title: Aberrant lncRNA and mRNA expression in patients with anti-N-methyl-D-aspartate receptor encephalitis

status: Public on Aug 09 2025

city: Jinan

first: Xiaoyu

last: Ma

address: 247 Beiyuan Street

institute: The Second Hospital of Shandong University

summary: Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a nervous autoimmune disorder discovered in the recent more than fifteen years. To understand potential involvement of epigenetic mechanisms in pathogenesis of anti-NMDAR encephalitis, we initiated a study to compare the expression profiles of long non-coding RNAs (lncRNAs) and messenger RNA (mRNAs) in patients of anti-NMDAR encephalitis and healthy controls. Methods: 11 patients who were diagnosed with anti-NMDAR encephalitis were enrolled in our observational studies. Total RNA was extracted from patients’ plasma and the expression levels of lncRNAs and mRNAswere determined. Differential expression analysis via RNA sequencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as a co-expression network of lncRNA-mRNA were performed in 5 patients and 5 healthy controls to evaluate potential the changes in expression patterns. The expression levels of certain lncRNAs and mRNAs were further validated in 11patients and 11 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR). Results: It was found that a total of 83 lncRNAs and 2345 mRNAs were differentially expressed in five patients with anti-NMDAR encephalitis compared with five healthy controls.  Of those lncRNAs, 63 were upregulated and 20 downregulated, while 1509 mRNAs were upregulated and 836 downregulated. GO and KEGG pathway analyses showed that a wide range of biological functions were perturbed during acute anti-NMDAR encephalitis. Differentially expressed genes were found to be involved in autoimmune, B cell signaling, neuroinflammation, or synaptic plasticity. qRT-PCR was conducted in 11 patients and 11healthy controls to further confirm the levels of six lncRNAs and four mRNAs, and the results were found to be consistent with those by RNA sequencing. The co-expression networks of lncRNA-mRNA were performed in some meaningful KEGG analyses, including chemokine signaling pathway, Long-term potentiation, B cell receptor signaling pathway and MAPK signaling pathway. Conclusions: Taken together, these findings suggest the involvement of a number of molecular pathways in anti-NMDAR encephalitis, some of which could serve as potential biomarkers to assist in diagnosis, treatment and prognosis.

overall_design: RNA-seq of human plasma in health and disease group


title: Synthetic mRNA Vaccines and Transcriptomic Dysregulation: Evidence from New-Onset Adverse Events and Cancers Post-Vaccination

status: Public on Aug 08 2025

city: Rockwall

first: Wei

last: Zhang

state: TX

address: 2500 Summer Lee Dr

country: USA

institute: Neo7 Bioscience

type: Expression profiling by high throughput sequencing

summary: Background/Objectives: Synthetic mRNA vaccines have raised concerns regarding prolonged spike protein expression, immune activation, and potential off-target effects. This study investigates transcriptomic alterations in individuals with new-onset adverse events or cancer following mRNA COVID-19 vaccination. Methods: Bulk RNA sequencing was performed on peripheral blood from two patient groups: individuals with new-onset nonmalignant adverse events and individuals newly diagnosed with cancer post-vaccination. A control group of healthy individuals was used for comparison. Differential gene expression was analyzed using DESeq2, and Gene Set Enrichment Analysis (GSEA) was conducted using the MSigDB database and custom gene sets. Results: Both vaccine patient groups displayed widespread transcriptional dysregulation. In the nonmalignant adverse event group, hallmark enrichments included mitochondrial dysfunction, proteasome-mediated stress, transcriptomic instability, and systemic inflammation. The cancer group exhibited additional hallmarks of genomic instability, and epigenetic reprogramming. Nonsense-mediated decay (NMD), ribosomal stress, and MYC activation were prominent in both groups, while immune signaling via TLRs and type I interferons was particularly elevated in cancer patients.

overall_design: We enrolled adult participants (ages 18–70) who developed either new-onset symptoms following administration of mRNA-based COVID-19 vaccines (BNT162b2 [Pfizer] or mRNA-1273 [Moderna]). Total RNA was extracted using the Quick-DNA/RNA Viral Kit (Zymo Research), following the manufacturer’s protocol for whole blood RNA extraction. RNA libraries were prepared using the Illumina TruSeq Stranded Total RNA Kit, incorporating ribosomal RNA depletion and strand-specific cDNA synthesis. RNA-seg profiling of whole blood cells were conducted.

first: Natalia

last: von Ranke

first: Philipp

last: Anokin

first: Nicolas

last: Hulscher

first: Kevin

middle: J

last: McKernan

first: Peter

middle: A

last: McCullough

first: John

last: Catanzaro


title: NUDT21 Shapes Macrophage Transcriptomes through alternative polyadenylation in ARDS

status: Public on Aug 11 2025

city: Houston,

first: Hari Krishna

last: Yalamanchili

address: 1250 Moursund St #1125,

institute: Baylor College of Medicine

summary: Defining the molecular mechanisms governing macrophage-driven inflammation is essential for developing targeted interventions for ARDS. One such mechanism could be alternative polyadenylation (APA), a post-transcriptional regulatory process that plays a critical role in gene regulation. Most mammalian genes, including key proinflammatory mediators, contain multiple polyadenylation sites (PAS). APA regulates the addition of poly(A) tails at alternative PAS, generating transcripts with different 3' UTR lengths. One key regulator of APA is Nudix Hydrolase 21 (NUDT21), a critical cleavage factor Im (CFIm) component. However, whether NUDT21-mediated APA plays a role in inflammation during ARDS is not known. Thus, the goal of this study is to identify the APA genes regulated by NUDT21 in macrophages.

overall_design: Comparative analysis of alternative polyadenylation using polyA-click seq (PAC-seq) on Bone marrow derived macrophages collected from mice with myeloid NUDT21 deletion (NUDT21 f/f LysmCre) mice or control LysmCre mice treated with/without 1 ug/ml LPS for 3 hrs.

first: Hui

last: Liu

first: Yu

last: Wang

first: Scott

last: Column

first: Maria

last: Gacha-Garay

first: Sarah

last: Shin

first: Rahat

last: Hussain

first: Jayeshkumar

last: Patel

first: Manish

first: Kai-Lieh

last: Huang

first: Eric

last: Wagner

last: Yamalanchili

first: Xiaoyi

last: Yuan

first: Harry

last: Karmouty-Quintana

first: Tingting

last: Mills


title: RP105 exerts hepatoprotective effects in sepsis by modulating the SOCS2/JAK2/STAT3 signaling pathway

city: wuhan

first: Hong

last: Duo

address: No. 169 East Lake Road, Wuchang District

country: China

institute: Zhongnan Hospital of Wuhan University

summary: During the occurrence of sepsis, the liver plays a crucial role in immune defense. However, the excessive immune response within the liver can also make it the main target organ for sepsis-related injuries. In this paper, our aim is to explore the protective role of RP105 in liver injury caused by sepsis and clarify its underlying molecular mechanisms. We established a cecal ligation and puncture (CLP) model using RP105 knockout mice. We observed the protective effect of RP105 on liver damage caused by sepsis. We also conducted RNA sequencing (RNA-Seq) analysis on the CLP group and the RP105 knockout CLP group. Furthermore, through in vitro and in vivo experiments, we found that RP105 alleviated liver injury caused by sepsis through the classical regulation of SOCS2 via the JAK2/STAT3 signaling pathway.

overall_design: To investigate the role of RP105 in sepsis-induced liver injury, we employed both in vivo and in vitro approaches. An in vivo mouse model of sepsis was established using the cecal ligation and puncture (CLP) technique. RP105 knockout (RP105⁻/⁻) mice and wild-type (WT) littermates were subjected to CLP surgery, and liver tissues were harvested 24 hours post-surgery for histological and molecular analyses. To elucidate the molecular mechanisms underlying the protective effects of RP105, RNA sequencing (RNA-Seq) was performed on liver samples from WT-CLP and RP105⁻/⁻-CLP groups (n=3 per group).

first: Qin

last: Deng

first: Ruoping

last: Chen

first: Zhihui

last: Fu

first: Huaqin

last: Pan

first: JianSheng

last: Xiao

first: Qifa

last: Ye

first: Qi


title: Analysis of the genes and mechanisms responsible for the cytotoxicity of the Legionella Ofk308 strain in the Tetrahymena host

city: Yamaguchi City

first: Istiana

middle: Nur

last: Vidayanti

state: Yamaguchi Prefecture

address: 1677-1 Yoshida

country: Japan

institute: Yamaguchi University

summary: Legionella pneumophila, an intracellular pathogen responsible for the pneumonia-like Legionnaires’ disease in humans, inhabits aquatic environments, including man-made water systems such as water fountains, foot spas, and tap water, and exists as part of biofilms or as a protozoan parasite. As a bacterivore, Tetrahymena thermophila provides a favorable environment for Legionella to establish a replicative niche (Legionella-containing vacuole; LCV) under environmental stress. Conversely, the L. pneumophila Ofk308 strain, isolated from an Ashiyu foot spa, has been found to be cytotoxic to the ciliate T. thermophila CU427. This study aimed to identify the cytotoxicity-related genes of Legionella and elucidate their mechanisms specific to the Tetrahymena host. A comparative analysis using RNA-sequencing was conducted with two Legionella strains, Philadelphia-1 and Ofk308, to select several candidate genes. Deletion mutants of Ofk308 were constructed by homologous recombination. Eight out of ten candidate gene deletion mutants were successfully generated. These mutants were analyzed for cytotoxicity against T. thermophila and intracellular bacterial growth at 2 h, 24 h, and 48 h postinfection. Among the deletion mutants, ∆vicinal oxygen chelate (VOC) and msrB/A exhibited reduced cytotoxicity. Furthermore, LCVs formed in T. thermophila infected with ∆VOC and msrB/A were smaller in size compared to those formed by the parental strain Ofk308, suggesting a role in both cytotoxicity and intracellular growth. Multiple factors contribute to the cytotoxicity exhibited by the Ofk308 strain in protozoan host cells, and gene expression analysis may reveal additional relevant factors.

sample_organism: Legionella pneumophila subsp. pneumophila str. Philadelphia 1

overall_design: Legionella pneumophila Phil-1 (control) and Ofk308 strains were cultured at 37°C to the exponential phase in AYE, then diluted and cultured again at 30°C for 24 h. The total RNA were extracted in triplicates for each strain.

first: Istiana Nur

first: Kenta

last: Watanabe

first: Ema

last: Fujino

first: Takashi

last: Shimizu

first: Masahisa

last: Watarai


title: Conservation and alteration of mammalian striatal interneurons

city: San Francisco

first: Alex

last: Pollen

state: CA

institute: University of California San Francisco

summary: Mammalian brains vary in size, structure, and function, but the extent to which evolutionarily novel cell types contribute to this variation remains unresolved. Recent studies suggest there is a primate-specific population of striatal inhibitory interneurons, the TAC3 interneurons. However, broader taxonomic and developmental characterization is required to address novelty in cell type evolution. Here, we examine gene expression in inhibitory neurons across 11 mammalian species, spanning 160 million years divergence from primates. We find that the initial class of newborn TAC3 interneurons specified during development represents an ancestral, MGE-derived striatal population also present in pig and ferret cortex. This discovery prompted a reexamination of the Glire clade, including mice which are thought to lack the TAC3 type. Targeted enrichment of MGE precursors in mice reveals conservation of the TAC3 initial class, camouflaged by reduced expression of Tac2 (the mouse ortholog of TAC3) and a gain of Th expression. Extending our analysis to the adult striatum further supports the homology of primate TAC3 and mouse Th striatal interneurons, while uncovering a rare Tac2 subpopulation in mouse ventromedial striatum. This study suggests that initial classes of telencephalic inhibitory neurons are largely conserved and that during evolution, neuronal types in the mammalian brain change through redistribution and fate refinement, rather than by derivation of novel precursors early in development.

