title: Transcriptomic alterations induced by low-intensity ultrasound (LIUS) in non-small cell lung carcinoma (NSCLC) cell lines.

city: Zhunan Miaoli County

first: Chia

middle: Huei

last: Lee

address: 35, Keyan Rd.

department: National Institute of Cancer Research

country: Taiwan

institute: Taiwan National Health Research Institute

summary: Ultrasound therapy has emerged as a promising, non-invasive modality for cancer treatment, although its underlying mechanisms remain incompletely understood. Immunoblotting analysis revealed that low-intensity ultrasound (LIUS) alters global levels of histone modifications, including monoubiquitinated H2B (H2Bub1), H3K4me3, and H3K27me3, in NSCLC A549 and H1299 cell lines. Given the pivotal role of histone marks in transcriptional regulation, we further investigated the effect of LIUS on transcriptional control in A549 and H1299 cells.

overall_design: Total RNA was extracted from A549 or H1299 cells 48 hours after LIUS (T2) treatment, with the corresponding untreated cells serving as controls.

first: Chia-Huei

first: Pin-Feng

last: Hung

first: Gin-Shin

last: Chen

first: Bikash

last: Mallick


title: BMP–Smad1/9 signaling plays a critical role in regulating zebrafish PGC proliferation

status: Public on Feb 25 2026

city: Beijing

first: Tao

last: Zheng

state: Beijing

address: Medical Building, Tsinghua University

country: China

institute: Tsinghua University

type: Expression profiling by high throughput sequencing

summary: The specification and maintenance of germ cell lineage are vital for reproductive development and heredity. The germ cell fate in some species, such as zebrafish and Xenopus, is determined by maternally supplied germ plasm, whereas in mammals it is induced by bone morphogenetic protein (BMP) signaling after implantation. It remains elusive whether BMP signaling is implicated in zebrafish germ cell development. Here, we demonstrate that, in zebrafish, BMP–Smad1/9 signaling is required for primordial germ cell (PGC) maintenance but not for PGC fate determination or migration. BMP inhibitor treatment or whole-embryo smad1/9 knockdown reduces the number of PGCs. To investigate cell-autonomous roles of BMP–Smad1/9 in PGCs, we generated PGC-specific smad1/9 knockouts using a double-transgenic approach with PGC-specific expression of Cas9 and ubiquitous expression of guide RNAs (gRNAs). Loss of Smad1/9 in PGCs leads to impaired PGC proliferation and increased apoptosis, resulting in reduced PGC numbers and adult sex bias. Moreover, transcriptome analysis of smad1-deficient PGCs revealed no significant changes in the expression of PGC-specific genes, but a marked upregulation of genes involved in cell cycle checkpoints and DNA damage repair. Notably, ectopic ATR–pChk1 activation in smad1-cKO PGCs validates cell cycle defects and DNA replication stress. ATR inhibition restores PGC numbers in mutant embryos. Collectively, these findings underscore a critical role of BMP–Smad1/9 signaling in zebrafish PGC population maintenance, while it is dispensable for PGC fate determination and migration.

overall_design: PGCs were sorted from control and germline-specific smad1 knockout (smad1-cKO) zebrafish embryos at the 75%-epiboly stage and 1 day post-fertilization (1 dpf) for transcriptome analysis. Additionally, PGCs were collected from smad1 morphants (smad1-KD) and control morpholino-injected embryos (control MO). PGCs and somatic cells were sorted from control and germline-specific smad1 knockout (smad1-cKO) zebrafish embryos at the 15-somite stage for targeted amplicon sequencing.

first: Xiaotong

last: Wu


title: A bacterial CARD-NLR immune system controls the release of gene transfer agents [RNA-Seq]

city: Norwich

first: Tung

last: Le

address: Colney Lane

department: Molecular Microbiology

country: United Kingdom

institute: John Innes Centre

summary: Bacteria have evolved a wide array of immune systems to detect and defend against external threats including mobile genetic elements (MGEs) such as bacteriophages, plasmids, and transposons. MGEs are often selfish, exploiting their bacterial hosts to propagate, however they can also provide adaptive advantages through horizontal gene transfer. Gene transfer agents (GTAs), which are non-infectious domesticated prophages, represent a unique class of beneficial MGEs that facilitate bacterial gene transfer. Despite their domestication, GTAs retain phage-like features, including the requirement for host cell lysis to release particles, that may inadvertently trigger host immunity. How GTAs might avoid, subvert, or possibly adopt host immune systems to complete their life stages is poorly understood. Here, we identify a tripartite system, LypABC, that is essential for GTA-mediated cell lysis in Caulobacter crescentus. LypABC resembles caspase recruitment domain-nucleotide-binding leucine-rich repeat (CARD-NLR) anti-phage defence systems that mediate abortive infection wherein infected cells die to prevent phage proliferation, thereby protecting the overall bacterial population. LypABC-deficient cells produce host DNA-packed GTA particles and eventually die but cannot lyse to release GTA particles. Moreover, overproduction of LypABC is highly toxic to both GTA-producing and non-producing cells, highlighting the need for strict regulation. We find that such regulation is achieved transcriptionally by a repressor, CdxB, which binds the promoters of lypABC and of essential GTA activator genes, thus coupling GTA activation and host cell lysis. While traditionally considered antagonistic towards MGEs, our findings here suggest that immunity components are versatile and can be adapted to support MGEs.

overall_design: RNA-seq profiling of stationary-phase Caulobacter crescentus cells. Four different strains were assayed in biological triplicate. 1: wildtype (WT), 2: delta cdxB, 3: delta rogA + delta GTA, and 4: delta cdxB + delta rogA + delta GTA

first: Emma

last: Banks


title: Genetically engineered mouse models and syngeneic graft models of bladder cancer

city: Madrid

first: Cristian

last: Suarez Cabrera

state: Madrid

address: Av. Complutense 40

country: Spain

institute: CIEMAT

summary: We have generated various genetically engineered mouse models (GEMMs) of advanced bladder that recapitulate various morphological variants of human tumors, with distinct histological characteristics, differing onset times or growth rates, and varying incidences of dissemination. To investigate the molecular pathways underlying these features, we performed a transcriptomic analysis of these models in comparison with control urothelium. Given that concurrent TP53 and RB1 alterations are frequently observed in human tumors and are associated with specific molecular subtypes and increased aggressiveness, this study aimed to develop and characterize new models comparing the combined loss of Pten, Trp53, and Rb1 (in an Rbl1-null background, due to functional compensation of Rb1 loss in mouse tissues) with the loss of Pten and Trp53 alone, where the retinoblastoma (Rb) family remains intact.  In both models, basal urothelial cells were targeted using adenoviruses expressing Cre unther de control of the Krt5 promoter (Ad5-Krt5-Cre), while luminal urothelial cells were targeted using the murine Krt20 promoter (Ad5-Krt20-Cre).  Despite the advantages offered by these GEMMs, their limitations—including unpredictable tumor onset, long latency periods, and difficulties in early tumor detection—led us to develop immunocompetent heterotopic models using tumor cell lines derived from primary tumors arising in GEMMs. These models enable more accurate tumor monitoring and synchronized growth, thereby improving the robustness of preclinical studies.

overall_design: Gene expression was compared among bladder tumors generated in conditional Quadruple Knock-Out (QKO; Ptenflox/flox, Trp53flox/flox, Rb1flox/flox, Rbl1-/-) and Double Knock-Out (DKO; Ptenflox/flox, Trp53flox/flox) mice, as well as control urothelium and syngeneic graft tumors derived from the genetically engineered mouse models. This transcriptomic study included 5 bladder tumor samples from DKO mice injected with Ad5-Krt5-Cre (DKO-K5), 5 samples from DKO-K20, 5 samples from QKO-K5, and 5 samples from QKO-K20. Additionally, 5 samples of control urothelium from both DKO and QKO mice were included. Finally, 3 tumor samples from syngeneic grafts generated by injecting 4K5 cells into DKO mice and 3 samples from syngeneic grafts generated by injecting K5.6 cells into QKO mice were also included.

first: Ester

last: Munera-Maravilla

first: Mercedes

last: Pérez-Escavy

first: Carolina

last: Rubio

first: Cristina

last: Segovia

first: Iris

last: Lodewijk

first: Sandra

middle: P

last: Nunes

first: Álvaro

last: Martín de Bernardo

first: Ignacio

middle: A

last: Reina

first: Esther

last: Montesinos

first: Lucía

last: Morales

first: Victor

middle: G

last: Martínez

first: Mónica

last: Martínez-Fernández

first: Marta

last: Dueñas

first: Jesús

middle: M

last: Paramio

last: Suárez-Cabrera


title: Transcriptomic analysis of the midbrain in A53T alpha-synuclein transgenic mice and Myriocin-treated model

city: Gwangju

first: Eunkyung

last: Lee

address: 123 Cheomdan-gwagiro, Buk-gu

country: South Korea

institute: Gwangju Institute of Science and Technology

summary: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of α-synuclein aggregates, yet no disease-modifying therapies currently exist. Ceramide metabolism is increasingly implicated in protein aggregation and mitochondrial dysfunction, both of which are prevalent in neurodegenerative disorders. While prior studies using cell lines have hinted at ceramide's role in PD, the in vivo relevance and therapeutic efficacy of inhibiting its synthesis remained largely unexplored. We aimed to evaluate the therapeutic potential of inhibiting ceramide synthesis in various models of PD, including the A53T α-synuclein transgenic mouse model, primary neurons from patients with PD, and patient-derived midbrain organoids. We found that inhibiting de novo ceramide biosynthesis decreases α-synuclein aggregation and improves motor and cognitive function in A53T α-synuclein transgenic mice, a well-established PD model. Treatment with myriocin, a serine palmitoyltransferase inhibitor, restored mitochondrial morphology, enhanced mitophagy, and reduced neuroinflammation. Single-nucleus transcriptomic analysis revealed that myriocin normalized gene networks related to synaptic transmission, mitochondrial homeostasis, and inflammation. Additionally, human midbrain organoids derived from PD patient-induced pluripotent stem cells exhibited reduced α-synuclein aggregation and preserved dopaminergic neurons following myriocin treatment. Together, these results suggest that targeting ceramide synthesis is a promising strategy for addressing protein aggregation and neuronal death in PD.

overall_design: This study investigates transcriptomic changes in the midbrain of homozygous A53T alpha-synuclein transgenic mice (JAX#004479, M83 line), Myriocin-treated transgenic mice, and their wildtype littermate controls (B6C3F1/J). Total RNA sequencing was performed on midbrain tissue isolated from each group. This dataset provides insights into the molecular effects of Myriocin treatment in a Parkinson's disease mouse model.

