title: Cyclosporine A Accelerates Neurorecovery Transcriptional Trajectory in a Swine Model of Diffuse Traumatic Brain Injury

city: Villanova

first: Susan

last: Margulies

address: 805 Stoke Road

institute: Emory University

summary: Mild traumatic brain injury (mTBI) is a leading cause of morbidity in children with both short and long-term neurological, cognitive, cerebrovascular, and emotional deficits. Given limited understanding of the transcriptional changes associated with its pathophysiological cascades, we studied formalin fixed paraffin embedded (FFPE) tissues from the frontal cortex (FC) and the hippocampus + amygdala (HA) regions of swine (N=40) after a sagittal rapid non-impact head rotation (RNR). We then sequenced RNA to define transcriptional changes at 1 day and 1 week after injury and investigated the protective influence of cyclosporine A (CsA) treatment.  Differentially expressed genes (DEGs) were classified into 5 temporal patterns (Early, Transient, Persistent, Intensified, Delayed, or Late), and were more abundant at 1 week than 1 day. Shared significant gene ontology annotations in both regions included terms associated with neuronal distress at 1 day and neurorecovery at 1 week. CsA (20mg/kg/day) infused for 1 day, (beginning at 6 hours after injury) accelerated 466 DEGs in the FC and 2794 DEGs in the HA, such that the CsA treated transcriptional profile were associated with neurorecovery. Overall, our data reveals the effects of anatomic region and elapsed time on gene expression post-mTBI and motivates future studies of CsA treatment.

overall_design: To investigate temporal transcriptional profiles and the neuroprotective effect of CsA treatment, we utilized piglet FFPE brain tissue from sham/naïve animals, animals sacrificed at 1 day, 1 week, and 30 hours following CsA treatment. All samples underwent RNA-sequencing and gene expression profiling was conducted on samples that passed library prep (i.e. 40 subjects).

first: Oluwagbemisola

last: Aderibigbe

first: Levi

middle: B

last: Wood


title: Effect of sleep deprivation on non-small cell lung cancer metastasis

status: Public on Apr 30 2025

city: Shijiazhuang

first: Shuxian

last: Yin

state: Hebei province

address: zhongshan road

country: China

institute: Hebei Medical University

type: Expression profiling by high throughput sequencing

summary: Recent research has shed light on the influence of sleep deprivation on tumor progression, particularly in non-small cell lung cancer (NSCLC), although the precise underlying mechanisms remain poorly understood. Several studies have highlighted alterations in immune cell dynamics and intercellular communication as key consequences of sleep deprivation. Moreover, heightened sympathetic nervous system activity has been implicated in this context. To explore these phenomena further, transcriptome sequencing was conducted in tumor-bearing mice subjected to normal sleep conditions versus sleep deprivation. This approach aimed to delineate the molecular mechanisms linking sleep deprivation to NSCLC progression.

overall_design: To examine the impact of sleep deprivation on the regulation of the tumor microenvironment, we categorized tumor-bearing mice into three groups: a control group with undisturbed sleep patterns, an experimental group subjected to sleep deprivation, and a treatment group with clozapine N-oxide. This approach aimed to elucidate how sleep deprivation influences the dynamics of the tumor microenvironment in this model.


title: Effect of isoproterenol on RAW264.7 in vitro

summary: Recent research has shed light on the neuroimmunomodulation of macrophages, but the precise underlying mechanisms remain poorly understood.The maintenance of homeostasis in various organizations requires neuroimmune communication between the sympathetic nervous system and the immune system. The sympathetic nervous system adjusts macrophage phenotype via the adrenergic pathway.This study aimed to delineate the molecular mechanisms linking adrenergic pathway to RAW264.7.

overall_design: To examine the impact of adrenergic pathway on the regulation of RAW264.7, we categorized the RAW264.7 cells  into three groups. The first group was stimulated solely with IL-4 to induce M2 polarization. The second group was stimulated with IL-4 along with the β2 adrenergic receptor agonist isoproterenol (ISO), activating the β2 adrenergic signaling pathway in RAW264.7 cells. The third group was pre-treated with the β2 adrenergic receptor antagonist ICI118,551, followed by stimulation with IL-4 and ISO, effectively blocking the β2 adrenergic signaling pathway in RAW264.7 cells. This approach aimed to elucidate how adrenergic pathway influences the dynamics of RAW264.7.


title: Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [Multiome]

city: Cambridge

first: Bertie

last: Gottgens

address: Jeffrey Cheah Biomedical Centre

country: United Kingdom

institute: University of Cambridge

type: Genome binding/occupancy profiling by high throughput sequencing

summary: During mouse gastrulation, extraembryonic mesoderm (ExEM) contributes to the extraembryonic yolk sac (YS) and allantois, both of which are essential for successful gestation. Although the genetic networks coordinating intra-embryonic mesodermal subtype specification are well-studied, the mechanisms driving ExEM diversification are poorly understood. Here, we reveal that embryoid body (EB) in vitro differentiation generates two distinct lineages of mesodermal cells matching YS and allantois respectively. Combining in vitro models with in vivo chimeric embryo analysis, we discover that Eomesodermin (Eomes) regulates the formation of a subset of YS-fated ExEM but is dispensable for allantois formation. Furthermore, simultaneous disruption of Eomes and T impedes the specification of any YS or allantois mesoderm, indicating compensatory roles for T during allantois formation when Eomes is disrupted. Our study highlights previously unrecognized functional and mechanistic diversity in ExEM diversification and endothelial development and introduces a tractable EB model to dissect the signaling pathways and transcriptional networks driving the formation of key extraembryonic tissues.

overall_design: 10x Genomics single-cell multiome (RNA + ATAC) sequencing was performed on ESC EB cultures at 12 hour intervals from D3 to D5 of cultures. Either DMSO (WT) or dTAG (Eomes-KD) was added to the samples between D3 and D5.

first: Bart

last: Theeuwes

first: Luke

middle: T

last: Harland

first: Elizabeth

middle: J

last: Robertson

first: Berthold


title: SGLT2 inhibitor upregulates myocardial genes for oxidative phosphorylation and fatty acid metabolism in Gαq mice

city: Boston

first: Boston University

last: Microarray and Sequencing Resource

state: MA

address: 72 East Concord Street, E631

department: Microarray and Sequencing Resource

country: USA

institute: Boston University

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

overall_design: Refer to individual Series


title: CaMKK2 regulates mechanically-induced macrophage fate

city: Madison

first: jianhong

last: ou

state: WI

address: 330 N Orchard Street

institute: Morgridge institute for research

summary: Macrophages play crucial roles in immunity and tissue homeostasis, exhibiting diverse phenotypes influenced by their microenvironment. While matrix stiffness is recognized as a key regulator of macrophage fate, the underlying mechanism remains elusive.  Here, we investigate primary bone marrow-derived macrophages (BMDMs) in a physiologically relevant 3D environment using a dynamic stiffening collagen-based hydrogel system. We show that increasing matrix stiffness promotes BMDM polarization towards a pro-regenerative phenotype, characterized by elevated CD206 levels, and M2-like gene signature. Mechanistically, we identify the calcium/calmodulin-dependent kinase kinase 2 (CaMKK2) as an important component of molecular machinery controlling BMDM response to stiff microenvironment. Surprisingly, the blocking of CaMKK2 does not interfere with the IL-4-induced pro-regenerative programs. On the contrary, the inhibition of this kinase abolishes phenotypic and transcriptional changes induced by stiffness, highlighting the specific function of the CaMKK2-STAT6 axis in macrophage mechanosensory signaling. Functionally, matrix stiffening promotes M2-like/pro-tumoral polarization of BMDM in a CaMKK2-dependent manner, confirming the critical role of this kinase in the tumor microenvironment and identifying a direct pro-tumoral effect mediated by Camkk2-signaling in macrophages. In a murine wound healing model, stiffened matrices drive immune cell recruitment and macrophage polarization towards a pro-regenerative phenotype, facilitating vascularization, while deletion of Camkk2 impairs this phenomenon. Our findings elucidate the mechanistic basis of matrix stiffness-mediated macrophage fate determination, identifying CaMKK2 as a druggable target to selectively modulate the mechanoresponsiveness of macrophages in malignant and injured tissues.

overall_design: To investigate the effect of matrix stiffness on the regulation of macrophages activation programs, we leveraged 3D dynamics hydrogels cultures. Immunoprofiling, transcriptomics, and phospho-proteins analysis were used to determine the effects of matrix stiffness on BMDM. WT and Camkk2-/- BMDM were used to determine the role on CaMKK2 in mechanosensory signaling.

first: Ya

last: Guan

first: Min

last: Zhang

first: Luigi

last: Racioppi

first: Sharon

last: Gerecht


title: Arf1-deficiency-induced neuronal surplus fatty acid synthesis evokes neurodegeneration through mtDNA releasing and inflammatory activating in microglia

city: 上海

first: Xv

last: Li

address: 复旦大学

institute: fudan university

summary: The crucial role of lipid metabolism disorders and neuronal inflammation has been revealed in many studies of neurodegenerative diseases. However, the pathological connection between lipid droplets and neuronal immune circuits remains poorly understood. We have previously reported a neuronal-specific Arf1-knockout mouse as an ideal lipid metabolism disorder-induced neurodegeneration model. Here, we found that Arf1-deficiency first induced surplus fatty acid synthesis and lipid droplets (LDs) accumulation through the AKT-mTORC1-SREBP1-FASN axis, which further triggered endoplasmic reticulum (ER)-mitochondrial stress cascade via calcium flux. The organelle stress cascade further induced mitochondrial DNA (mtDNA) to be released into the cytoplasm. Meanwhile, the FASN-driven fatty acid synthesis in the Arf1-deficient neurons also induced lysosomal sphingolipids accumulation that caused dysfunction of autophagy and lysosomes, which enables the neuronal mtDNA to transfer to microglia via extracellular vesicles (EVs) and activates the inflammatory pathways to aggravate neurodegeneration. Furthermore, inhibition of FASN or boosting autophagy in vivo reversed neuronal degeneration disease in Arf1-knockout mice. Our study suggests a unified pathological function of LD in NDs and proves that inhibition of fatty acid synthesis-induced inflammation might be a therapeutic route to neuronal degeneration disease.

overall_design: To investigate the functions of Arf1 on regulating lipid metabolism. We knocked down Arf1 in N2a cells via shRNA and then performed gene expression profiling analysis from the RNA-seq data of the control and Arf1-deficient N2a cells.

first: Xu

first: Yuetong

last: Wang

first: Seven

middle: X

last: Hou


title: Comparison of the responses of alveolar macrophages from rats, mice and humans following particle overload [human]

city: Woluwé

first: Jérôme

last: Ambroise

address: Avenue Hippocrate 54

department: Institut de Recherche Expérimentale et Clinique

country: Belgium

institute: Université catholique de Louvain

summary: Chromic inhalation of poorly soluble low toxicity particles, like titanium dioxide or carbon black, at high exposure levels leading to particle overload in alveolar macrophages, can induce chronic inflammation and lung cancer in rats, but not in mice. Whether this rat adverse response is predictive for humans remains unsettled for more than 40 years. In order to clarify the human relevance of the adverse rat response to particle overload, primary rat, mouse and human alveolar macrophages were exposed in vitro to overload of titanium dioxide or carbon black particles, and their activation profile was analyzed by RNAseq. We report, here, a robust transcriptomic signature of poorly soluble low toxicity particle overload in rat alveolar macrophages in vitro ,which was not observed in mouse macrophages. A similar but markedly lower response was recorded in human macrophages.