sample_organism:
Mustela putorius furo
Sus scrofa
Oryctolagus cuniculus
Mus musculus
Rattus norvegicus
Monodelphis domestica
Petaurus breviceps

overall_design: 10x Genomics Chromium next GEM single cell 3' RNA-sequencing of developing ferret, pig, rat, rabbit, mouse, opossum and sugar glider developing brain.

first: Emily

middle: K

last: Corrigan


title: PML is crucial for neural stem cell differentiation, stress tolerance and mitochondrial integrity

city: Heraklion-Voutes

first: Syrago

last: Spanou

address: N.Plastira 100

country: Greece

institute: IMBB-FORTH

summary: The tumor suppressor promyelocytic leukemia protein (PML) has important roles in brain development; however, the molecular and cellular pathways regulated by PML in neuronal cells remain largely unknown. To address this issue, we analyzed gene expression changes caused by loss of PML in neural stem cells. Our findings revealed that PML-deficient cells exhibited increased mTOR (mammalian target of rapamycin) pathway activation and protein translation, as well as impaired autophagy and proteasome activity, resulting in increased formation of aggregates and stress-induced death. Loss of PML disrupted mitochondrial integrity, leading to impaired respiration, membrane potential, morphology, and production of increased reactive oxygen species. These mitochondrial defects were caused by diminished PGC-1α expression and PPARγ (peroxisome proliferator-activated receptor gamma) signaling and could be reversed using a PPAR agonist. Together, our results indicate that PML is a critical regulator of neuronal survival and protection from stress. We propose that enhancing PML expression may offer therapeutic benefits in neurological disorders.

overall_design: RNAseq profiling in mouse embryonic neural stem cells (E13.5) WT and Pml-/-.

first: Takis

last: Makatounakis

first: Elena

last: Deligianni

first: Sofia

last: Papanikolaou

first: Martina

last: Samiotaki

first: Fabien

last: Moretto

first: Christoforos

last: Nikolaou

first: Joseph

last: Papamatheakis

first: Androniki

last: Kretsovali


title: In vitro and in vivo models to predict ADAR RNA editing oligonucleotides potential in human liver tissue

status: Public on Aug 07 2025

city: Leiden

first: Monica

last: Aguila

address: Zernikedreef 9

country: Netherlands

institute: ProQR Therapeutics

summary: Liver-originated diseases remain a significant global health burden, with limited treatment options available. RNA therapeutics, particularly adenosine deaminase acting on RNA (ADAR)-mediated  editing using editing oligonucleotides (EONs) offer a novel approach to address these unmet medical needs. This study evaluates in vitro and in vivo liver models to predict the therapeutic potential of chemically modified EONs in human liver tissue, using ACTB as target. Multiple liver models, including primary human hepatocytes (PHH), cancer-derived cell lines, and iPSC-derived hepatocytes in both 2D and 3D formats, were characterized for ADAR expression, liver functionality, and RNA editing efficiency. The results show consistent ADAR expression across most models, with 3D models, particularly PHH spheroids and liver microtissues, closely mimicking human liver tissue in gene expression and editing capacity. In vivo, non-human primate liver biopsies showed high levels of ACTB editing, consistent with findings from PHH models. These findings highlight the critical role of preclinical models in EON selection, where multiple factors must be carefully considered. A multimodel assessment utilizing composite scoring to comprehensively assess the key parameters seems to be the approach of choice to maximize translatability across preclinical models and increase the likelihood of success in clinical applications

overall_design: RNA-seq profiling comparison between different hepatic cell lines cultured in vitro for 3 days and human liver tissue


title: Bronchial epithelial cells transcriptomics upon flagellin stimulation (Microarray)

status: Public on Aug 10 2025

city: Paris

first: Rachel

last: Legendre

address: 28, rue du docteur Roux

department: Research and Resource Center for Scientific Informatics

country: France

institute: Institut Pasteur

summary: Innate immune memory is a new concept describing ability of innate myeloid and lymphoid cells to gain memory characteristics after transient stimulation, resulting in an nonspecific modified response upon secondary challenge. In recent work, we demonstrated that bronchial epithelial cells, non immune cells, that are the first immune cells of the lower respiratory tract to encounter pathogens were capable of innate immune memory after pre-exposure to Pseudomonas aeruginosa flagellin. In the present study  we identified chromatin modifications induced by flagellin pre-exposure that sustain reprogramming of transcriptional patterns. We researched chromatin structure modifications responsible for the modulation of gene expression and thus of innate memory induced by the exposure of cells to flagellin.

overall_design: 15 samples, 5 conditions in triplicate

first: Jeanne

last: Bigot

first: Juliette

last: Hamroune

first: Sébastien

last: Jacques

first: Mathieu

last: Legars

first: Loïc

last: Guillot

first: Harriet

last: Corvol

first: Christophe

last: Hennequin

last: Guitard

first: Viviane

last: Balloy

first: Claudia

last: Chica


title: Hypersonic Levitation and Spinning: Paving the Way for Enhanced Single-Cell Analysis via Contactless Tissue Dissociation

city: Tianjin

first: Yang

last: Bai

address: Tianjin

institute: Tianjin University

summary: In the realm of single-cell analysis, effective tissue dissociation is a cornerstone yet often hampered by the drawbacks of traditional methods. Mechanical and enzymatic dissociation methods suffer from long processing times, reduced cell viability, and the loss of rare cell populations. Herein, we introduce a revolutionary tissue dissociation approach, Hypersonic Levitation and Spinning (HLS), which capitalizes on a uniquely designed triple-acoustic resonator probe. This probe enables the target tissue sample to levitate and execute a 'press-and-rotate' operation within a confined flow field, generating microscale 'liquid jets' that exert precise hydrodynamic forces in a non-contact manner. Through this mechanism, the shear forces on the tissue are enhanced, facilitating rapid and efficient dissociation while safeguarding cell integrity. We have further developed an automated tissue dissociation apparatus integrating dissociation, fluid replacement, filtration, and output functions. Our comprehensive experiments, including flow cytometry, primary cell culture, immunofluorescence, and single-cell RNA sequencing, unequivocally demonstrate that the HLS method not only markedly outperforms traditional techniques in tissue utilization and dissociation rate but also excels in maintaining high cell viability and preserving rare cell populations. This non-contact, gentle yet highly efficient dissociation method holds immense promise in diverse fields such as cell biology, single-cell sequencing, and precision medicine, extending new possibilities in tissue dissociation technology and its applications.

overall_design: Comparative analysis of enzymatic and acoustic streaming-based dissociation methods for renal carcinoma tissue.


title: The PAS domain of the Polarly-Localized Histidine Kinase FlrB in Vibrio cholerae Controls Class III Flagellar Transcription and Contributes to Intestinal Colonization

city: San Antonio

first: Venus

middle: Shawn

last: Stanton

state: Texas

address: One UTSA Circle

department: Molecular Microbiology and Immunology (MMI)

institute: University of Texas, San Antonio

summary: FlrB is a histidine kinase and along with FlrC it represents the two-component system that regulates flagellar transcription within Vibrio cholerae. FlrB autophosphorylates the conserved histidine at amino acid position 135, then transfers the phosphate to the conserved aspartate residue at position 54 in FlrC.  FlrC-P binds promoter regions and activates sigma54-dependent transcription of class III flagellar genes. By mutating the histidine at position 135 to an asparagine (H135N), FlrB is unable to undergo autophosphorylation, prohibiting phosphorylation of FlrC and transcription of FlrC-dependent genes. Mutating the leucine residue at position 36 in the PAS domain of FlrB to a phenylalanine (L36F) results in increased FlrC-dependent transcription. We hypothesize that V. cholerae with the FlrB L36F mutant form produces significantly higher amounts of FlrC-dependent transcripts. Conversely, FlrB H135N mutants will be significantly downregulated for the same genes.

overall_design: Mid-log cultures of V. cholerae O395 strains WT (KKV598), DflrB, FlrB H135N, FlrB L36F, DflaBCDE, DflaBCDE + FlrB L36F, DflaBCDE + FlrB H135N, and DflaBCDE + FlrB L36F H135N underwent Trizol-mediated RNA extraction and RNA-seq analysis. RNA extraction was performed on 3 biological replicates. FlrB is a histidine kinase and member of the two-component flagellar-regulated transcriptional system. By phosphorylating the histidine at amino acid position 135, FlrB is activated, permitting transfer of the phosphate from H135 to aspartate residue D54 on FlrC, which in turn binds with sigma-54 and RNAP to facilitate transcription of class III and class IV flagellar genes. By mutating the histidine at position 135 to an asparagine (H135N), FlrB is unable to undergo autophosphorylation, prohibiting phosphorylation of FlrC and transcription of FlrC-dependent genes. Mutating the leucine residue at position 36 in the PAS domain of FlrB to a phenylalanine (L36F) results in constitutive activation of FlrB and FlrC-dependent transcription. We hypothesize that V. cholerae with the FlrB L36F mutant form produce significantly higher amounts of FlrC-dependent transcripts. Conversely, FlrB H135N mutants will be significantly down-regulated for the same genes.

first: Bradley

last: Himes

first: Adrian

last: Meija-Santana

first: Jesus

last: Romo

first: Jiawei

last: Xing

first: Hong

last: Cai

first: Yufeng

last: Wang

first: Karl

last: Klose


title: Eosinophils protect against SARS-CoV-2 following a vaccine breakthrough infection

city: Atlanta

first: Gregory

last: Tharp

state: GA

address: 954 Gatewood Dr

department: Developmental and Cognitive Neuroscience

institute: Yerkes National Primate Research Center

summary: Waning immunity and the emergence of immune evasive SARS-CoV-2 variants jeopardize vaccine efficacy and contribute to breakthrough infections. The immune response that promotes vaccine-induced protection against SARS-CoV-2 breakthrough infection remains poorly understood. To model breakthrough infections, we vaccinated mice with a low dose vaccine formulation containing MF59-like adjuvant with prefusion-stabilized SARS-CoV-2 spike protein and challenged with immune evasive B.1.351 variant. Here, we show that eosinophils are required for protection against SARS-CoV-2 during a vaccine breakthrough infection. We found that vaccine breakthrough infection leads to a 2-log reduction in lung viral burden with restricted replication within the large airways as compared to naïve infected mice. Despite reduced antiviral gene expression, infected vaccinated mice show increased immune cell infiltration, characterized by monocytes, interstitial macrophages, and eosinophils, but with reduced activation markers into the lung parenchyma as compared to infected naïve mice. Single cell RNA-seq revealed that viral RNA was highly associated with eosinophils that corresponded to an IFN-γ biased phenotype and expression of antiviral genes including Cystatin B, an inhibitor of cysteine protease involved in SARS-CoV-2 entry via the endosome. Monocytes from infected vaccinated, but not naïve, mice showed high expression for eosinophil chemoattractant Ccl24 (eotaxin-2). Antibody-mediated depletion of eosinophils prior to infection of vaccinated mice resulted in increased virus replication and viral antigen staining deep in the lungs as compared to isotype control infected vaccinated mice. These results demonstrate the importance of eosinophils in vaccine-mediated protection and highlight the need for durable antibody responses that protect against lung infection and inflammation.

