title: Blood-based epigenetic instability linked to human aging and disease [MDS_CML]

status: Public on Jan 06 2026

city: Toronto

first: Sagi

last: Abelson

state: ON

address: 661 University Avenue

country: Canada

institute: Ontario Institute for Cancer Research

summary: The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception. Here, we report 31,744 CpG sites exhibiting highly consistent methylation profiles in the blood of young, healthy individuals. We assess alterations at these epigenetically stable loci in 8,886 individuals across 29 diverse cohorts, including those with hematological cancers (n = 3,159), cardiovascular complications (n = 2,788), and healthy controls (n = 2,939). Our findings reveal methylation pattern disruption in myeloid and lymphoid malignancies, correlating with clonal burden dynamics and mutation frequency throughout leukemia treatment. In non-cancer cohorts, we observe that methylation levels at epigenetically stable loci become increasingly variable with age, a shift linked to higher cardiovascular disease risk and lower survival rates. This study highlights DNA methylation instability as a blood-based biomarker for both hematological cancer and cardiovascular disease and uncovers a mechanistic link between methylation dynamics and the expansion of maladaptive hematopoietic clones.

overall_design: Diagnosis samples from 57 MDS patients (bone marrow) and 69 CML patients (65 bone marrow, 4 peripheral blood) were analyzed using the Infinium MethylationEPIC array.

first: Dennis

last: Kim

first: Jae-Sook

last: Ahn


title: Blood-based epigenetic instability linked to human aging and disease [cardiogenic_shock]

type: Methylation profiling by genome tiling array

overall_design: Peripheral blood samples from 64 cardiogenic shock patients were analyzed using the Infinium MethylationEPIC array. The cohort consisted of patients with clonal hematopoiesis defined by DNMT3A/TET2 mutations (n=29) and those without clonal hematopoiesis (n=35).

first: Filio

last: Billia


title: Histone lactylation maintains bovine early embryo development via regulating embryonic genome activation [scRNA-Seq]

city: Hefei

first: Wenjie

last: Yu

address: No.130 West Changjiang Road

country: China

institute: Anhui Agricultural University

type: Expression profiling by high throughput sequencing

summary: Early embryo loss is an important factor affecting the reproductive capacity of cattle. Recent studies have revealed that during the process of the embryonic genome activation (EGA), epigenetic modification, such as, histone lactylation modification remodeling is crucial for early embryonic development. However, the effect and mechanism of histone lactylation modification on bovine early embryo development remain unknown. In this study, we found that histone lactylation, including pan Kla, H3K9la, and H3K18la were mainly located in nuclear, and were significantly decreased from 8-cell to morula stage as well as increased from morula to blastocyst stage in bovine IVF embryos. Decreased or increased levels of histone lactylation by GSKA or NaLa supplementation inhibited bovine early embryo development and blastocyst lineage differentiation. Furthermore, combined with scRNA-Seq data and EU straining revealed that reduction of histone lactylation levels altered expression of genes associated with DNA transcription and RNA polymerase activity, thereby impairing the process of EGA. Importantly, NMN rescued the inhibitory effects of GSKA supplementation in bovine EGA and early embryonic development. Altogether, these results indicated that histone lactylation maintains bovine early embryo development via regulating EGA process. These findings provide theoretical references for addressing early embryo loss and thereby enhancing the reproductive capacity of cattle.

overall_design: Utilizing single-cell RNA sequencing technology, we conducted an in-depth investigation into how histone lactylation modification affects bovine embryonic genome activation

first: Yi

last: Xia

first: Wenzhuo

last: Wang

first: Zhiyuan

last: Yang

first: Zhengqiu

last: Liu

first: Xinqi

last: Gan

first: Mengya

last: Zhang

first: Beibei

last: Zhou

first: Yunsheng

last: Li

first: Yunhai

first: Zubing

last: Cao


title: Single-cell insights into trophoblast heterogeneity and adaptive dysfunction in selective fetal growth restriction

city: Shanghai

first: Yan

last: Bi

state: Shanghai

address: 910 Hengshan Road, Xuhui District

institute: International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University

