title: Influenza A virus infection sustainably rewires pneumocyte gene regulatory network responses to different pneumococcal serotypes in secondary Streptococcus pneumoniae infection [ATAC-seq]

city: Braunschweig

first: Andreas

last: Jeron

state: Nierdersachsen

address: Inhoffenstraße 7

department: Viral Immunology

institute: Helmholtz Center for Infection Research

summary: Background: Pneumococcal secondary infection following influenza A virus (IAV) pneumonia is a synergistic complication with high mortality. While varying invasiveness of pneumococcal serotypes is an important pathogenic factor, serotype-specifc immediate-early transcriptional responses of the IAV-perturbed alveolar epithelium have not been adressed. We comprehensively analyzed gene transcription in alveolar type II epithelial cells (AECII) isolated from mice infected with IAV and/or S. pneumoniae (S.pn.) serotypes 4, 7F and 19F.    Results: IAV, 14 days post infection, rendered the lung susceptible to invasive secondary S.pn. infection with serotypes 4 and 7F but not 19F. Only secondary 7F infection induced exacerbated cytokine/chemokine responses. IAV/7F infection induced superior protein expression of type I and II interferons, acesserbated expression in IAV/serotype 4 infection. Inference of a scale-free-like ARACNE gene co-expression network revealed interferon-response network modules in AECII and network-mapping unfolded S.pn. serotype-specific transcriptional network responses/usage. Secondary S.pn. infection abrogated the IAV-induced pneumocyte proliferative configuration and preceeding IAV infection rendered the transcriptional response to 7F infection comparable to that towards serotype 4. This related especially to network genes correlating with the expression of two master regulators of interferon responses: Irf7 and Stat1. Epigenetic ATAC-seq analysis of AECII in resolved IAV infection identified enhanced expression of ARACNE network genes Hist1h2bf, Igtp, Mki67, Rasl10b, H2-Q6 and H2-Q7 to be associated with increased chromatin accessability at promoter regions.    Conclusions: We show that AECII sustainably retain an IAV-associated transcriptional configuration with epigenetic involvement, that serotype-specifically affects proliferation and accelerates and enhances the AECII transcriptional response, mainly to interferons, in secondary S.pn. infection.

overall_design: ATAC-sequenceing of AECII from PBS treated control mice and IAV infected (day 14) mice in duplicate experiments was performed

first: Julia

middle: D

last: Boehme

first: Kristin

last: Schultz

first: Lars

last: Melcher

first: Katharina

last: Schott

first: Elif

last: Gelmez

first: Andrea

last: Kröger

first: Sabine

last: Stegemann-Koniszewski

first: Dunja

last: Bruder


title: RNA-seq analysis in progeny leaves on rice seed treatd with heat

status: Public on Mar 31 2025

city: Fukuoka

first: Yushi

last: Ishibashi

state: Fukuoka

address: 744 Motooka, Nishi-ku

department: Department of Bioresource Sciences

country: Japan

institute: Kyushu University, Faculty of Agriculture

type: Expression profiling by high throughput sequencing

summary: We report the relationship between transgenerational growth and  transcriptome in progeny leaves on rice seeds treated with heat.

overall_design: Examination of RNA-seq in progeny leaves on rice seeds treated with heat.

first: Ishibashi

last: Yushi

first: Suriyasak

last: Chetphilin


title: SINE-MIR enhancer rewiring by Esrrb architecturally reprogram the pluripotency spectrum [RNA-Seq]

city: Singapore

first: Yingying

last: Zeng

state: --- Select a state ---

address: 61 Biopolis Drive

country: Singapore

institute: Institute of Molecular and Cell Biology

summary: Bulk RNA-seq were performed on E14 cells after knockdown with shRNA

overall_design: Transcritional profiles of mouse embryonic stem cells upon factor knockdowns or CRISPR inactivation of MIR-regions were shown by RNA-seq

first: N

middle: O

last: Cipta

first: Y

middle: Y

first: Yi

last: Yao

first: H

last: Li

last: Loh


title: Obesity-instructed TREM2-high macrophages identified by comparative analysis of diabetic mouse and human kidney at single-cell resolution [scRNA-seq: Baseline_mouse]

city: Cambridge

first: Ayshwarya

last: Subramanian

state: MA

address: 415 Main Street

department: Klarman Cell Observatory

country: USA

institute: Broad Institute

summary:
The cross-species molecular heterogeneity from mice to patients poses grand challenges for translational research endeavors. A high-fat diet (HFD) model and a genetic model (BTBR ob/ob) at different stand points were used to generate cell atlases of diabetic and obese mise.
We identified a previously unrecognized, expanding Trem2-High macrophage population in kidneys of HFD mice that modeled human TREM2-high macrophages in obese patients. Taken together, our cross-species comparison highlights shared immune and metabolic cell-state changes.

overall_design: For establishing the baseline atlas, the most commonly used lab mouse strain C57BL/6J between ages of 10 and 12 weeks, was used. We included biological replicates (n=5 for coronal section, n= 3 for renal hilum, medulla, cortex) from both male (M) and female (F) sexes. A mouse either donated a coronal section or a section each of cortex, medulla and hilum.

first: Anna

last: Greka


title: Total RNAseq from patient DM1 cell line

city: Paris

first: Florent

last: Hubé

address: 9 quai saint Bernard

department: LBD

country: France

institute: Sorbonne Université, CNRS, Paris, France

summary: Recently, the repertoire of human small nucleolar ncRNAs (snoRNAs) and their potential functions have been expanded by the discovery of new snoRNAs and mRNA targets, for which snoRNA-guided modifications may influence their stability, translatability, or splicing. We previously identified snoRNAs that are abundant in healthy human muscle progenitors. Here, we showed that SNORA40 and SNORA70 loss-of-function impairs myogenic differentiation. Strikingly, their gain-of-function can rescue the impaired differentiation muscle progenitor cells in Myotonic Dystrophy type 1 (DM1). We identified the CCND3 mRNA, partly located in the nucleolus, as a target of SNORA40 and SNORA70, which are needed for its pseudouridylated status. Expression of the CCND3 protein is required for muscle progenitors to exit the cell cycle when they are induced to differentiation. Here, we revealed that this switch requires SNORA40/70. Finally, we showed that rescuing reduced levels found in DM1 cells restores the expression of CCND3 through pseudouridylation of its mRNA, and ultimately resumes the cell fusion capacity of DM1 muscle progenitors.

overall_design: Total RNAseq from patient DM1 cell line

first: Claire

last: Francastel


title: Regulation of host RNA splicing in Mycobacterium tuberculosis infected macrophages

city: New Delhi

first: Dhiraj

last: Kumar

state: Delhi

address: Aruna Asaf Ali Marg

country: India

institute: ICGEB, New Delhi

summary: Here using a high-throughput yeast two-hybrid and mass spectrometry approach we show that mycobacterial proteins can access the RNA splicing machinery of the host, thereby playing a critical role in infection-induced perturbation of alternative splicing.

overall_design: We then performed gene expression profiling analysis using data obtained from RNA-seq of THP-1 macrophages infected with H37Rv and H37Rv::Rv1435KO at 48hr post infection.

first: Komal

last: Chauhan

first: Mrinmoy

last: Das


title: MBNL overexpression rescues cardiac phenotypes in a myotonic dystrophy type 1 heart mouse model

status: Public on Mar 30 2025

city: Portland

first: Zheng

last: Xia

state: Oregon

address: 2720 S. Moody Avenue

institute: OREGON HEALTH & SCIENCE UNIVERSITY

summary: Myotonic Dystrophy Type 1 (DM1) is an autosomal dominant disease caused by a CTG repeat expansion in the DMPK gene. The expanded CUG repeat RNA (CUGexp RNA) transcribed from the mutant allele sequesters the muscleblind-like (MBNL) family of RNA-binding proteins, causing their loss of function and disrupting regulated pre-mRNA processing. We used a DM1 heart mouse model that inducibly expresses CUGexp RNA to test the contribution of MBNL loss to DM1 cardiac abnormalities and explore MBNL restoration as a potential therapy. AAV9-mediated overexpression of MBNL1 and/or MBNL2 significantly rescued DM1 cardiac phenotypes including conduction delays, contractile dysfunction, hypertrophy, and mis-regulated alternative splicing and gene expression. While robust, rescue was partial compared to reduced CUGexp RNA and plateaued with increased exogenous MBNL expression. These findings demonstrate that MBNL loss is a major contributor to DM1 cardiac manifestations, and suggest that additional mechanisms play a role, highlighting the complex nature of DM1 pathogenesis.

overall_design: TREDT960I (Hom)/ MHCrtTA (Hemi) (CUG960) mice used in this RNA-seq study were separated into 6 groups, 3 experimental cohorts with AAV9-delivered heart-specific expression of 3XFLAG-MBNL1 and/or 3XMYC-MBNL2, as well as three control cohorts (on dox, on/off dox, and no dox control).  For all cohorts except no dox cohort, CUG960 mice were put on dox since post-natal day 1. The three experimental cohorts received AAV9 through tail vein injection at 9 weeks of age and remained on dox as the on dox cohort till last time point (21 weeks of age). For the on/off dox cohort, the mice were taken off dox feed at 9 weeks of age and remained on normal chow till last time point. Ventricular and atrial tissues of all cohorts were collected at 12 weeks post-delivery (21 weeks of age) and three samples from each cohort were used for RNA isolations.

first: Rong-Chi

last: Hu

last: Zhang

first: Larissa

last: Nitschke

first: Sara

middle: J

last: Johnson

first: Ayrea

middle: E

last: Hurley

first: William

middle: R

last: Lagor

first: Thomas

middle: A

last: Cooper


title: Single cell RNA-seq analysis of Tbx4+ and Tbx4- mouse lung mesenchymal cells

city: Los Angeles

first: ting

last: Xie

state: CA

address: 127 San Vicente Blvd

department: Pulmonary

institute: Cedars-Sinai Medical Center

summary:
Purpose: The goals of this study are to analyze Tbx4 lineage+ and Tbx4 lineage- cells sorted from Tbx4cre;RosaTm mouse lung.
Methods: Tbx4 lineage+ and Tbx4 lineage- cells within epcam+ CD31- CD45- 7AAD- cells were sorted from Tbx4cre;RosaTm mouse lung, and run on the C1 chip (Fluidigm). Cell capture, lysis, reverse transcription and cDNA amplification was performed on the C1 IFC for mRNA-seq on Fluidigm C1 Single-Cell Auto Prep System following the manufacturer’s protocol.
Results: C1 single cell RNA-seq platform captured and sequenced 54 Tbx4 lineage+ cells and 39 Tbx4 lineage - cells.
Conclusions: Our study analyzed transcriptomes of Tbx4 lineage+ and Tbx4 lineage- lung mesenchymal cells. This study provides a framework for the application of transcriptome profiling towards characterization of differentiated genes Tbx4 lineage+ and Tbx4 lineage - cells.

overall_design: Tbx4 lineage+ and Tbx4 lineage- mesenchymal cells were sorted from Tbx4cre;RosaTm mouse lung, and run on the C1 chip (Fluidigm).

