title: CsdA-LaeB Regulatory Hub Contributes to Aspergillus fumigatus Virulence via Fumiquinazoline C Biosynthesis

status: Public on Dec 31 2025

city: Beijing

first: Zili

last: Song

address: Beichen West Road 1

country: China

institute: Institute of Microbiology, Chinese Academy of Sciences

type: Expression profiling by high throughput sequencing

summary: Fungal secondary metabolism plays a critical role in pathogen-host interactions, yet the regulatory networks linking metabolic reprogramming to virulence remain poorly understood. This study identifies a conserved regulatory hub in the human pathogen Aspergillus fumigatus, where the RNA-binding protein (RBP) CsdA interacts with the global regulator LaeB in the nucleus to control biosynthesis of the secondary metabolite fumiquinazoline C (FqC). Disruption of the CsdA-LaeB interaction hyperactivates FqC production, enhancing fungal colonization and lethality in murine invasive aspergillosis models. Integrative metabolomic and transcriptomic analyses reveal that CsdA and LaeB function as co-regulators of a broader secondary metabolic gene cluster network, with FqC emerging as an effector that mediates virulence in vivo. Genetic validation confirms that FqC is strictly required for the increased virulence phenotype of CsdA- or LaeB-deficient strains, while analyses of clinical isolates demonstrate a striking inverse correlation: reduced CsdA and LaeB expression coincides with elevated FqC production, showing consistency with the infection outcomes of the deletion mutants. This work identifies the RBP-based interaction that coordinates fungal metabolic virulence, shedding new light on the post-transcriptional regulatory logic linking secondary metabolism to pathogenicity and offering alternative strategies for diagnostic development and therapeutic intervention in invasive fungal diseases.

overall_design: RNA-seq profile of wildtype CEA17 and their knockdown derivatives (csdA and laeB) at Day5 of metabolic differentiation.

first: Hongjiao

last: Zhang

first: Wen-Bing

last: Yin


title: Effect of QPRT overexpression on gene expression in cancer pericyte cells

city: Guangzhou

first: Yuning

last: Lin

address: No. 603 Huangpu Avenue, Tianhe District, Guangzhou City, Guangdong Province

department: State Key Laboratory of Bioactive Molecules and Druggability Assessment

institute: Jinan University

summary: Cancer pericytes are core components of the tumor microenvironment, governing tumor angiogenesis, invasion, and therapeutic resistance; QPRT (quinolinic acid phosphoribosyltransferase), a key metabolic enzyme, is implicated in modulating cellular metabolic homeostasis and malignant progression. We here investigate the transcriptomic impact of QPRT overexpression in cancer pericyte cells. QPRT overexpression induces widespread alterations in gene expression profiles, with dysregulated genes predominantly enriched in pathways related to tumor-associated angiogenesis, pericyte activation, and cell-matrix adhesion. Functional characterization shows that QPRT overexpression upregulates pro-angiogenic factors (e.g., VEGF, PDGF-BB) and adhesion molecules, enhancing the paracrine regulatory capacity of cancer pericytes on adjacent tumor vasculature. Mechanistically, QPRT-mediated metabolic reprogramming contributes to the activation of these pro-tumorigenic pathways. Taken together, our data reveal a critical role of QPRT overexpression in remodeling the transcriptome of cancer pericyte cells, providing insights into metabolic modulation of tumor microenvironment function.

overall_design: RNA-seq profiling of control (empty vector-transfected) cancer pericyte cells and QPRT-overexpressing cancer pericyte cells, analyzed at the logarithmic growth phase (Day 4 post-transfection) to identify QPRT-mediated transcriptomic changes.

first: Maohua

last: Huang


title: Oriented Cell Divisions Induce Basal Progenitors and Regulate Neural Expansion Across Tissues and Species

city: Montreal

first: Benoit

middle: Charles

last: Boulan

state: Quebec

address: 110, avenue des Pins Ouest

country: Canada

institute: IRCM

summary: GPSM2 and SAPCD2 as major regulator of mitotic spindle orientation regulate basal progenitor production in retina and cortex

overall_design: scRNA-seq analysis of Gpsm2/Sapcd2 double-het versus double-KO in developing retina and cortex

first: Michel

last: Cayouette


title: Transcriptome comparison of tobacco cell cultures in various stages of their life cycle

city: Praha 6

first: Karel

last: Muller

address: Rozvojová 263

department: Lab. of hormonal regulations in plants

country: Czech Republic

institute: Institute of Experimenal Botany of the Czech Academy of Sciences

summary: Plant tissue repair is essential for survival, yet unlike mobile animal cells, rigid cell walls anchor plant cells in place. Here we show how plants reorganize damaged tissue through active cellular remodeling. We demonstrate that wounded tissues enhance cell-to-cell contacts, a process crucially coordinated by actin and the cell wall component pectin. We further show that the extent of cell-to-cell contact directly governs cell division potential in the root meristem, highlighting the vital necessity of physical connection for subsequent growth and repair. To complement these in situ findings and understand the cell-to-cell contact mechanism, we integrated single-cell analyses and RNA-seq in a tobacco cells and identified critical players in this process.

overall_design: To compare transcriptomic profiles of tobacco BY-2 cell culture during its life cycle, we isolated total RNA from cells harvested at the early exponential (1 day old) and stationary (7 and 10 day old) stages of their growth cycle, three replicas for each sample group.

last: Müller

first: Jan

last: Petrášek


title: Contact with smooth muscle cells dictates the endothelial transcriptome

city: Charlottesville

first: Brant

middle: E

last: Isakson

state: Virginia

department: Cardiovascular Research Center

country: USA

institute: University of Virginia

summary: The phenotypes of endothelial cells (ECs) in conduit and resistance arteries differ in part due to the presence of myoendothelial junctions in resistance arteries. These are direct contact points between ECs and smooth muscle cells (SMCs) that form through holes in the inner elastic lamina. To investigate the consequences of SCM contact on endothelial phenotypes, we used transwells to culture ECs in three conditions: cultured without SMCs (monolayer ECs), co-cultured without direct contact with SMCs (no-contact ECs), and co-cultured with SMCs such that myoendothelial junctions could form (contact ECs). We then collected the ECs and performed bulk RNA sequencing. These data demonstrate the impact of SMC-derived signals on endothelial phenotypes.

overall_design: To model resistance arteries, endothelial cells were cultured following the vascular cell co-culture model as previously reported. Briefly, human coronary artery smooth muscle cells (SMCs) were plated (75,000 cells/well) on the bottom of a 6-well plate or on the underside of the transwell. The following day, human coronary artery ECs were seeded on the top side of the transwell. An additional group of ECs were plated in a transwell dish without smooth muscle cells. In all three conditions, endothelial cell growth media MV (Promocell) was placed on the top of the transwell and SMC media (Lonza) was placed in the bottom chamber of the transwell. Two days after plating ECs, the media was changed, and ECs were collected the following day. For transcriptomics, RNA was isolated using Quick-RNA MiniPrep (Zymo Research). PE150 reads were generated with the Illumina NovoSeq platform. The paired-end reads were mapped to the hg38 reference genome using STAR (v2.7.9a). Gene counts were generated with featureCounts in the Subread package. For all datasets, DESeq2 (v1.34.0) was used to identify differentially expressed genes (DEGs) (Padj < 0.05). Ensemble IDs were converted to gene symbols using the org.Hs.eg.db package.

first: Luke

middle: S

last: Dunaway


title: RNA-seq profiling of PRAME knockdown in A375SM skin cutaneous melanoma cells

city: Seoul

first: Hyeon Ho

last: Heo

address: 209 Neungdong-ro, Gwangjin-gu

department: Department of Integrative Bioscience and Biotechnology

country: South Korea

institute: Sejong University

summary: This study investigates the transcriptomic effects of PRAME knockdown in the A375SM skin cutaneous melanoma cell line. Cells were transduced with either control shRNA (shCtrl) or PRAME-targeting shRNA (shPRAME), followed by paired-end RNA sequencing. The dataset provides gene expression changes associated with PRAME silencing and offers insights into PRAME-regulated pathways in melanoma.

overall_design: A total of six RNA-seq samples were generated using the A375SM melanoma cell line: three biological replicates transduced with control shRNA (shCtrl) and three replicates transduced with PRAME-targeting shRNA (shPRAME). Total RNA was extracted, polyA-enriched, and sequenced using paired-end 150 bp reads on an Illumina NovaSeq platform. Raw FASTQ files and processed gene expression matrices are provided for differential expression analysis.


title: Iron chelation shifts endothelial phenotypes

summary: Iron deficiency is a highly prevalent nutrient deficiency and the most common cause of anemia. Although iron deficiency exacerbates cardiovascular disease, the direct impact of iron deficiency on the vasculature remains unstudied. Human lymphatic and arterial endothelial cells were treated with deferoxamine for 24 hours to assess the impact of iron deficiency on endothelial cell phenotypes. We found iron chelation upregulated the expression of arterial makers in both cell types. In lymphatic endothelial cells, iron chelation decreased the expression of lymphatic markers. These data suggest iron chelation shifts endothelial cells toward an arterial phenotype.

overall_design: To deplete iron, human coronary artery ECs and human dermal lymphatic ECs were grown to confluence and treated with 100 mM deferoxamine (DFO; MedChemExpress) for 24 hours. RNA was isolated with Quick-RNA MiniPrep (Zymo Research). PE150 reads were generated with the Illumina NovoSeq platform. The paired-end reads were mapped to the hg38 reference genome using STAR (v2.7.9a). Gene counts were generated with featureCounts in the Subread package. For all datasets, DESeq2 (v1.34.0) was used to identify differentially expressed genes (DEGs) (Padj < 0.05). Ensemble IDs were converted to gene symbols using the org.Hs.eg.db package.


title: Sepsis-induced changes in hepatic cell communication in mice: RNA-seq on purified cells

city: Gent

first: Steven

last: Timmermans

address: Technologiepark 71

country: Belgium

institute: VIB-UGent

summary: Sepsis, which affects 49 million people yearly, killing 11 million of them, involves activation of inflammation, as well as significant metabolic reprogramming. The liver is affected by these changes and is confronted with pathogens and is a key organ in restoring homeostasis. We addressed the question to what extent cell-cell communication between hepatic cell types is affected in sepsis, using the CLP model of sepsis in mice. We sorted the four major hepatic cell types, hepatocytes (HEPs), hepatic stellate cells (HSCs), liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs) as well as non-KC CD45+ cells and performed bulk deep RNAseq. Cell-specific pathways were studied, and we focused on cell-cell interactions between the cell types. We found that HSCs, which in control (Sham) animals are not significantly communicative, in sepsis behave as the major signal-spreading cell type, primarily stimulated by LSECs. The impact of the HSC signals on the other cell types was investigated by NicheNet and reveals interesting new insights into the initiation of diverse hepatic responses in sepsis, such as pathogen clearance, ECM remodeling, chemotaxis and metabolic reprogramming. HSCs may therefore be considered as primary cells to targets in sepsis.

