistry

country: Germany

institute: Ulm University

summary: Activation of the transcription factor FOXO1 contributes to multiple pathological processes. The FOXO1 inhibitor AS1842856 demonstrated strong therapeutic effects in pre-clinical models of common diseases like diabetes and anthracyclines-induced heart failure. We have previously identified FOXO1 as a B-ALL dependency and demonstrated in in vivo B-ALL models that AS1842856 increased the survival and decreased B-ALL tumor load in all critical organ compartments, but most efficiently in the CNS. Here, we interrogated the underlying molecular mechanisms by comparison of the transcriptomic effects of AS1842856 and Foxo1-KO in a B-ALL mouse model. Despite the significant similarity in sets of regulated genes, we identified GSK3B inhibition as a signature enriched only in AS1842856-treated cells. Using an in vitro kinase assay, we identified AS1842856 as a direct GSK3B inhibitor that ultimately stabilizes CTNNB1. CTNNB1-KO partially protected B-ALL cell lines from the cytotoxic effect of AS1842856. At the same time, using a chemical protein degradation model, we found that FOXO1 indeed contributes to the cytotoxic effect of AS1842856. We conclude that AS1842856 targets two known B-ALL vulnerabilities: GSK3B and FOXO1. The unique mode of action, low toxicity, and ability to penetrate the blood-brain barrier warrant further investigation of the therapeutic potential of AS1842856 in B-ALL.

overall_design: RNA-sequencing was performed in BCR-ABL1+ Cre-ERT2 Foxo1fl/fl murine B-ALL cells treated with 200 nM 4-OHT or equivalent amount of vehicle EtOH or with 70 nM AS1842856 or equivalent amounts of DMSO vehicle. RNA was isolated after 24 hours and 48 hours.

first: Franz

last: Ketzer

first: Ulrike

last: Büttner

first: Daniel

last: Geist

first: Anita

last: Kick

first: Thomas

last: Wirth


title: Paracrine regulation of pancreatic cancer cell response to chemotherapy by GLI2-Collagen I signaling

city: Rochester

first: Renzo

middle: Emanuel

last: Vera

state: Minnesota

address: 305 4th Ave SW

country: USA

institute: Mayo Clinic

summary: Despite the well described role of non-cellular components of the tumor microenvironment (TME) in regulating tumor growth, the molecular events dictating expression and biological functions of key components of the TME remain elusive. Here, using pancreatic cancer (PC) models, we describe a novel mechanism through which the zinc finger transcription factor GLI2 in cancer associated fibroblasts (CAFs) induces expression of COL1A1, which is a major component of Collagen I and the most abundant collagen variant in the tumor milieu. Bulk and single nuclei RNA-seq showed that GLI2 expression in CAF strongly correlates with COL1A1 levels, fibrosis, and CAF activation. ChIP-qPCR and expression studies of the PC matrisome identified COL1A1 as the direct target of GLI2 in CAFs. We also provide evidence that GLI2 is an effector that mediates COL1A1 induction by transforming growth factor β1 (TGFβ1). RNA-seq analysis of PC cells treated with Collagen I revealed enrichment of chemotherapeutic gene expression profiles, which includes irinotecan resistance signature. Viability studies confirmed that Collagen I promotes irinotecan resistance in PC cells. Altogether, our results uncover a novel role for the TGFβ1-GLI2 axis within CAFs to modulate Collagen I expression and promote chemoresistance in PC cells. Our findings increase our understanding of the complex molecular network operating in the TME.

overall_design: We performed RNA-seq analysis in human  cell line, PANC-1, derived from a primary tumor of pancreatic ductal adenocarcinma . PANC-1 cells were starved  incubating the cells overnight with DMEM 1% FBS. Next, cells were treated for 0, 3, and 24 hours in DMEM media supplemented with 10% FBS and with or without 10 ug/mL of collagen I. Each condition has three replicates.

middle: E

first: Ezequiel

middle: J

last: Tolosa

first: Huocong

last: Huang

first: Rolf

middle: A

last: Brekken

first: Martin

last: Fernandez-Zapico


title: Chromatin landscape alteration uncovers multiple transcriptional circuits during memory CD8+ T cell differentiation

city: Guangzhou

first: Zhonghui

last: Tang

state: Guangdong

address: No. 74 Zhongshan Second Road, Guangzhou

institute: Sun Yat-sen University

summary: RNA-seq of shSox4 and vector transduced  MPEC P14  cells

overall_design: CD45.1+ pMKO.1 vector or CD45.1+ CD45.2+ shRNA targeting Sox4 transduced P14 were 1:1 mixed, and 1 x 10^5 cells were transferred into the CD45.2+ recipients followed by 2 x 10^5 PFU of LCMV-Arm+ infection. On D8, vector transduced MPECs were sorted as L/D-CD44+CD8+CD45.1+CD127+KLRG-,shSox4 transduced MPECs were sorted as L/D-CD44+CD8+CD45.1+CD45.2+CD127+KLRG-

first: Liu

last: Qiao

first: Wei

last: Dong

last: Rong

first: Ye

last: Lilin

first: Tang

last: Zhonghui


title: Effect of Sirt2 deletion in mouse hepatocytes on gene experession in mouse livers overexpressed with GFP or MET/CAT

city: Maywood

first: wei

last: Qiu

state: IL

department: Surgery

institute: Loyola University Chicago

summary: There is a gap in our understanding of mechanisms promoting hepatocellular carcinoma (HCC), and this limits our ability to provide targeted therapy interventions for HCC. In HCC samples, NAD-dependent deacetylase sirtuin 2 (SIRT2) levels are increased and associated with a significantly worse prognosis, but the role of SIRT2 in hepatocarcinInogenesis remains controversial. In this study, we investigated the role of SIRT2 in HCC development and examined the effect of Sirt2 deletion in hepatocytes on gene expression in mouse livers overexpressed with GFP control or MET/CAT.

overall_design: To assess the role of SIRT2 in hepatocarcinogenesis, we used a hepatocyte-specific knockout of SIRT2 and two plasmid overexpression  MET/CAT HCC model. RNA-sequencing of mouse liver tissue was performed,

first: Fang

last: Wang

first: Jun

last: Li


title: Integrated metabolomic and transcriptomic analysis reveals distinct accumulation patterns in three Brassicaceae crops

city: Saskatoon

first: Isobel

last: Parkin

address: 107 Science Pl

country: Canada

institute: Agriculture and Agri-Food Canada

summary: Brassica napus, Camelina sativa and field pennycress (Thlaspi arvense) are three important oilseed crops in the Brassicaceae family. As sessile organisms, these crops are continuously exposed to various stresses when grown in the field. Interestingly, the responses of these three crops to different environmental stimuli vary to a great extent, but there is very limited knowledge about the molecular basis of these discrepancies. In this study, we employed untargeted metabolomics to compare the metabolic profile of these crops, and examined the potential causal genes through further integration with transcriptomic analysis. Our data revealed distinctive overall metabolic profiles among these three crops, where in particular, a variety of phenylpropanoids showed differential accumulation and the corresponding putative genes’ expression varied significantly. Our results here will provide valuable insight into the understanding of metabolic variations among these three important oilseed crops, and provide potential targets for the future breeding of stress tolerant crops.

sample_organism:
Brassica napus
Thlaspi arvense
Camelina sativa

overall_design: Untargeted metabolomics and RNAseq data were collected from the leaves and cotyledons of three Brassicaceae crops to compare their metabolic profiles

first: Liyong

last: Zhang


title: ICE-A: A chromatin interaction-based tool for improved annotation of distal cis-regulatory elements reveals novel regulatory functions of lineage-restricted transcription factors in lymphocytic development [ChIP-Seq]

city: Linköping

first: Mikael

last: Sigvardsson

address: Lab1, Level 13

department: Department of Biomedical and Clinical Sciences

country: Sweden

institute: Linköping University

summary: Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the 3-dimensional (3D) structure of the DNA. The 3D structure is of great importance because it allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for functional synergy and high-level transcription of a given target gene. However, chromatin loops can be highly complex and can span several megabases of genomic context and where one enhancer can interact with several promoters during cell development affecting gene regulation in a time and cell context dependent manner. Thus, our understanding of gene regulation is largely dependent upon our ability to link regulatory elements to the correct target genes. For this purpose, several approaches have been developed, including proximity annotation, linking a given regulatory element to the closest coding gene, and correlation of gene expression to changes in DNA accessibility. While these approaches are valuable, they are based on rather simplified assumptions that disregard the stage- and lineage-restricted 3D organization of the genome. To facilitate the linkage of regulatory elements to their target genes, we have developed a novel tool for easy incorporation of chromatin configuration data into the annotation process. Using this annotation procedure to explore gene regulatory networks in early lymphocyte development, we show that lineage-specific transcription factors target regulatory elements that are annotated to both lineage-specific and broadly expressed genes. Furthermore, several regulatory elements annotated to lineage-specific genes were annotated to alternative promoters in a context dependent manner. These data highlight how efficient annotation procedures for linking distal regulatory elements to target genes provide valuable insights into gene regulatory networks.

overall_design: H3K4me3  Chromatin immunoprecipitation DNA sequencing (ChIP-seq) of Scid.adh.2C2 T-cell progenitor and 230-238 B-cell progenitor cell line.

first: Johanna

last: Tingvall-Gustafsson

first: Christina

middle: T

last: Jensen

first: Jonas

last: Ungerbäck


title: Secretory IgA dysfunction underlies poor prognosis in Fusobacterium-infected colorectal cancer

city: Seoul

first: IlSeok

last: Choi

address: 50, Yonsei-ro, Seodaemun-gu

department: Biotechnology

institute: Yonsei University

summary: Fusobacterium nucleatum (Fn), enriched in human colorectal cancer (CRC), is linked to a worse prognosis. To uncover the cellular and molecular mechanisms behind this Fn-associated prognostic effect, we conducted single-cell transcriptomic analyses on 42 surgically removed colon tissues from newly diagnosed colon cancer patients. Through single-cell and spatial transcriptome data analyses, we found that the development of IgA plasma cells producing functional secretory IgA was impaired due to disrupted communications between IgA plasma cells and macrophages in Fn-positive CRC. Additionally, we identified a dysregulated IgA maturation (IGAM) module in Fn-positive patients, indicating compromised IgA-mediated mucosal immunity. This finding was further supported by observed increases in bacterial infiltration within tumors of Fn-positive patients. Remarkably, we were able to stratify Fn-positive patients based on IGAM activity, which could lead to novel treatment strategies for Fn-positive CRC patients. Our findings indicate that impaired secretory IgA activity by Fn infection increases the bacterial burden within tumors and worsens prognosis through chronic inflammation. Additionally, identifying a novel gene expression biomarker for stratifying Fn-positive patients promises to refine CRC treatment strategies, offering a more tailored approach to patient care.

