title: The SGLT2 Inhibitor Empagliflozin Enhances Metabolic Efficiency and Ameliorates Left Ventricular Hypertrophy in Myosin R403Q Mutant Hypertrophic Cardiomyopathy Mice

first: Boston University

last: Microarray and Sequencing Resource

address: 72 East Concord Street, E631

department: Microarray and Sequencing Resource

institute: Boston University

summary:
Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and impaired metabolic efficiency. This study investigates the therapeutic potential of the sodium-glucose cotransporter 2 inhibitor empagliflozin (EMPA) in ameliorating these pathological features in a mouse model carrying the myosin R403Q mutation.
Methods: Male mice harboring the R403Q mutation were treated with EMPA for 16 weeks. We utilized multinuclear magnetic resonance spectroscopy (31P, 13C, 23Na MRS), alongside echocardiography, transcriptomic, proteomic, and phosphoproteomic profiling to assess metabolic, structural, and functional changes.
Results: EMPA facilitated the coupling of glycolysis with glucose oxidation and normalized elevated intracellular sodium levels. Treatment resulted in a significant reduction in LVH and myocardial fibrosis as evidenced by echocardiography and histopathology. These structural improvements correlated with enhancements in mitochondrial ATP synthesis, fatty acid oxidation (FAO), and branched-chain amino acid (BCAA) catabolism. Furthermore, empagliflozin improved left ventricular diastolic function and contractile reserve, underscored by improved ATP production and reduced energy cost of contraction. Notably, these benefits were linked to downregulation of the mTOR signaling pathway and normalization of myocardial substrate metabolic fluxes.
Conclusion: EMPA significantly mitigates structural and metabolic dysfunctions in a mouse model of HCM, underscoring its potential as a therapeutic agent for managing this condition. These findings suggest broader applicability of SGLT2 inhibitors in cardiovascular diseases, including those due to myocardial-specific mutations, warranting further clinical investigation.

overall_design:
We hypothesized that treatment with EMPA would improve cardiac energetics, contractile function and structure in HCM. To test this hypothesis, we studied mice carrying the myosin R403Q mutation treated with EMPA for 16 weeks. Through the application of multinuclear MR spectroscopy (31P, 13C, and 23Na MRS), alongside transcriptomic, proteomic, and phosphoproteomic profiling, we determined that EMPA treatment facilitates the coupling of glycolysis with glucose oxidation and normalizes the elevated intracellular sodium levels observed in HCM myocardium.
Nine-to-ten-week-old male mice harboring R403Q mutation in cardiac myosin heavy chain or wild-type littermates were fed ad libitum a control diet or the same diet enriched with EMPA for 16 weeks. Transcriptomic analysis was conducted in 12-week-old R403Q hearts prior to the onset of left ventricular hypertrophy.

first: Tomas

last: Baka

first: Ivan

last: Luptak


title: Transcriptome changes in MCF7 cells after treatment with NONO ligands and controls

status: Public on Jun 09 2025

city: La Jolla

first: Garrett

middle: Lee

last: Lindsey

state: CA

address: 10650 N Torrey Pines Rd

department: Chemistry

country: USA

institute: Scripps Research

type: Expression profiling by high throughput sequencing

summary: RNA-Sequencing to determine transcriptome changes in MCF7 cells after treatment with NONO ligands and controls. NONO knockout (sgNONO) or control (sgControl) cells were treated.

overall_design: sgControl or sgNONO MCF7 cells were treated in biological triplicate with DMSO (0.1%) or (R, R)-GL-373 (20µM) or (S, S)-GL-373 or (R)-SKBG-1(5µM) or (S)-SKBG-1(5µM) for 6 hours

middle: L

first: Benjamin

middle: F

last: Cravatt


title: Fetal liver macrophage development and function require Xpr1 [RNA-Seq]

city: Zurich

first: Sebastian

middle: A

last: Stifter

address: Winterthurerstrasse 190

country: Switzerland

institute: University of Zurich

summary: Erythroblastic island macrophages (EBI-Macs) support the development of red blood cellsby recycling iron, producing growth factors,and clearing nuclei expelled from erythroblasts. In the developing embryo, the liver is the primary site of hematopoiesis,andfetal liver macrophagesperform the function ofEBI-Macs.Here, weshowthatthephosphate exporterXpr1is critical for the development offetal macrophagesin the liver and the spleen.Single-cellRNA-seqand flow cytometryanalysesin conditional mice lackingXpr1in hematopoietic and/orCD206+cellsrevealedloss of the Kupffercelltranscriptional program anda shift in the development offetal livermonocytes towards an interferon-activated monocyte/macrophage state.Functionally, thisled tothefailure to clear pyrenocytes.In adulthood,splenic red pulp and bone marrow macrophages were alsoabsent upon lossof intrinsicXpr1.Collectively,these findings reveal thatXpr1is required for the development, identity, and function ofEBI-Macs.

overall_design: CD45+ F4/80hi CD11blow fetal liver macrophages were sorted from E15.5 Xpr1fl/fl and Mrc1Cre Xpr1fl/fl embryonic livers. Gene expression analysis was performed on four Xpr1fl/fl and five Mrc1Cre Xpr1fl/fl samples

first: Melanie

last: Greter


title: Mettl3 maintains genome stability of erythroid cells via Mthfd1-mediated nucleotide biosynthesis

city: zhengzhou

first: Hengchao

last: Zhang

state: Henan

address: 河南省郑州市高新技术开发区科学大道100号郑州大学新校区

country: China

institute: zzu

type: Methylation profiling by high throughput sequencing

summary: N6-methyladenosine (m6A) is a prevalent modification of mammalian mRNA. Increasing evidence has documented diverse roles of m6A in normal cell physiology and diseases. However, our knowledge on the role of the m6A in erythropoiesis is very limited. A previous study implicated the role of METTL3, the catalytic enzyme for m6A modification, in human erythropoiesis in vitro. But the function role of METTL3 in vivo has yet to investigated. In this study, we found that deletion of Mettl3 using EpoR-Cre mouse led to microcytic/hypochromic anemia due to defective erythropoiesis along with impaired hemoglobin biosynthesis. Mechanically, Mettl3 deficiency disrupted nucleotide biosynthesis which induced DNA damage, leading to apoptosis of CFU-E cells and cell cycle arrest of erythroblasts. Integrated m6A sequencing and RNA-seq analysis along with biochemical studies identified Mthdf1, a key enzyme involved in nucleotide biosynthesis, as a Mettl3 direct target gene. Furthermore, deletion of Mettl3 led to decreased expression of Mthdf1 accompanied by a shortage of nucleotides dTMP and IMP in erythroid cells. Additionally, inhibition of METTL3 in human erythroid cells led to similar phenotypic and molecular changes, indicating conserved role of METTL3 in human and murine erythropoiesis. Our findings have identified a novel Mettl3-m6A-Mthfd1 axis that plays a critical role in erythropoiesis by maintaining genome stability of erythroid cells via regulation of nucleotide biosynthesis. These findings provide novel insights into the regulatory mechanisms of erythropoiesis.

overall_design: Mouse erythroid progenitor cells and proerythroblasts were sorted, collected, and washed twice with PBS, then amplified by the Smart-Seq2 method. An Oligo-dT primer was used in the reverse transcription reaction for first-strand cDNA synthesis, followed by PCR amplification to enrich the cDNA and a magbeads purification step to clean up the product.  Next, the cDNA was randomly fragmented by ultrasonic waves prior to Illumina library preparation. After library preparation, PerkinElmer LabChip® GX Touch and Step OnePlus™ Real-Time PCR System were introduced for library quality inspection. Qualified libraries were then loaded on Illumina Hiseq platform for PE150 sequencing.For m6A-seq, m6A immunoprecipitation was performed according to the standard protocol. The cDNA was fragmented to ~300 bp using Tn5 transposase and processed using the TruePrep DNA Library Prep Kit V2 (Vazyme, TD501). Final libraries were amplified with the Tn5 adaptor and 3' primer (AATGATACGGCGACCACCGAGATCTACACTAGATCGCTCGTCGGCAGCGTCAGATGTGTATAAGAGACAGGTAATACGACTCACTATA) and sequenced as 150-bp paired-end reads on an Illumina HiSeq X Ten platform.

first: Linlin

first: Huizhi

last: Zhao

first: Xiaoli

last: Qu


title: Single-cell and spatial transcriptomics reveal the pathogenesis of chronic granulomatous disease under natural conditions [SPF or CL]

city: Tianjin

first: Hanzhi

last: Yu

address: 22 Meteorology Station Road, Heping District, Tianjin

institute: Tianjin Medical University

summary: Chronic granulomatous disease (CGD) is a rare and hereditary immunodeficiency disorder attributed to a malfunction in the NADPH oxidase 2 (NOX2) of phagocytes. Owing to the deficiency of NOX2-derived reactive oxygen species, individuals with CGD exhibit increased susceptibility to pathogens, including bacteria and fungi. This defect also contributes to an excessive inflammatory response, leading to tissue damage. In this study, we established a CGD infection model with Ncf2-/- genetic background through controlled environmental exposure. Within Specific Pathogen-Free (SPF) facilities, Ncf2-/- mice showed no signs of infection. However, under CL grade conditions (CL), these mice spontaneously developed fibro-encapsulated necrotizing lung granulomas. Through single-cell RNA sequencing (scRNA-seq) and flow cytometry, we detected a significant expansion of neutrophils and monocyte-derived macrophages (MDMs) in the lung tissues of CGD mice, identifying a NOS2high neutrophil subset characterized by a proinflammatory transcriptional signature and a specific MDMs subset marked by NOS2 and ARG1. In the spatial transcriptomics data, the NOS2high neutrophils were located in the core area of granulomas, promoting the inflammatory response by highly expressing Mif, Il1b, and Il1a, while the specific macrophage subset was situated at the periphery of granuloma lesions, facilitating extracellular matrix remodeling by expressing Fn1, Mmp9, Mmp12, and Mmp14. Pharmacological inhibition of MIF can significantly diminish neutrophil infiltration and granuloma formation via MIF/NLRP3/IL1β axis. Furthermore, loss of the myeloid-specific pro-survival gene Morrbid resulted in the apoptosis of myeloid cells in CGD and loss of Il1r1 also mitigated diseases, leading to reduction of systemic inflammation in the two compound mutants. In summary, through controlling the environmental factors, we constructed a natural model of CGD infection, elucidated granuloma formation by single-cell and spatial transcriptomics, and developed three interventions.

overall_design: We compared changes in lung tissue in WT and Ncf2-/- mice under different environmental conditions (SPF or CL). We performed Single-cell RNA sequencing (SPF WT, SPF NCF2-/-, CL WT, CL NCF2-/-) and spatial transcriptome sequencing (CL WT, CL NCF2-/-) on mouse lung tissue. In addition, we extracted mouse bone marrow cells for Single-cell RNA sequencing (CL WT, CL NCF2-/-) and sorted bone marrow lin cells for bulk RNA sequencing.