overall_design: Two mice in each group were either unvaccinated and mock infected, unvaccinated and infected, or vaccinated and infected using the AddaVax protein subunit vaccine and B.1.351 strain of the SARC-CoV-2 virus

first: Kathryn

middle: M

last: Moore

first: Stephanie

middle: L

last: Foster

first: Elizabeth

last: Elrod

first: Katharine

last: Floyd

first: M

middle: E

last: Williams

first: Meenakshi

last: Kar

first: Jacob

last: Vander Velden

first: Madison

last: Ellis

first: Ansa

last: Malik

first: Bushra

last: Wali

first: Stacey

last: Lapp

first: Amanda

last: Metz

first: Steven

last: Bosinger

first: Robert

last: Seder

first: Rama

middle: R

last: Amara

last: Kohlmeier

first: Arash

last: Grakoui

first: Mehul

middle: S

last: Suthar


title: Nuclear Paxillin Modulates Alternative Splicing Programs in Neurons during Sensitive Periods of Brain Development

city: Taipei

first: Pei-Lin

last: Cheng

address: No. 128 Acdemia Rd., Section 2, Nankang

country: Taiwan

institute: Institue of Molecular Biology, Academia Sinica

summary: During sensitive postnatal periods, brain neural circuits undergo significant refinement coincident with widespread neuronal alternative splicing events in which hundreds of genes alter their splice site selection to generate isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent serine119 phosphorylation of paxillin (p-paxillin S119) acts as a molecular switch in the nucleus to modulate alternative splicing during this period. We report that following NMDA receptor activation, nuclear p-paxillin S119 is recruited to nuclear speckles, where it interacts with U2AFs and splicing factors. Neuronal paxillin expression is required for timely alternative splicing of synaptic factors, including Snap25. Consequently, young mice lacking paxillin S119 phosphorylation exhibit significantly reduced levels of Snap25-5b isoforms, impaired presynaptic function at hippocampal Schaffer collateral-CA1 synapses, and deficits in short-term learning and memory. These findings support the idea that nuclear p-paxillin S119 is a critical mediator of alternative splicing programs in postnatal neurons during a sensitive period essential for neural plasticity.

overall_design:
RNA-seq of mouse primary neuronal cells with/without BDNF treatment and with/without paxillin knockdown by siRNA. Collect cells at DIV(days in vitro) 3, 5, 10.
Nanopore-based RNA-seq of mouse hippocampus tissue from wild type and paxillin KO/paxillin-S119A KI mice. Collect these mice at postnatal day10 (P10), P15 and P21.

first: Chien-Hsin

last: Chu

first: Guan-Zhu

last: Pan

first: Hung-Lun

last: Chiang

first: Chen

last: Chen

first: Ting-Ya

last: Chang

first: Chien-Lin

last: Lin


title: Glycerol-3-phosphate activates ChREBP, FGF21 transcription and lipogenesis in Citrin Deficiency

city: Duarte

first: Hung-Ping

last: Shih

address: 1500 E. Duarte Road

department: Translational Research and Cellular Therapeutics

institute: City of Hope

summary: Citrin Deficiency (CD) is caused by inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. We discovered that SLC25A13 loss causes accumulation of glycerol-3-phosphate (G3P), which activates carbohydrate response element binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol, and to transcribe key genes of de novo lipogenesis. Mouse and human data establish G3P-ChREBP as a new mechanistic component of the Randle Cycle that contributes to metabolic dysfunction-associated steatotic liver disease (MASLD) and forms part of a system that communicates metabolic states from liver to brain in a manner that alters food and alcohol choices. The data provide a framework for understanding FGF21 induction in varied conditions, suggest ways to develop FGF21-inducing drugs, and suggest drug candidates for both lean MASLD and support of urea cycle function in CD.

overall_design: To determine whether deletion of NADH shuttle systems and/or provision of glycerol resulted in a ChREBP transcriptional program, we harvested livers from 40 mice representing water and glycerol-exposed males of the four genotypes, prepared cDNA and performed bulk paired-end 150 base-pair RNA sequencing (RNAseq)61 using an Illumina NovaSeq X Plus sequencer at >20 million paired reads per sample.

first: Vinod

last: Tiwari

first: Byungchang

last: Jin

first: Olivia

last: Sun

first: Charles

last: Brenner


title: Effect of deplation of vtRNA1-1 and vtRNA1-2 on gene expression in  Huh7 hepatocellular carcinoma cells

city: Bern

first: Daniel

last: Sanchez-Taltavull

address: Murtenstrasse 35

department: Department of BioMedical Research

country: Switzerland

institute: University of Bern

summary: Non-coding RNAs (ncRNAs) are pivotal in tumorigenesis and cancer progression, and recent evidence highlights the class of human vault RNAs as important regulators of cellular homeostasis. The human genome encodes four vtRNA paralogs that are differentially expressed in cancer tissues and have thus been implicated in tumor onset and progression. The so far best studied paralog of the vault RNA family, vtRNA1-1, is involved in crucial cellular processes such as resistance to apoptosis, regulation of autophagy, control of lysosomal biogenesis, and drug resistance. In this study, we present a comprehensive characterization of a vtRNA1-2 knockout (KO) hepatocellular carcinoma cell line, marking the first detailed research study on this specific vtRNA paralog. Our findings indicated that the absence of vtRNA1-2 resulted in reduced viability and proliferation of cancer cells, by modulating the MAPK signaling pathway. Significantly, vtRNA1-2 KO cells displayed impaired motility, leading to a marked reduction in the invasiveness of malignant cells. Intriguingly, vtRNA1-2, unlike the vtRNA1-1 paralog, did not affect autophagy or lysosomal activity. Instead, our data demonstrate that vtRNA1-2 is critically involved in angiogenesis, a key process in tumor progression, by reducing vascular endothelial growth factor A secretion and inhibiting tube formation. These insights revealed a distinct role of vtRNA1-2 in tumorigenesis and positioned it as a promising target for the development of novel anti-cancer therapies. Our study advances the understanding of vault RNAs in cancer biology and strongly suggests that each vtRNA paralog possesses a unique role, rather than being mere molecular doppelgangers.

overall_design: To investigate the role of vtRNA1-1 and vtRNA1-2 in hepatocellular carcinoma,we sequenced the transcriptome of Huh7 cells in which it was knocked out either the VTRNA1-1 gene or VTRNA1-2 gene via CRISPR/Cas9 editing. RNA was extracted from cells grown to 80% confluency in complete medium

first: Stefano

last: Gallo

first: Deborah

last: Keogh-Stroka

first: Norbert

last: Polacek


title: Spermatogenesis, hormonal fluctuations, and testicular gene expression changes in male blue catfish, Ictalurus furcatus, throughout pubescent and early adult stages of development

city: Auburn

first: Ian

last: Butts

state: Alabama

address: 203, Swingle Hall

department: School of Fisheries, Aquaculture & Aquatic Sciences

institute: Auburn University

summary: Male blue catfish (Ictalurus furcatus) mature at 4-7 years and cannot be hand-stripped, making sperm collection a lethal procedure. Sperm are also highly variable in quality/quantity. Therefore, establishing links between seasonality, aging, and reproductive success is essential. Since there are no prior studies regarding seasonal and age-related changes in the testis transcriptome of male blue catfish, we evaluated global gene expression in testicular tissue over a 34-month period (2.3 to 4.9 years old; y/o). Significant differential expressed genes and gene ontology of pairwise comparisons are presented and discussed.

overall_design: A total of 15 testis tissue samples from blue catfish males were used in this study, corresponding to ages 2.9, 3.1, 3.9 and 4.2. Three-four testis tissue samples were collected per age group and extracted for RNA-seq.

first: Jason

last: Abernathy

first: Kaylan

last: Martin


title: A loss-of-function human ADAR variant activates innate immune response and triggers bowel inflammation

city: Wuhan

first: pengfei

last: xu

address: Donghu Road 115

institute: Wuhan University

summary: The goals of this study are to compare transcriptomes of mouse Ileal crypts isolated from Adarfl/fl and Adar iΔgut mice at 3 dpi of tamoxifen by RNA-seq.

overall_design: RNA-seq analysis of Ileal crypts were isolated from Adarfl/fl and Adar iΔgut mice at 3 dpi.

first: Yue

last: Xi

first: Pengfei

last: Xu

first: Min

last: Zhang

first: Wen

last: Xie


title: Genetic Ptbp1 depletion does not induce neuronal RNA splicing patterns in mature astrocytes (Single-cell RNA-seq)

status: Public on Aug 06 2025

city: Riverside

first: Sika

last: Zheng

address: University Ave 900

department: School of Medicine

institute: University of California, Riverside

summary: Neuronal reprogramming of astrocytes poses a promising therapeutic approach to replace degenerating cells with newly converted neurons. Recent studies reported depletion of polyprimidine tract binding protein PTBP1, a repressor of neuronal alternative splicing, could induce astrocyte to neuron conversion and rescue functional deficits in models of neurodegenerative disease, while others disputed the astrocytic origin of converted neurons. Mechanistic understanding of the conversion, or the lack thereof, requires investigating the transcriptomic effects of Ptbp1 loss of function in mature astrocytes on RNA splicing, in conjunction with lineage tracing, which have not yet been examined. Here, we used genetic depletion of Ptbp1 in adult Aldh1l1-Cre/ERT2 reporter mice to determine whether lineage traced Ptbp1 knockout astrocytes exhibited RNA splicing alterations underlying potential neuronal transdifferentiation. Our analysis employed an alternative genetic Ptbp1 knockout mouse model and an extended 12-week window of Ptbp1 knockout to match previous reports of positive conversion. We found no widespread induction of neuronal identity, despite detecting a minuscule fraction of Cre-positive cells with neuronal transcriptomic features following Ptbp1 deletion. Importantly, PTBP1 depletion in mature astrocytes induces splicing alternations unlike neuronal features of alternative splicing. These findings highlight the challenge of targeting astrocytes for neuronal conversion via Ptbp1 knockout and underscore the importance of cellular gene expression profiling and genetic lineage tracing for in vivo studies of cell type conversion.

overall_design: Gene expression analysis for tdTomato+ cells from brains of control (+/+;tdT+/-;Aldh1l1-Cre+/-) and (Ptbp1loxp/loxp;tdT+/-;Aldh1l1-Cre+/-) mice.

first: David

last: Nikom

first: Naoto

last: Kubota


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SYATAC_ATAC-seq]

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Synovial Sarcoma (SS) is driven by the SS18::SSX translocation event and is often diagnosed in patients under 30. In general, SS is refractory to chemotherapy and other therapeutic approaches. SS18::SSX does not directly bind to DNA. Instead, SS18::SSX alters ATP-dependent chromatin remodeling complex BAF (mammalian SWI/SNF complex) complexes away from a wild-type SS18-containing canonical (cBAF) complex towards a SS18::SSX-containing non-canonical (nc)BAF complex to drive a SS-specific transcription program with subsequent tumor formation. Small molecule targeted therapies are expanding beyond the kinome, providing additional tools to treat cancers that are not yet amenable to targeted therapies. Here, we demonstrate that SS18::SSX activates the SUMOylation program and SS are sensitive to the small molecule SAE1/2 inhibitor, TAK-981 (subasumstat). Mechanistically, we demonstrate TAK-981 de-SUMOylates the cBAF and Polybromo-associated BAF complex (PBAF) complex member, SMARCE1. The result of which is stabilization and restoration of cBAF complexes on chromatin, shifting away from the dominant SS18::SSX-ncBAF-complex driven transcriptome. This phenotypic shift is associated with DNA damage and cell death, resulting in tumor inhibition across both human and mouse SS tumor models. As such, TAK-981 combined with standard-of-care chemotherapy enhances induced synergistic activity through increased DNA damage, leading to tumor regressions. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, and positioning the in-clinic TAK-981 as a novel candidate to treat this refractory cancer.