overall_design: To uncover the cellular and molecular mechanisms behind this Fn-associated prognostic effect, we conducted single-cell transcriptomic analyses on 42 surgically removed colon tissues from newly diagnosed colon cancer patients. Then we determined Fusobacterium nucleatum infection status through 16S rRNA-seq analysis.

first: Ilseok

first: Kyung-A

last: Kim

first: Sang

middle: C

first: Insuk

last: Lee

first: Han

middle: S

first: Yoon

middle: D

last: Han


title: Loopsim: Enrichment Analysis ofChromosomeConformation Capture with Fast EmpiricalDistribution Simulation

city: Ann Arbor

first: Poulami

last: Dey

address: 1301 Catherine St

institute: Michigan Medicine

summary: The three-dimensional organization of the genome intricately influences the regulation of genes.In particular, chromatin can exist as loop structures that enable long-range regulatory interactions. By utilizingchromosome conformation capture techniques such as Hi-C, valuable information regarding the organizationof these loop structures in 3D space can be obtained. While gene-set enrichment has become a standard down-stream analysis for different genomic data to provide biological context, tools that providefunctionalenrich-ment for high throughput assays capturing chromosome conformation are relatively limited. Here, we presentLoopsim, a command-line application that performs enrichment analysis on Hi-C loop profiles against user-defined regions. Loopsim efficiently simulates a background distribution using a distinctive sampling approachthat considers loop size, intervals, loop-loop distances, and structure;itthencomputes statistics based on theempirical null distribution.

overall_design: To evaluate Loopsim's performance, we used a Hi-C loop profile generated by deep sequencing Hi-C libraries (~1 billion reads/reaction). Then, using a contact map combining resolutions (resolution in this case meaning the length of the interval of loop ends) of 5Kb and 10Kb, we identified Hi-C loops in each library using Mustache.

first: Johann

last: Gudjonsson

first: Lam

last: Tsoi


first: Eri

last: Wada

overall_design: We fed high-fat diet (HFD) to eight-week-old male C57BL/6J mice for 8 weeks (pre weight loss; preWL), followed by standard diet for 2 weeks (WL1w, WL2w) for weight loss We collected  epididymal adipose tissue samples from the mice.

first: Miyako

last: Tanaka

first: Takayoshi

last: Suganami


title: Immune System Modulation with Oral Vancomycin in combination with Stereotactic Body Radiotherapy (SBRT) for medically inoperable Early-Stage Non-small Cell Lung Cancer

city: Philadelphia

first: Andrea

last: Facciabene

state: PA

address: 3400 Civic Center Bulevard

department: Radiation Oncology

institute: University of Pennsylvania

summary: We report the results of a randomized, open-label pilot study evaluating oral vancomycin combined with SBRT in early-stage non-small cell lung cancer. Building on prior research, vancomycin was found to enhance antitumor effects by modulating gut microbiota and boosting immune responses notably improving progression-free and overall survival (P.F.S. and O.S.). Patients treated with vancomycin (125 mg QID for 5 weeks starting one week before SBRT) showed increased expression of antigen presenation machinary in PBMCs and councurrent T-cell activation, and significant changes in gut microbiome composition and metabolite profiles, including reduced Short Chain Fatty Acids and elevated TNF-beta levels. With minimal adverse events, vancomycin appears to synergistically enhance RT-induced antitumor immunity, positioning it as a viable strategy for improving oncological outcomes. Further studies with larger cohorts are needed to confirm these results.

overall_design:
To gain a better understanding of the effects of Vancomycin on the systemic immune response, we performed bulk RNA sequencing on PBMCs from NSCLC patients treated with either radiation therapy (RT) alone or in combination with Vancomycin (RT + Vancomycin).
Bulk RNA sequencing was conducted on 17 PBMC samples, with 8 receiving only radiation therapy (RT) and 9 treated with a combination of radiation therapy and Vancomycin (RT + Vancomycin).

first: Giorgos

last: Skoufos


title: A repeatedly evolved mutation in Cryptochrome-1 of subterranean animals alters behavioral and molecular circadian rhythms

city: Kansas City

first: Andrew

middle: Joseph

last: Price

state: MO

address: 1000 E. 50th Street

department: Computational Biology

institute: Stowers Institute for Medical Research

summary: The repeated evolution of similar phenotypes in independent lineages often occurs in response to similar environmental pressures, through similar or different molecular pathways. Recently, a repeatedly occurring mutation R263Q in a conserved domain of the protein Cryptochrome-1 (CRY1) was reported in multiple species inhabiting subterranean environments. Cryptochromes regulate circadian rhythms, and glucose and lipid metabolism. Subterranean species show changes to their circadian rhythm and metabolic pathways, making it likely that this mutation in CRY1 contributes to adaptive phenotypic changes. To identify the functional consequences of the CRY1 R263Q mutation, we generated a mouse model homozygous for this mutation. Indirect calorimetry experiments revealed delayed locomotor activity, energy expenditure and feeding patterns of mutant mice in the dark phase, but no further metabolic phenotypes – unlike a full loss of function of CRY1. Gene expression analyses showed altered expression of several canonical circadian genes in the livers of the mutant mice, fortifying the notion that CRY1 R263Q impacts metabolism. Our data provide the first characterization of a novel mutation that has repeatedly evolved in subterranean environments, supporting the idea that shared environmental constraints can drive the evolution of similar phenotypes through similar genetic changes.

overall_design: We collected brain and liver tissues at two different zeitgeber times (ZT, ZT12 and ZT22) from wild-type and CRY1 R263Q homozygote mice from both sexes, and then extracted and sequenced the mRNA. Samples from each ZT were collected, sequenced and analyzed separately. Comparisons were made within the same ZT, tissue type and sex, and between genotypes.

first: Amruta

last: Swaminathan

first: Alexander

last: Kenzior

first: Colin

last: McCoin

first: Kyle

last: Weaver

first: Aurélie

last: Hintermann

first: NatiCia

last: Morris

first: Alex

last: Keene

first: Nicolas

last: Rohner


title: Single-stranded DNA binding proteins are essential components of the architectural LDB1 protein complex [ChIP-seq]

first: Xiaokang

last: Wang

address: 315 A  Abramson Research Center, 3615 Civic Center Blvd.

department: Hematology

institute: Children's hospital of Philadelphia

summary: Transcriptional enhancers are brought into proximity with promoters via chromatin looping. The architectural transcription cofactor LDB1 facilitates spatial connectivity among enhancers and promoters, but whether this occurs through simple dimerization or requires heterotypic protein assemblies is unknown. Here we investigated single-stranded DNA binding proteins (SSBPs) in regulating LDB1-mediated chromatin looping and transcription. SSBP2, SSBP3, and SSBP4 colocalize with LDB1 genome-wide. Among these, only SSBP3 is essential for murine erythroid cell viability, LDB1 function, and transcription. LDB1 but not single-stranded DNA is the predominant genome-wide tether of SSBP3 to chromatin. SSBP3 depletion in SSBP2/4 knockout cells globally weakened LDB1-dependent chromatin loops and lowered nascent transcription without impacting LDB1's chromatin binding. Chromatin tethering experiments revealed SSBP3 and LDB1 mutually depend on each other to form looped contacts. SSBP3 stabilizes LDB1 dimerization in vitro, providing a possible mechanism. SSBPs emerge as key functional components of the architectural LDB1 complex.

overall_design: LDB1, SSBP3, SSBP2, SSBP4, LMO2, H3K27ac, CTCF ChIP-seq were performed in a variety of cell lines under different treatments and perturbations.

first: Gerd

last: Blobel


title: Hepatoprotective effect of cinnabarinic acid in metabolic dysfunction-associated steatohepatitis

city: College Station

first: Aditya

last: Joshi

state: Texas

address: 560 Raymond Stotzer Pkwy

institute: Texas A&M University

summary: Metabolic dysfunction-associated steatohepatitis (MASH) is an advanced form of metabolic dysfunction-associated steatotic liver disease (MASLD) characterized by accumulation of fats in liver, chronic inflammation, hepatocytic ballooning, and fibrosis. This study investigates role of endogenous Aryl hydrocarbon Receptor (AhR) agonist, cinnabarinic acid (CA) in protection against in vivo mouse model of MASH. To analyze the transcriptomic changes in response to CA treatment, male AhRfl/fl (AhR-floxed) mice were subjected to control diet (CD), high-fat high-fructose high-cholesterol diet (MASH diet, MD), and fed with MASH diet and treated with CA thrice a week for 20-week period. RNA sequencing revealed altered expression of multiple genes involved in fatty acid metabolism and inflammation in response to CA treatment. Gene set enrichment analysis indicated enrichment of AMPK among other kinases. Subsequent immunoblotting and immunofluorescence studies performed on CA-treated livers and primary hepatocytes confirmed activated AMPK signaling. Moreover, in a hepatocyte-specific AhR knockout mice livers (AhR-hKO, constructed by crossing AhRfl/fl with alb-Cre), CA failed to phosphorylate AMPK strongly indicating that CA-induced AMPK mediated protection against lipotoxicity in MASH is dependent on hepatic AhR signaling.

overall_design: Eight-week-old male AhRfl/fl (AhR-floxed) mice were subjected to control diet, CD (10 kcal% fat and matching sucrose), high-fat, high-fructose, high-cholesterol diet termed MASH diet, MD (40 kcal% fat, 20 kcal% fructose, and 2% cholesterol), and MD + cinnabarinic acid (MD + CA) for 20-weeks, ad libitum. For the MD + CA group, 12 mg/kg body weight CA (in 0.2% DMSO) was intraperitoneally injected thrice a week on Mondays, Wednesdays, and Fridays for the entire duration of the study (20-weeks). Mice in the MD group were treated with vehicle (0.2% DMSO + 98.8% saline) via i.p. three days a week (Mondays, Wednesdays, and Fridays) for 20 weeks. At end of the 20-weeks, livers were collected, frozen in liquid nitrogen, and stored at -80°C. RNA was extracted from ~50 mg snap-frozen liver tissue using Trizol and subjected to library preparation for subsequent RNA sequencing.