first: Ting

first: Paul

middle: W

last: Noble


title: RNA Sequencing Analysis of Wild Type and ColcreER; Tbx4flox/flox Whole Lung and Mesenchymal Extracellular Vesicle Transcriptomes

summary:
Purpose: The goals of this study are to compare wild type (WT) and ColcreER; Tbx4flox/flox whole lung to lung mesenchymal extracellular vesicle (EV) trasncriptome profilling by RNA sequencing (RNA-seq) and to analyze the differentiated genes.
Methods: Total RNA was isolated from WT and ColcreER; Tbx4flox/flox whole lung and cultured lung mesenchymal extracellular vesicle. mRNA profiles were generated by deep sequencing, using Illumina HiSeq 3000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with two methods: Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA) and TopHat followed by Cufflinks.
Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 16,014 transcripts in the retinas of WT and Nrl−/− mice with BWA workflow and 34,115 transcripts with TopHat workflow. RNA-seq data confirmed stable expression of 25 known housekeeping genes, and 12 of these were validated with qRT–PCR. RNA-seq data had a linear relationship with qRT–PCR for more than four orders of magnitude and a goodness of fit (R2) of 0.8798. Approximately 10% of the transcripts showed differential expression between the WT and Nrl−/− retina, with a fold change ≥1.5 and p value <0.05. Altered expression of 25 genes was confirmed with qRT–PCR, demonstrating the high degree of sensitivity of the RNA-seq method. Hierarchical clustering of differentially expressed genes uncovered several as yet uncharacterized genes that may contribute to retinal function. Data analysis with BWA and TopHat workflows revealed a significant overlap yet provided complementary insights in transcriptome profiling.
Conclusions: Our study analyzed transcriptomes of WT and ColcreER; Tbx4flox/flox whole lungs and cultured lung mesenchymal extracellular vesicle, with biologic replicates, generated by RNA-seq technology. This study provides a framework for the application of transcriptome profiling towards characterization of differentiated genes in whole lung and mesenchymal extracellular vesicle of WT and Tbx4creER; Ghrflox/flox mice .

overall_design: lung and extracellular vesicle mRNA profiles of adult wild type (WT) and Tbx4creER; Ghrflox/flox mice were generated by deep sequencing using Illumina HiSeq 3000.


title: Effects of Continuous in situ Low-Dose Ionizing Radiation Exposure on Pseudomonas putida KT2440

city: Newark

first: Mark

last: Blenner

state: DE

department: Chemical and Biomolecular Engineering

institute: University of Delaware

summary: The ability to detect trace amounts of ionizing radiation is a paramount concern for chemical, biological, radiological, nuclear, and explosives (CBRNE) operations and observation of clandestine activities in the event of source relocation and contamination. Microbes respond to environmental stress such as fluctuations in pH and temperature, nutrient limited conditions, and oxidative stress with morphological and behavioral changes, and induced responses are known to persist after the stressor is removed. Innate responses to other external stressors like exposure to low-dose ionizing radiation could be measured and characterized by changes in gene expression and resulting transcriptional changes could by engineered into biosensors to monitor and discern the presence and type of radiation, respectively, in the environment. The current understanding of the biological and transcriptional responses of bacteria to various doses of ionizing radiation is minimal. The work in this study expands upon the findings in our previous study of the response of a model bacterium to low doses of ionizing radiation soil bacterium, Pseudomonas putida KT2440. Following exposure to an approximate absorbed dose rate of 9 mGy d-1 of a 239Pu, 3H, or 55Fe source, RNA-seq analysis revealed key changes in gene expression of P. putida of genes encoding membrane components, central carbon metabolism, DNA repair pathways, and motility. Several genes were differentially expressed genes in P. putida after exposure to multiple radionuclide sources. Moreover, other genes were uniquely differentially expressed by a single radionuclide source. These findings expand upon the limited understanding of the biological response to low doses of ionizing radiation and provide fundamental characterization required to develop discriminatory RNA-based biosensors.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for P. putida KT2440 cells subjected to an absorbed dose of 9 mGy d-1 of in situ Pu-239, H-3, or Fe-55 radionuclide source or non-irradiated chemical equivalent control for one and 15-days at room temperature.

first: Molly

last: Wintenberg

first: Lisa

middle: M

last: Manglass

first: Nicole

last: Martinez


title: Inhibition of MAFB and PI3K/AKT-signaling reveals a potential therapeutic strategy for multicentric carpotarsal osteolysis-associated nephropathy

city: Tsukuba

first: Akihiro

last: Kuno

state: Ibaraki

address: 1-1-1 Tennodai

institute: University of Tsukuba

summary: Multicentric carpotarsal osteolysis (MCTO) is an ultra-rare skeletal dysplasia characterized by aggressive osteolysis and in many patients, progressive renal failure. Previous work identified autosomal dominant missense mutations in the transactivation domain of the transcription factor MAFB as the cause of MCTO. Because the pathological mechanism resulting in MCTO is not clear, we used mice carrying the MCTO mutation (MafbMCTO/MCTO mice) to determine the role of MAFB. Using a cycloheximide chase assay in HEK293T cells, we found that the MCTO mutation resulted in reduced degradation and thus accumulation of recombinant MAFB protein. MafbMCTO/MCTO mice exhibited focal segmental glomerulosclerosis (FSGS) similar to what is observed in MCTO patients. To analyze the effect of the excessive presence of MAFB, we generated heterozygous MafbMCTO/- mice by crossing MafbMCTO/MCTO and Mafb+/- animals. Such MafbMCTO/- mice did not suffer albuminuria and exhibited histologically normal kidney appearance. The finding that MCTO mutation haploinsufficiency rescues animals from nephropathy is consistent with the mutation resulting in excess MAFB as the cause of disease. Next, we performed RNA-seq of the glomeruli from MafbMCTO/MCTO mice. We found marked up-regulation of the PI3K/AKT signaling pathway. Because receptor tyrosine kinases are PI3K/AKT activators, we administered the specific inhibitor imatinib to MafbMCTO/MCTO mice. This resulted in a significant reduction of urinary albumin relative to untreated animals. Taken together, these results suggest that excess MAFB and the activation of PI3K/AKT signaling induce nephropathy in MCTO. MAFB and/or PI3K/AKT signaling may therefore represent new treatment targets in MCTO patients.

overall_design: Glomeruli mRNA profiles of WT and MCTO mice

first: Satoru

last: Takahashi

first: Naoto

last: Morito


title: Chromatin Modification Abnormalities by CHD7 and KMT2C Loss Promote Medulloblastoma Progression

city: Tokyo

first: Kohei

last: Kumegawa

address: 3-8-31 Ariake, Koto-ku

institute: Japanese Foundation for Cancer Research

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Identification of miRNAs and their target genes in Bemisia tabaci when feeding on Nicotiana tabacum plants

status: Public on Mar 29 2025

city: Hangzhou

first: fan

last: xiaoping

state: zhejiang

address: Hangzhou, China

country: China

institute: LC-Bio Technology Co.

type: Non-coding RNA profiling by high throughput sequencing

summary: The study aims to identify and analyze the miRNAs in Bemisia tabaci that feed on Nicotiana tabacum cv. NC89 plants. This allows for the investigation of insect miRNAs that play important physiological roles in Bemisia tabaci. Additionally, it enables the analysis and identification of miRNAs that are transferred from Nicotiana tabacum to Bemisia tabaci. These data can further help us understand the role of miRNAs in the interaction between Bemisia tabaci and its host plants.

overall_design: The experimental design involves identifying miRNAs in MEAM1 Bemisia tabaci while they are feeding on Nicotiana tabacum plants.

first: Wenhao

last: Han

first: Shunxia

last: Ji

first: Fengbin

first: Junxia

last: Wang

first: Xiaoping

last: Fan

first: Shusheng

last: Liu

first: Xiaowei


title: Cellular senescence and its associated AKR1B1 promote cyst growth in ADPKD

city: Rochester

first: Xinyue

last: Mao

state: Minnesota

address: 150 3rd St SW

department: Nephrology and Hypertension

institute: Mayo Clinic

summary: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common, life-threatening inherited kidney diseases. Cellular senescence regulates not only physiological and homeostatic processes, particularly during embryonic development and wound healing, but also pathological processes that contribute to aging, cancer, and other diseases in response to endogenous and exogenous stresses. However, the role of cellular senescence in ADPKD remains elusive. To determine whether D-gal induces differential senescence response in Pkd1-null vs. wild-type cells, we performed RNA-sequencing (RNA-seq) analysis.

overall_design: To determine whether D-galactose (D-gal) induces differential senescence response in Pkd1-null vs. wild-type cells, we firstly treated Pkd1 WT MEK and Pkd1 null MEK  cells with D-gal (40g/l) for 48 hours and then performed RNA-sequencing (RNA-seq) analysis.

first: Lu

last: Li

first: Geoffray

last: Lee

first: Ewud

last: Agborbesong

first: Xia

last: Zhou

first: James P

last: Calvet

first: Xiaogang


title: Chromatin Modification Abnormalities by CHD7 and KMT2C Loss Promote Medulloblastoma Progression [RNA-seq]

summary: Medulloblastoma, a common malignant pediatric brain tumor that typically originating from the cerebellum, is characterized by mutations in chromatin modifiers, highlighting the significance of epigenomic abnormalities in their progression. To prove this significance, the development and use of animal models that closely recapitulate the disease have been highly effective. However, due to substantial time and cost limitations of developing genetically engineered mouse models, a complete understanding of the oncogenic potential of chromatin modifiers’ mutations found in human medulloblastomas is still elusive. In this study, we address this by CRISPR-mediated gene editing platform to knock out chromatin modifiers mutated human in SHH-subgroup medulloblastoma as well as the Ptch1 gene in cerebellar granule neuron progenitors. We functionally screened molecules involved tumor formation, identifying CHD7 and KMT2C as tumor suppressor genes. Multi-layered omics analysis revealed that these molecules epigenetically regulate the expression of Neurod1 that encodes a transcription factor crucial for neuronal differentiation, through histone H3 modification. Mutations impairing these factors suppress Neurod1, accelerating tumor growth. Conversely, forced expression of Neurod1 inhibits proliferation and promotes differentiation, underscoring its role as a key regulator in medulloblastoma aggressiveness. These findings not only demonstrate converging epigenomic abnormalities in SHH-subgroup medulloblastoma but also hold significant potential for evaluating epigenetic drugs targeting medulloblastoma, advancing the development of novel treatments.

overall_design: To investigate transcriptomic changes of SHH medulloblastoma tumors induced by sgPtch1 and sgChd7/sgKmt2c; and transcriptome in spontaneous SHH MB tumors; and also transcriptome in group3 medulloma

first: Wanchen

first: Reo

last: Maruyama

first: Daisuke

last: Kawauchi


title: Chromatin Modification Abnormalities by CHD7 and KMT2C Loss Promote Medulloblastoma Progression [ATAC-seq]

first: Kohei

overall_design: To investigate chromatin accessiblity changes of SHH medulloblastoma tumors induced by sgPtch1 and sgChd7; and in tumorigenesis


title: Chromatin Modification Abnormalities by CHD7 and KMT2C Loss Promote Medulloblastoma Progression [scMultiome]

overall_design: Chromium Single-Cell Multiome ATAC + Gene Expression for mouse medulloblastoma GEMM model


title: Recognition and processing of long double-stranded RNA in mammalian cells

city: San Francisco

first: Stefan

last: Oberlin

address: 505 Parnassus Ave

department: Department of Microbiology and Immunology

institute: University of California, San Francisco

summary: In A. thaliana, C. elegans and Drosophila, long dsRNA accumulation during virus infection, transposon activation or transgene expression, elicits a potent RNAi response: long dsRNA processing into siRNAs by Dicer, loading into Argonaute and assembly of the RNA-induced silencing complex to slice complementary RNA. In mammals, recognition of long dsRNA by type I interferon (IFN) factors, results in a mitigated RNAi response in some cell types. Here we uncover key mechanisms associated with recognition and processing of long dsRNA by both pathways. First, we demonstrate that exogenous long dsRNA rapidly congregates into granules recruiting key RNA silencing and type I IFN factors, suggesting an interaction between these pathways. Second, we confirm that inactivation of PKR, unleashes a potent RNAi response on transgene and endogenous mRNA targets in HEK293T cells. Finally, we observe different Dicer processing modes and uncovered a role for TRBP as regulator of RNAi in a template-dependent manner.