overall_design: Primary human alveolar macrophages were exposed in vitro for 4 days to control, non-overload or overload conditions of Printex90 (carbon black) or G1-1 (titanium dioxide) particles. For each condition, three replicates were analyzed

first: Laeticia

last: Perez

first: Bertrand

last: Bearzatto

first: François

last: Huaux

first: Dominique

last: Lison

first: Charles

last: Pilette

first: Antoine

last: Froidure


title: Eomesodermin dependence delineates the formation of spatially and functionally diverse extra-embryonic hematovascular tissues [scRNA-seq: chimera]

first: Bertie

last: Gottgens

overall_design: Single-cell RNA sequencing was performed on chimeric embryos containing Eomes KO and wild-type (WT) cells. Chimeras were produced by injecting WT blastocysts with tdTomato+ Eomes KO embryonic stem cells (ESCs). Embryos were collected in several pools (replicates) at around stage E8.5 and then dissociated into single-cell suspensions. The cells were sorted using FACS based on tdTomato expression to distinguish between WT (tdTom-) and Eomes KO (tdTom+) cells in each pool. The sorted cells were then prepared for scRNA-seq using the 10x Genomics 3' v3 kit.

first: Bart

last: Theeuwes

first: Luke

last: Harland

first: Elizabeth

last: Robertson

first: Berthold


title: The Myocardial Infarction Platelet Transcriptome

city: New York City

first: Florencia

last: Schlamp

state: New York

address: 435 East 30th Street

institute: NYU Langone Health

summary: Despite the abundance of data demonstrating the critical role of platelets in myocardial infarction (MI), few studies have characterized the MI-platelet transcriptome in the acute or chronic setting. The association between MI subtype and platelet transcriptomic signature have not been explored. We report that transcripts associated with actin cytoskeleton and Rho family GTPase signaling, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n=40 MI, n=38 controls), and do not significantly change over time. We identified 79 platelet genes chronically altered post-MI that are also associated with future cardiovascular events in independent cardiovascular disease validationcohort (n=135). Compared to patients with MI with non-obstructive coronary arteries (MINOCA), platelets from patients with MI due to obstructive coronary artery disease (MI-CAD) were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased TNFα signaling. Hierarchical clustering identified three MI transcriptomic subgroups with disinctive pathways and MI correlates, including a group with MI-CAD, and a group that was predominantly MINOCA. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients, in the acute and chronic setting, and reveal a transcriptomic signature with distinct clinical features.

overall_design: 38 controls and 40 MI patients, in some subjects samples collected at a followup time point

first: Tessa

last: Barrett

first: Matthew

last: Muller

first: Angela

middle: H

last: Lee

first: Macintosh

middle: G

last: Cornwell

first: Elliot

middle: L

last: Williams

first: Nathaniel

middle: R

last: Smilowitz

first: Judith

last: Hochman

first: Kelly

middle: V

last: Rugles

first: Harmony

last: Reynolds

first: Jeffrey

middle: S

last: Berger


title: Comparison of the responses of alveolar macrophages from rats, mice and humans following particle overload [2nd exp]

first: Jérôme

last: Ambroise

overall_design: Primary rat alveolar macrophages were exposed in vitro for 4 days to control, non-overload or overload conditions of Printex90 (carbon black) or G1-1, G3-1 or Bayertitan (all three titanium dioxide) particles. For each condition, three replicates were analyzed

first: Laeticia

last: Perez

first: Bertrand

last: Bearzatto

first: François

last: Huaux

first: Dominique

last: Lison


title: Comparison of the responses of alveolar macrophages from rats, mice and humans following particle overload


title: Fecal Microbiota Transplantation Alters Lung Transcriptome and Signaling Pathway

city: beijing

first: xiaoyan

last: liu

address: Gongti South Road

institute: Capital Medical University

summary:
Rationale: Recent studies suggest a potential link between gut bacterial microbiota dysbiosis and PAH, but the exact role of gut microbial communities, including bacteria, archaea, and fungi, in PAH remains unclear.
Objectives: To investigate the role of gut microbiota dysbiosis in idiopathic pulmonary arterial hypertension (IPAH) and to assess the therapeutic potential of fecal microbiota transplantation (FMT) in modulating PAH progression.
Methods: Using shotgun metagenomics, we analyzed gut microbial communities in IPAH patients and healthy controls. FMT was performed to transfer gut microbiota from IPAH patients or MCT-PAH rats to normal rats and from healthy rats to MCT-PAH rats. Hemodynamic measurements, echocardiography, histological examination, metabolomic and RNA-seq analysis were conducted to evaluate the effects of FMT on PAH phenotypes.
Measurements and Main Results: Gut microbiota analysis revealed significant alterations in the bacterial, archaeal, and fungal communities in IPAH patients compared to healthy controls. FMT from IPAH patients induced PAH phenotypes in recipient rats. Conversely, FMT from healthy rats to IPAH rats significantly ameliorated PAH symptoms, restored gut microbiota composition, and normalized serum metabolite profiles. Specific microbial species were identified with high diagnostic potential for IPAH, improving predictive performance beyond individual or combined microbial communities.
Conclusions: This study establishes a causal link between gut microbiota dysbiosis and IPAH and demonstrates the therapeutic potential of FMT in reversing PAH phenotypes. The findings highlight the critical role of bacterial, archaeal, and fungal communities in PAH pathogenesis and suggest that modulation of the gut microbiome could be a promising treatment strategy for PAH.

overall_design: To explore the therapeutic mechanism of FMT on pulmonary arterial hypertension (PAH), we conducted RNA-seq analysis to compare the transcriptomic differences in lung tissues between monocrotaline-induced PAH rats (MCT) and FMT-treated rats (NTM).


title: Single-cell landscape of peripheral immune cells in MAFLD/MASH [scRNA-seq]

city: Biberach a.d. Riss

first: Eric

last: Simon

address: Birkendorfer Str. 65

country: Germany

institute: Boehringer Ingelheim Pharma GmbH & Co KG

summary: Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to metabolic dysfunction-associated steatohepatitis (MASH) and is a major cause of liver cirrhosis. Although liver inflammation is the hallmark feature of MASH vs MAFLD, the involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study. Patients have been histologically stratified and further characterized by liver bulk RNA-Seq. Peripheral immune cells from patients and control blood samples have been comprehensively profiled using bulk and single RNA-Seq. Results: 22 patients with fibrosis stage less then F3 have been histologically stratified into patients with low, medium and high disease activity score (NAS). In contrast to fibrosis, NAS group correlated with non-invasive imaging readouts and blood biomarkers of liver damage and inflammation (ALT, AST). Prevalence of type 2 diabetes and obesity was increased with NAS stage. Bulk RNA-seq profiling of patient liver biopsies revealed gene signatures that were positively and negatively associated with NAS. Known marker genes for liver fibrosis where up-regulated on RNA level.  Blood bulk RNA-sequencing showed only moderate differences in patients versus healthy controls. In contrast, single cell analysis of white blood cells revealed multiple alterations of immune (sub-) populations including increased abundance of immature B-cells and myeloid suppressor cells in MAFLD/MASH patients as well as disease-association of neutrophil sub-populations.

overall_design: scRNAseq samples were collected from white blood cells from healthy controls and MAFLD/MASH patients

first: Agnes

middle: A

last: Steixner-Kumar

first: Diana

last: Santacruz

first: Tobias

last: Geiger

first: Werner

last: Rust

first: Dennis

last: Böttner

first: Oliver

last: Krenkel

first: Ehsan

last: Bahrami

first: George

last: Okafo

first: Thomas

middle: F

last: Barth

first: Mark

last: Haenle

first: Wolfgang

last: Kratzer

first: Patrycja

last: Schlingeloff

first: Julian

last: Schmidberger

first: Heike

last: Neubauer

first: Alec

last: Dick

first: Markus

last: Werner


title: Cell of origin and expression profiles of pseudomyxoma peritonei derived from the appendix

city: Tsukiji

first: Rei

last: Noguchi

state: Tokyo

address: 5-1-1, Chuo-ku, Tokyo, Japan

department: Division of Rare Cancer Research

country: Japan

institute: National Cancer Center Research Institute

summary: Pseudomyxoma peritonei (PMP) is a rare disease caused by mucin-producing tumors developed most frequently from the appendix. This disease shows distinct clinical features by the cancerous cells producing mucin in the abdominal cavity. Although frequent mutations in the KRAS and GNAS genes have been reported in PMP, gene expression profiles of the tumors remain to be fully clarified because of its rarity and the difficulties in collecting pure cancerous cells scattered with a large volume of mucins. To disclose the molecular features of PMP cells, we performed RNA-seq analysis of ten PMPs and their matched non-tumorous colonic epithelium in combination with laser-microdissection. As a result, we identified a total of 5,747 differently expressed genes (DEGs) between the tumors and non-tumorous colonic epithelium. A cell-of-origin subtype analysis with nearest template prediction algorithm corroborated that PMP tumor cells belonged to the goblet cell subtype, suggesting that tumorous cells of PMP have a feature of differentiation to goblet cells. Interestingly, gene set enrichment analysis (GSEA) uncovered that the tumors were significantly associated with three ontology terms, namely epithelial mesenchymal transition (EMT), tumor necrosis factor-alpha (TNF-α), and angiogenesis. Comparison of gene expression profiles between disseminated peritoneal adenomucinosis (DPAM) and peritoneal mucinous adenocarcinomas (PMCA) identified a total of 687 DEGs. Additional GSEA revealed that ontology terms “G2M checkpoint” and “E2F targets” were significantly enriched in PMCA supporting the view that PMCA has more aggressive properties than DPAM. These data may be useful for the understanding of molecular characteristics of PMP.

first: Kiyoshi

last: Yamaguchi

first: Yoichi

last: Furukawa


title: Coilin, the Cajal body marker protein, is regulated by SUMOylation and mediates expression of innate immune response genes in human

city: Jackson

first: Lavanya

last: Challagundla

state: MS

address: 2500 North State Street

department: Cell and Molecular Biology

institute: University of Mississippi Medical Center

summary: Cajal bodies (CBs) are membraneless organelles whose mechanism of formation is still not fully understood. Many proteins contribute to the formation of CBs, including Nopp140, WRAP53, and coilin. SUMOylation, a post-translational modification, of coilin involves multiple different lysine residues. Additionally, coilin is also found in the nucleoplasm where its role is still being understood. Here, we demonstrate a novel mechanism examining the interaction changes of coilin when its SUMOylation is disrupted. We look at both global SUMOylation inhibition and its effect on CB formation, as well as targeted SUMOylation inhibition of coilin itself in cells by developing a coilin SUMO mutant. We found upon two types of global SUMOylation inhibition, as well as upon transfection of the coilin SUMO mutant, that CBs increased in number and decreased in size. Additionally, we saw via coimmunoprecipitation the coilin SUMO mutant has altered interaction with Nopp140. This demonstrates increased mechanistic ties to CB formation and SUMOylation. Furthermore, RNA sequencing and small RNA sequencing on a primary cell line with few CBs showed that coilin impacts the response to lipopolysaccharide-induced stress. Collectively, our results identify SUMOylation as a novel mechanism driving CB formation and highlights a positive role for human coilin in innate immunity.