overall_design: RNA-seq profiling of purified hepatocytes, liver sinusoidal endothelial cells, hapatic stellate cells, kupfer cells and infiltrating CD45+ cells from mice after CLP or Sham surgery

first: Céline

last: Van Dender

first: Maxime

last: Roes

first: Elise

last: Moens

first: Tineke

last: Vanderhaeghen

first: Jolien

last: Vandewalle

first: Claude

last: Libert


title: The miR4261/PAMM axis in multiple myeloma promotes bone resorption

city: Taiyuan

first: Jiangxia

last: cui

address: xinjian road

institute: Shanxi Natural Science Foundation of China

summary: Myeloma bone disease (MBD) affects ~80% of multiple myeloma (MM) patients and remains a major cause of morbidity despite anti-resorptive therapies. Here we identify a previously unrecognized exosome-mediated mechanism by which MM cells directly promote osteoclastogenesis. Tumor-derived exosomal miR-4261 is transferred to monocyte precursors, directly targets and represses PAMM (PRXL2A/FAM213A)—an antioxidant protein that negatively regulates osteoclast differentiation—and thereby accelerates osteoclast formation and bone resorption. In two independent MM cohorts, serum exosomal miR-4261 was significantly elevated in patients with MBD, whereas PAMM expression was reduced; low PAMM strongly correlated with hypercalcaemia. PAMM knockdown recapitulated the pro-osteoclastogenic effects of miR-4261, and RNA-seq/GSEA revealed selective downregulation of negative regulators of osteoclast differentiation (including TNFAIP6, CCL3, and TLR3). These findings establish the miR-4261/PAMM axis as a novel driver of myeloma-induced bone destruction and suggest serum exosomal miR-4261 as a promising liquid-biopsy biomarker and therapeutic target in MBD.

overall_design: Comparative RNA-seq analysis between control Scrambled and shPAMM cells in wild-type THP-1 cells.

last: Cui

first: Sicheng

last: Bian

first: Zhuanghui

last: Hao

first: Xialin

last: Zhang

first: Chen

first: Yun

last: Zhao

first: Xiuyan

first: Hongwei

last: Wang


title: Comprehensive long-read transcriptome analysis uncovers alternative RNA processing feature and isoform diversity in ovarian cancer progression

city: Tianjin

first: liu

last: tianxiang

address: No.94 Weijin Road, Nankai District

institute: Nankai University

summary: Post-transcriptional processing has a crucial but still largely unresolved dynamic change and role during the malignant progression of ovarian cancer, especially due to the limited read length of widely used short-read RNA sequencing being not enough to capture the transcript diversity. Here, we performed both Iso and RNA sequencing on paired normal ovarian tissues, primary tumors, and metastatic lesions from patients with ovarian cancer. We generated a comprehensive isoform atlas containing over 41,000 full-length transcripts, including many previously unannotated isoforms with coding potential. Integrative analyses revealed extensive isoform-level remodeling across disease stages, involving alternative splicing and polyadenylation. These changes often occurred without concordant alterations at the gene level, emphasizing the importance of qualitative transcript regulation.

overall_design: We collected nine tissues from three patients with high-grade serous ovarian cancer (HGSOC), including normal tissues, primary ovarian tumors, and omental metastases. These samples were sequenced using PacBio long-read and DNBSEQ-T7 RNA-seq


title: Expression Data from ST2 cells treated with recombinant Wnt1

city: Hamburg

first: Thorsten

last: Schinke

address: Martinistr. 52

department: Department of Osteology and Biomechanics

country: Germany

institute: University Medical Center Hamburg-Eppendorf

summary:
Wnt1 has major anabolic functions in bone metabolism. We investigated the effect of recombinant murine Wnt1/Sfrp1 complex on the mesenchymal cell line ST2.
We used microarray analysis to detail the global gene expression of ST2 cells in response to 6 hour of treatment with 100 ng recombinant Wnt1/Sfrp1 complex.

overall_design: 6 samples from 2 conditions with 3 independent experiments each were analyzed. Effects of 6h treatment with 100 ng recombinant Wnt1/Sfrp1 complex were compared to PBS.

first: Timur

last: Yorgan

first: Leon

last: Grahn


title: Regulation of ABC Transporters and Ergosterol Biosynthesis by the Transcription Factor FvADS-1 Controls Azole Resistance and Virulence in Fusarium verticillioides

first: Yajing

last: Yin

address: No. 409 Guangrong Road

institute: Tianjin University of Commerce

summary: Fusarium verticillioides is a significant agricultural pathogen and an emerging causative agent of invasive fusariosis in clinical settings. Fusarium species frequently exhibit resistance to available antifungal agents, yet the molecular mechanisms underlying azole resistance remain poorly characterized. In this study, we identified the Zn(II)2Cys6 transcription factor FvADS-1 as a positive regulator of the azole stress response in F. verticillioides. The transcription of FvADS-1 was significantly induced by ketoconazole (KTC), and its deletion increased the susceptibility to multiple azole compounds. Mechanically, FvADS-1 positively regulates the KTC-induced expression of genes encoding ABC transporters and ergosterol biosynthesis enzymes, thereby modulating intracellular KTC accumulation and sterol homeostasis under azole stress. Furthermore, FvADS-1 positively regulates the transcriptional response of peroxisomal genes and contributes to fungal tolerance to oxidative stress. Notably, deletion of FvADS-1 attenuates the virulence of F. verticillioides on maize.

overall_design: For F. verticillioides, 107 conidia were inoculated in YPD liquid medium and cultured at 28°C with shaking (200 rpm) for 20 h. Then the mycelia were treated with or without 2 μg/mL KTC for 16 h. After harvest, the mycelia were finely grounded into powder in liquid nitrogen. RNA was extracted according to standard TRIzol method (Invitrogen, Carlsbad, CA, United States) and followed by sample analysis. Transcriptomic profiles of the F. verticillioides wild-type and FvADS-1 deletion strains, either treated with or without KTC, were analyzed by high-throughput RNA sequencing (RNA-seq).


title: Real-time quantitative PCR analysis of human glioblastoma and astrocytes

city: Isparta

first: Berrin

last: Ozdil

address: Cunur

department: Histology and Embryology

country: Turkey

institute: Suleyman Demirel University

summary: cell line of control and test groups

overall_design: qPCR gene expression profiling of glioblastoma and astrocyte cells with control and test group..  Cells were used and treated separately as indicated in the summary. Equal amount total RNA from each group was pooled prior to gene expression analysis.

first: Ozdil

last: Berrin

first: Kocaturk

last: Duygu


title: Dasatinib resensitizes BRAF/MEK inhibitor efficacy in patient-derived xenografts from patients with progression on BRAF/MEK inhibitor treatment

city: Philadelphia

first: Haiyin

last: Li

state: PA

address: 3601 Spruce Street

institute: The Wistar Institute

summary: Although BRAF/MEK inhibitor (BRAFi/MEKi) therapy initially shows high efficacy in patients with BRAFV600E/K cutaneous melanoma, resistance develops in over 75% of cases. We tested robustness of the umbrella trial strategy in this population by analyzing relationships between genomic status of a gene and associated downstream consequences at the protein level, which reveal poor relationships between mutations, copy number amplification, protein expression and activation.  An in vivo compound repurposing screen using 11 clinically relevant agents from an NCI-portfolio with pan-RTK, non-RTK and/or PI3K-mTOR specificity identified dasatinib as most capable of restoring sensitivity to BRAFi/MEKi in patient-derived xenograft (PDX) models originating from tumors that had progressed on BRAFi +/- MEKi. High baseline expression of BRAFi/MEKi resistance-associated proteins (e.g., AXL, YAP, HSP70, phospho-AKT) was predictive of response to BRAFi/MEKi plus dasatinib combination therapy. These findings suggest that adding dasatinib may help overcome resistance and restore anti-tumor activity in patients with BRAFi/MEKi-refractory cutaneous melanoma.

overall_design: Bulk RNAseq on melanoma patient-derived xenograft (PDX) models originating from tumors that had progressed on BRAF/MEKi.

first: Vito

middle: W

last: Rebecca

first: Min

last: Xiao

first: Yeqing

last: Chen

first: Meenhard

last: Herlyn


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

city: Chongqing

first: shuai

last: yue

state: Chongqing

address: Gaotanyan street

institute: army medical university

summary: The efficacy of combined chemotherapy and PD-1 immune checkpoint blockade (ICB) is constrained by a fundamental pharmacological conflict, as chemotherapy indiscriminately eliminates the proliferating tumor-specific CD8+ T (TTST) cells that PD-1 ICB aims to expand. To overcome this limitation, we targeted the chemotherapy-resistant bystander CD8+ T (TBYS) cell niche. We found that within the tumor microenvironment, CD8+ TBYS cells persist in a quiescent state, in stark contrast to chemotherapy-susceptible TTST cells. Leveraging this, we developed an oncolytic virus (OV-BYTE) engineered to redirect TBYS cells against tumors. In preclinical models and patient-derived organoids, OV-BYTE synergized with chemotherapy to control tumor progression. This synergy stemmed from direct engagement of the TBYS cell reservoir and concurrent restoration of TTST cell function via reduced apoptotic susceptibility and promotion of a polyfunctional effector state. Importantly, integrating OV-BYTE into standard chemo-PD-1 ICB regimens yielded superior anti-tumor efficacy. Collectively, our work establishes TBYS cells as a pivotal therapeutic target and presents OV-BYTE as a translatable strategy that resolves a core constraint in current cancer therapy, unlocking more effective combination regimens.

overall_design: The library preparation for single-cell RNA sequencing (scRNA-seq) using the BD Rhapsody platform to study P14/OT1 CD8+ T cells in tumor when undergoing OV-BYTE treatment w/o chemotherapy. Here, we further demonstrate that OV-BYTE and chemotherapy activate tumor-specific and bystander T cells in pre-clinical models, thus jointly killing tumor cells. This study gives a transcriptome profiles of P14/OT1 CD8+ T cells in tumor with administration of OV-BYTE treatment and chemotherapy.

first: Yang

last: yang

first: Shuai

last: Yue

first: Junjian

last: He

first: Lilin

last: Ye

first: Xiangyu


title: Fluconazole reverses SHANK3-related autism-like deficits via lipid raft-driven IGF1R activation and prefrontal circuit remodeling

city: Shanghai

first: Hanyu

last: Wang

address: Siping Road

institute: Tongji University

summary: Autism spectrum disorder (ASD) is a neurodevelopmental condition that affects approximately 61.8 million people globally1. Mutations in the postsynaptic scaffolding protein SHANK3 define a high-penetrance ASD subgroup characterized by excitatory synaptic dysfunction2,3, yet disease-modifying therapies are lacking. Although transient IGF1 application ameliorates synaptic defects in Shank3-deficient models4, strategies for sustained activation of IGF1 receptor (IGF1R) signaling remain elusive. Here, we repositioned the FDA-approved antifungal agent fluconazole5 as an effective therapy for SHANK3-related ASD. In Shank3-deficient mice, fluconazole restored social deficits and repetitive behaviors through remodeling postsynaptic scaffold proteins. Mechanistically, fluconazole promoted lipid raft assembly to drive IGF1R homodimerization and activation, triggering ERK-mediated antioxidant responses to restore synaptic architecture, evidenced by Homer1/PSD95 re-colocalization. Integrated single-cell/nucleus RNA sequencing revealed fluconazole-induced prefrontal circuit remodeling, involving expansion of Homer1⁺ glutamatergic neurons and enhanced VIP⁺ GABAergic interneuron function. Fluconazole specifically potentiated communication from VIP⁺ interneurons to synapse-proficient glutamatergic neurons, leading to the restoration of postsynaptic ultrastructure in deep-layer prefrontal cortex. This reconfigured network induced by fluconazole supported a sustained recovery through a self-reinforcing IGF1-IGF1R-ERK signaling loop, with VIP⁺ interneurons serving as a potential IGF1 source. Collectively, our findings establish fluconazole as a clinically translatable therapy for SHANK3-related ASD via IGF1R-driven synaptic remodeling.