overall_design: Total and Ago-pulldown sRNA sequencing of different HEK293T knock-out backgrounds transfected with various long dsRNA templates to elucidate the mechanism of mammalian RNAi and genetically dissect which proteins are involved

first: Daniël

last: van Leeuwen

first: Bogdan

last: Mateescu


title: Tet2 and Tet3 functionally overlap in vitamin C-induced epigenomic alterations in acute myeloid leukemia

city: Vancouver

first: Martin

last: Hirst

state: British Columbia

address: 2125 East Mall

department: Microbiology and Immunology

country: Canada

institute: University of British Columbia

type: Methylation profiling by high throughput sequencing

summary: Heterozygous mutations that impair the demethylase activity of the ten eleven translocation (TET) enzyme family are frequent events in de novo acute myeloid leukemia (AML). Although both TET2 and TET3 are highly expressed in AML blasts and murine leukemic models, only TET2 is mutated in AML patients, suggesting a divergent oncogenic relevance. To define the individual functions of TET2 and TET3, we inactivated both genes individually and in combination in a HoxA9/IDH1R132H murine AML model and analyzed the resulting transcriptional and epigenetic states in the presence and absence of the TET co-factor vitamin C. Despite their distinct DNA-binding characteristics, we found that Tet2- and Tet3- regulated enhancer:gene networks largely overlap and that they elicit similar cytomorphological changes when perturbed. Overall, our findings suggest that despite their divergent oncogenic relevancy, Tet2 and Tet3 act on a common myeloid differentiation pathway that can independently be activated by either Tet2 or Tet3.

overall_design: Examination of immunoprecipitated 5hmC, 5mC, and total RNA in a HoxA9/IDH1-R132H murine cell line with Tet2 and Tet3 genetically inactivated separately or in combination. Each cell line was treated daily with 0.345mM vitC and was processed after 15hrs and 72hrs.

first: Jasper

last: Wong

first: Sarah

last: Grasedieck

first: Marcus

first: Mansen

last: Yu

first: Qi

last: Cao

first: Michelle

last: Moksa

first: Avinash

last: Thakur

first: Florian

last: Kuchenbauer

first: Richard

middle: K

last: Humphries

first: Michael

last: Heuser


title: Effect of simulated galactic cosmic radiation on mouse lung gene expression

city: Atlanta

first: Mac

last: Mao

state: GA

address: 101 Woodruff Cir

institute: Emory University

summary: C57LBL/6 mice (age 24 weeks) were exposed to 0,75 Gy of Si ions, 5-ion simplified GCR simulation, or reference gamma rays. Some mice received nicotinamide riboside countermeasure. Lung tissue was collected after 30 days and flash frozen.

overall_design: Mice were irradiated as listed in the samples section.  5-ion simplfieid GCR simulation is defined as 1 GeV 1-H (34.8%), 600 MeV/U 28-Si  (1.1%), 250 MeV/U 4-He ((18.0%), 350 MeV/U 16-O (5.8%), 600 MeV/U 56-Fe (1.0%) and 250 MeV 1-H (39.2%). Nicotinamide riboside was administered continuously in drinking water, starrting prior to irradiation, at a concentration of 12 mM.

first: William

last: Dynan

first: Lahcen

last: Jaafar

first: Alexis

last: Chan


title: Transcriptome profiles of mouse cortical cultures and the brain treated with fluoxetine, sertraline or citalopram

city: Sendai

first: Hajime

last: Yamamoto

address: 2-1-1 Katahira, Aoba-ku

institute: Tohoku university

summary: Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed antidepressant classes in recent decades, with the development of numerous variants. While the primary action of these medications involves the inhibition of serotonin reuptake, the observed therapeutic efficacy exhibits interindividual variability. In order to elucidate the molecular mechanisms underlying their pharmacological actions, this study examined the alteration in the transcriptome following treatment of each SSRI—fluoxetine, sertraline, or citalopram— or vehicle in cultured cortical neurons and the medial prefrontal cortex (mPFC) of mice (Mus musculus, Slc:ICR).

overall_design: In vitro experiment: Cortical cultures were obtained from the mouse embryo on embryonic day 15. Fluoxetine, sertraline, or citalopram were administered for each culture for 24 hours from 16 days in vitro (div). In vivo experiment: Male mice at 8 weeks of age were isolated and treated with either fluoxetine, sertraline, or citalopram for 2 weeks via drinking water, and then their mPFC regions were dissected. Those samples were subjected to RNA extraction and library preparation.

first: Kentaro

last: Abe


title: CXCL1+ perivascular cells enable dissemination of blood stem cells that preserve hematopoietic fitness

city: New Haven

first: Andrés

last: Hidalgo

address: 10 Amistad Street

institute: Yale University

summary:
Purpose: The goals of this study are to compare bulk RNA-seq profiles of circulating LSK cells to non-circulating LSK cells
Methods: Bulk RNA-seq of sorted LSK from BM of parabiotic mice from germ-free mice, using Illumina.

overall_design: Examination of different transcriptomic profiles in circulating LSK that have circulated to the BM of an irradiated parabiotic mice

first: Cossío

last: Itziar

first: Rubio-Ponce

last: Andrea

first: Hidalgo

last: Andrés


title: A Deep Dive into the Functional and Spatial Heterogeneity of Lung Interstitial Macrophages [Xenium]

status: Public on Mar 28 2025

city: Lebanon

first: Claudia

middle: V

last: Jakubzick

state: NH

address: 1 Medical Center Drive, Rm 626 W Borwell, PO#1250960

institute: Dartmouth College

summary: Interstitial macrophages (IMs) are increasingly recognized for their vital roles in maintaining tissue homeostasis and orchestrating immune responses. Here, we present a comprehensive transcriptomic analysis of murine lung IMs that highlights their diverse functional roles, specialized divisions of labor, and distinct spatial organization within the lung microenvironment. Building on earlier work showing that two overarching IM subsets—CD206hi and CD206lo—encompass ten unique chemokine-expressing subpopulations that regulate immune cell recruitment and tertiary lymphoid structures, we now demonstrate that these IM subsets also exhibit distinct cytokine and receptor gene profiles, along with an extensive autocrine network that influences their migration and cytokine-driven functions. Furthermore, we identify distinct innate immune signatures, including complement components, scavenger receptors, and pattern recognition pathways (e.g., Toll-like receptors and C-type lectins), underlining their broad contributions to innate immunity. Using Xenium spatial transcriptomics, we show that IMs predominantly localize to three lung regions: bronchovascular bundles, interstitium, and periphery. CD206hi and CD206lo IMs preferentially occupy specific sub-tissular niches, likely driven by differential integrin and metallopeptidase gene expression. Additionally, chemokine expression within IMs exhibits distinct spatial localization patterns, directing the recruitment of T cells and B cells. Two summary tables were provided to outline the differential gene expression across IM subsets in the dataset. Overall, our findings advance the understanding of IM heterogeneity and their multifaceted roles in chemoattraction, inflammation regulation, innate immune defense, and tissue maintenance, while providing a high-resolution framework for investigating their localization, interactions, and contributions to lung immunity and disease.

overall_design: Two groups of C57BL/6 mice (n = 2 per group) were used for analysis: Group 1 (Naive), which received no treatment and was expected to contain steady-state interstitial macrophages (IMs); and Group 2 (LPS), treated with lipopolysaccharide (LPS; Sigma-Aldrich) administered intranasally at 10 μg in 50 μl sterile PBS (Corning) 24 hours before collection, expected to contain stimulated IMs and recruited monocytes. The samples were analyzed using Xenium spatial transcriptomics with a 100-gene panel.

first: Xin

last: Li


title: Coxsackievirus A10 impairs nail regeneration and induces onychomadesis by mimicking DKK1 to attenuate Wnt signaling

city: Beijing

first: Ye-guang

last: Chen

address: Tsinghua Road, Medical Building

department: School of life science

institute: Tsinghua University

summary: Coxsackievirus A10 (CV-A10) infection, a prominent cause of childhood hand-foot-and-mouth disease (HFMD), frequently manifests with the intriguing phenomenon of onychomadesis, characterized by nail shedding. However, the underlying mechanism is elusive. Here, we found that CV-A10 infection in mice could suppress Wnt/β-catenin signaling by restraining LDL-receptor-related protein 6 (LRP6) phosphorylation and β-catenin accumulation and led to onychomadesis.  Mechanistically, CV-A10 mimics Dickkopf-related protein 1 (DKK1) to interact with Kringle-containing transmembrane protein 1 (KRM1), the CV-A10 cellular receptor. We further found that Wnt agonist (GSK3β inhibitor) CHIR99021 can restore nail stem cell differentiation. These findings provide novel insights into the pathogenesis of CV-A10 and related viruses in onychomadesis and guide prognosis assessment and clinical treatment of the disease.

overall_design:
Examination the gene expression profiles from PBS and Coxsackievirus A10 infection mice digits.
Examination the gene expression profiles from PBS+Vaseline and Coxsackievirus A10-Vaseline and Coxsackievirus A10-CHIR  treated mice digits.

first: Ye-Guang

first: George

middle: F

last: Gao

first: Yingzi

last: Cui

first: Xiaodan

last: Wang

first: Qiaoni

last: Shi

first: Yuxuan

last: Zheng

first: Jianyu

last: Tong

first: Zhou


title: Expression data from HEK293T cells

first: Meng

last: Lou

address: 88 Jiefang Road, The Second Affiliated Hospital, School of Medicine

institute: Zhejiang University

summary:
Abnormal DNA sensing mediated by cGAS-STING is pivotal for host defenses. Activation of cGAS-STING triggered interferon dependent anti-viral functions have been well characterized but this function is missing in more ancient animal STING. Whether more primitive animal STING can generate non-canonical pathway dependent anti-viral activities is unclear. Here, we discovered potent anti-viral activities of ancient animal STING in the absence of all three canonical pathways. Various ancient animal STING-stimulated genes (ASGs) with unique and synergistic anti-viral functions were induced by this newly identified pathway through an ancient transcriptional regulator IRF1 and a separate unique functional domain in STING. Some ASGs are both necessary and sufficient as host restriction factors and under positive selection during animal evolution. Diverse viruses have developed strategies to evade this newly identified cGAS-STING function. Our findings reveal an ancient, conserved cGAS-STING pathway mediated anti-viral activities through previously unrecognized cellular restriction factors.
Various animal STING expression in HEK293T cells could up regulate a series of genes. To screen candidates for anti-viral host factors stimulated by STING in the absence of the known canonical pathways, we identified the factors that were regulated by the IFN induction and NF-κB induction-defective Nematostella vectensis (N.v) STING and the IFN induction-defective human STING variant (H.s STING ΔCTT) by microarray assay. Multiple rounds of confirmative and comparative experiments narrowed down to 10 such factors, i.e., ancient animal STING stimulated genes (ASGs). ASGs were significantly upregulated by STING activation in various human cell types.