summary: Selective fetal growth restriction (sFGR) in monochorionic twins reflects placental dysfunction, but trophoblast adaptation mechanisms remain unclear. Using single-cell RNA sequencing of three MCDA twin pairs, we reveal villous cytotrophoblasts (VCT) in growth-restricted placentas shift from TP63/SOX6-expressing barrier phenotypes to metabolically stressed YY1/RELA-activated states, with upregulated glycolysis/mitochondrial dysfunction and downregulated adhesion pathways. Trajectory analysis shows diminished syncytial precursors, suggesting impaired fusion capacity. Immune profiling identifies depleted TREM2+ Hofbauer macrophages and expanded interferon-responsive NK cells. Cell-cell interaction mapping demonstrates enhanced IFNG-IFNGR1-STAT1 signaling between VCT_LDHA and immune cells, alongside weakened VCT_TP63-stromal crosstalk. This study defines a maladaptive triad of metabolic stress, inflammation, and structural disintegration in sFGR, contributing to sFGR pathogenesis.

overall_design: We conducted single-cell RNA sequencing (scRNA-seq) of three pairs of MCDA twin pregnancies discordant for fetal growth (sFGR_Smaller and sFGR_Larger placental territories). A total of six placental samples were processed using the 10x Genomics Chromium platform to characterize cellular heterogeneity and microenvironmental remodeling.

first: Jiawen

first: Yanlin


title: Single-Cell Omics Analysis of Human Basophils Reveals Two Transcriptionally Distinct Populations

status: Public on Jan 07 2026

city: Solna

first: Joakim

middle: S

last: Dahlin

address: CMM, Visionsgatan 18

department: Department of Medicine, Solna

country: Sweden

institute: Karolinska Institutet

summary: Single-omics technologies have been extensively used to study the heterogeneity of cell populations. However, human basophils are remarkably underrepresented in single-cell RNA-sequencing studies. Here, we used CITE-seq (single-cell RNA-sequencing with feature barcoding) to profile the basophil transcriptome, to detect cell surface epitopes, and to barcode specific cell populations.

overall_design:
We performed CITE-seq of low-density leukocytes and isolated basophils from the peripheral blood of 4 healthy donors. For the first dataset, side scatter (SSC) low leukocytes were sorted and mixed with SSClow Lin- CCR3+ FCεR1+ basophils. To generate the second dataset, we sorted SSClow Lin- CCR3+ FCεR1+ basophils and mixed them with SSClow Lin- CCR3+ FCεR1+ c-KIT+ basophils. To generate the third dataset, we MACS-enriched CCR3+ cells from low density leukocytes, producing 3 datasets from 2 donors in 2 indepedent experiments. To generate the fourth dataset, we repurposed the full-length amplified cDNA material used to produce the third dataset. Specifically, we performed long-read sequencing of 2 samples (1 library from each donor) using the Oxford Nanopore Technology.

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Please note that Swedish legislation and GDPR prevent unrestricted distribution of raw sequencing data and thus raw data is not provided.
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first: Sofia

last: Papavasileiou

first: Daryl

last: Boey


title: Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade

city: Seattle

first: Shivani

last: Srivastava

state: WA

address: 1100 Fairview Ave N

country: USA

institute: Fred Hutchinson Cancer Center

summary: CAR-T therapy has shown limited synergy with PD-1/PD-L1 blockade, but the mechanisms underlying resistance remain unclear. PD-1⁺TCF1⁺ stem-like T cells mediate responses to PD-1/PD-L1 blockade and are maintained by MHC-dependent interactions with DCs in tumor-draining lymph nodes (dLN). Because CAR-Ts recognize intact antigen, not peptide-MHC, their activation is confined to tumors, potentially preventing maintenance of this critical subset. In ROR1⁺ lung cancer models, ROR1-targeting CAR-Ts rapidly down-regulated TCF1, became exhausted, and were not enhanced by PD-L1 blockade. Overexpression of the AP-1 transcription factor c-Jun, but not BATF, enabled formation of PD-1⁺TCF1⁺ reservoirs in tumors, not dLN, but did not prevent exhaustion, as PD-1 induced post-transcriptional c-Jun down-regulation. Remarkably, PD-L1 blockade restored c-Jun levels, dramatically increased CAR-Ts, and enabled near-complete ROR1+ tumor clearance. These findings identify PD-1 as a suppressor of c-Jun and reveal that MHC-independent CAR-Ts can be engineered to establish intratumoral stem-like reservoirs that overcome resistance to PD-1 blockade.