first: Moon-young

last: Park

first: Minkuk

first: Na-Yeong

last: Kim

first: Shibo

last: Wei

first: Nahee

last: Hwang

first: Dongryeol

last: Ryu

first: Dohyun

first: Gakyung

first: Chang-Myung

last: Oh


title: BiTE® Molecule vs. CAR-T targeting FLT3 in AML: How Positive Co-Stimulation Tips the Scale

city: Munich

first: Lisa

last: Rohrbacher

address: Marchioninistraße 15

department: MED III

country: Germany

institute: LMU University Hospital

summary: T-cell-based immunotherapies have revolutionized treatment paradigms in B-cell malignancies, yet their translation to acute myeloid leukemia (AML) has been hindered by a scarcity of tumor-restricted antigens and the risk of on-target off-leukemia toxicity. FLT3 has emerged as a promising therapeutic target with limited expression in healthy hematopoietic tissues. Here, we perform a head-to-head preclinical comparison of a FLT3-directed bispecific T-cell engager (BiTE® molecule) and second-generation FLT3-specific chimeric antigen receptor (CAR) T cells. Both approaches induced potent cytotoxicity against AML cell lines and primary patient-derived blasts while sparing healthy hematopoietic stem and progenitor cells. Despite similar short-term efficacy, prolonged antigen exposure demonstrated progressive functional decline and metabolic exhaustion; however, CAR T cells maintained cytotoxic capacity and proliferative potential over time. In AML xenograft models, CAR T cells achieved superior tumor control, prolonged survival, and greater T-cell infiltration than BiTE® molecule-treated counterparts. Transcriptomic profiling of T cells recovered from bone marrow further revealed a distinct exhaustion-associated gene signature in BiTE®-redirected T cells. Importantly, provision of CD86-mediated co-stimulation significantly enhanced the antitumor activity of BiTE®-redirected T cells in vitro and in vivo. These findings establish FLT3 as a viable and selective immunotherapeutic target in AML and underscore the functional and transcriptional differences between BiTE® molecule-redirected T cells and CAR T cells. Moreover, they reveal the critical role of co-stimulatory signaling in sustaining the efficacy of T-cell-based therapies in vivo, offering a rational path for improving T-cell redirection strategies in myeloid malignancies.

overall_design: RNA bulk sequecing profile of human BiTE or CART-redirected T cells after a 18 day in vivo AML xenograft model

first: Marion

last: Subklewe


title: A bacterial CARD-NLR immune system controls the release of gene transfer agents [ChIP-Seq]

first: Tung

last: Le

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: ChIP seq experiment to determine binding sites of CdxB protein on the Caulobacter crescentus genome. CdxB-flag tagged alleles were constructed in either delta cdxB or delta cdxB + delta rogA backgrounds. Non-tagged alleles were included as negative controls. Two biological replicates were carried out per strain. Anti-FLAG agarose beads were used for the ChIP experiment.

first: Emma

last: Banks


title: Physical Crowding in 3D Niche Regulates NSCs of Cell Junction and Differentiation

city: Changsha

first: Chaoyong

last: He

address: Tianma road

institute: Hunan university

summary: Neural stem cells (NSCs) maintain central nervous system (CNS) homeostasis through self-renewal and differentiation into neurons and glia. While physical crowding dynamically regulates NSCs niches during CNS development, yet its role in regulating NSCs fate remains unclear. Herein, we systematically investigated how NSCs crowding influences intercellular junction formation and differentiation in 2D and 3D niches. Using RNA sequencing, RT-qPCR, Western blotting, and immunofluorescence, we found that cell crowding promotes neuron differentiation in both systems. Notably, in 3D cultures, crowding robustly upregulated cell-cell junction genes and enhanced junction-mediated communication. These findings reveal that the 3D environment provides essential biophysical contexts for NSCs, in which cell crowding synergistically enhances differentiation through coordinated cell-cell and cell-ECM signaling. This study offers new insights into the role of physical niche cues in NSCs biology and provides valuable guidance for the design of biomimetic 3D culture platforms and regenerative strategies for neural tissue engineering.

overall_design: NSCs were isolated from cerebral cortices of 1–day-old neonatal Sprague-Dawley rats. After tissue pieces of dissociation, the mixed cortical cells were first passed through a 100 μm mesh of nylon cell strainer, then plated into tissue culture flasks. RNA-seq library preparation. Total RNA was isolated from each sample using the RNAmini kit (Qiagen, Germany). RNA quality was examined by gel electrophoresis and with Qubit (Thermo, Waltham, MA, USA). Strand-specific libraries were constructed using the TruSeq RNA sample preparation kit (Illumina, San Diego, CA, USA), through reverse transcription using S1000TM Touch Thermal Cycler (Bio Rad) at 53°C (45 min) - 85°C (5 min) - 4°C cycle. The generated cDNA was amplified, and quality estimated using Agilent 4200 (performed by CapitalBio Technology, Beijing). The sequences of libraries were finally obtained using the Illumina Novaseq6000 sequencer with pair-end 150 bp (PE150).

first: Yuyun

last: Liang

first: Xiaonan

last: Wang

first: Zhiyan

last: Wu

first: Jing

last: Yang

first: Ziyan

last: Chen

first: Hexu

last: Zhang

first: Cheng

last: Zhao

first: Liyang

last: Shi


title: Leveraging single cell multiomic analyses to identify gene regulatory networks that drive human articular cartilage cell fate

city: Boston

first: Andrew

middle: Bruce

last: Lassar

state: MA

address: 240 Longwood Ave.

department: Biological Chemistry and Molecular Pharmacology

country: USA

institute: Harvard Medical School

summary: Cartilage plays a crucial role in skeletal development and function, and abnormal development contributes to genetic and age-related skeletal disease. Compromises to the integrity of joint-lining articular cartilage in particular lead to debilitating chronic degenerative diseases including osteoarthritis.  To better understand how human articular cartilage develops in vivo, we jointly profiled the transcriptome and open chromatin regions in individual nuclei recovered from distal femurs at 2 fetal timepoints. We used these multiomic data to predict transcription factor-based regulatory networks that are important for articular chondrocyte differentiation.  We developed a human pluripotent stem cell platform for interrogating the function of predicted transcription factors during chondrocyte differentiation and identified new biological roles for CREB5. We have identified genes whose expression is regulated by over-expression of CREB5 in either human iPS-derived cartilage or in bovine deep zone articular chondrocytes.

overall_design: We have identified genes expressed in bovine deep zone articular chondrocytes whose expression was altered following forced overexpression of the transcription factor, CREB5. We performed RNA-Seq analysis of bovine deep zone articular chondrocytes that had been infected with lentivirus programmed to express doxycycline-inducible bovine CREB5 lentivirus. We cultured the infected deep zone articular chondrocytes for three days with TGFb2 (20 ng/ml) and TGFa (100 ng/ml) either in the absence (DZCiCreb5-L, Dox-) or in the presence (DZCiCreb5-L, Dox+) of doxycycline (1mg/ml)

first: Divya

last: Venkatasubramanian

first: Sarah

middle: K

last: Jachim

middle: S

last: Zhu

first: Gayani

last: Senevirathne

first: Concetta

last: Vitale

first: Delmy

middle: L

last: Melendez

first: Cheng-Hai

middle: B

first: Terence

middle: D

last: Capellini

first: April

last: Craft


title: A bacterial CARD-NLR immune system controls the release of gene transfer agents [Tn-Seq]

first: Tung

last: Le

overall_design: Tn-seq experiment to compare wildtype and delta rogA strains of Caulobacter crescentus in biological triplicate.

first: Emma

last: Banks


title: BALF gene expression profiling reveals innate immune activation bias in persistent post-COVID-19 ILD

city: Athens

first: Vasilis

last: Aidinis

state: Vari

address: Fleming 34

country: Greece

institute: Institute for Fundamental Biomedical Research, BSRC Alexander Fleming

summary: Survivors of COVID-19 can experience long-term lung complications (pulmonary sequelae), but the underlying mechanisms remain unclear. While most patients with major COVID-19 lung injury eventually recover essentially completely, some experience significant residual damage.   To investigate the underlying differences, we analyzed, using bronchoalveolar lavage fluid (BALF), the alveolar immune cell compartments of a group of patients with post-COVID-19 interstitial lung disease (ILD) six months after acute COVID-19. Patients were categorized into two groups, based on High-Resolution Computed Tomography (HRCT) evaluation a year later: those with persistent HRCT abnormalities compatible with fibrosis (persistent post-COVID-19 ILD, n=6) and those with resolved lung lesions (resolved post-COVID-19 ILD, n=13). Additionally, 6 patients with pre-existing ILD were included in the study, after recovery from COVID-19.  Bulk RNA transcriptomics analyses of BALF cells revealed pathways of neutrophil and monocyte chemotaxis to be enriched in patients with persistent HRCT abnormalities, consistent with increased monocyte-like cell recruitment in the lungs. Furthermore, increased gene expression of markers of pro-fibrotic macrophages/monocytes, such as SPP1 and pro-inflammatory cytokines, such as Il-1b, was also observed. Conversely, patients with resolved post-COVID-19 ILD displayed BALF cell gene expression signatures indicative of T-cell activation. Additionally, BALF gene expression patterns associated with pro-fibrotic macrophage activation, neutrophil chemotaxis and downregulation of T-cell activation were also observed in patients with pre-existing fibrotic ILD following COVID-19.   These findings suggest that immune response imbalance leading to prolonged activation of innate immunity and subdued adaptive immune responses may be associated with persistent post-COVID-19 ILD.

overall_design: We analysed the BALF cells from patients with residual lung abnormalities on average 6 months post severe COVID-19 that were categorized into two groups, based on High-Resolution Computed Tomography (HRCT) evaluation a year later: those with persistent HRCT abnormalities compatible with fibrosis (persistent post-COVID-19 ILD, n=6) and those with resolved lung lesions (resolved post-COVID-19 ILD, n=13). Additionally, 6 patients with pre-existing ILD were included in the study, after recovery from COVID-19.

first: Katerina

last: Antoniou

first: Eliza

last: Tsitoura

first: Eirini

last: Vasarmidi


title: RNAseq of Mineralocorticoid Receptor (MR) overexpression in UVB-induced ocular rosacea model on meibomian glands of rats

city: Paris

first: Linxin

state: Paris

address: 15 Rue de l'École de Médecine, Centre de Cordeliers

department: Centre de la recherche des corderliers

country: France

institute: INSERM

summary: The aim of this study was to analyse the transcriptional regulation of UVB-induced ocular rosacea model on the meibomian glands of rats that overexpress the human NRC32 gene coding for mineralocorticoid receptor (P1.hMR) and age- and sex- matched wild type (WT) littlemates. 10-12 weeks old female Wild-Type (WT) and P1.hMR rats were subjected to 5-days UVB irrdiation on eyelids (UVB_WT: n = 3, UVB_P1.hMR: n = 5), together with age- and sex- matched rats without UVB-induced model (Control_WT: n = 4, Control_P1.hMR: n = 5), they were euthanized and the meibomian glands were dissected for RNA-sequencing. Total RNA samples were sequenced at the iGenSeq transcriptomic platform of the Brain and Spine Institute (ICM, Paris, France). RNA quality was checked by capillary electrophoresis and RNA integrity numbers (RIN) ranging from 8.8 to 9.3 was accepted for library generation. Quality of raw data was assessed using FastQC. Poor quality sequences and adapters were trimmed or removed with fastp, using default parameters, to retain only good quality paired reads. Illumina DRAGEN bio-IT Plateform (v3.8.4) was used for mapping on rn7 reference genome. Library orientation, library composition and coverage along transcripts were checked with Picard tools. Differential analysis has been also conducted with DESeq2. Multiple hypothesis adjusted p-values were calculated with the Benjamini-Hochberg procedure to control FDR. FDR threshold was set at 0.05, log2 fold-change threshold was set at 0.5. We identified genes differentially regulated in UVB-treated WT as compared to Control WT, and genes differentially regulated in UVB-treated P1.hMR rats as compared to Control P1.hMR.

overall_design: UVB-induced gene regulation on meibomian glands mRNA profiles of rats that overexpressed the human NR3C2 gene coding for mineralocorticoid receptor.