overall_design: The H.sSTING ΔCTT, N.vSTING or empty vector were co-transfected with cGAS in HEK293T cells. Twenty hours later, mRNA samples were prepared and analyzed using Affymetrix microarrays. We sought to obtain up-regulated genes by the IFN induction-defective human STING variant (H.s STING ΔCTT) and IFN induction and NF-κB induction-defective N.v STING

first: Xinyu


title: Multi-Omics Analysis of Ovine Atretic Follicles：Linoleic Acid Metabolite 13-Hydroxyoctadecadienoic Acid as a Biphasic Ferroptosis Modulator in Granulosa Cells

city: Hohhot

first: Song

last: Yukun

state: Inner Mongolia

address: Inner Mongolia Key Laboratory of Sheep & Goat Genetics Breeding and Reproduction

institute: Inner Mongolia Agricultural University

summary: Follicular atresia is a complex physiological process involving multiple forms of cell death. Ferroptosis, an iron-dependent form of programmed cell death, has been less studied in the context of follicular atresia. 13-Hydroxyoctadecadienoic acid (13(S)-HODE) is a bioactive lipid derived from linoleic acid. To investigate the association between ovine follicular atresia and ferroptosis, we performed transcriptomic and metabolomic analyses of healthy and atretic sheep follicles. The metabolomic analysis identified 87 and 48 differentially expressed metabolites in healthy and atretic follicles, respectively. Functional enrichment of atretic follicle fluid highlighted pathways related to linoleic acid and purine metabolism. Transcriptomic analysis revealed 250 highly expressed genes in ovarian granulosa cells of atretic follicles. Enrichment analysis indicated that these differentially expressed genes were associated with fatty acid metabolism and ferroptosis. Integration of multi-omics data demonstrated the occurrence of ferroptosis in atretic follicles, where 13(S)-HODE drives granulosa cell ferroptosis via the linoleic acid metabolism pathway

overall_design: RNA-seq profiling of granulosa cells from healthy and atretic Follicle


title: Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator [ChIP-Seq]

city: Temuco

first: Mauricio

middle: A.

last: Saez

address: Manuel Montt 56

country: Chile

institute: Universidad Catolica de Temuco

summary: Background  Oncogenes drive cancer progression, but few are active exclusively in tumor cells. Connexins (Cxs), traditionally recognized as ion channel proteins, can localize to the nucleus and regulate gene expression, playing key roles in both physiological and pathological processes. Cx46, once thought to be restricted to the eye lens, has been implicated in tumor growth, though its underlying mechanisms remain unclear. This study investigates the nuclear presence of Cx46 in cancer cells and its potential role as a transcriptional modulator. Methods We employed ChIP-Seq, confocal immunofluorescence, and nuclear protein purification to assess Cx46 localization and DNA interactions. Functional assays were conducted to evaluate its effects on invasion, division, spheroid formation, and mesenchymal marker expression. Single-point mutations and molecular dynamics simulations were used to explore potential Cx46-DNA interactions. Results Cx46 mRNA upregulation was found in a variety of tumors compared to adjacent healthy tissue. In HeLa cells, which do not express Cx46, its transfection promoted proliferation, invasion and self-renewal capacity, cancer stem cell traits and mesenchymal features. Consistently, in Sk-Mel-2, which naturally express Cx46, reduced Cx46 expression led to a decrease in the similar parameters. In HeLa cells, nuclear Cx46 was detected in two forms, full length 46 kDa and a 30 kDa fragment (GJA3-30 k), ChIP-Seq experiments revealed that Cx46 binds to the DNA at intergenic and promoter regions, leading to the activation of oncogenic pathways. Molecular dynamics simulations suggest that GJA3-30 k dimerizes in a RAD50-like structure, forming stable DNA complexes. Cx46 and in some cases GJA3-30 k were detected in the nuclei of multiple cancer cell lines, including prostate, breast and skin cancers. Conclusions Our findings reveal a novel nuclear role for Cx46 in cancer, demonstrating its function as a transcriptional regulator and its potential as a therapeutic target.

overall_design: Cells that do not express CX46 (Hela cells) were transfected and selected to obtain stable clones that express CX46. Cultures of Helas-Cx46 and were collected for analysis Chromatin immuprepipitation with anti-CX46 antbody (SC-365394, Santa Cruz Biotechnology)

first: Ainoa

last: Fernandez

first: Viviana

middle: P

last: Orellana

first: Jesús

last: Llanquinao

first: Gonzalo

last: Nuñez

first: Pablo

last: Pérez-Moreno

first: Sebastian

last: Contreras-Riquelme

first: Alberto

last: Martin

first: Fabio

last: Mammano

first: Ivan

last: Alfaro

first: Juan

last: Calderón

first: Jimmy

last: Stehberg

last: Sáez

last: Retamal


title: Connexin46 in the nucleus of cancer cells: a possible role as transcription modulator


title: Probe Sequencing Analysis of Regenerating Lizard Tails Indicates Crosstalk Among Osteoclasts, Epidermal cells, and Fibroblasts.

first: Darian

middle: Jordan

last: Gamble

address: 1450 Biggy St Nrt 4513

institute: University of Southern California

summary: Abstract: Lizards are distinguished as the only amniotes, and closest relatives of mammals, capable of multilineage epimorphic regeneration. Tail blastemas of green anole lizards (Anolis carolinensis) consist of col3a1+ fibroblastic connective tissue cells enclosed in krt5+ wound epidermis (WE), both of which are required for regeneration. Blastema and WE formation are known to be closely associated with phagocytic cell populations, including macrophages and osteoclasts. However, it remains unclear what specific phagocytic cell types are required to stimulate regeneration. Here we explicitly assess the roles of osteoclast activity during blastema and WE formation in regenerating lizard tails. First, probe-sequencing was perfomed at regenerative timepoints on fibroblasts isolated based on col3a1 expression toward establishing pathways involved in stimulating blastema formation and subsequent regeneration. Next, treatments with osteoclast inhibitor zoledronic acid (ZA) was used to assess roles of osteoclast activity in lizard tail regeneration and fibroblast signlaing. ZA treatment stunted lizard tail regrowth, suggesting osteoclast activity was required for blastema formation and regeneration. Transcriptomic profiling of fibroblasts isolated from ZA- treated and control lizards linked inhibition of oseolat activity with limitations in fibroblats to form extracellular matrix and support WE formation. These results suggests that crosstalk between osteoclasts and fibroblasts regulate blastema and WE formation during lizard tail regeneration.

overall_design: RNA-seq profiling of fixed, FISH sorted anolis carolinensis fibroblasts at 7,14, and 28 days post amputation as well as D21 treated with zoledronic acid (za) or a PBS control.

first: Thomas

last: Lozito


title: Single-cell transcriptome analysis of low-dose radiotherapy-mediated alleviation of LPS-induced acute lung injury

city: Seoul

first: dongryul

last: oh

address: Samsung Medical Center

country: South Korea

institute: Department of Radiation Oncology

summary: Acute lung injury (ALI), a condition with a high incidence and mortality rate worldwide, is a type of acute respiratory failure characterized by infiltrative lesions in the lungs. Low-dose radiation therapy (LDRT), which uses less than 1 Gy X-ray per session, has been tested for its clinical feasibility in suppressing lung inflammation in conditions that cause ALI. However, a mechanistic understanding of how LDRT alleviates inflammation in the lungs and restores balance in the immune environment is still lacking. In this study, we assessed the immunomodulatory effects of LDRT using single-cell RNA sequencing (scRNA-seq) and flow cytometry in a lipopolysaccharide (LPS)-induced ALI mouse model. LDRT with 1 Gy X-rays reduced the lung inflammation, immunostimulatory cells such as M1 macrophages, and pro-inflammatory cytokines such as interleukin 6 in the bronchoalveolar lavage fluid, while increasing the levels of immunosuppressive cells such as M2 macrophages and the anti-inflammatory cytokine TGF-β. Furthermore, scRNA-seq analysis of whole lung tissues confirmed that LDRT reduced the number of macrophages and neutrophils and downregulated the genes involved in inflammatory response pathways. Flow cytometry showed that LDRT effectively eliminated pro-inflammatory immune cells via apoptosis. Our findings underscore the potential utility of LDRT in ALI treatment by rebalancing immune homeostasis.

overall_design: RNA-seq profiling of mouse lung tissue after injection of PBS or LPS for 48 hours, and low-dose radiation for 24 hours.

first: Sung Eun

last: Lee

first: Sang Hoon

last: Seo

first: Yeon Joo

last: Kim

first: Yeeun

first: Junhun

last: Cho

first: Jun-Gi

last: Jeong

first: Seungcheon

last: Yong

first: Hyung-Yong

first: Changhoon

last: Choi

first: Dongryul

last: Oh


title: Chromatin Modification Abnormalities by CHD7 and KMT2C Loss Promote Medulloblastoma Progression [CUT&Tag]

first: Kohei

last: Kumegawa

overall_design: To investigate various histone mark changes of SHH medulloblastoma tumors induced by sgPtch1 and sgChd7/sgKmt2c

first: Wanchen

last: Wang

first: Reo

last: Maruyama

first: Daisuke

last: Kawauchi


title: Gene expression profile of modified gapmer antisense oligonucleotides treated mouse liver

city: Fujisawa

first: Shinya

last: Asano

state: Kanagawa

address: Muraoka-Higashi 2-chome

institute: Axcelead Drug Discovery Partners, Inc.

summary: To investigate gene expression change induced by modified gapmer antisense oligonucleotides, we performed transcriptome analysis of Scarb1 ASO or PBS treated mouse livers.

overall_design: Gene expression profiling of mouse liver treated 3 modified gapmer antisense oligonucleotides targeting Scarb1 or PBS at day 1, 3, and 7 after first administration.

first: Takaaki

last: Kawanobe


title: Inherent Specificity and Mutational Sensitivity as Quantitative Metrics for RBP Binding

city: Cleveland

first: Soon Yeul

last: Yi

state: OH

address: CWRU Wood Research Building W127A, 2109 Adelbert Rd,

department: Biochemistry

institute: Case Western Reserve University

summary: Interactions between RNAs and RNA binding proteins (RBPs) regulate gene expression in eukaryotic cells. RNA-RBP affinities measured in vitro reveal diverse binding specificities, yet approaches to directly compare specificities across RBPs are lacking. Here, we introduce two quantitative metrics: inherent specificity, which measures how selectively an RBP distinguishes its strongest binding motif from all possible motifs, and mutational sensitivity, which assesses tolerance to single nucleotide variations within preferred motifs. Analyzing high-throughput sequencing datasets, we compared these metrics across 100 RBPs in vitro and 27 RBPs in cells, finding strong correlation between in vitro and cellular measurements for RBPs that bind RNA independently of a local structural context. Through CLIP experiments with swapped RNA recognition motifs between a low-specificity RBP (RBM25) and a high-specificity RBP (HNRNPC), we demonstrated that sequence specificity can be transferred between protein contexts. Using these insights, we developed mathematical models showing how RBPs with different specificity profiles compete for binding sites, revealing how variations in inherent specificity and mutational sensitivity influence target selection. Together, our results provide a quantitative framework for modeling RNA-RBP interactions and designing RBPs with targeted specificity.