first: Ge

last: Dong

first: Zhigang

last: Cai


title: Hypoimmunogenic hPSC-derived cardiac organoids for immune evasion and heart repair [bulkRNA-seq]

status: Public on Jun 08 2025

city: Charleston

first: Nathaniel

last: Hyams

state: SC

address: 68 President St

department: Bioengineering

institute: Clemson University

summary: Human pluripotent stem cell (hPSC)-derived cardiac therapies hold great promise for heart  41 regeneration but face major translational barriers due to allogeneic immune rejection. Here, we  42 engineered hypoimmunogenic hPSCs using a two-step CRISPR-Cas9 strategy: (1) B2M  43 knockout, eliminating HLA class I surface expression, and (2) knock-in of HLA-E or HLA-G trimer  44 constructs in the AAVS1 safe harbor locus to confer robust immune evasion. Hypoimmunogenic  45 hPSCs maintained pluripotency, efficiently differentiated into cardiac cell types that resisted both  46 T and NK cell-mediated cytotoxicity in vitro, and self-assembled into engineered cardiac  47 organoids. Comprehensive analyses of the hypoimmunogenic cells and organoids revealed  48 preservation of transcriptomic, structural, and functional properties with minimal off-target effects 49 from gene editing. In vivo, hypoimmunogenic cardiac organoids restored contractile function in  50 infarcted rat hearts and demonstrated superior graft retention and immune evasion in humanized  51 mice compared to wild-type counterparts. These findings establish the therapeutic potential of  52 hypoimmunogenic hPSC-CMs in the cardiac organoid platform, laying the foundation for off-the shelf cardiac cell therapies to treat cardiovascular disease, the leading cause of death worldwide.

overall_design: Control (19-9-11) and hypoimmune (B2M KO/HLA-E KI) hiPSC lines were developed. mRNA from both hiPSC conditions was isolated for RNA-seq (n = 4 per condition). Following this, hiPSCs were differentiatied into four terminal cell types: hPSC-cardiomyocytes (iCMs), hPSC-epicardial cardiac fibroblasts (iECFs), hPSC-endothelial cells (iECs), and hPSC-pericytes (iPCs). mRNA was isolated from each terminal cell for both conditions for RNA-seq (n = 4 per condition). Cardiac organoids were fabricated from terminally differentiated cells for each condition, cultured for 5 days, where they were dissociated and mRNA was isolated for RNA-seq (n = 4 per condition).

first: Bain

last: Jacelyn

first: Bao

last: Xiaoping

first: Barrs

last: Ryan

first: Ferreira

last: Leonardo

first: Floy

last: Martha

first: Haideri

last: Tahir

first: Howells

last: Alessandro

first: Hyams

last: Nathaniel

first: Kerr

last: Charles

first: Li

last: Mei

first: Lian

last: Xiaojun

first: McDougal

last: Thomas

first: Mei

last: Ying

first: Morningstar

last: Jordan

first: Norris

last: Russel

first: Palecek

last: Sean

first: Randolph

last: Lauren

first: Ream

last: Michael

first: Robino

last: Rob

first: Ruddy

last: Jean Marie

first: Silver

last: Sophia


title: Oridonin as a Novel KDM5C Inhibitor Alleviates Clonal Hematopoiesis Induced Cardiac Aging via H3K4me3 Dependent SASP Suppression [RNA-seq]

city: Guangzhou

first: Lu

last: Lu

address: No.12,Airport Road,Baiyun District

institute: Guangzhou University of Chinese Medicine

summary: We applied Tet2⁺/⁻ bone marrow transplantation (BMT) mouse model to investigate the contribution of clonal hematopoiesis to cardiac aging. A transcriptome-guided small-molecule screening strategy was employed to identify potential therapeutic compounds. Target validation involved molecular docking, enzymatic inhibition, and surface plasmon resonance assays.  Genetic and pharmacological perturbation experiments were conducted to examine pathway involvement. Tet2⁺/⁻-BMT mice exhibited age-progressive myocardial fibrosis, inflammation, senescence, and functional decline. Oridonin reversed CHIP- and aging-associated transcriptional signatures and attenuated cardiac remodeling. Mechanistically, oridonin inhibited KDM5C histone demethylase. Downregulation of the pro-senescent factor S100A8 and suppression of SASP-associated inflammation were observed.

overall_design: RNA-seq profiling was performed on cardiac tissues from wild-type and Tet2-deficient mice 12 months after bone marrow transplantation and treatment with Oridonin 2 months.

first: Xingling

last: Chen

first: Qiangqiang

last: Zhao

first: Linhuang

first: Shengrong

last: Lin


title: Transcriptomic analysis of Vibrio parahaemolyticus interaction with phage VpP2326.

status: Public on Jun 10 2025

city: 扬州市

first: Mengxian

last: Wang

state: 江苏省

address: 扬州市邗江区扬州大学文汇路校区7号楼313

institute: Yangzhou University

summary: The transcriptome changes of Vibrio parahaemolyticus in normal culture and pahge VpP2326 infection were studied by RNA sequencing. The data showed that  39 genes were up-regulated and 2 genes were down-regulated.

overall_design: The transcription profiles of Vibrio parahaemolyticus after water treatment and  were phage VpP2326 treatment compared. Each condition contains three biological copies.

first: Chengkun

last: Zheng


title: Spatial transcriptomics unveils novel potential disease mechanisms associated with the microenvironment in Multiple Myeloma

city: Thuwal

first: Laura

last: Sudupe

address: King Abdullah University of Science and Technology (KAUST)

country: Saudi Arabia

institute: KAUST

summary: Understanding the spatial organization of the bone marrow (BM) microenvironment at single cell resolution and the niche specific transcriptional regulatory programs remains a challenge. Using formalin-fixed paraffin-embedded (FFPE) samples from our recently described MIcγ1 multiple myeloma (MM) mouse model (Larrayoz et al, Nat Med. 2023), we performed spatial transcriptional profiling of healthy and multiple myeloma BM using the Visium Spatial Gene Expression analysis (10x Genomics). A custom data-analysis framework that combines spatial with single-cell transcriptomic profiles allowed us to identify cell type composition and establish specific cell relations within the bone marrow. As a result, we defined the spatial distribution of transcriptionally heterogenous MM plasma cell (MM-PC) groups. Furthermore, we spatially defined transcriptional programs involved in the pathogenesis of MM within the BM microenvironment that were associated with MM-PC density gradient, such as the spatial location of T cells with effector and exhausted phenotypes. Application of spatial transcriptomics to FFPE human BM biopsies with varying degrees of PC infiltration validated findings from our murine model. The application of spatial transcriptomics to fully mineralized tissues provides a comprehensive spatial overview of the BM microenvironment allowing the identification of deregulated mechanism involved in the pathogenesis of diseases such as MM.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: This study includes spatial transcriptomics analysis of bone marrow samples from healthy mice (YFPcγ1 model) and Multiple Myeloma (MM) mice (MIcγ1 model), as well as human bone marrow biopsies from healthy individuals and MM patients. The analysis aims to compare the spatial and transcriptional profiles of healthy and diseased bone marrow, focusing on cell type composition and specific transcriptional programs associated with MM pathogenesis. No external treatments were applied, and samples were processed using 10x Genomics Visium Spatial Gene Expression technology.

first: Emma

last: Muiños-Lopez

first: Ana

middle: R

last: Lopez-Perez

first: Amaia

last: Vilas-Zornoza

first: Sarai

last: Sarvide

first: Purificacion

last: Ripalda-Cemborain

first: Paula

last: Aguirre-Ruiz

first: Patxi

last: San Martin-Uriz

first: Marta

last: Larrayoz

last: Alvarez-Gigl

last: Abengozar

first: Itziar

last: Cenzano

first: Miguel

last: Cócera

first: Javier

last: Ruiz

first: Ignacio

middle: S

last: González

first: Azari

last: Bantan

first: Aleksandra

last: Kurowska

first: Jin

last: Ye

first: Vincenzo

last: Lagani

first: Bruno

last: Paiva

first: Phillip

last: Newton

first: Jesper

last: Tegner

first: Borja

last: Saez

first: Jose

last: Martinez-Climent

first: Isabel

last: Calvo

first: David

last: Gomez-Cabrero

first: Felipe

last: Prosper


title: Analyzing small RNA sequences from canine stem cell-derived extracellular vesicles primed with TNF-α and IFN-γ

city: Chuncheon si

first: JuHyun

last: AN

address: 1 Kangwondaehak-gil

country: South Korea

institute: Kangwon National University

type: Non-coding RNA profiling by high throughput sequencing

summary: Acute lung injury is an acute inflammation disorder that disrupts the lung endothelial and epithelial barriers. In this study, we investigated the extracellular vesicles (EVs) obtained via priming inflammatory cytokines such as tumor necrosis factor (TNF)-α and interferon (IFN)-γ on canine adipose mesenchymal stem cells in improving their anti-inflammatory and/or immunosuppressive potential, and/or their ability to alleviate lipopolysaccharide-induced lung injury in vitro. We also explored the correlation between epithelial-to-mesenchymal transition and the inflammatory repressive effect of primed EVs. Using small RNA-Seq, we confirmed that miR-16 and miR-502 significantly increased in EVs from TNF-α and IFN-γ-primed canine adipose mesenchymal stem cells. The pro and anti-inflammatory cytokines were analyzed in a lipopolysaccharide-induced lung injury model and we found that the EV anti-inflammatory effect improved on priming with inflammatory cytokines. EVs obtained from primed stem cells effectively suppress endothelial-to-mesenchymal transition in a lung injury model. Our results suggest a potential therapeutic approach utilizing EVs obtained from adipose mesenchymal stem cells primed with TNF-α and IFN-γ against lung inflammation and endothelial to mesenchymal transition.

overall_design: to investigate small RNA sequences from canine stem cell-derived extracellular vesicles primed with TNF-α and IFN-γ

first: Ju-Hyun


title: FACT Complex Recruitment and the Role of H2A.Z in Transcriptional Regulation [ChIP-seq]

city: Xianyang

first: Weiye

last: Qian

state: Shanxi

address: Yangling District

institute: State Key Laboratory for Crop Stress Resistance and High-Efficiency Production, Northwest A&F University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The FACT complex (FAcilitates Chromatin Transcription) plays a key role in chromatin remodeling during transcription, enhancing DNA accessibility. It is believed to alter chromatin by temporarily displacing histones, enabling RNA polymerase II (Pol II) to engage, and then reinstating the original chromatin structure after transcription is complete. In this study, we show that FACT complex subunit ssrp1 undergoes neddylation in vivo, which might be important for its subcellular localization and its interaction with Pol II. This, in turn, promotes the recruitment of the FACT complex to actively transcribed chromatin, establishing a positive feedback loop. In addition, the FACT complex mediates H3K4me3 while not influencing the transcriptional rate. Lastly, in contrast to its canonical form, ubiquitinated H2A.Z does not impede FACT's binding to chromatin and may alleviate the transcriptional repression associated with canonical H2A ubiquitination.

overall_design: ChIP-seq of NRPB1 in Columbia-0(WT) and nrpb2-3, ssrp1-2 mutant background;ChIP-seq of H3K4me3 in Columbia-0(WT) and nrpb2-3 ssrp1-2 spt16-2 mutant.Flag ChIP used Flag antibody, and HA ChIP used beads In all cases, seeds were stratified for 4 days at 4°C, and seedlings were harvested 12 days after germination.

first: Israel

last: Ausin

first: Yafei

last: Wang

first: Chao

last: Xu


title: Oridonin as a Novel KDM5C Inhibitor Alleviates Clonal Hematopoiesis Induced Cardiac Aging via H3K4me3 Dependent SASP Suppression [ChIP-seq]

first: Lu

last: Lu

summary: We applied Tet2⁺/⁻ bone marrow transplantation (BMT) mouse model to investigate the contribution of clonal hematopoiesis to cardiac aging. A transcriptome-guided small-molecule screening strategy was employed to identify potential therapeutic compounds. Target validation involved molecular docking, enzymatic inhibition, and surface plasmon resonance assays. Epigenetic regulation was assessed using chromatin immunoprecipitation sequencing (ChIP-seq) and transcriptomic profiling.  Genetic and pharmacological perturbation experiments were conducted to examine pathway involvement.Genetic manipulation confirmed the KDM5C–SIRT2–SASP regulatory axis mediates oridonin’s effects.TET2-driven clonal hematopoiesis promotes cardiac aging via inflammatory and epigenetic pathways. These finding point that oridonin, as a novel epigenetic modulator, attenuates myocardial dysfunction by inhibiting the KDM5C–SIRT2–SASP axis, supporting its potential as a targeted therapeutic candidate for CHIP-associated cardiac aging.