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP seq) for SS18::SSX, SMARCA4, KDM2B and H3K27ac in SYO.1 and SYO.1 synovial sarcoma cell lines

first: Konstantinos

middle: V

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

middle: I

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

middle: D

last: Hill

first: Jamie

last: Slaughter

first: Mayuri

last: Shende

first: Madelynk

last: Lorenz

first: Mandy

last: Hinojosa

first: Benjamin

last: Belvin

first: Zhao

last: Lai

first: Sosipatros

last: Boikos

first: Angeliki

last: Stamatouli

first: Janina

middle: P

last: Lewis

first: Masoud

middle: H

last: Manjili

first: Kristoffer

last: Valerie

first: Renfeng

first: Ana

last: Banito

first: Andrew

last: Poklepovic

first: Jennifer

last: Koblinski

first: Trevor

last: Siggers

middle: G

first: Kevin

middle: B


title: Human iPSC-derived cell grafts promote functional recovery by molecular interaction with stroke-injured brain

city: Los Angeles

first: Ruslan

last: Rust

address: 1501 San Pablo Street

institute: University of Southern California

summary: IPSC-NPC were transplanted in a mouse model of stroke. To dissect the molecular graft composition and identify graft-host interactions, single nucleus profiling of the cell transplants and host stroke tissue was performed. We identified graft differentiation preferentially towards GABAergic cells with remaining cells acquiring glutamatergic neuron, astrocyte, and NPC-like phenotypes. Interaction between graft and host transcriptome indicated that GABAergic cell grafts were primarily involved in graft-host communication through the regeneration-associated NRXN, NRG, NCAM and SLIT signalling pathways

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: IPSC-NPC were transplanted in mice one week after stroke. Nuclei from cell grafts and stroke-injured tissue were isolated and analysed using single nucleus RNAseq


title: Testis mRNA expression profiling of Atlantic salmon (Salmo salar) age-at-maturity-associated genes during different maturation stages

status: Public on Aug 05 2025

city: Helsinki

first: Ehsan

middle: Pashay

last: Ahi

address: Biocenter 1, Viikinkaari 9

country: Finland

institute: University of Helsinki

summary: Study revealed new information about molecular functions of the vgll3 gene associated with age-at-maturity in the testis of Atlantic salmon

overall_design: In the study presented here, expression patterns of a gene associated with age-at-maturity in Atlantic salmon, its paralogs and 340 additional genes were studied in whole hatchery-derived individuals of three maturation stages, immature-1 and immature-2, and mature, in the testis of two vgll3 genotypes (early and late maturation genotypes).

last: Pashay Ahi

first: Craig

last: Primmer

first: Johanna

last: Kurko


title: Genetic Ptbp1 depletion does not induce neuronal RNA splicing patterns in mature astrocytes (Bulk RNA-seq)

first: Sika

last: Zheng

overall_design: Comparative gene expression and splicing analysis for tdTomato+ cells from brains of control (+/+;tdT+/-;Aldh1l1-Cre+/-) and (Ptbp1loxp/loxp;tdT+/-;Aldh1l1-Cre+/-) mice.

first: Min

last: Zhang

first: David

last: Nikom

first: Naoto

last: Kubota


title: NRCAM variant defined by microexon skipping is a targetable surface proteoform in high-grade gliomas

city: New York

first: Julien

last: Jarroux

address: 413 E 69th St

department: Brain and Mind Research Institute

institute: Weill Cornell Medicine

summary: To overcome the paucity of known tumor-specific surface antigens in pediatric high-grade glioma (pHGG), we contrasted splicing patterns in pHGGs and normal brain samples. Among alternative splicing events affecting extracellular protein domains, the most pervasive alteration was the skipping of ≤30 nucleotide-long microexons. Several of these skipped microexons mapped to L1-IgCAM family members, such as NRCAM. Bulk and single-nuclei short- and long-read RNA-seq revealed uniform skipping of NRCAM microexons 5 and 19 in virtually every pHGG sample. Importantly, the Δex5Δex19 (but not the full-length) NRCAM proteoform was essential for pHGG cell migration and invasion in vitro and tumor growth in vivo. We developed a monoclonal antibody selective for Δex5Δex19 NRCAM and demonstrated that “painting“ of pHGG cells with this antibody enables killing by T cells armed with an FcRI-based universal immune receptor. Thus, pHGG-specific NRCAM and possibly other L1-IgCAM proteoforms are promising and highly selective targets for adoptive immunotherapies.

overall_design: Our recently developed SnISOr-Seq approach allows for the accurate cataloging of full-length transcripts devoid of intronic sequences. We applied this approach to the pediatric high-grade glioma cell line 7316-3058. The short-read part of the workflow was used to determine expression level of select genes in individual cells. The long-read part of the workflow was used to determine whether microexons of interest are processed in a uniform or in a stochastic manner.

first: Hagen

middle: U

last: Tilgner

first: Priyanka

last: Sehgal

first: Andrei

last: Thomas-Tikhonenko

first: Berk

last: Mankaliye

first: Taewoo

last: Kim


title: RNA-seq datasets of the mTOR signalling pathway and the estrogen-dependent regulation of the transcriptome in mouse mammary gland epithelial organoids

city: Québec

first: Étienne

last: Audet-Walsh

state: Québec

address: 2705 boulevard Laurier

country: Canada

institute: CRCHU de Québec

summary: This GSE covered two different but complementary works on mouse mammary epithelial organoids. The first one is a publication from 2025 in Data in Brief entitled "RNA-seq dataset of the estrogen-dependent regulation of the transcriptome in mouse mammary gland epithelial organoids”. The second one is a publication from 2026 in Scientific Reports entitled “The mTOR signalling pathway regulates key steps of mammary gland organoid genesis in a temporal manner”. The mammary gland development in utero and during life is strongly regulated by hormones. We first studied the impact of estradiol during 11 days in culture and performed bulk mRNA sequencing to better understand the impact of estrogen signalling on the mammary epithelial cell transcriptome. Besides, the development of the gland is also a complex process that evolves throughout life. In developmental assays, the mechanistic target of rapamycin (mTOR) was shown to be a regulator of cellular lineage determination and branching morphogenesis, acting in a time-dependent manner to control these processes. We treated our organoids with Torin 1 at two different growing points and used bulk mRNA sequencing to demonstrate the regulatory functions of mTOR in controlling mammary epithelial cells’ capacity to generate organoids. Altogether, these two datasets help understand the function of the mammary gland. They can be reanalyzed and combined with recent single-cell RNA-seq data to better understand the role of the estrogen receptor and the mTOR signalling pathway in the functions of the gland in physiological conditions, such as lactation or pathological conditions, such as breast cancer.

overall_design: 3 mammary glands from 3 nulliparous mature adult (~24 weeks for estradiol treatment and ~15 weeks for Torin 1 treatment) Mus musculus C57BL/6 were used to produce organoids. Organoids were then treated with either ethanol or estradiol for a duration of 11 days for the estradiol treatment (See Data in Brief, n=6 samples starting with "AL146_GM_org") or either DMSO or Torin 1 for a duration of 12 days (D6) or 6 days (D12) for the Torin 1 treatment (See Scientific Reports, n=24 samples starting with "AL196_org_GM_ARN"). All experiments were done in triplicate. RNA has been extracted and sequenced using Illumina NovaSeq 6000 in paired ends 100bp reads.

first: Aurélie

last: Lacouture

first: Mame Sokhna

last: Sylla

first: Lucas

last: Germain


title: Development of long non-coding RNA (LncRNAs) signature for T-DM1 treatment outcome

city: Riyadh

first: Syed

last: Islam

address: Thakkassassi Street

department: Molecular Oncology

country: Saudi Arabia

institute: King Faisal Specialist Hospitalm Research Center

summary: To extend our understanding of the role long non-coding RNAs in treatment outcome, we have analyzed microarray expression profiling as a discovery platform to identify  LncRNAs  for distinguishing patients who response to T-DM1 for decision making segregation of patients who to reveice further treatment.  Blood samples from HER2-positive metastatic breast cancer patients were collected, and a 4-lncRNA signature was identified that distinguished bwteen treatment resistant and sensitive patients.

overall_design: Gene expression profiling from blood serum was analyzed from 10 T-DM1 resistant and 10 T-DM1 sensitive patients

first: Abdelillah

last: Aboussekhra


title: Transcriptomic analysis of sarcopenic obese mice reveals alterations in regulators of muscle force production, such as extracellular matrix remodeling and shifts in muscle fiber type

city: Fayetteville

first: Eleanor

last: Schrems

state: Arkansas

address: 155 Stadium Dr.

department: Health, Human Performance, and Recreation

institute: University of Arkansas

summary: Sarcopenic obesity (SO) is the combined condition of sarcopenia and obesity most commonly occurring in the older adult population. SO is associated with poor physical function, increased risk of musculoskeletal injury, and reduced quality of life and independence. There is little information on the molecular underpinnings of this condition. The aim of this study was to provide a transcriptomic analysis characterizing SO and to provide deeper understanding to the etiology of the condition. Young (Y) (6 mo) and aged (A) (21-24 mo) mice were fed either normal chow (L) (12% kcal from fat) or high-fat (O) (60% kcal from fat) diets ad libitum. Through multiple analyses, we observed genes related to ECM remodeling are downregulated with aged-obesity compared with young obesity, providing insight to the effects of age in a life-long obese condition. Furthermore, genes related to slow-twitch muscle contraction and fast-to-slow muscle fiber type transitions were upregulated in with obesity in the aged condition. Together, our results demonstrate avenues of dysregulation in SO skeletal muscle, providing the molecular building blocks expanding our understanding of the etiology of poor muscle function in this condition. Further understanding and exploration of these dysregulations is critical to identify therapeutic treatments targeting the source of muscle functional impairment, reducing the risk of musculoskeletal injury, and improving quality of life and independence SO individuals.