overall_design: This study administered fluconazole orally to Shank3-/- mice via drinking water for two weeks. The mice were divided into two groups: SHANK3 KO MOCK (vehicle control) and SHANK3 KO Flu (fluconazole-treated). After the treatment period, the mice were euthanized by cervical dislocation, and fresh prefrontal cortex tissue was rapidly dissected for subsequent combined single-cell and single-nucleus RNA sequencing (sc/sn-RNA-seq).

first: Xinming

last: Jia

first: Yebo

last: Gu

first: Siyu

last: Zhang


title: Transcriptomic effects of EZH2 inhibition by DZNep in VEGF-stimulated HUVECs

first: Sok I

last: Sok I

address: No. 639, Zhizaoju Road, Shanghai.

institute: shanghai jiaotong university

summary: Purpose: To compare transcriptome profiles of VEGF-treated HUVECs with or without the EZH2 inhibitor DZNep. Methods: HUVECs were treated with VEGF(20 ng/mL) or VEGF(20 ng/mL)+DZNep (10 μM) for 48 h. Total RNA was extracted using TRIzol, and poly(A)+ RNA was used for library construction following standard Illumina protocols. Sequencing was performed on an Illumina NovaSeq 6000 (PE150). Clean reads were obtained using fastp, mapped to the Homo sapiens genome (GRCh38) with HISAT2, assembled and quantified by StringTie, and differential expression was analyzed using edgeR. GO/KEGG analyses were performed using DAVID. Results: DZNep altered VEGF-induced gene expression, reducing pro-angiogenic genes and modulating pathways related to angiogenesis and endothelial function. Conclusions: This dataset provides RNA-seq profiling of VEGF-stimulated HUVECs with or without EZH2 inhibition and supports analysis of EZH2-regulated angiogenic signaling.

overall_design: RNA-seq was performed on HUVECs treated with 20 ng/mL VEGF or 20 ng/mL VEGF+10 μM DZNep for 48 h.

last: Ho


title: Incorporation of genomic determinants improves diagnostic accuracy of oligomonocytic chronic myelomonocytic leukemia

city: Houston

first: Ziyi

state: TX

address: 1400 Pressler Street

institute: MD Anderson Cancer Center

summary: Recent updates to the monocyte count thresholds for diagnosing chronic myelomonocytic leukemia (CMML) have been implemented to recognize oligomonocytic CMML (OM-CMML) as an early stage within the CMML spectrum. However, the clinical validity of these changes remains uncertain without considering biological factors. In this study, we compared a large cohort of patients (N=911) with OM-CMML (n=249), CMML (n=359), and myelodysplastic syndromes (n=303) using unsupervised clustering to assess the role of genomic determinants in improving CMML diagnostic accuracy. Our findings show that CMML molecular signatures, characterized by biallelic TET2 mutations or SRSF2-TET2 co-mutations, are associated with a distinct transcriptome, monocytic bias, classical monocytosis, and progression to overt CMML in OM-CMML cases. By developing a weighted and reproducible model, we demonstrate that genomic features, combined with bone marrow monocyte frequencies, can reliably predict CMML progression in OM-CMML. These results support the integration of genomic determinants into the CMML diagnostic framework to enhance diagnostic accuracy and suggest that incorporation of our proposed clinic-ready diagnostic workflow into clinical practice might reliably identify early stage CMML with oligomonocytic features.

overall_design: Bulk RNA sequencing in bone marrow CD34+ cells from patients with CMML, MDS and OM-CMML

first: Guillermo

last: Montalban Bravo


title: Single-cell transcriptomic profiling reveals sex-specific microglial responses to simulated galactic cosmic radiation without classical inflammatory activation

city: Rochester

first: Mark

middle: Ayor

last: Osabutey

state: New York

address: 601 Elmwood Avenue

institute: University of Rochester Medical Center

summary: Long‑duration deep space missions expose astronauts to galactic cosmic radiation (GCR), a complex mixture of high‑ and low‑LET ions that can compromise central nervous system (CNS) health. Microglia, the resident immune cells of the brain, are highly sensitive to radiation, yet their cell‑state adaptations to space‑relevant mixed‑field exposure remain poorly defined. Here, we performed single‑cell RNA sequencing (scRNA‑seq) of hippocampal microglia isolated from male and female C57BL/6J mice 53 days after acute 100 cGy 5‑ion GCR simulation. Behavioral testing showed no overt deficits, but scRNA‑seq revealed subtle, sex‑specific transcriptional remodeling. Male microglia engaged a stress‑adaptive program characterized by upregulation of Fkbp5, Rtp4, Creb5, and metabolic regulators, with concurrent downregulation of ER chaperone and ribosomal genes. Female microglia displayed a transcriptionally blunted phenotype with selective induction of Fkbp5, Ccnd3, and Tnfaip3, and broad downregulation of inflammatory and NOD/TNF pathways. Canonical inflammatory or disease‑associated microglia signatures were absent and homeostatic markers (P2ry12, Cx3cr1) were preserved. These findings define a non‑inflammatory, sex‑specific microglial response to space‑relevant GCR and provide a cellular framework for sex‑informed CNS risk assessment and countermeasure development for deep space travel.

overall_design: Six‑month‑old male and female C57BL/6J mice were randomly assigned to sham irradiation or exposure to 100 cGy simplified 5‑ion galactic cosmic radiation simulation (GCRsim) at the NASA Space Radiation Laboratory (Brookhaven National Laboratory). Behavioral testing (open field, novel object recognition, contextual fear conditioning) was performed 48–51 days post‑irradiation. At 53 days post‑irradiation, mice were euthanized by injection with a mixture of xylazine (10 mg/kg, i.p.) and ketamine (100 mg/kg, i.p.) and perfused intracardially with 0.15 M PBS containing 0.5% sodium nitrite and 2 IU heparin/mL. Hippocampus and overlying cortex were dissected and CD11b+ microglia were isolated by fluorescence‑activated cell sorting. Samples were multiplexed using TotalSeq‑B anti-CD45 antibody hashing and profiled by 10x Genomics single‑cell 3′ gene expression sequencing. Single‑cell transcriptomes were analyzed to quantify sex‑ and radiation‑dependent changes in microglial cell states, differential gene expression, and pathway enrichment.

middle: A

first: Lia

last: Calcines-Rodríguez

first: Lee

last: Trojanczyk

first: John

last: Oslchowka

first: M. Kerry

last: O'Banion


title: Effects of oxytocin receptor agonists on the hair growth ability of dermal papilla cells

city: Kawasaki

first: Tatsuto

last: Kageyama

state: Kanagawa

address: Life Innovation Center, 3-25-22 Tonomachi

country: Japan

institute: Kanagawa Institute of Industrial Science and Technology

summary: We examined effects of oxytocin receptor agonists on the hair growth ability of dermal papilla cells.

overall_design: We annalysed gene expression of human dermal papilla cells with/without oxytocin receptor agonists treatment for 6 days.

first: Junji

last: Fukuda


title: Study on the mechanism of olfactory neurons in regulating circadian rhythm

city: Beijing

first: Pengfei

last: Lv

address: No. 2, Old Summer Palace West Road

institute: China agricultural university

summary: The olfactory neural circuitry plays a crucial role in regulating circadian rhythms. Our data demonstrate that mutation of the olfactory receptor orco in Drosophila significantly reduces rhythmicity in aged flies. Through neuPrint+ analysis and RNA-seq, we revealed that SIFamide (SIFa) neurons—which are associated with locomotor regulation—are closely connected to the olfactory neural circuit, and that the expression of the SIFa neuropeptide receptor (SiFaR) is significantly downregulated in orco mutants. Genetic evidence further indicates that olfactory receptor neurons receive external environmental signals and relay this information to SIFa neurons, thereby modulating the expression pattern of the core clock gene Period (Per), which ultimately affects circadian behavior in aging flies. Notably, the lifespan extension observed in orco mutants is closely associated with reduced Per expression in the gut. In summary, this study reveals that orco-dependent expression of Per in both the brain and the gut collectively contributes to age-related changes in circadian rhythmic behavior. This research provides new insights and a theoretical foundation for studying the mechanisms of aging by uncovering the intrinsic connection between olfactory neural circuits and circadian rhythmic behavior during aging.

overall_design: RNA-seq was performed on head tissues of wildtype (w1118) and orco2 mutant Drosophila at Day 3 and Day 40, respectively, and on intestinal tissues of wildtype (w1118), orco2, and per01 mutants at Day 40.

first: Lin

last: Wan


title: Defining the role of RNase E in the mycobacterial degradosome-like network

city: Worcester

first: Scarlet

last: Shell

state: MA

address: 100 Institute Rd

department: Biology and Biotechnology

institute: Worcester Polytechnic Institute

summary: mRNA degradation is a fundamentally important process that is regulated in response to stress in the globally important pathogen Mycobacterium tuberculosis.  Several mycobacterial ribonucleases (RNases) are hypothesized to function together to coordinate mRNA degradation, but the interactions among them are mostly undefined.  One of these enzymes, RNase E, contains intrinsically disordered regions (IDRs) and initiates mRNA degradation.  Here, we aimed to define the interactions between major mycobacterial mRNA degradation enzymes and identify the function(s) of the two IDRs of RNase E in the nonpathogenic model Mycolicibacterium smegmatis.  We found that the two IDRs differentially impact mRNA degradation rates in vivo but are largely functionally redundant in their impacts on steady-steady transcript abundance.  In vitro, the IDRs are uninvolved in catalysis but play major roles in RNA binding and interactions with other mRNA degradation enzymes, namely PNPase, RNase J, and RhlE1.  In vivo, these enzymes localize with RNase E, but its IDRs play only a minor role, suggesting substantial redundancy in subcellular localization mechanisms.  Collectively, we propose a degradosome-like network model in mycobacteria, held together by dynamic, transient interactions among RNA degradation enzymes and RNA that can be disrupted during physiologically relevant stress to allow for adaptability.

overall_design: M. smegmatis strains were constructed in which the native copy of rne (encoding RNase E) was deleted and a copy of rne with its native promoter and 5' UTR was inserted into the L5 phage integration site. All rne versions had N-terminal 6xhis-3xFLAG tags. The N-terminal deletion lacked codons 2-329, the C-terminal deletion lacked codons 824-1037, and the N- and C-terminal double deletion lacked both.

first: Abigail

middle: R

last: Rapiejko

first: Ying

last: Zhou

first: Junpei

last: Xiao

first: Vidhyadhar

last: Nandana

first: Jared

middle: M

last: Schrader


title: Inhibiting Aberrant Interfacial Friction Regulates Cell Fate and Promotes Cartilage Regeneration

first: Hongyu

last: Zhang

address: No. 30 Shuangqing Road, Haidian District

department: State Key Laboratory of Tribology in Advanced Equipment

institute: Department of Mechanical Engineering, Tsinghua University

summary: Aberrant interfacial friction, both within tissues and between tissues and implanted biomaterials, is an overlooked factor that can lead to suboptimal outcomes of tissue regeneration. The role of aberrant interfacial friction in modulating cell behavior and influencing tissue regeneration is poorly understood.