first: Nikhil

middle: Y

last: Patil

first: Iulia

last: Rus

first: Felix

last: Ampadu

first: Hassan

middle: M

last: Abushukair

first: Sarah

last: Bovincino

first: Richard

last: Brush

first: Elena

last: Eaton

first: Martin-Paul

last: Agbaga

first: Tae Gyu

last: Oh

first: Jacob

last: Friedman


title: Transcriptomic analysis of kidney cortex following knockdown of endothelial Klf4 on wild-type and Nos3 deficient backgrounds.

city: STONY BROOK

first: chelsea

last: estrada

state: NY

address: Nicolls Road

institute: STONY BROOK MEDICINE

summary: The goal of this study was to identify transcriptomic changes, mediated by the loss of endothleial Klf4, seen in glomerular microangiopathy in kidney endothelial cells. We recently reported that the endothelial-specific knockout of Krüppel-like factor 4 (Klf4) increases the susceptibility to GEnC injury and subsequent development of subacute thrombotic microangiopathy. However, the mechanism(s) mediating GEnC response to injury in thrombotic microangiopathy are poorly understood. Single nucleus RNA sequencing demonstrated an enrichment in pathways involved in angiogenesis, permeability, focal adhesion and cytoskeletal organization, specifically in the endothelial cluster in mice with endothelial loss of Klf4.

overall_design: Mouse renal cortex from four distinct genotypes were analyzed with one replicate per genotype.

first: Chelsea

last: Estrada

first: Craig

last: Wilson

first: Nehaben

last: Gujarati

first: Sumaya

last: Ahmed

first: Monica

middle: P

last: Revelo

first: Yiqing

last: Guo

first: Ilse

last: Daehn

first: Sandeep

middle: K

last: Mallipattu


title: Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans cells (mouse)

city: Taipei City

first: Yeh Fong

last: Tan

state: Taipei

address: No. 128, Section 2, Academia Rd, Nangang District

department: Institute of BioMedical Sciences

country: Taiwan

institute: Academia Sinica

summary: Serotonin and its receptor are known to play a role in regulating immune cells. However, how they affect an autoimmune disease like psoriasis is not well-established and the mechanism remains to be elucidated. Here, we investigated the role played by serotonin 2A receptor (HTR2A) in regulating psoriasis. HTR2A antagonistic drug worsens psoriatic outcome and HTR2A modulation reduced psoriatic inflammation. Using Imiquimod-induced psoriasiform inflammation model, HTR2A-deficient mice experienced exacerbated inflammation. Hematopoietic cells, particularly monocyte-derived Langerhans cells, were responsible for this exacerbated inflammation. Mechanistically, the exacerbated inflammation is due to increased interleukin-23 (IL-23) secretion and HTR2A suppresses it by inhibiting the activation of non-canonical NFkB pathway. Platelet-derived serotonin is the putative agonist modulating HTR2A attenuating psoriatic inflammation. Lastly, our findings in mice were also reproduced clinically. Thus, our data demonstrate platelet serotonin putatively modulates HTR2A attenuating psoriatic inflammation by suppressing IL-23 secretion via inhibiting non-canonical NFkB pathway in monocyte-derived Langerhans cells.

overall_design: Transcriptomic analysis of RNA-seq data of isolated HTR2A deficient Langerhans cells treated with Imiquimod and a-CD40L.

first: Yeh

middle: F

first: Chen-Yun

last: Yeh

first: Ching-Hui

last: Tsai

first: Yungling

middle: L

last: Lee


title: Gene expression profiles of stimulated CAR-T cells targeting TNF-NTF

city: Tokyo

first: Yuki

last: Kagoya

address: 35 Shinanomachi, Shinjuku

department: School of Medicine

institute: Keio University

summary: Chimeric antigen receptor (CAR)-T cell therapy is a promising therapeutic approach for relapsed or refractory acute myeloid leukemia (AML). However, optimal target antigens have yet to be established. A subset of AML cells express TNF, which is initially expressed on the cell surface and subsequently secreted by proteolytic cleavage of the extracellular portion. We generated CAR-T cells targeting the N-terminal fragment of TNF (TNF-NTF) that remains on the cell surface after shedding. We ablated TNF gene to avoid fratricide and coexpressed chimeric cytokine receptor (G6/7R) that we had previously developed in CAR-T cells to provide constitutive IL-7 signaling. The G6/7R-expressing TNF-TNF CAR-T cells exhibited potent and durable therapeutic efficacy in vivo. Our data suggest that TNF-TNF may be a promising target antigen for CAR-T cells applicable to AML.

overall_design: Human CD8+ T cells derived from three different healthy donors with TNF gene knockout were retrovirally transduced with an anti-TNF-NTF CAR gene or the CAR gene + G6/7R. The CAR-T cells were then stimulated with NALM-6 transduced with TNF NTF (NALM-6 TNF-NTF, high antigen density) or THP1, which endogenously expresses TNF (low antigen density) for 24h. Total RNA was collected, and gene expression profiles were analyzed by RNA sequencing.

first: Kagoya

last: Yuki

first: Nakashima

last: Takahiro


title: Vericiguat reduces atrial fibrillation recurrence by alleviating myocardial fibrosis via the TGF-β1/Smad2/3 pathway

city: Taizhou

first: Xiaolin

last: Sun

state: Jiangsu Province

address: 366 Taihu Road, Taizhou Pharmaceutical High-tech Zone, Jiangsu Province

department: Department of Cardiology

institute: The Affiliated Taizhou People's Hospital of Nanjing Medical University

summary: Atrial fibrillation (AF) and heart failure (HF) are mutually reinforcing, and the prognosis for both diseases is poor. Vericiguat is the first oral soluble guanylate cyclase (sGC) stimulator to be approved for the treatment of symptomatic, ejection fraction-reduced chronic heart failure (HFrEF) in adults. It exerts a general therapeutic effect on cardiovascular diseases, with a particular efficacy in the treatment of HF. However, the mechanism of vericiguat treatment of atrial fibrillation remains unclear. The objective of this study was to investigate the potential mechanism of vericiguat in the treatment of atrial fibrillation. A retrospective analysis was conducted to investigate the effects of vericiguat on patients with heart failure and paroxysmal AF. Furthermore, the effects of vericiguat on AF and the degree of myocardial fibrosis in rat AF models and cells were observed. It was found that vericiguat can control the recurrence of AF in clinical studies and can control the fibrosis of AF rats in vivo and in vitro experiments. RNA-Seq sequencing revealed that the TGF-β1/Smad pathway in cells treated with vericiguat was significantly enriched. In vitro validation demonstrated that the anti-fibrotic effect of Vericiguat was weakened by the TGF-β1/Smad pathway when Protein Kinase G (PKG) was knocked down. The findings indicate that vericiguat can inhibit myocardial fibroblast activation and collagen synthesis via the TGF-β1/Smad pathway, thereby exerting a controlling effect on the recurrence of atrial fibrillation.

overall_design: To explore the mechanisms by which vericiguat treats atrial fibrillation and controls myocardial fibrosis, we sequenced and compared cardiac fibroblasts, Angii-treated CFs, and vericiguat-treated AngII-treated CFs, and analyzed the differentially differentiated genes therein, enriched for relevant key signaling pathways.


title: Kindlin-2/Moesin interaction orchestrates sprouting angiogenesis via modulating endothelial membrane mechanics and VEGF signaling

city: TianJin

first: Lu

last: Wang

address: No22.Qixiangtai Rd.

institute: Tianjin medical university

summary: Membrane mechanics play a crucial role in cellular signaling and fate determination, yet their impact on angiogenesis remains poorly understood. Here, we identify Kindlin-2 as a key regulator of sprouting angiogenesis via regulating endothelial membrane tension through its interaction with Moesin, a crucial linker protein between the cell membrane and the actin cortex, a process crucial for sprouting angiogenesis. Mechanistically, Kindlin-2 binds to the N62 residue of Moesin, limiting its overactivation and maintaining proper membrane tension to facilitate VEGFR2 endocytosis and downstream signaling. Using both developmental and pathological models, we demonstrate that the interaction of Kindlin-2 and Moesin is enhanced in high angiogenic conditions, and endothelial Kindlin-2 deletion reduces angiogenesis. Furthermore, mutation of Moesin at N62 phenocopies the effects of Kindlin-2 loss. Together, these findings uncover a previously unrecognized mechanism linking membrane tension regulation to angiogenesis and provide new insights into targeting the Kindlin-2–Moesin axis for therapeutic intervention in neovascular diseases.

overall_design: RNA-seq profile of Human Umbilical Vein Endothelial Cells infected with adenovirus expressed WT Moesin or T558D Moesin

first: Yuxin

last: Fu

first: Zeyang

last: Yu

first: Yi

last: Lei

first: Tianjing

last: Yang

first: Jing

last: Zhou

first: Xiaohong


title: Serotonin 2A Receptor Attenuates Psoriatic Inflammation by Suppressing IL-23 Secretion in Monocyte-derived Langerhans cells

overall_design: Transcriptomic analysis of RNA-seq data of human skin treated with 2,5-Dimethoxy-4-iodoamphetamine (DOI) or Phosphate Buffered Saline.


title: Targeting COP I elicits CD8+ T cell-mediated anti-tumor immunity in preclinical models of Intrahepatic Cholangiocarcinoma (scRNA-seq)

city: Shanghai

first: Li

last: Zhang

address: Dongchuan road 800

institute: Shanghai Cancer Institute

summary: To illustrate the effects of COPI on the tumor immune microenvironment, we performed single-cell RNA sequencing (scRNA-seq) analysis to interrogate phenotypic and functional alterations of immune cells in Myr-AKT/YAPS127A- driven iCCA with (NAV) or without NAV2729(MOCK,30mg/kg) treatment.

overall_design: CD45+ population isolated from single cells pooled with six tumors per group were used for scRNA-seq.

first: Zehong

last: Chen

first: Guiqin

last: Xu

first: Chen

first: Yun

last: Liu

first: Zhaojuan

first: Lvzhu

last: Xiang

first: You

last: Zuo

first: Ningqian

last: Zheng

first: Zhiqian

last: Ye

first: Xiaoren

first: Yingbin

first: Yongzhong


title: Targeting COPI elicits CD8+ T cell-mediated anti-tumor immunity in preclinical models of Intrahepatic Cholangiocarcinoma (RNA-seq)

summary: To investigate the function of COPA in the regulation of anti-tumor immunity, we generated Copa-knockdown (shCopa) and control (shCon) AY-mICC cells for RNA-seq

overall_design: Comparative gene expression profiling analysis of RNA-seq data for shCon or shCopa AY-mICC cells.


title: AI-Identified CD133-Targeting Natural Compounds Demonstrate Different Anti-tumor Effects and Mechanisms in Pan-cancer

city: shenzhen

first: Yibo

last: Hou

state: State...