last: ZHU

first: Min

last: ZHAO

first: Francine

last: Behar-Cohen


title: IL-36 family cytokines mediate immune activation in Sjogren’s disease and may represent a novel biomarker of disease

city: Buffalo

first: Jill

last: Kramer

state: NY

address: 3435 Main St

institute: SUNY at Buffalo

summary: The primary goal was to sorted-purify cLN B cells from female NOD.B10 mice at the clinical disease stage and age and sex-matched BL/10 controls to detemine if IL-1 signaling is dysregulated in SD mice.

overall_design: Bulk RNA-sequencing was performed on cLN

first: Rose-Anne

last: Romano


title: Cellular NAD+ availability constrains developmental speed in the Drosophila eye

first: Francois

last: SCHWEISGUTH

address: 25 rue du Dr Roux

institute: CNRS - Institut Pasteur

summary: The cellular and biochemical processes that limit the rates at which embryos develop, tissues form, and cells differentiate remain largely unknown. Using the speed of progression of a differentiation front in the developing eye of Drosophila as a proxy for developmental speed, we identified genetic perturbations that slowed down the progression of this front. We found that inhibition of the Electron Transport Chain (ETC), and more generally of energy production in mitochondria, reduced developmental speed, led to increased NADH/ NAD+ ratio but did not change ATP levels due to a compensatory increase in glycolysis. Using targeted perturbations, we further showed that the metabolic state of cells located at and ahead of the differentiation front determined the speed of this front. Additionally, increasing the rate of regeneration of the NAD+ pool suppressed the defects resulting from the inhibition of the ETC whereas inhibition of the NAD+ salvage pathway led to reduced developmental speed. Thus, developmental speed appeared to be limited by the demand for NAD+, at least upon reduced energy supply.

overall_design: A mirr-Gal4 driver was used to direct gene-based perturbation in the eye imaginal disc. Here, brain complexes from control OreR larvae were compared with those from mirr-Gal4 UAS-ND-42RNAi (BL-28894) larvae (grown at 25°C).

first: Nisha

last: Veits

first: Yuting

last: Guo

first: Jingjing

last: He

first: Yan

last: Yan

last: Schweisguth


title: Acute testicular hyperthermia leads to a rapid loss of global piRNA levels and a consequent increase in transcript abundance, including LINE1 activity within heat-sensitive male germ cells

city: Callahagn

first: benjamin

last: Robinson

state: NSW

address: University Drive

department: School of Biomedical Science and Pharmacy

country: Australia

institute: University of Newcastle

summary: Spermatogenesis is a highly temperature sensitive process, occurring 2-8°C lower than core body temperature. Testicular hyperthermia rapidly affects male precursor germ cells including spermatocytes and spermatids. To understand the immediate transcriptional response, we gave mice testicular heat stress and isolated round spermatids. Using next-generation RNA sequencing we found 134 differentially expressed transcripts, 93% of which were upregulated. In addition, testicular hyperthermia induced 395 differential splicing events and altered the usage of 61 polyadenylation sites. To explain these observations and understand why transcript abundance appears to favour upregulation following testicular hyperthermia, we assessed global piRNA levels and found an overall, rapid reduction. Concomitantly, we observed an increase in transposable element RNA (LINE1) and protein (ORF1p) abundance. Furthermore, increased LINE1 expression appeared to be correlated with DNA damage in the male germline. At 24 hours post heat stress, piRNA levels recovered close to control levels, coincident with a significant reduction in LINE1 transcript expression within spermatocytes. These findings suggest that piRNA-mediated transposon suppression is a critical mechanism underlying the temperature sensitivity of spermatogenesis and may be one of the reasons why the testis require lower temperatures.

overall_design: Adult male CD1 mice were subject to In vivo testicular heat stress (heat group; 30 minutes at 42°C N=5, control group; 30 minutes at 33 °C N=5. RNA was extracted from isolated round spermatids and Illumina NocaSeq 150bp paired end total transcriptome RNA sequencing performed.

first: Benjamin

middle: R

first: Jacob

last: Netherton

first: Sean

last: Burnard

first: Mark

last: Baker


title: Single-Cell Transcriptomics of Multi-Site Cell Therapy in Osteoarthritis: Tissue-Specific Traits and Treatment Correlations [Full Trial]

city: Atlanta

first: Krishnendu

last: Roy

state: Georgia

address: 345 ferst drive NW, marcus nanotechnology building, room no 3102B, 3rd floor

department: IBB

institute: Georgia tech

summary: Knee-Osteoarthritis (Knee-OA) is a prevalent joint disorder lacking FDA-approved cell-therapies to halt its progression. This study uses single-cell RNA sequencing to analyze bone marrow aspirate concentrate (BMAC) and stromal vascular fraction (SVF) samples in a clinical trial of autologous cell therapies. Trial site-specific variability was significant in BMAC, necessitating tailored normalization, whereas SVF was less affected, likely due to uniform subcutaneous fat sampling. Variance partitioning and tensor decomposition identified site effects in BMAC but revealed shared pathways across cell types in both tissues. Differential gene expression (DEG) analysis between responders and non-responders yielded no significant findings, though likelihood ratio testing (LRT) revealed enrichment for DEG patterns linked to disease severity, potentially masked by patient heterogeneity. Key BMAC pathways included oxidative phosphorylation, unfolded protein response, and TNFα signaling. Cell-cell communication analysis suggested enhanced HLA signaling in non-responder MSCs, consistent with inflammation, while responders showed more coordinated immune interactions. BMAC-MSCs promoted chondrocyte proliferation, whereas SVF-MSCs emphasized immune regulation. Variability in therapy outcomes reflects patient heterogeneity beyond genomic factors, complicating the immediate use of genomic profiling to guide treatment. Nonetheless, as molecular pathways are better understood, integrating genomic insights into personalized strategies may become feasible.

overall_design: scRNAseq data generation and analysis to find knee-OA-related changes in patient bone marrow and adipose tissue derived cells.

first: Paramita

last: Chatterjee

first: Hazel

last: Stevens

first: Linda

last: Kippner

first: Greg

last: Gibson

first: Krish


title: Ferroptosis Induction by DGAT1 Inhibition Enhances Cancer Immunotherapy

first: yanyan

last: zhu

address: 10 Xitoutiao, Youanmen Wai, Fengtai District

institute: Chinese Institutes for Medical Research, Beijing

summary: Ferroptosis, a form of regulated cell death driven by lipid peroxidation, has emerged as a promising mechanism in cancer therapy. However, the lack of clinically viable ferroptosis inducers has precluded its therapeutic evaluation in patients. Here, we demonstrate that inhibition of diacylglycerol O-acyltransferase 1 (DGAT1) induces a ferroptosis-like phenotype in cancer cells and enhances the efficacy of immune checkpoint blockade (ICB) therapy. In human cancer cohorts, low DGAT1 expression correlated with improved prognosis and elevated ferroptosis-associated gene signatures. In murine models, both genetic knockout and pharmacological inhibition of DGAT1 enhanced ICB therapy efficacy by promoting increased infiltration of cytotoxic T lymphocytes (CTLs). Mechanistically, DGAT1 inhibition reduced lipid droplet (LD) accumulation, triggering elevated lipid peroxidation, mitochondrial dysfunction, and reactive oxygen species (ROS) production. These events culminated in glutathione peroxidase 4 (GPX4) depletion and ferroptosis. Given the availability of clinical-stage DGAT1 inhibitors, our findings provide a strong rationale for repurposing these agents as ferroptosis inducers to enhance cancer immunotherapy.

overall_design: To investigate the mechanisms underlying the enhanced antitumor effects of DGAT1 deficiency in combination with immune checkpoint blockade (ICB) therapy, we examined the tumor immune microenvironment (TIME) in DGAT1-deficient tumors. CD45⁺ immune cells were isolated from subcutaneously implanted control and DGAT1-knockout (KO) B16F10 tumors and subjected to single-cell RNA sequencing (scRNA-seq).


title: HIF-1α+ CD4 T cells coordinate a tissue resident immune cell network in the lung [scRNA-seq]

city: Basel

first: Carolyn

last: King

address: Hebelstrasse 28

department: Department of Biomedicine

country: Switzerland

institute: University of Basel

summary: Pulmonary infection leads to the development of CD4+ T resident helper (TRH) cells in the lung. TRH cells generated after influenza infection support local humoral responses and exhibit differentiation plasticity following infectious challenge. A subset of TRH cells is enriched for expression of the transcription factor HIF-1α which has unknown function in the lung. Here we find that inducible deletion of HIF-1α in CD4 T cells leads to decreased numbers of CXCR6+ tissue resident T cells with minimal impact on peripheral lymphoid responses. At the same time, HIF-1α deletion impairs the replenishment of tissue resident macrophages and NK cells, as well as influenza specific IgA titers. These seemingly disparate responses converge upon a requirement for IL-21 produced by HIF-1α+ CD4 T cells. A similar HIF-1α dependent network is engaged in a lung adenocarcinoma model, highlighting novel roles for HIF-1α+ CD4 T cells in coordinating protective immunity during infection and cancer.

overall_design: Following influenza infection control (Hif1a wt/wt CD4 ert2 ki wt ROSA ki wt) and Hif1a KO mice (Hif1a fl/fl CD4 ert2 ki wt ROSA ki wt) were treated with tamoxifen to delete Hif1a in CD4 T cells.  Individual mice were hashtagged, and CD45+ cells were sorted from lungs at d45 p.i. and submitted for library preparation.


title: Docosahexaenoic Acid Protects the Lungs from Ozone-Induce Inflammation Via its Oxylipins

city: Columbus

first: Michael

middle: J

last: Yaeger

state: OH

address: 473 W 12th Ave

institute: The Ohio State University

summary: Ozone (O3) is an air pollutant that induces pulmonary inflammation and injury, leading to increased susceptibility and exacerbation of chronic lung diseases. Furthermore, ambient O3 levels are expected to rise with increasing global temperatures. Docosahexaenoic acid (DHA) is an omega-3 (n-3) polyunsaturated fatty acid (PUFA) primarily found in oily fish that reduces inflammation and enhances the resolution of inflammation. This is partially attributed to DHA-derived oxylipins termed specialized pro-resolving mediators (SPMs) that have anti-inflammatory/pro-resolving properties. However, whether dietary DHA protects the lungs from O3-induced inflammation and injury is unclear. We hypothesized that dietary DHA supplementation increases pulmonary SPMs and thereby decreases O3-induced pulmonary inflammation. To test this, C57BL/6J mice were fed control diet or DHA-enriched diet (2% kcal from DHA) for 6 weeks, exposed to filtered air (FA) or 1 ppm O3 for 3h (comparable to an O3 Action Day for humans), and necropsied 24h or 48h following exposure. DHA supplementation reduced airspace neutrophilia, decreased cytokine production, and promoted transcriptomic signatures for leukocyte chemotaxis and fatty acid oxidation. Furthermore, dietary DHA increased pulmonary DHA and its oxylipins while decreasing pro-inflammatory n-6 PUFAs and their oxylipins. Oropharyngeal aspiration of DHA-oxylipins 14-HDHA or maresin 1 (MaR1) decreased O3-induced airspace neutrophilia and reduced bone marrow-derived macrophage production of neutrophil chemokines Cxcl1 and Cxcl2. These findings reveal that dietary DHA protects the lungs from O3 exposure by driving 14-HDHA and MaR1 production, which reduces neutrophil recruiting chemokine production by macrophages. This pathway highlights a potential therapeutic dietary approach for mitigating air pollution-induced pulmonary inflammation.