overall_design: Bulk RNA-seq profiling of ROR1 CAR-T and cJun.ROR1 CAR-T cells sorted 5 days after infusion from KP-ROR1 lung tumor–bearing mice treated with either vehicle (PBS) or anti–PD-L1 checkpoint blockade immunotherapy.

first: Andrew

middle: J

last: Snyder


overall_design: Bulk RNA-seq profiling of ROR1 CAR-T, cJun.ROR1 CAR-T, and BATF.ROR1 CAR-T cells pre-infusion or sorted 8 days post-infusion from KP-ROR1 tumors


type: Genome binding/occupancy profiling by high throughput sequencing

summary: This SuperSeries is composed of the SubSeries listed below: GSE310249 and GSE310250

overall_design: Refer to individual Series


title: Bulk RNA sequencing to investigate transcriptional profiles of lung macrophage subpopulations isolated from wild-type C57BL/6J and Spp1-EGFP knock-in reporter mice subjected to intratracheal administration of bleomycin or PBS.

city: Tokyo

first: Kohsuke

last: Shirakawa

address: 35 Shinanomachi, Shinjuku-ku

department: Cardiology

country: Japan

institute: Keio University School of Medicine

summary: This study aimed to characterize the transcriptomic landscape of Spp1-expressing interstitial macrophages (IMs) in the lungs of a bleomycin-induced pulmonary fibrosis mouse model using single-cell RNA sequencing (scRNA-seq). We utilized Spp1-EGFP knock-in reporter mice, in which EGFP marks Spp1-expressing cells. Pulmonary fibrosis was induced by intratracheal administration of bleomycin. Lung  cells were isolated, and Spp1-EGFP⁺ SiglecF⁻ CD11b⁺ interstitial macrophages were enriched by flow cytometric sorting. Approximately 10,000 viable sorted cells were processed for single-cell transcriptome profiling using the Chromium Next GEM Single Cell 3' Reagent Kits v3.1 (10x Genomics), and libraries were sequenced on a DNBSEQ-G400 platform. This dataset provides a high-resolution view of the cellular states and gene expression profiles of interstitial macrophages during lung fibrosis.

overall_design: Spp1-EGFP knock-in mice and wild-type C57BL/6J mice were intratracheally administered bleomycin (3 μg/g body weight) or PBS as control. At day 7, 14, or 30 post-administration, mice were euthanized, and lung tissues were harvested. Lung single-cell suspensions were prepared by enzymatic digestion and mechanical dissociation, followed by red blood cell lysis and Percoll density gradient centrifugation. Alveolar and interstitial macrophages were isolated by flow cytometry based on SiglecF and CD11b expression. In Spp1-EGFP knock-in mice, both EGFP⁺ and EGFP⁻ subsets were sorted. Total RNA was extracted from each population, and cDNA libraries were prepared using polyA selection. Sequencing was performed on an MGISEQ-2000RS platform with 150-bp paired-end reads. Raw reads were processed and mapped to the GRCm38 mouse reference genome using HISAT2, and gene-level quantification was conducted with featureCounts. Differentially expressed genes were identified using DESeq2, and downstream analyses included hierarchical clustering, PCA, and gene ontology enrichment using Metascape.


overall_design: CUT&Tag for the histone modificiations H3K4me3 and H3K27me3 in ROR1 CAR-T, cJun.ROR1 CAR-T, and BATF.ROR1 CAR-T cell infusion products.