overall_design: RNA was isolated by TRIzol Reagent (Invitrogen Life Technologies, Grand Island, NY, USA) and purified with RNeasy Mini Kit (QIAGEN; Hilden, Germany) according to manufacturer’s instructions. RNAseq was used to analyze differential expression between the following groups. RNA was evaluated for quality (Qubit fluorimeter) and fidelity using Qiagen QIAxcel Advanced System, with all sample demonstrating and RIS > 8. Libraries were generated with TruSeq stranded mRNA kit (Illumina; San Diego, CA, USA), indexed with TruSeq RNA CD indexes (Illumina; San Diego, CA, USA), and sequenced with NextSeq 2000 P3 (PE200) flow cell (Illumina; San Diego, CA, USA)

first: Sara

middle: K

last: Tucker

first: Douglas

middle: M

last: McLaurin

first: Shanzida

last: Siddique

first: Michael

middle: D

last: Hebert


title: microRNA396 is a coordinative regulator that can be modulated to reconcile the reverse relationship between fruit size and quality in tomato

city: COLLEGE PARK

first: Xudong

last: Zhu

state: Maryland

address: 10300 Baltimore Ave.

institute: USDA-ARS-BARC-FQL

type: Non-coding RNA profiling by high throughput sequencing

summary: The microRNA396 (miR396) family is a group of small, non-coding RNA molecules that regulates expression of growth-regulating factors (GRFs) in plants. In this study, the researchers used short tandem target mimic (STTM) and artificial miRNA (amiRNA) techniques to either decrease or increase the expression of miR396 in tomatoes to investigate its role in regulating organ size and nutrition accumulation. Decreasing the expression of miR396 increased organ size, total soluble solids (TSS), and secondary metabolites in the fruits. The researchers also observed that increased miR396 expression reduced fruit size and weight but promoted the growth of axillary buds. These results suggest that modulating the expression of miR396 may be a way to improve the productivity and quality of tomatoes by reconciling fruit size and nutrition. Analysis of mRNA profiling in tomato fruits from mature-green and red-ripe stages in the three genotypes, STTM396, amiR396, and the wild-type, demonstrated an accountable altered expression of genes involved in photosynthetic capacity, sugar synthesis and unloading, and starch synthesis. The researchers tentatively concluded that modulating miR396 expression in tomatoes could be a useful approach for improving both productivity and quality through genetic modifications.

overall_design: In this study, we used short tandem target mimic (STTM) and artificial miRNA (amiRNA) technologies to generate a set of experimental materials with up- or down-regulated miR396 expression and studied the effect of miR396 on fruit size, productivity, and quality in tomatoes.

first: Haiping

last: Liu

first: Tianbao

last: Yang


title: Canagliflozin-induced sex-specific adaptive metabolism in bone

city: New York

first: Shoshana

last: Yakar

state: NY

address: 345E 24th Street

institute: New York University

summary: Sodium glucose transporter-2 inhibitors (SGLT2i) were designed to increase the excretion of glucose through urine and lower blood glucose levels independent of insulin. Beyond their primary functions, SGLT2i have been observed to induce a wide range of metabolic effects.  To understand how SGLT2i-mediated metabolic changes affect skeletal metabolism, six months old  genetically diverse UM-HET3 mice were treated with canagliflozin (CANA), a SGLT2i, for 1, 3, and 6 months. The comprehensive analysis included assessments of serum hormones, morphological and mechanical properties of long bones and vertebrae, and the bone tissue metabolome. The findings demonstrated significant sex-specific metabolic adaptations to CANA treatment, evident as early as one-month post-treatment. Male mice treated with CANA exhibited notable reductions in body weight, serum leptin, and insulin levels, alongside decreases in proinflammatory markers TNFα and MCP-1. These changes were accompanied by decreased serum levels of bone remodeling markers P1NP and CTX, and by reduced periosteal bone remodeling as determined by histomorphometry. The bone tissue metabolome analysis further underscored distinct sex-specific metabolic responses and adaptations to CANA treatment. Specifically, CANA-treated female mice demonstrated enhanced adenine and adenosine salvage pathways and purine metabolism relative to female controls. In contrast, CANA-treated male mice exhibited increased activity in the FXR/RXR pathway and the GABAergic receptor signaling pathways compared to their control counterparts. Notably, the most significant difference in the metabolome between CANA-treated males and females was observed in the Branched-Chain Amino Acid (BCAA) Catabolism pathway. This study highlights the novel finding of sex-specific metabolic and skeletal adaptations to SGLT2i treatment, providing new insights into the complex interplay between glucose metabolism and bone health, while emphasizing the need for tailored therapeutic strategies that consider sex-specific responses to SGLT2i treatment.

overall_design: To test the effects of CANA treatment on the potential of bone MSCs to differentiate to osteoblasts, bone marrow was isolated from mice treated with control or CANA-containing diet for three months. Bone marrow MSCs cultured for 7-days in -modified minimum essential medium (MEM, CAT#) containing 10% fetal calf serum (FBS), penicillin/sterptomycin and fungizone. At day 8 cells were cultured in osteoblast induction media containing: MEM, 10%FBS,  penicillin/streptomycin, fungizone, dexamethasone (Sigma Cat # D8893), ß-glycerol phosphate (Sigma Cat # 50020), and ascorbic acid (Sigma cat# A4403-100MG). Cells from each mouse were cultured for several assays: 1) RNAseq analysis following 10 days in culture, 2) alkaline phosphatase staining (Sigma cat#) following 14 days in culture, 3) alizarin red staining (Sigma cat#), following 21 days in culture 4) VonKosa staining (Sigma cat#) following 21 days in culture.

first: Sher

last: Bahadur Poudel

first: Carolyn

last: Chlebek

first: Ryan

last: Ruff

first: Gozde

last: Yildirim

first: Bin

last: Hu

first: Zhiming

last: He

first: Ankita

last: Shinde

first: Christopher

last: De Jesus

first: Lukasz

last: Witek

first: Timothy

last: Bromage

first: Thomas

last: Neubert

first: Clifford

last: Rosen


title: RNA-seq of murine MA9 Gata2 f/f and Gata2 -/- (Gata2 KO)  leukemias with Nutlin

city: Philadelphia

first: Kathrin

last: Bernt

state: PA

address: 3501 Civic Center Boulevard,

institute: Children's Hospital of philadelphia

summary: Transcriptional effects of Nutlin treatment in murine MA9 leukemia after loss of Gata2.

overall_design: RNA-seq of murine MA9 Gata2 f/f and Gata2 KO leukemias with Nutlin. Three independent samples for each condition.

first: Fatemeh

last: Alikarami

first: Michael

last: Xie


title: Coilin, the Cajal body marker protein, is regulated by SUMOylation and mediates expression of innate immune response genes in human (miRNA)

first: Lavanya

last: Challagundla

overall_design: The Revvity Nextflex Small RNA NGS Kit v4 was employed to construct small RNA libraries from total RNA samples following the manufacturer's protocols. The procedure included adapter ligation, reverse transcription, and PCR amplification, culminating in size selection to enrich for small RNA species. Libraries were quantified, pooled (n=24), and sequenced on an Illumina platform to generate high-throughput sequencing data for downstream analysis. Library was sequenced with NextSeq 2000 P3 (50 cycle) flow cell (Illumina; San Diego, CA, USA)

first: Sara

last: Tucker

first: Douglas

last: McLaurin

first: Shanzida

last: Siddique

last: Hebert


title: Bulk Liver in MAFLD/MASH

first: Eric

last: Simon

summary: Background & Aims: Metabolic dysfunction associated steatotic liver disease (MAFLD) progresses to steatohepatitis (MASH) and is a major cause of liver cirrhosis. In the early disease stage, liver inflammation is absent. However, the early involvement of the peripheral immune cell compartments in disease progression is poorly understood and single cell profiles of peripheral immune cells in MAFLD/MASH are not known. Methods: MAFLD/MASH patients and healthy volunteers have been prospectively enrolled into a cross-sectional study. Patients have been histologically stratified and characterized by liver bulk RNA-Seq.

overall_design: Bulk RNA-seq samples were collected from liver needle biopsies from MAFLD/MASH patients and histologically stratified by disease stage (NAS score)

first: Agnes

last: Steixner-Kumar

first: Diana

last: Santacruz

first: Tobias

last: Geiger

first: Werner

last: Rust

first: Dennis

last: Böttner

first: Oliver

last: Krenkel

first: Ehsan

last: Bahrami

first: George

last: Okafo

last: Barth

first: Mark

last: Haenle

first: Wolfgang

last: Kratzer

first: Patrycja

last: Schlingeloff

first: Julian

last: Schmidberger

first: Heike

last: Neubauer

first: Alec

last: Dick

first: Markus

last: Werner


title: SGLT2 inhibitor upregulates myocardial genes for oxidative phosphorylation and fatty acid metabolism in Gαq mice (genotype x ERTU)

first: Boston University

last: Microarray and Sequencing Resource

summary: Background. Mitochondrial dysfunction with decreased ATP production and increased release of reactive oxygen species (ROS) is a hallmark of the failing heart. Although SGLT2 inhibitors have been shown to improve myocardial metabolism in the failing heart, independent of diabetes, the mechanism of this effect is not clear.  Objectives. Our goal was to test the effect of the SGLT2 inhibitor ertugliflozin on mitochondrial gene expression and function in myocardium and isolated mitochondria from non-diabetic mice with dilated cardiomyopathy due to cardiac-specific over-expression of Gαq. Methods. Gαq and wild-type (WT) littermates 4 weeks of age were treated for 16 weeks with or without the SGLT2 inhibitor ertugliflozin (ERTU) formulated in the chow (0.5 mg/g chow).  Results. From weeks 4 to 20, Gαq mice developed progressive cardiac hypertrophy, dilation, contractile dysfunction, myocyte apoptosis and interstitial fibrosis – all of which were prevented by ERTU treatment. Isolated cardiac mitochondria from Gαq mice had decreased maximal ATP production and increased ROS release - both of which were normalized by ERTU. In isolated beating hearts from Gαq mice, contractile reserve and high energy phosphates measured simultaneously by 31P NMR spectroscopy were decreased - and both were improved by ERTU. In Gαq mice, marked suppression of myocardial gene programs for oxidative phosphorylation and fatty acid metabolism was reversed by ERTU. Conclusions. The SGLT2 inhibitor ERTU corrected the expression of myocardial gene programs for oxidative phosphorylation and fatty acid metabolism, thereby leading to increased production of ATP, decreased release of mitochondrial ROS, and amelioration of the consequences of mitochondrial dysfunction on myocardial structure and function.

overall_design: To investigate the effect of the SGLT2 inhibitor, ertugliflozin, on the cardiac phenotype of a dilated cardiomyopathy mouse model via cardiac-specific over-expression of Gαq, all mice were fed a control chow diet with or without the SGLT2 inhibitor ertugliflozin formulated into the chow from 4 weeks of age until sacrifice at 20 weeks of age. 5 representative left ventriclar cardiac tissue samples per group were assessed, for a total of 20 samples in the RNAseq. The reference group is the Wild-type Control Diet (WT CD) group without Ertugliflozin treatment. Gene expression profile analysis was performed using this RNAseq dataset.

first: Dominique

last: Croteau

first: Wilson

last: Colucci


title: Sustained-release anti-JUN therapeutic abrogates post-operative adhesions [scRNA-Seq]

city: Stanford

first: Michael

last: Januszyk

state: CA

address: 257 Campus Dr

institute: Stanford University

summary: Radiation therapy is an important treatment component for a majority of cancer patients but involves significant side effects. In this study, we establish a large animal (porcine) irradiation model that recapitulates key clinical features of skin radiation induced fibrosis. We perform single cell-RNAs seq on porcine tissue following irradiation. Furthermore, we analyze the effect of Deferoxamine (DFO) treatment on Radiation Induced Fibrosis (DFO).

overall_design: scRNA-seq of unsorted cells from pig skin tissue following various radiation regiments.