overall_design: Gene expression of RNA isolated from lung tissue of mice fed a control diet or docosahexanoic acid rich diet prior to a filtered air or ozone exposure

first: Tyson

last: Ngatikaura

first: Natali

last: Zecchino

first: Hannah

last: Lovins

first: Evangeline

last: Schott

first: Samuel

last: Cochran

first: Grace

last: Hutton

first: Jessica

last: Ray

first: Brett

last: Saunders

first: Laura

last: Leuenberger

first: Brita

last: Kilburg-Basnyat

first: Rafia

last: Virk

first: Rachel

middle: V

last: Duinen

first: Xiaokui

last: Mo

last: Armstrong

first: Matthew

middle: I

last: McFadden

first: Jennifer

last: Fenton

first: Nichole

last: Reisdorph

first: Adriana

last: Forero

first: Megan

middle: N

last: Ballinger

first: Robert

last: Tighe

first: Saame

last: Shaikh

first: Kymberly

last: Gowdy


title: Transcriptomic profiling of NAV3 knock-down in human cardiac fibroblasts (HCFs)

city: Rochester

first: Duan

last: Liu

email: liud25@gmail.com, liu.duan@mayo.edu

state: MN

address: 200 1st ST SW

department: MPET

institute: Mayo Clinic

summary: To investigate the function of NAV3 in regulation of HCF proliferation and transdifferentiation, we cultured primary HCFs and transfected with non-targeting siRNA and NAV3 siRNAs. Total RNA samples were extracted for RNA-seq to identify transcriptome-wide gene expression changes in the HCFs after NAV3 knock-down (KD).

overall_design:
Comparative gene expression profiling (RNA-seq) of HCF cells transfected with non-targeting (Control) and NAV3 siRNAs (NAV3 KD). These NAV3 KD samples shared the same non-targeting Controls with our previously published study (GSE222695). Specifically, these NAV3 KD RNA-seq data were generated in the same experiments (including cell culture, siRNA KD and RNA-seq) as did of data which has been uploaded to the GSE222695. The current study reanalysized the "non-targeting control siRNA" samples in the GSE222695 as control samples for the NAV3 KD.

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

first: Vishakantha

last: Murthy

first: Thanh Thanh L.

last: Nguyen


title: An anti-adhesive compound modulating the production of Staphylococcus aureus cell wall-anchored proteins

city: Guelph

first: Georgina

last: Cox

state: Ontario

address: Summerlee Science Complex

department: Molecular and Cellular biology

country: Canada

institute: University of Guelph

summary: Staphylococcus aureus is the leading global cause of death associated with antimicrobial resistance, driven by its ability to colonize the human nasal cavity and adhere to the keratinized skin epithelium. These colonizers are the primary source of subsequent infections, underscoring the need for decolonization strategies. Using a high-throughput whole cell-based S. aureus adhesion screen, we identified a naturally occurring polyunsaturated branched-chain fatty acid, geranylgeranoic acid (GGA), that inhibits S. aureus adhesion to keratin at concentrations that do not affect cell growth. Mechanistic characterization demonstrated that GGA is a broad-spectrum anti-adhesive compound, inhibiting S. aureus adhesion to keratin, fibronectin, fibrinogen, and immunoglobulins. Structure-activity studies revealed that the carboxylic acid moiety and the presence of one or more double bonds in the carbon chain are key to activity, with various unsaturated fatty acids, including host-derived compounds, showing potent anti-adhesive properties. GGA was found to modulate the production of several S. aureus cell wall-anchored (CWA) proteins; for the fibronectin-binding proteins, this was linked to inhibition of the SaeRS two-component system, impairing S. aureus invasion of endothelial cells. In summary, GGA is a potent, naturally occurring anti-adhesive compound that modulates the production of CWA proteins in S. aureus. Our findings further emphasize the complex role of unsaturated fatty acids in host-pathogen interactions and their potential as S. aureus antivirulence agents.

overall_design:
(1) RNA-seq analysis of wildtype JE2 Staphylococcus aureus treated and untreated with geranylgeranoic acid

(2) RNA-seq analysis of wildtype JE2 Staphylococcus aureus treated and untreated with geranylgeranoic acid at early exponential (OD600nm=0.3), mid-exponential (OD600nm=0.6), early stationary (OD600nm=1.0).

(2) RNA-seq analysis of wildtype JE2 Staphylococcus aureus versus JE2-saeS::Tn at the same timepoints as above.

first: Allison

last: Leonard

first: Ruina

last: Bao


title: Interstitial Pneumonia associated with an autoimmune background; miRNA discovery cohort

first: Olga

last: Sanchez Pernaute

address: Avda reyes Catolicos 2

department: Rheumatology

institute: Jimenez Diaz Foundation and Health Research Institute (IIS-FJD)

type: Non-coding RNA profiling by high throughput sequencing

summary: We aim to identify miRNA signatures of clinical subgroups and disease pathways in patients with interstitial pneumonia (IP) and an underlying autoimmune condition. Phenotypes are segregated attending to disease duration, fibrotic disease, radiographic patterns of IP (including UIP, NSIP, others), forced vital capacity (FVC: lower or higher than 80% from ref.) and outcomes (loss of 10% FVC during 24 months of follow up). The sample is enriched in treatment-naïve patients with pulmonary-dominant syndromes. Clinical diagnosis include Interstitial Pneumonia with Autoimmune Features (IPAF), Systemic sclerosis (SSc), Rheumatoid arthritis (RA), anti tRNA synthetase syndrome (ARS), and SSc/ARS overlapping disease. Those patients not fulfilling criteria for IPAF or definite connective tissue diseases are classified as undifferentiated autoimmune IP (uAIP)

overall_design:
Cross-sectional case-control study with follow-up data over a 2 year period
[contributor]  NEREA Autoimmune ILD Study Group

last: Sanchez-Pernaute

first: Mª Jesús

last: Rodríguez-Nieto

first: Cristina

last: Vadillo Font

first: Mª Asunción

last: Nieto Barbero

first: Fredeswinda

last: Romero-Bueno

first: Lydia

last: Abasolo

first: Belén

last: López-Muñiz

first: Laura

last: Cebrián

first: Hilda

last: Godoy Tundidor

first: Rosalía

last: Laporta

first: Mª Gema

last: Bonilla

first: Luis

last: Gómez Carrera

first: Rosario

last: García Vicuña

first: Claudia

last: Valenzuela

first: Irene

last: Llorente Cubas


title: A single cell transcriptional profile of benign prostatic hyperplasia

city: San Francisco

first: Jon

last: Akutagawa

address: 513 Parnassus Ave

institute: UCSF

summary: Benign prostatic hyperplasia (BPH) is characterized by excessive cell proliferation and inflammation and affects most aging men. The development of new therapies for BPH requires a deeper understanding of the underlying pathophysiology and cellular components of BPH. Single-cell RNA-sequencing was performed on prostate tissue from 15 patients undergoing holmium laser enucleation of the prostate for treatment of BPH. Clustering and differential expression analysis on aligned single cell RNA-seq data was performed to annotate all cell types. 16,234 cells were analyzed and specific stromal, epithelial, and immune subgroups were found to be strongly associated with inflammation. A rare luminal subgroup was identified and pseudotime analysis indicated this luminal subgroup might give rise to other luminal cells. Using a gene set derived from epithelial stem cells, we found that this luminal subgroup had a significantly higher stem cell signature score than all other epithelial subgroups, suggesting this subgroup is a luminal precursor state. Ligand-receptor interactions between stromal, epithelial, and immune cells were explored with CellPhoneDB. Significant interactions involving MIF, a pro-inflammatory cytokine that promotes epithelial cell growth and inflammatory response in the prostate, were identified between the progenitor-like luminal subgroup and both fibroblasts and macrophages. Our single-cell profiling of BPH provides a roadmap for investigating inflammation-linked cell subgroups and highlights a progenitor-like luminal subgroup interacting with other cell groups via MIF that may contribute to the inflammation and cell proliferation phenotype associated with BPH.

overall_design: Prostate tissues from BPH patients undergoing Holmium laser enucleation of the prostate (HoLEP) were dissociated into single cells and then captured and sequenced using the Seq-well single-cell RNA-sequencing platform.

first: Rei

last: Unno

first: Hanbing

last: Song

first: Keliana

last: Hui

first: Yih-an

last: Chen

first: Julia

last: Pham

first: Jean

last: Lee

first: Heiko

last: Yang

first: Franklin

last: Huang

first: Thomas

last: Chi


title: RNA-sequencing from nasal curettes or swabs collected from young children aged 1-5

city: Leiden

first: Simon

last: Jochems

address: P4-32, LUMC, Albinusdreef 2

country: Netherlands

institute: LUMC

summary: There is a paucity of data on how the mucosal immune system changes with age. Moreover, the link between nasal presence of  bacteria and viruses with the immune system in young children is  still poorly understood. To address these questions we collected nasal curettes, nasal swabs and filter papers from young children undergoing anesthesia for surgery unrelated to respiratory complaints. Microbial and host parameters were analysed from these samples, including transcriptomics from nasal curettes and swabs. Results revealed strong differences in nasal mucosal immunity in children compared with adutls, as well as clear effects of the presence of bacteria such as pneumococcus and haemophilus on the local immune system

overall_design: Rna-sequencing from nasal curettes using Lexogen FWD Quantseq 75bp reads, with UMI and 15M reads per samples. No experimental groups were defined. Samples were extracted with the SPLIT RNA extraction kit.


title: Transcriptome dynamics reveals the resilience of liver and spleen during avian pathogenic Escherichia coli challenge

city: Nanjing

first: Tailong

last: Wang

state: Jiangsu

address: Xuanwu

department: College of Veterinary Medicine

institute: Nanjing Agricultural University

summary: In this study, chicken pectoral muscle injection of Escherichia coli O18 were used as a systemic infection model to detect the changes in organ weight, blood biochemical parameters, and histopathology during infection and to profile transcriptome dynamics in the liver and spleen at different stages of infection. It was shown that Escherichia coli O18 induced a severe immune response in chickens at 2 dpi, whereas the indices gradually recovered at 5 dpi. The liver differential express genes (DEGs) were mainly enriched in the C-type lectin receptor signaling pathway , suggesting that APEC infection activates immune response-related pathways, and down-regulated genes were enriched in the DNA replication pathway, suggesting that APEC infection inhibits cell proliferation-related pathways. Surprisingly, 5dpi showed opposite gene expression results, suggesting that the host may begin to control APEC pathogenicity. Spleen transcriptomics showed similar dynamic expression results, with DEGs enriched mainly in the C-type lectin receptor signaling pathway and MAPK signaling pathway pathways. In this study, we elucidated the dynamic expression changes of mRNA levels in chicken livers and spleens after APEC infection and identified candidate genes during dynamic host infection of APEC.

overall_design: One hundred chickens were divided into Avian Pathogenic Escherichia coli infected and uninfected groups, and liver and spleen samples were collected 2 and 5 days after infection, with five replicates in each group for RNA-seq sequencing.

first: Tingyu

last: Zhang

first: Yimin

last: Jia


title: To study the changes in downstream genes before and after treatment with TP1

city: Nanchang

first: Yi

last: Sang

state: Jiangxi

address: No.128,Xiangshan North Road

institute: Nanchang University

summary: To characterize the biological effects of TP1 PROTAC, we next treated lung cancer cells with equivalent volume of DMSO or TP1 for 48 hours and performed bulk RNA-sequencing (RNA-seq) analysis.