overall_design: Young (Y) (6 mo) and aged (A) (21-24 mo) mice were fed either normal chow (L) (12% kcal from fat) or high-fat (O) (60% kcal from fat) diets ad libitum. Tibialis anterior muscles were collected from young and age mice at expeerimental endpoint (young: 6 months old; aged 21-24 months old). Total RNA from the Tibialis anterior muscle underwent paired end mRNA sequencing.

first: Ana

last: Cabrera

first: Ronald

last: Jones III

first: Francielly

last: Morena

first: Kevin

middle: A

last: Murach

first: Nicholas

last: Greene

first: Tyrone

last: Washington


title: Single-cell RNA Sequencing Reveals Immune Cell Alterations in Patients with Allergic Rhinitis Treated with Peiyuan Tongqiao Decoction

city: Zhengzhou City

first: Jingbo

last: Li

state: Henan Province

address: No. 6, Dongfeng Road

department: Department of Otorhinolaryngology

institute: Henan Province Hospital of Traditional Chinese Medicine

summary: Allergic rhinitis (AR), a chronic inflammatory disorder with complex causative mechanisms,  threat to human physical and mental health. Traditional Chinese medicine (TCM) are gaining attention due to their potential ability to treat AR. The aim of this study was to elucidate biological activity of Peiyuan Tongqiao Decoction that can act on the different processes of AR through cell abundance, DEGs, pathways and transcription factors (TFs) through single-cell RNA sequencing (scRNA-seq)

overall_design: PBMCs from pre-treatment group and post-treatment group of AR patients were obtained and used to construct single-cell RNA sequencing (scRNA-seq) libraries

first: Li

last: Jingbo

first: Lu

last: Yinian

first: Wang

last: Junjie

last: Yan

first: Cao

last: Yang


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma

first: Mikhail

last: Dozmorov

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

overall_design: Refer to individual Series


title: LAM cell mTOR dysregulation induces IL6 and paracrine AT2 cell senescence impeding lung repair in lymphangioleiomyomatosis.

city: Nottingham

first: Roya

last: Babaei Jadidi

state: Nottinghamshire

address: Biodiscovery institute

country: United Kingdom

institute: University of Nottingham

summary: LAM is a rare disease which causes lung cysts and respiratory failure. TSC2 deficient ‘LAM cells’ with dysregulated mTOR signalling form nodules with fibroblasts causing lung injury. We examined if mTOR dysregulation could induce senescence and impair responses to lung injury. Senescence markers p21 and p16 were increased in LAM lungs and co-localised with alveolar type 2 cells. The SenMayo senescence gene panel was upregulated in LAM alveolar type 2 cells with senescence supressed by mTOR inhibition in patients. LAM cell / fibroblast spheroid cultures induced senescence markers in alveolar type 2 cell organoids, altered their growth and delayed epithelial scratch wound repair. Upstream regulator analysis predicted alveolar type 2 cell IL6 receptor activation. IL6 was produced by LAM cells, was overexpressed in LAM serum and related to lung function, induced p16 and p21 in alveolar type 2 cells and inhibited epithelial wound resolution. Wound repair in the presence of TSC2 null but not TSC2 addback LAM cell / fibroblast spheroids was enhanced by the IL6 receptor antagonist Tocilizumab. Our findings show TSC2 loss induces senescence and IL6 production which are associated with impaired lung repair. Targeting IL6 signalling in parallel with mTOR inhibition, may reduce lung damage in LAM.

overall_design: To understand the processes driving senescence we used laser capture micro-dissection to isolate LAM nodules from lung tissue from 19 women with LAM and 3 controls. Lung tissue used for laser capture microdissection was obtained from patients at the UK LAM. RNA was extracted from laser capture and rest of lungs and analysed gene expression by RNA sequencing.

first: Debbie

last: Clements

first: Yixin

last: Wu

first: Ken

last: Chen

first: Suzanne

last: Miller

first: Manuela

last: Plate

first: Kyungtae

last: Lim

first: Rachel

last: Chambers

first: Emma

last: Rawlins

first: Yan

last: Xu

first: Simon

last: Johnson


title: IFN-γ induced the formation of foamy macrophages by CD40 signaling control during Mycobacterium abscessus pulmonary infection

city: shanghai

first: Xianwei

address: No.725 South Wanping Road

department: Institute of Respiratory Diseases

institute: Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

summary: Transcriptome sequencing was performed to identify genes that might be responsible for the formation of a large number of lipid droplets with a combination of IFN-γ pretreatment and M. abscessus infection

overall_design: For transcriptome sequencing analysis of BMDM (2.5×106/well), cells were plated on 6 well glass bottom plate. Media was changed to either BMDM media, or BMDM media with 6.25 ng/mL recombinant murine IFN-γ (Novoprotein, Suzhou, China). After overnight IFN-γ pretreatment, BMDM were infected with M. abscessus at an MOI of 10. Following the 2-hour phagocytosis period, media was changed and IFN-γ was added again at 6.25ng/mL to all IFN-γ pre-treated wells. 48 hours post-infection, discard the supernatant and wash twice with sterile PBS. Total RNA was extracted from BMDM cells using TRIzol (Invitrogen, Carlsbad, California, USA) according to manual instruction.

first: Shaoyan

last: Zhang

first: Ya

last: Feng

first: Jiajun

last: Tian

first: Hai

last: Lou

first: Liping

last: Wang

first: Ben

last: Su

first: Xing

last: Huang

first: Lei

last: Qiu

first: Dingzhong

first: Wei

last: Sha

first: Zhenhui

last: Lu


title: Decoding the Variant-to-Function Relationship for LIPA, a Risk Locus for CAD

first: Fang

last: Li

state: NY

department: Medicine

institute: Columbia University Irving Medical Center


title: Single cell RNA sequencing of post-radiation mouse jejunum with or without DIZE

status: Public on Aug 04 2025

city: Milwaukee

first: Joseph

last: Zenga

state: WI

address: 9200 W WISCONSIN AVE

institute: MEDICAL COLLEGE OF WISCONSIN

summary: In a radiation mass casualty event, exposed populations will suffer dose-dependent toxicity to multiple-organ systems.  Although several therapies are FDA-approved for treatment of the hematopoietic acute radiation syndrome (H-ARS), there are no FDA-approved medical countermeasures (MCM) for either acute gastrointestinal injury (GI) or late multi-organ toxicities known as the delayed effects of acute radiation exposure (DEARE).    Prior data suggest activation of the alternative renin angiotensin (RAS) enzyme angiotensin-converting enzyme 2 (ACE2) has therapeutic potential for mitigating multi-organ radiation injury, including GI acute radiation syndrome (GI-ARS).  Here, we evaluated whether pharmacologic activation of ACE2 mitigates GI-ARS in rodent models and protects against DEARE in GI-ARS survivors.

overall_design: 6 mice underwent radiation with sacrifice at post-radiation day 5. Single cell RNA seq was then performed from jejunum.

first: Zenga

last: Joseph

first: Himburg

last: Heather


title: A Basophil-Fibroblast Pro-inflammatory Axis Fuels Type 2 Skin Inflammation

first: Raman

last: Gill

address: 1428 Madison Ave

department: Dermatology

institute: Icahn School of Medicine at Mount Sinai


title: A Basophil-Fibroblast Pro-inflammatory Axis Fuels Type 2 Skin Inflammation [RNA-Seq]

summary: To better understand the contribution of basophils and fibroblast IL-4 signaling on type 2 skin inflammation, we conducted bulk-RNA seq on from normal and MC903 treated Isotype Cntrl + Mar1 and Il4rafl/fl  + Il4raΔPdgfra models respectively.

overall_design: MC903 treated or vehicle control neck skin was harvested from WT Isotype control and MAR1 injected mice, Il4rafl/fl and, Il4raΔPdgfra mice (n=1 mice per sample). Briefly, skin samples were harvested, snap frozen, and cryosectioned. RNA was isolated and purified from each sample using the Quick-RNA Micro Prep Kit (Zymo Research). Libraries were prepared and sequenced by Novogene

first: Ichiro

last: Imanishi

first: Andrew

last: Ji


title: A Basophil-Fibroblast Pro-inflammatory Axis Fuels Type 2 Skin Inflammation [scRNA-Seq]

summary: To better understand cell-cell interactions driving type 2 skin inflammation, we conducted scRNA-seq on two murine models of type 2 skin inflamation, MC903 and Oxazolone (OXA), using the 10X genomics platform

overall_design: MC903/OXA treated or normal ear+neck skin were harvested and pooled for each sample (n=3 mice per condition). Briefly, skin samples were digested using the Miltenyi Multi-tissue dissociation kit. Dead cells were removed using the biolegend mojosort mouse dead cell removal kit. scRNA-seq libraries were generated and analyzed in-house using the 10X genomics platform

first: Alexis

last: Wilder


title: mRNA-seq of individual genetically identical Caenorhabditis elegans adults

city: Eugene

first: Amy

middle: K

last: Webster

state: Oregon

address: Institute of Ecology and Evolution

institute: University of Oregon

summary: Individual phenotypic differences persist even in genetically identical individuals, although separating genetic and environmental causation is difficult or impossible in most organisms. To understand the basis of individual differences in the absence of genetic differences, we measured two quantitative reproductive traits in genetically identical young adult Caenorhabditis elegans roundworms in a shared environment and performed single-individual mRNA-seq on each worm. We identified hundreds of genes for which expression variation was strongly associated with reproductive traits, some of which depended on prior environmental experience and some of which was random. Multiple small sets of genes together were highly predictive of reproductive traits across individuals.

overall_design: In the P0 generation, adult C. elegans hermaphrodites were allowed to lay progeny at day 1 or day 3 of adulthood. F1 progeny were then left at 20C throughout their life or shifted to 25C for 8 hours early in life. It was documented when each F1 worm reached egg-laying onset, and 24 hours after egg-laying onset, each F1 young adult worm was collected for individual worm mRNA-seq. The number of progeny laid in the first 24 hours was also measured for each worm.

first: John

last: Willis

first: Erik

last: Johnson

first: Patrick

middle: C

last: Phillips


title: ARD1 facilitates ferroptosis evasion via the induction of glutathione synthesis through catalysis of PABPC1 acetylation in HCC [CRISPR screen]

status: Public on Aug 02 2025

first: Minghe

last: Zhang

state: Hubei

address: Donghu Road

institute: WuHan University

summary: Aberrant upregulation of intracellular antioxidant glutathione (GSH) is implicated in promoting tumor proliferation, inducing drug resistance, and inhibiting ferroptosis across various malignancies, including hepatocellular carcinoma (HCC). However, the mechanism underlying the GSH metabolism reprogramming in HCC remains poorly understood. In this study, we employed a genome-wide CRISPR‒Cas9 screen and RNA-seq to identify ARD1 as a pivotal facilitator of de novo GSH synthesis in HCC. Notably, ARD1 upregulation is positively correlated with elevated GSH levels and a poor prognosis in HCC patients. In vivo and in vitro functional assays revealed that ARD1 promotes HCC cell proliferation and inhibits ferroptosis in a GSH-dependent manner. LC‒MS/MS-based stable isotope labeling revealed that ARD1 increases GSH levels by stabilizing the γ-glutamylcysteine ligase catalytic subunit (GCLC) transcript.  Overall, this research underscores the crucial role of ARD1 in GSH metabolic reprogramming and ferroptosis regulation in HCC and reveals a novel strategy for ferroptosis-based targeted therapy for HCC.