first: Michelle

last: Griffin


title: RNA-seq of murine MA9 Gata2 f/f and Gata2 -/- (Gata2 KO) leukemias.

first: Kathrin

last: Bernt

summary: Transcriptional effects of Gata2 deletion in murine MA9 leukemia.

overall_design: RNA-seq of murine MA9 Gata2 f/f and Gata2 KO leukemias. Four replicate samples for each condition.

first: Fatemeh

last: Alikarami

last: Xie


title: Direct lineage conversion of postnatal mouse cortical astrocytes to oligodendrocyte lineage cells

city: Toronto

first: Maryam

last: Faiz

address: 1 Kings College Circle

country: Canada

institute: University of Toronto

summary: The conversion of mouse postnatal astrocytes to induced oligodendrocyte lineage cells by ectopic expression of Sox10, Olig2 and Nkx6.2.

overall_design: Lentiviral delivery of transcription factors (TF: Olig2, Sox10, and Nkx6.2) to postnatal mouse astrocytes from Ai14 mice (LV-GFAP::TF-P2A-Cre)

first: Justine

last: Bajohr

first: Erica

last: Scott


title: Transcriptome analysis of chemically polarised rat macrophages: in search of target genes for ARDS therapy

city: Moscow

first: Evgeny

last: Karpulevich

address: Alexandra Solzhenitsina

department: Information Systems

country: Russia

institute: ISP RAS

summary: Acute respiratory distress syndrome (ARDS) is a severe clinical manifestation of an acute lung injury (ALI), which is characterized by poor oxygenation and non-compliant or "stiff" lungs. Modern guidelines for the treatment of ARDS include only symptomatic therapy: ventilator support, prone positioning, sedation and medications to prevent movement, diuretic medication for excess liquid removing, extracorporeal membrane oxygenation (ECMO). Lack of the pathogenic ARDS treatment contributed to the actualization of the search for new therapeutic approaches. Cell therapy is one of such approaches which are now of great interest in the ARDS therapy. Macrophages are known to play a key role in the pathogenesis of ARDS. Depending on the stage of the disease, macrophages exhibiting pro-inflammatory (M1) and anti-inflammatory (M2) states. It has been suggested that the utilisation of M2 macrophages in the early stages of the disease may contribute to a positive disease outcome. The aim of this study was to induce an anti-inflammatory phenotype of macrophages by knockdown of genes selected on the basis of transcriptome analysis of chemically polarised macrophages.

overall_design: Intact rat macrophages were obtained by differentiating CD43-positive rat blood monocytes for 7 days in the presence of MCSF. Lipopolysaccharide endotoxin (LPS) was added at 7 days of culturing to induce a pro-inflammatory phenotype (M1). A mixture of interleukins IL4 and IL10 was used to activate cells via an alternative anti-inflammatory pathway. Samples were lysed in Extract RNA isolation solution (Evrogen, Russia). Preparation of libraries for sequencing was performed using TruSeq RNA Sample Prep Kit v2 according to the manufacturer's recommendations. Raw data were processed using Nextflow nf-core/rnaseq bioinformatic analysis to compare the control and one of the experimental groups. Candidate genes whose decreased expression level would potentially lead to an anti-inflammatory phenotype of macrophages were selected based on transcriptome analysis data.

first: Polina

last: Vishnyakova


title: MACE-seq transcriptomic analysis of MtCLE35 overexpressing roots of M. truncatula without rhizobia inoculation and at 11 dpi after inoculation with S. meliloti.

city: Saint-Petersburg

first: Maria

last: Lebedeva

address: 7-9 Universitetskaya Emb.

department: Genetics and Biotechnology

institute: St Petersburg University

summary: CLE (CLAVATA3/ENDOSPERM SURROUNDING REGION-related) peptides are systemic regulators of legume-rhizobium symbiosis that negatively control the number of nitrogen-fixing nodules. In Medicago truncatula, the expression of the MtCLE35 gene is activated in response to rhizobial inoculation and nitrate treatment, and its overexpression systemically inhibits nodulation. However, little is known about the molecular mechanisms underlying MtCLE35-mediated inhibition of nodulation. In order to elucidate target genes regulated by the MtCLE35-induced signaling cascade, we analyzed the transcriptome of MtCLE35 overexpressing roots inoculated by rhizobia using MACE (Massive Analysis of cDNA Ends) sequencing. Totally, 1390 genes were found to be differentially expressed between MtCLE35-overexpressing (35S::MtCLE35) and control  (35S::GUS) roots after rhizobial inoculation, among them 268 genes were upregulated and 1122 genes were downregulated. Among downregulated genes, many known regulators of legume-rhizobia symbiosis were found, where upregulated genes included, among others, genes associated with defense response and cellular redox status. Furthermore, stable transgenic plants overexpressing the MtCLE35 gene were obtained in this study, and gene expression analysis of selected differentially expressed genes in rhizobia inoculated roots was performed in such plants. Collectively, our data suggest that overexpression of the MtCLE35 gene prevents the induction of nodulation program, which is accompanied by the expression of defense-related gene in MtCLE35-overexpressing rhizobia-inoculated M. truncatula roots.

overall_design: To study the effect of MtCLE35 overexpression on gene expression, composite Medicago truncatula plants were obtained with p35S::MtCLE35 transgenic roots and  p35S::GUS roots used as control. RNA was extracted from non-inoculated transgenic roots (grown under nitrogen-free conditions) and from transgenic roots at 11 dpi after inoculation with S. meliloti.


title: 7aaRGD - a novel SPP1/integrin signaling-blocking peptide reverses immunosuppression and improves anti-PD-1 immunotherapy outcomes in experimental gliomas

city: Barcelona

first: Adria-Jaume

last: Roura

address: Carrer de Baldiri Reixac, 10

country: Spain

institute: IRB Barcelona

summary: Clinical trials with immune checkpoint inhibitors have benefited many cancer patients but were unsuccessful in a number of tumors, including glioblastoma (GBM), the most common and aggressive primary brain tumor in adults. The main obstacle is the immunosuppressive and continuously evolving tumor microenvironment (TME) in which antitumor immunity is inhibited or eluded by tumor-secreted factors. Reprogramming of glioma associated myeloid cells (GAMs) creates a “cold” immunosuppressive TME resulting in a poor infiltration, exhaustion or death of effector T cells. We have developed a synthetic RGD peptide that blocks the reprogramming of GAMs by targeting tumor-GAMs interactions. Here, we explored if the RGD can revert tumor induced changes in the TME of experimental gliomas and improve anti-PD-1 immunotherapy. We demonstrate that RGD efficiently blocks microglia-dependent invasion of murine and human glioma cells in vitro. While RGD alone did not reduce tumor growth in vivo, it prevented tumor-induced transcriptomic changes in GAMs, augmenting the expression of immune response genes. Interestingly, intratumoral RGD delivery led to the normalization of peritumoral blood vessels. Combining RGD with anti-PD-1 antibody reduced tumor growth and induced profound changes in the immune composition of TME as demonstrated using multiparametric flow cytometry. Interferon-ɣ producing capacity of effector T cells and its intratumoral levels increased in mice treated with RGD and anti-PD-1 antibody. Transcriptomic profiles of GAMs were altered by the combined treatment, consistently with the restored inflammatory TME and boosted immunotherapy responses. Intratumoral RGD similarly modified the myeloid cells in TME of human U87MG gliomas in immunocompromised mice.

overall_design:
We demonstrate that RGD efficiently blocks microglia-dependent invasion of murine and human glioma cells in vitro. While RGD alone did not reduce tumor growth in vivo, it prevented tumor-induced transcriptomic changes in GAMs, augmenting the expression of immune response genes. Interestingly, intratumoral RGD delivery led to the normalization of peritumoral blood vessels.
Intratumorally delivered RGD as a monotherapy effectively blocks the reprogramming of GAMs and shifts the glioma TME towards a ‘hot’ phenotype.
We provide the evidence that combining the integrin blockade with ICI reinvigorates antitumor immunity by boosting both innate and adaptive immune responses, and indicates a novel strategy to enhance the efficacy of immunotherapy.

first: Ellert-Miklaszewska

last: Aleksandra

first: Pilanc-Kudlek

last: Paulina

first: Poleszak

last: Katarzyna

first: Roura

last: Adria-Jaume

first: Cyranowski

last: Salwador

first: Ghosh

last: Mitrajit

first: Baluszek

last: Szymon

first: Pasierbinska

last: Maria

first: Gielniewski

last: Bartlomiej

first: Swatler

last: Julian

first: Hovorova

last: Yuliana

first: Wojnicki

last: Kamil

first: Kaminska

last: Bozena


title: Extracellular vesicles from adipose-derived mesenchymal stem cells promote stemness and EMT of corneal epithelial stem cells

city: Suita

first: Xiaoqin

last: Li

state: Osaka

department: Ophthalmology

institute: Osaka University

summary: Corneal diseases are a leading contributor of vision impairment and their treatment remains challenging. It’s known that enhancement of the stemness of corneal epithelial stem cells (CECs) plays a pivotal role in effective treatments. In this study, we evaluated the effects of extracellular vesicles from human adipose-derived mesenchymal stem cells (AdMSC-EVs) on CECs. Firstly, colony formation assays showed that the colony-forming efficiency (CFE) of CECs significantly increased in the presence of AdMSC-EVs. Then we demonstrated that AdMSC-EVs accelerated migration of CECs in a scratch assay, whereas the proliferation of CECs was suppressed by AdMSC-EVs in cell proliferation assay. RNA Sequencing (RNA-Seq) analysis of CECs implied that AdMSC-EVs maintained the stemness, as well as improved epithelial-mesenchymal transition (EMT). Furthermore, having identified the six top microRNAs (miRNAs) of AdMSC-EVs, CEC transfection with those miRNA mimics, indicated that miR-25, miR-191, and miR-335 were the most effective molecules for improving stemness and EMT. Taken together, our findings indicated that AdMSC-EVs can enhance stemness and EMT of CECs, and AdMSC-EV effects are exerted by the contained miRNAs.

overall_design: RNA-Seq analysis of CECs from control group and AdMSC-EV-treated groups (at concentration of 30 μg/ml and 120 μg/ml). Three biological replicates in each group.

first: Ryuhei

last: Hayashi


title: Gata2 promotes drug resistance in Acute Myeloid Leukemia (AML) [ChIP-Seq]

first: Kathrin

last: Bernt

summary: In this study, we generated mouse models of MLL-AF9-driven AML (MA9) harboring conditional alleles for Gata2 gene to precisely investigate the role of Gata2 in drug resistance and progression of MLL-rearranged (MLL-r) AML. Our findings revealed a novel mechanism for Gata2 in blunting p53 mediated apoptosis via transcriptional repression of Rassf4, a regulator of Mdm2 protein stability.

overall_design: ChIP-seq of Gata2, H3K27ac, H3K4me1 in murine Gata2 f/f and Gata2 -/- (Gata2 KO) MA9 cells.

first: Fatemeh

last: Alikarami

first: Michael

last: Xie


title: Extracellular vesicles from adipose-derived mesenchymal stem cells promote stemness and EMT of corneal epithelial stem cells [RNAseq_Exo]

overall_design: Small RNA-Seq analysis of AdMSC-EVs (four biological replicates).


city: Montréal

first: Jean-Philippe

last: Goulet

state: Québec

address: C.P. 6128, succursale Centre-ville

institute: Université de Montréal

summary: Pharmacological Targeting of REV-ERBa/bPromotes HIV-1 Reactivation in CD4+T-Cells while Limiting Cell-to-Cell Dissemination.