overall_design:
ChIP-seq profiling was performed on bone marrow-derived macrophages(BMDMs) from Tet2-deficient mice 12 months after bone marrow transplantation and treatment with Oridonin 2 months.
ChIP-seq of the histone modification H3K4me3 in BMDMs.

first: Xingling

last: Chen

first: Qiangqiang

last: Zhao

first: Linhuang

first: Shengrong

last: Lin


title: Single-cell and spatial transcriptomics reveal the pathogenesis of chronic granulomatous disease under natural conditions [BMK]

first: Hanzhi

last: Yu

first: Ge

last: Dong

first: Zhigang

last: Cai


title: Defective plasticity in dermatomyositis patients muscle stem cells is associated with sustained intrinsic inﬂammatory signaling and disruption of the histone H3.3 chromatin loading pathway [CUT&RUN]

city: Leuven

first: Wilhelm

last: Bouchereau

email: wilhelm.bouchereau@kuleuven.be, patrick.lomonte@univ-lyon1.fr, benedicte.chazaud@inserm.fr, armelle.corpet@univ-lyon1.fr

state: Vlaams brabant

address: ON4 - Herestraat 49 PB 804

department: Stamcelinstituut Leuven

country: Belgium

institute: KU-Leuven

summary: Skeletal muscle regeneration is driven by muscle stem cells (MuSC). They proliferate then differentiate to restore muscle function. This process, known as myogenesis, is driven both by intrinsic properties of MuSCs and by extrinsic inflammatory signals. While proinflammatory signals are necessary for healthy muscle regeneration, chronic inflammation participates in different pathologies affecting the skeletal muscle, including cancer-associated cachexia, Duchenne muscular dystrophy (DMD) or auto-immune disorders. Dermatomyositis (DM) is characterized by infiltration of immune cells in the peri-fascicular area which is associated with chronic inflammation. Although anti-inflammatory treatments are commonly used to combat the disease, most patients never fully regain their muscle strength. MuSCs derived from dermatomyositis patients exhibit impaired myogenesis in vitro, indicating that these cells may have acquired intrinsic defects that contribute to the disease. We compared the transcriptomes of MuSCs from healthy individuals and DM patients, finding that the latter are unable to effectively execute the myogenic transcriptomic program during ex vivo differentiation. Additionally, they exhibit an intrinsically activated canonical TNF signaling. MuSC from DM patients also exhibit reduced expression of H3.3 and its chaperone genes, coupled with a decrease in H3.3 deposition across the entire genome. The global loss of H3.3 combined with elevated intrinsic TNF signaling is associated with a failure of DM-derived MuSCs to suppress inflammatory signals and achieve proper myogenesis, suggesting a mechanistic link between epigenetic dysregulation and defective muscle regeneration.

overall_design: CUT&RUN against H3.3 profiling of human skeletal muscle stem cells derived from either healthy control or dermatomyositis patients grown in vitro in either proliferating condition and after day 3 of switch to differentiating condition.

first: Linda

last: Chenane

first: Lola

last: Lessard

first: Michèle

last: Weiss-Gayet

first: Yseult

last: Cardona

first: Rémi

last: Mounier

first: Laure

last: Gallay

first: Yves

last: Allenbach

first: Olivier

last: Benvéniste

first: Armelle

last: Corpet

first: Bénédicte

last: Chazaud

first: Patrick

last: Lomonte


title: Dual-Color MicroRNA Array Analysis Reveals Compartment-Specific Differential Expression in Diabetic vs. Normal DBA/2J Mouse Kidney Cortex and Medulla

city: Isfahan

first: Yousof

last: Gheisari

state: Isfahan

address: Isfahan university of medical sciences, isfahan, iran

department: Genetics and Molecular Biology

country: Iran

institute: Isfahan University of Medical Sciences

summary: This study profiles microRNA expression in mouse kidney tissues comparing diabetic and normal conditions. A total of 16 samples from the cortex and medulla compartments were analyzed from male DBA/2J mice (6–8 weeks old). RNA quality was rigorously assessed, followed by labeling with the miRCURY LNA™ microRNA Hi-Power Labeling Kit. In a dual-color experimental setup, the sample RNA was labeled with Cy3, and a Cy5-labeled reference was used. Arrays were hybridized under automated conditions, scanned with an Agilent G2565BA Microarray Scanner, and the data were processed using background correction and global Lowess normalization. Differential expression analysis, performed using both t-tests (with Benjamini–Hochberg correction) and ANOVA, identified a subset of microRNAs with significant expression differences between diabetic and normal kidneys.

overall_design: The experimental design compares microRNA expression profiles between diabetic and normal mouse kidneys, with additional segmentation into cortex and medulla compartments. Key aspects include:  Sample Collection: Sixteen samples from male DBA/2J mice (6–8 weeks) covering both kidney compartments.  RNA Quality Control: Evaluation via Agilent Bioanalyzer and Nanodrop to ensure high integrity and purity of RNA.  Labeling & Hybridization: Dual-color labeling where sample RNA is conjugated with Cy3 and reference RNA with Cy5; note that while all samples include Cy3 data. Hybridization was performed using automated Tecan hybridization stations following manufacturer protocols.  Scanning & Data Acquisition: Arrays were scanned in an ozone-controlled environment (to prevent dye bleaching) with the Agilent G2565BA scanner. Images were analyzed using ImaGene® software.  Data Processing & Analysis: Background correction (using the Normexp method with an offset of 10) and global Lowess normalization were applied to the data. Subsequent statistical analyses (t-tests with multiple testing correction and ANOVA) were used to determine differentially expressed microRNAs.

first: Gheisari

last: Yousof

first: Kiyanpour

last: Farnoush

first: Abedi

last: Maryam


title: Effect of trmA on tRNA expression in Pseudomonas aeruginosa

city: Lak Si

first: Jurairat

last: Chittrakanwong

address: Kamphaeng Phet 6

department: Applied Biological Sciences

country: Thailand

institute: Chulabhorn Graduate Institute

summary: Goal: to study the differences in P. aeruginosa tRNA expression resulted from absence of trmA, a tRNA m5U modifying enzyme. Results: In exponential-phase wild-type and trmA mutant cells, seven tRNAs comprised almost 50% of the total tRNA abundance (Gly-GCC, Arg-ACG, Ala-GGC, Asp-GTC, Gln-TTG, Leu-CAG, and Tyr-GTA), whereas Arg-CCT had the lowest expression (0.04-0.08%) of the tRNA pool. In the trmA mutant compared to the wild type, 3 genes were up-regulated, and 3 genes were down-regulated in the trmA mutant. Conclusion:  This observation shows that the m5U modification affect certain tRNA expression in the tRNA pool in P. aeruginosa, even though it presents in all tRNA species.

overall_design: To investigate the effect of the loss of TrmA on the abundance of tRNAs, we constructed the trmA mutant strain. Small RNAs were extracted from exponential phase cells of both the wild-type and trmA mutant strains with three biological replicates. cDNA libraries were constructed following the protocol of Absolute Quantification RNA Sequencing (AQRNA-seq) and sequenced on an Illumina MiSeq platform. Differential expression analysis was performed on the AQRNA-seq data to identify tRNAs that were significantly up- or down-regulated in response to the loss of TrmA.

first: Ruixi

last: Chen


title: Rejuvenating Senescent Cells and Organisms with Only Ultrasound

city: Galveston

first: Steven

middle: G

last: Widen

state: Texas

address: 301 University Blvd

department: BMB

institute: University of Texas Medical Branch

summary: Low frequency ultrasound alone rejuvenates senescent cells and aged mice by activating autophagy.

overall_design: Differentiatial Gene expression was determined between LFU mediated rejuvenated late passage HFF cells and late passage replicative senescent HFF cells. Gene expression of early passage LFU treated HFF cells was analyzed against the untreated early passage HFF cells.

first: Sanjay

last: Kumar Kureel

first: Rosario

last: Maroto

first: Erik

middle: D

last: Marchant

first: Ekta

last: Singh

first: Simon

last: Powel

first: Felix

last: Margadant

first: Brandon

last: Blair

first: Blake

middle: B

last: Rasmussen

first: Michael

last: Sheetz


title: FACT Complex Recruitment and the Role of H2A.Z in Transcriptional Regulation [RNA-seq]

first: Weiye

last: Qian

overall_design: RNA-Seq profiling of wildtype Columbia-0, nrpb2-3, ssrp1-2 and spt16-2 mutants at 12 days after germination (12DAG) seedlings.

first: Israel

last: Ausin

first: Yafei

last: Wang

first: Chao

last: Xu


title: The PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons controls neuropathic pain

city: Suzhou

first: Jin

last: Tao

state: Jiangsu

address: 199 Ren-Ai Road

department: Physiology and Neurobiology

institute: Soochow University

summary: Although miRNA-mediated epigenetic regulation has been investigated as a potential therapeutic strategy for diseases, its exact functional regulatory contributions to neuropathic pain have not yet been fully elucidated. Herein, we revealed miR-323-3p as a key functional noncoding RNA in modulating trigeminal neuropathic pain. Through combined high-throughput sequencing and qPCR analysis, we revealed that miR-323-3p was most significantly upregulated in the injured trigeminal ganglion (TG). The administration of a miR-323-3p antagomir via intra-TG injection or blockade of miR-323-3p through lentiviral delivery specifically targeting neurons in injured TGs suppressed established trigeminal neuropathic pain. While miR-323-3p inhibition had no effect on inflammatory pain, local induction of miR-323-3p in naive TGs directly elicited pain hypersensitivity. Mechanistically, nerve injury caused upregulated protein expression of arginine methyltransferase 2 (PRMT2), which promotes asymmetric demethylation of H3R8 (H3R8me2a), thereby facilitating the binding of the forkhead box A2 (FOXA2) transcription factor to the miR-323-3p promoter and resulting in the upregulation of miR-323-3p expression. Furthermore, the increase in miR-323-3p expression induced significant reductions in Kv2.1 protein expression and channel currents, resulting in TG neuronal hyperexcitability. Conversely, downregulation of miR-323-3p in the injured TG reversed the decrease in Kv2.1 expression and attenuated nerve injury-induced mechanical allodynia. Thus, miR-323-3p upregulation is causally involved in the development of trigeminal neuropathic pain through the regulation of Kv2.1 channels in the TG. The mechanistic understanding of the PRMT2/FOXA2/miR-323-3p/Kv2.1 signaling axis in sensory neurons may enable the discovery of new therapeutic targets for neuropathic pain management.

overall_design: mRNA profiles in rat TG tissue on day 14 after CCI-ION operation (n=3) or sham operation (n=3)

first: Renfei

last: Qi


title: Hypoimmunogenic hPSC-derived cardiac organoids for immune evasion and heart repair [scRNA-seq]

first: Nathaniel

last: Hyams

overall_design: Organoids were cultured for 5 days, then disscociated into single cells to be used for scRNAseq using the 10X genomics platform. Libraries were constructed in duplicate (L3 and L4).