title: Single-cell transcriptomic profiling of lung interstitial macrophages in bleomycin-induced pulmonary fibrosis in Spp1-EGFP reporter mice

overall_design: To investigate the transcriptional states of interstitial macrophages (IMs) during pulmonary fibrosis, Spp1-EGFP knock-in reporter mice were used. Pulmonary fibrosis was induced by intratracheal administration of bleomycin (3 μg/g body weight). Mice were anesthetized with 1.0–1.5% sevoflurane during the procedure. Seven days after bleomycin administration, mice were sacrificed, and lung and peripheral blood cells were harvested. Lungs were enzymatically digested using type I collagenase, and immune cells were isolated using a Percoll density gradient. Spp1-EGFP⁺ SiglecF⁻ CD11b⁺ IMs were sorted via flow cytometry on a BD FACSAria III instrument. Sorted cells were pooled, counted, and loaded into a Chromium Controller (10x Genomics) for single-cell capture and library preparation. Libraries were constructed using Chromium Next GEM Single Cell 3' Reagent Kits v3.1, and sequenced with a DNBSEQ-G400 sequencer (MGI Tech) with paired-end 150-bp reads, generating ~350 million reads per sample. The Cell Ranger pipeline was used for data processing including alignment, barcode processing, and gene expression quantification.


title: Ovarian Tumor FAK Inhibition Releases Omega-3 Fatty Acids Stimulating GATA6 Peritoneal Macrophage CXCL13 Production Enhancing Immunotherapy

city: La Jolla

first: Dwayne

middle: G

last: Stupack

state: CA

address: 3855 Health Sciences

department: Obstetrics and Gynecology

institute: UC San Diego Moores Cancer Center

summary: Genetic or pharmacolgic inhibition of Focal Adhesion Kinase in the murine KMF tumor model is compared to the growth of untreated tumors and with  those treated with first line or second line chemotherapies.  Impact upon the tumor subpopulations and immune compartment is evaluated via scRNAseq..

overall_design: KMF cells were seeded at 5 million per C57bl/6 mouse IP and mice were untreate or were treated serially with standard of care chemotherapy (platinum + taxane) or pegylated doxorubicin.  Alternatively, mice were treated with an inhibitor of FAK (VS4718) or with cells deficient in FAK expression(KO) of catalytic activity(KD, Kinase dead).

first: Duygu

last: Ozmadenci

first: David

last: Schlaepfer

first: James

last: Lee


title: Disrupted Energy Metabolism is Associated with Retinal Ganglion Cell Degeneration in Autosomal Dominant Optic Atrophy

city: New York

first: Eugene Yu-Chuan

last: Kang

state: NY

address: 701 W. 168 St, HHSC 2nd floor, 210

institute: Columbia University Irving Medical Center

summary: This study investigated the impact of an Opa1 variant on mitochondrial function and retinal metabolism using a novel knock-in mouse model (Opa1V291D/+) that mirrored autosomal dominant optic atrophy (ADOA). The model recapitulated RGC-specific structural and functional deficits, highlighting mitochondrial dysfunction characterized by reduced Complex I activity, increased oxidative stress, and diminished ATP production. Spatial metabolomics revealed metabolic imbalances, with heightened glycolysis in the outer retina but an energy deficit in the inner retina, particularly affecting RGCs. Single-nucleus RNA sequencing (snRNA-seq) confirmed a selective downregulation of energy-production genes in RGCs, underscoring their susceptibility to energy deficits. These findings established a mechanistic link between disrupted energy metabolism and RGC degeneration in ADOA and provided a valuable platform for exploring therapeutic strategies targeting energy pathways to prevent vision loss.

overall_design: To investigate transcriptomic changes underlying RGC degeneration in ADOA, we performed single-nucleus RNA sequencing (snRNA-seq) on retinal tissues from Opa1V291D/+ and WT mice at 360 days, enabling the identification of cell-type-specific gene expression alterations, particularly in energy metabolism pathways across different retinal cell populations.