overall_design: Memory CD4+ T cells from 7 HIV-uninfected donors; 3 conditions: DMSO, SR9011, SR8278.

first: Christ

last: Ngassaki-Yoka

first: Debashri

last: Chatterjee

first: Jean

middle: P

first: Yuwei

last: Zhang

first: Laurence

last: Marchand

first: Tomas

last: Wiche Salinas

first: Brendan

last: Bell

first: Nicolas

last: Cermakian

last: Routy

first: Laural

last: Solt

first: Petronela

last: Ancuta


title: Eicosapentaenoic acid induces an anti-inflammatory transcriptomic landscape in T cells implicating a pathway independent of triglyceride lowering in cardiovascular risk reduction [ATAC-seq]

city: Leiden

first: Thomas

last: Kuipers

address: Einthovenweg 20

country: Netherlands

institute: LUMC

summary: A twice-daily dose of highly purified eicosapentaenoic acid (EPA) reduces the risk of atherosclerotic cardiovascular disease among patients with high triglycerides and either known cardiovascular disease or those at high risk for developing it. However, the process by which EPA exerts its beneficial effects remains ill understood. Here, we show that EPA can induce an anti-inflammatory transcriptional profile in non-activated CD4+ T cells. We find that EPA exposed CD4+ T cells downregulate immune response related genes, such as HLA-DRA, CD69, and IL2RA, while upregulating genes involved in oxidative stress prevention, such as NQO1. Furthermore, transcription footprint analysis reveals downregulation of GATA3 and PU.1, key transcription factors in TH2 and TH9 differentiation, and upregulation of REV-ERB, an antagonist of TH17 differentiation. Additionally, we examine T cell responses to two other fatty acids of varying degrees of saturation, namely oleic and palmitic acid, and find EPA has a distinct effect on CD4+ T cells transcriptomic landscape as compared to control. Thus, our study shows that EPA can already induce beneficial transcriptomic profiles in CD4+ T cells prior to activation, a process that may contribute to the unexpectedly strong beneficial effects of EPA on atherosclerotic cardiovascular disease observed in clinical trials.

overall_design: Comparative open chromatin analysis of ATAC sequencing data for resting human buffy coat derived CD4+ T cells exposed to control or 100μM of either eicosapentaenoic, oleic, or palmitic acid for 48 hours.

first: Nathalie

last: Reilly

first: Koen

last: Dekkers

first: Jeroen

last: Molenaar

first: Sinthuja

last: Arumugam

first: Yavuz

last: Ariyurek

first: Marten

last: Hoeksema

first: J

middle: W

last: Jukema

first: Bastiaan

last: Heijmans


title: Eicosapentaenoic acid induces an anti-inflammatory transcriptomic landscape in T cells implicating a pathway independent of triglyceride lowering in cardiovascular risk reduction.

middle: B

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

overall_design: Refer to individual Series


title: SAS shKDM4C cell line RNA sequencing

city: Hsinchu

first: Wen-Ching

last: Wang

address: NO.101, Sec. 2, Kuang-Fu Road, Hsinchu 300044, Taiwan (R.O.C)

department: Insitute of Molecular & Cellular Biology

country: Taiwan

institute: National Tsing Hua University

summary: This study uses RNA-seq analysis to explore the impact of KDM4C, a histone lysine demethylase, on head and neck squamous cell carcinoma (HNSCC). KDM4C modifies histone proteins by removing methyl groups from H3K9me3/2, which affects gene expression. The study focuses on the role of KDM4C in SAS cells, a type of HNSCC cell line, specifically concerning metastasis. Gene Set Enrichment Analysis analyzed RNA-seq data comparing SAS cells with and without KDM4C depletion (sh4C#1 vs. LKO). The result showed that KDM4C significantly influences various metabolic processes, including heme metabolism, peroxisome function, and bile acid metabolism in SAS cells. Additionally, the study performed a KDM4C-ChIP seq analysis on SAS cells to gain further insight into its role. According to Enrichr analysis, GATA1 was the top-ranking transcription factor in these pathways, suggesting its potential interaction with KDM4C in HNSCC.

overall_design: RNA-seq analysis (shKDM4C vs. LKO) was conducted on SAS cells to investigate how KDM4C affects metastasis.

first: Mengjen

last: Wu


title: Eicosapentaenoic acid induces an anti-inflammatory transcriptomic landscape in T cells implicating a pathway independent of triglyceride lowering in cardiovascular risk reduction [RNA-seq]

overall_design: RNA-Seq data for resting human buffy coat derived CD4+ T cells exposed to control or 100μM of either eicosapentaenoic, oleic, or palmitic acid for 48 hours.

middle: T


title: Genome-wide DNA methylation profiles of well-differentiated liposarcomas (WDLPS), dedifferentiated liposarcomas (DDLPS), and normal adipose tissues

city: Maebashi

first: Naoko

last: Hattori

state: Gunma

address: 3-39-15 Showa-mach

department: Institute for Molecular and Cellular Regulation

institute: Gunma University

type: Methylation profiling by genome tiling array

summary: Liposarcoma (LPS) is the most common soft-tissue sarcoma in adults, and well-differentiated LPS (WDLPS) and dedifferentiated LPS (DDLPS) are the most frequent subtypes.  These LPSs are considered to develop due to disturbances in the process of adipogenic differentiation of mesenchymal stem cells.  However, the molecular mechanism of the disturbances remains unclear.  Here, we aimed to identify the mechanism and take its advantage in therapy.

overall_design: Bisulfite converted DNA was hybridized to the Infinium Human MethylationEPIC BeadChip.

first: Toshikazu

last: Ushijima


title: Genetic background and aging-driven neuroimmune and disc changes underscore herniation susceptibility and pain-associated behaviors in SM/J mice

first: Makarand

last: Risbud

address: 1025 Walnut Street

department: Orthopaedic Surgery

institute: Thomas Jefferson University

summary: SM/J mice experience spontaneous age-associated intervertebral disc herniations, with molecular analyses indicating a dysregulated immune system may contribute to this disc pathology. To investigate this, we analyzed the circulating immune cells of these mice during aging, in relation to BL/6 mice, which do not experience disc herniation.

overall_design: PBMCs were isolated from the whole blood of 12-month-old and 20-month-old BL/6 and SM/J mice, using standardized Lymphoprep protocols. Single-cell sequencing was conducted on PBMCs using the 10X-genomic platform. Samples were multiplexed, to consolidate both timepoints for each strain into a single sample per strain.

first: Olivia

last: Ottone

first: Emanuel

middle: J

last: Novais

first: Alexandra

last: Manchel


title: Splicing factor PTBP1 promotes hepatocarcinogenesis via oncogenic splice-switching of MAPT

city: Guangzhou

first: wenying

last: zheng

state: --- Select One ---

address: No.78 Hengzhigang Road, Yuexiu District, Guangzhou City, Guangdong Province, Chi

institute: Affiliated Cancer Hospital & Institute of Guangzhou Medical University

summary: Changing splicing factors leads to abnormal alternative splicing (AS), which results in tumor progression.Splicing factor polypyrimidine tract binding proteins (PTBP1) facilitate cancer progression by modulating oncogenic variants. However, its role and mechanism in hepatocellular carcinoma (HCC) remains unclear. Our findings confirm that PTBP1 is highly expressed in HCC cells lines and tissues. Moreover, its expression correlated negatively with overallanddisease-freesurvivalrates, but inversely with tumor grade and stage. PTBP1 knockdown decreases HCC cell proliferation, migration, and invasion in vitro and inhibits hepatoma xenograft growth and infiltration in vivo. We identified PTBP1-mediated AS events and PTBP1 functionally promoted cell proliferation, invasion, and migration by altering the AS of the protein tau (MAPT) gene and promoting the oncogene expression. Strikingly, the dysregulation of MAPT splicing was paralleled by the increased expression of PTBP1 in HCC, which predicted the poor prognosis of the patients. According to additional research, AS of the MAPT gene guided by PTBP1 increases tumorigenicity in HCC by activating the MAPK/ERK pathways. In summary, our results suggest that PTBP1 plays an oncogenic role in HCC partially through the regulation of MAPT's AS, which could be a promising treatment target.

overall_design: The alternative splicing events associated with PTBP1 were  identified using RNA-Seq

first: Wenying

last: Zheng

first: Yanyan

last: Shang

first: Kai

last: Du

first: Ailing

last: Luo


title: Activation of RAS/MEK/ERK signaling drives biliary differentiation in primary liver cancer [112UE]

city: Munich

first: Ursula

last: Ehmer

address: Ismaninger Str. 22

department: Internal Medicine II

institute: Klinikum rechts der Isar, TU München

summary: RAS mutations are frequently observed in human cholangiocarcinoma (CCA), while they are relatively rare in hepatocellular carcinoma (HCC). In a genetically engineered mouse model with liver specific conditional deletion of tumor suppressors Rb and p53 together with activation of oncogenic KRAS, intrahepatic CCA develop primarily from hepatocytes. CCA show activation of PI3K/AKT and MEK/ERK signaling pathways. targeted genetic inactivation of each of these downstream pathways of KRAS leads to delayed tumor growth and profound alterations in tumor differentiation. Specifically, reduced PI3K/AKT signaling promotes the formation of well-differentiated tumors, whereas the inactivation of MEK/ERK signaling induces a differentiation switch towards a more hepatocyte-like phenotype.

overall_design: gene expression data from tumors of KRAS-driven liver cancer (RPK) compared to KRAS-driven tumors deficient for either MEK/ERK or PDK1/AKT signaling

first: Ehmer

last: Ursula

first: Öllinger

last: Rupert


title: Activation of RAS/MEK/ERK signaling drives biliary differentiation in primary liver cancer


title: Mutant IDH1 activates JOSD2-YAP/TAZ in a non-classical manner to sustain intrahepatic cholangiocarcinoma cell growth

city: Hang Zhou

first: Meijia

last: Qian

state: Zhejiang

address: No.866 Yuhangtang Road, Xihu District

department: Zhejiang University

institute: College of Pharmaceutical Sciences

summary: Gain of function mutations in isocitrate dehydrogenase 1 are one of the most common genetic lesions in intrahepatic cholangiocarcinoma (ICC). The mutant IDH1 (mIDH1) causes aberrant metabolic, epigenetic and differentiation process by converting α-ketoglutarate (α-KG) to onco-metabolite 2-hydroxyglutarate (2-HG). However, mIDH1 inhibitor ivosidenib appears much more effective in acute myeloid leukemia than that in ICC, suggesting that in addition to these common mechanisms, other pathways may be also involved. Our results indicated that mIDH1 exhibited high correlation of transcription profiles with JOSD2, a deubiquitinating enzyme reported to stabilize YAP/TAZ by our previous work. Further exploration suggested that mIDH1 up-regulated JOSD2 protein stability independent of 2-HG and couldn’t be intervened by ivosidenib. The targeted silence of JOSD2 exhibited more potent anti-tumor effect in cells with mIDH1 than wild type cells. Together, this study may provide novel insights for understanding the tumor-promoting effects of mIDH1 to derive new therapeutic strategies.

overall_design: RBE cells infected with scramble, shIDH1 or shJOSD2 lentivirus were performed RNA-sequencing. Each group has three replicates.