overall_design: To investigate the effect of RRM swap in the biological specificity of an RBP, four different cell lines expressing the wildtype hnRNPC and RBM25 and the mutant RBPs with their RRMs swapped were expressed in HEK293 cells. These exogenously expressed RBPs were tagged with V5 tag at the N-terminus for efficient immunoprecipitation. Then, UV crosslinking and immunoprecipitation using V5 antibody followed by hight-throughput sequencing (CLIP-Seq) was performed in the four cell lines.

first: Joseph

last: Luna

first: Soon

first: Shashi

last: Singh


title: Repeated head-exposures to a 5G-3.5 GHz signal do not alter behavior but modify intracortical gene expression in adult male mice.

city: Paris

first: Michel

last: Mallat

address: Boulevard de l'Hôpital

institute: ICM

summary: The fifth generation (5G) of mobile communications promotes human exposure to electromagnetic fields exploiting the 3.5 GHz frequency band. We analyzed behaviors, cognitive functions, and gene expression in mice submitted to asymmetrical head exposure to a 5G-modulated 3.5 GHz signal. The exposures were applied for 1 h daily, 5 days per week over a six-week period, at a specific absorption rate (SAR) averaging 0.19 W/kg over the brain. Locomotor activities in an open field, object location, and object recognition memories were assessed repeatedly after four weeks of exposure and did not reveal any significant effect on the locomotion/exploration, anxiety level, or memory processes. mRNA profiling was performed at the end of the exposure period in two symmetrical areas of the right and left cerebral cortex, in which the SAR values were 0.43 and 0.14 W/kg, respectively. We found significant changes in the expression of less than 1% of the expressed genes, with over-representations of genes related to glutamatergic synapses. The right cortical area differed from the left one by an over-representation of responsive genes encoded by the mitochondrial genome. Our data show that repeated head exposures to a 5G-3.5 GHz signal can trigger mild transcriptome alterations without changes in memory capacities or emotional state.

overall_design: Tissue samples  extracted from a brain region covering adjacent area of the entorhinal and the piriform cortex (Ent-Pir Cx) of the right and the left hemispheres in 13 week-old male C57 BL/6J mice, following daily 1h  head exposures or pseudo exposures to a 5G-3.5GHz electromagnetic field carried out over 4 weeks.

first: Julie

last: Lameth


title: Insulin post-transcriptional regulation via PARP12-mediated ADP-ribosylation

city: Richland

first: Ernesto

middle: S.

last: Nakayasu

state: WA

address: 902 Battelle Blvd

institute: Pacific northwest national laboratory

summary: ADP-ribosylation is a common modification that occurs in proteins and nucleic acids, regulating many cellular processes ranging from DNA repair to inflammatory signaling. ADP-ribosylation plays an important role in cancer biology, infectious diseases, and obesity, but its role in the development of type 1 diabetes (T1D) is not well understood. Here, we studied the role of ADP-ribosyltransferase PARP12 in T1D development. PARP12 expression is highly induced in human islets treated with pro-inflammatory cytokines or β cells from diabetic donors. Proteomics analysis of MIN6 insulin-producing cells identified that the RNA machinery is regulated by PARP12 during inflammation. PARP12 also ADP-ribosylates 150 mRNAs, including the insulin mRNA. This mRNA ADP-ribosylation in turn modifies transcript localization and halts translation. Overall, our data identified a role for PARP12 in ADP-ribosylation and translation halting of mRNAs, which may affect insulin production during insulitis.

overall_design: We have No Cytokine cocktail Nontarget siRNA and PARP12 siRNA treated group and Cytokine cocktail Nontarget siRNA and PARP12 siRNA treated groups (4 groups total). Each of those groups is split to be treated with Control and AF1521 beads making a total 8 groups. Each group have 4 biological replicates.

first: Soumyadeep

last: Sarkar

first: Fangjia

last: Li

first: Youngki

last: You

first: Emily

middle: C

last: Elliott

first: Kevin

last: Zemaitis

first: Hyeyoon

last: Kim

first: Meng

last: Markillie

first: Jeremiah

last: Traeger

first: Samantha

last: Powell

first: Mireia

last: Ramos-Rodriguez

first: Xiaoyan

first: Jacob

last: Enriquez

first: Marina

last: Gritsenko

first: Hugh

last: Mitchell

first: Decio

middle: L

last: Eizirik

first: Anthony

last: Leung

first: Lorenzo

last: Pasquali

first: Lori

last: Sussel

first: Thomas

last: Metz

first: Raghavendra

middle: G

last: Mirmira

middle: S


title: Direct targeted degradation of transposon RNAs by the non-canonical RNAi pathway of the fungus Mucor lusitanicus

city: Murcia

first: Carlos

last: Lax

address: Facultad de Biología

department: Genetics and Microbiology

country: Spain

institute: University of Murcia

summary: Mucor lusitanicus has emerged as a model organism for studying RNAi in early-diverging fungi. This fungus exhibits intricate RNAi pathways that play crucial roles in regulating gene expression, de-stroying invasive exogenous genetic material, and controlling the movement of transposable ele-ments (TEs) to ensure genome stability. One of the most fascinating RNAi pathways of this fungus is the non-canonical RNAi pathway (NCRIP), which is independent of Dicer and Argonaute proteins and uses the atypical RNase III R3B2 to degrade specific target mRNAs, playing an essential role in genome stability and virulence. Despite accumulating data suggesting that this pathway is a deg-radation mechanism, there has been no conclusive evidence. Here, we conducted a comparative transcriptomic analysis of mRNA and small RNAs regulated by r3b2, identifying 35 direct NCRIP targets. Most of these direct NCRIP targets correspond to TEs, highlighting the significant role of this RNAi pathway in TE control. Detailed functional analysis of the NCRIP targets confirms the crucial role on r3b2 in regulating gene expression of protein-coding genes and controlling TEs other than centromeric GremLINE1 transposons, emphasizing the important role of r3b2 in genome stability. Interestingly, the RNAs of the NCRIP targets harbor a unique motif consisting of CAG repeats which are known to form hairpin structures which are targeted by RNA interference. Additionally, the generation of transformants expressing mRNAs containing the luciferase reporter gene along direct NCRIP targets reveals that this RNAi pathway is a true degradation mechanism for specific mRNAs. These results are expected to contribute to the understanding of the regulation of the NCRIP pathway through the analysis of its direct targets identified here.

overall_design: RNA-seq experiment to analyze the differences in gene expression at the sRNA and mRNA levels caused by R3B2 KO in M. lusitanicus. Total RNA was extracted from MU636 and MU412 (r3b2 KO) for 24 hours on YPG media (solid) at 26 ºC. For each strain, we performed three biological replicates

first: Ghizlane

last: Tahiri


title: CREsted: modeling genomic and synthetic cell type-specific enhancers across tissues and species

city: Leuven

first: Stein

last: Aerts

address: ON6 Herestraat 49

department: Center for Brain and Disease Research

country: Belgium

institute: VIB-KU Leuven

summary: Sequence-based deep learning models have become the state of the art for the analysis of the genomic regulatory code. Particularly for transcriptional enhancers, deep learning models excel at deciphering sequence features and grammar that underlie their spatiotemporal activity. To enable end-to-end enhancer modeling and design, we developed a software and modeling package, called CREsted. It combines preprocessing starting from single-cell ATAC-seq data; modeling with a choice of several architectures for training classification and regression models on either topics or pseudobulk peak heights; sequence design using multiple strategies; and downstream analysis through a collection of tools to locate transcription factor (TF) binding sites, infer the effect of a TF (activating or repressing) on enhancer accessibility, decipher enhancer grammar, and score gene loci. We demonstrate CREsted using a mouse cortex model that we validate using the BICCN collection of in vivo validated mouse brain enhancers. Classical enhancers in immune cells, including the IFN-β enhanceosome are revisited using a PBMC model, and we assess the accuracy of TF binding site predictions with ChIP-seq. Additionally, we use CREsted to compare mesenchymal-like cancer cell states between tumor types; and we investigate different fine-tuning strategies of Borzoi within CREsted, comparing their performance and explainability with CREsted models trained from scratch. Finally, we train a CREsted model on a scATAC-seq atlas of zebrafish development, and use this to design and in vivo validate cell type-specific synthetic enhancers in 3 tissues. For varying datasets we demonstrate that CREsted facilitates efficient training and analyses, enabling scrutinization of the enhancer logic and design of synthetic enhancers across tissues and species. CREsted is available at https://crested.readthedocs.io.

overall_design: ATAC-seq profiling of 3 glioblastoma cell lines (A-172, M059J, LN229) to compare and derive insights of the underlying enhancer logic across cell lines and states.

first: Niklas

last: Kempynck

first: Seppe

last: De Winter

first: Casper

middle: H

last: Blaauw

first: Vasileios

last: Konstantakos

first: Sam

last: Dieltiens

first: Eren Can

last: Ekşi

first: Valérie

last: Bercier

first: Ibrahim

middle: I

last: Taskiran

first: Gert

last: Hulselmans

first: Katina

last: Spanier

first: Valerie

last: Christiaens

first: Ludo

last: Van Den Bosch

first: Lukas

last: Mahieu


title: Gene expression profile at single cell level of isofortex from Control and AS3MTd2d3-Tg mice

city: Pohang-si

first: Dahun

last: Um

address: 77 Cheongam-Ro. Nam-Gu. Pohang. Gyeongbuk. Korea 37673

department: Life science

institute: Pohang University of Science and Technology(POSTECH)

summary: Cell-type specific changes of isocortex in schizophrenia patients play critical roles in perception, cognition, emotion, and learning. We used single cell RNA sequencing(scRNA-seq) to analyze cell-type specific changes in AS3MTd2d3-Tg mice as a schizophrenia model.

overall_design: To analyze using scRNAseq with E15.5, isocortex of AS3MT-Tg mice are dissected, digested with trypsin, and pipetted with Pasteur pipette to dissociate cells. To analyze using snRNAseq with P60, isocortex of AS3MT-Tg mice are applied to singulator to extract nuclei from cells.

first: Seunghyun

last: Kim

first: Youngsik

last: Woo

first: Namyoung

last: Jung


title: Transcriptomic profiling of baricitinib effects on host immune response to RVFV infection in A549 cells and organoids

city: Trondheim

first: Aleksandr

last: Ianevski

address: Høgskoleringen 1

country: Norway

institute: NTNU

summary: This study investigates the modulatory effects of baricitinib on the host immune response to Rift Valley Fever Virus (RVFV) infection. A549 cells and organoids were treated with 5 µM baricitinib or vehicle control prior to infection with recombinant RVFV (rRVFV) or mock treatment. Total RNA was isolated at 8 and 24 hours post-infection, and mRNA was enriched for transcriptome sequencing. We performed RNA-seq analysis to identify differentially expressed genes and pathways affected by baricitinib treatment during RVFV infection, providing insights into potential therapeutic mechanisms of JAK inhibition in viral infections.

overall_design: This study investigates the effects of baricitinib on the host immune response to Rift Valley Fever Virus (RVFV) infection. We employed a 2×2×2×2 factorial design examining the following variables: cell system (A549 cells vs. lung organoids), treatment (5 µM baricitinib vs. vehicle control), infection status (recombinant RVFV vs. mock infection), and time point (8h vs. 24h post-infection). Each condition was performed in biological triplicate.