first: Bain

last: Jacelyn

first: Bao

last: Xiaoping

first: Barrs

last: Ryan

first: Ferreira

last: Leonardo

first: Floy

last: Martha

first: Haideri

last: Tahir

first: Howells

last: Alessandro

first: Hyams

last: Nathaniel

first: Kerr

last: Charles

first: Li

last: Mei

first: Lian

last: Xiaojun

first: McDougal

last: Thomas

first: Mei

last: Ying

first: Morningstar

last: Jordan

first: Norris

last: Russel

first: Palecek

last: Sean

first: Randolph

last: Lauren

first: Ream

last: Michael

first: Robino

last: Rob

first: Ruddy

last: Jean Marie

first: Silver

last: Sophia


title: Microglial cGAS Deletion Preserves Intercellular Communication and Alleviates Amyloid-β-Induced Pathogenesis of Alzheimer's Disease

status: Public on Jun 07 2025

city: SAN ANTONIO

first: Sijia

last: He

address: 7703 Floyd Curl Dr.

institute: uthealth sa

summary: This study investigates the impact of microglial cGAS deficiency on gene expression in the 5xFAD mouse cerebrum tissues, using the single cell sequencing  method. The relevant publication is PMID: 39908354

overall_design: The measurement set is composed of 2 genotypes (cGAS Loxp/5xFAD, and cGAS mKO/5xFAD). Note that mKO indicate mice with microglial cGAS deficiency.

first: Xin

last: Li

first: Namrata

last: Mittra

first: Anindita

last: Bhattacharjee

first: Hu

last: Wang

first: Shujie

last: Song

first: Shangang

last: Zhao

first: Feng

last: Liu

first: Xianlin

last: Han


title: Defective plasticity in dermatomyositis patients muscle stem cells is associated with sustained intrinsic inﬂammatory signaling and disruption of the histone H3.3 chromatin loading pathway [RNA-seq]

first: Wilhelm

last: Bouchereau

overall_design: RNA-seq profiling of human skeletal muscle stem cells derived from either healthy control or dermatomyositis patients grown in vitro in either proliferating condition and after day 1 and day 3 of switch to differentiating condition.

first: Linda

last: Chenane

first: Lola

last: Lessard

first: Michèle

last: Weiss-Gayet

first: Yseult

last: Cardona

first: Rémi

last: Mounier

first: Laure

last: Gallay

first: Yves

last: Allenbach

first: Olivier

last: Benvéniste

first: Armelle

last: Corpet

first: Bénédicte

last: Chazaud

first: Patrick

last: Lomonte


title: Effect of trmA on mRNA expression in Pseudomonas aeruginosa

first: Jurairat

last: Chittrakanwong

summary: tRNA modification involves in regulation of gene expression in bacterial response to environmental stresses. Here, we aimed to study the transcriptional profiling in the absence of trmA, a tRNA uracil-5-methyltransferase, compared to that of the wild type in Pseudomonas aeruginosa PA14 strain using Illumina sequencing. The disruption of trmA resulted in up and down regulated genes in many pathways based on gene ontology biological processes. One of these pathways was heme biosynthesis, in which the genes were down regulated in the trmA mutant. The finding was consistent with hypersensitivity towards hydrogen peroxide in the trmA mutant strain compared to that of the wild-type strain.

overall_design: Comparison of mRNA expression between P. aeruginosa wild type and trmA mutant in three biological replicates using Illumina Miseq

first: Mayuree

last: Fuanthong


title: Acute Sleep Deprivation Accelerates Brain Endothelial Cell Senescence and Functional Changes of Endothelial Cells in Mice

city: Beijing

first: Lu

last: Changqing

address: No.10 Xitoutiao Road, Youanmenwai Avenue, Fengtai District

institute: Capital Medical University

summary: Sleep, a fundamental physiological process occupying approximately one - third of the human lifespan, is essential for maintaining overall health. Acute sleep deprivation (ASD), a prevalent condition in modern society, has been strongly associated with the pathogenesis of various neurodegenerative diseases. Endothelial cells play a pivotal role in regulating vascular tone, modulating inflammatory responses, and maintaining barrier integrity. While previous research has indicated that sleep deprivation can contribute to endothelial cell dysfunction, potentially leading to the development of atherosclerosis, hypertension, and other vascular disorders, the precise effects of ASD on brain endothelial cells and the underlying molecular mechanisms remain incompletely understood. Our study focuses on exploring the specific effects of acute sleep deprivation on the phenotypic characteristics and molecular functions of brain endothelial cells. Through bioinformatics analysis and multiple experimental approaches, it reveals the close relationship between acute sleep deprivation and endothelial cell senescence as well as alterations in molecular functions. By uncovering the molecular change, we provides a theoretical basis and novel perspectives for the research and treatment of related diseases.

overall_design: A total of 12 samples from cerebral cortex endothelial cells of male C57BL/6J mice were analyzed. Sleep deprivation was induced using a rotarod at 6 rpm for 6, 12, or 24 hours, with interventions starting at 08:00 am. Endothelial cells were isolated by magnetic-activated cell sorting (MACS) with CD31 microbeads. The control group underwent no interventions and was maintained under normal housing conditions.

first: Jinglin

last: Qin

first: Changqing

last: Lu

first: Yongjing

last: Wang

first: Zhenwei

last: Qian

first: Chen

last: Zhang

first: Xiannian


title: In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vivo]

city: Cambridge

first: Robert

middle: T

last: Manguso

state: MA

address: 75 Ames Street, Rm 7053

institute: Broad Institute of MIT & Harvard

summary: Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a high unmet need for enhancing immunotherapy given current modest responses. Here, we performed an in vivo CRISPR screen in a HNSCC mouse model to identify immune evasion genes. We identified several epigenetic regulators of immune checkpoint blockade (ICB) response, including the ubiquitin C-terminal hydrolase 5 (UCHL5). Loss of Uchl5 in tumors increased CD8+ T cell infiltration and improved ICB responses. Uchl5 deficiency reduced extracellular matrix (ECM) production and epithelial-mesenchymal-transition (EMT) transcriptional signatures, which contribute to stromal desmoplasia, a histologic finding associated with reduced anti-PD1 response in human HNSCCs. We identified a functional role for COL17A1, a collagen highly and specifically expressed in HNSCC, in Uchl5-mediated immune evasion. Our findings suggest an unappreciated role for UCHL5 in promoting EMT in HNSCC and highlight ECM modulation as a strategy to improve immunotherapy responses.

overall_design: Control and Uchl5-deficient MOC1-esc1 cells we inoculated into wild-type C57BL/6 mice treated with or without anti-PD-1. Tumors were collected on day 15, weighed, mechanically diced, digested with a tumor dissociation kit and a gentleMACS dissociator. After filtering through a 70-μm strainer, tumor cells were isolated using the Mouse Tumor Cell isolation kit and subsequently subjected to RNA-seq

first: Cong

last: Fu

first: Ashwin

middle: V

last: Kammula

first: Sarah

middle: Y

last: Kim

first: Ravindra

last: Uppaluri


title: TNFα-NF-κB activation through pathological α-Synuclein disrupts the BBB and exacerbates axonopathy

city: Daegu

first: Mookyung

last: Cheon

address: 61, Cheomdan-ro, Dong-gu

department: Dementia Research Group

institute: Korea Brain Research Institute

summary: Dysfunction of the blood brain barrier (BBB) is recognized as a key factor in the progression of neurodegenerative diseases, but the detailed mechanisms behind its pathogenesis and impact on neurodegeneration remain elusive. This study aimed to reveal the pathological effects of α-Synuclein (α-Syn), an aggregation protein in Synucleinopathy, on BBB integrity and function, and identify therapeutic targets for α-Syn-related vasculopathy. Using a brain endothelial cell model, we investigated the pathological effect of preformed fibril α-Syn (PFF) on BBB integrity, employing generative adversarial network (GAN) deep learning to analyze pathological changes. We found that PFF activates immune responses, increasing endothelial monolayer permeability via the TNFα-NF-κB pathway. Further in vivo studies with PFF induced α-Synucleinopathy and transgenic animal model (G2-3) revealed that α-Syn aggregation, disrupts the BBB, leading to axonal degeneration that was mitigated by treatment with a non-BBB-penetrating TNFα inhibitor, Etanercept. These findings suggest that targeting brain endothelial TNFα signaling could be a potential therapeutic approach for Synucleinopathy-related NDs.

overall_design: Primary human brain microvascular endothelial cells (HBMVECs) were cultured and treated with control, monomeric α-synuclein, or pre-formed fibrils (PFF) of α-synuclein for 24 or 72 hours. After treatment, RNA was extracted for transcriptomic analysis to investigate gene expression changes induced by different forms of α-synuclein.

first: Min-Tae

last: Jeon

first: Sinnead

last: Cogill

first: Kyu-Sung

first: Yongjin

first: Hyerin

first: Chung-Yeol

last: Lee

first: Suji

first: Suhyeon

last: Son

first: Jeongyeon

first: Jaehyeok

first: Inyeong

last: Park

first: Do-Geun


title: LIN28B-mediated activation of the PI3K/AKT pathway promotes metastasis and unravels a new therapeutic vulnerability in colorectal cancer

city: New York

first: Alice

middle: E.

last: Shin

state: NY

address: 1130 St. Nicholas Ave. 202-2

department: Herbert Irving Comprehensive Cancer Center

institute: Columbia University Irving Medical Center

summary: Colorectal cancer (CRC) remains a leading cause of cancer death, primarily due to metastatic spread. LIN28B, an RNA-binding protein overexpressed in 30% of CRCs, acts as an oncogene and promotes CRC metastasis. However, the mechanisms through which LIN28B drives these effects remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, leading to enhanced activation of the PI3K/AKT pathway and increased metastatic potential in mice. We developed genetically engineered mouse models (GEMMs) with mutant PIK3CA that are the first to exhibit primary intestinal tumors progressing to liver metastases with an intact immune system. Pharmacological inhibition with the PI3Kα-specific inhibitor alpelisib effectively reduced migration and invasion in vitro, as well as metastasis in vivo. Treatment of CRC patient-derived organoids (PDOs) with alpelisib, the AKT inhibitor capivasertib, and/or the S6K inhibitor LY2584702 demonstrated the potential of pathway inhibition to impair tumor growth. Tissue microarrays from CRC patients further indicated that pathway activation correlates with disease progression. These findings underscore the critical role of the PI3K/AKT pathway in CRC metastasis and open new avenues in targeted inhibition and combination therapies in metastatic CRC (mCRC).

overall_design: LoVo and DLD-1 cells treated with

middle: E

first: Anil

middle: K

last: Rustgi


title: The Effects of MIZ1 Deficiency on Germinal Center B Cells in the Light Zone [RNA-seq]

city: London

first: Dinis

middle: Pedro

last: Calado

address: Midland Road

country: United Kingdom

institute: The Francis Crick Institute

summary: The germinal center (GC) reaction is a critical process for the generation of high-affinity antibodies and the establishment of immunological memory. Within the GC, B cells undergo a series of tightly regulated molecular and cellular events. MIZ1, a transcription factor, has recently emerged as a key regulator of B cell fate during the GC response. This study aims to investigate the impact of MIZ1 deficiency specifically on B cells located in the light zone (LZ) of the germinal center.

overall_design: Control and MIZ1KO mice were intravenously immunized with sheep red blood cells (SRBCs). Ten days post-immunization, spleens were collected from both groups. Light zone (LZ) germinal center (GC) B cells were sorted from the spleens of both control and MIZ1KO mice and subsequently subjected to bulk RNA sequencing (RNA-seq).