first: Fangjie

last: Yan

first: Xiangning

last: Liu

first: Yonghao

last: Li

first: Fujing

last: Ge

first: Hongdao

last: Zhu

first: Tao

last: Yuan

first: Peiying

last: Zhang

first: Churun

first: Bo

last: Yang

first: Hong

first: Qiaojun

last: He


title: Oocyte cryopreservation

city: Hefei

first: Tie

last: Chang

address: Huangshan Road

institute: University of Science and Technology of China

summary: Cryopreservation of mature oocytes is a critical means for female fertility preservation. Despite clinical advances using vitrification preservation method, the high concentrations of toxic penetrating cryoprotectant agents (CPA, up to 4.3 M) and low throughput (only one every experiment) put forward a challenge. Here, we report a synergetic ice inhibition platform via PVA/Fe3O4/GO nanoparticles (PFG NPs), that achieves sharp ice morphology, ice recrystallization, and devitrification inhibition, thus reducing cryodamage both in cooling and warming stages. Oocyte cryopreservation experiment demonstrates the survival rate can attain 98.6% using 2.5 M penetrating CPA while ensuring the scalability (ten oocytes each cryopreservation procedure). In contrast, recovered oocytes via PFG platform show 85 gene variation compared with fresh oocytes, whereas tradition CPA (TCPA) formulation induces 1396 gene changes. Meanwhile, the PFG-cryopreservation oocytes maintain normal ability of fertilization, development, and birth of offspring.

overall_design: A-fresh; B-cryopreservation-1 method; C- cryopreservation-2 method; method-1 is using the 15 % EG + 15 % DMSO + 0.5 M sucrose, and cryotop to freeze oocyte.  method-2 is using 17.5 % EG + 1 M trehalose + PVA/Fe3O4/GO nanoparticles and straw to cryopreserve oocyte.


title: MEF2C hypofunction in GABAergic cells alters neurotypical behavior and prefrontal cortex inhibitory synaptic transmission in a sex-dependent manner

city: Charleston

first: Stefano

last: Berto

state: SC

address: 68 President Street

department: Neuroscience

institute: Medical University of South Carolina

summary: Heterozygous loss-of-function mutations or deletions of the MEF2C gene cause a neurodevelopmental disorder, termed MEF2C Haploinsufficiency syndrome (MCHS), that is characterized by autism spectrum disorder, intellectual disability, seizures, and other neurological symptoms. In mice, global Mef2c heterozygosity produces numerous behavioral phenotypes reminiscent of MCHS. MEF2C is highly expressed in multiple cell populations in the developing brain, including GABAergic inhibitory neurons. While MEF2C hypofunction in excitatory neurons or microglia alter neurotypical behaviors and brain circuit function, the impact of MEF2C heterozygosity in GABAergic neurons remains unknown.

overall_design: We employed GABAergic cell type-specific manipulations to study mouse Mef2c heterozygosity in a battery of MCHS-like behaviors. We also performed single cell transcriptomics and patch-clamp electrophysiology and optogenetics to assess intrinsic excitability and synaptic transmission.

first: Yongjoo

last: Cho

first: Chirstopher

last: Cowan


title: Activation of RAS/MEK/ERK signaling drives biliary differentiation in primary liver cancer [396UE]

first: Ursula

last: Ehmer

first: Ehmer

first: Öllinger


title: PRL-3 induces Kupffer cells to recruit MDSCs in liver through exosome ITGαvβ5

first: Zhonghua

last: Chu

state: Guangdong

address: 107 Yan Jiang West Road

institute: Sun Yat-sen Memorial Hospital,Sun Yat-sen University

summary: Previous studies have found that PRL-3 promotes liver metastasis of colon cancer, but whether it is involved in promoting liver PMN formation remains unclear.It was found that MDSC is the main cellular component of PMN formation and plays an immunosuppressive role.We found that PRL-3 can up-regulate the expression of ITGαvβ5 in exosomes of colon cancer cells through proteomics identification and extractor identification, and further verified that exosome ITGαvβ5 uptake by Kupffer cells can participate in inducing liver infiltration of MDSCs by exosome pre-education and mouse liver metastasis model construction，thus promoting liver metastasis of colon cancer. Then we extracted exosomes from colon cancer cells, induced Kupffer cells in vitro, and conducted RNA-seq sequencing to screen and identify genes involved in regulating MDSC infiltration.

overall_design: We carefully selected Kupffer cells with robust viability and exposed them to MC38-PRL-3 Exo and MC38-VT Exo for 48 hours (with biological replicates, n=2/group). Total RNA was extracted from Kupffer cells using the Trizol method. The mRNA library construction, sequencing, and bioinformatics analysis of the sequencing results were outsourced to IGE Biotechnology

first: Qiusheng

last: Lan

first: Heyang

last: Xu


title: Transcriptome of migrating mouse dendritic cells

city: Martinsried

first: Tobias

last: Straub

address: Großhadener Str. 9

department: Biomedical Center, Bioinformatics

institute: LMU Munich

summary: The ability of cells to migrate is essential for development, tissue homeostasis, and immune responses. To screen for pathways relevant for migration in tissue-like 3D environments, we here employed fast migrating dendrtic cells as a cellular model and established transcriptomics of migrating DCs in collagen networks of lower and higher complexity, in comparison to DCs without a surrounding collagen matrix.

overall_design: bone-marrow derived LPS stimulated mouse dendritic cells migrating in 3D collagen matrices of different densities; transcriptome analysis after 5 hours.

first: Jörg

last: Renkawitz

first: Thomas

last: Penz

first: Christoph

last: Bock


title: RNA sequencing to study the molecular relationships between temperature, aging, and OCTR-1

city: Spokane

first: Yiyong

last: Liu

state: WA

address: 412 E Spokane Falls Blvd

institute: Washington State University

summary: To gain molecular insights into OCTR-1-dependent longevity responses to temperatures, we employed RNA-seq to compare gene expression in young and old wild-type and octr-1(ok371) animals propagated at different temperatures (15°C, 20°C and 25°C).

overall_design: Five replicates of eight groups of RNA samples (young and old wild-type and octr-1(ok371) animals propagated at 15°C, 20°C or 25°C) were collected and subjected to RNA-seq analysis.

first: Phillip

last: Wibisono

first: Jingru

last: Sun


title: Effect of knockdown of BAP18 on gene expression of PLC/PRF/5 cells

city: Shenyang

first: Chunyu

last: Wang

state: Liaoning

address: No.77 Puhe Road, Shenyang North New Area, School of Life Sciences, China Medical University

department: Cell biology

institute: China medical university

summary: The goals of this study are to screen out BAP18-regulated differentially expressed genes in HCC cells by utilizing RNA-sequencing. Firstly, PLC/PRF/5 cells were respectively transfected with lentivirus-delivered shBAP18 and shcontrol. Then, the cells were harvested by Trizol RNA isolater and analyzed by High througput RNA-sequencing.  And gene expression profiling was analyzed using data obtained from RNA-sequencing.

overall_design: Cellular mRNA sequencing of BAP18-knockdown and the control PLC/PRF/5 cells

first: Liu

last: Wei

first: Wang

last: Chunyu

first: Zhao

last: Yue


title: Analysis of miRNA expression profiles in reactivated neurons from latent PRV infection

city: Chongqing

first: Zhang

last: Chen

address: No. 160 Xueyuan Road, Changyuan Street

institute: Southwest University

summary:
Little is known about the latent infection period and lytic infection mechanism of pseudorabies virus. The advent of high-throughput sequencing technologies has allowed us to examine many different biological components simultaneously.
To examine the effects of glucocorticoids on latently infected PRV neurons, we constructed gene expression profiles of RNA-seq data for miRNA expression from PC-12 cell with a PRV latent infection model group (PRV group), a reactivation model group (DEX group) and a blank control group (CON group).

overall_design: miRNA expression profiling of RNA-seq data from PC-12 cells in different states of PRV infection.

first: Chen

last: Zhang

first: Ling

last: Gan


title: Effects of TNFR1 deletion on gene expression in mouse colonoic epithelial organoids

city: Chicago

first: Cambrian

middle: Yangshao

state: IL

address: 5841 S Maryland Ave

department: Department of Medicine

institute: The University of Chicago

summary: Colonic deep crypt secretory cells are a recently identified population of Paneth-like cells located near the base of the colonic crypt. In mice, these cells express the marker gene Reg4 and contribute to the maintenance of the epithelial stem cell niche during normal cellular turnover and repair. During colitis, the epithelium adopts a regenerative program that involves the upregulation of proliferative activity, reprogramming of stem cells, and increased expression of Reg4. Whether these changes are associated with increased deep crypt secretory cell specification and how they could be linked to the inflammatoy milieu of colonic injury remain to be resolved. Here, we demonstrate in human specimens that inflammatory bowel disease induces a population of Reg4+ cells at the base of the colonic crypt. In mice, murine organoids, and human organoids, we find that tumor necrosis factor (TNF) amplified the specification of deep crypt secretory cells, and that this effect depends on the expression of tumor necrosis factor receptor 1 (TNFR1). Thus, TNF signaling links colonic inflammation to the differentiation of a specialized deep crypt secretory cell type that may promote epithelial regenerative function.

overall_design: A total of 6 samples were analyzed. Each sample is composed of total RNA isolated from wildtype or Tnfr1-/- mouse colonic organoids grown for 7 days after passage. Three biological replicates (i.e., mice) per genotype were studied.

middle: Y

first: Safina

last: Gadeock

first: David

last: Polk


title: The gene expression changes in mouse brain lacking NDRG2

city: Kanazawa

first: Takumi

last: Nishiuchi

address: 13-1 Takaramachi

institute: Kanazawa University

summary: Microarray analysis identified genes differently expressed in NDRG2 knockout brain, and upregulated gene expressions of Bmp4 and Per2 were confirmed by quantitative PCR analysis.

overall_design: Four sets of samples, total RNA derievd from NDRG2 knockout and wild type mouse brain were prepared. Genes up-regulated or down-regulated more than 1.5 fold were analyzed.

first: Mika

last: Takarada-Iemata


title: Total RNA-Seq in MCF-7 cells stably expressing shCtrl or shEXOSC3 RNA.

city: Pittsburgh

first: Da

last: Yang

address: 3501 Terrace

department: School of Pharmacy

institute: University of Pittsburgh

summary: MYC binds to thousands of promoters and exerts an amplification effect on expression of most genes. Meanwhile, MYC drives tumourigenesis through the regulation of a unique set of cancer-specific targets that differ from its targets in normal cells. The discrepancy in MYC-mediated gene regulation in tumours versus normal cells has not been fully elucidated. In this study, we discovered that MYC protein has a broad RNA binding spectrum including promoter-associated RNAs (paRNAs) and enhancer RNAs (eRNAs). MYC RNA binding peaks colocalize with its DNA binding sites, but they are not dependent on its HLHLZ domain or transactivation domain. By integrating multiple dimensional data sets from cancer cells and tumour samples, we show that the MYC-bound paRNAs and eRNAs can shape MYC chromatin interaction to regulate gene transcription. Finally, we identified and characterized a novel MYC-bound eRNA, which we refer to as MERG1, that plays essential roles in the ERα+ breast cancer tumourigenesis. Mechanistically, MERG1 interacts with MYC and enhances MYC binding to the enhancer and promoter of the GREB1 gene. This process specifically amplifies expression of the MYC target gene GREB1 and accelerates tumour progression. Our study demonstrates that MYC interaction with paRNAs and eRNAs contribute to its specific amplification of gene expression in tumourigenesis.