first: Yun-Ju

last: Tseng

first: Nan-Kai

last: Wang

first: Chyuan-Sheng

last: Lin


title: Porcine induced pluripotent stem cells generated in LACID medium

city: Hangzhou

first: Chengchen

last: Zhao

state: Zhejiang

address: Dunyu Road No.600, Xihu District

institute: Westlake University

summary: Pigs are becoming increasingly important for disease model generating, xenotransplantation and interspecies organogenesis due to their similarity to human in anatomy and physiological structure. Porcine induced pluripotent stem cells (piPSCs) induced from porcine somatic cells are believed to support porcine application. But the establishment of piPSCs capable of feeder-free culture, robust development potential, and blastocysts generation through SCNT has yet to be achieved. Further investigation is needed to explore porcine pluripotency. And the reprogramming medium for piPSCs is few optimized. We found that the induced iPS chemically defined medium 3 (iCD3) promoted the formation of epithelium-like colonies in porcine reprogramming. Then Culturing medium containing LIF, activin A, GSK3 inhibitor, IWR-1, (S)-(+)-dimethindene maleate (LACID) was utilized to achieve stable piPSCs. The LACID piPSCs were identified to exist strong pluripotent characteristics. (1) LACID piPSCs had fundamental pluripotent characters, displaying flat morphology, expressing pluripotent transcription factors and surface marker. Stable Feeder-free culture for LACID piPSCs were carried out by laminin 511 coating and the addition with LDN-193189. (2) These cells exhibited a strong ability to differentiate and form teratoma in NOD-SCID mice, containing three germ layers. Additionally, cardiomyocytes, PEFs, and blastoids were achieved successfully by differentiation. (3) These piPSCs had a good ability to proliferate and their genome could be edited using CIRSPR/Cas9 for knock-in and knockout.  Blastocysts from piPSCs were also achieved by SCNT, which indicated the application value of piPSCs for transgenic pig generation. (4) LACID piPSCs could form chimeric blastocysts and contribute to intraembryonic parts of chimeric blastocysts. (5) Compare with other reported porcine stem cells, LACID piPSCs had advantage in the expression of pluripotent gene and signaling pathways regulating pluripotency of stem cells. In summary, LACID piPSCs exhibited favorable pluripotency features, which renders them ideal for investigating porcine medical applications and achieving naïve or more advanced porcine stem cells.

overall_design: Porcine induced pluripotent stem cells (piPSCs) were induced from porcine embryonic fibroblasts. Three piPSC lines were established from single colonies and maintained in LACID medium. The pluripotency of these piPSCs was thoroughly evaluated. Then three cardiomyocyte lines were differentiated from these piPSCs. For feeder free culturation, LACID piPSCs were seeded on the plate coated with laminin 511 and passaged more than three times to achieve stable piPSCs (Laminin). To optimize the culture medium for feeder-free culture, 100 nM LDN-193189 was added to the LACID medium to culture piPSCs on laminin 511. These piPSCs were passaged more than three times to obtain more compact piPSCs (Laminin-LDN). For the defined culture conditions, the basal medium was prepared by mixing DMEM-F12 and Neural basal medium in a 1:1 ratio, supplemented with 1% N2 and 1% B27. This medium was tested for LACID piPSCs culture. After more than three passages, the piPSCs in N2B27-LACID showed more dome-shaped and compact colony morphology.

first: Bingbo

last: Shi

first: Dong

last: Liu

first: Duanqing

last: Pei


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (CUT&RUN)

city: Lausanne

middle: Michael

last: Suter

address: EPFL SV-IN Station 19

department: Institute of Bioengineering

country: Switzerland

institute: École polytechnique fédérale de Lausanne

summary: Discriminating regulatory functions of chromatin composition from those of chromatin-modifying complexes is a central problem in gene regulation. This question remains unexplored in the context of histone variants and their dedicated chromatin remodelers. Here we dissect the distinct and cell cycle-dependent functions of Snf2 Related CREBBP Activator Protein (SRCAP) and H2A.Z in gene regulation of pluripotent stem cells. Using acute degradation of endogenous SRCAP, we uncover dynamic changes of H2A.Z occupancy and continuous requirement of SRCAP over the cell cycle. We also engineered an SRCAP mutant, defective for H2A.Z deposition, allowing us to distinguish H2A.Z-dependent and independent functions of SRCAP. We discover that SRCAP exhibits essential H2A.Z-independent functions in inhibiting DNA binding of dozens of pioneer transcription factors at enhancers by steric hindrance. In contrast, H2A.Z acts mainly as a transcriptional repressor gatekeeping the expression of lineage-specific genes. Our study establishes the catalytic-independent role of a chromatin remodeler in broadly regulating transcription factor binding, and demonstrates how a chromatin remodeler-histone variant pair orchestrates transcription to maintain self-renewal and plasticity of pluripotent stem cells.