overall_design: In this study, using cartilage as a model tissue, we demonstrated that interfacial friction was exacerbated following cartilage injury in both humans and rats, driving increased wear of the opposing articular surface. For concept validation, we engineered an automatic cell friction generating system (ACF-GenSys) to emulate the interfacial friction between implanted biomaterials and native cartilage in vitro. Our results demonstrated that aberrant frictional force was directly responsible for triggering cell apoptosis through Piezo1-dependent calcium ion influx. To mitigate these effects, we developed a super-lubricating gel (SL-Gel) that protected cells from frictional force and inhibited in vitro apoptosis. We achieved proof of concept in both rabbits and non-human primates with cartilage defects, where implantation of the SL-Gel reduced interfacial cartilage wear and enhanced defect regeneration. Using an animal model with high clinical relevance, this study unveiled the detrimental impact of interfacial friction between tissues and biomaterials on cell fate and tissue regeneration, and suggests that a super-lubricating biomaterial could enhance the outcomes of interfacial tissue regeneration in the presence of aberrant frictional forces.


title: RBPscan: A Quantitative, In Vivo Tool for Profiling RNA-Binding Protein Interactions

city: Québec

first: Dmitry

last: Kretov

state: Québec

department: Oncology Division

institute: CRCHU de Québec - Université Laval

summary: RNA-binding proteins (RBPs) are essential regulators of gene expression at post-transcriptional level, yet obtaining quantitative insights into RBP–RNA interactions in vivo remains a challenge. Here we developed RBPscan, a method that integrates RNA editing with massively parallel reporter assays (MPRAs) to profile RBP binding in vivo. RBPscan fuses the catalytic domain of ADAR to the RBP of interest, using RNA editing of a recorder mRNA as a readout of binding events. We demonstrate its utility in zebrafish embryos, human cells, and yeast, where it quantifies binding strength, resolves dissociation constants, identifies high-specificity motifs for a variety of RBPs, and links binding affinities to their impact on mRNA stability. RBPscan also provide positional information of conserved and novel Pumilio-binding sites in lncRNA NORAD. With its simplicity, scalability, and compatibility across systems, RBPscan offers a versatile tool for investigating RBP–RNA interactions and complements established methods for studying post-transcriptional regulatory networks.

overall_design: RBPscan analysis of hsaPum2 binding to various PREs was performed in HEK293T cells. Expression of the hsaPum2-ADAR fusion protein was induced by doxycycline. The reporter mRNA library contained 1,000 distinct PREs and other control sequences. Each experiment was conducted in three biological replicates.

first: Owen

last: Sanborn

first: Thora

last: McIssac

first: Elaine

last: Park

first: Imrat

last: Imrat

first: Marianne

last: Régis

first: Louis-Mathieu

last: Harvey

first: Samuel

last: Wu

first: Daniel

last: Cifuentes


title: Pollutant retrorsine induces hepatotoxicity through ATF3-mediated ferroptosis in mouse primary hepatocytes and Cyp3a4-HepG2 cells

city: Guiyang

first: Qing

last: Rao

address: Natural Products Research Center of Guizhou Province

summary: Pyrrolizidine alkaloid (PA) contamination in food poses a global health risk, primarily entering the human food chain through contaminated food. Given that ferroptosis—a form of cell death characterized by glutathione depletion—is involved in toxicant-induced liver injury and that retrorsine (RTS, A typical toxic PA) depletes glutathione, we investigated whether RTS induces hepatotoxicity via ferroptosis. This study demonstrates that RTS induces acute hepatotoxicity and ferroptosis in vitro and in vivo, RTS triggers mitochondrial dysfunction and activates ATF3, which translocates to the nucleus to directly repress PLA2G6 expression. Genetic studies revealed ATF3's dual role in enhancing RTS-induced cytotoxicity and oxidative stress, while its target PLA2G6 confers protection, unveiling a novel mechanism of RTS-induced liver injury centered on the ATF3-PLA2G6 axis. These findings demonstrates that RTS-induced hepatotoxicity, driven by ferroptosis, is governed by the ATF3-PLA2G6 axis, thus revealing a pivotal mechanism and a promising therapeutic target for PA-related liver injury.

overall_design: We set up control group (NaCl group), retrorsine 25mg/kg group, and 50mg/kg group, three repetitions per group, and collected mouse liver samples for RNA seq after intraperitoneal injection 2 hours.

first: Weiwei

last: Li

first: Jiang

last: Zheng


title: Transcriptional profiling of ageing muscle satellite cells treated with recombinant human MG53

city: Columbus

first: Jethro

middle: WANG

last: Zih-Shuo

state: Ohio

address: 460 W 12th Ave.

department: Department of Surgery

institute: Ohio State University

summary: Purpose: Skeletal muscle satellite cells (SCs) are essential for muscle regeneration. MG53 (TRIM72) is a key regulator of membrane repair, but its role in SC fate decisions remains elusive. This study aims to investigate the transcriptional regulatory role of MG53 in satellite cell quiescence maintenance, activation, and proliferation. Methods: Primary satellite cells were isolated from hindlimb muscles of C57BL/6 mice. Cells were cultured and treated with either recombinant human MG53 protein (rhMG53) or BSA (Vehicle Control) for 3 Days. Total RNA was extracted and subjected to high-throughput RNA sequencing (RNA-seq) to identify differentially expressed genes (DEGs). Results: Our analysis reveals that MG53 treatment significantly alters the transcriptomic landscape of satellite cells. Specifically, MG53 treatment upregulated genes associated with activation pathways, while downregulating genes related to inflammation or lineage differentiation. Conclusions: This dataset provides novel insights into the molecular mechanisms by which MG53 promotes satellite cell maintenance and regenerative capacity, highlighting its potential therapeutic value for muscle wasting diseases.

overall_design: Primary satellite cells were isolated from C57BL/6 mice. Cells were cultured in growth medium and treated with either rhMG53 protein or BSA (as vehicle control) for 3 days. Total RNA was harvested from 3 biological replicates per group (Total N=6). Comparative gene expression analysis was performed to identify differentially expressed genes (DEGs) between MG53-treated and Control groups.

first: Yanping

last: Xu

first: Hua

last: Zhu


title: Cell-dependent contributions of thrombospondin-1 to the rupture of abdominal aortic aneurysm in mice

city: Madison

first: Bo

last: Liu

state: WI

address: 1111 Highland Ave

institute: University of Wisconsin - Madison

summary: Rationale: Abdominal aortic aneurysms (AAA) rupture is a life-threatening event with unclear molecular mechanisms. Our previous work demonstrated elevated levels of the matricellular protein thrombospondin-1 (TSP1, encoded by Thbs1) in human and mouse AAA tissues. Single-cell RNA sequencing analysis identified macrophages, endothelial cells, and smooth muscle cells as the major TSP1-expressing cells in aneurysmal tissues. Global Thbs1 deletion reduces aneurysm formation by inhibiting vascular inflammation. Aims: To investigate how TSP1 deficiency in different cell types affects AAA rupture. Methods and Results: AAA and rupture were induced by angiotensin II infusion in hypercholesterolemic mice. In global Thbs1 deficient mice, hypercholesterolemia was achieved by crossing them with Apoe knockout mice. To generate cell type–specific TSP1 deficient mice, Thbs1 flox/flox mice were crossed with VE-cadherin-Cre, SMMHC-iCreERT2, and Lyz2-Cre mice to target endothelial cells, smooth muscle cells, and myeloid cells, respectively. In these conditional knockout models, hypercholesterolemia was induced via AAV-PCSK9. We found that both global and myeloid-specific Thbs1 deletion increased rupture rate over twofold, whereas endothelial- or smooth muscle cell–specific deletion had no significant effect. Endothelial-specific Thbs1 deletion reduced aneurysm size in the CaCl₂ model. Single-cell RNA sequencing and histology in myeloid-specific Thbs1 knockout aortas revealed broad suppression of inflammation and extracellular matrix production. Conclusions: Myeloid-derived TSP1 plays a critical role in inhibiting aneurysm rupture in mice, likely by promoting matrix repair phenotypes in vascular smooth muscle cells, enhancing vascular wall integrity.

overall_design: Male Thbs1fl/fl/Lyz2-Cre and Thbs1wt/wt/Lyz2-Cre mice (8-12 weeks of age) were subjected to the PCSK9-AAV/Angiotensin II model of AAA. Abdominal aortas were collected after 7 days of Angiotensin II infusion and digested into a single-cell suspension. For each genotype, cells from five mice were pooled into one sample and subjected to scRNA-seq.

first: Ting

last: Zhou

first: Huan

last: Yang


title: scRNAseq data of healthy and agangionic colon whole-tissue samples from three Hirschsprung's disease patient

city: Salt Lake City

first: Xiaomeng

last: Huang

state: Utah

department: Department of Human Genetics

institute: University of Utah

summary: The enteric nervous system (ENS) is a complex network of neurons and glial cells. Hirschsprung's disease (HSCR) is a congenital condition characterized by the absence of ganglion cells in the distal colon, leading to functional bowel obstruction. In this study, we used single-cell RNA sequencing (scRNA-seq) and whole genome sequencing (WGS) to analyze healthy and aganglionic colon segments from HSCR patients. Using scRNA-seq, we identified 13 major cell types in patient samples and observed that neural progenitor cells were present in both healthy and aganglionic colon regions, while mature neurons were absent from aganglionic colon. In these progenitor cells, critical differentiation pathway genes displayed reduced expression in the aganglionic colon, suggesting a disruption in their transition to mature neuronal cell types. Furthermore, transcriptomic analysis revealed significant alterations in gene expression across several stromal cell types. These transcriptomic shifts, particularly in mast cells, support the hypothesis that altered gene expression in the microenvironment of neural progenitor cells contributes to impaired differentiation. Our findings support the hypothesis that neural precursors in HSCR are capable of migration, but they are defective in their differentiation to mature cell types. Our analysis provides insights into potential therapeutic targets to stimulate neurogenesis in the aganglionic colon.

overall_design:
Tissue samples were collected from Hirschsprung's disease patients who went through surgery. Resected colon was examined by a pathologist and was separated into healthy and agangionic colon samples based on histochemistry. Following tissue homogenization single cell suspensions were subject to 10X 3' capture scRNAseq.