overall_design: The CRISPER-PoolTM KOUT human library containing 123,441 sgRNAs targeting 19,050 genes and 1,864 miRNAs was purchased from Genechem Co., Ltd. (Shanghai, China). After Huh-7 cells were transduced with various concentrations of the lentiviral library (2.5%-60%) for 72 hours, 2.5 μg/ml puromycin (Biosharp, China) was added to the medium, and the functional multiplicities of infection (MOIs) were assessed via a CCK-8 assay. A total of 2 × 108 Huh-7 cells were transduced with the corresponding amounts of lentiviral particles at functional MOIs to ensure 500-fold coverage and subjected to selection for cells stably infected for 72 hours with 2.5 μg/ml puromycin. The transduced cells were then divided into two groups and treated with or without the glutathione synthesis inhibitor buthionine sulfoximine (BSO; MCE, USA) at the IC20. Following 24 days of selection, at least 5 × 107 cells were collected and subjecred to  DNA extraction, PCR amplification and sgRNA sequencing.

first: Yingyi

last: Liu

first: MInghe

first: Yufeng

last: Yuan


title: Transcriptomic profiling of LNCaP cells treated with enzalutamide, olaparib, or combination across multiple time points

city: Cambridge

first: Robert

last: Hanson

address: Hills Rd

department: Oncology

institute: Early Cancer Institute

summary: To explore the mechanisms underpinning the combinatorial effects of androgen pathway and PARP inhibition on global gene expression in prostate cancer, we performed RNA sequencing analysis in LNCaP prostate cancer cells. Cells were treated with either single agents or the combination, and transcriptomic changes were asssed at early (8 hours), intermediate (24 hours), and late (72 hours) timepoints to assess temporal dynamics of treatment response. Comparative analyses between single-agent and combination treatments enabled the characterisation of transcriptional programs induced by the combinatorial regimen.

overall_design: LNCaP cells were treated with 3 μM olaparib, 3 μM enzalutamide, or the combination, with each condition performed in triplicate cultures and incubated for 8, 24, or 72 hours prior to RNA extraction, library preparation, and high-throughput sequencing.

first: Harveer

last: Dev

first: Charles

last: Massie

first: Giuditta

last: Illuzzi

first: Alessandro

last: Galbiati

first: Josep

last: Forment


title: A scalable two-step genome editing strategy for generating full-length gene humanized mice at diverse genomic loci

status: Public on Aug 01 2025

city: Minato

first: Manabu

last: Ozawa

state: Tokyo

address: 4-6-1, Shirokanedai

department: Institute of Medical Science

institute: The University of Tokyo

summary: Full-length gene-humanized mice, generated by replacing mouse loci with their human counterparts including untranslated and regulatory regions, offer a powerful in vivo platform to study human gene function. However, reliable humanization of large genomic regions remains challenging due to limitations in DNA insert size, complex protocols, and reliance on specialized materials.  Here, we present a streamlined approach that enables full-length gene humanization through two sequential CRISPR-assisted homologous recombination steps in embryonic stem cells. This method supports targeted knock-in of genomic fragments exceeding 200 kbp and is applicable across multiple mouse strains. Humanized alleles generated using this strategy recapitulate human-like splicing isoforms and organ-specific gene expression, and restore essential functions in hematopoiesis, spermatogenesis, and survival. Furthermore, disease-associated mutations can be introduced into humanized alleles to generate in vivo models of human genetic disorders. This versatile platform enables creation of physiologically relevant, fully gene-humanized mouse models for broad applications in biomedical research.

first: Hideto

last: Mori

first: Jumpei

last: Taguchi


title: Direct and indirect regulation of fetal globin transcript by RNA-binding protein IGF2BP1

city: Boston

first: Steven

last: Coyne

state: MA

address: 1 Blackfan Ave. Karp Building RB8005G Karp Building RB8005G

department: Dept. of Hematology/Oncology

institute: Boston Children's Hospital

summary: Despite extensive investigation, mechanisms of developmental hemoglobin expression remain incompletely understood. Hemoglobin switching is controlled by transcription factors, miRNAs, and RNA-binding proteins (RBPs) that enforce gene regulatory changes through development. Here we examine the role of the heterochronically silenced N-6 methyladenosine (m6A) RNA-binding protein, IGF2BP1 that was previously described to regulate HBG1/2 indirectly by suppressing BCL11A expression through a poorly understood mechanism. We find that IGF2BP1 binds and activates HIC2, itself a BCL11A repressor. Furthermore, we identify that IGF2BP1 plays a BCL11A-independent role by direct binding to HBG1/2 to promote its translation. Stop codon-proximal m6A-modified coding sequences within HBG2 transcripts are necessary and sufficient for direct positive regulation mediated by IGF2BP1. Together this work deepens the mechanistic understanding of hemoglobin switching and suggests a physical relationship between heterochronic RBPs and globin transcripts.

overall_design: HUDEP-2 cells were treated with a lentiviral overexpression vector for IGF2BP1, an empty control vector, or untreated. These HUDEP-2 cells as well as wild-type HUDEP-1 cells were then differentiated for 8 days in erythroid differentiation media (EDM-II) before RNA was collected and RNAseq was paired-end RNAseq was performed with truseq adapters. Additionally, we performed RNAseq from in vitro erythroid differentiated primary cells isolated from adult bone marrow, cord blood, or fetal liver CD34+ hematopoietic stem and progenitor cells (HSPCs). Samples were quantitated using salmon and resulting counts were used for differential gene expression analysis using DEseq2.

first: Mir

last: Hossain

first: Daniel

last: Bauer


title: The Acetyltransferase ARD1 Induces Glutathione Synthesis to Facilitate Ferroptosis Evasion in Hepatocellular Carcinoma

city: Wuhan

summary: Aberrant upregulation of the intracellular antioxidant glutathione (GSH) is implicated in promoting tumor proliferation, inducing drug resistance, and inhibiting ferroptosis across various malignancies, including hepatocellular carcinoma (HCC). Targeting the mechanism underlying GSH upregulation in HCC could represent a therapeutic strategy to improve patient outcomes. In this study, we employed a genome-wide CRISPR‒Cas9 screen and targeted metabolomics to identify the acetyltransferase ARD1 as a pivotal facilitator of de novo GSH synthesis in HCC. Notably, ARD1 upregulation was positively correlated with elevated GSH levels and poor prognosis in HCC patients. In vivo and in vitro functional assays revealed that ARD1 promoted HCC cell proliferation and inhibited ferroptosis in a GSH-dependent manner. LC‒MS/MS-based stable isotope labeling revealed that ARD1 increased GSH levels by stabilizing γ-glutamylcysteine ligase catalytic subunit (GCLC) mRNA, which was mediated by the RNA-binding protein PABPC1. Mechanistically, ARD1 acetylated PABPC1 at K167, augmenting its cytoplasmic retention by disrupting PABPC1-importin α7 complex formation. Cytoplasmic PABPC1 then interacted with eIF4G to collaboratively stabilize GCLC mRNA, preventing its degradation, increasing GSH synthesis, and ultimately conferring ferroptosis resistance in HCC cells. Furthermore, oxidative stress induced by hydrogen peroxide suppressed ARD1 ubiquitination and degradation, thereby promoting PABPC1 cytoplasmic translocation and inducing GCLC expression. ARD1 suppression promoted sorafenib-mediated ferroptosis in HCC patient-derived xenograft tumors with high ARD1 and GCLC expression. Overall, this research uncovers an oxidative stress–ARD1–PABPC1–GCLC axis with a crucial role in GSH metabolic reprogramming and ferroptosis regulation in HCC and reveals a strategy for ferroptosis-based targeted therapy for HCC.

overall_design: Huh-7 and Hep-3B cells were transfected with siRNA targeting ARD1 or negative control.After validation of transfection efficiency, cells were collected and utilized for RNA sequencing transcriptome analysis.


title: Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [cutandtag]

city: Lausanne

first: Julien

last: Duc

state: VAUD

address: Station 19 CH-1015 Lausanne

department: School of Life Science

institute: EPFL

summary: The primate-restricted KRAB zinc finger protein (KZFP) ZNF93 represses a subset of L1 transposable elements (TEs) that propagated in the human ancestral genome some 20 to 12 million years ago and have all become transposition-incompetent due to inactivating mutations. Here, we demonstrate that these L1 integrants encode a highly genotoxic endonuclease, and that ZNF93 also represses other full-length L1 integrants via indirect effects as well as APOBEC3B. Consistent with the exquisite sensitivity of single-stranded DNA to attack by both the L1 endonuclease and the cytidine deaminase, ZNF93 expression peaks in S phase and correlates with cell proliferation. ZNF93 is induced in most cancers, and ZNF93-depleted cells exhibit defects in DNA synthesis and activation of the replication and DNA damage checkpoints. These results suggest a model whereby ZNF93 is a major guardian of genome integrity subverted by cancer cells to escape L1-mediated epigenetic surveillance and achieve a proper balance of APOBEC3B-induced tumor heterogeneity and overall genome stability.

overall_design: Cut & Tag of H3K9 and H3K4 in WT and

first: Romain

last: Forey


title: ARD1 facilitates ferroptosis evasion via the induction of glutathione synthesis through catalysis of PABPC1 acetylation in HCC

first: Minghe

last: Zhang

overall_design: PLC/PRF/5 cells were transfected with ARD1 overexpressing plasmids or control vector. After validation of transfection efficiency, cells were collected and utilized for RNA sequencing transcriptome analysis.

first: Yingyi


title: Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_3]

overall_design: RNA-seq of SW480, U2932, OCILY7 cell line in WT or ZNF93 KD condition


title: Immunostimulatory CELMoD combination overcomes resistance to T cell engagers caused by high multiple myeloma burden

city: Broomfield

first: Caleb

middle: Karl

last: Stein

state: CO

address: 12735 Yates Street

institute: Mayo Clinic

summary: Bispecific T cell engagers (TCE) targeting BCMA and CD3 induce deep hematologic responses in approximately 60% of heavily pre-treated multiple myeloma (MM) patients. Pre-treatment with iberdomide and dexamethasone reshaped the bone marrow T cell compartment, promoted infiltration of naïve T cells, and generated 100% response rates and the longest survival in subjects with high tumor burden. This was accompanied by more favorable T cell profiling, with limited expansion of regulatory T cells and exhaustion. In total, administering TCE following dexamethasone and iberdomide treatments provided deeper and more durable responses with reduced risk of CRS. Whole Bone Marrow single cell profiling of immune phenotype of untreated and treated de novo Vk murine model.

overall_design: Age matched de novo Vk*MYChCRBN mice with MM received vehicle, dexamethasone at 10 mg/kg, IBER at 10 mg/kg or combination. 23 hours later, mice were euthanized and BM cells collected. After ACK lysis, 8,000 mononuclear cells/sample were processed using the 10XGenomicsChromium single cell 3’V2 kit. For a subsequent repeat, we performed ACK lysis of samples from one mouse per treatment to obtain 5,000 mononuclear cells which were processed using the 10XGenomicsChromium automated single cell 5’v2 kit. Illumina libraries were sequenced on a partial Novaseq S4 lane to obtain 50,000 reads/cell. Gene counting was performed using Cell Ranger version 7.1.0 or higher.