first: Lingling

first: Amparo

last: Toboso-Navasa


title: In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion

first: Robert

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

overall_design: Refer to individual Series


title: In vivo CRISPR screens in Head and Neck Cancer reveal that Uchl5 modulates extracellular matrix deposition to promote immune evasion [in vitro]

overall_design: The preclinical murine oral carcinoma MOC1-esc1 cell line (sgCtrl and sgUchl5) were treated for 24h with either DMSO or 10ng/ml IFNγ. Cells were collected for RNA-seq after 24h treatment.

first: Cong

first: Ashwin

first: Sarah

first: Ravindra


title: Transcriptomic and epigenetic profiling of adrenergic and mesenchymal neuroblastomas with cell state conversion

status: Public on Jun 06 2025

city: Memphis

first: Hongjian

last: Jin

state: TN

address: 262 Danny Thomas Place

department: Center for Applied Bioinformatics

institute: St Jude Children's Research Hospital

relation:
SuperSeries of: GSE299169
SuperSeries of: GSE299170
SuperSeries of: GSE299173


title: Hemolytic stress leads to expansion of erythropoiesis in the spleen

city: Zurich

first: Florence

last: Vallelian

address: Rämistrasse 100

institute: University Hospital Zürich

summary: In anemia-stressed mice, compensatory RBC production occurs primarily in the spleen. We have compared erythropoiesis across the three models with a multiplexed single cell-RNA sequencing experiment of formalin-fixed spleen cell suspensions of one spherocytosis (Spta), two sickle cell disease (Berk) and one thalassemia (Thal) spleen. After de-multiplexing, batch correction, and Leiden clustering, Ptprc (CD45) negative cells were extracted, and pseudotimes were calculated to establish the erythropoietic differentiation trajectory. Along this trajectory, three cell populations could be delineated representing (1) Kit+Runx3+ hematopoietic stem cells (2) highly proliferative Mki67+Gata1+ Klf1+ Epor+ Tfrc+ early-stage erythropoietic progenitors; and (3) Gypa+ Xpo+ late-stage erythropoietic progenitors with active heme synthesis (Alas2+).

overall_design: We performed a multiplex single cell-RNAsequencing analysis on spleen tissues of one spherocytosis (SPH), two sickle cell disease (SCD ) and one thalassemia (THAL) mouse.

first: Irina

last: Dubach

first: Livio

last: Baselgia

first: Elena

last: Duerst


title: Identification of Transcription Factor MIZ1 Binding Sites in Human B Cell Lines [ChIP-seq]

summary: A previous study has successfully identified the binding sites of Transcription Factor MIZ1 in murine B cells. In order to shed light on the potential relevance between mouse and human, this experiment aimed to identify MIZ1's binding sites in human B cell lines. By uncovering these binding sites, we can gain insights into the conservation and potential functional significance of MIZ1 in B cell biology across species.

overall_design: We conducted ChIP (Chromatin Immunoprecipitation) experiments using the MIZ1 antibody on two distinct cell lines, namely P493-6 and Raji. DNA fragments were generated from non-treated cell replicates and subsequently subjected to sequencing to identify potential MIZ1 binding sites. For each cell line, we included one input sample and three IP (Immunoprecipitation) samples.

first: Arief

last: Gunawan

last: Zhang


title: Regulatory T cells in lung tumor shape an anti-inflammatory myeloid-landscape recovery after chemotherapy

city: PARIS

first: Alexandre

last: Boissonnas

address: 91 boulevard de l'hôpital

country: France

institute: Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris)

summary: Tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) are major immune components of the tumor microenvironment, promoting tumor growth and limiting the efficacy of chemotherapy in almost all cancer indications. While Tregs are well known for their immune suppressive activity toward the adaptive immune system, less is known about their regulatory activity toward the innate compartment. We showed in human and mouse lung cancer, that chemotherapy transformed the myeloid landscape of the tumor microenvironment, inducing a transient monocyte accumulation and exhibiting a stronger pro-inflammatory signature along with increased TGFβ expression. Prevent Treg recovery further increased the recruitment of monocytes and limited TGFβ expression upon TAM differentiation arguing for a role of Tregs in the anti-inflammatory polarization of the myeloid compartment. Using anti-TNFR2, to target preferentially tumor-infiltrating Treg, affected their recruitment and dynamic of interaction with myeloid cells into the tumor. This was associated with a sustained pro-inflammatory signature of the myeloid cells and improved survival in the mouse model. Chemo-immunotherapy targeting the cross-talk between tumor-associated Tregs and myeloid compartments may provide alternative or complementary benefit in the context of immune-checkpoint blockade therapies.

overall_design: Seven sorted tumor samples from NSCLC patients were analyzed: 3 untreated (N) and 4 treated by neoadjuvant chemotherapy (CH). The samples include myeloid cells, T and B lymphocyte populations analyzed using scRNA-seq.

first: Eleonore

last: Weber-Delacroix

first: Marylou

last: Panouillot

first: Marie

last: Laviron

first: François

last: Lanthiez

first: Tristan

last: Philippe

first: Sandrine

last: Barthélémy

first: Solène

last: Fastenackels

first: Armanda

last: Casrouge

first: Benoît

last: Salomon

first: Ingrid

last: Sassoon

first: Jeremy

last: Baudhuin

first: Ilaria

last: Onorati

first: Mariane

last: Kambouchner

first: Nahla

last: Cucherousset

first: Christophe

last: Combadière

first: Boris

last: Duchemann

first: Marie-Caroline

last: Dieu-Nosjean


title: The effect of DOT1L on human retinal microvascular endothelial cells

city: Quzhou

first: Si-wei

last: Wang

address: No.100 Minjiang Road

institute: Quzhou people's hospital

summary: Clarifying the mechanism of DOT1L on retinal microvascular endothelial cells

overall_design: Comparative gene expression profiling analysis of RNA-seq data for high glucose-treated RME cells and high glucose treated DOT1L knockdown RME cells

first: Zhu-jun

last: Mao


title: RNA Sequencing of 16D prostate xenograft tumors with genetic knockout of OGDHL

city: Los Angeles

first: Andrew

middle: Scott

last: Goldstein

address: 610 Charles E Young Dr East

department: Urology

institute: University of California, Los Angeles

summary: The goal of this study was to perform transcriptomics of xenograft tumors generated from prostate cancer cells with genetic knockout of OGDHL vs a control knockout

overall_design: Prostate cancer cells were infected with lentivirus containing CAS9 and a control gRNA (AAVS) or gRNA targeting OGDHL (sgOGDHL). Cells were then implanted with matrigel into immune deficient NOD-SCID-IL2Rgnull (NSG) mice and allowed for tumors to form.

first: Goldstein

last: Andrew

first: Bernard

last: Matthew


title: Generation and Characterization of Tcf4 CTG Trinucleotide Repeat Expansion Knock-in Mouse as a Model for Fuchs Endothelial Corneal Dystrophy

city: Kyotanabe

first: Taisuke

last: Numao

state: Kyoto

department: Department of Biomedical Engineering, Faculty of Life and Medical Sciences

country: Japan

institute: Doshisha University

summary: RNA sequencing analysis was performed using corneal endothelial tissue from 60-week-old Tcf4(CTG)100/(CTG)100 mice and wild type controls (n=5 per group). Among 26,133 expressed genes, we identified 4,510 differentially expressed genes (DEGs) with |Log2 Fold Change| ≥ 1 and adjusted P-value < 0.05, including 539 upregulated and 3,971 downregulated genes. Gene Ontology and pathway analyses revealed significant enrichment in pathways related to muscle system processes, visual system development, and ion channel activities. The most significantly enriched pathways included extracellular matrix organization, peptide ligand-binding receptors, and neuronal system pathways.

overall_design:
Tissue: Corneal endothelial tissue isolated from mouse cornea
Genotype comparison: Tcf4(CTG)100/(CTG)100 vs. wild-type mice
Age: 60-week-old mice
Sample size: n=5 per group
Sequencing: RNA-seq using NovaSeq 6000 platform

first: Suguru

last: Ito

first: Yuki

last: Oyama

first: Taichi

last: Yuasa

first: Mizuki

last: Ueda

first: Satoshi

last: Chiba

first: Tatsuya

last: Nakagawa

first: Ayaka

last: Izumi

first: Masahito

last: Ikawa

first: Noriko

last: Koizumi

first: Naoki

last: Okumura


title: Cyclosporine A Enhances the Efficacy of Venetoclax Against FLT3-ITD AML via the PI3K/AKT/mTOR Signaling Pathway

city: Chongqing

first: CHENGFANG

last: ZHOU

address: No. 30, Gaotanyan Street.

department: Department of Hematology, Southwest Hospital

institute: Army Medical University

summary: Acute myeloid leukemia (AML) with the Fms-like tyrosine kinase 3 internal tandem duplication (FLT3-ITD) mutation accounts for approximately 25-30% of cases and is associated with a poor prognosis, characterized by high relapse rates and significantly reduced overall survival. The use of single-agent venetoclax in FLT3-ITD AML has shown limited efficacy, with drug resistance frequently emerging. In this study, we demonstrate that cyclosporine A (CsA) sensitizes FLT3-ITD AML cells to venetoclax by inhibiting cell proliferation, promoting apoptosis, and disrupting mitochondrial function. Mechanistically, CsA enhances the anti-AML effects of venetoclax by inhibiting NFATC1 through the PI3K/AKT/mTOR signaling pathway. These findings offer promising new therapeutic strategies for managing refractory and relapsed AML, providing a basis for future combination therapies targeting FLT3-ITD mutations.

overall_design:
To study the effects of venetoclax and CSA combination treatment on FLT3-ITD cells, we set up the following groups: control group, venetoclax monotherapy group, CSA monotherapy group, and venetoclax + CSA combination treatment group, treating MV4-11 cells for 24 hours.
Then, we performed gene expression profiling analysis on the RNA data obtained from the four groups.

first: Chengf

last: Zhou

first: Yu

last: Luo


title: A distinct mechanism of epigenetic reprogramming silences PAX2 and initiates endometrial carcinogenesis

city: Dallas

first: Ram

last: Mani

address: 5323 Harry Hines Blvd NB6.444

department: Pathology

institute: UT Southwestern Medical Center

summary: Functional inactivation of tumor suppressor genes drives cancer initiation, progression, and treatment responses. Most tumor suppressor genes are inactivated through one of two well-characterized mechanisms: DNA-level mutations such as point mutations or deletions, and promoter DNA hypermethylation. Here, we report a distinct third mechanism of tumor suppressor inactivation based on alterations to the histone rather than DNA code. We demonstrated that PAX2 is an endometrial tumor suppressor recurrently inactivated by a distinct epigenetic reprogramming event in >80% of human endometrial cancers. Integrative transcriptomic, epigenomic, 3D genomic, and machine learning analyses showed that PAX2 transcriptional downregulation is associated with replacement of open/active chromatin features (H3K27ac/H3K4me3) with inaccessible/repressive chromatin features (H3K27me3) in a framework dictated by 3D genome organization. The spread of the repressive H3K27me3 signal resembled a pearl necklace with its length modulated by cohesin loops, thereby preventing transcriptional dysregulation of neighboring genes. This mechanism, involving the loss of a promoter-proximal super-enhancer, underlied transcriptional silencing of PAX2 in human endometrial cancers. Mouse and human preclinical models established PAX2 as a potent endometrial tumor suppressor. Functionally, PAX2 loss promoted endometrial carcinogenesis by rewiring the transcriptional landscape via global enhancer reprogramming. The discovery that most endometrial cancers originate from a recurring epigenetic alteration carries profound implications for their diagnosis and treatment.

overall_design: Cleavage Under Targets and Tagmentation (CUT&Tag) for histone modifications H3K27me3, H3K4me3, H3K27ac and negative control IgG in AN3CA, Ishikawa cells, and patient-derived xenograft tissues.