overall_design: we treated lung cancer cells with equivalent volume of DMSO or TP1 for 48 hours

first: Chun

last: Cheng

first: Longhua

last: Sun

first: Jiaxue


title: Offspring Mouse Testes: Control vs. High Dose Cadmium exposure

city: hefei

first: Hua-Long

last: Zhu

address: No. 81, Meishan Road, Hefei City

department: department of toxicology

institute: anhui medical university

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

summary: Transcriptional profiling of offspring testes comparing untreated offspring testes with high dose cadmium exposure offspring reporter gene.  Differentially m6A-methylated RNAs between two comparison groups were identified by filtering with the P-value < 0.05 and log2(|Fold Changes (FC)|) > 0.5 and visualized by heatmap using MEV software.

overall_design: Two-condition experiment, Control vs. High Dose Cadmium testes. Biological replicates: 3 control replicates, 3 High-Cd exposure.

first: Yong-Wei

last: Xiong

first: Zhi

last: Yuan

first: Ye-Xin

last: Luo

first: Hua


title: MafB is a conserved transcriptional regulator of macrophage development and identity across tissues and species [scRNA-Seq]

city: Liège

last: Marichal

address: Avenue de l'Hopital 11

department: GIGA Institute

country: Belgium

institute: University of Liege

summary: Resident tissue macrophages (RTM) are characterized by a remarkable diversity but also share common features that are thought to be driven by conserved transcriptional programs. While the transcription factor MafB is highly expressed in the macrophage lineage, little is known about its role in establishing RTM identities. Here, we show that the absence of MafB results in a profound imbalance across many RTM populations and in a disruption of global and tissue-specific RTM signatures in mice. Furthermore, we found that MafB was required for the differentiation of bone-marrow-derived macrophages (BMDMs) ex vivo and of RTM populations from monocytes in vivo. Mechanistically, epigenetic profiling of MafB binding sites in BMDMs revealed that MafB directly regulated expression of key RTM differentiation and identity genes, including Csf1r and Fcgr1. Finally, in silico analyses showed that MafB binding sites were highly conserved across vertebrates. Our findings demonstrate the crucial and evolutionarily conserved role of MafB as regulator of RTM development and identity, connecting MafB-dependent transcriptional programs with unique defining features of RTM.

overall_design: We sought to investigate whether MafB deficiency could alter the transcriptional identity of RTM. Live peritoneal lavage CD45+Lin−Ly6C−CD11b+CD115+ cells, liver CD45+Lin−Ly6C−CD11bint/+F4/80+CD64+ cells, colon CD45+Lin−CD11b+F4/80+CD64+ cells and brain CD45+Lin−Ly6C−CD11b+F4/80+CD64+ cells were FACS-sorted from Lyz2CreMafbfl/fl and Mafbfl/fl littermate controls, were hashtag-barcoded and subjected to scRNA-seq.

first: Domien

last: Vanneste

first: Joan

last: Abinet


title: MafB is a conserved transcriptional regulator of macrophage development and identity across tissues and species [CUT&Run]

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: To identify MafB binding sites we performed CUT&RUN for MafB on wild-type BMDM.


title: Mechanosensitive Role of Snx5 in Alveolar Bone Remodeling

city: shanghai

first: xue

last: jiang

state: shanghai

address: No. 399, Yanchang Middle Road, Jing 'an District

institute: Tongji University

summary: The placement of implants induces a compressive effect on the adjacent bone tissue, serving as a form of mechanical stimulation. Insufficient mechanical stimulation may result in diminished bone quality or even implant failure. Nevertheless, the underlying causes and specific mechanisms of this phenomenon remain unclear.

overall_design: Through the analysis of RNA-Seq data, we identified Snx5 as a mechanosensitive factor. By generating Snx5 whole-body knockout (Snx5-/-) mice, this research demonstrates that Snx5 plays a regulatory role in mechanoreception within mouse bone marrow stromal cells. To elucidate the molecular mechanism, we conducted RNA sequencing of wild-type(WT) and Snx5-/- mouse BMSCs.


title: The role of LEDGF in transcription is exploited by HIV-1 to position integration [ChIP-Seq]

city: Bethesda

first: Caroline

last: Esnault

state: md

address: 9000 Rockville Pike,

institute: NICHD NIH

summary: HIV-1 integration occurs across actively transcribed genes due to the interaction of integrase with chromatin factor LEDGF. Although LEDGF was originally purified as a co-activator that stimulates promoters, this role is inconsistent with LEDGF-mediated integration across gene bodies and with data indicating LEDGF promotes transcriptional elongation. We found LEDGF is enriched primarily at transcription start sites (TSSs) of active promoters. Additional data shows MLL1 recruits LEDGF to promoters and LEDGF recruits RNA Pol II.  Contrary to existing models, we find that integration into genes is independent of interactions between H3K36me3 and the PWWP domain of LEDGF. Instead, it is the level of LEDGF at TSSs that determines gene specificity of integration. These data support a dual role model of LEDGF where it is tethered to promoters by MLL1 and recruits RNA Pol II. Subsequently, LEDGF travels across the sequences of genes to effect HIV-1 integration.

overall_design: ChIPseq experiment of LEDGF, RNA POL II, H3M4me3, MLL1 in Human cell line (HEK293T).

first: Rakesh

last: Pathak

first: Rajalingam

last: Radhakrishnan

first: Parmit

last: Singh

first: Hongen

first: Ryan

last: Dale

first: Abhishek

last: Anand

first: Gregory

last: Bedwell

first: Alan

last: Engelman

first: Ali

last: Rabi

first: Priyanka

first: Henry

last: Levin


title: Lymphatic endothelial CCL2 enhances lymphangiogenesis and lymphatic clearance of macrophages following myocardial infarction

city: Shanghai

first: yunhao

last: duan

address: 150 Jimo Rd, Pudong New District

institute: Shanghai East Hospital

summary: Inflammatory responses are crucial in the pathological cardiac remodeling and repair after myocardial infarction (MI). The lymphatic endothelial cells (LECs) significantly influence immune cell clearance and mitigate cardiac inflammation. Chemokines are known to tightly regulate immune cell mobilization within the infarcted heart, thereby significantly influencing cardiac inflammation and remodeling. However, the role of chemokines expressed by LECs in the regulation of cardiac inflammation post-MI remains unclear. Our study revealed that the expression of CC chemokine CCL2 in cardiac LECs was sharply un-regulated following MI. We thus hypothesized that lymphatic endothelial CCL2 might be involved in post-MI cardiac remodeling. To test this hypothesis, we generated LEC-conditional Ccl2 knock-out mice. In vivo experiments demonstrated that the LEC-Ccl2 deficiency deteriorated cardiac function and worsened adverse cardiac remodeling after MI. Further analysis showed that the loss of CCL2 in LECs impeded post-MI lymphangiogenesis and increased macrophage infiltration in post-MI myocardium and impaired macrophages clearance via afferent cardiac lymphatics. This led to exacerbated inflammatory responses and pathological cardiac remodeling after MI. Mechanistically, our study identified that LECs expressed and secreted CCL2, which played a dual role. LEC-CCL2 recruit macrophages from the infarcted myocardium into the lymphatic system and activated AKT/ETS1 signaling, enhancing VEGFC expression and promoting lymphangiogenesis in an autocrine manner. This study reveals that cardiac LEC-expressing CCL2 tightly control macrophage trafficking via lymphatic vessels in injured hearts and thus diminished post-MI inflammatory responses and lessened adverse cardiac remodeling. This study demonstrates that CCL2 expression in cardiac LECs tightly controls macrophage trafficking via lymphatic vessels in injured hearts, thereby diminishing post-MI inflammatory responses and lessening adverse cardiac remodeling. This study suggests that modulating CCL2 signaling in LECs could provide a promising therapeutic target for resolving excessive inflammation and ameliorating adverse cardiac remodeling after MI.

overall_design: The heart tissues or primary heart endothelial cells were obtained as previously described. Isolated RNA was subsequently used for RNA-sequencing analysis. cDNA library construction and sequencing were performed by the Beijing Genomics Institute using BGISEQ-500 platform. Sequences of the clean data were mapped to the mouse reference genome (version GRCm38).

first: Shengqiong

last: Deng

first: Kang

last: Zhao

first: Cai

last: Zeen

first: Qingyu

last: Li

first: Shan

first: Caixia

last: Zhou

first: Yunhao

last: Duan

first: Jinnan

last: Yue

first: Xiuxiang

last: Liu

first: Lin

last: Zhang

first: Yu


first: Yi

last: Sang

summary: To explore MBD1-related ferroptosis targets, we performed Cut&Tag sequencing using MBD1 antibody in lung cancer

overall_design: 100000 lung cancer cells were incubated with ConA magnetic beads for 10min at room temperature, followed by performing Cut&Tag sequencing using MBD1 antibody

first: Chun

last: Cheng


title: Differential Expression of Mitochondrial Natural Antisense Transcripts in Clinical Samples of Plasmodium falciparum Across Multiple Disease Phenotypes

city: Bangalore

first: Genotypic

last: technology

state: Karnataka

address: 259, Apoorva 4th cross,80 feet Road,RMV 2ND STAGE

country: India

institute: Genotypic Technology

summary: The malaria parasite mitochondria are critical targets for antimalarial drugs, but emerging drug resistance against existing protein targets necessitates novel therapeutic approaches. Using custom-designed, multi-probe microarrays and pooled RNA sequencing experiments in patient samples of Plasmodium falciparum, we identified specific Natural Antisense Transcripts (NATs) encoded by both the mitochondrial genome and the nucleus, which are directed to the parasite mitochondria. These findings span three clinical manifestations of malaria - hepatic dysfunction (HD), cerebral malaria (CM), and thrombocytopenia. Although mitochondrial activity is known to be reduced in blood-stage malaria, a significant number of mitochondrial sense-antisense transcript pairs show correlated gene expression in the CM cluster. The thrombocytopenia cluster shows the most upregulated antisense transcripts. This study provides direct evidence for the origin of NATs from the mitochondrial genome. It further provides a dynamic gene regulation profile of key sense and antisense transcripts responsible for mitochondrial translation and bioenergetics. Our findings suggest that active-post transcriptional gene regulation effectively sustains the metabolic flexibility of the parasite mitochondria. Identifying key genes with differentially regulated NATs specific to the observed disease phenotypes presents novel chemotherapeutic targets, disrupting essential functions of the parasite mitochondria.

overall_design: Total RNA from 28 clinical isolates of Plasmodium falciparum was isolated from malaria patients with differing clinical conditions (n=28). Each of these samples was hybridized individually on custom-designed 8*60K arrays printed on the Agilent platform for their sense and antisense transcriptional profiling

first: Sukriti

last: Gujarati

first: Ashis

last: Das


title: Single-cell transcriptomics reveals heterocellular g-globin gene expression in Agdb-thalassemia

city: Memphis

first: Mitchell

last: Weiss

state: TN

address: 262 Danny Thomas Place, MS #341 Memphis, TN   38105

department: Department of Hematology

institute: St. Jude Children’s Research Hospital

summary: To determine the heterogeneity of g-globin expression in the context of deletions that induce fetal hemoglobin, single-cell RNA-seq was performed on primary reticulocytes and undifferentiated HUDEP-2 cells. Single-cell RNA-sequencing (10x Genomics) showed participants and cell lines with the Agdb-thalassemia deletion had overall lower g-globin expression and maintained a lower %HBG expression (HBG/(HBG+HBB)) compared to participants and cell lines with deletional HPFH.