overall_design: Total RNA-seq data for MCF-7 cell line and its KD derivative (shEXOSC3)

first: Sihan

last: Li

first: Zehua


title: Transcriptome analysis of E15.5 wild-type (Tbr2-f/+) andTbr2-Isl1/+ retinae

city: Houston

first: Chai-An

last: Mao

state: Texas

address: 6431 Fannin Street, MSB7.242

department: Ophthalmology And Visual Scien

institute: University of Texas McGovern Medical School

summary: Isl1 encodes a member of the LIM/homeodomain family of transcription factors. During retinal development. Isl1 plays a critical role in RGC fate specification. Tbr2 is essential for the formation and maintaining the survival of ipRGCs. In this study, we tested whether ectopically expressing Isl1 in Tbr2-expressing cells affects the developmental program of Tbr2-expressing retinal neurons, including ipRGCs and a subset of wide-field displaced amacrine cells. We generated a Tbr2-Isl1 knock-in allele using gene targeting technique, and then used RNA-seq approach to compare transcriptome profiles between E15.5 wild-type (Tbr2-flox/+) and Tbr2-Isl1/+ retinas to uncover how Isl1 affects Tbr2-regulated genes.

overall_design: Retinal mRNA profiles of E15.5 wild-type (Tbr2fx) and Isl1 knockin (T2Isl1) retinas were generated by deep sequencing, in triplicate, using Illumina.

first: Takae

last: Kiyama

first: Tzung-Fu

last: Hsieh


title: Influence of the anti-MUC16 humanized monoclonal antibody AR9.6 on gene expression in MUC16 expressing cancer cells in patient-derived organoids

city: omaha

first: Prakash

last: Radhakrishnan

state: NE

address: 986805 Nebraska Medical Center

department: Eppley Institute for Research in Cancer

institute: University of Nebraska Medical Center

summary:
To investigate the differentially expressed genes and the pathways they might alter upon humanized AR9.6 mediated blockade of MUC16 and subsequent perturbation of its downstream signaling
We then performed gene expression profiling analysis using data obtained from RNA-seq of the two different conditions (organoids treated with huAR9.6 versus huIgG) (three replicates each).

overall_design: Comparative gene expression profiling analysis of RNA-seq data from patient-derived organoids treated with huAR9.6 and isotype control huIgG for 24 hours at a dose of 40 µg/mL


title: Gene expression profiles of cKit positive bone marrow cells from six genotype mice - WT, Idh1R132, Npm1c, Flt3ITD, Idh1R132+Npm1c, and Idh1R132+Flt3ITD

city: New York

first: Cem

last: Meydan

state: New York

address: 1305 York

department: Physiology & Biophysics

institute: Weill Cornell Medical College

summary: Here we show that the combination of Idh1R132 plus Npm1c mutations cooperatively induced overt AML in vivo, using genetically engineered mouse model. In contrast, the combination of Idh1R132 plus Flt3ITD led to myeloid proliferation disease, but not AML. The mice harboring both of Idh1R132 and Npm1c mutations got fatal (median survival, 254 days) due to AML, which demonstrated rapid lethality on recipient mice in secondary transplantation experiments. We analyzed cKit-positive bone marrow cells from six genotype mice - WT, Idh1R132, Npm1c, Flt3ITD, Idh1R132+Npm1c, and Idh1R132+Flt3ITD. We isolated cKit positive BM cells from the mice of the two different ages (3 and 6 months old), and subjected to RNA-seq, bisulfite-seq, and ATAC-seq.

overall_design: Using RNA-Seq, we examined gene expression profiles of cKit positive BM cells from six genotype mice - WT, Idh1R132, Npm1c, Flt3ITD, Idh1R132+Npm1c, and Idh1R132+Flt3ITD, with 4-5 biological replicates for each genotype. We examined the cells from mice of the two different ages (3 and 6 months old).

first: Takashi

last: Sakamoto

first: Jonathan

last: Foox

first: Julie

last: Leca

first: Christopher

middle: E

last: Mason

first: Ari

last: Melnick

first: Tak

last: Mak


title: Single cell analysis of naïve or AAV transduced NSG-PiZ mouse livers

status: Public on Apr 29 2025

city: Seattle

first: Pavitra

last: Roychoudhury

state: Washington

address: 1100 Fairview Ave N, PO Box 19024, E5-110

institute: University of Washington

summary: To determine whether different hepatotropic AAV capsids can mediate transduction of human hepatocytes in liver-humanized chimeric mice we performed an experiment in NSG-PiZ mice. NSG-PiZ mice were simultaneously administered barcoded AAV vectors with capsids derived from AAV8, AAV9, AAVrh10, AAVDJ/8 and AAV.LK03 at a total dose of 1E12 vg per mouse. At 14 days post delivery naïve and AAV treated mice were sacrificed and livers perfused to generate single cell suspensions for scRNA-seq. We transplanted mice with human hepatocytes from 2 donors (4 mice per donor) and half of the mice from each donor were adminsitered AAV.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Four NSG-PiZ mice were transplanted with human hepatocytes from Donor A and 4 NSG-PiZ mice were transplanted with human hepatocytes from Donor B. Two Donor A and 2 Donor B mice were kept as untransduced contols.  The remaining 2 Donor A and 2 Donor B mice were transduced with a mixture of AAV8 (2E11 vgs/mouse), AAV9 (2E11 vgs/mouse), AAVrh10 (2E11 vgs/mouse), AAVDJ/8 (2E11 vgs/mouse) and AAV.LK03 (2E11 vgs/mouse) for a total dose of 1E12 vgs by retroorbital IV injection. The AAVs carried a barcoded GFP gene specific to each serotype.  At 14 days post transduction, hepatic cells were collected and pooled from the 4 untransduced mice and separately from the 4 AAV transduced mice and immediately processed for 10X single cell RNA seq.

first: Hong

last: Xie

first: Daniel

last: Strongin

first: Harrison

last: Dulin

first: Michelle

last: Loprieno

last: Stone

first: Saraswathi

last: Sathees

first: Keith

last: Jerome


title: ChIP-Seq of MYC in MCF-7 cells treated with AM (Actinomycin D and MG132) or DMSO.

first: Da

last: Yang

summary: MYC has been known to bind to thousands of promoters and exert an amplification effect on expression of most genes. Meanwhile, MYC drives tumorigenesis through the regulation of a unique set of cancer-specific targets that differ from its targets in normal cells. However, the mechanism underlying this discrepancy in MYC’s regulation in tumor and normal cells has not been fully elucidated. In this study, we discovered that MYC protein has a broad RNA binding spectrum including promoter-associated RNAs (paRNAs) and enhancer RNAs (eRNAs). MYC’s RNA binding peaks colocalize with its DNA binding sites, but not dependent on its HLHLZ domain or transcription activation domain. By further integrating multiple dimensional data from cancer cells and tumors samples, we have shown that the MYC-bound paRNAs and eRNAs can shape MYC chromatin interaction to regulate gene transcription. Finally, we have mechanistically characterized a MYC-bound eRNA, MERG1, that plays essential roles in the ERα+ breast cancer tumorigenesis. Mechanistically, MERG1 interacts with MYC and enhances MYC’s binding to the enhancer and promoter of GREB1 gene. This process specifically amplifies the target gene GREB1 expression and accelerates tumor progression. Our study demonstrates that MYC’s interaction with paRNAs and eRNAs contribute to its specific amplification of gene expression in tumorigenesis.

overall_design: Chromatin immunoprecipitation assays followed by sequencing (ChIP-Seq) of MYC in MCF-7 cells treated with AM (ActinomycinD and MG132) or DMSO

first: Sihan

last: Li

first: Zehua

last: Wang


title: Gene expression analysis in Ndrg2KO after permanent cerebral ischemia

first: Takumi

last: Nishiuchi

summary: N-myc downstream-regulated gene 2 (Ndrg2) is a differentiation- and stress-associated molecule. We showed that astrocytic Ndrg2 can function as a modulator of the BBB permeability following ischemic stroke in mice. To further identify the Ndrg2-dependent pathways, we compared global expression profiles of ischemic brains in Ndrg2KO mice and in wild-type mice.

overall_design: Four sets of samples derievd from WT mice and Ndrg2KO mice were analyzed. All samples were obtained from the ipsilateral cortex 24 hours after pMCAO.

first: Mika

last: Takarada-Iemata


title: UHRF1 regulates AR ubiquitination to promote the loss of AR Signaling and Enzalutamide Resistance in Progression of Prostate Cancer

first: Yifan

last: Zhang

address: Department of Urology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong,China

summary: In this study, we demonstrated the critical role of the epigenetic regulator UHRF1 in the enzalutamide resistance development of prostate cancer. We have shown that UHRF1 is highly expressed in enzalutamide-resistant prostate cancer cells and its expression correlates with the loss of androgen receptor (AR)-dependent glandular features. Knocking down UHRF1 led to increased AR expression and enhanced the activity of canonical AR signaling pathway in prostate cancer cells.

overall_design: Expression profiling by high throughput sequencing.


title: Single-cell transcriptomic analyses unveil exercise-induced changes in murine skin vascular endothelial cells

city: Montreal

first: Guillaume

last: Lettre

state: Quebec

address: 5000 Belanger

institute: Montreal Heart Institute

summary: Physical activity (PA) is a fundamental aspect of preventive medicine, offering profound benefits for cardiovascular health and overall well-being. Despite its widespread benefits, the molecular mechanisms underlying PA-induced improvements in microvascular functions remain poorly understood. The skin microvasculature is uniquely affected by exercise-induced shear stress, especially during thermoregulation. Using single-cell RNA sequencing, we investigated how voluntary exercise influences the transcription profile of endothelial cells in the skin microvasculature of mice. We assigned 20 mice to either a sedentary group or a 1-month voluntary exercise program involving running wheels. Post-intervention, we collected skin biopsies from twelve mice for transcriptomic analyses. The differential expression analysis showed a significant increase in the expression of the Zbtb16 gene in vascular endothelial cells (vECs). The expression of Zbtb16 in vECs was correlated with genes involved in angiogenesis. Additionally, Gene Set Enrichment Analysis (GSEA) with nominally differentially expressed genes in vECs highlighted the suppression of pathways related to oxidative stress, cell proliferation and metabolism in the exercise group. This suggests an exercise-triggered transition towards improved metabolic efficiency and enhanced homeostasis in vECs. These results begin to reveal how exercise induces molecular changes in vECs of the skin microvasculature, highlighting PA's role in influencing endothelial function.

overall_design: Single cells were isolated from mice subjected to physical activity and from sedentary controls. Libraries were prepared using the 10x Genomics Chromium single-cell RNA-sequencing (scRNA-seq) protocol.

first: Pegah

last: Hejazi

first: Pauline

last: Mury

first: Éric

last: Thorin


title: the ac4C-epitranscriptome of schizophrenia animal model

city: Beijing

first: Liting

last: Xue

address: 10 Xitoutiao Road, You'anmenwai, Fengtai District

department: Department of Medical Genetics and Developmental Biology School of Basic Medical Sciences

institute: Capital Medical University

summary: When we analyzed ribosome profiling in the acute prefrontal cortex of MK-801-exposed male mice, 357 differentially translated genes were identified, with the N4-acetylcytidine (ac4C) consensus motif enriched in the transcripts with increased translation efficiency.We then used acetylated RNA immunoprecipitation sequencing to investigate the epigenetic modification of ac4C motifs in this animal model.

overall_design: acetylated RNA immunoprecipitation sequencing (acRIP-seq) for the PFC of MK-801-exposed male C57/BL6 mice and vehicle mice.