title: Gene expression by AR agonism and AR antagonism in isotope-labeled PCa cells

city: Vancouver

first: Anne

last: Haegert

state: BC

address: 2660 Oak Street

department: Genomics Core

institute: Vancouver Prostate Centre

summary: Systematic investigation of gene expression by R1881 and Enzalutamide in SILAC assay of LNCaP cells

overall_design: LNCaP cells labeled with light-, medium-, or heavy-amino acids were treated with Enzalutamide (10 µM) or R1881 (1 nM) and proceeded for the gene-expression microarray analysis

first: Fan

last: Zhang

first: Robert

last: Bell


title: Regulation of gene expression by AR agonism and AR antagonism in prostate cancer cells

summary: Systematic investigation of gene expression by Dihydrotestosterone and Enzalutamide in LNCaP cells

overall_design: LNCaP cells were treated with Enzalutamide (10 µM) or Dihydrotestosterone (1 nM) and proceeded for the gene-expression microarray analysis

first: Chidi

last: Molokwu


title: Exploring and Validating the Marmoset as a Primate Model for Chromosomal Instability in Early Development

city: Seattle

first: Min

last: Yang

address: 850 Republican St S280

department: Ob/Gyn

institute: University of Washington

summary: The presence of aneuploidy (chromosomal abnormalities) in embryos is one of the main barriers to successful human reproduction, causing nearly 50% of early miscarriages. Despite its high incidence in human embryos, our understanding of the molecular mechanisms and cellular developmental fate of aneuploid cells is limited. In this study, we demonstrate that the New World primate marmoset (Callithrix jacchus) is an excellent model for investigating aneuploidy. We developed an efficient method to generate naïve marmoset embryonic stem cells (cj-ESCs) from cj-ESCs in the primed state, resulting in cells that resemble preimplantation epiblast-like cells and possess ground-state pluripotency, allowing them to contribute to all cell lineages, including trophoblasts, and form blastocyst-like structures. We observed that naïve marmoset ESCs are highly chromosomally unstable, making them prone to aneuploidy. We identified inherently less stringent mitotic checkpoints in ground-state embryonic stem cells as a potential cause of chromosomal instability, shedding light on the mechanisms underlying the prevalence of aneuploidy in primates during early embryonic development. Our findings establish that naïve marmoset ESCs faithfully replicate the cellular phenotypes of early embryonic cells, offering a powerful tool for studying the fate of aneuploid cells post-implantation in vivo.

overall_design: Bulk RNA-seq data of primed cj-ESCs, euploid Naive cj-ESCs converted and cultured under two different conditions (PLAXA cj-ESCs, PLAXAW cj-ESCs), and 100% aneuploid PLAXAW cj-ESCs. All samples were run with two biological replicates.

first: Andrew

last: Cearlock

first: Hubert

last: Mysliwiec

first: Margarita

last: Agarsheva

first: Joanna

last: Krzyspiak

first: Mohammad

middle: Z

last: Ozair

first: Ali

last: Brivanlou


title: Tumor-Derived Exosomal CCT6A Serves as a Matchmaker Introducing Chemokines to Tumor-Associated Macrophages in Pancreatic Ductal Adenocarcinoma [mouse RNA-seq]

city: Wuhan

first: Minghe

state: Hubei

address: Donghu Road

institute: WuHan University

summary: M2-polarized tumor-associated macrophages (TAMs) are a key factor contributing to the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). While various factors within the tumor microenvironment drive their formation, the role of PDAC-derived exosomes in this process remains unclear. We aim to clarify the regulatory impacts of tumor-derived exosomes to TAMs. Through multi-Omics analysis, we identified CCT6A as a novel tumor-derived exosomal protein, bridging TAMs M2 polarization and PDAC prognosis. Co-culture with exosomes derived from CCT6Ahigh PDAC leads to greater M2 phenotype of TAMs via PI3K-AKT signaling. According to proteomics data, chemokines’ abundance reduces over tenfold once exosomal CCT6A absence, including CXCL1, CXCL3, CXCL20 and CCL5, whose interaction with CCT6A in PDAC cells was confirmed by interactomics data. Morever, we found CCT6A clearance abrogated the antagonism effects of CD47 antibody immunotherapy. The subunit of the T-complex protein Ring Complex (TRiC) CCT6A serves as a matchmaker, during exosomes-mediated chemokines transfer from PDAC to TAMs.

overall_design: Subcutaneous mouse models of pancreatic cancer were established using KPC cells. The mice were then treated with either KPC-derived exosomes or PBS, and tumor tissues were subsequently harvested for RNA sequencing and transcriptome analysis.

first: Tianyin

last: Ma

first: Yufeng

last: Yuan


title: Gene expression changes induced by eltanexor in the FKH-1 cell line and PDX model

city: Halle

first: Razif

last: Gabdoulline

state: Sachsen-Anhalt

address: Ernst-Grube-Straße 40

department: Innere Medizin IV Haematologie und Onkologie

country: Germany

institute: Universitätsklinikum Halle

summary: We aimed to investigate the role of XPO1 in this rare leukemia subtype. RNA-seq was performed in DEK::NUP214 expressing cell line in control and eltanexor-treated samples, an inhibitor of XPO1, to elucidate the genes and pathways involved in DEK::NUP214 AML

overall_design: To investigate the role of XPO1 in DEK::NUP214 leukemia, cell line and PDX model expressing the fusion gene were treated with the XPO1 inhibitor eltanexor. Gene expression profile was investigated after treatment. .The human FKH-1 cell line was cultured in vitro in RPMI supplemented with 20% FCS. Cells were treated with 400nM eltanexor or vehicle (DMSO) for 24h. Total RNA was isolated using the Rneasy kit from Qiagen, followed by DNAse treatment before sending for sequencing. Human AML cells isolated from bone marrow of DEK::NUP214 mice (PDX1) and sorted for expression of hCD45+ cells after 11 days of treatment with vehicle or eltanexor 12.5 mg/kg

first: Fiorella

last: Charles Cano

first: Michael

last: Heuser


title: XPO1-dependency of DEK::NUP214 leukemia sensitizes against eltanexor

summary: We aimed to investigate the role of XPO1 in this rare leukemia subtype. ChIP-sequencing was performed for XPO1 and NUP214 (as surrogate for DEK::NUP214 protein), and found co-occupancy of both proteins in putative DEK::NUP214 target genes.

overall_design: Chromatin immunoprecipitation in FKH-1 cells. 24h after treatment with DMSO or eltanexor 400 nM, using antibodies against XPO1 and NUP214


title: Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution II

city: Edinburgh

first: Stuart

last: Forbes

address: 5 Little France Drive

department: Centre for Regenerative Medicine

country: United Kingdom

institute: The University of Edinburgh

summary: Alcohol-associated hepatitis (AH) is an acute form of alcohol-related liver disease (ArLD) with high mortality rate. AH is histologically characterised by cellular processes including steatosis, inflammation and cell death. Apoptosis is the most studied form of cell death in AH; however, the role of cellular senescence, another response to cellular injury, in AH is unknown. Here we aim to explore the mechanisms of ArLD pathophysiology and define the role of senescence in AH.

overall_design: Transjugular liver biopsies were extracted from AH patients participating in the ISAIAH clinical trial (clinicaltrials.gov identifier NCT03775109) and flash frozen. Biopsies were taken for RNA sequencing at baseline (d0) and 28-days post treatment with either placebo or canakinumab (d28). N=65 samples sequenced.

first: Daniel

last: Rodrigo-Torres

first: Alastair

last: Kilpatrick

first: Sofia

last: Ferreira-Gonzalez

first: Stephen

middle: R

last: Atkinson

first: Nikhil

last: Vergis

first: Mark

last: Thursz

first: Laura

last: Martinez-Gili

middle: J


title: Identifying transcriptomic pathways mediating radiotherapy response in malignant peripheral nerve sheath tumors

city: San Francisco

first: Iowis

last: Zhu

address: 1450 3rd Street, HD449

institute: University of California, San Francisco

summary: We identified transcriptomic changes between pNF and MPNST cell lines post treatment with radiotherapy that underlie differences in radiotherapy response.

overall_design:
We irradiated the pNF cell line NF9511.b and the MPNST cell line ST88-14 with 5 daily fractions of 2 Gy and collected cells at day 5 and day 14 post-RT for bulk RNA-sequencing. Data for pNF controls were seperately submitted under GSM6566477 and GSM6566479.

***************************************************************
The table below lists GEO accessions reused/reanalyzed for this study.
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first: Harish

last: Vasudevan


title: Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution I

overall_design: VL-17A cells (a modified human hepatocellular HepG2 cell line which overexpress CYP2E1 and ADH1) were treated with 100mM ethanol for 48 hours and compared to untreated VL-17A cells using RNA-seq. Media was replaced every 24 hours with fresh media and ethanol to minimize effects of evaporation. 4x samples per condition.

middle: M


title: Transcriptomic changes in HT29 cells and a patient-derived CRC 3D model after CRISPRi-based KAT2A knockdown

city: Dresden

first: Alexander

middle: Arthur

last: Wurm

address: Fetscherstrasse 74

institute: NCT Dresden

summary: We were interested in transcriptional changes after depletion of histone acetyltransferase KAT2A in human colorectal cancer. Therefore, we utilized HT29 cells and a patient-derived CRC 3D spheroid line (CRC3) as model, and analyzed global alterations of gene expression.

overall_design: RNA-Sequencing from HT29/CRC3 cells stably expressing dCas9-KRAB-GFP after transduction with either a sgRNA against a non-targeting control (NTC) or human KAT2A. Experiment was performed in biologically independent triplates.

middle: A


title: Transcriptomic changes in CRC1 and CRC2 patient-derived CRC 3D models after CRISPRi-based KAT2A knockdown

summary: We were interested in transcriptional changes after depletion of histone acetyltransferase KAT2A in human colorectal cancer. Therefore, we utilized patient-derived CRC 3D spheroids CRC1 and CRC2 as models, and analyzed global alterations of gene expression.

overall_design: RNA-Sequencing from CRC1/CRC2 cells stably expressing dCas9-KRAB-GFP after transduction with either a sgRNA against a non-targeting control (NTC) or human KAT2A. Experiment was performed in biologically independent triplates.

first: Vida

last: Kufrin


title: Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccine

city: Madrid

first: Álvaro

middle: Fernando

last: García-Jiménez

state: Madrid

address: Darwin st, 3

department: Immunology and Oncology

institute: CNB-CSIC

summary: In this work, we performed in-depth analyses of the immune populations proliferating 7 days after encounter with MTBVAC. We found that CD4+ and gd T cells were the main populations expanded.

overall_design: PBMCs of 3 healthy donors were stimulated with MTBVAC for 7 days. Cells were used for scRNA-seq analysis (10x Immune Profiling protocol).

middle: F

first: Mar

last: Valés-Gómez

first: Gloria

last: Esteso

first: Maria

last: Felgueres


title: Role of Retinol Saturase (RetSat) in the thyroid.

city: Berlin

first: Michael

last: Schupp

address: Hessische Str. 3-4

department: Institute of Pharmacology

institute: Charite Universitätsmedizin Berlin

summary: This study investigates the transcriptional consequences of genetic RetSat deletion in thyrocytes.

overall_design: Male C57BL/6J mice with floxed RetSat alleles with (Cre+) or without (Cre-) TPO (thyroid peroxide)-Cre were analyzed at an age of  22 weeks. Total RNA from thyroid was isolated and RNA was DNAse digested and profiled by RNAseq.