overall_design: Single-cell RNA-sequencing analysis of HUDEP-2 cells and reticulocytes from HbS/Agdb-thal and HbS/HPFH participants

first: Phillip

last: Doerfler

first: Yichao


title: HIV-1 integration sites in the absence of host factors SET2D and MLL1.

city: Boston

first: Parmit

middle: Kumar

last: Singh

address: 450 Brookline Avenue

department: Department of Cancer Immunology and Virology

institute: Dana-Farber Cancer Institute

summary: HIV-1 integration sites were determined in wild-type HEK293T cells and cells lacking SET2D or MLL1. These experiments were performed to test the role of SET2D and MLL1 in LEDGF/p75-dependent HIV-1 integration site selection. Integration libraries were prepared by ligation-mediated PCR and sequenced on Illumina NextSeq 2000 for 150 bp paired-end sequencing.

first: Rajalingam

last: Radhakrishnan

first: Alan

last: Engelman

first: Henry

last: Levin


title: Unraveling age-related cellular and molecular changes associated with vestibular hair cells

city: Omaha

first: David

middle: Z

last: He

state: NE

address: 2500 California Plaza

department: Biomedical Science

institute: Creighton University

summary: The cochlear and vestibular sensory epithelia contain four types of hair cells (HCs) for detecting sound and head motion respectively. In the current study, we comprehensively assessed the molecular changes associated with vestibular HCs with aging to identify age-related marker genes for age-related vestibular dysfunction and performed a comparative analysis with cochlear aging to assess the aging patterns in the two organs of the inner ear.

overall_design: HCs from cochlear and vestibular sensory organs were isolated from 22-month-old CBA/J mice. cDNA library was constructed using the 10x Genomics Chromium Single Cell 3’ V3.1 dual index kit. Seven mice were used for each biological replicate. Six and four biological replicates were prepared for cochlear sensory epithelium and vestibular sensory epithelia respectively. Illumina NextSeq 6000 sequencer was used for sequencing.

first: Samadhi

last: Kulasooriya

first: Huizhan


title: The role of LEDGF in transcription is exploited by HIV-1 to position integration [RNA]

first: Caroline

last: Esnault

overall_design: Poly RNAseq experiment of WT HEK293T and LEDGF-KO cells, with 4 biological replicates

first: Rakesh

last: Pathak

first: Hongen

first: Ryan

last: Dale

first: Abhishek

last: Anand

first: Gregory

last: Bedwell

first: Ali

last: Rabi

first: Priyanka


title: Effect of IL-7 therapy on virus-specific CD8 T cell response during chronic viral infection

city: Atlanta

first: Donald

last: McGuire

state: GA

address: 1462 Clifton Road room 412

institute: Emory University School of Medicine

summary: PD-1+TCF-1+ stem-like CD8 T cells, also referred to as progenitors of exhausted T cells (TPEX), are a crucial resource pool for maintaining CD8 T cell during chronic viral infections and cancer. These stem-like CD8 T cells are a key therapeutic target in antiviral and anticancer immunotherapy as they provide a proliferative burst of effector CD8 T cells upon PD-1 blockade therapy. In our study we show that IL-7 therapy preferentially expands these stem-like CD8 T cells, using NT-I7, a long-acting hybrid Fc-fused recombinant human IL-7 (rhIL-7-hyFc, efineptakin alfa). Single-cell gene profile analysis revealed a proliferating cluster induced by NT-I7, distinct from previously described stem-like, transitory effector, or terminally exhausted subset cluster. This cluster exhibited an enriched stem-like signature, including transcription factors and costimulatory molecules associated with stem-like CD8 T cells. Notably, the cluster was enriched with genes related to lymphocyte migration. Consistent with this gene profile, there was a significant increase in stem-like CD8 T cells in circulation and peripheral tissues after NT-I7 treatment, contrasting with their resident property in lymphoid organs. Our data suggest the potential of NT-I7 therapy to enhance antiviral and anticancer immunotherapies by amplifying the stem-like CD8 T cell pool and mobilizing them to the peripheral target sites.

overall_design: C57Bl/6J mice were intravenously infected with 2x10^6 LCMV clone-13 with transient CD4 depletion. >45 days post infection, mice were treated with a single dose of injection buffer or NT-I7, a hybrid Fc-fused recombinant human IL-7 (hIL-7-hyFc, efineptakin alfa). 8 days after the injection, LCMV-GP33 Tet+ CD8 T cells from the spleen were sorted for single cell RNA sequencing.

first: Judong

last: Lee

first: Christina

last: Niavi

first: Eunseon

last: Ahn

first: Haydn

middle: T

last: Kissick

first: Rajesh

last: Valanparambil

first: Rebecca

last: Obeng

first: Alexandra

last: Wolfarth

first: Danielle

last: Borgonia

first: Sara

last: Ferrando-Martinez

first: Donghoon

last: Choi

first: Byung Ha

first: Rafi

last: Ahmed


title: NTN1 cell-autonomously promotes fibrotic response in HSCs

first: Jiahui

last: Zhao

address: Dongan road 130

institute: Fudan university

summary: Liver fibrosis is a hallmark of progressive liver diseases including metabolic dysfunction-associated steatohepatitis (MASH). Activated hepatic stellate cells (HSCs) are responsible for the excessive synthesis of extracellular matrix(ECM) proteins and collagen deposition in the liver, leading to progressive loss of hepatic functions. However, the nature of paracrine and autocrine signals driving HSC activation and fibrotic response within the liver microenvironment remains incompletely delineated. Here we uncover Netrin-1 (NTN1) as a crucial HSC-derived autocrine factor that promotes HSC activation and liver fibrosis. Hepatic NTN1 mRNA and protein levels were elevated during fibrosis associated with MASH and CCl4-induced liver injury. Hepatic NTN1 overexpression exacerbated diet-induced MASH pathologies and CCl4-induced liver fibrosis. Conversely, HSC-specific conditional ablation of NTN1 alleviated the progression of liver fibrosis. Mechanistic studies using cultured HSCs demonstrated that NTN1 promoted HSC activation in a cell-autonomous manner via a UNC5B and Ca2+-dependent signaling pathway. These findings illustrate the causative role of NTN1-mediated autocrine signaling in driving HSC activation and fibrotic response during liver disease, suggesting potential therapeutic targets for anti-fibrosis therapy.

overall_design: RNA-seq profiling of wildtype C57BL/6J hepatic stellate cells which were treated with PBS or 300ng/ml Netrin-1 recombinant protein for 12h

first: Yajie

last: Peng

first: Hongyan

last: Lei

first: Tianyi

last: Wang

first: Huajuan

first: Xuelian

last: Xiong


title: MafB is a conserved transcriptional regulator of macrophage development and identity across tissues and species [RNA-seq]

first: Thomas

last: Marichal

overall_design: We sought to identify transcriptional programs affected by MafB deficiency and performed bulk RNA-seq on BMDM from Lyz2CreMafbfl/fl and Mafbfl/fl littermate control mice.

first: Domien

last: Vanneste

first: Joan

last: Abinet


title: Annexin A13 protects against acute kidney injury by inactivating TGF-β/Smad3 signaling

city: Guangzhou

first: Jiaxiao

last: Li

state: Guangdong

address: Guangdong, China

institute: The Third Affiliated Hospital of Southern Medical University

summary: Acute kidney injury (AKI) is a common cause of chronic kidney disease, but the pathogenic mechanisms remain unclear and treatments remain limited. Here we report that Annexin A13 (ANXA13), the founder member of Annexins is renal protective in AKI. Clinically, ANXA13 was lost in the AKI kidney in both patients and ischemic-reperfusion injury (IRI)-induced mice. This was associated with declined serum levels of ANXA13 but elevated urinary ANXA13. To explore the functional role of ANXA13 in AKI, we kidney-specifically overexpressed ANXA13 and found that overexpressing ANXA13 protected against IRI-AKI by significantly inhibiting tubular necrosis and lowering serum creatinine. In contrast, kidney-specifically silencing ANXA13 largely promoted AKI.  Mechanistically, renal ANXA13 was downregulated by TGF-β1 via Smad3 signaling as mice lacking Smad3 were protected from the loss of renal ANXA13 and the development of AKI. More importantly, we also uncovered that ANXA13 could directly bind TGF-β receptor type 1 and inhibit its phosphorylation, thereby inactivating Smad3 signaling and  Smad3-mediated tubular cell death via the p21-dependent G1cell cycle arrest. In conclusion, ANXA13 is renal protective and may be a potential new biomarker and a novel therapeutic agent for AKI.

overall_design: To investigate the role of ANXA13 in AKI, we overexpressed ANXA13 in  ischemic-reperfusion injury (IRI) induced AKI mice.

first: Junzhe

last: Chen

first: Huiyao

last: Lan

first: Ying

last: Tang


title: Drugging the intrinsically disordered transactivation domain of androgen receptor [LNCaP95]

city: Vancouver

first: Marianne

last: Sadar

state: BC

address: 675 West 10th Ave

department: Genome Sciences Centre

institute: BC Cancer Research Institute

summary: Androgen receptor (AR) is a therapuetic target for prostate cancer. Despite therapuetic approaches  against its ligand-binding domain (LBD), resistance ultimately develops by mechanisms which result in reactivaton of AR signaling. These mechanisms include expression of constitutively active AR that lacks LBD and fueled the discovery of inhibitors to AR's N-terminal intrinsically disordered transactivation domain (TAD). AR-TAD inhibitors are unique as there is a paucity of small molecule inhibitors that bind directly to intriniscally disordered TADs. Here we reveal gene- and cell specific sensitivities in human prostate cancer cells and xenografts to small molecule inhibitors to AR-TAD. These inhibitors have unique biological functions compared to an AR-LBD inhibitor, including being more efficacious in vivo in a non-castrate setting of androgen-sensitive prostate cancer. These data support a new therapuetic approach for prostate cancer and more broadly reveal the sensitivity of an IDR TAD to small molecule inhibitors on gene expression and cellular pathways.

overall_design:
To better characterize the differences between AR-TAD inhibitors (ARTADI) EPI-002 and BU3-12 from  the AR-LBD inhibitor enzalutamide, we performed whole genome transcriptional profiling on LNCaP95 cells in the absence of androgen to look at genes regulated by constitutively active AR splice variant (AR-V7).
A control group (those samples treated with DMSO vehicle in the absence of synthetic androgen R1881) was included.  Three biological replicates were included for each group.

first: Jon

last: Obst

first: Carmen

middle: A

last: Banuelos

first: Kunzhong

last: Jian

first: Amy

middle: H

last: Tien

first: Jun

first: Nasrin

last: Mawji

first: Teresa

last: Tam

first: Raymond

last: Andersen


title: MafB is a conserved transcriptional regulator of macrophage development and identity across tissues and species [CUT&RUN 2]

overall_design: To quantify transcriptional activity at MafB binding sites we performed CUT&RUN for H3K27ac on BMDM from Lyz2CreMafbfl/fl (Mafb KO) and Mafbfl/fl littermate controls (Mafb WT).


title: The role of LEDGF in transcription is exploited by HIV-1 to position integration

first: Caroline

last: Esnault

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

overall_design: Refer to individual Series


title: Drugging the intrinsically disordered transactivation domain of androgen receptor [LNCaP]

overall_design:
To better characterize the molecular differences between AR-TAD inhibitors (ARTADI) EPI-002 and BU3-12 from the AR-LBD inhibitor (enzalutamide), we performed whole genome transcriptional profiling on LNCaP cells in the presence of androgen to specifically look at the effect of each drug on gene expression, and specifically on genes regulated by full length AR.
Two control groups (those samples treated with DMSO vehicle in the presence and absence of synthetic androgen R1881) were included to define AR-FL regulated genes.  Three biological replicates were included for each group.