address: Guangdong province

institute: TsingHua university

summary: Advanced algorithms have significantly improved the efficiency of in vitro screening for protein-interactive compounds. However, target antigen (TAA/TSA)-based drug discovery remains challenging, as predictions of compound-protein interaction (CPI) based solely on molecular structure fail to fully elucidate the underlying mechanisms. In this study, we utilized deep learning, specifically TransformerCPI to screen active molecules from a Chinese herb compound library based on protein sequences. Two natural products, Polyphyllin V and Polyphyllin H, were identified as targeting the pan-cancer marker CD133. Their anti-tumor efficacy and safety were confirmed across validation in cancer cell lines, tumor patient-drived organoids, and animal models. Despite their analogous structures and binding affinity to CD133, Polyphyllin V suppresses the PI3K-AKT pathway, inducing pyroptosis and blockage of mitophagy, whereas Polyphyllin H inhibits the Wnt/β-catenin pathway and triggers apoptosis. These distinct mechanisms underscore the potential of combining AI-driven screening with biological validation. This AI-to-patient pipeline identifies Polyphyllin V and Polyphyllin H as CD133 targeted drugs for pan-cancer therapy, and reveals the limitations of virtual screening alone and emphasizes the necessity of live model evaluation in AI-based therapeutic discovery.

overall_design: RNA-seq profile of HCT116 and DLD1 cells with or without treatment of PP10 and PP24

first: Shaohua

last: Ma

first: Xiaoyong

last: Dai

first: Zixian


title: Effect of miR-34a overexpression on the transcriptome of HEK293T cells

city: Solna

first: Emma

middle: R

last: Andersson

address: Solnavägen 9

department: Department of Cell and Molecular Biology

institute: Karolinska Institute

summary: MicroRNAs regulate gene expression post-transcriptionally through binding to target sites in mRNAs. Predictions of target site efficiency are limited by our understanding of the structure-function relationship of microRNA-target complexes. Here, we overexpressed miR-34a in HEK293T cells and performed RNA-sequencing in order to study how different structural features of predicted miRNA-target complexes correlate with changes in gene expression.

overall_design: To investigate how different structural features of microRNA-target complexes affect target gene repression, we transfected HEK293T cells with miR-34a duplex or AllStars negative control miRNA (Qiagen). Total RNA was collected 18 h post-transfection and samples were analyzed for differential gene expression using bulk RNA-sequencing. Three biological replicates were included for each condition.

first: David

last: Kosek

first: Katja

last: Petzold


title: CEBPB-mediated transcriptional regulation in Kupffer cells in metabolic dysfunction-associated steatohepatitis [RNA-seq]

first: Yuanwen

state: None Selected

address: No.221 West Yan'an Road

institute: Huadong Hospital

summary:
Background & Aims: Kupffer cell (KC) participates in hepatic inflammation and fibrosis in metabolic dysfunction-associated steatohepatitis (MASH), but underlying molecular mechanisms are not fully resolved. Transcription factor CCAAT/enhancer binding protein β (C/EBPβ) has been implicated in both metabolic and immune dysregulations. In this study, we aimed to investigate the role of C/EBPβ in KCs under the context of MASH pathogenesis.
Approach & Results: A 12-week high-fat and high-cholesterol diet (HFHCD) model was used in wild-type or KC-specific Cebpb heterozygous knockout mice (Cebpbfl/+;Clec4f-iCre), followed by evaluation of liver using histopathology, analytical flow cytometry and RNA-seq. We found that HFHCD in wild-type mice induced significant inflammatory immune cell infiltration, including increased proportion of monocyte-derived macrophages (MoMFs), accompanied with concomitant increase in C/EBPβ protein level in KCs. KC-specific Cebpb heterozygous knockout significantly reduced HFHCD-induced immune cell (including MoMFs, neutrophils and CD8+ T cells) infiltration and inflammation-related gene expression in liver. FACS-sorted KCs of HFHCD-treated mice were used for C/EBPβ CUT&Tag-seq. We found that C/EBPβ activity was increased in MASH KCs, leading to selective promotion on part of MASH-induced genes. Combined analysis of RNA-seq and CUT&Tag-seq, along with dual luciferase reporter assay identified Vcam1 (encoding vascular cell adhesion molecule 1, VCAM1) as a key downstream gene of C/EBPβ in KCs of murine MASH liver. In both murine liver and MASH patients, VCAM1 was predominantly expressed in KCs. Its expression in liver was significantly increased after MASH onset, and it was involved in promoting immune cell infiltration in MASH.
Conclusions: In MASH pathogenesis, increased C/EBPβ in KCs act as a MASH-associated stimulus-regulated TF, and has a direct transcriptional activation effect on Vcam1 promoter, leading to abnormal elevation in VCAM1 expression in KCs and subsequent immune cell infiltration. Our findings suggest that C/EBPβ in KCs can be a potential therapeutic target for NASH inflammation.

overall_design: KC-specific Cebpb monoallelic knockout (Clec4f-iCre;Cebpbfl/+) mice, and utilized littermate mice (Clec4f-iCre;Cebpb+/+) were fed with high-fat high-cholesterol diet (HFHCD) for 12 weeks. Total mRNA of murine  liver tissue was extracted and subjected to RNA-seq.

first: Shuangzhe

last: Lin


title: Neutrophil extracellular DNA traps promote  neutophils migration and activation by TLR9 signalling in type 2 autoimmune pancreatitis

city: Beijing

first: yuyang

last: wang

address: 5 Dong Dan San Tiao, Beijing

institute: Peking Union Medical College

summary: Neutrophil infiltration around the pancreatic  ducts has been found to be associated with type 2 autoimmune pancreatitis (AIP). However, the functional role and clinical importance of neutrophils migration on the progress of pancreatitis is not fully understood. Here, we found that neutrophil extracellular traps (NETs) are abundant around the pancreatic duct in type 2 AIP patients. Moreover, we observed the expression of TLR9 is higher in pancreatic ductal epithelial Cells (HPDEC) in type 2 AIP patients than in other pancreatic diseases. TLR9 acts as a NET-DNA receptor on HPDEC that senses extracellular DNA and subsequently activates the NF-κB pathway to attract neutrophils motility and induce NETs formation. In addition, the TLR9 antagonist hydroxychloroquine (HCQ) can effectively inhibit the activation of inflammatory pathways, reduce the migration of neutrophils and block the positive feedback mechanism, which can be used as a potential target drug for the clinical treatment of type 2 AIP.

overall_design: To determine the effect of upregulated TLR9 in the  pathogenesis of type 2 AIP, we generated TLR9-overexpressing HPDEC stably expressing YFP-tagged  TLR9 (WT and TLR9) and performed transcriptome-wide RNA sequencing (RNA-seq) after NETs treatment (Ctrl and NETs).


title: Lymphoma B cells remodel bone marrow stromal cell network into  extracellular matrix-producing cancer-associated fibroblasts (bulk rnaseq)

city: Rennes

first: Simon

last: Leonard

address: 2 avenue du Prof Léon Bernard

country: France

institute: Université Rennes

summary: Bone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis of in vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRpos MSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma.

overall_design: The DOHH2 cells harboring the mention D19 or D40 in the sample name were sorted using flow cytometry associated cell sorting, from DOHH2 grafted RAGγc femurs. The number indicates the day post-graft when we sorted the DOHH2 cells. The "D0" samples represent a sample of cultured DOHH2 from the day of the graft (to compare the cells that were injected before and after in-vivo growth.

first: Elise

last: Dessauge

first: Baptiste

last: Brauge

first: Karin

last: Tarte


title: Lymphoma B cells remodel bone marrow stromal cell network into  extracellular matrix-producing cancer-associated fibroblasts (scRNAseq)

overall_design: We extracted stromal and endothelial cells from the femurs of ungrafted RAGγc KO mice (control), PBS-grafted mice (SHAM) and DOHH2-grafted (within the femur) mice at D19 and D40 post-graft. We sorted them using Flow cytometry associated cell sorting.


title: scramble control and Hif-1a knockdown mESCs cultured under normoxia and two-day hypoxia

city: Wuhu

first: Xiaopeng

last: Shen

address: 1 East Beijing Rd.

institute: Anhui Normal University

summary: we performed RNA-seq on the total RNA samples collected from the  scramble and Hif-1a knockdown AB2.2 mESCs cultured under normoxia and two-day hypoxia, respectively. Sramble and Hif-1a knockdown AB2.2 mESCs were  built by  infecting AB2.2 cells with lentiviruses. Each group contained three biological replicates. The expression matrix was obtained by Hisat2 followed by Stringtie.

overall_design: RNA-seq of scramble and shHif-1a AB2.2 cells cultured under normoxia and two-day hypoxia

first: Meng

last: Li


title: CEBPB-mediated transcriptional regulation in Kupffer cells in metabolic dysfunction-associated steatohepatitis [CUT&Tag]

last: Chen

overall_design: Wildtype mice were fed with HFHCD or normal diet (ND) for 12 weeks. FACS-sorted KCs were used for library preparation of C/EBPb CUT&Tag


title: Effects of dietary carbohydrate source on Florida pompano growth and nutritional physiology

city: Fort Pierce

last: Bradshaw

state: FL

department: Aquaculture & Stock Enhancement

institute: Florida Atlantic University at Harbor Branch Oceanographic Institute

summary: A 10-week feeding trial was conducted to determine an appropriate carbohydrate source evaluating growth performance, feed utilization, hepatic activity, whole-body fatty/amino acid composition, liver transcriptomics and gut microbiome for Florida pompano (Trachinotus carolinus). Five isonitrogenous (46.67% crude protein), iso-lipidic (15.15% crude lipid) and isocaloric (385Kcal/100g digestible energy) diets were formulated containing 14% of different source of carbohydrates: whole wheat grain flour (WG), wheat starch (WS), whole corn grain flour (CG), corn starch (CS) and dextrinized corn starch (DCS). The results indicated that: highest percentage weight gain (PWG) and specific growth rate (SGR) were found in fish fed with whole wheat grain flour (WG) diet, the highest feed efficiency (FE) was shown in WG and WS diets, lowest conversion index (CI) was observed in fish fed with WG diet and the highest protein efficiency ratio (PER) was shown in in WS diet. The poorest values were observed in fish fed with CS and DCS diets. The whole-body crude protein and total amino acid and fatty acids composition was not significantly affected by different sources of carbohydrates in the diets. In fish fed with the WG diet, glucose levels in plasma and liver were significantly low while liver glycogen content was statistically high compared to the other diets. Liver transcriptomics analysis revealed differentially expressed genes (DEGs) and gene ontology (GO) enrichment analysis highlighting up/down regulated biological functions depending on the carbohydrate source. The microbial community presented high diversity and richness among treatments. Overall, results indicated that whole wheat grain flour is the more adequate dietary carbohydrate source based on production performance, physio-biochemical and molecular approaches. These data are critical when formulating a complete commercial feed for sustainable and profitable culturing of Florida pompano

overall_design: Our study was designed to determine how different types of carbohydrate sources affects Florida Pompano fish health with transcriptomics (RNA-Seq), gut mucosa microbiome analysis, fatty acid analysis, proximate composition, amino acid analysis, and biochemical analysis. Five isonitrogenous, iso-lipidic and isocaloric diets were formulated meeting the requirements for Florida pompano to contain 14% of different carbohydrate sources: whole wheat grain flour (WG), wheat starch (WS), whole corn grain flour (CG), corn starch (CS) and dextrinized corn starch (DCS).