first: Erin

last: Meermeier

first: Marta

last: Chesi


title: RNA-seq result of yeast cells grown in glucose and glycerol condition

city: Novato

first: Fan

last: Zheng

state: California

address: 8001 Redwood Blvd, Novato, CA 94945

institute: BUCK INSTITUTE FOR RESEARCH ON AGING

summary: This project investigates transcriptomic changes in Saccharomyces cerevisiae in response to distinct metabolic environments. RNA-seq was performed on wild-type yeast cultured in glucose (fermentative) and glycerol (respiratory) media. The goal is to understand how mitochondrial ribosomal genes and nuclear gene expression are regulated in different metabolic states.

overall_design: Saccharomyces cerevisiae wild-type strain BY4741 was cultured in synthetic complete (SC) medium supplemented with either glucose or glycerol as the carbon source. Total RNA was extracted from cells grown under both conditions and submitted to Novogene for library preparation and RNA sequencing.

first: Zanlin

last: Yu

first: Yifan

last: Cheng

first: Chuankai

last: Zhou


title: Disruption of the Placenta-Brain Axis in Transgenic Mice Lacking Serotonin Transporter (SERT) in Trophoblast Cell

city: Columbia

first: Trupti

last: Joshi

state: Missouri

address: 103 Math Science Building

department: Department of Biomedical Informatics, Biostatistics and Medical Epidemiology (BBME)

institute: University of Missouri-Columbia

summary: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed drugs to pregnant women experiencing depression. While such drugs might be beneficial in combating depression by competitively binding to serotonin transporter (SERT), they can adversely affect the placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4. The placenta provides the initial source of 5-HT to the emerging brain via the placental-brain axis. Disruption of 5-HT acquisition by pTGCs due to genetic deletion of Slc6a4 is hypothesized to impact placental and fetal brain development. A transgenic mouse line with the SERT transporter selectively deleted was created by pairing mice with Cre-recombinase linked to proliferin (Prl2c2) with LoxP sites flanking the Slc6a4 gene. Proliferin is solely expressed by pTGCs and other giant cells of the placenta. To compare placental and fetal brain development in selective Sl6a4 KO and WT mice, 5-HT content in the placenta and fetal brains of the mice was measured. No significant differences in 5-HT content were evident between knockout (KO) and wild-type (WT) placenta and fetal brain. However, there was significantly lower average number of pTGCs in KO placentas compared to WT (p ≤ 0.05). Sexually dimorphic differences in gene expression were evident in the placenta and fetal brain between KO and WT counterparts with female conceptuses showing the most dramatic responses. Findings suggest that ablation of SERT in pTGC disrupts the placenta-brain axis in a sex-dependent manner. These results might have important clinical ramifications for pregnant women being treated with SSRIs.

overall_design: RNAseq profiling of Slc6a4 WT and Slc64a4/SERT KO fetal brain and placenta mouse samples that were extracted at E12.5.

first: David

middle: T

last: Ellenberger

first: Zhen

last: Lyu

first: Rosalind

last: Herrington

first: Jessica

last: Kinkade

first: Gustavo

middle: W

last: Leone

first: Ji Ying

last: Sze

first: Nathan

middle: J

last: Bivens

first: Robert

middle: F

last: Baker

first: Michael

last: Roberts

first: Cheryl

last: Rosenfeld


title: Single-cell transcriptomic profiling of aortic plaque cells from myeloid-specific Lipa overexpression and control mice on an Ldlr-/- background

city: New York

first: Fang

last: Li

summary: We performed single-cell RNA sequencing (scRNA-seq) to determine the relative abundance and transcriptomic profiles of cell subclusters in atherosclerotic aortas from control mice and mice with myeloid-specific Lipa overexpression, both on the Ldlr-/- background and fed a Western diet for 16 weeks.

overall_design: We generated a knock-in (KI) mouse model for Cre-loxP–mediated overexpression of Lipa (NM_001111100) on a C57BL/6 background by targeting the Rosa26 locus. Mice heterozygous for the insertion (LipaKI/WT) were bred to obtain homozygous LipaKI/KI mice. We bred LipaKI/KI, Ldlr-/- mice with LysMCre+/-, Ldlr-/- mice, generating mice on an atherosclerosis-prone Ldlr-/- background to assess the impact of myeloid Lipa overexpression on atherosclerosis. The LysMCre+/-, LipaKI/WT, Ldlr-/- mice (M-LipaKI) demonstrated myeloid-specific Lipa overexpression. LysMCre-/-, LipaKI/WT, Ldlr-/- (Ctrl) littermates were used as controls. Aortas were harvested from Ctrl and M-LipaKI mice fed a Western diet for 16 weeks and subsequently enzymatically digested into single cells. Viable single cells, pooled from three male mice, were subjected to scRNA-seq immediately.

first: Chenyi

last: Xue

first: Hanrui

last: Zhang


title: Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_1]

first: Julien

last: Duc

overall_design: RNA-seq of K562 cell line in WT or ZNF93 KD condition

first: Romain

last: Forey


title: Epigenetic Editing Balances TCR Suppression and Persistence in CAR T cells

city: Dresden

first: Frank

last: Buchholz

address: Tatzberg 47/49

department: UCC / Medical Faculty and University Hospital Carl Gustav Carus

country: Germany

institute: Technische Universität Dresden

summary: Allogeneic chimeric antigen receptor (CAR) T cell therapies offer a scalable, off-the-shelf option for cancer treatment, but their clinical use is limited by the risk of graft-versus-host disease (GvHD), mediated by the endogenous T cell receptor (TCR). Conventional strategies to eliminate TCR expression rely on genome editing tools such as CRISPR/Cas9 or base editing, which introduce permanent DNA changes and pose safety concerns. Here, we present an epigenetic editing approach that enables efficient, specific, and reversible silencing of the CD3ε gene, a critical component of the TCR complex, without altering the genome. Through systematic optimization of the epigenetic editor and guide RNA design, we achieved robust TCR silencing in primary T and CAR T cells while preserving CAR expression, activation, and effector function. Transcriptome analysis confirmed minimal off-target effects. In vivo observation suggest the epigenetically silenced T cells to prevent GvHD while persisting longer than TCR-knockout cells, supporting the notion that transient TCR suppression may help balance safety and long-term efficacy. Our findings establish epigenetic editing as a non-genotoxic alternative to genome editing, offering a flexible and safer route to generate next-generation allogeneic CAR T cells.

overall_design: RNA-seq profiling of human T cells samples from the same donor which were either untreated, mock electroporated, CRISPR/Cas9 TRAC knocked out or CD3E epigenetically silenced

first: Pascal

middle: Y

last: Schönberg

first: Ángela

middle: M

last: Ovalle

first: Haidy

last: Saleh

first: Eugenia

last: Crespo

first: Anja

last: Feldmann


title: The effects of myeloid-specific Lipa overexpression on the transcriptomic profile of aortic plaque macrophages in mice on the Ldlr-/- background and fed a Western diet for 16 weeks

summary: We analyzed the transcriptomic profile of aortic macrophages directly sorted from atherosclerotic aortas of two groups of mice fed a Western diet for 16 weeks: (1) mice with LysMCre-mediated myeliod-specific Lipa overexpression on the Ldlr-/- background; (2) LysMCre-negative littermates on the Ldlr-/- background.

overall_design: We generated a knock-in (KI) mouse model for Cre-loxP–mediated overexpression of Lipa (NM_001111100) on a C57BL/6 background by targeting the Rosa26 locus. Mice heterozygous for the insertion (LipaKI/WT) were bred to obtain homozygous LipaKI/KI mice. We bred LipaKI/KI, Ldlr-/- mice with LysMCre+/-, Ldlr-/- mice, generating mice on an atherosclerosis-prone Ldlr-/- background to assess the impact of myeloid Lipa overexpression on atherosclerosis. The LysMCre+/-, LipaKI/WT, Ldlr-/- mice (M-LipaKI) demonstrated myeloid-specific Lipa overexpression. LysMCre-/-, LipaKI/WT, Ldlr-/- (Ctrl) littermates were used as controls. Whole aortas were harvested from Ctrl and M-LipaKI mice fed a Western diet for 16 weeks and subsequently enzymatically digested into single cells. Viable aortic macrophages (DAPI-CD45+CD11b+CD64+) were sorted and subjected to low-input RNA-seq. n = 4 biological replicates per genotype, with each replicate comprising pooled samples from 2-3 male mice, resulting a total of 10 male mice per genotype.


title: Maternal TDP43 Orchestrates Nuclear Speckle Assembly and Zygotic Splicing Activation During Oocyte-to-embryo Transition in Mouse [RIP-seq]

city: Hangzhou

first: Heng-yu

last: Fan

state: Zhejiang

address: Yuhangtang Road

institute: Life Sciences  Institute

summary: Zygotic splicing activation (ZSA) is an important means for mRNA post-transcriptional regulation during the maternal-to-zygotic transition (MZT) progress, ensuring normal embryonic development. However, the key factors and mechanisms of ZSA regulation are still unclear. Here, we found that nuclear speckle (NS), a key splicing region, is newly established at the 2-cell stage in mice, which is consistent with the period of ZSA. Moreover, NS and TDP43, an important component of paraspeckle, always have a partially adjacent and mutually exclusive localization relationship. TDP43 shuttles from the paraspeckle through liquid-liquid phase separation to perform its function: that is, it acts as a match-maker, binding to the transcribed RNAs on the one hand, and directly binding to the NS proteins on the other hand to ensure the correct assembly of NS. Maternal TDP43 deficiency leads to NS assembly failure in 2-cells, resulting in the inability of transcripts to skip; while injection of excessive TDP43 in zygotes leads to abnormal enlargement of NS in 2-cells, resulting in excessive skipping of transcripts. Both bidirectional ZSA disorders lead to 2-cell arrest in early embryogenesis. The ZSA defect caused by TDP43 deficiency also impairs the cell totipotency-pluripotency conversion. Collectively, our study discovered a NS upstream regulatory factor TDP43, which help maintain the balance of ZSA, providing a new perspective on post-transcriptional regulation of early embryos.

overall_design: Ten embryos per sample were washed in 0.2 BSA in 1X PBS and collected for lysis in 4.2 μl lysis buffer (0.2% Triton X-100, RNase inhibitor, deoxyribonucleotide triphosphate (dNTPs), oligo-dT primers, and 1:1000 ERCC spike-in). Then the samples were reverse transcribed and amplificated using the Smart-seq2 method, as described previously. Sequencing libraries were constructed from 500 pg of amplified cDNA using TruePrep DNA Library Prep Kit V2 for Illumina (Vazyme, TD503). Barcoded libraries were pooled and sequenced on the HiSeq X Ten platform with 150-bp paired-end reads.