first: Subhransu

last: Sahoo

first: Yunpeng

last: Gao

first: Sora

last: Lee

first: Diego

middle: H

last: Castrillon


title: RNA Sequencing of 16D Prostate Cancer Cell Lines with genetic knockout of OGDHL

first: Andrew

last: Goldstein

summary: The goal of this study was to perform transcriptomics of prostate cancer cells with genetic knockout of OGDHL treated with the Androgen Receptor Pathway Inhibitor Enzalutamide (Enza) or Vehicle (DMSO)

overall_design: Prostate cancer cells were infected with lentivirus containing CAS9 and a control gRNA (AAVS) or gRNA targeting OGDHL (sgOGDHL). Cells were then maintained in vehicle (DMSO) or Androgen Receptor Pathway Inhibitor (Enza) for 6 weeks to adapt.

first: Goldstein

last: Andrew

first: Bernard

last: Matthew


title: Transcriptomic and epigenetic profiling of adrenergic and mesenchymal neuroblastomas with cell state conversion [CUT&TAG]

first: Hongjian

last: Jin

summary: Neuroblastoma accounts for 15% cancer related deaths in children, largely due to the disease relapse after multimodal therapy. Understanding the mechanism by which cancer cells acquire therapy resistance is critical to develop therapies for eradicating all cancer cells. Neuroblastoma are composed of two major cell states, adrenergic (ADRN) and mesenchymal (MES), which are presumed to interconvert and contribute to therapy resistance. To better understand the cell plasticity of neuroblastoma in chemoresistance, we repeatedly treated human and murine neuroblastoma models with indisulam, a molecular glue drug that selectively degrades RBM39, a splicing factor critical to neuroblastoma cell survival. until these tumors developed full resistance.  We then generated transcriptomic data, ATAC-seq data, CUT&Tag for H3K27Ac from these tumors, and defined their cell state features. These datasets provided a comprehensive transcriptomic and epigenetic profiling on ADRN and MES neuroblastoma cells after they developed therapy resistance. Here, we provided a detailed description of these unique datasets to facilitate their reusing. We anticipate that these datasets are useful resources to understand the role of cell lineage switching in therapy resistance.

relation:
Reanalysis of: GSM7989951
Reanalysis of: GSM7989952
Reanalysis of: GSM7989953
Reanalysis of: GSM7989954
Reanalysis of: GSM7989955
Reanalysis of: GSM7989956
Reanalysis of: GSM7989957
Reanalysis of: GSM7989958
Reanalysis of: GSM7989959
Reanalysis of: GSM7989960
SubSeries of: GSE299174

overall_design:
Examination of chromatin changes with various indusilam treated tumor by CUT&TAG. This study represents a re-analysis of all of the raw data generated for GSE251915.

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

first: Fang

last: Jie

first: Shivendra

last: Singh

first: Jun

last: Yang


overall_design: Profiling the histone mark H3K27ac in cell lines (AN3CA cell line with PAX2 knock-down, Ishikawa cell line with PAX2 overexpression) and in Patient Derived Xenograft models of Endometrial Cancer by Chromatin Immunoprecipitation sequencing (ChIP-seq).

first: Susmita

last: Ramanand


overall_design: Analysis of open Chromatin regions in the Patient Derived Xenograft models of Endometrial Cancer.


title: RNA sequencing data of mouse caecum tissue following different dietary treatments

city: Frederiksberg C

last: Williams

address: Dyrlægevej 100

country: Denmark

institute: University of Copenhagen

summary: Mice were fed either a semi-synthetic diet ('SSD'), or the same diet supplemented with the fiber inulin ('inulin'). Mice were then infected with Trichuris muris ('Tm').

overall_design: Mice recevied the diets 14 days prior to infection. After infection mice either continued on their pre-assigned diet, or were swtiched to an alternative diet. Mice were killed at either 7 or 11 days post-infection


title: Transcriptomic and epigenetic profiling of adrenergic and mesenchymal neuroblastomas with cell state conversion [ATAC-Seq]

relation:
Reanalysis of: GSM5012393
Reanalysis of: GSM5012394
Reanalysis of: GSM5012395
Reanalysis of: GSM5012396
Reanalysis of: GSM5012397
Reanalysis of: GSM5012398
SubSeries of: GSE299174

overall_design:
To explore chromatin accessibility in vechile treated and indisulan resistant neuroblasoma xenograft. This study represents a re-analysis of all of the raw data generated for GSE164504.

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

first: Jie

last: Fang


title: The Regulatory Logic of Planarian Stem Cell Differentiation [ATAC-Seq]

status: Public on Jun 15 2025

city: Exeter

first: Jordi

last: Solana

address: Northcote House

department: Health and Life Sciences

institute: University of Exeter

summary: Stem cell differentiation underlies development and regeneration in multicellular organisms. Cell type identity is determined by the expression of specific transcription factors (TFs) regulating target genes (TGs) via binding to open chromatin regions (OCRs). The regulatory logic of differentiation includes factors specific to one or multiple cell types, functioning in a combinatorial fashion. Single cell transcriptomics has emerged as a revolutionary approach to study gene expression with cell type resolution, but integrating it with single cell analysis techniques to study chromatin remains challenging. Planarians, with their pluripotent neoblast stem cells continuously giving rise to all cell types, offer an ideal model to attempt this integration. Despite extensive single cell transcriptomic studies, the transcriptional and chromatin regulation at the cell type level remains unexplored. Here, we investigate the regulatory logic of planarian stem cell differentiation by obtaining an organism-level integration of single cell transcriptomics and single cell ATAC-seq. We identify specific open chromatin profiles for major differentiated cell types and analyse their transcriptomic landscape, revealing distinct gene modules expressed in individual types and combinations of them. Integrated analysis unveils gene networks reflecting known TF interactions in each type and identifies TFs potentially driving differentiation across multiple cell types. To validate our predictions, we combined TF knockdown RNAi experiments with single cell transcriptomics. We focus on hnf4, a TF known to be expressed in gut phagocytes, and confirm its influence on other types, including parenchymal cells. Our results demonstrate high overlap between predicted targets and experimentally-validated differentially-regulated genes. Overall, our study integrates TFs, TGs and OCRs to reveal the regulatory logic of planarian stem cell differentiation, showcasing the potential of single cell methods for characterising differentiation trajectories and their regulation.

overall_design: One ATAC-Seq library of whole S. mediterranea animals in unperturbed conditions.

first: Alberto

last: Perez-Posada

first: Helen

last: Garcia-Castro

first: Elena

last: Emili

first: Virginia

last: Vanni

first: Cirenia

middle: C

last: Arias-Baldrich

first: Siebren

last: Frolich

first: Simon

last: Van Heeringen

first: Nathan

middle: N

last: Kenny

middle: J


first: Ram

last: Mani

overall_design: Analysis of open chromatin regions in fresh endometrial tumor samples.

first: Subhransu

last: Sahoo

first: Yunpeng

last: Gao

first: Diego

last: Castrillon


title: Vaccine Educated T cells and a CD123 Bi-Specific T-Cell Engager for Treatment of Acute Myeloid Leukemia

city: Boston

first: Yuling

last: Ma

address: 330 Brookline Ave

institute: Beth Israel Deaconess Medical Center

summary: Immunotherapy strategies in acute myeloid leukemia remain limited. CD123 is a promising target as it is overexpressed in myeloid blasts. This preclinical work investigates possible synergy of CD123 T cell engager and dendritic cell based vaccine, which can induce the expansion of leukemia specific T cells. Efficacy of combination therapy was evaluated in a patient-derived xenograft model and the infused T cells were later collected for single cell rnaseq to determine effects on gene expression pathways and clonality. In the present study, we demonstrated that the combination of DC/AML fusion vaccine and a CD123 T cell engager SAR440234 led to an increase in tumor specific T cell immunity and enhanced anti-leukemia effect in vitro. Furthermore, the combination treatment was shown to increase cytotoxic T cell subsets and clonotypic expansion and eradicate disease in vivo. Thus the combination of T cell engager and vaccination or adoptive T cell transfer is a novel approach that merits further investigation in clinical trials.

overall_design: Cell suspensions following harvesting of bone marrow and spleen tissues from individual mice were cryopreserved. NSG mice had been injected with human T cells. Upon thawing, samples underwent dead cell removal (Miltenyi MACS kit) and human CD45 enrichment (Stem Cell Technologies). Based on cell yield, samples from 4 mice per treatment group (no treatment, Tc+IgG, uTc+SAR, veTc+IgG, veTc+SAR) were chosen for single cell RNA and TCR sequencing, yielding 20 samples from bone marrow and spleen compartments each. 5 spleen or bone marrow samples were pooled together (one sample per treatment group), and 32,000-40,000 cells were loaded in one channel of a Chromium Chip K (10x Genomics) and profiled using the Chromium Next GEM Single Cell 5' Kit v2 (10x Genomics). Full-length paired α/β TCR libraries were obtained using the Chromium Single Cell V(D)J Enrichment Human T Cell (10x Genomics). cDNA, gene expression, and TCR library quality was assessed using the DNA High Sensitivity Bioanalyzer Chip (Agilent). Gene expression or TCR libraries were pooled and sequenced on a NovaSeq 6000 sequencer (Illumina).


title: Application of Transcriptomics Dose-Response Modeling to Risk-Based Prioritization of Contaminants Detected in Tributaries of the North American Great Lakes [D. magna]

city: Duluth

first: Peter

last: Schumann

state: MN

address: 6201 Congdon Blvd

institute: United States Environmental Protection Agency

summary: As part of the Great Lakes Restoration Initiative, a series of chemical monitoring and surveillance efforts have detected approximately 550 chemicals in Great Lakes tributaries. Among these, there were 140 chemicals for which no empirical toxicity data were available to support prioritization. The aim of the present study was to generate transcriptomic points of departure (tPODs) for 10 of these compounds and demonstrate how they could be applied in a screening-level prioritization. Organisms representing three different trophic levels of the aquatic food-web (Pimephales promelas – secondary consumer, Daphnia magna-primary consumer, and R. subcapitata-primary producer). were exposed for 24 h to a ½-log dilution series of nominal exposure concentrations typically ranging from 66.7 to 0.021 µM of each chemical. In addition to observations of apical effects such as survival and morphology, whole body transcriptomic responses to each chemical were evaluated with targeted analysis using TempO-seq for P. promelas and D. magna and non-targeted full RNA-seq for R. subcapitata. Benchmark concentrations (BMCs) were calculated for each gene showing a concentration-dependent expression pattern. The tPOD for each chemical-species combination was defined as the 10th percentile of the BMCs. The tPODs ranged from 0.18 to 10.8 µM for P. promelas and 0.32 to 29 µM for D. magna, with the most potent of the chemicals tested being fipronil carboxamide. For R. subcapitata, the tPODs ranged from 0.04 to 1.77 µM, with gabapentin as the most potent chemical tested. Empirically derived tPODs from these data poor chemicals, as well as tPODs from previously tested data rich chemicals, were compared with concentrations detected in the Great Lakes basin. This work demonstrates the potential utility of emerging ecological high-throughput transcriptomics assays to support timely screening and prioritization of data poor environmental contaminants.

overall_design: RNA-seq was performed using the TempO-Seq protocol on RNA extracted from whole Daphnia magna that were exposed for 24 h to a ½-log dilution series of nominal exposure concentrations (typically ranging from 66.7 to 0.021 µM) of the following 12 chemicals: 1(2H)-Phthalazinone, cis-nonachlordane, Metolachlor OA, 3,4-Dichlorophenyl isocyanate, Gabapentin, Metribuzin-DA, 2-tert-butyl-4-methoxyphenol, Hydrochlorothiazide, 4-chlorophenyl methyl sulfone, Cetirizine Hydrochloride, Fipronil carboxamide, Fexofenadine. Samples were pooled by treatment concentration within each plate, resulting in n=3 replicates per treatment, each containing five pooled organisms. Each assay included DMSO controls, with final in-well DMSO concentrations never exceeding 0.34% in the exposure plate wells.