first: Juan

last: Paredes

first: Michael

last: Habet-Tsion

first: Martin

last: Riche

first: Sahar

last: Mejri

last: Bradshaw II

first: Carlie

last: Perrricone

first: PaulS

last: Wills


title: ALKBH1-mediated tRNA 5-formylcytidine modification facilitates codon-biased translation and leukemogenesis [Ribosome-seq]

city: Monrovia

first: Jianjun

state: CA

department: Systems Biology

institute: Beckman Research Institute of City of Hope

summary: Here, we show that ALKBH1 is overexpressed in acute myeloid leukemia (AML) and required for AML development/maintenance and leukemia stem cell (LSC) self-renewal, but is dispensable for normal hematopoiesis. ALKBH1 plays a pivotal role in regulating mitochondrion structure/functions and facilitating oxidative phosphorylation (OXPHOS) to generate energy for AML cell survival/proliferation. Mechanistically, we uncover that ALKBH1 specifically promotes 5-formylcytidine (f5C) formation in tRNAs to expand tRNA decoding capacity and promote translation of essential targets. This mechanism/phenomenon is termed “epitranscriptomic Midas touch”, which promotes expression of WDR43 and BCL2, two crucial targets of ALKBH1 in AML. ALKBH1 targeting markedly enhances BCL2 inhibitor (Venetoclax)’s efficacy in AML treatment. Collectively, our studies reveal the functional importance of a previously unappreciated signaling (i.e., ALKBH1/tRNA-f5C/WDR43/BCL2) in AML, and highlight the potential of targeting ALKBH1 for cancer therapy.

overall_design: ALKBH1 KD was induced after 4 days treatment with doxycycline (1 ug/ml), then were treated with 100 μg/ml cycloheximide for 7 min at 37 ℃ to prevent translation before standard ribosome profiling protocol.

first: Chao

first: Keren

last: Zhou

first: Tong

last: Wu


title: ICE-A: A chromatin interaction-based tool for improved annotation of distal cis-regulatory elements reveals novel regulatory functions of lineage-restricted transcription factors in lymphocytic development [PLAC-seq]

city: Linköping

first: Mikael

last: Sigvardsson

address: Lab1, Level 13

institute: Linköping University

summary: Stage- and lineage-specific gene expression patterns are controlled by a complex interplay between transcription factors, the epigenetic landscape, and the 3-dimensional (3D) structure of the DNA. The 3D structure is of great importance because it allows for the formation of DNA loops that juxtaposition distal regulatory elements to the promoters, allowing for functional synergy and high-level transcription of a given target gene. However, chromatin loops can be highly complex and can span several megabases of genomic context and where one enhancer can interact with several promoters during cell development affecting gene regulation in a time and cell context dependent manner. Thus, our understanding of gene regulation is largely dependent upon our ability to link regulatory elements to the correct target genes. For this purpose, several approaches have been developed, including proximity annotation, linking a given regulatory element to the closest coding gene, and correlation of gene expression to changes in DNA accessibility. While these approaches are valuable, they are based on rather simplified assumptions that disregard the stage- and lineage-restricted 3D organization of the genome. To facilitate the linkage of regulatory elements to their target genes, we have developed a novel tool for easy incorporation of chromatin configuration data into the annotation process. Using this annotation procedure to explore gene regulatory networks in early lymphocyte development, we show that lineage-specific transcription factors target regulatory elements that are annotated to both lineage-specific and broadly expressed genes. Furthermore, several regulatory elements annotated to lineage-specific genes were annotated to alternative promoters in a context dependent manner. These data highlight how efficient annotation procedures for linking distal regulatory elements to target genes provide valuable insights into gene regulatory networks.

overall_design: H3K4me3 Proximity ligation-assisted chromatin immunoprecipitation sequencing (PLAC-seq) of Scid.adh.2C2 T-cell progenitor cell line.

first: Johanna

last: Tingvall-Gustafsson

first: Christina

last: Jensen

first: Jonas

last: Ungerbäck


title: Genomic and Behavioral Signatures of Selection for Ethanol Preference from the Heterogeneous Stock Collaborative Cross Mice – The Central Nucleus of the Amygdala

city: Portland

first: Justin

last: Anderson

state: OR

address: 3181 S.W. Sam Jackson Park Road

department: Behavorial Neuroscience

institute: Oregon Health & Science University

summary: Alcohol use disorder (AUD) is a complex disease with heritability of ~0.5, indicating genetic and non-genetic factors contribute to risk. Identifying gene expression networks contributing to risk using post-mortem human brain tissue has the limitation of conflating risk for AUD with consequences of alcohol use. We leveraged mice selectively bred for differential ethanol preference from a highly genetically diverse population to overcome this limitation. Ethanol intake was highly correlated with preference, high-preferring (HP) mice consumed more sweet- but not bitter-tasting solutions compared to low-preferring (LP) mice, and the lines did not differ in rate of ethanol elimination. Adult, ethanol-naïve HP and LP mice contributed tissue from the central nucleus of the amygdala (CeA), a region critical to ethanol preference and intake. Single-nuclei and bulk RNA sequencing data were used to identify cell types and transcriptome changes related to selective breeding for differential risk for ethanol preference. Single nuclei analysis identified populations of inhibitory (~48% of cells) and excitatory (~23%) neurons, and non-neuronal (~29%) cells, but no differences in cell-type composition or gene expression were identified between the lines. Bulk CeA analysis identified differences between the lines for: (1) gene expression (2996 genes), (2) expression variability (426 genes), and (3) wiring (407 significant gene-gene correlations). Overall, lower variance was found in the HP line. Reduced gene-gene correlation, also found in HP mice, suggested that selection for high preference induced changes in transcriptional regulation resulting in reduced connectivity, specific to gene networks enriched in markers for inhibitory neurons expressing Isl1 and Tac1.

overall_design: Mice underwent bidirectional selective breeding for ethanol intake (10% ethanol v/v in water, two bottle choice) for 5 generations starting from the Heteroengeous Stock - Collaborative Cross, a strain which emcompasses ~90% of all genetic diversity known in Mus Musculus. After 5 generations, high and low preference  mouse had ~10fold different prefernce for ethanol and consumed 7fold differently. Ethanol naive mice from generation 5 were sacrificied at adulthood and brain tissue was collected for the central nucleus of the amygdala, a region important for addiction. bulk RNA sequencing (paired-end) was run on 200 samples (n=50/sex/strain) to a mean depth of 20M, and aligned to the GRCm39 using STAR. Raw counts were normalized using the limma+voom method, and differential expression and weighted gene co-expression analysis were carried out to identify risk vs protection markers for ethanol drinking.

middle: Q

first: Priscila

last: Darakjian

first: Robert

last: Hitzemann

first: Rita

last: Cervera-Juanes

first: Kip

last: Zimmerman

first: Cheryl

last: Reed

first: Denesa

last: Lockwood

first: Angela

last: Ozburn

first: Tamara

last: Phillips


title: Effect of PLEK2 knockdown on the gene expression of HCT116 cells

city: jinan

first: qian

last: zhou

state: li xia

address: wenhua western road

institute: shandong university

summary: To investigate the effect of PLEK2 in the regulation of HCT116 cells. We then performed gene expression profiling analysis using data obtained from RNA-seq of HCT116 cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for  HCT116 cells from shNC and shPLEK2.

first: Qian

first: Baobing

last: Zhao


title: PLEK2 functions as a co-factor of YTHDF2 to enhance TYMS mRNA stability in colorectal cancer

summary: High expression of nucleotide synthetic enzyme thymidylate synthase (TYMS) is responsible for the resistance to fluorouracil (FU) treatment and worse survival in colorectal cancer. Herein, we revealed that Pleckstrin-2 (PLEK2), highly expressed in CRC, enhanced TYMS mRNA stability via its interaction with YTHDF2 in a m6A-dependent manner. Silencing of PLEK2 led to the downregulation of TYMS, and consequent inhibition of CRC cell proliferation via the cellular senescence. Additionally, PLEK2 is also required for CRC cell migration, invasion and stemness-like properties. PLEK2 inhibition is sufficient to ameliorate the progression of CRC. Moreover, loss of PLEK2 inhibited AOM/DSS-induced colonic tumorigenesis in vivo. Together, our study identified PLEK2 as a key regulator for the progress of CRC via the regulation of TYMS expression, and demonstrated that PLEK2 is a novel therapeutic target for CRC.

overall_design: 1X107 HCT116 cells transduced with retroviruses encoding HA tagged PLEK2 and empty vector were collected and lysed according to the instructions of RIP Immunoprecipitation Kit (Geneseed, P0101). Briefly, Agarose beads coated with 2µg of HA antibodies against human PLEK2 were incubated with prepared cell lysates overnight at 4°C. RNA was eluted by 15 µL of RNase-free water in the following steps, then ribominus rRNA were depleted by the rRNA depletion kits (Thermo, K155001), for high-throughput sequencing, the libraries were prepared following the manufacturer’s instructions and applied to Illumina NovaSeq 6000 system for 150 nt paired-end sequencing (Novogene).

last: Zhou


title: Effect of ablation of CEACAM1 on gene expression in human regulatory T cells

city: Miami

first: Ying

last: Ding

address: 1600 NW 14th st

department: Microbiology and Immunology

institute: University of Miami

summary: To study the contribution of CEACAM1 in human Tregs, CEACAM1 was knocked out in ex-vivo expanded human Tregs by Crispr/Cas9. Tregs transfected with scramble gRNAs were used as controls. After electroporation, scramble or CEACAM1KO Tregs were subcultured with IL-2 for 7 days and RNA was isolated for genome-wide RNA-seq. Gene expression profiling analysis was performed using data obtained from RNA-seq of two replicates of CEACAM1KO and control cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for CEACAM1KO and scramble control human Tregs.