last: Wang


title: MafB is a conserved transcriptional regulator of macrophage development and identity across tissues and species

first: Thomas

last: Marichal


title: The gene differential expression analysis of TFE3 rearranged renal cell carcinoma UOK120 cell line after knocking down PRCC-TFE3 fusion gene

first: Fan

last: Feng

department: Urology

institute: Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

summary: TFE3 rearranged renal cell carcinoma (TFE3-rRCC), previously known as Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), is a relatively rare type of renal cell carcinoma, accounting for about 1-4% of adult cases. To date, 23 subtypes of TFE3-rRCC have been identified, among which the NONO-TFE3 (UOK109 cell line) and PRCC-TFE3 (UOK120 cell line) fusion are two of the more common subtypes. In the UOK109 and UOK120 cell line, we knocked down the TFE3 fusion gene and attempted to study the important role this fusion gene plays in tumor initiation, progression, and metastasis through various mechanisms by analyzing differential gene expression

overall_design: We hypothesize that the TFE3 fusion protein regulates the quantity and function of lysosomes by affecting genes related to the lysosomal pathway. By performing RNA-seq on UOK109 and UOK120 cells before and after interfering with TFE3, we confirmed this hypothesis. Analysis of differentially expressed genes (DEGs) (fold change >1.5, p<0.05) revealed that compared to the shNC group, the shTFE3 group of UOK109 cells enriched 516 upregulated genes and 117 downregulated genes, while the shTFE3 group of UOK120 cells enriched 175 upregulated genes and 338 downregulated genes. Further GO and KEGG enrichment analysis of DEGs showed that genes related to lysosomes and autophagy were affected in both UOK109 and UOK120 cells, and they were all in pathways with downregulated differential expression

first: Wenliang

last: Ma

first: Dongmei

first: Weidong

last: Gan


title: Genomics Analysis of met1-derived epiRILs

city: Birmingham

first: Marco

last: Catoni

address: Edgbaston

department: School of Biosciences

institute: University of Birmingham

summary: Epigenetic recombinant inbred lines (epiRILs) are a set of Arabidopsis line obtained by crossing the Arabidopsis mutant in the main DNA METHYLTRANSFERASE 1 (MET1) with the wild-type Col-0 background. A wild-type selection of F2 plants have been then propagated by single-seed descent. In this dataset, we provide a complete genomic analysis of these lines, including the DNA methylation profile at single cytosine resolution (WGBS) for 68 epiRILs, and expression profile (RNAseq) for 37 lines. A genomic DNA resequencing for the same epiRILs is provided in GSE120571 (Catoni et al. 2018).

overall_design: Examination of trascriptome in Arabidopsis thaliana epigenetic recombinant imbred lines (epiRILs), build by propagation (9th generation) of a cross between the mutant met1-3 and the wild type Col-0 control.


title: Conserved transcriptional response to adversity-related inflammation contributes to Meniere’s disease progression [RNA-Seq 1]

city: Jinan

first: Xiaofei

last: Li

address: Duanxing Road 4

institute: Shandong Provincial ENT Hospital, Shandong University

summary: Meniere’s disease (MD) is a common chronic inner ear disease of largely unknown etiology. Several psychobehavioral stressors and alterations in the immune system have been linked to MD attacks and disease progression. Nevertheless, the molecular basis of alterations in systemic immunity in individuals with MD remains unclear. This study aimed to demonstrate the roles of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis in patients with MD in regulating the lineage commitment and response pattern of myeloid cells and the potential implications on the function of the inner ear in MD.  The peripheral blood transcriptome from patients with MD showed elevated levels of inflammation and decreased antiviral response, and myeloid cells were the main source of conserved transcriptional response to adversity (CTRA)-related inflammation. The expression of transcription factors regulating myeloid lineage commitment was altered, and flow cytometry analysis showed an expanded monocyte population, characterized by an increased subset of immature proinflammatory monocytes. Sympathetic signaling was activated in patients with MD, as evident by elevated norepinephrine levels and up-regulated adrenergic receptor β1 expression. LPS-induced inflammation in vitro was almost completely reversed by β blockers and an adenylate cyclase inhibitor in MD myeloid cells, and partially reversed by β1 and β2 subtypes, suggesting that the β-ADR-cAMP signaling pathway mediates exaggerated proinflammatory responses in myeloid cells. Although no significant change was observed in plasma cortisol levels in patients with MD, the increased ratio of the glucocorticoid receptor NR3C1 to the mineralocorticoid receptor NR3C2 suggested that MD myeloid cells were more sensitive to glucocorticoids. In vitro experiments confirmed that glucocorticoids significantly reduce LPS-induced inflammation. G-CSF levels were significantly elevated in patients with MD and correlated well with the levels of other cytokines. Cross-sectional and longitudinal follow-up data showed that the group with high or increased G-CSF over time had worse inner ear function, reflecting the potential effect of systemic inflammation on inner ear function in patients with MD. Our data provide an additional mechanism to elucidate the regulation of the transcriptome of MD myeloid cells by the HPA axis and SNS, and their potential effects on inner ear function. Conclusively, our results imply that good management of stress and prevention of CTRA development may benefit patients with MD.

overall_design:
To observe the transcriptional changes of immune cells in peripheral blood, whole blood drawn on PAXgene tubes from MD patients and matched healthy controls,  were used for total RNA extraction using the PAXgene Blood RNA Kit (Qiagen) .
To compare the contribution of myeloid cells to CTRA, flow cytometry was used to sort CD11b+ cells and CD11b- cells from peripheral bloodCD11b+ myeloid cells, and CD11b- immune cells were used for total RNA extraction using TRIzol reagent, according to the manufacturer’s protocols (Invitrogen).

last: Zhang

first: Yongdong

last: Song

first: Yafeng

last: Lyu

first: Huirong

first: Yawei

first: Jing

first: Wenjuan

first: Ruyan

first: Yinghui

last: Hu

first: Xiaoyi

first: Zhaomin

last: Fan

first: Daogong

first: Haibo


title: Conserved transcriptional response to adversity-related inflammation contributes to Meniere’s disease progression


title: A temperature increase induces Atf1/Pcr1-dependent rapid depletion of histone in transcriptionally activated gene bodies in fission yeast

city: Bunkyo, Tokyo

first: Soichi

last: Inagaki

department: Department of Biological Sciences

country: Japan

institute: Graduate School of Science, The University of Tokyo

summary: Transcriptional regulation is central to organisms’ response and adaptation to environmental changes. However, the coordination of transcriptional machinery with chromatin when rapid transcriptional changes are needed is largely unknown. Here, we studied the rapid response of histone modifications upon heat treatment of fission yeast Schizosaccharomyces pombe. We observed a significant eviction of H3 in the transcribed regions of upregulated genes, named Hasty Overheat-Triggered Differentially Occupied Genes (HOT-DOGs), including Heat Shock Protein-encoding genes. The loss of H3 in a third of the HOT-DOGs were dependent on the Atf1-Pcr1 transcription factor complex. Furthermore, the H3K9 methyltransferase Clr4 likely modulates the rate of transcription elongation and helps prevent transcriptional read-through beyond polyadenylation sites in these genes. Our results unveiled a novel function of Clr4 in regulating the dynamics of transcription within gene bodies and provided insights into how cells cope with rapid environmental changes while preserving chromatin integrity.

overall_design: Schizosaccharomyces pombe cells cultured in YES media with/without heat treatment are used for mRNA-seq, ChIP-seq and PRO-seq

first: Arata

last: Hoshino


title: The effect of BCAT1 inhibition on activated human CD8+ T cells

city: Washington

first: Adonia

middle: Evangelos

last: Papathanassiu

state: DC

address: 416 Marietta PL, NW

institute: Ergon Pharmaceuticals LLC

summary: Branched chain amino acid transaminase 1 (BCAT1) moderates iron balance during CD8+ T cell activation by limiting the conversion of iron regulatory protein 1 (IRP1) to aconitase 1 (ACO1). BCAT1 inhibition (BCAT1i) increases ACO1 activity, prevents iron uptake by activated CD8+ T cells, increases iron-sulfur (Fe-S) clusters in the mitochondria, arrests the timely degradation of nuclear ACO1, and inhibits CD8+ T cell differentiation in vitro and in vivo. The effects of BCAT1i on CD8+ T cell activation  include upregulation of genes associated with DNA damage response and pro- and anti-apoptotic pathways and downregulation of genes involved in cell cycling, DNA replication, mRNA splicing, and ribosome biogenesis. The majority of the affected processes require iron as a co-factor.

overall_design: CD8+ T cells were isolated from the peripheral blood of 3 individual donors. Approximately 3x106 cells were activated with anti-CD3/anti-CD28 Dynabeads for 24h in the presence or absence of 200 mM ERG245 (BCAT1 inhibitor). The beads were subsequently removed and cells were collected.

middle: E


title: Genomics Analysis of met1-derived epiRILs [BiSulfite-seq]

first: Marco

type: Methylation profiling by high throughput sequencing

overall_design: Examination of the genomic DNA methylation profiles of Arabidopsis thaliana epigenetic recombinant imbred lines (epiRILs), build by propagation (9th generation) of a cross between the mutant met1-3 and the wild type Col-0 control.


title: Conserved transcriptional response to adversity-related inflammation contributes to Meniere’s disease progression [RNA-Seq 2]

first: Xiaofei

last: Jian


title: Role of copper in the brain development and autism spectrum disorder pathogenesis

city: Charleston

first: Stefano

last: Berto

state: SC

address: 68 President Street, BE208

institute: MUSC

summary: To investigate the role of copper-deficient in mice for autism spectrum disorder study

overall_design: Comparative gene expression profiling analysis of RNA-seq data for control mice and drug-treated copper-deficient mice (CTL, CU-KD).

first: Noriyoshi

last: Usui


title: Transcriptomic differences in cabozantinib-resisant AML cells.

city: Taipei

first: Yu-Hsuan

last: Fu

address: No.1, Chang-Te St

department: Department of Clinical Laboratory Sciences and Medical Biotechnology

institute: National Taiwan University

summary: Cabozantinib is a type II tyrosine kinase inhibitor (TKI), which is approved by FDA for treating several solid tumors including advanced/progressive metastatic medullar thyroid cancer, advanced renal cell carcinoma, and advanced and progressive hepatocellular carcinoma. Moreover, we and others revealed its cytotoxicity on FLT3-ITD, KIT-driven t(8;21) AML cells, and its efficacy on promoting erythroid differentiation of leukemic cell line K562. A clinical trial report also suggested that cabozantinib is well tolerated in FLT3-ITD AML patients. While those findings highlighted the feasibility of cabozantinib targeting specific AML subtypes, it is unclear whether cabozantinib treatment arises resistance in cancer cells. To identify the mechanism and transcriptomic change of cabozantinib resistance, we established drug-resistant cell lines by culturing Molm13 and MV4-11 leukemic cell lines in increasing drug concentrations.

overall_design: The cabozantinib-resistant cells (Molm13-XR and MV4-11-XR cells) were derived by culturing the parental cells in low-concentration cabozantinib and escalating the dose once the cells were recovered.