overall_design: Chromatin immunoprecipitation on H2A.Z, histone PTM and several TF in mESC depleted or not for SRCAP

first: Armelle

last: Tollenaere

first: Enes

last: Ugur

first: Cedric

last: Deluz

first: Heinrich

last: Leonhardt

middle: M


title: Cartography and mechanism of enhanced transcriptome plasticity by transposable elements

city: Irvine

first: Ivan

last: Marazzi

address: 839 Health Sciences Road

department: Department of Biological Chemistry

institute: University of California

summary: Transposable elements (TEs) in our genome are the heritage of ancient parasitic infections. While most of human DNA is comprised of TEs and TE-derived elements, their repetitive nature poses technical challenges and thus little is known about their positional identity and regulatory roles. Here, by integrating long-read and multidimensional transcriptional analyses, we investigated when, where and how TEs become part of a gene. We characterized how TE-derived isoform and new genes change across mouse-human variation and are linked to gene regulatory networks controlling cell states during differentiation, organogenesis and health (aging and pathological states). Mechanistically, we identified an RNA degradation-dependent and a splicing-dependent quality control mechanism that operate independently of conventional mechanisms of TE suppression (DNA methylation and heterochromatinization) and prevents TE-exonization and TE-induced cell differentiation. Overall, our findings reveal new mechanisms by which viral-derived elements enhance transcriptome plasticity.

overall_design: RNA-seq profiling of WT and Exosc3 cKO mESCs treated with major and minor splicing inhibitors (U1 and U6atac AMO) and MERVL ASO.

first: Youngseo

last: Cheon

first: Erik

last: Alvstad


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (RNA-Seq)

first: David

overall_design: nuclearRNASeq in duplicates in mESC depleted for 2, 4, 6 or 8h for SRCAP or for 1h and sorted for earlyG1 or lateG1 phase or for mESC expressing wtSRCAP or cdSRCAP


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (ChIP-Seq)


title: Cerebrospinal fluid-driven ependymal motile cilia defects are implicated in multiple sclerosis pathophysiology

city: Montreal

first: Jo Anne

last: Stratton

address: 3801 Rue University

institute: McGill University

summary: Background: Multiple sclerosis is a neurodegenerative autoimmune disorder of the central nervous system (CNS) in which autoreactive immune cells migrate through a damaged blood brain barrier, resulting in focal demyelinating lesions of both the white and grey matter. Of increasing interest is the repeated observation that beyond focal lesions, there are also diffuse, surface-in gradients of pathology in MS, wherein damage is most severe directly adjacent to cerebrospinal fluid (CSF)-contacting surfaces, such as the subpial and periventricular areas. This observation suggests that toxic factors within MS CSF may be contributing to the emer-gence and/or evolution of surface-in gradients. Directly separating the CSF from the periventricular parenchyma are ependymal cells – a glial epithelium that expresses tufts of motile cilia which are critical for circulating CSF solutes and regulating local fluid flow. While damage to ependymal cilia has the potential to drastically modify CSF homeostasis and thus contribute to the damage of CSF exposed regions, these motile cellular structures have yet to be investigated in the context of MS. Methods: We first conducted single cell RNA sequencing of fresh human periventricular brain tissue containing ependymal cells from MS patients and non-MS disease controls. We subse-quently collected CSF from MS patients and exposed cultured rodent ependymal cells to this CSF in order to evaluate impact on ependymal ciliary function. To complement our direct eval-uation of cilia in the context of MS, we also confirmed whether cilia were altered in a classic animal model of MS, experimental autoimmune encephalomyelitis (EAE), and also designed a novel transgenic animal model to evaluate the cellular and behavioural effect(s) of adult ep-endymal ciliary disruption. Results: Single cell RNA sequencing analysis of human ependymal cells in MS demonstrated largescale dysregulation of ciliary genes; in situ stains of MS brain tissue confirmed a loss of ependymal cilia in MS compared to control. Exposure of ependymal cells to MS CSF led to transcriptional modification of ciliary gene expression and reduced ciliary beating frequency. Likewise, analysis of ependymal cells in EAE also demonstrated altered cilia gene expression. Conditional knockout of the critical cilia-associated gene Ccdc39 in ependymal cells led to transient ventricular enlargement, increased periventricular microglial density, and alterations in nesting behaviour. Conclusion: These data suggest that cilia are dysregulated in CNS autoimmunity. More im-portantly, however, they provide evidence to suggest that ependymal cilia disruption could play an active role in the development of periventricular pathology in MS, and can lead to behav-ioural deficits that may underlie aspects non-motor MS symptomatology.