first: Xue

last: Liting

first: Liu

last: Xu

first: Zhao

last: Jialu


title: Gastric epithelial cells infected with Helicobacter pylori for 24 hours

city: Changsha

first: Minglin

state: China

address: tongzipo road

department: Department of Gastroenterology

institute: The Third Xiangya Hospital, Central South University

summary: Helicobacter pylori (H. pylori) infects nearly half of the global population. H. pylori infection is associated with various gastric diseases and is a recognized causative factor for gastric cancer. The mechanisms underlying the persistent colonization of H. pylori and its role in the development and progression of gastritis-associated carcinogenesis remain unclear. To investigate the pathogenic mechanisms of H. pylori infection, we performed RNA sequencing (RNA-seq) on H. pylori-infected gastric epithelial cells and analyzed the gene expression patterns induced by H. pylori infection, aiming to provide critical insights for understanding its disease-driving pathways.

overall_design: Compare the gene expression profiles between H. pylori(ATCC26695) infected and uninfected gastric epithelial cells under the condition of a multiplicity of infection (MOI) = 100 for 24 hours.

first: Fen


title: Tumorigenic p53S Balances Aging and Tumorigenesis via Regulating DREAM/MMB and its Downstream Telomere DNA Replication Pathways

city: Kunming

first: Juhua

last: Dan

address: 727 of Jingming Road

institute: Kunming University of science and technology

summary: The Werner Syndrome (WS) is characterized with both premature aging and tumorigenic phenotypes. We introduced a tumorigenic mutation p53S found in immortalized WS mouse embryo fibroblasts (MEFs) back into WS mice to investigate the impact of p53S in telomere dysfunction induced aging process. We found that the introduction of p53S rescued the aging phenotypes of Werner syndrome, showing as the extension of life span, and the delay of organ degeneration. Further studies revealed that the introduction of p53S transcriptionally upregulated DREAM/MMB pathway and its downstream DNA helicase and telomere maintenance proteins, and facilitated the recruitment of these proteins to G4 DNA structures and DNA replication forks, which compensated the loss of Wrn and telomerase function and solved the DNA replication, telomere lengthening, and cell proliferation problems via unwinding G4 structures, which ultimately, rescue the aging phenotypes of WS.  Together, our data reveal that certain features of tumorigenesis can be applied to balance with premature aging, rescue aging phenotype without tumor risk. This study suggests a new mechanism and potential tumor-free longevity strategy in aging regulation.

overall_design: To understand how p53S rescues the aging phenotypes in WS, we performed RNA-seq with the MEFs derived from G1, G3, G5 DM and TM mice, the WT and p53S MEFs were used as control.

first: Qianqian

first: Jun

first: Haili

first: Quan

last: Zheng

first: Kailong

last: Hou

first: Liangxia

last: Jiang

first: Bin

last: Guo

first: Shuting

last: Jia

first: Xiaoming

last: Wu

first: Ying

last: Luo


title: Chromation accessibility profiles of cKit positive bone marrow cells from six genotype mice - WT, Idh1R132, Npm1c, Flt3ITD, Idh1R132+Npm1c, and Idh1R132+Flt3ITD

first: Cem

last: Meydan

overall_design: We examined gene-wide chromatin accessibility profiles of cKit positive BM cells from six genotype mice - WT, Idh1R132, Npm1c, Flt3ITD, Idh1R132+Npm1c, and Idh1R132+Flt3ITD, with 3-4 biological replicates for each genotype. We examined the cells from mice of the two different ages (3 and 6 months old).

first: Takashi

last: Sakamoto

first: Jonathan

last: Foox

first: Julie

last: Leca

first: Christopher

last: Mason

first: Ari

last: Melnick

first: Tak

last: Mak


title: LINC01963 Promotes Pancreatic Cancer Proliferation via METTL3/IGF2BP2 Axis-Mediated m6A Modification of c-Myc

first: Qixian

last: Liu

state: Beijing

address: Peking Union Medical College Hospital (Dongdan campus)

institute: Peking Union Medical College Hospital

summary: C-Myc overexpression is an important molecular hallmark of pancreatic ductal adenocarcinoma (PDAC), but directly targeting c-Myc is extremely challenging. Identifying key upstream factors involved in c-Myc overexpression provides promising indirect targets for c-Myc. Herein, the long noncoding RNAs (lncRNAs) highly expressed in PDAC and significantly correlated with c-Myc expression were identified using RNA sequencing datasets. Among them, LINC01963 was found to interact with c-Myc, as confirmed by RNA pull-down and RIP-qPCR assays. Furthermore, high LINC01963 expression was correlated with poor PDAC prognosis, and functional studies demonstrated that its knockdown inhibited PDAC cell proliferation and xenograft tumor growth. Mechanistic studies identified LINC01963 as a key regulator of c-Myc stability, consequently affecting cell cycle through the c-Myc/p21-related signaling pathways. Further investigation revealed that LINC01963 enhanced N6-methyladenosine (m6A) modification of c-Myc mRNA by protecting methyltransferase-like 3 (METTL3) protein from KDM1B-mediated ubiquitin-proteasome degradation. Intriguingly, LINC01963 also stabilized c-Myc mRNA by facilitating the formation of a ternary complex with insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and m6A-modified c-Myc. Our study reveals that LINC01963 promotes PDAC tumorigenesis through METTL3/IGF2BP2 axis-coordinated regulation of c-Myc, suggesting a new strategy for indirectly targeting c-Myc.

first: Huanwen

first: Zhiyong

last: Liang


title: Gene expression differences in primary Human Ectocervix and Endocervix Chips

city: Denver

first: Pluto

last: Bio

state: CO

address: 3575 Ringsby Ct Suite 414

institute: Pluto Bio

summary: Cervical dysfunction, a major contributor to preterm labor and neonatal mortality, remains poorly understood due to the absence of physiologically relevant human models. Here, we show that a microfluidic human Endocervix Chip lined by primary endocervical epithelial interfaced with stromal cells and cultured under pregnancy-like hormonal conditions recapitulates key aspects of the biology of the endocervix, including formation of a mucus plug-like structure with antimicrobial properties. Culturing a dysbiotic cervico-vaginal microbiome on-chip increased secretion of pro-inflammatory cytokines observed in patients with preterm labor and enhanced production of matrix metalloproteinases (MMPs) that degrade stromal extracellular matrix (ECM). Perfusion with inflammatory cytokines at clinically relevant concentrations altered cervical mucus composition, upregulated prostaglandin-endoperoxide synthase 2 expression, increased MMP secretion, and reduced collagen production, which together drive dissolution of the stromal ECM and promote cervical ripening. Addition of circulating peripheral blood mononuclear cells (PBMCs) amplified these effects. Administration of a clinically approved drug for prevention of preterm labor that the FDA recently deemed ineffective was also found to be inactive in the chip, while an approved therapeutic antagonist of the IL-1 receptor successfully protected against cervical dysfunction in this model. These findings demonstrate that IL-1 acts directly on human cervical tissues to promote changes associated with initiation of labor and that primary human endocervix chips may represent a useful preclinical model for studies on cervical dysfunction associated with preterm birth.

overall_design: Global RNA expression profiles of primary human Cervix Chips (n=3-4 chips, N=3 donors, epithelial and stromal compartments) were generated.

first: Anna

last: Stejskalova

first: Karina

last: Calderon

first: David

last: Chou

first: Aakanksha

last: Gulati

first: Jessica

last: Feitor

first: Zohreh

last: Izadifar

first: Ola

last: Gutzeit

first: Yasmine

last: Bouchibti

first: Siyu

last: Chen

first: Roberto

last: Plebani

first: Justin

last: Cotton

first: Jasmine

middle: G

last: Hughes

first: Thomas

last: Ferrante

first: Bogdan

last: Budnik

first: Girija

last: Goyal

first: Abidemi

last: Junaid

first: Carlito

last: Lebrilla

first: Donald

last: Ingber


title: The first molecular characterization of Solanum lycopersicum-Phytophthora cinnamomi Rands Phytopathosystem: the essential role of pectin

city: Madrid

first: Marta

last: Berrocal-Lobo

state: Madrid

address: Antonio Nováis 10, s/n

department: System and Natural Resources

institute: School of Forestry Engineering and Natural Resources

summary: This study aimed to investigate the physiological and molecular responses of Solanum lycopersicum (tomato) to Phytophthora cinnamomi infection. The initial defense response in tomato seeds included the production of reactive oxygen species (ROS) and callose deposition. Screening of commercial tomato varieties revealed varying levels of susceptibility, with the variety Marmande exhibiting heightened vulnerability. Three days post-inoculation, Marmande showed increased expression of genes associated with ROS generation, and biosynthesis pathways for phenylpropanoids and flavonoids. Additionally, 850 genes related to cell wall remodeling, including those involved in lignin biosynthesis and pectin methyl esterase inhibitors (PMEIs), were significantly upregulated. Seven days post-inoculation, a stronger transcriptional response was observed, with activation of ethylene (ET) and jasmonic acid (JA) signaling pathways, while salicylic acid (SA) showed minimal activity. Metabolomic analysis of infected roots revealed elevated levels of metabolites linked to lycopene, flavonoids, and phenylpropanoids. Furthermore, infected roots exhibited a significant reduction in pectin levels, which was corroborated by in vitro assays showing zoospore-mediated pectin degradation. These results suggest that degradation of root pectin is a key mechanism facilitating zoospore invasion in susceptible tomato hosts. This study provides new insights into the molecular mechanisms underlying host-pathogen interactions and identifies potential targets for managing Phytophthora cinnamomi-induced diseases in crops.

overall_design: Roots of tomato (Marmande variety), seedlings were inoculated with a stock of Phytophthora cinnamomi oomycete zoospores stock, tissue samples were harvest after three and seven days of inoculation, controls were treated similarly with water.

first: César

last: Poza-Carrión


title: Sox9 in the Epicardium: Implications for Cell Invasion, Differentiation, and Coronary Vascular Development

city: Charleston

first: Allison

last: Trouten

address: 173 Ashley Ave Room BSB 642

department: Regenerative Medicine and Cell Biology

institute: Medical University of South Carolina

summary: The epicardium is the mesothelial lining of the heart which acts as a source of progenitor cells during heart development, giving rise to an invasive population of mesenchymal cells which differentiate into cardiac fibroblasts, mural cells, and other cell types essential for heart structure and function. Previously, we showed that epicardial-specific deletion of the gene encoding SRY-box transcription factor 9 (SOX9) impairs epicardial-derived cell invasion and reduces their contribution to the atrioventricular valve mesenchyme. In this study, we use single-cell RNA-sequencing to investigate broader roles of Sox9 in the epicardium as it relates to epicardial invasion, differentiation, and vascular development. We identified transcriptional changes indicative of decreased epicardial-to-mesenchymal transformation consistent with histological observations. Sox9-deficient epicardial cells exhibited elevated expression of vascular smooth muscle cell genes, suggesting that Sox9 may influence epicardial cell fate decisions. Immunofluorescence analyses revealed defective epicardial attachment and decreased epicardial-derived cell invasion into the ventricular myocardium associated with delayed coronary plexus formation. This study expands our understanding of the role of Sox9 in epicardial biology, demonstrating an important function in regulating epicardial cell invasion, differentiation, and coronary vasculature development. These insights provide a foundation for further investigations into epicardial-mediated mechanisms underlying congenital heart abnormalities.

overall_design: This study focused on single-cell RNA-sequencing to further characterize the role of SOX9 in epicardial development. Transcriptomic analyses of E14.5 epicardial-Sox9 knockout and control hearts indicated dysregulation of genes implicated in epicardial invasion, differentiation, and vascular development.

first: Andrew

last: Harvey

first: Renelyn

last: Wolters

first: Jenna

last: Drummond

first: Raymond

last: Deepe

first: Hannah

last: Tarolli

first: Andy

last: Wessels