***************************************************************
Raw files for human/patient samples were not submitted to GEO due to concerns about submitting personally identifiable sequence data for open access.
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first: Szabolcs

last: Tarapcsak

first: Yi

last: Qiao

first: Andrew

last: Farrell

first: Lija

last: Mammen

first: Amy

last: Lowichik

first: Gayatri

middle: D

last: Khanderao

first: Teresa

last: Musci

first: Philip

middle: J

last: Moos

first: Matthew

last: Firpo

first: Michael

last: Rollins

first: Gabor

middle: T

last: Marth


title: Bulk transcriptomic profiling reveal the epithelial-protective role of ITGBL1 during the progression of colitis

city: Nantong

first: Mengmeng

last: Sang

address: Qixiu

institute: Nantong Unversity

summary: Inflammatory bowel disease (IBD) is characterized by progressive epithelial injury, chronic inflammation, and impaired intestinal barrier function. To comprehensively delineate the epithelial alterations and stress-related responses that occur during colitis progression, we investigated the functional role of integrin beta-like 1 (ITGBL1) in intestinal epithelial cells (IECs). Using patient specimens and DSS-induced colitis models, we identified marked upregulation of ITGBL1 in inflamed intestinal tissues. Loss of ITGBL1 resulted in the emergence of ferroptosis-prone epithelial subsets exhibiting elevated ACSL4 expression, lipid peroxidation, mitochondrial shrinkage, and enhanced oxidative stress, all of which were associated with aggravated epithelial damage and worse inflammatory outcomes. We further demonstrated that ITGBL1 deficiency activated the ANGPT2/PI3K-AKT signaling axis in IECs, leading to exaggerated oxidative stress and ferroptosis, accompanied by reduced expression of key tight-junction proteins including E-cadherin, ZO-1, occludin, and claudin-1. These alterations impaired epithelial cohesion and barrier integrity during disease progression. In contrast, supplementation with recombinant ITGBL1 suppressed ANGPT2 expression, mitigated PI3K-AKT hyperactivation, restored mitochondrial structure, alleviated ferroptosis, and improved epithelial barrier function. In conclusion, ITGBL1 serves as a critical regulator of epithelial stress responses and barrier stability during colitis, acting by restraining ANGPT2-mediated PI3K-AKT activation and ferroptotic cell death. These findings highlight a previously unrecognized epithelial-protective mechanism and identify the ITGBL1–ANGPT2 axis as a potential therapeutic target in IBD.

overall_design: Bulk transcriptomic profiling from colonic tissue samples of wild-type mice with 3% DSS–induced colitis(WT,n=3)and from ITGBL1-knockout mice with 3% DSS–induced colitis(ITGBL1-KO,n=3).

first: Kaitao

last: Lu

first: Gaoyang

last: Yuan

first: Chenghao

last: Ou


title: Involvement of pinin in terminal differentiation of human keratinocytes.

city: Toyama

first: Yoshiaki

last: Tabuchi

state: Toyama

address: 2630 Sugitani

department: Life Science Research Center

institute: University of Toyama

summary:
Pinin (PNN) was originally identified as a 140-kDa desmosome-associated protein located on the cytoplasmic face of desmosome for reinforcing the desmosome and intermediate filament complex. Recent studies showed that PNN is also a ubiquitously expressed nuclear protein located in nuclear speckle domains. Recent reports showed that PNN play a role in regulating RNA alternative splicing, gene regulation, cell–cell connection, embryogenesis, tumorigenesis, and cellular proliferation.
In the present study, to clarify a role of PNN in the terminal differentiation of keratinocytes, we performed global-scale gene expression analysis in PNN-knockdown keratinocytes using an Affymetrix GeneChip® system.

overall_design: Normal human epidermal keratinocytes (negative control siRNA), and normal human epidermal keratinocytes (siRNA for PNN) were used. Total RNA samples were prepared from the cells, and quality of the RNA was analyzed using a Bioanalyzer 2100. Gene expression was analyzed by an Affymetrix GeneChip® system with a Human Genome U133-plus 2.0 array. Sample preparation for array hybridization was carried out as described in the manufacturer’s instructions.

first: Teruhiko

last: Makino


title: Contrasting Mutant and Overexpressor Phenotypes Position KIN10 as a Central Growth-Defense Integrator

city: Praha 6

first: Karel

last: Muller

address: Rozvojová 263

institute: Institute of Experimenal Botany of the Czech Academy of Sciences

summary: Plants continuously balance growth and defense in dynamic environments where energy supply, microbial cues, and developmental programs interact intimately. The Sucrose non-fermenting-1 Related Kinase 1 (SnRK1) complex is widely recognized as a central metabolic hub, yet how its catalytic subunit KIN10 coordinates energy status with organ-specific developmental and immune outputs remains poorly understood. Our work fills this knowledge gap by combining transcriptomics, hormone profiling, pathogen assays, and redox phenotyping to elucidate how SnRK1/KIN10 shapes biotic stress responses in both roots and shoots. Our dataset shows how KIN10 orchestrates distinct root vs. shoot transcriptional landscapes and tunes whole-plant immune amplitude and biotic stress outcomes.

overall_design: RNAseq profiling of wild-type A.thaliana (Col-0 and Ler-0) and mutants with knock-out (kin10) or overexpression (KIN10-OE) of SnRK1.1/KIN10.

last: Müller

first: Tetiana

last: Kalachova

first: Katarzyna

last: Retzer


title: Umbilical cord mesenchymal stem cell spheroids loaded decellularized liver hydrogel rescues liver fibrosis by inhibiting hepatic stellate cells autophagy

city: JinZhong

first: Haichao

last: Diao

state: 山西省

address: 55 Wenhua Street, Yuci District, Jinzhong City, Shanxi Province, China

institute: Shanxi Medical University

summary: Liver fibrosis (LF), driven primarily by activated hepatic stellate cells (aHSCs), progresses to life-threatening end-stage diseases such as cirrhosis, hepatocellular carcinoma. As the only effective treatment, liver transplantation remains limited by donor scarcity. While mesenchymal stem cells (MSCs) exert anti-fibrotic effects via immunomodulation, autophagy regulation, and tissue regeneration, their clinical application is hindered by poor survival, short residence time, and inefficient homing after systemic administration. Recent advances indicate that 3D MSCs spheroids enhance cell viability and paracrine function compared to monodispersed cells. Human umbilical cord MSCs (HUMSCs) are ideal due to low immunogenicity and minimal ethical concerns. Injectable decellularized extracellular matrix (dECM) hydrogels, particularly liver-derived ECM (LdECM), offer a bioactive microenvironment to support cell retention and sustained release.HUMSCs spheroids (HUMSCs sph) were engineered using AggreWell™ plates. An injectable hydrogel was fabricated from decellularized Sprague-Dawley (SD) rat liver scaffolds (LdECM). A novel therapeutic strategy for LF was developed by encapsulating HUMSCs sph within LdECM hydrogels. The structure and characteristics of HUMSCs sph/sus and LdECM were assessed. The efficacy of localized high-density HUMSCs sph delivery was evaluated in a C57BL/6 mouse model of bile duct ligation/carbon tetrachloride (BDL/CCL4)-induced LF, comparing outcomes against equivalent doses of HUMSCs suspension (HUMSCs sus). HSCs autophagy and activation were detected while co-cultured with HUMSCs sph/sus.

overall_design: Transcriptome sequencing analysis was performed on the cell suspension of 2D-cultured human umbilical cord mesenchymal stem cells and the aggregates of human umbilical cord mesenchymal stem cells prepared using AggreWell™ culture plates

first: Tingjuan

last: Huang

first: Jun

last: Xie


title: Early skin seeding regulatory T cells modulate PPARγ-dependent skin pigmentation [IC_early_late_skin_bulk]

city: London

first: Niwa

last: Ali

address: King’s College London, 28th Floor, Tower Wing  Guy’s Hospital, Great Maze Pond

country: United Kingdom

institute: King's College London

summary: To understand the role of early skin-seeding neonatal Tregs, we performed scRNA-seq of Treg-sufficient and Treg-depleted skin on postnatal day 9 (P9). Further, we performed bulk RNA-seq of sorted Tregs from P9 and Treg-sufficient and Treg-depleted skin from P9 and P13 mice.

overall_design: For whole skin bulk RNA-seq, (n=2-3 per condition), individual samples represent one biological replicate from each mouse. Bulk RNA-seq of Tregs were performed by sorting Tregs from the skin and skin draining lymph nodes into trizol.

first: Inchul

last: Cho

first: Jessie

middle: Z

last: xu

first: Monica

last: Sen


title: KRAS-ERK Signaling Drives Metastasis in Colorectal Cancer via Phosphorylation Dependent Activation of the ZBTB20-TGFBR2 Axis

city: Guangzhou

first: jieru

last: huang

address: 195 Dongfeng West Road, Yuexiu District, Guangzhou

institute: Guangzhou Medical University

summary: We integrated data from clinical databases (TCGA, CPTAC) with experimental validation using human CRC cell lines, a tissue microarray, and two distinct in vivo metastasis models (liver and lung colonization). ZBTB20 expression and function were analyzed by IHC, Western blotting, Transwell assays, and RNA-seq integrated with ChIP-seq data. The mechanism of ZBTB20 regulation was investigated via co immunoprecipitation, mass spectrometry, truncation analysis, site-directed mutagenesis, and luciferase reporter assays. Statistical significance was determined using Student's t tests, ANOVA, and survival analysis. Our findings delineate a novel KRAS-ERK-ZBTB20-TGFBR2 signaling axis that is a critical driver of metastasis in KRAS-mutant CRC. The robust efficacy of a TGFBR2 degrader in multiple in vivo models validates this axis as a viable therapeutic target, offering a promising strategy to inhibit metastatic progression in patients with this aggressive disease.

overall_design: RNA-seq profiling of wildtype SW620 cells and their knockdown derivatives (shZBTB20).

first: Qincheng

last: Liu

first: Jieru

first: Zhe

last: Zhang

first: Zhijian

last: Xu

first: Shanshan

last: Li

first: Wu

last: Guo

first: Xi

first: Tao

last: Shen

first: S

last: Vega-Rubín-de-Celis

first: Qiang

first: Runya

last: Fang

first: Yongjie

last: Wei


title: Turning foes to friends: H2S-Consumed Multifunctional Nanoplatform for Photothermal–Nanocatalytic Synergistic Therapy Inducing Ferroptosis to Enhance Colorectal Cancer Immunotherapy

city: Changchun City

first: bin

last: yang

state: Jilin

address: No. 4110, Yatai Street, Nanguan District, Changchun City, Jilin Province

institute: jilin university

summary: Colorectal cancer treatment remains difficult, with traditional approaches restricted by indications, toxicity, and resistance. In this study, we present a tumor microenvironment-responsive nanoplatform, Cu2O@AuMn@HA, that induces ferroptosis through photothermally enhanced dual enzyme-like activities, thereby improving the immunotherapy outcome of CRC. Leveraging hyaluronic acid, the platform selectively targets CD44-overexpressing cells and undergoes conversion to CuxS in response to the elevated H2S levels within tumors, achieving in situ photothermal therapy (PTT) while consuming endogenous hydrogen sulfide (H2S). The nanoplatform exhibits both peroxidase-like (POD-like) and glutathione oxidase-like (GSHOx-like) catalytic activities, promoting reactive oxygen species (ROS) generation while depleting glutathione, thereby disrupting redox homeostasis and driving ferroptosis. Simultaneously, the photothermal effect accelerates these catalytic reactions, further enhancing therapeutic efficacy. Ferroptosis, combined with photothermal stress, provokes immunogenic cell death (ICD), which facilitates immune cells infiltration, and alleviates the immunosuppressive tumor microenvironment. Moreover, the incorporation of Au and Mn endows the platform with triple-modal imaging capabilities -fluorescence imaging, computed tomography (CT), and magnetic resonance imaging (MRI)- enabling precise localization and real-time monitoring at both the cellular and animal levels. In vitro and in vivo experiments demonstrate near-complete tumor eradication in CRC models via a photothermal-nanocatalytic-immune triple-synergistic mechanism, with favorable safety profiles. This study introduces a multifunctional, scalable, precision-based diagnostic and therapeutic strategy for CRC, providing novel insights for future clinical translation.

overall_design: Following treatment in the control group and the Cu₂O@AuMn@HA + NaHS + NIR group, CT26.WT cells were harvested using Trizol (Invitrogen) for mRNA sequencing and analysis.