first: Jenna

last: Cavallin

first: Kendra

last: Bush

first: Steven

middle: R

last: Corsi

first: Laura

middle: A

last: DeCicco

first: Kevin

last: Flynn

first: Monique

last: Hazemi

first: Erin

last: Maloney

first: Alex

last: Kasparek

first: Daniel

middle: L

last: Villeneuve


title: Transcriptomic and epigenetic profiling of adrenergic and mesenchymal neuroblastomas with cell state conversion [RNA-Seq]

first: Hongjian

last: Jin

relation:
Reanalysis of: GSM5012421
Reanalysis of: GSM5012422
Reanalysis of: GSM5012423
Reanalysis of: GSM5012424
Reanalysis of: GSM5012425
Reanalysis of: GSM5012426
Reanalysis of: GSM5012415
Reanalysis of: GSM5012416
Reanalysis of: GSM5012417
Reanalysis of: GSM5012418
Reanalysis of: GSM5012419
Reanalysis of: GSM5012420
Reanalysis of: GSM7989980
Reanalysis of: GSM7989981
Reanalysis of: GSM7989982
Reanalysis of: GSM7989983
SubSeries of: GSE299174

first: Jie

last: Fang

first: Shivendra

last: Singh

first: Jun

last: Yang


title: Single-nucleus transcriptomic atlas of spinal cord cells in human

city: Chengdu

first: Cheng

last: Zhou

state: Sichuan

address: No.37, guoxue lane, wuhou district, chengdu city, sichuan province

institute: West China Hospital of Sichuan University

summary: Despite the recognized importance of the spinal cord in sensory processing, motor behaviors, and/or neural diseases, the underlying organization of its cells, including both neuronal and non-neuronal clusters remain elusive. Recently, several studies have attempted to define the cellular subtypes in the spinal cord and their functional heterogeneity using single-cell and/or single-nucleus RNA-sequencing in various animal models. However, molecular evidence of cellular heterogeneity in the adult human spinal cord has not yet been established. Here, we sought to classify spinal cord neurons and glial cells from human donors using high-throughput single-nucleus RNA-sequencing. Moreover, we compared the transcriptional patterns obtained in human samples with previously published single-nucleus transcriptomic profiles of the mouse spinal cord. The functional heterogeneity among the identified cell subtypes were also explored by Gene ontology (GO) term analysis. As a result, we generated the first comprehensive transcriptomic atlas of adult human spinal cord neurons and defined 24 neuronal clusters. For glial cells, astrocytes, microglia, and oligodendrocytes were divided into ten, eight, and eleven distinct transcriptomic subclusters, respectively. The comparison with mouse transcriptomic profiles revealed an overall similarity in the neuronal composition of the spinal cord between the two species, while simultaneously highlighting some degree of heterogeneity. In summary, these results illustrate the complexity and diversity of neuronal and glial types in the human spinal cord and provide an important resource for future research to explore the molecular mechanisms underlying spinal cord physiology and diseases.

overall_design: Single-nucleus transcriptomic profiles of spinal cord cells in 3 human donors

first: Donghang

last: Zhang

first: Yiyong

last: Wei

first: Jin

last: Liu

first: Hongjun

last: Chen

last: Li

first: Changhong

last: Miao

first: Tao

last: Zhu


title: Points of departure for an algal species (Raphidocelis subcapitata) exposed to 22 per- and polyfluoroalkyl substances

first: Peter

last: Schumann

summary: Due to their environmental prevalence, persistence, and potential toxicity, per- and polyfluoroalkyl substances (PFAS) are contaminants of concern. However, except for a few well studied PFAS, hazard data required to evaluate their risk to aquatic ecosystems are limited. The present study used a 24-hour, high throughput assay to screen 22 PFAS with varying chain lengths and functional groups for effects on the transcriptome of a green algal species, Raphidocelis subcapitata. The tested PFAS included perfluoroalkyl carboxylic acids, perfluoroalkyl carboxylic acid ethers, alcohols, sulfonic acids, and sulfonamides. Algae were exposed in a 96-well microplate format to 8 concentrations (nominally, 100 to 0.03 uM) of each PFAS, in a 1/2 log dilution series. Analytical measurements of PFAS concentration were made at the initiation of exposure and after 24 hours. In addition to traditional endpoints (i.e., biomass, viability, and chlorophyll), RNA was extracted for sequencing of the transcriptome. Concentration response curves were fit to the resulting transcriptomic data to calculate gene-specific benchmark concentrations. The distribution of benchmark concentrations was subsequently used to calculate a transcriptomic point of departure (tPOD) which represents a concentration below which no concerted molecular change is detected in response to PFAS exposure. The resulting tPODs were compared with traditional endpoints and environmentally detected concentrations of specific PFAS.

overall_design: RNA-seq was performed using mRNA extracted from Raphidocelis subcapitata that were exposed for 24 h to a dilution series of 22 different PFAS. The nominal exposure concentrations ranged from 100-0.03 µM. All assays were conducted in four replicate, 96-well plates. Control wells contained the same concentration as PFAS wells (0.33%) of either DMSO or methanol (depending on which solvent the test chemical was solubilized in).

last: Flynn

first: Kendra

last: Bush

first: Moique

first: Jenna

last: Cavallin

middle: G


title: Impaired cortical neuronal homeostasis and cognition after diffuse traumatic brain injury are dependent on microglia and type I interferon responses

status: Public on Jun 05 2025

city: Columbus

first: Jonathan

last: Godbout

state: OH

address: 460 Medical Center Drive

institute: The Ohio State University

summary: Neuropsychiatric complications including depression and cognitive decline develop in the years after traumatic brain injury (TBI), negatively affecting quality of life. Microglial and type 1 interferon (IFN-I) responses are associated with the transition from acute to chronic neuroinflammation after diffuse TBI in mice. Thus, the purpose of this study was to determine if impaired neuronal homeostasis and increased IFN-I responses intersected after TBI to cause cognitive impairment. Here, the RNA profile of neurons and microglia after TBI (single nucleus RNA-sequencing) with or without microglia depletion (CSF1R antagonist) was assessed 7 dpi. There was a TBI-dependent suppression of cortical neuronal homeostasis with reductions in CREB signaling, synaptogenesis, and synaptic migration and increases in RhoGDI and PTEN signaling (Ingenuity Pathway Analysis). Microglial depletion reversed 50% of TBI-induced gene changes in cortical neurons depending on subtype. Moreover, the microglial RNA signature 7 dpi was associated with increased stimulator of interferon genes (STING) activation and IFN-I responses. Therefore, we sought to reduce IFN-I signaling after TBI using STING knockout mice and a STING antagonist, chloroquine (CQ). TBI-associated cognitive deficits in novel object location and recognition (NOL/NOR) tasks at 7 and 30 dpi were STING dependent. In addition, TBI-induced STING expression, microglial morphological restructuring, inflammatory (Tnf, Cd68, Ccl2) and IFN-related (Irf3, Irf7, Ifi27) gene expression in the cortex were attenuated in STINGKO mice. CQ also reversed TBI-induced cognitive deficits and reduced TBI-induced inflammatory (Tnf, Cd68, Ccl2) and IFN (Irf7, Sting) cortical gene expression. Collectively, reducing IFN-I signaling after TBI with STING-dependent interventions attenuated the prolonged microglial activation and cognitive impairment.

overall_design: Here, microglia were depleted prior to midline fluid percussion (TBI) using a CSF1R antagonist, PLX5622. Male mice were maintained on vehicle or PLX diet for the duration of the experiment. Cortical nuclei were isolated, fixed, and barcoded at 7 dpi. snRNA-seq was performed on nuclei from the cortex.

first: Packer

last: Jonathan

first: Bray

last: Chelsea

first: Beckman

last: Nicolas

first: Wangler

last: Lynde

first: Davis

last: Amara

first: Goodman

last: Ethan

first: Godbout


title: Generation of cellular diversity through temporal patterning of radial glia during mouse corticogenesis II

city: Shanghai

first: XIAOSU

last: LI

state: Shanghai

address: 131 Dongan Road

institute: Fudan University

summary: Neural cell type diversity arises from both spatial and temporal patterning of neural stem cells. Although spatial patterning mechanisms have been extensively studied, temporal patterning mechanisms remain relatively unexplored. In this study, we addressed generation of diverse neural cell types through lineage progression of mouse cortical radial glia. The time series scRNA-seq and snATAC-seq of mouse cortical development revealed that radial glia temporally transitioned from neurogenesis to gliogenesis.  During gliogenic stages, various cell types were generated simultaneously along multidirectional lineage trajectories. We established comprehensive molecular maps for cortical lineage commitment and cellular diversification. The transcriptome and epigenome of cortical radial glia exhibit temporal dynamics, as revealed by scRNA-seq and snATAC-seq. Lhx2, a transcription factor with temporal dynamic chromatin binding activities, was identified as a key regulator of the neurogenesis-to-gliogenesis transition. It maintains neurogenic competence by establishing the active epigenetic state of its target genes.

overall_design: Bulk RNA-seq of control and Lhx2 cKO cortices at E15.

first: Xiaosu

first: Lin

last: Yang

first: Zhengang


title: Scalable generation and functional classification of genetic variants in inborn errors of immunity to accelerate clinical diagnosis and treatment

city: New York

first: Zachary

last: Walsh

state: New York

address: 650 West 168th Street, Rm 1708

department: Hematology/Oncology

institute: Columbia University

summary: Next-generation sequencing is pivotal for diagnosing inborn errors of immunity (IEI) but predominantly yields variants of uncertain significance (VUS), creating clinical ambiguity. Activated-PI3Kδ syndrome (APDS) is caused by gain-of-function (GOF) variants in PIK3CD or PIK3R1, which encode the PI3Kδ heterodimer. We performed massively parallel base-editing of PIK3CD/PIK3R1 in human T-cells and mapped thousands of variants to a clinically important readout (phospho-AKT/S6), nominating >100 VUS and unannotated variants for functional classification, and validated 27 hits. Leniolisib, an FDA-approved PI3Kδ-inhibitor, rescued aberrant signaling and dysfunction in GOF-harboring T-cells, and revealed partially drug-resistant PIK3R1 hotspots that responded to novel combination therapies of Leniolisib with mTORC1/2-inhibition. We confirmed these findings in T-cells from APDS patients spanning the functional spectrum discovered in the screen. Integrating our screens with population-level genomic studies revealed that APDS may be more prevalent than previously estimated. This work exemplifies a broadly applicable framework for removing ambiguity from sequencing in IEI.

overall_design: Primary human T cells were lentivirally transduced with a custom base editing sgRNA library targeting PIK3CD and PIK3R1, and then base edited with the adenine base editor ABE8e. Base edited T cells were then either re-expanded for 14 days ("proliferation screen") or stimulated acutely for 20 minutes with CD3/CD28 antibody, stained for phosphoproteins pAKT and pS6, and sorted into either [pAKT/pS6 - high] or [pAKT/pS6 - negative] bins by FACS ("AKT/S6 screen"). An additional AKT/S6 screen was performed (with the same conditions and same human T cell donors) using the narrow editing-window adenine base editor ABE9. For all experiments sgRNA sequences were amplified and sequenced using an Element AVITI.