first: Molly

last: Dalzell

first: Alejandro

last: Villarino

first: Thomas

last: Malek


title: FAD4T mouse model reflects Alzheimer’s disease pathobiology in bone marrow-brain axis

first: Junjie

last: Gao

address: 600 Yishan Road

institute: Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: In this study, we established a FAD4T mouse model, which reflects Alzheimer’s disease pathobiology in bone marrow-brain axis.

overall_design: To construct the map of FAD4T mouse model, we generated scRNA-seq profiles from bone marrow and brain samples obtained from 2-month and 8-month FAD4T mouse and WT mouse on the 10x platform.


title: Nasal epithelium gene expression profiles from vaccinated or non-vaccinated humans challenged with influenza viruses

city: Seattle

first: kathie

last: walters

state: WA

address: 401 Terry Ave N

institute: Institute for Systems Biology

first: Kathie-Anne

last: Walters

first: John

last: Kash

first: Jeffery

last: Taubenberger


title: Anther transcriptome analysis of Lycium barbarum at different developmental stages

city: yinchuan

first: ru

middle: ya

last: wei

address: helanshanxilu

institute: NingxiaUniversity

summary: The causes of male sterility of Lycium barbarum  were analyzed by comparing the anther transcriptomes of fertile and sterile lines

overall_design: The reason for male sterility of Lycium barbarum was found by the transcriptome analysis of anthers of fertile and sterile lines of Lycium barbarum at different periods.

first: Shujuan

last: Yang

first: Yaru

last: Wei


title: Mimicking   gastric  bypass glucotonic effect: the role of atypical PKC activation and GLUT1

city: Seoul

first: UnHo

last: Kang

address: 15F, 241, Gangnam-daero, Seocho-gu

institute: Arontier

summary: Bariatric surgery has demonstrated a significant therapeutic impact in reducing obesity and achieving euglycemia in diabetic patientspatients with diabetes. We previously demonstrated that iIntestinal glucotonic transformation, defined as increased intestinal serum glucose uptake and secretion into the lumen, has anplays a vital  important role in bypass surgeryies. Altered transcriptomes were evaluated in variable intestinal glucotonic models and big-data artificial  intelligence AI-based drug discovery systems. We found noted  that protein kinase C (PKC) activation mimics the intestinal transcriptome changes alterations observed in during intestinal glucotonic transformation. Among PKC subfamilies, atypical PKC promotes GLUT1- mediated  intestinal glucotonic transformation without inducing oncogenic proliferation. Intestinal aPKC activation through via the transposon expression vector induces serum glucose uptake into intestinal tissue and excretion into the lumeinal space. . Prostratin, a non-tumorigenic phorbol ester, was found observed to activate aPKC and induce a similar glucotonic effect. Taken together, our study results highlightCollectively, we identified  a a new chemical compound and target molecular pathways  that may provide a distinct and effective approach to to treating diabetes .

overall_design: DEG collection from five pairwise comparisons;  Transcriptome data from five different pairwise comparisons of glucotonic and non-glucotonic tissue/cells were applied to screen for potential drugs/targets through REMEDY platform. Three comparisons are from RYGB operated glucotonic tissue and sham operated non-glucotonic tissue. These are pair one: RYGB alimentary limb (AL) vs. Sham, jejunum part (Sham JEJU), pair two: RYGB common limb (CL) vs. Sham, ileum part (Sham IL), and pair three: RYGB distal intestine from Otsuka Long-Evans Tokushima Fatty (OLETF) rat (OLE-RYGB CL) vs. sham distal intestine from OLETF rat (OLE-Sham IL). Another comparison involves the glucotonic and non-glucotonic sections of the intestine in rats that underwent RYGB, indicated as pair four: RYGB CL+ vs. RYGB CL-. The last one is from heparin-binding epidermal growth factor-like growth factor (HB-EGF) treated and non-treated (NT) cells, indicated as pair five: intestine epithelial cell line (IEC18)-HBEGF vs. IEC18-NT.

first: Zhenyu

last: Hong

first: Mohamed

middle: E

last: Farh

first: Chan

middle: W


title: Effect of knockdown of miR-BART19-3p on gene expression of AGS EBV cells

status: Public on Jul 22 2025

city: Hengyang

first: Jing

state: Hunan Province

address: 28# Changsheng west Road, Zhengxiang District

department: The First Affiliated Hospital of University of South China

institute: South China University

summary: EBV microRNAs, especially rightward transcript (BART) microRNAs play key roles in the tumor growth of EBVaGC. However, the effects of EBV-miR-BART19-3p in EBVaGC remain largely unknown. Here, we report that EBV-miR-BART19-3p is highly expressed in EBVaGC and promoted the proliferation of EBV-associated gastric cancer cells in vitro and accelerate xenograft tumor growth in vivo. Molecularly, EBV-miR-BART19-3p directly targets the growth arrest and DNA damage-inducing protein Beta mRNA (GADD45B) and downregulates its protein expression, which consequently reduce cell cycle G2/M phase arrest. Reconstitution of GADD45B can rescue the proliferation phenotype caused by EBV-miR-BART19-3p in EBVaGC cells, highlighting the role of GADD45B in EBV-miR-BART-driven Gastric cancer. Our study indicated Epstein-Barr Virus MicroRNA BART19-3p played an oncogenic role by a novel mechanism of inhibiting GADD45B in EBVaGC, which provides new insights and might be a potential therapeutic strategy for EBVaGC patients.

overall_design: Total RNAs of AGS EBV cells respectively transfected with EBV-miR-BART19-3p antagomir and NC antagomir for 48 huors were isolated using TRIzol, by triplicated.  RNA-seq profiling  was conducted on the DNBSEQ platform by BGI Genomics (Shenzhen, China) after RNA quality control.

first: Runliang

last: Gan


title: Microarray detection of m5C RNA methylation modification in human lung cancer tissues

city: Nanning

first: Aruo

address: No.22 Shuangyong Road, Qingxiu District

institute: Guangxi Medical University

summary: A microarray assay of circRNA  m5C methylation modification in human lung cancer tissues compared the altered RNA  m5C methylation modification in cancerous and paraneoplastic tissues of lung cancer patients.

overall_design:
Two-condition experiment, cancerous tissue vs. paraneoplastic tissue, three individuals mixed samples
Please note that each raw file contains both Cy5 (IP) and Cy3 (Sup) data and is linked to the corresponding IP sample records.


title: Effect of ablation of PRDM1 on gene expression in human regulatory T cells

first: Ying

summary: To gain an insight into the contribution of BLIMP-1 in human Tregs, we ablated PRDM1 in ex-vivo expaned human Tregs by Crispr/Cas9. Tregs transfected with scramble gRNAs were used as controls. 7 days after transfection, Tregs were rested overnight in media, and were re-stimulated through the TCR and IL2R for 16 hr prior to isolation of RNA for genome-wide RNA-seq. Gene expression profiling analysis was performed using data obtained from RNA-seq of four replicates of PRDM1KO and control cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PRDM1KO and control cells.

first: Luis

last: Nivelo

first: Alejandro


title: Aging Induces CD8+ T Cells to Support Cancer Progression

city: Baltimore

first: Bongsoo

last: Park

state: Maryland

address: 251 Bayview Blvd

department: Translational Gerontology Branch

institute: National Institute on Aging

summary: The role of CD8+ T cell exhaustion in cancer in aging remains poorly understood. Although it is assumed that the age-related accumulation of exhausted, and thus dysfunctional, CD8+ T cells would increase tumor growth, in this study we provide an alternative  paradigm: tumors in aged, but not young hosts, progress by actively using CD8+ T cells. These CD8+ T-cells are transcriptionally and epigenetically distinct and non-exhausted expressing the cell surface immunophenotype CXCR6+ CD39+ CD73+ CD101+ CD8+ (termed DP8). They accumulate in healthy aging, and at least in part, after induction with B cells presenting cognate antigens.  Tumors that progress in aged mice recruit DP8 cells via the CXCL16/CXCR6 axis to suppress anti-tumor CD4+ T cells in an ADP/adenosine-dependent manner. This tumor-enhancing mechanism of DP8 cells appears to be active in older humans, as we detected DP8-like cells in various tumors, including late-onset breast cancer. We propose this novel tumor-promoting role of CD8+ T cells should be considered in the development of therapeutics tailored for the elderly as, targeting DP8 cell function or recruitment can reverse tumor growth in aged mice.

overall_design: ATAC sequencig were performed to compare the epigenome between AT3 and B16 tumor samples

first: Ioana

last: Bodogai

first: Fatima

middle: Z

last: Brakia

first: Isabel

last: Beerman

first: Bira

last: Arya


title: Gene expression profiles of E. coli in the gut of inflammatory bowel disease models.

city: Suwon-si, Gyeonggi-do

first: kim

last: jungtak

state: suwon

address: Yeongtong-gu, 206, World cup-ro, songjaegwan 711

institute: Microbiology part/ajou University

summary: Gut microbiota modulation has emerged as a potential therapeutic and diagnostic approach for inflammatory bowel disease (IBD). We generated transcriptomic data by Record-seq, a method based on CRISPR-Cas system, that enables recording of gene expression in reporter bacteria within the mouse gut.

overall_design: IBD was induced in male C57BL/6 mice by DSS or DNBS administration. Additionally, feed containing Lactobacillus crispatus was provided to the mice to modulate the gut microbiota. For record sequencing, we utilized Escherichia coli BL21(de3) transformed with pFS_0453 plasmid containing a CRISPR array. Plasmid-derived spacer libraries were constructed according to original Record-seq protocol and sequenced on a Illumina NovaSeq X Plus platform.

first: Jungtak

last: Kim

first: Karolina

middle: H

last: Prazanowska

first: Su Bin

last: Lim

first: Sun


title: Transcriptomic analysis of lncrna NRAD1 knockdown in SUM149 Breast cancer cells

city: Halifax

first: Paola

last: Marcato

address: 5850 College street

department: Pathology

institute: Dalhousie university

summary: SUM149 breast cancer cells were treated with NRAD1 gapmers for 48 hrs and RNA was extracted. RNA was analysed on affymetrix human transcriptome array 2.0

overall_design: Three replicates per treatment

first: Hannah

last: Cahill

first: Jaganathan

last: Venkatesh


title: Effect of Lactobacillus crispatus on E. coli gene expression profiles in the gut of mice with inflammatory bowel disease.