first: Bin

last: Yang

first: Annan


title: Remarkable composition shift of cone subtypes combined with changes on phototransduction due to cone mosaicism induced by ARR3 variants

first: Jiamin

last: Ouyang

state: Guangdong

address: 7 Jinsui Road

institute: Zhongshan Ophthalmic Center, Sun Yat-sen University

summary: Heterozygous variants in ARR3, encoding cone arrestin, have been identified to cause high myopia with a unique X-linked female limited inheritance but the potential mechanism for the unusual anti-X-linked pattern is still unclear. Arr3 expression profiles showed that Arr3, with significant expression in retina since P14, was almost co-stained with Opsin red/green in cones including some partially co-stained with both Opsin red/green and Opsin blue. And then Arr3 knock-in mice and Arr3 knock-out rats were generated. A mosaic expression of Arr3 was present in rodents with Arr3 heterozygous deficiency according to retinal flat-mount staining. Retinal single-cell RNA sequencing revealed significant changes in proportion of three cone sub-clusters in Arr3+/- rats, namely significantly decreased M/S cones, and significantly increased S cones. Pde6h was the only one differentially expressed genes (DEGs) shred in M/S cones in the comparison group Arr3+/+ vs. Arr3+/- and Arr3-/0 vs. Arr3+/-, but not in Arr3+/+ vs. Arr3-/0. These results suggest that heterozygous Arr3 loss in cones causes mosaic changes of cone subtypes that might mimic defocus visual signals in phototransduction.

overall_design: Retinal single-cell RNA sequencing (scRNA-seq) for subcluster of cones and  gene expression changes in samples of the induced Arr3+/+, Arr3+/- and Arr3-/0 rats.


title: Transcriptomics Analysis of bulk RNA from dissected brain regions (medial prefrontal cortex, cerebellum, and hippocampus) from 129/Sv-Cyp2e1tm1Gonz/J (CYP2E1-KO) and 129S1/SvImJ (WT) mice

city: Charleston

first: Jessica

middle: H

last: Hartman

state: South Carolina

address: 70 President St., Drug Discovery Bldg/Rm DD220

department: Biochemistry and Molecular Biology

institute: Medical University of South Carolina

summary: To establish the consequences of whole-animal deletion of CYP2E1, we isolated RNA from dissected brain tissue (cerebellum, medial prefrontal cortex, dorsal hippocampus, and ventral hippocampus) of 16-week male and female WT and KO mice. Mice were maintained on a normal chow diet and were euthanized using CO2 and decapitation prior to brain dissection.

overall_design: Samples include WT and KO groups, with males and females in three biological replicates (1,2, and 3) for each of 4 brain regions

first: Hyland

middle: C

last: Gonzalez

first: Kelly

last: Misare

first: Kate

last: Glorioso

first: Joe

last: Delaney

first: Howard

last: Becker

first: Marcelo

middle: F

last: Lopez

first: Patrick

last: Mulholland


title: Sex specific correction of maternal inflammation-induced behavioral abnormalities by the inhibition of colony-stimulating factor 1 receptor

city: Bordeaux

first: Charlotte

last: Madore

address: 146 rue Leo Saignat

department: Alimentation Humaine

country: France

institute: INRAE

summary: We have previously reported the therapeutic effect of depletion and regeneration of endogenous microglia on autism spectrum disorder-like behaviors in offspring from the dams under maternal immune activation (MIA) by dampening their neuritogenic activation. Here we show a long-lasting pathological effect by MIA, leading to abnormal behaviors in offspring mice in a sex-specific manner at 3 months of age. MIA was induced by injecting Polyinosinic:polycytidylic acid [Poly(I:C)] at 10mg/kg at E9.5 with preselected dams based on the immunoreactivity to low-dose Poly(I:C) injection. MIA offspring show impairments in sociability, repetitive behavior, and spatial working and associative memories in both sexes, whereas only male offspring show social novelty deficit. MIA has no effect on anxiety-like behavior nor sensori-motor or locomotor activity. Administering colony stimulating factor receptor (CSF1R) inhibitor in young adult MIA offspring regenerates microglia and ameliorates sociability deficits in males and spatial working and associative memory impairments in both sexes without effect on social novelty impairments. Transcriptomic analysis of prefrontal cortex and hippocampal tissues revealed MIA and sex-specific pathways and highlighted potential key genes involved in the corrective effect of microglial regeneration in MIA offspring. Our results reveal the sex specific therapeutic applications of CSF1R inhibitor for MIA-related social and cognitive disorders.

overall_design: Illumina NovaSeq™ 6000 was used to identify bulk hippocampal and prefrontal cortex transcriptomic signatures in MIA vs Saline injected-mice +/- CSF1R inhibitor (PLX5622, Plexxikon) injections to target and renew microglia populations.

first: Seiko

last: Ikezu

first: Tsuneya

first: Delpech

last: Jean-Christophe


title: Coumarin accumulation inthe root and canopy of Notopterygium franchetii at different growth stage

city: xining

first: Shengrong

last: Xu

address: kunlun

institute: qinghai university

summary: Transcriptomics analyses indicated that there were multiple genes differentially expressed between the root system and the canopy at different growth stages. These genes were associated with multiple pathways contributing to phenylalanine synthesis and metabolism. Moreover, the transcriptional activity of related enzyme-encoding genes did not differ significantly at each step of the pathway from the synthesis of umbelliferone to the formation of various coumarin compounds. Metabolomics analyses of the root and canopy indicated 491 differentially accumulated metabolites were involved in 82 metabolic pathways during the vegetative growth stage, while 572 differentially accumulated metabolites were associated with 76 metabolic pathways during the reproductive growth stage. Additionally, 307 differentially accumulated metabolites in both growth stages were involved in 14 metabolic pathways, many of which were related to coumarin biosynthesis.

overall_design: the aboveground and belowground parts of 2-year-old plants were collected during the vegetative growth and reproductive growth periods

first: Lili

last: Pei

first: Ruili

last: Ma

first: Shibing

first: Shengping

last: Qi

first: Zhuofei

last: Wang

first: Xiaoyue


title: Single cell RNA-seq reveals that the Vibrio cholerae Mak toxins are required for killing of Tetrahymena pyriformis and for survival in protozoan expelled food vacuoles

city: Sydney

first: M. Mozammel

last: Hoque

state: NSW

address: 15 Broadway, Ultimo

department: Australian Institute for Microbiology & Infection (AIMI)

country: Australia

institute: University of Technology Sydney

summary: Vibrio cholerae uses multiple strategies to resist predation by heterotrophic protozoa. For example, V. cholerae releases toxic compounds such as ammonium and pyomelanin, that can kill protists such as Tetrahymena pyriformis. V. cholerae also survives intracellularly and escapes as viable cells inside protozoan expelled food vacuoles (EFVs). We previously reported that V. cholerae encased in EFVs are hyperinfectious, establishing an important link between anti-protozoal strategies and bacterial virulence. Although the intracellular resistance and escape of V. cholerae in EFVs has been reported, the molecular mechanisms behind this remain poorly understood. Here, we used single cell transcriptomics of V. cholerae exposed to T. pyriformis and captured a total of 5,344 bacterial cells with heterogeneous gene expression. Cells with the same pattern of gene expression were grouped, resulting in eleven clusters of cells with a unique gene expression profile. Genes encoding outer membrane proteins, F1F0-Na+/H+ ATPase, metabolites and toxins showed differential expression among the clusters. Furthermore, the motility-associated killing factor (Mak) toxins (makA, makB and makC) were differentially expressed. Individual  V. cholerae ΔmakA, ΔmakB, and ΔmakE strains were not capable of killing T. pyriformis and ΔmakA and ΔmakE showed reduced survival inside EFVs compared to the wild type. Our findings reveal new insights into the grazing resistance mechanisms of V. cholerae, identify factors associated with the survival of V. cholerae within EFVs and more broadly, highlight the connection between antiprotozoal and virulence factors displayed by pathogenic bacteria.

overall_design: Intracellular Vibrio cholerae bacteria recovered from Tetrahymena pyriformis and from EFVs were fixed in 4% formaldehyde at 4 degc overnight and then the MicroSPLiT protocol was perfromed to individalluy tage the mRNA of the bacteria

first: M

first: Diane

last: McDougald

first: Jonah

last: Moon

first: Gustavo

last: Espinoza-Vergara


title: microRNA-17-5p Modulates Ventral Hippocampal Transcriptome and Synaptic Proteome: Implications for Emotional Regulation in Adult Male Rats

city: Independencia

first: Wladimir

middle: Antonio

last: Corrales

address: Olivos 1007

country: Chile

institute: Universidad de Chile

summary: The hippocampus plays a crucial role in memory and emotional regulation, with its dorsal pole supporting cognitive functions and the ventral hippocampus modulating anxiety and affective processing via limbic interactions. Chronic restraint stress induces anxious- and depressive-like behaviors in rodents, alongside transcriptomic changes in the ventral hippocampus. Emerging evidence highlights microRNAs as modulators of synaptic architecture and gene expression. Notably, miR-17-5p—part of the miR-17-92 cluster— shows increased cortical expression in individuals with mood disorders, and its levels in neural extracellular vesicles correlate directly with depressive symptom severity in male patients, suggesting translational relevance. In rodent models, chronic stress exposure produces divergent hippocampal expression patterns of miR-17-5p. Whether miR-17-5p acts as a passive biomarker of mood disorder or actively contributes to stress adaptation remains unclear.  In the present study, chronic stress exposure increased miR-17-5p expression specifically in the ventral hippocampus of male rats, with no changes detected in females. To assess its functional relevance, we reproduced this alteration in the ventral hippocampus of naïve male to evaluate behavioral outcomes and characterize both global and synaptic transcriptomic and proteomic profiles. Behaviorally, miR-17-5p mimic administration increased the sucrose preference, revealing an antidepressant-like effect. On the other hand, open field tests did not reveal anxiety-related differences, whereas the novelty-suppressed feeding test indicated a decrease in anxious-like behavior following miR-17-5p administration. Molecular analyses in ventral hippocampus homogenates and synaptic-enriched fractions revealed modulation of ribosomal protein composition and translational regulation—likely through mTOR pathway activation—favoring GABAergic adaptation and synaptic remodeling. These findings suggest a region-specific role of miR-17-5p in the ventral hippocampus that may contribute to its anxiolytic and antidepressant-like effects.  These results provide novel insights into miR-17-5p-mediated mood regulation, highlighting its potential as a therapeutic target for anxiety and depressive disorders.

overall_design: Adult male Sprague-Dawley rats weighing 300-350g at the beginning of the procedures were housed in groups of four per cage. Rats were maintained with controlled temperature (22–23 °C) and humidity (45%), with a standard light: dark cycle (12 h:12 h between 7 am and 7 pm). Additionally, the animals were handled daily for two weeks before starting the interventions, determining their weight and food consumption evolution. To evaluate the effects of chronic stress on the levels of miRNAs in the vHPC, the animals were randomly assigned to control (n=5) and stressed group (n=5). The stressed group was restrained for 2.5 hours per day for 2 weeks. Another cohort of animals was used to evaluate the role of miR-17-5p in the vHPC. For this, at the age of 2 months, the rats were randomly assigned to 2 different experimental conditions (11 - 13 animals per condition): A group was injected with a scrambled sequence of small RNA without target mRNAs (Control), and another group was injected with a miR-17-5p mimic (Mimic) into the vHPC.