last: Yang

first: Sascha

last: Wulff


title: Alcohol-associated hepatitis induces hepatocyte senescence which is reduced following disease resolution

first: Stuart

last: Forbes

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

overall_design: Refer to individual Series


title: MicroRNA expression levels in plasma exosomes from liver cancer patients before and after surgery [miRNA-Seq]

city: Hefei

first: Qianqian

last: Tao

state: Anhui

address: Meishan Road, Shushan District, Hefei City, Anhui Province

institute: The First Affiliated Hospital of Anhui University of Chinese Medicine

summary: Exosomes play a crucial role in the occurrence and development of tumors. To investigate the levels of different exosome expressions in the plasma of liver cancer patients before and after liver tumor resection, we conducted high-throughput sequencing of miRNA in preoperative and postoperative blood exosomes from liver cancer patients.

overall_design: Blood samples were collected from liver cancer patients before and after surgery. Exosomes were isolated using ultracentrifugation, and RNA was extracted using an RNA extraction kit to extract microRNA from the exosomes. Subsequently, high-throughput sequencing was performed on the isolated microRNA.


title: GPI transamidase complex is required for primordial germ cell migration and development in zebrafish

city: Beijing

first: Xiaotong

last: Wu

address: Haidian

institute: Tsinghua University

summary: Proteins without transmembrane domains could be anchored to the cell surface for regulating various biological processes when covalently linked to glycosylphosphatidylinositol (GPI) molecules by the GPI transamidase (GPIT) complex. However, it remains poorly understood whether and how the GPIT complex affects primordial germ cell (PGC) development. In this study, we report the important roles of GPI transamidase in PGC migration and development in zebrafish embryos. Mutation of pigu or pigk, both encoding essential GPIT complex subunits, resulted in defective PGC migration with ectopically located PGCs and reduction of PGC counts. Notably, a detailed analysis of filopodia in PGCs reveals the attenuated polarity of filopodia distribution along the migration direction in mutant embryos. PGC transplantation and PGC-specific rescue experiments demonstrate that both PGC and somatic cell-expressed Pigu are required for PGC migration. Furthermore, expression levels of PGC-specific genes are decreased in pigu mutant PGCs with the derepression of somatic cell genes. Hence, we propose that the GPIT complex plays a critical role during PGC migration and development.

overall_design: To reveal molecular mechanisms underlying GPI transamidase-mediated PGC migration regulation, we performed RNA-seq of PGCs in wild type and pigu-/- embryos at the shield and bud stages. We manually picked GFP-positive PGCs after cell dissociation of embryos at the shield and bud stages. Then, after genotyping of rest somatic cells, PGCs with the same genotypes were pooled together and lysed for Smart-seq of two biological replicates.

first: Weiying

last: Zhang

first: Jing

last: Chen

first: Likun

last: Yao

first: Bingjie

first: Lin

first: Boqi

last: Liu

first: Weimin

last: Shen

first: Anming

last: Meng


title: microRNA sequencing of plasma exosomes from normal individuals, patients with type 2 diabetes.

summary: To investigate the differences in microRNA expression in plasma exosomes among normal individuals, patients with type 2 diabetes, we employed Agilent microarray expression profiling as a discovery platform to detect changes in microRNA levels in different target populations.

overall_design: Blood from different individuals was centrifuged to obtain plasma, from which exosomes were then isolated using ultracentrifugation. MicroRNA from the exosomes was extracted using a kit and detected using probes.


title: Fingerprint of circulating microRNAs identify acute ischemic stroke patients

city: Warsaw

first: Zofia

last: Wicik

state: mazovia

address: Pawinskiego 5

department: Department of Human Epigenetics

country: Poland

institute: Mossakowski Medical Research Center

summary:
Aim of the present study is to identify all circulating miRNAs that are modulated in patients with stroke, to select specific miRNAs to be used as disease biomarkers to improve both diagnosis and prognosis.
Background. Stroke is the second-most common cause of death worldwide. The major factor limiting prognosis in patients affected by acute stroke is the very limited therapeutic window, so that most patients are not able receive the most successful treatments because of delays in diagnosis and to differentiate between ischemic and hemorrhagic etiology. Circulating levels of selected microRNAs (miRNAs) were found to be modulated both in animal experimental models and in patients with stroke, opening up new avenues for the identification of more effective and specific biomarkers to identify and risk-stratify stroke patients.  Study aim. Aim of the present study is to identify all circulating miRNAs that are modulated in patients with stroke, to select specific miRNAs to be used as disease biomarkers to improve both diagnosis and prognosis.  Methods. RNA was extracted from plasma samples using a commercial RNA extraction kit and quality of extracted material was assessed using a fluorometric electrophoretic assay (Agilent 4200 TapeStation, Santa Clara, CA, USA). MiRNA profiling was performed using the Affymetrix platform using GeneChip 4.0 (Thermo Fischer Scientific, Waltham, MA, USA). RT-PCR was performed using the Taqman protocol. MiRNA were chosen among those with the most relevant modulation between the groups.  Results. Among the circulating miRNAs that were most down-regulated in stroke patients, we identified miR-3135b (20-fold, p<0.001), associated with vascular calcifications and heart failure; miR-1275 (18-fold, p=0.028), involved in cardiovascular atherosclerotic diseases and a sponge for circMAN2B2 in cancer; miR-4467 (13-fold, p=0.003), modulated in neurodegenerative diseases; and miR-7170 (7-fold, p<0.001).  Among the circulating miRNAs that were most up-regulated in stroke patients, we identified miR-18a (35-fold, p=0.004), associated with stroke in the Framingham Cohort; the platelet-enriched miR-22-5p (24-fold, p=0.004), that is modulated in Huntington Disease; miR-199a (11-fold, p=0.012), a marker of brain microvascular injury and of stroke severity in rats, and miR-106b (10-fold, p=0.009), a regulator of neural stem-cell proliferation/differentiation whose level are modulated in patients with neurodegenerative diseases.  Conclusions. Our results identified several circulating miRNAs that are down- of up-regulated in stroke patients. Among those with the most relevant differential expression, several miRNAs were identified that are known to play a role in the pathophysiology of neurovascular diseases, paving the way to a new class of smart pathophysiology-based biomarkers in stroke.

overall_design: We evaluated mirNA expression levels in platelet-depleted plasma samples from treatment group of  patients with the diagnosis of the acute IS based on clinical features according to the World Health Organisation definition and supported by brain imaging (CT or MRI).  Patients with IS were on ASA therapy 24 hours after onset of acute IS. The control group consisted of 35 age- and gender-matched patients on acetylsalicylic acid  (ASA) therapy without history of stroke and/or transient ischemic attack (TIA) with established stable coronary artery disease (CAD) and concomitant cardiovascular risk factors.

first: Ceren

last: Eyileten

first: Aleksandra

last: Gasecka

middle: T

last: Di Martino

first: Joanna

last: Mucha

first: Iwona

last: Kurkowska-Jastrzebska

first: Anna

last: Czlonkowska

first: Marek

last: Postula


city: Indianapolis

first: Gabor

last: Varga

state: Indiana

address: Lilly Corporate Center

institute: Eli Lilly

summary: Tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor (GIPR/GLP-1R) agonist, has, in clinical trials, demonstrated greater reductions in glucose, body weight and triglyceride levels compared with selective GLP-1R agonists in people with type 2 diabetes (T2D). However, cellular mechanisms by which GIPR agonism may contribute to these improved efficacy outcomes have not been fully defined. Using human adipocyte and mouse models, we investigated how long-acting GIPR agonists regulate fasted and fed adipocyte functions in the presence and absence of insulin to model post-prandial and post-absorptive states. Transcriptional profiling of human adipocytes demonstrated differential gene, pathway, and upstream regulation by GIP indicative of modulation of both carbohydrate and lipid metabolism. In functional assays, GIPR agonism enhanced insulin signaling, augmented glucose uptake, and increased the conversion of glucose to glycerol in a cooperative manner with insulin. GIPR agonists increased lipolysis in the absence of insulin, an effect that was fully suppressed when co-administered with insulin. In diet-induced obese mice treated with a long-acting GIPR agonist, circulating triglyceride levels were reduced during oral lipid challenge and lipoprotein-derived fatty acid uptake into adipose tissue was increased. Our findings support a model for long-acting GIPR agonists to modulate both fasted and fed adipose tissue function differentially, by cooperating with insulin to augment glucose and lipid clearance in the fed state, while enhancing lipid release when insulin levels are reduced in the fasted state. This novel paradigm illustrates key mechanisms by which GIPR/GLP-1R agonists such as tirzepatide likely regulate adipocyte function to enhance weight loss as well as improve glucose and lipid metabolism in T2D.

overall_design:
Expression data from from human differentiated primary adipocytes treated with GIP alone and in combination with Insulin
36 Total samples were analyzed utilizing the quantile normalization method, followed by principal component analysis (PCA) and outlier analysis to check any potential pattern or outliers among the samples. One-way ANOVA using R software was applied to the normalized mRNA expression to test the comparisons between each treatment and vehicle. For each comparison, both the p values and the fold changes were reported, and the mRNAs with p value less than 0.05 and fold change no less than 1.5 were selected for further analysis.

first: Ajit

last: Regmi

first: Yanzhu

last: Lin

first: William

last: Roell


title: Comparison the transcriptional changes of HEK293T cells transfected with synthesized vcDNA

city: Shenzhen

first: SHAO

middle: MIN

last: YANG

state: guangdong

address: Nanshan

department: Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center

institute: Department of Pain Medicine and Shenzhen Municipal Key Laboratory for Pain Medicine

summary:
Extrachromosomal circular DNA (eccDNA) is generated from chromosomal templates to play multiple biological roles in different types of cells. However, it is unknown whether viral infection could cause cells to generate viral non-genomic circular DNA (vcDNA). Here, we demonstrated for the first time that Varicella zoster virus (VZV)-infected cells and tissues generate an abundance of vcDNA.
We developed a Cre/loxP-mediated in vitro vcDNA/eccDNA synthesizing method. We transfected the synthesized vcDNA into HEK293T cells, RNA-seq analysis indicated that VZV vcDNA 76509|75569 effectively mitigated the innate immune response that was stimulated by linear VZV 75569-76509 DNA.

overall_design: HEK293T cells were transfected the synthesized vcDNA. RNA-seq was used to quantify the expression of genes

first: Shaomin

last: Yang


title: Dynamic Single Cell Transcriptomics Defines Kidney FGF23/KL Bioactivity and Novel Segment-Specific Inflammatory Targets

first: Kenneth

last: White

state: IN

address: 635 Barnhill Drive

institute: Indiana University School of Medicine

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: E-cigarettes induce dysregulation of autophagy leading to endothelial dysfunction in pulmonary arterial hypertension

city: Macau

first: Ning-Yi

last: Shao

address: University of Macau

department: Faculty of Health Sciences

institute: University of Macau

summary: To investigate whether differential susceptibility exists between healthy and PAH patients to e-cig exposure and the molecular mechanisms, human iPSC lines from two healthy volunteers and two FPAH patients were first differentiated into ECs. iPSC-ECs were then treated with and without e-cigarette extract for 24 hours.

overall_design: RNA-seq of iPSC-ECs with and without e-cigarette extract treatment over a period of 24 hours.