first: Chris

last: Frangieh

first: Neeha

last: Kothapalli

first: Benjamin

last: Izar


title: Adipocyte thyroid hormone receptor β determines the intracellular usage and fate of glucose and governs systemic homeostasis

city: shanghai

first: Yiruo

last: Ma

state: shanghai

address: 320 Yueyang Road, Shanghai

institute: Shanghai Institute of Nutrition and Health Chinese Academy of Sciences, CAS

summary: To investigate the effect of thyroid hormone and its receptor on glucose and lipid metabolism in white adipose tissue (WAT), and the effect of thyroid hormone and its receptor on WAT regulation on glucose metabolism and obesity. We constructed mice with adipose tissue-specific knockout of thyroid hormone receptor beta（ATRβKO mice）. ATRβKO mice were given T3 stimulation or high-fat feeding. We then performed gene expression profiling analysis using data obtained from RNA-seq of White adipose tissue from knockout ATRβKO mice treated with T3 or HFD feeding.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Floxed (Veh) , Floxed (T3)  and ATRβKO  (T3),and  for Floxed (HFD) with ATRβKO  (HFD)

first: Jingjing

last: Jiang

first: Yuying

last: Li

first: Hao

last: Ying


title: Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy

city: Duarte

first: Hsun

middle: Teresa

last: Ku

state: CA

address: 1500 E. Duarte Road

department: Translational Research and Cellular Therapeutics

institute: City of Hope

summary: Although most patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) receiving CD19-targeted chimeric antigen receptor (CAR) T cell therapy achieve remission, loss of CAR T cell functionality and subsequent relapse remains an unmet therapeutic need. We applied an integrative approach to study the immunometabolism of pre- and post-infusion CD19-CAR T cells of patients with relapsed/refractory B-ALL. Pre-infusion CAR T cells of long-term responders (LTR) had increased oxidative phosphorylation, fatty acid oxidation, and pentose phosphate pathway activities, higher mitochondrial mass, tighter cristae, and lower mTOR expression compared to products of short-term responders. Post-infusion CAR T cells in bone marrow (BM) of LTR had high immunometabolic plasticity and mTOR-pS6 expression supported by the BM microenvironment. Transient inhibition of mTOR during manufacture induced metabolic reprogramming and enhanced anti-tumor activity of CAR T cells. Our findings provide insight into immunometabolic determinants of long-term response and suggest a therapeutic strategy to improve long-term remission.

overall_design: Generation of CAR T cells with rapamycin. Enriched Tn/mem cells from leukapheresis products were stimulated with GMP Human T-expander CD3/CD28 Dynabeads™ (Dynal Biotech Cat#11141D) at a ratio of 1:3 (T cell:bead) overnight. Activated T cells were subsequently transduced with CD19R(EQ):CD28:ζ/EGFRt clinical construct at MOI=1 in RPMI 1640 containing 10% FBS and 5μg/ml protamine sulfate (Fresenius Kabi, 22905), 50U/mL rhIL-2 (Novartis Pharmaceuticals, NDC0078-0495-61), and 0.5 ng/mL rhIL-15 (CellGenix, 1013-050). Beginning 4 days after bead stimulation, CAR T cells were treated with rapamycin (50 nmol/L) (LC Laboratories, R-5000) or vehicle (DMSO) and refreshed with media containing rapamycin or vehicle every other day. Six days after stimulation, CD3/CD28 Dynabeads™ beads were removed using a DynaMag™-5 Magnet (Invitrogen, 12303D), and cells were maintained at a concentration of 1x106 cells/mL in RPMI 1640/10% FBS, 25U/mL rhIL-2, and 0.25 ng/mL rhIL-15 throughout T cell expansion.

first: Lior

last: Goldberg

first: Min-Hsuan

last: Chen

first: Xiwei

last: Wu

first: Xiuli

last: Wang


title: Fetal liver macrophage development and function require Xpr1

city: Zurich

first: Sebastian

last: Stifter

address: Winterthurerstrasse 190

institute: University of Zurich

summary: Erythroblastic island macrophages (EBI-Macs) support the development of red blood cells by recycling iron, producing growth factors,and clearing nuclei expelled from erythroblasts. In the developing embryo, the liver is the primary site of hematopoiesis,andfetal liver macrophagesperform the function ofEBI-Macs.Here, weshowthatthephosphate exporterXpr1is critical for the development offetal macrophagesin the liver and the spleen.Single-cellRNA-seqand flow cytometryanalysesin conditional mice lackingXpr1in hematopoietic and/orCD206+cellsrevealedloss of the Kupffercelltranscriptional program anda shift in the development offetal livermonocytes towards an interferon-activated monocyte/macrophage state.Functionally, thisled tothefailure to clear pyrenocytes.In adulthood,splenic red pulp and bone marrow macrophages were alsoabsent upon lossof intrinsicXpr1.Collectively,these findings reveal thatXpr1is required for the development, identity, and function ofEBI-Macs.

overall_design: E15.5 embryonic livers were dissociated and cells isolated. Three Xpr1fl/fl and three Vav1iCre Xpr1fl/fl were pooled and CD45+CD19-CD3-B220-Ter119-CD49b-CD90.2- cells sorted from each pooled sample and subjected to scRNA-seq.

first: Melanie

last: Greter


title: Transcriptomic profiling of endometrial and dermal mesenchymal stromal cells before and after treatment with menstrual fluid

city: Moscow

first: Roman

last: Eremichev

address: 27, b. 10, Lomonosovsky av.

department: Centre for Regenerative Medicine

country: Russia

institute: Lomonosov Moscow State University

summary: Introduction: Human endometrium is one of the unique organs, capable of scarless regeneration after injury during menstrual cycle. However, it is disputable whether this feature should be attributed to specific regulatory molecules present in the wound environment (menstrual fluid) or to the tissue-specific properties of endometrial mesenchymal stromal cells (eMSC), which are the main participants of wound healing. We aim to elucidate the role of eMSC tissue-specificity in wound healing. Methods: We compared eMSC and dMSC transcriptomic profiles in response to MF with those of stromal cells from scar-forming organs - dermal MSC. Results: We have found that menstrual fluid induces a profound inflammatory response in both eMSC and dMSC, but a tissue-specific component was present in the transcriptomic changes. Furthermore, transcriptomic tissue-specificity is present as after MF treatment as before it, and was validated by in vivo single-cell RNA-sequencing data from Human Protein Atlas. This tissue-specificity is related to embryonic development and morphogenesis, suggesting the role of “developmental imprinting” in its establishment. Finally, we refined transcription factors from stably tissue-specific genes that may explain the unique properties of eMSC and endometrium itself and may serve as the potential targets to induce regeneration in scar-forming organs. Conclusion: eMSC possess tissue-specific properties, including stable expression of transcription factors that may explain the scarless regeneration of endometrium.

overall_design: RNA-seq profiling of endometrial mesenchymal stromal cells (eMSC) and dermal mesenchymal stromal cells (dMSC) at baseline (BL) and after menstrual fluid treatment (MF)

first: Mikhail

last: Khandokhin

first: Natalya

last: Alexandrushkina

first: Peter

last: Nimiritsky

first: Vsevolod

last: Tkachuk

first: Pavel

last: Makarevich


title: Biological Responses During High-dose Protein Nutrition

city: Montréal

first: Alex

last: Gregorieff

state: QC

address: 1001 Decarie Boulevard

department: Department of Pathology

country: Canada

institute: RI-MUHC

summary: Reduced protein intake is associated with adverse outcomes in critically ill patients. Paradoxically, large scale randomized clinical trials have failed to demonstrate a beneficial effect of protein supplementation, perhaps because biological mechanisms associated with individual patient responses to nutrition, are poorly understood. The objective of this study was to determine the effect of exogenous protein dose on whole body protein balance (WBPB) and associated blood transcriptomic markers of metabolic response.

overall_design: We conducted a randomized controlled trial to determine the effect of high dose (2.5 g/kg/d by parenteral amino acid infusion for 48 h) versus usual (0.8 g/kg/d) or moderate (1.75 g/kg/d) doses on metabolic response as measured by whole body protein balance (WBPB). As a comprehensive and well annotated method to achieve untargeted biomarker identification, the blood transcriptome was interrogated by RNA sequencing every 12 h to identify molecular signatures that reflect the propensity to experience an anabolic response during protein supplementation.

first: Arnold

middle: S

last: Kristof

first: Mengyin

last: Hong

first: Nadia

last: Boufaied

first: Nihad

last: Tousson-Abouelazm

first: Surya

last: Dandamudi

first: Kwang-bo

last: Joung

first: Roupen

last: Hatzakorzian

first: Michelle

last: Port

first: Giuseppina

last: Campisi

first: Ciro

last: Piccirillo

first: Gregory

last: Fonseca

first: Jun

last: Ding

first: Daren

last: Heyland

first: David

middle: P

last: Labbé

first: Linda

last: Wykes

first: Thomas

last: Schricker


title: SFRS8 regulates memory by modulating pre-mRNA splicing of synaptic genes in mice

city: Hefei

first: d

last: z

address: shushan

institute: University of Science and Technology of China

summary: SFRS8 is a member of SR family protein. It is also a known splicing factor that is highly expressed in the brain. However, its function in the brain remains elusive. Here, we find that SFRS8 is required to maintain normal synaptic protein levels as well as synaptic densities. Mechanistically, we demonstrate that SFRS8 interacts with SF3B3, a major component of U2 snRNP complex, and regulates the RNA alternative splicing process. Specifically, SFRS8 regulates the levels of PSD95, through enhancing the loading of Psd95 mRNA on the U2 snRNP complex and increasing the skipping of exon18 of Psd95. We further demonstrate that SFRS8 knockdown in the hippocampus leads to reduced synaptic protein expression, decreased spine density, consequently defective memory in mice. Similar reduction in synaptic protein expression and synaptic density are also evident in cultured neurons. Taken together, SFRS8 regulates memory function in mice through altering the alternative splicing and expression of synaptic genes via SFRS8-SF3B3 interaction.

overall_design: We conducted RNA sequencing on the hippocampal tissues collected from control and SFRS8 KD mice


title: Downregulated Kcnd3 in the PSTh is vital for CSDS-induced anxiety-like behavior

city: Hangzhou

last: Liu

address: 866 Yuhangtang Road

institute: Zhejiang University

summary: Anxiety disorders seriously damage our mental health, with chronic stress identified as a major etiologic factor. However, the precise neural mechanisms underlying the transition from chronic stress to anxiety remain unclear. In this study, with the chronic social defeat stress (CSDS) paradigm in mice, we verified a critical role of the parasubthalamic nucleus (PSTh) in anxiety regulation and found that CSDS results in a lasting increase in PSTh neuronal activity. Here, we explored the molecular substrates responsible for the increased intrinsic excitability of PSTh neurons following CSDS by RNA-sequence experiments. We found that CSDS downregulated Kcnd3 in PSTh neurons. Kcnd3 knockdown enhanced PSTh neuronal activity and produced anxiogenic effects in unstressed naïve mice, whereas overexpression of Kcnd3 in PSTh neurons dampened neuronal over-excitability and alleviated anxiety-like behavior in CSDS animals. Taken together, our results provide a cellular mechanism that the downregulated Kcnd3 induced by CSDS mediates intrinsic excitability of PSTh neurons, leading to anxiety-like behavior.

overall_design: RNA-seq profiling of PSTh tissues from unstressed control mice (Control) and chronic social defeat mice (Defeat).

last: Wang

first: Huan

first: Bin

last: Gao

first: Zheng

last: Lin

first: Tian-Le

last: Xu

first: Shumin

last: Duan

first: Han