first: Zuoqi

last: Deng

first: Zhiyan

last: Jiang

first: Yunwen

last: Wu

first: Hengyu


title: Cancer cells subvert ZNF93 to escape surveillance by L1 epigenetic sentinels and control APOBEC3B [RNA-seq_2]

overall_design: RNA-seq of K562 cell lines overexpressing ZNF93


title: A host-directed adjuvant sensitizes intracellular bacterial persisters to antibiotics

city: Chapel Hill

first: Kuan-Yi

last: Lu

state: NC

address: 125 Mason Farm Road

institute: UNC Chapel Hill

summary: Intracellular bacterial reservoirs contribute to antibiotic treatment failure by fostering metabolically dormant persister cells that are highly tolerant to killing. However, strategies to effectively target intracellular persister cells remain limited. Here, we developed a high-throughput screen to identify compounds that modulate the metabolic activity of intracellular Staphylococcus aureus. The identified compound, KL1, increases intracellular bacterial metabolic activity and sensitizes persister populations of S. aureus to antibiotics, without causing cytotoxicity or bacterial outgrowth. KL1 also exhibits adjuvant activity against intramacrophage Salmonella enterica Typhimurium and Mycobacterium tuberculosis, as well as in murine infection models of S. aureus and S. Typhimurium infection. Transcriptomic analysis and further mechanistic studies reveal that KL1 modulates host immune response genes and suppresses the production of reactive species in host macrophages, alleviating a key inducer of antibiotic tolerance. Our findings highlight the potential to target intracellular persisters by stimulating their metabolism.

overall_design: To interrogate the mechanism of action of the compound KL1, RAW264.7 cells infected with S. aureus strain JE2-Lux at an MOI of 20 were treated with and without 40 uM KL1 for 24 h in triplicate and harvested for RNA-seq. Only the host transcripts were analyzed. The data were processed based on the standard procedure by Azenta Life Sciences.

first: Brian

last: Conlon


title: Transcriptome analysis of gene expression in control and circFUT8 Knockdown MK cultures at day 13.

city: Chongqing

first: Huang

state: Chongqing

address: 10 Changjiang Access Road

department: Department of Blood Transfusion

institute: Daping Hospital, Army Medical University

summary: We have used RNA-seq to explore  gene expression profiles in  control and circFUT8 Knockdown MK cultures at day 13.

overall_design: Three biological replicates for control and circFUT8 Knockdown MKs.


title: Integrated Single-Cell Multiomic Profiling of Caudate Nucleus Suggests Key Mechanisms in Alcohol Use Disorder

city: Indianapolis

first: Yunlong

last: Liu

state: IN

address: 410 West 10th Street, HITS 5001

institute: Indiana University School of Medicine

summary: Alcohol use disorder (AUD) induces complex transcriptional and regulatory changes across multiple brain regions including the caudate nucleus, which remains understudied. Using paired single-nucleus RNA-seq and ATAC-seq on caudate samples from 143 human postmortem brains, including 74 with AUD, we identified 17 distinct cell types. A significant portion of the alcohol-related differences in gene expression were accompanied by a corresponding difference in chromatin accessibility within the gene. We found novel transcriptional differences in medium spiny neurons that impact RNA metabolism and immune response pathways. A small cluster of D1/D2 hybrid neurons showed AUD-induced differences distinct from the D1 and D2 types, suggesting a unique role in AUD. Those with AUD had a higher proportion of microglia in an inflammatory state; astrocytes entered a reactive state partially regulated by JUND. Oligodendrocyte dysregulation was driven in part by OLIG2 activity and increased TGF-β1 signaling from microglia and astrocytes. We also observed increased microglia-astrocyte communication via the IL-1β pathway. These findings provide valuable insights into the genetic and cellular mechanisms in the caudate related to AUD. They also demonstrate the broader utility of large-scale multiomic studies in uncovering complex gene regulation across diverse cell types, which has implications beyond the substance use field.

overall_design: Single-nucleus RNA-seq and single-nucleus multiome (RNA+ATAC-seq) data from caudate tissue of human post-mortem brains, with and without alcohol use disorder. Multiple samples were pooled for sequencing, which were demultiplexed following sequence alignment, and each barcode in the pools were assigned to a sample. Raw data (bam) files include demultiplexed (sample-level) mapped snRNA-seq and snRNA-seq+snATAC-seq sequencing reads. Multiple files per sample indicate that the sample was sequenced multiple times. Processed data (.rds files) consist of Seurat objects for each sequencing pool (one for the RNA-seq assay, and one for the multiome assay), containing read counts for each cell and sample-level metadata. AUD-associated differences in gene expression and chromatin accessibility were investigated by comparing the RNA and ATAC data from individuals with AUD to those without.

first: Nick

last: Green

first: Hongyu

last: Gao

first: Xiaona

last: Chu

first: Quiyue

last: Yuan

first: Patrick

last: McGuire

first: Dongbing

last: Lai

first: Guanglong

first: Xiaoling

last: Xuei

first: Jill

middle: L

last: Reiter

first: Julia

last: Stevens

first: Greg

last: Sutherland

first: Alison

last: Goate

first: Zhiping

last: Pang

first: Paul

last: Slesinger

first: Ronald

last: Hart

first: Jay

last: Tischfield

first: Yue

last: Want

first: Zhana

last: Duren

first: Howard

last: Edenberg


title: Histone H3K27 acetylation mediated by KAT8 maintains antiviral immunity in shrimp trained with inactivated WSSV

city: Qingdao

first: Li-Xia

last: Lv

address: Ao Shanwei 72

institute: Shandong University

summary: The phenomenon of trained immunity, which facilitates vaccine development for disease control, has been identified in shrimp; however, the mechanism remains elusive. In the present study, we found that histone H3K27 acetylation (H3K27ac) mediated by the lysine acetyltransferase KAT8 plays an important role in preventing white spot syndrome virus (WSSV) infection in the shrimp Marsupenaeus japonicus. We then successfully established a model of trained immunity via the use of UV-inactivated WSSV to explore the underlying mechanism(s) in shrimp. In UV-WSSV-trained shrimp, the glycolysis and tricarboxylic acid (TCA) cycle metabolic pathways were enhanced and acetyl-CoA concentrations were increased. As the acetyl group donor, acetyl-CoA promotes KAT8 activity to increase H3K27 acetylation. H3K27ac is deposited at the promoter region of the transcription factor Dorsal to facilitate its expression and then Dorsal promotes the expression of an interferon-like cytokine, Vago5, and antimicrobial peptides that act against WSSV infection. H3K27ac is also deposited at the promoter region of hexokinase 2 and isocitrate dehydrogenase, which positively regulates glycolysis and the TCA cycle in a feedforward manner. Our results reveal a novel mechanism of trained immunity induced by UV-WSSV in shrimp and provide a theoretical basis for the development of antiviral vaccines for disease control in shrimp aquaculture.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP‑seq) for histone modification H3K27ac in hemocytes from UV-WSSV-trained shrimp, PBS-trained shrimp were used as controls


title: Targeting peroxiredoxin 2 prevents hepatocarcinogenesis in metabolic liver disease models

city: Strasbourg

first: Frank

last: Jühling

address: 3 Rue Koeberlé

institute: Université de Strasbourg, Inserm, Institut de Recherche sur Les Maladies Virales et Hépatiques UMR_S1110

summary: Chronic liver disease and hepatocellular carcinoma are a global health burden, causing approximately two million deaths globally per year. Treatment options for advanced liver disease are limited and strategy to prevent hepatocellular carcinoma (HCC) development are lacking. Peroxiredoxin 2 (PRDX2) PRDX2 is a soluble cellular enzyme that detoxify peroxides generated during oxidative stress. This protein is involved in the control of various physiological process including cell growth and differentiation by regulating numerous signaling pathways. PRDX2 was also reported to promote tumor growth including colorectal and breast cancers. Since its role in liver disease progression and HCC development is unknown, we therefore further explored the role of PRDX2. This study aims to understand the mechanistic events of Prdx2 KO on the cell circuits driving metabolic liver disease progression and HCC development. We induced a liver-specific Prdx2 KO in a Cas9 transgenic mouse model for NASH and HCC. Prdx2 gene was specifically targeted in hepatocytes by combining a Cre-dependent expression of the Cas9 endonuclease in the liver and the hepatic delivery of specific single guide (sg) RNA to hepatocytes using Adeno-associated virus 8 (AAV8) as vector. Chronic liver disease and HCC were thereafter induced by a single dose of diethylnitrosamine (DEN), followed by a 6-month choline-deficient L-amino acid-defined high-fat diet (CDAHFD). At the time of sacrifice, animals were anesthetized, weighted and a terminal blood collection was performed by cardiac puncture. Total RNA from mice liver were obtained using Tri Reagent (MRC) and Direct-zol RNA Miniprep kit (Zymo Research).

overall_design: Three biological replicates per mice group (sgCTRL, sgPrdx2). mRNA was isolated individually from each replicate. Three biological replicates from each mice group were sequenced and analyzed.

first: Emilie

last: Crouchet

first: Eugénie

last: Schaeffer

first: Laurent

last: Mailly


title: Profibrotic monocyte-derived alveolar macrophages as a biomarker and therapeutic target in systemic sclerosis-associated interstitial lung disease [Northwestern]

status: Public on Jul 31 2025

city: Chicago

first: Alexander

middle: V

last: Misharin

state: Illinois

address: 303 E Superior St

department: Pulmonary and Critical Care

institute: Northwestern University

summary: Interstitial lung disease (ILD) is present in over 60% of patients with systemic sclerosis (SSc) and is the leading cause of SSc-related deaths. Profibrotic monocyte-derived alveolar macrophages (MoAM) play a causal role in the pathogenesis of pulmonary fibrosis in animal models where their persistence in the niche requires signaling through the Colony Stimulating Factor 1 Receptor (CSF1R). We hypothesized that the presence and proportion of MoAM in bronchoalveolar lavage (BAL) fluid from patients with SSc-ILD may be a biomarker of ILD severity. To test this hypothesis, we performed BAL in 9 prospectively enrolled patients with SSc-ILD on imaging and 13 healthy controls and analyzed the cellular fraction using flow cytometry and single-cell RNA sequencing. Compared to healthy controls, patients with SSc-ILD showed increased abundance of MoAM and interstitial macrophages in BAL fluid that was associated with worse lung function and lung disease on imaging. We identified changes in the MoAM transcriptome as a function of treatment with mycophenolate, an effective therapy for SSc-ILD.

overall_design:
Bronchoalveolar lavage (BAL) fluid from 10 patients 5 heathy volunteers was obtained at the bronchoscopy suite of Northwestern Memorial Hospital or Yale New Haven Hospital.l. Single cell RNA-seq libraries were prepared with 10x 3' gene expression kit. Libraries were sequenced on Illumina NovaSeq 6000. Gene expression matrices were generated with 10x Cell Ranger v3.1.0 (exon-only mode) software and reads were mapped to GRCh38.84 reference genome (10x Genomics Cell Ranger Human 1.2.0 GRCh38 reference).

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Protected Health Information: fastq files have been omitted.
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first: Nikolay

middle: S

last: Markov

first: Anthony

last: Esposito

first: Maxwell

last: Schleck

first: Radmila

last: Nafikova

first: Zhan

last: Yu

first: Ziyan

last: Lu

first: Monique

middle: E

last: Hinchcliff


title: Maternal TDP43 Orchestrates Nuclear Speckle Assembly and Zygotic Splicing Activation During Oocyte-to-embryo Transition in Mouse [RNA-seq]

first: Heng-yu

last: Fan

first: Zuoqi

last: Deng

first: Yuke

last: Wu

first: Yunwen

first: Hengyu