title: RNA sequencing of flow-sorted lung parenchymal CD226+ and CD226- CD8 T cells from mice chronically infected with Mycobacterium tuberculosis

city: Worcester

first: Tomoyo

last: Shinkawa

address: 55 N Lake Ave

institute: UMass Chan Medical School

summary: Lung CD8⁺ T cells induced during chronic tuberculosis exhibit functional heterogeneity, comprising both effector and exhausted states. CD226 is the most differentially expressed gene distinguishing effector from exhausted CD8⁺ T cells. Functionally, CD226 serves as a costimulatory molecule that promotes recognition of Mtb-infected macrophages. Loss of CD226 expression correlates with the onset of CD8⁺ T cell exhaustion during tuberculosis.

overall_design: This study compared lung parenchymal (CD45-IV-) antigen-experienced (CD44+) CD226+ and CD226- CD8 T cells, sorted from C57BL/6 mice infected with Mycobacterium tuberculosis for 24-28 weeks.

first: Samuel

last: Behar


title: Cathelicidin LL-37-induced transcriptome of human keratinocyte identifies chemokine CXCL10 link to T cell-mediated rosacea pathogenesis via JAK-1/STAT-1 pathway

city: Doha

first: Tanwir

last: Habib

address: Al Luqta Street

country: Qatar

institute: Weill Cornell Medicine Qatar

summary: Rosacea is a chronic inflammatory disease of facial skin with unknown pathophysiology. Abnormal overexpression of human antimicrobial peptide LL-37 is a hallmark of rosacea. However, its significance in the rosacea pathogenesis is not fully understood. We sought to understand the molecular mechanisms of LL-37-mediated rosacea-like inflammation in an in-vitro model of normal human epidermal keratinocytes. Transcriptome profiling of LL-37-treated keratinocytes identified signatures of interferon (IFN)-stimulating genes (ISGs) such as CXCL10, IFIT2, RSAD2 and CXCL11 among the top upregulated differentially expressed genes. Gene ontogeny (GO) enrichment of biological processes revealed activation of cellular response to molecules of bacterial origin, response to chemokines, and cytokine mediated signaling pathways. While KEGG enrichment analysis revealed the activation of TNF signaling, IL-17 signaling, NF-kB signaling and chemokine signaling among the most significant pathways.  Remarkably, T cell recruiting chemokine CXCL10 turns out to be the most abundant inflammatory mediator overexpressed upon LL-37 exposure. Mechanistically, LL-37 induced CXCL10 production relied on JAK-1/STAT-1 signaling pathway. In summary, our findings provide a crucial link to keratinocyte: T cell crosstalk and blockade of CXCL10:CXCR3 axis or JAK-1/STAT-1 pathways can be an effective anti-inflammatory strategy to reduce rosacea inflammation by restricting pathogenic T cells infiltration.

overall_design: Primary keratinocytes (NHEK) from three healthy donors were stimulated with or without LL-37 in a 6-well collagen 1-coated culture plate for 6-hours. Cells were lysed and RNA was isolated using RNAeasy Mini kit (Qiagen). RNA was further processed for Affymetrix microarray.

first: Abdul

last: Ansari

first: Fareed

last: Ahmad

first: Thesni

last: Raheed

first: Cynthia

last: Elizabeth

first: Sara

last: Alharami

first: Anh

last: Jochebeth

first: Martin

last: Steinhoff


title: RNA-seq profiling of CD34-high and CD34-low fibroblasts from pubertal mouse mammary glands

city: Parkville

first: Gordon

last: Smyth

state: Vic

address: 1G Royal Pde

department: Bioinformatics

country: Australia

institute: Walter and Eliza Hall Institute of Medical Research

summary: CD34-high and CD34-low fibroblast cells were FACS sorted from the mammary glands of 6-week-old (pubertal) female FVB/N mice and profiled by RNA-seq.

overall_design: Three biological replicates were obtained, each replicate being a pool of two mice. CD34-high and CD34-low cell populations were sorted from each replicate, to make six samples in total.

first: Goknur

last: Giner


title: Aging evokes immunosuppressive CD8+ T cells actively to support cancer

first: Bongsoo

last: Park

summary: Age-associated dysregulation and exhaustion of CD8+T cells is thought to impair antitumor responses and thus, increase cancer. Here we present evidence that CD8+T cells also actively promote tumor progression with age. We find that aging induces an expansion of a unique population of CXCR6+CD101+CD8+T cells expressing ectonucleotidases CD39 and CD73 (termed DP8 cells) via B cells presenting cognate antigen. We show that progressive (but not regressive) tumors in aged mice recruit these DP8 cells by expressing CXCL16 to suppress antitumor effector cellsusingthe ectonucleotidases. As a result, tumor growth in aged mice can be reversed by blockingthe function and/or recruitment of DP8 cells to tumors, while check-point inhibition with anti-PD1 Ab increases DP8 cells and drives tumor expansion.This tumor-enhancing mechanism of DP8 recruitment appears to be also active in older humans, aswe find DP8-like cells in various tumors, including late onset breast cancer.We propose that this novel tumor-promoting activity of CD8+T cells needs to be considered in the development of therapeutics tailored for the elderly.

overall_design: Transcriptome analysis of CD45+ cells from Young AT3 (n=3), Old AT3 (n=3) Young B16 (n=3), and Old B16 (n=3) tumors

first: Ioana

last: Bodogai

first: Isabel

last: Beerman

first: Bira

last: Arya


title: PELO-1/Pelota-mediated ribosome-associated quality control counteracts aging and age-associated pathologies across species.

city: Daejeon

first: Seung-Jae

middle: V

last: Lee

address: 291, Daehak-ro, Yuseong-gu, Daejeon, Republic of Korea

institute: Korea Advanced Institute of Science and Technology

summary: Ribosome-associated quality control (RQC) is a pivotal biological process that governs the fidelity of mRNA homeostasis and protein synthesis. Here, by focusing on PELO-1/Pelota, the ribosome rescue factor crucial for RQC and mRNA surveillance, we sought to determine how RQC and the mRNA surveillance contributed to longevity and the prevention of premature aging and age-associated diseases. We performed RNA sequencing (RNA seq) analysis that compared the transcriptome of long-lived daf-2(-) with that of short-lived daf-2(-) pelo-1(-); skih-2(-) mutant C. elegans.

overall_design: The investigation of the changes of gene expression in long-lived daf-2(-) with that of short-lived daf-2(-) pelo-1(-); skih-2(-) mutant C. elegans.

first: Jongsun

first: Eun Ji

last: Kim

first: Seokjin

last: Ham


title: Gene expression profiling of mir-1825 alteration in Head and neck squamous cell carcinomas

city: Houston

first: Chad

last: Creighton

state: TX

address: One Baylor Plaza, Mail Stop: BCM305

department: Biostatistics, Ducan Cancer Center

institute: Baylor College of Medicine

summary: Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common malignant cancer worldwide. To understand the pathogenesis of HNSCC, we investigated the effects of miR-1825 overexpression on tumor formation capacity of head and neck cancer cells in vivo using NUDE mice. We searched for potential targets of miR-1828 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene.

overall_design: Gene expression microarray analyses were performed on FGFR1 KO K19-tva/fgfr1loxP/loxP mice and control K19-tva  mice.

first: Omer

last: Karatas

first: Fengju

last: Chen


title: Epigenome-wide Analysis of Asthma from The Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE) Project

city: Boston

first: Benjamin

middle: A

last: Raby

address: 300 Longwood Ave

institute: Boston Children's Hospital

type: Methylation profiling by genome tiling array

summary: Epigenetic analysis of DNA methylation for whole blood and CD4+ cell types was performed. Gene expressions were compared betweenpatients with asthma and the control groups.

overall_design: The Asthma BioRepository for Integrative Genomic Exploration (Asthma BRIDGE) was a multicenter North American initiative to establish a cohort of asthmatic and healthy subjects for the study of integrative genomics. It includes Asthma BRIDGE participants for whom genotype, methylation and gene expression data were available. Asthma BRIDGE recruited subjects from six cohorts participating in the EVE Consortium for an asthma GWAS: the Chicago Asthma Genetics (CAG) study, the Childhood Asthma Management Program (CAMP), the Childhood Asthma Research and Education Network (CARE), the Children’s Health Study (CHS), the Genomic Research on Asthma in the African Diaspora (GRAAD) study, and the Mexico City Childhood Asthma Study (MCCAS). Written informed consent was obtained from all subjects prior to enrollment in the study, in accordance with the local ethics committees at each institution.

first: Raby

last: Benjamin A

first: Carey

last: Vincent

first: Chun

last: Sung Gook

first: Millstein

last: Joshua

first: Nguyen

last: My-Nhi


title: Next generation sequencing facilitates quantitative analysis of transcriptional profiling of  Candida albicans wild type treated or not with SP1

city: Jinan

first: Wenqiang

last: Chang

state: Shandong

address: No. 44 West Wenhua Road

institute: Shandong University

summary: Fungi have developed a variety of mechanisms to resist antifungals for survival. Uncovering their resistance mechanisms will aid in development of alternative therapeutics for fungal infections. In our study, a time-lapse microscopic imaging method was used to screen a molecule library and SP1 was identified as a short-time antifungal agent and exhibited biphasic killing pattern. Investigation of the underlying mechanism for the biphasic killing pattern and short-time activity of SP1 may expand the utility of this important class of spirobisnaphthalenes and uncover a new drug-resistant mechanism in fungi. mRNA profiles of SP1 treated Candida albicans SC5314, untreated Candida albicans SC5314 were generated by deep sequencing, in triplicate, using illumina NovaSeq 6000. The sequence reads that passed quality filters were analyzed at the transcript isoform level. qRT-PCR validation was performed using SYBR Green assay. The RNA-seq and qPCR results revealed an upregulation of heat shock response related genes including HSP90, SSA1 and osmotic and oxidative stress related genes including HOG1 and PBS2 and CAP1. Some common transporters encoding genes were also accordingly altered in SP1 treated group.

overall_design: mRNA profiles of SP1 treated Candida albicans SC5314,untreated Candida albicans SC5314 were generated by deep sequencing, in triplicate, using illumina NovaSeq 6000.

first: Hongxiang

last: Lou


title: The effect of lncRNA NRAD1 knockdown on mature miRNA levels in MDA-MB-468 and SUM149 cells

first: Paola

last: Marcato

summary: NRAD1 was knocked  down using GapmeRs specific to NRAD1.  The breast cancer cells used in this study were confirmed to have NRAD1 expression by qPCR and knockdown of NRAD1 was confirmed by qPCR.