first: Felipe

last: Olave

first: Tatiana

last: Guarnieri

first: Juan

middle: P

last: Silva

last: Aguayo

first: Matías

last: Alarcón

first: Luciano

last: Román-Albasini

first: Julia

last: Catalán

first: Pablo

middle: I

last: González

first: Nicolas

last: Palacios

first: Valentina

last: Mora-González

first: Carlos

last: Álvarez-Navarro

first: Esteban

last: Aliaga

first: John

last: Cidlowski

first: Pedro

last: Zamorano

first: Jenny

middle: L

last: Fiedler


title: Discovery of a Selective RXRγ Degrader WCF-598 for the Treatment of Castration-Resistant Prostate Cancer

first: Hong

last: Wang

address: 132, Waihuandonglu, Daxue Cheng

department: School Of Pharmaceutical Sciences

institute: Sun Yat-sen University

summary: Castration-resistant prostate cancer (CRPC) remains a significant therapeutic challenge with limited effective treatment options. We identified retinoid X receptor γ (RXRγ) as a critical regulator of CRPC cell proliferation, highlighting it as a previously unrecognized and tractable target for therapeutic intervention. However, no RXRγ-selective modulators have been reported. Herein, we utilized the PROTAC approach to develop WCF-598 as a selective RXRγ degrader, which exhibits excellent specificity over RXRα and RXRβ isoforms. WCF-598 promoted efficient RXRγ degradation through the ubiquitin–proteasome system, leading to robust anti-proliferative activity in CRPC models. In vivo, WCF-598 induced significant tumor regression in 22Rv1 xenografts-bearing mice without observable toxicity. Notably, WCF-598 also exhibited a secondary activity by degrading androgen receptor splice variant 7 (AR-V7), a clinically relevant driver of therapy resistance in CRPC. These results establish WCF-598 as a selective chemical probe for investigating the function of RXRγ in CRPC and potentially other RXRγ-related diseases.

overall_design: 22Rv1 cells treated with WCF-598 or untreated.

first: Chaofan

first: Jieying

last: Lin

first: Junping

last: Pei

first: Zhanfang

last: Kang

first: Zhuoheng

last: Liu

first: Junwei

last: Li

first: Guodi

last: Cai

first: Yang

last: Zhou

first: Junjian

first: Xiaoyun

last: Lu


title: Synergistic Stromal Remodeling and Dual Chemo-Immunotherapy in Pancreatic Cancer: A Two-Stage Losartan-Primed followed Nanocarrier Strategy for Tumor Microenvironment Reprogramming

city: Beijing

first: Xun

last: Hu

address: Student Dormitory, No. 17, Panjiayuan So

institute: Department of Imaging Diagnosis National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital

summary: Pancreatic ductal adenocarcinoma (PDAC) is marked by a dense, fibrotic stroma that hinders drug delivery and promotes an immunosuppressive microenvironment. We developed a two-stage therapeutic strategy (LIGEL) that combines losartan-mediated stromal preconditioning with the targeted delivery of a hybrid nanocarrier (IGEL) co-loaded with gemcitabine and IL-12 circRNA. The efficacy of this approach was evaluated in vitro and in vivo, with RNA sequencing used to explore transcriptomic changes in the tumor microenvironment after treatment. Losartan pretreatment significantly reduced extracellular matrix deposition and cancer-associated fibroblast activation, enhancing cellular uptake and tumor penetration. This resulted in notable tumor growth inhibition, prolonged survival, and minimized gemcitabine-associated systemic toxicity. Transcriptomic analysis revealed tumor cell depletion and immune microenvironment activation. These findings highlight the potential of losartan-primed nanotherapy to reprogram the tumor microenvironment and improve the efficacy of combined chemotherapy-immunotherapy.

overall_design: pancreatic tumor samples of mice from the GEM, IGEL, LIGEL, and control groups (n=6) were collected, and total RNA was extracted and quality-controlled. All samples underwent transcriptomic library preparation and quality assessment prior to sequencing.

first: Qian


title: Vitamin B12 Ameliorates Diabetic complications: potential role of Circadian pathway and the NAMPT–NAD⁺–SIRT1 Pathway

city: CHAPEL HILL

first: Yukako

last: Kayashima

state: NC

address: 710 BRINKHOUS-BULLITT BUILDING CB #7525

department: Pathology Lab Med

institute: University of North Carolina at Chapel Hill

summary: Vitamin B12 is emerging as a potential therapeutic agent for diabetes-associated complications, with roles in redox balance, methylation, and mitochondrial function. Recent evidence suggests that B12 may also regulate circadian rhythms, which are closely linked to metabolic health. However, the connection between B12, circadian regulation, and protection against early diabetic liver and kidney damage remains unclear. Diabetic (Elmo1H/HIns2Akita/+) and non-diabetic (Elmo1HH) mice were treated with or without Vitamin B12 (10 mg/kg/day) in drinking water for 8 weeks, starting at 8 weeks of age. At 16 weeks, blood, liver, and kidney samples were collected for biochemical, transcriptomic, and histological analysis. Vitamin B12 significantly reduced serum triglycerides, improved mesangial expansion in kidneys, and improved liver cellular structure in diabetic mice. B12 also modulated circadian gene expression, downregulating Clock, Bmal1, and Npas2 (40–50%) while upregulating Cry1/2, Per1–3, Nr1d2, and Dbp in both liver and kidney (130–180%), regardless of diabetic status. Importantly, B12 significantly increased Nampt expression in the liver (p = 0.0062) and kidney (p = 0.0013) of diabetic mice, suggesting enhancement of the NAMPT–NAD⁺–SIRT1 axis, a key pathway for mitochondrial redox control and circadian stability. Additionally, B12 upregulated several solute carrier (SLC) transporters involved in nutrient and ion homeostasis. Together, these findings indicate that Vitamin B12 offers early protective effects against diabetic complications by improving metabolic balance and enhancing Nampt expression, supporting its potential role in preventing liver and kidney damage via circadian and NAD⁺-dependent mechanisms.

overall_design: RNA Seq profiling of liver and kidney tissues of non-diabetic Elmo1H/HIns2+/+  and diabetic Elmo1H/HIns2Akita/+ mice were tretaed with and without vitamin B12 via drinking water.

first: Niroshani

last: Wariyapperuma

first: Anshulika

last: Deshmukh

first: Rachel

last: Moser

first: Qiing

last: Ma

first: Feng

last: Hagaman

first: Nobuyo

last: Maeda


title: Early skin seeding regulatory T cells modulate PPARγ-dependent skin pigmentation [IC_LN_skin_Tregs_bulk]

first: Niwa

last: Ali

first: Inchul

last: Cho

first: Jessie

last: xu

first: Monica

last: Sen


title: GVH_transcriptomic_validation_cohort

city: Paris

first: David

last: Michonneau

address: 1 avenue Claude Vellefaux

department: Hematology and transplantation

institute: Assistance Publique des Hôpitaux de Paris

summary: Transcriptomic analysis from patient's samples after hematopoietic stem cell transplantation with or without acute GVHD

overall_design: PBMC samples of patients treated with haematopoietic stem cell transplant, presenting with or without aGVHD

first: Sophie

last: Le Grand

first: Nicolas

last: Vallet

first: Yannick

last: Marie

first: Delphine

last: Bouteiller

first: Margo

last: Fernandez

first: Gwendolyn

last: Marguerit

first: Émeline

last: Mundwiller

first: Émilie

last: Robert

first: Régis

last: Peffault de Latour

first: Gérard

last: Socié


title: RNA-seq analysis of p62 knockout in murine oral carcinoma MOC2 cells

city: Toyoake

first: Juntaro

last: Yamasaki

state: Aichi

address: 1-98 Dengakugakubo, Kutsukake-cho

institute: Fujita Health University

summary: p62/SQSTM1 is an autophagy adaptor protein that regulates stress responses and contributes to tumor progression. To clarify its role in oral cancer, we generated p62 knockout clones of the murine oral carcinoma cell line MOC2 using CRISPR-Cas9. RNA-seq was performed on parental and p62-deficient cells to assess transcriptomic changes associated with p62 loss. The dataset includes raw FASTQ files and processed gene-level count matrices, providing a resource for the study of p62-dependent molecular pathways in cancer biology.

overall_design: Bulk RNA-seq was performed on the murine oral carcinoma cell line MOC2 to compare transcriptomes of parental versus p62 knockout cells. Three biological replicates were generated per condition (n = 6 total). RNA was extracted using the RNeasy Mini Kit (Qiagen). Poly(A) RNA was isolated with the NEBNext Poly(A) mRNA Magnetic Isolation Module, and stranded libraries were constructed using the NEBNext Ultra II Directional RNA Library Prep Kit for Illumina (New England Biolabs). Sequencing was performed on an Illumina NextSeq 2000 using NextSeq 1000/2000 P2 Reagents (100 Cycles, v3; cat. no. 20046811) to generate 2 × 50 bp paired-end reads. Libraries from both groups were prepared in parallel to minimize batch effects. Raw FASTQ files and processed gene-level count matrices are provided.

first: Kentaro

last: Suina

first: Tatsuya

last: Sakaguchi


title: Mitochondrial Microprotein MOCCI Controls Neuroinflammation by Altering Glial Activation States [scRNA-seq]

city: South San Francisco

first: Kimberle

last: Shen

state: CA

address: 1 Dna way

institute: Genentech

summary: MOCCI, discovered in a screen for mitochondrial peptides that modify inflammatory outcomes, has emerged as a significant regulator of neuroinflammation. Here, we show that MOCCI is upregulated in microglia and astrocytes in both the mouse and human brain upon neuroinflammation, and is required for orchestrating proper, complete, and beneficial activation of microglia and astrocytes. Induction of MOCCI triggers the transition of glial into a neuroprotective state and promotes the resolution of inflammation. In vitro, MOCCI deficiency leads to reduced migration, phagocytosis and cytokine secretion in glia. In the cuprizone mouse model of Multiple Sclerosis, MOCCI plays a role in both demyelination and remyelination: MOCCI deficiency protects against cuprizone-induced oligodendrocyte death and prevents remyelination by inhibiting the clearance of cellular debris.

first: Lena

last: Ho


title: Linear Ubiquitination in Keratinocytes Amplifies Psoriatic inflammation via TNF-α/NF-κB Signaling [RNA-seq 2]

city: Kyoto

first: Satoshi

last: NAKAMIZO

state: Kyoto

address: 54 Shogoin-Kawahara, Sakyo

institute: Kyoto University

summary: Psoriasis is a chronic inflammatory skin disorder driven by dysregulated immune signaling and keratinocyte activation. While the importance of proinflammatory cytokines such as TNF-α, IL-23, and IL-17 in psoriasis is well established, the upstream mechanisms amplifying these pathways, particularly within keratinocytes, remain incompletely defined. Here, we investigate the role of linear ubiquitination—a post-translational modification catalyzed by the linear ubiquitin chain assembly complex (LUBAC)—in psoriasis pathogenesis using a transgenic mouse model (HOIL-1LΔRING1) with enhanced LUBAC activity. In the imiquimod-induced psoriasis model, HOIL-1LΔRING1 mice exhibited exacerbated skin inflammation characterized by increased epidermal thickness, leukocyte infiltration, and elevated expression of Tnf and Il23a. Transcriptomic and pharmacologic analyses showed that linear ubiquitination amplified TNF-α/NF-κB signaling, and TNF-α blockade ameliorated disease severity. BM chimera experiments demonstrated that this effect was mediated by radio-resistant skin cells, particularly keratinocytes. Flow cytometry and in vitro assays confirmed that keratinocyte-intrinsic linear ubiquitination promotes TNF-α production, which was suppressed by a LUBAC inhibitor. Finally, analyses of human psoriatic skin confirmed elevated linear ubiquitination and LUBAC component expression in keratinocytes. These findings identify linear ubiquitination in keratinocytes as a key amplifier of psoriatic inflammation and a potential therapeutic target.