first: Won

last: Lee


title: Transcriptome analysis reveals LZ-8 promotes the differentiation of Th17 cells [RNASeq2]

city: Changchun

first: Wei

last: Huang

state: Jilin

address: Xinmin Street No. 1163

department: Modern biology

institute: nstitute of Frontier Medical Science, Jilin University

summary: LZ-8 is an immunomodulatory protein derived from the large edible fungus Ganoderma lucidum. LZ-8 has therapeutic effects on several disorders of the immune system. T lymphocytes are considered to be one of the target cells of LZ-8. In order to comprehensively and systematically study the immunomodulatory effect of LZ-8 on T lymphocytes at the transcriptome level, we used RNA-seq technology to sequence the transcriptome of mouse T lymphocytes treated with LZ-8 for 10 hours and 0 hour. Differential gene analysis showed that 1275 genes were up-regulated and 2273 genes were down regulated after LZ-8 treatment for 10h. The pathway enrichment analysis showed that differential genes were enriched in terms of "Th1 and Th2 cell differentiation", "Th17 cell differentiation" and "IL-17 signaling pathway". RT-qPCR experiment confirmed that LZ-8 could upregulate the transcription level of Il4, Il13, Il17f and Csf2 in T lymphocytes, and the inhibitor Bay 11-7082 which inhibited NF κ B signaling pathway can reverse the transcriptional upregulation of Il2, Il17a and Irf4 by LZ-8. In conclusion, transcriptome sequencing data combined with RT-qPCR confirmed the promoting effect of LZ-8 on Th17 differentiation.

overall_design: mRNA profiles of T lymphocytes treated by LZ-8 for 10h were generated by deep sequencing, in triplicate, using  Ion PITM Chip.

first: Fei

last: Sun

first: Chongyang

last: Liang


title: Transcriptome analysis reveals LZ-8 triggers antiviral innate immunity in mouse T lymphocytes [RNASeq1]

summary: Ganoderma lucidum is a traditional medicinal herb that has commonly been used for treating virus infections. Protein LZ-8 comes from Ganoderma lucidum and has immunomodulatory and antiviral activities. However, the potential molecular antiviral mechanism of LZ-8 is still unclear. In this study transcriptome analysis was used to gain a deeper insight into the antiviral effects of LZ-8 on T lymphocytes. Deseq analysis showed that 2724 genes were upregulated and 3314 genes were downregulated after LZ-8 treatment for 5 hours. GO enrichment analysis showed that the upregulated genes were significantly enriched in biological processes including defense response to virus, ribosome biosynthesis, RNA processing, etc. The downregulated genes were significantly enriched in biological processes including cell cycle, signal transduction, etc. Pathway enrichment analysis indicated that NF- κB signaling pathway was closely related to LZ-8. RT-qPCR confirmed that inhibition of the NF-κB signaling pathway reversed the elevated transcriptional level of antiviral genes including Ifit1, Isg15, Mx1, Ifit3, and Ifih1 in T lymphocytes triggered by LZ-8. In a word, our study demonstrated that LZ-8 triggered the antiviral innate immunity of T lymphocytes through the NF-κB signaling pathway.

overall_design: mRNA profiles of T lymphocytes treated by LZ-8 for 5h and 0h were generated by deep sequencing, in triplicate, using  Ion PITM Chip.


title: The CoREST complex inhibitor, corin, leads to decreased tumor growth, increased cellular differentiation and extended lifespan in atypical teratoid rhabdoid tumor xenograft models [RNA-seq]

status: Public on Mar 27 2025

city: Boston

first: Robert

last: Fisher

state: MA

address: 609 Albany St

department: Dermatology

institute: Boston University

summary: Background. Atypical teratoid rhabdoid tumor (ATRT) is the most common malignant brain tumor in infants, and more than 60% of children with ATRT die from their tumor. ATRT is associated with mutational inactivation/deletion of SMARCB1, a member of the SWI/SNF chromatin remodeling complex, suggesting that epigenetic events play a critical role in tumor development and progression. Moreover, disruption of SWI/SNF allows unopposed activity of epigenetic repressors, which contribute to tumorigenicity. We therefore explored the role of the CoREST repressor complex in ATRT. Methods. We evaluated the effects of the bifunctional LSD1/HDAC1/2 small molecule CoREST inhibitor, corin, on ATRT tumor cell growth, apoptosis, differentiation, gene expression and chromatin accessibility. Results. We found that corin inhibited the growth of ATRT cells regardless of their epigenetic subgroup, and was associated with increased tumor cell apoptosis and differentiation. ATAC-seq showed increases in chromatin accessibility in corin-treated ATRT cells, with changes seen at genes associated with neuronal differentiation and synaptic function. RNA-seq confirmed increased expression of neuronal differentiation genes and decreased DNA replication/cell cycle-associated genes in ATRT cells treated with corin. Corin suppressed orthotopic ATRT tumor growth, leading to significant extension of lifespan. In addition, increased histone acetylation (H3K9ac, H3K27ac) and methylation (H3K4Me1) was seen in corin-treated ATRT orthotopic xenografts, consistent with on-target pharmacodynamics. Conclusion. The CoREST inhibitor, corin, suppresses tumor growth, induces differentiation, and promotes apoptosis in ATRT, leading to significantly increased survival of mice bearing ATRT orthotopic xenografts. Our results suggest a potential application of CoREST complex inhibitors in patients with ATRT.

overall_design: RNA was extracted from ATRT cells, BT37 and CHLA06 treated with corin or DMSO (RNAeasy Mini kit, Cat# 73404, Qiagen, Hilden, Germany) using the protocol described in Supplementary Methods Section. RNA samples passing the initial QC parameters (A260/280 and A230/280 ≥ 2.0, RIN score > 7), were selected for RNA sequencing using the Illumina NovoSeq 6000 platform (Novogene Corporation Inc, CA, USA).

first: Anupa

last: Geethadevi

first: Nikhil

last: Vaidya

first: Tyler

last: Findlay

first: Yiming

last: Deng

first: Khoa

last: Pham

first: Vikas

last: Kumar

first: Samuel

last: Beck

first: Lucas

last: Calixto-Hope

first: Charles

last: Eberhart

first: Jinchong

last: Xu

first: Philip

last: Cole

first: Jeffrey

last: Rubens

first: Marianne

last: Collard

first: Eric

last: Raabe

first: Rhoda

last: Alani


title: Effects of noc2l-deficiency in gene expression at 24, 36 and 48 hpf zebrafish embyos.

city: Sagamihara City

first: Kenta

last: Watai

address: 5-10-1 Fuchinobe

institute: Aoyamagakuin University

summary: To solve the cause of noc2l mutant abnormal formation, we performed time-course individual RNA-Seq.

overall_design: noc2l+/+ and noc2l-/- zebrafish embyo were sacrificed at 3 time point between 24 and 48 hpf with 6-9 biological replicates.

first: Kenichiro

last: Sadamitsu

first: Makoto

last: Kashima

first: Seiji

last: Wada

first: Hiromi

last: Hirata


title: Nat10-mediated N4-acetylcytidine modification enhances Nfact1 translation to exacerbate osteoclastogenesis in postmenopausal osteoporosis [Ribo-seq]

city: Guangzhou

first: Yuke

last: Meng

state: Guangdong

address: 1023-1063, South Shatai Road, Baiyun dictrict

institute: Southern Medical University

summary: Increased differentiation or activity of osteoclasts is the key pathogenic factor of postmenopausal osteoporosis (PMOP). N4‐acetylcytidine (ac4C) modification, catalyzed by Nat10, is a novel post-transcriptional mRNA modification related to many diseases. However, its impact on regulating osteoclast activation in PMOP remains uncertain. Here, we initially observed that Nat10-mediated ac4C positively correlates with osteoclast differentiation of monocytes and low bone mass in PMOP. The specific knockout of Nat10 in monocytes and remodelin, a Nat10 inhibitor, alleviates ovariectomized (OVX)-induced bone loss by downregulating osteoclast differentiation. Mechanistically, epitranscriptomic analyses reveal that the nuclear factor of activated T cells cytoplasmic 1 (Nfatc1) is the key downstream target of ac4C modification during osteoclast differentiation. Subsequently, translatomic results demonstrate that Nat10-mediated ac4C enhances the translation efficiency of Nfatc1, thereby inducing Nfatc1 expression and consequent osteoclast maturation. Cumulatively, these findings reveal the promotive role of Nat10 in osteoclast differentiation and PMOP from a novel field of RNA modifications and suggest that Nat10 can be a target of epigenetic therapy for preventing bone loss in PMOP.

overall_design: To investigate the role of NAT10-mediated ac4C modification in osteoclastogenesis, we utilized ribo-seq to detect differences in osteoclast differentiation between WT and Nat10 conditional knockout mice BMDMs.

first: Zhongmin

last: Zhang


title: The effect of creatine supplementation on AOM/DSS induced colitis associated colorectal cancer in C57BL/6 mice

first: Nianchen

last: Liu

address: No. 95 Yong'an Road, Xicheng District, Beijing

institute: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical Universit

summary: Colitis-associated colorectal cancer (CAC) is a serious complication of inflammatory bowel disease (IBD) with complex etiology involving chronic inflammation, immune dysregulation, and gut microbiota dysbiosis. Creatine, a natural nitrogenous com-pound, possesses anti-inflammatory and immunomodulatory properties, but its role in CAC remains unclear.We established an AOM/DSS-induced mouse model of CAC and supplemented mice with creatine. We assessed the effects of creatine on colitis severity, tumor burden, and histopathology. Additionally, we investigated the impact of crea-tine on gut barrier function, macrophage polarization, and gut microbiota composi-tion.Creatine supplementation significantly alleviated DSS-induced colitis, reduced tumor burden, and delayed CAC progression in mice. Mechanistically, creatine im-proved gut barrier function by protecting tight junction proteins from degradation in-duced by the modeling stimulus，influenced macrophage polarization, and main-tained gut microbiota diversity, promoting the abundance of beneficial bacteria while reducing harmful ones.Our findings suggest that creatine supplementation may rep-resent a promising supportive therapy for IBD and CAC by modulating the gut micro-biota and immune microenvironment. Further investigation is warranted to explore the clinical potential of creatine in the management of CAC.

overall_design: The CAC model was established by intraperitoneal injection of AOM at a dose of 10 mg/kg body weight while the control group received an equivalent volume of normal saline via intraperitoneal injection. One week later, the animals were given drinking water containing 2.5% DSS for 7 days, followed by nor-mal drinking water for 14 days. This cycle was repeated three times.


title: Transcriptome analysis reveals the effect of LZ-8 on CD4+ T cells and CD8+  T cells [RNASeq3]

first: Wei

last: Huang

summary: LZ-8 is a dimeric protein isolated from Ganoderma lucidum. It has immunomodulatory activity on T cells. In order to fully analyze the immunomodulatory effect of LZ-8 on CD4 + T cells and CD8 + T cells, we first sequenced the transcriptome of mouse T lymphocytes treated with LZ-8 for 15 hours, then compared the differential genes regulated by LZ-8 with those activated in CD4 + T cells and CD8 + T cells in GSE126116 data, and finally obtained the core biological process and signal pathway induced by LZ-8 to regulating the activation state of CD4 + T cells and CD8 + T cells.

overall_design: mRNA profiles of T lymphocytes treated by LZ-8 for 15h were generated by deep sequencing, in triplicate, using  Ion PITM Chip.

first: Fei

last: Sun

first: Chongyang

last: Liang