first: Hannah

last: Cahill

first: Jaganathan

last: Venkatesh


title: Tumor suppressive activities for pogo transposable element derived with KRAB domain via ribosome biogenesis restriction [RNA-seq]

first: Mahmoud

middle: Adel

last: Bassal

state: Massachusetts

address: 3 Blackfan Circle

department: Hematology and Oncology

institute: Beth Israel Deaconess Medical Center

summary: Transposable elements play indispensable roles in human development, contributing significantly to pluripotency and embryogenesis. However, Transposable elements sequences also play a role in human pathologies, particularly cancer, where they function as cis/transcriptional regulators, produce non-coding RNAs, and act as mutagens disrupting tumor suppressors. Despite this understanding, the involvement of Transposable elements-derived genes in tumor pathogenesis remains poorly understood. In this study, we conducted systematic analyses of TEG expression across various human cancers, highlighting the significant role of POGK. Our findings demonstrate that POGK functions as a tumor suppressor in TNBC. We found that POGK globally inhibits ribosomal gene expression using RNA-Seq. Furthermore, we reveal that POGK interacts with the co-repressor TRIM28 to directly block the transcription of ribosomal genes RPS16 and RPS29 through ChIP-Seq data, thereby leading to widespread inhibition of ribosomal biogenesis. Crucially, our findings reveal that POGK is deactivated through isoform switching in clinical TNBC. This discovery sheds new light on its previously unidentified and repurposed roles in regulating tumor growth.

overall_design: To identify genes regulated by POGK, we analyzed the gene expression profiles of POGK-overexpressing stable cells compared to control cells in the SUM159 cell line using HISEQ.

first: Zhenbo

last: Tu

first: George

last: Bell

first: Yanzhou

last: Zhang

first: Yi

last: Hu

first: Liza

last: Quintana

first: Deeptha

last: Gokul

first: Daniel

middle: G

last: Tenen

first: Antoine

last: Karnoub


title: Tumor suppressive activities for pogo transposable element derived with KRAB domain via ribosome biogenesis restriction [ChIP-Seq]

overall_design: To identify the direct binding targets (DNAs) by POGK, we conducted chromatin immunoprecipitation (ChIP) assays using POGK-overexpressing stable cells compared to control SUM159 cells, followed by Illumina NovoSeq sequencing of the ChIP DNA samples.


title: RNA-seq profiling of CD34-high and CD34-low fibroblasts from mouse mammary tumors

first: Gordon

last: Smyth

summary: A mouse model of Wnt1-driven mammary tumors was generated. Specifically,  PdfraH2B-GFP mice (C57BL/6) were crossed to MMTV-cre(A)-Wnt1 transgenic mice (FVB/J) to generate the raGFP-Wnt1 mouse line. CD34-high and CD34-low fibroblast cells were then FACS sorted from mammary tumors from the raGFP-Wnt1 mice.

overall_design: CD34-high and CD34-low fibroblast cells were sorted from three raGFP-Wnt1 tumors, to create six samples in total.

first: Goknur

last: Giner


title: Sulfur assimilation improves SAM-dependent methylation

city: Tianjin

first: Xinchen

address: No. 92 Weijin Street

institute: Tianjin University

summary: We employed omic data and conducted comparative analysis in Saccharomyces cerevisiae strains with different S-adenosine-L-methionine (SAM) level. This strategy can help us locate the limiting factor for SAM availability. We found sulfur assimilation emerged as the most significantly enriched pathway and further confirmed that sulfur assimilation was the dominant limiting step of SAM biosynthesis in the whole cell system.

overall_design: Transcriptome analysis of Saccharomyces cerevisiae strains with different SAM levels

first: Ying

last: Wang

first: Yingjin

last: Yuan


title: miRNA profiling of human muscle and serum exosomes samples throughout TRAD and HITT training and detraining

city: Dayton

first: Madhavi

last: Kadakia

state: OH

address: 3640 Colonel Glenn Hwy

department: Biochemistry and Molecular Biology

institute: Wright State University

type: Non-coding RNA profiling by high throughput sequencing

summary: The randomized, dose-response PHITE (Precision High-Intensity Training Through Epigenetics) clinical trial used molecular and phenomic profiling to compare responses to traditional (TRAD) endurance -plus resistance training (TRAD) and high-intensity tactical training (HITT). Serum exosomal-derived microRNAs were profiled from 90 individuals throughout a 12-week traditional (TRAD) or high-intensity tactical training (HITT) intervention and after a subsequent 4-week detraining period. miRNA data and associated molecular and phenomic profiling was used to (1) assess the affects of TRAD and HITT on physiological performance and body composition, (2) assess the integrated biocircuitry driving exercise adaptations and response heterogeneity and (3) define the effects of early-phase detraining.

overall_design: Small RNA sequencing of miRNA was performed on vastus lateralis muscle biopsies and seum exosome samples from male and female participants throughout 12 weeks of either TRAD or HITT exercsie and after a 4-week detraining period. Nine serum samples were collected from each individual (pre-exercise, 0, 3 and 24hr after the first week 0 round of exercise, repeated in week 12, and a final week 16 detraining sample). Seven muscle biopsies were collected in parallel (same timepoints as serum, but excluding the 0hr timepoint in week 0 and week 12). Exosomal RNA was purified from serum. Total mRNA was isolated from muscle and enriched for small RNA. Barcoded, pooled libraries were sequenced on the IonTorrent Proton using Ion P1 chips.

first: Michael

last: Craig

first: Jin

first: Akshay

last: Hira

first: Timothy

middle: J

last: Broderick


title: Iron deprivation affects aboveground cell wall biosynthesis in Populus and the role of PtrbHLH011 [RNA-seq]

city: Upton

first: Meng

last: Xie

state: NY

address: 50 Bell Ave

institute: Brookhaven National Laboratory

summary: Growing bioenergy crops like poplars on marginal land is appealing to minimize competition for arable land. However, this is hampered by a lack of insight into secondary cell wall (SCW) changes caused by environmental stress. Iron (Fe) deficiency is widespread and detrimental to plants. Here, we report that Fe deprivation increases SCW biosynthesis of poplar stem via the gene regulatory network (GRN) involving the transcription factor PtrbHLH011, whose expression is downregulated by Fe deprivation. PtrbHLH011 is a potent repressor of SCW, overexpression of which resulted in a reduction of stem SCW by over 65%. Furthermore, PtrbHLH011 overexpression induced foliar disease symptoms caused by reduced iron and flavonoid accumulations. By constructing PtrbHLH011-controlled GRN, we discovered that PtrbHLH011 binds to the AAAGACA sequence and represses essential genes for SCW biosynthesis, flavonoid biosynthesis, and iron homeostasis. Our results suggest that PtrbHLH011 functions as a co-regulator for the rapid activation of systematic Fe-deficiency responses.

sample_organism:
Populus trichocarpa
Populus tremula x Populus alba

overall_design: To study the biological impacts of iron deprivation on poplar, we treated poplar plants by either iron deprivation (0 µM Fe) or control (10 µM Fe) for 21 days in a hydroponic growth system. Tissues from young leaf and 3rd internode were then collected for total RNA extraction and paired-end 150 bp RNA-seq. Comparative gene expression profiling analysis of iron deprivation treated and control treated plants. To study the biological impacts of PtrbHLH011 overexpression, we extracted total RNAs from leaf and stem tissues of 4-month-old PtrbHLH011 overexpression and emptry vector control transgenic poplar plants. Paired-end 150 bp RNA-seq was performed. Comparative gene expression profiling analysis of PtrbHLH011 overexpression and empty vector control plants.


title: Iron deprivation affects aboveground cell wall biosynthesis in Populus and the role of PtrbHLH011 [ChIP-seq]

overall_design: PtrbHLH011-10xMyc was transiently expressed in poplar protoplasts. Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for PtrbHLH011 using anti-Myc antibody


title: Upregulated cholesterol biosynthesis facilitates the survival of methylation-retaining AML cells following decitabine treatment [pooled TEM-seq]

city: Newcastle

first: Heather

last: Lee

state: NSW

address: University Drive, Callaghan

institute: The University of Newcastle

type: Methylation profiling by high throughput sequencing

summary: DNA hypomethylating agents (HMAs) are used to treat acute myeloid leukaemia (AML) and myelodysplasia patients who are unsuitable for intensive chemotherapy, but low response rates and therapy-resistant relapse remain significant challenges. To optimise HMA efficacy, we must understand how resistance and relapse arise from cells that survive treatment. Here we combine single-cell multi-omic analysis with parallel colony-forming assays to link HMA-induced molecular heterogeneity with functional consequences in AML cells. HMAs, azacytidine cytidine (azacytidine ) and decitabine (decitabine ), induced global epigenetic heterogeneity associated with upregulation of inflammatory responses and cell death pathways in a subset of hypomethylated cells. Some AML cells maintained high DNA methylation during treatment, and these methylation-retaining cells had increased self-renewal capacity following decitabine , but not azacytidine . Molecular profiling of individual colonies revealed upregulated cholesterol biosynthesis as an adaptation to HMA treatment, and inhibition by rosuvastatin enhanced decitabine  effects in vitro and in vivo. Thus, HMA-induced heterogeneity has important implications for AML cell growth and statins are a candidate co-treatment strategy to delay or prevent HMA-resistant relapse.

overall_design: Leukaemia cell lines (HL-60, MOLM-13 and MV-4-11) were treated with hypomethylating agents (HMAs) over 72 hours (doses at 0, 24 and 48 hours) with either Decitabine (DAC), or azacytidine cytidine (AZA) and compared to untreated (Unt) cells. After 72 hours treatment (day 3), cells were seeded into MethoCult, with or without Rosuvastatin (ROS) added to the MethoCult (for DAC and Unt samples), and cultured for a further 14 days (all treatment combinations). Samples from whole well 'pooled' colonies were measured by TEM-seq to obtain global DNA methylation levels. Samples were taken from 3 time-points (days 6,10 and 17) for the time-course experiment and a single time-point (D17) for the statin treatment combination experiment, as indicated.

first: Danielle

last: Bond

first: Sean

middle: M

last: Burnard

first: Kumar

last: Uddipto

first: Kooper

last: Huntreated

first: Brooke

last: Harvey

first: Charley

last: Lawlor-O’Neill

first: Ellise

last: Roper

first: Sam

last: Humphries

first: Luiza

middle: S

last: Reinhardt

last: Murray

first: Nikola

last: Bowden

first: Anoop

last: Enjeti

first: Nicole

last: Verrills

first: Carlos

last: Riveros

first: Kim-Anh

last: Cao