overall_design: RNA-seq of primary cultured keratinocytes from wild-type and HOIL1 ΔRING1 mice before confluence.

first: Ken I

last: Kosaka

last: Nakamizo

first: Kenji

last: Kabashima


title: Investigating the mechanisms by which SMAD6 mutations cause tracheoesophageal birth defects

city: Cincinnati

first: Konrad

last: Thorner

state: OH

address: 3333 Burnet Ave

institute: Cincinnati Children's Hospital Medical Center

summary: Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) are tracheoesophageal (TE) birth defects which affect 1 in 3000 live births in the United States. EA occurs when the esophagus fails to form a continuous tube from the oral cavity to the stomach and TEF occurs when there is an abnormal connection between the trachea and esophagus. The etiology of EA/TEF arises when the common foregut tube fails to properly separate into the esophagus and respiratory tract during early embryogenesis. This process is essential for proper organ function and involves complex molecular and morphological processes. As part of a multi-institutional project aiming to identify genes causing tracheoesophageal defects, we identified two EA/TEF patients who presented with different mutations in SMAD6, a BMP signaling inhibitor. We used a CRISPR-based approach to knock down smad6 in frog embryos and observed separation defects of the esophagus and trachea, supporting the conclusion that SMAD6 mutations in humans may cause EA/TEF. To investigate the role of SMAD6 during human development, we used CRISPR to generate human pluripotent stem cell lines with loss-of-function alleles in SMAD6. The human foregut is comprised of an inner layer of endoderm-derived epithelium surrounded by mesenchyme, and it is not known if SMAD6 functions in either or both layers. To elucidate this, we investigated the role of SMAD6 in either foregut epithelium or mesenchyme, or both in combination. Our analysis of human SMAD6-/- tracheoesophageal epithelium and mesenchyme reveals an increase in BMP/TGFβ signaling, consistent with its role as a repressor of these pathways. We also observed patterning defects in both tissue types; SMAD6 mutant endoderm shows increased expression of distal gut tube markers and SMAD6 mutant mesenchyme shows increased expression of cardiac markers. Furthermore, we observed cell differentiation changes, where SMAD6-/- mesenchyme had decreased ability to form CD31-positive vasculature, as well as changes in genes involved in processes such as cell migration and extracellular matrix deposition, which are critical for mesenchyme morphogenesis and differentiation during the process of TE separation. Our results suggest SMAD6 mutations impact the identity and function of human engineered TE tissue. By identifying pathways significant for TE development during early embryogenesis, our results contribute to understanding how patient mutations cause congenital malformations.

overall_design: RNA-seq profiling of WT (iPSC115_3) and SMAD6-/- (CRISPR83_12) iPSCs differentiated  into endoderm and mesenchymal lineages: day 3 definitive endoderm, day 6 anterior foregut endoderm, day 9 dorsal anterior foregut endoderm and day 9 ventral anterior foregut endoderm as well day day 4 splanchnic mesoderm as well as day 7 esophageal and respiratory mesenchyme.

first: Sauer

last: Vivien

first: Thorner

last: Konrad


title: CD31+ Cell Enrichment Partly Enhances the Therapeutic Effects of Stromal Vascular Fraction in Experimental Primary Osteoarthritis

city: Berlin

first: January

last: Weiner

address: Charitéplatz 1

department: CUBI

institute: Berlin Institute of Health, Charité Medical University of Berlin

summary: Mesenchymal stromal/stem cell therapy has been extensively studied as a therapeutic strategy for osteoarthritis (OA). However, its clinical translation is hindered by multiple factors, including expansion-related senescence and regulatory hurdles. Stromal vascular fraction (SVF), a less processed and clinically accessible therapeutic option, offers logistical advantages but remains regenerative. We hypothesized that, as a more defined cell population, CD31⁺-enriched SVF (CD31⁺ SVF) would exhibit greater therapeutic efficacy than unselected SVF. To test this hypothesis, we conducted a comparative efficacy study using the Dunkin Hartley guinea pig model of spontaneous OA. Spatial analysis revealed that both treatments modulated extracellular matrix composition in cartilage, including reduced fibronectin and type I collagen levels, with CD31⁺ SVF showing more pronounced effects. Both therapies attenuated cartilage fibrosis, preserved cartilage by increasing aggrecan and suppressing catabolic enzymes such as MMP-13, and reduced inflammation, as evidenced by decreased TNF-α and MCP-1 expression. Notably, these protective effects may involve partially distinct molecular mechanisms. Compared to SVF, CD31⁺ SVF showed greater and more consistent improvements in trabecular bone integrity in OA. These effects may contribute to modulation of the osteochondral unit and warrant further mechanistic investigation.

overall_design: RNA-seq profiling of knee cartilage and infrapaterllar fat pad from Dunkin Hartley guinea pigs 6 months after receiving intra-articular injections of DPBS or SVF or CD31⁺ SVF.

first: Sijia

last: Zhou

first: Tobias

last: Winkler

first: Bin

last: Chen

first: Marta

last: Grzeski

first: Florian N.

last: Fleckenstein

first: Dominik

last: Geisel

first: Alexander

last: Hildebrandt

first: Daniela

last: Aschenbrenner

first: Marie Agatha

last: Mohn

first: Benjamin

last: Claass

first: Sven

last: Geissler

first: Georg N.

last: Duda

first: Søren P.

last: Sheikh

first: Oliver

last: Klein

first: Tazio

last: Maleitzke


title: Microglia-like cells derived from patients with obsessive-compulsive disorder and social anxiety disorder

city: Seongnam-si

first: Minsoo

last: Kwon

address: 335 Pangyo-ro

department: Pharmacology

institute: CHA University

summary: Microglia are central to neuroimmune surveillance and synaptic remodeling, yet their contribution to obsessive–compulsive disorder (OCD) remains unclear. Here, we generated patient-derived microglia-like cells (iMGs) from OCD (n = 19), social anxiety disorder (SAD; n = 16), and healthy control (HC; n = 20) participants to identify the molecular and functional alterations in OCD-iMGs and to find therapeutic targets capable of restoring their functions. Bulk transcriptomic profiling of iMGs identified a selective reduction of MDM2 in OCD-iMGs. Notably, MDM2 mRNA was negatively correlated with Dimensional Obsessive-Compulsive Scale (DOCS) scores. Functional assays in siRNA-transfected primary microglia demonstrated that MDM2 knockdown impaired synaptosome phagocytosis and blunted LPS induced inflammatory responses, validating MDM2 as a mechanistic node. A Connectivity Map analysis nominated bortezomib, and subsequent experiments showed that bortezomib restored MDM2 expression and rescued phagocytic and immune functions in both MDM2-deficient microglia and OCD-iMGs. Collectively, these findings implicate microglial MDM2 reduction as a feature of OCD with direct functional consequences.

overall_design: Human RNA samples isolated from peripheral blood monocyte–derived microglia-like cells of 13 healthy controls, 13 obsessive-compulsive disorder patients, and 11 social anxiety disorder patients were sequenced.

first: Soyoung

last: Sung

first: Chan

last: Rim

first: Hui-Ju

last: Kim

first: Junho

last: Park

first: Jae-Jin

first: Se-Joo

first: Min-Soo


title: Staphylococcus aureus intoxicates stem cells to accelerate repair

city: New York

first: Dr. Shruti

last: Naik

state: NY

address: 1425 Madison Ave

department: Immunology and Immunotherapy

institute: Icahn School of Medicine at Mount Sinai

summary: Pathogens are typically viewed as barriers to healing—but Staphylococcus aureus defies this paradigm. We identify its secreted toxin LukED as an unexpected accelerator of tissue repair. Through functional screening and bacterial genetics, we uncover LukED as a pro-repair virulence factor that enhances both epithelial and muscle healing. In skin, LukED drives migratory and senescence-associated programs in wound-edge epidermal stem and progenitor cells. Using organoid models and primary epithelial cultures, we show that LukED acts directly on skin epithelia to promote repair. Remarkably, this activity is independent of pore formation, revealing a noncanonical function for an otherwise cytolytic toxin. Our findings redefine microbial influence on host physiology and introduce microbial DAMPs (mDAMPs) as a new class of pro-reparative effectors.

overall_design: RNA-seq of murine skin wound edge tissue at D1 post-wounding. At D0, wounds were associated with PBS or S. aureus LAC (1000 CFU).

first: Ikjot

last: Sidhu

first: Rachel

last: Kratofil

first: Shruti


title: Whole-genome bisulfite sequencing (WGBS) for LKB1 overexpressing and NNMT knockdown A549 cells

city: Chongqing

first: He

last: Xiao

state: Chongqing

address: No. 10, Changjiang Branch Road, Yuzhong District, Chongqing 400042, China

department: Department of Cancer Center

institute: Daping Hospital, Army Medical University

type: Methylation profiling by high throughput sequencing

summary: Global hypomethylation is associated with senescence. Liver kinase B1 (LKB1) encoded by tumor suppressor gene serine/threonine kinase 11 (STK11) plays an important role in cellular senescence. LKB1 deficiency results in global DNA hypomethylation in lung adenocarcinoma accompanied by reduced DNA methyltransferase 1 (DNMT1) expression and elevated nicotinamide N-methyltransferase (NNMT) levels. However, whether LKB1 deficiency causes resistance to antitumor therapy by regulating cellular senescence through affecting global DNA methylation status remains unknown. Investigation by using A549 cells reveals that LKB1 deficiency inhibited DOX-induced senescence by upregulating NNMT to promote global DNA hypomethylation

overall_design:
Genome-wide DNA methylation profiling by whole-genome bisulfite sequencing

***************************************************************
because of some technological problems that should mainly be attributed to the failure to effectively repair the raw sequencing data container, we are afraid we could not able to provide fastq files for WGBS
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first: Zhaoqian

last: Dang

first: Han

last: Gao

first: Xiaoyan

last: Dai

first: Lujie

last: Yang

first: Jiangyang

last: Li

first: Jianwu

last: Zhu

first: Xueling

last: Tong

first: Lei

last: Zhang

first: Xiao

first: Mengxia


title: Astrocytic PEN-2 Governs Cerebral Edema via Autophagic Control of AQP4 Homeostasis

city: nanjing

first: Jinxing

last: Hou

state: china

address: Department of Orthopedic Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, 321 Zhongshan Road

department: Department of Orthopedic Surgery

summary: Cerebral edema, a life-threatening consequence of central nervous system (CNS) injury, lacks effective therapies. Aquaporin-4 (AQP4), the main water channel in astrocytes, plays critical roles in both the formation and resolution of edema, with unclear regulatory mechanisms. Here, we uncover a γ-secretase-independent function of presenilin enhancer 2 (Pen-2) in AQP4 turnover. Conditional Pen-2 inactivation in astrocytes results in metabolic alterations, severe cerebral edema and early lethality. Mechanistically, Pen-2 physically interacts with AQP4 to promote its degradation through the autophagy-lysosome pathway. Treatment with acetazolamide, an AQP4 inhibitor, reverses the edema phenotype in Pen-2-deficient mice, establishing AQP4 as a critical downstream effector. This study unveils a previously unrecognized Pen-2-AQP4 axis that governs brain water homeostasis and reveals a promising therapeutic target for edema treatment.

overall_design: RNA-seq profiling of wildtype and Pen-2 cKO mice cortex at P8.

first: Huiru

last: Bi

first: Guiquan

last: Chen