first: Chieh-Wen

last: Wu

first: Wen-Chun

last: Chen

first: Pei-Chi

last: Lang

first: Liang-In

last: Lin


title: The viral lncRNA LMP2A-IT1 promotes Epstein-Barr virus lytic replication

status: Public on Feb 24 2026

first: Zhengzhou

last: Lu

state: Guangdong province

address: 74 Zhongshan Second Road

institute: Sun Yat-Sen University

summary: The Epstein-Barr virus (EBV) employs lytic replication to facilitate viral propagation and pathogenesis; however, the regulatory mechanisms governing this process remain incompletely elucidated. Here, we identify LMP2A-IT1, a novel 276-nt RNA derived from the first intron of the LMP2A gene. This transcript directly interacts with the nuclear export factor exportin 5 (XPO5) and exhibits predominant cytoplasmic localization. Functionally, LMP2A-IT1 expression is markedly upregulated during EBV lytic reactivation and subsequently amplifies viral gene expression and DNA replication—a phenomenon further supported by the positive correlation between LMP2A-IT1 levels and EBV DNA copy numbers in human nasopharyngeal carcinoma tissues. Mechanistically, cytoplasmic LMP2A-IT1 likely activates inflammatory response, thereby upregulating the immediate-early transactivators BZLF1 and BRLF1 to initiate the EBV lytic cycle. Our study establishes LMP2A-IT1 as a novel EBV-encoded RNA and reveals its function as a key positive feedback regulator of EBV lytic replication. These findings provide new insights into EBV replication dynamics and underscore the functional significance of viral RNAs in EBV biology.

overall_design: We first constructed CNE2-EBV cell lines overexpressing inducible LMP2A-IT1 or vector. The cells were then treated with 1μg/ml Doxycycline for 48h. After that, RNA is extracted and used to construct libraries and paired sequenced using the Illumina NovaSeq PE150 platform.We first established CNE2-EBV cell lines with inducible overexpression of LMP2A-IT1 or a vector control. The cells were then treated with 1 μg/ml doxycycline for 48 hours. Afterwards, RNA was extracted and used for library construction, followed by paired-end sequencing using the Illumina NovaSeq PE150 platform. Both the vector and LMP2A-IT1 samples included two replicates.

first: Zheng-Zhou

first: Jun-Fei

first: Nannan

last: Zhu

first: Ming-Hui

last: Yang

first: Le-Le

first: Yuan-Tao

last: Liu

first: Wei-Jun

first: Jin-Kun

last: Tang

first: Jia-Wei

last: Ge

first: Chao-Bo

last: Lei

first: Tao

first: Yu

last: Wang

first: Jian-Zhou

last: Zhai

first: Qi-Cheng

first: Chao-Yun

last: Huang

first: Qian

last: Zhong

first: Mu-Sheng

last: Zeng

first: Yan

last: Li


title: Nuclear Speckles enable processing of RNA from GC-rich Isochores

city: Berlin

first: IBRAHIM

middle: AVSAR

last: ILIK

state: Berlin

address: Ihnestraße 63-73

institute: Max-Planck-Institut für molekulare Genetik

sample_organism:
Gallus gallus
Homo sapiens
Pimephales promelas


title: Anti-TIM3-IFN fusion protein rejuvenates tumor-infiltrating exhausted TIM3+CD8+ T cells through activating intratumoral dendritic cells

city: Haidian District

first: Wenbo

last: Hu

state: Beijing

address: 30 Shuangqing Road

institute: Tsinghua University

summary: While tumor-infiltrating T cells are central to tumor regression, their function is progressively compromised by the exhaustive conditions of the tumor microenvironment. The capacity of intratumoral dendritic cells (DCs) to mitigate this exhaustion state is not fully understood. Here, we investigate a therapeutic strategy that leverages a bispecific DC-T cell engager (BiDT), constructed from anti-TIM3 and IFNα, to simultaneously targeting TIM3 on exhausted TILs and the IFNAR receptor on DCs. Through transcriptional profiling, we elucidate the mechanism by which BiDT operates: it concurrently targets TIM3+ TILs and IFNAR+ DCs, triggering a reprogramming of the local immune repertoire. Mechanistic analysis indicates that BiDT rescues T cells from apoptosis by enhancing Bcl2 expression and restores their effector functions. Crucially, the data uncovers a reciprocal activation loop wherein BiDT-stimulated DCs further potentiate T cell responses via IL-2 and B7/CD28 signaling pathways. We further validated an engineered Pro-BiDT variant designed to limit systemic toxicity. These results underscore the importance of re-establishing functional DC-T cell circuitry as a viable strategy to enhance anti-tumor immunity.

overall_design: CD45+ TILs from MC38 tumor (day 19 post-inoculation, control group and BiDT-treated group) were isolated by FACS and anaylzed using single-cell RNA sequencing

first: Xuhao

last: Zhang

last: Gao


title: Assessing the cellular microenvironment in the skin of mice lacking epidermal Pparg compared with wildtype sibling controls.

city: Indianapolis

first: Raymond

middle: Lloyd

last: Konger

state: IN

address: 1481 West Tenth Street

department: Pathology & Laboratory Medicine

institute: Richard L. Roudebush VA Medical Center

summary: B6.129-Ppargtm2Rev/J mice (Stock Number: 004584, The Jackson Laboratory) were crossed with B6N.Cg-Tg(KRT14-cre)1Amc/J mice (Stock Number 018964, The Jackson Laboratory) to generate epidermal-specific PPARγ knockout mice in the C57BL/6J background (C57.Pparg-/-epi mice). Mice were housed under specific pathogen-free conditions at the Indiana University School of Medicine. The protocols were approved by the Indiana University School of Medicine Institutional Animal Care and Use Committee (IACUC). Using whole transcriptomic RNA sequencing (GSE164024), we had previously demonstrated that the skin of mice lacking epidermal Pparg exhibited signficant changes in approximately 12% of the expressed genes, formed spontaneous inflammatory skin lesions, and had prominent increases in pro-inflammatory genes and a reduction in genes associated with the epidermal lipid barrier function.  Mice lacking epidermal Pparg are also prone to increase chemical and photocarcinogenesis.  We therefore sought to determine the changes in gene expression at the cellular level to obtain information regarding changes to the cellular microenvironment within the skin of Pparg-/-epi mice.

overall_design: Two mice (one male and one female) mice from each genotype were age matched.  Skin was excised from areas of telogen phase hair cycling for each mouse.  Areas were chosen that lacked evidence of spontaneous inflammatory skin changes.  Other than the genotype changes, no treatment was performed on any of the mice.  Both dermal and epidermal cells were then isolated for single cell RNA sequencing.

first: Xiaoling

last: Xuei

first: Ethel

last: Derr-Yellin

first: Fang

last: Fang

first: Hongyu

first: Yunlong


title: Oncolytic virotherapy and platinum-based chemotherapy synergize to potentiate anti-tumor immunity through targeted engagement of chemo-persistent bystander CD8+ T cells [scRNA-seq]

city: Chongqing

first: shuai

last: yue

state: Chongqing

address: Gaotanyan street

institute: army medical university

summary: We reported the CD8+ T cell exhaustion differences between chronic viral infection and tumor regarding their transcriptomic and epigenetic landscapes, immune checkpoint blockade responsiveness and underlying molecular mechanisms by using single-cell RNA-seq.

overall_design: Exhausted P14 CD8+ T cells bearing a same TCR recognizing a same epitope presented in either chronic viral infection (LCMV-Cl13) or tumor (B16F10-GP) were harvested and performed with RNA-sequencing. Exhausted P14 CD8+ T cells were obtained from the livers or lungs of chronic virus-infected mice and from metastatic lungs/livers of tumor-engrafted mice. The chronic virus-infected or tumor-engrafted mice were treated with either anti-PD-L1 antibody or FTY720 or isotype antibody.

first: Xiangyu

last: Chen

first: Guoshuai

last: Cao

first: Shuai

last: Yue


title: Plasma miR-98-5p as a diagnostic biomarker for oxaliplatin-induced neuropathic pain related to NGF and catecholamine dysregulation

city: Gimcheon

first: Yeongdon

last: Ju

state: Gyeongsangbuk-do

address: 214, Daehak-ro, Gimcheon-si

department: Department of Biomedical Laboratory Science

institute: Gimcheon University

summary: This study aimed to identify differentially expressed microRNAs in plasma samples from patients with gastrointestinal cancer treated with oxaliplatin to elucidate the association between the expression levels of miRNA, nerve growth factor, catecholamines, and numeric rating scale score for peripheral neuropathic pain.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for plasma samples of patients with gastrointestinal cancer

first: Aelee

last: Jang


title: A selective and augmentable butyrate-FFAR2 signal circuitry programs the cellular identity of enteroendocrine L-cells

city: New York

first: Chia-Wei

last: Cheng

state: NY

address: 650 West 168th Street, Rm 1110

institute: Columbia University Irving Medical Center

summary: Activation of free fatty acid receptor 2 (FFAR2) on enteroendocrine L-cells mediates secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), key regulators of central appetite control with therapeutic relevance to obesity. Here, we show that butyrate, a metabolite derived from fermentation of dietary fibre and an FFAR2 agonist, stimulates a PYY-biased profile in a human L-cell model at the transcriptional, morphological and secretory level via an FFAR2-Gai axis that does not require dynamin-dependent receptor internalization. We observe that butyrate modulates active Notch cascades within a Hes1-GFP mouse organoid model, which are antagonistic to secretory differentiation, and identify butyrate-dependent regulation of late-stage human enteroendocrine maturation markers, NeuroD1 and Pax6. Butyrate-mediated upregulation of Pyy and Pax6 is enhanced by the FFAR2-selective Gai biased allosteric agonist AZ-1729. Our study reveals functions of spatiotemporally regulated butyrate-activated FFAR2 signalling mechanisms that could be pharmacologically amplified to fine-tune L-cell populations in the human colon.

overall_design: RNA-seq profiling of mouse colonic organoids at passage 3 +/- butyrate following 48h or 72h of treatment.

first: Aanya

last: Hirdaramani

first: Gary

last: Frost

first: Aylin

last: Hanyaloglu


title: Transcriptome analysis of the response of domesticated emmer wheat (Triticum turgidum subsp. dicoccum) to single vs. mixed infections with Zymosptoria tritici and Puccinia graminis

city: Uppsala

first: Salim

last: Bourras

address: Almas Alle 5

department: Plant Biology

country: Sweden

institute: Swedish University of Agricultural Sciences

summary: Tetraploid emmer Triticum turgidum subsp. dicoccum is one of the first wheat species to be domesticated. Emmer shares many pathogen species with modern durum wheat (Triticum turgidum subsp. durum) and hexaploid bread wheat (Triticum aestivum L.). Domesticated emmer is considered a highly valuable source of potentially novel disease resistance genes that can be introduced into modern wheat varieties, however, large gaps remain in our understanding of the basic immune responses of emmer to the most common wheat pathogens. In this work we describe the transcriptional response of emmer to single and mixed pathogen species infections with the ascomycete Zymoseptoria tritici, and the basidiomycete Puccinia graminis. In doing so, we here uncover unique patterns in the response of emmer to a more complex pathogen population with mixed species infections.

overall_design: Characterization of  the transcriptional response of domesticated emmer wheat to single and mixed infections with Z. tritici and P. graminis using RNA sequencing.

first: Miguel

last: Corrales-Gutiérrez

first: Luis

last: Sterling

first: Francesca

last: Desiderio

first: Dimitar

last: Douchkov

first: Jiasui

last: Zhan