overall_design: Primary rat ependymal cell cultures were exposed to MS patient CSF samples for 48 hours (controls were left untreated), then bulk RNA sequencing was conducted to assess the resulting transcriptomic effects.

first: Maxime

last: Bigotte

first: Adam

last: M.R. Groh

first: Elia

last: Afanisiev

first: Vincent

last: Wong

first: Kevin

last: Lancon

first: Moein

last: Yaqubi

first: Finn

last: Creeggan

first: Craig

last: S. Moore

first: Adil

last: Harroud

first: Raphael

last: Schneider

first: Philippe

last: Séguéla

first: Alexandre

last: Prat

first: Simon

last: Thebault

first: Stephanie

last: Zandee

first: Jo

last: Anne Stratton


title: An integrated drug repositioning analysis identifies rosiglitazone as a repurposing candidate for sarcopenia

city: changsha

first: L

middle: L

last: S

address: tongzipo roda  NO 172

department: csu

institute: csu

summary: Sarcopenia is characterized by age-related muscle/strength loss and is becoming a highly important public health issue. The development of sarcopenia increases the risk of various adverse health outcomes, including falls, functional decline, frailty, and mortality. Despite its significance, there are no approved drugs to prevent or treat age-related sarcopenia. In this study, we used an integrated drug repurposing approach to repurpose approved drugs for the treatment of sarcopenia. We first used a network-based proximity score to quantify the relationship between disease-gene and drug-gene modules and identify potential repurposing candidates. Then we used summary-data-based Mendelian randomization analysis to explore the potential causal association between drug targets and sarcopenia. In an aging mouse model, we demonstrated that rosiglitazone, an insulin sensitizer used to treat diabetes, could improve endurance exercise performance, and increase grip strength, muscle fiber area, and hind limb muscle mass. Furthermore, we conducted transcriptomics, metabolomics analyses, and 16s RNA sequencing analysis in mice to explore the underlying mechanism of action for rosiglitazone. The results suggested that rosiglitazone may be a promising therapeutic option for alleviating or treating age-related sarcopenia, although additional clinical validation is still needed.

overall_design: After the age of 17 months, mice in the experimental group received a commercially purified diet (AIN-93M) that contained rosiglitazone, while control mice received a standard purified diet (AIN-93M) without rosiglitazone.

first: Hongwen

last: Deng

first: Hongmei

last: Xiao


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (CUT&Tag)

first: David

last: Suter

first: Armelle

last: Tollenaere

first: Enes

last: Ugur

first: Cedric

last: Deluz

first: Heinrich

last: Leonhardt


title: Spatial transcriptomics of maize embryonic leaves

city: Taipei

first: Chi-Chih

last: Wu

address: 128 Academia Road, Section 2, Nankang

department: Biodiversity Research Center

country: Taiwan

institute: Academia Sinica

summary: To explore spatial genetic profiling with histological and cellular features, we conducted 10x Visium transcriptomic system from 8 maize seedling shoots, comprising SAM and serial 5 developing embryonic leaves.

overall_design: Maize seedlings were fresh frozen and sectioned at 12 um thickness onto spatial transcriptomics (ST) gene expression (GE) slides for in situ mRNA capture, library preparation, and sequencing.


title: Mechanisms of gene regulation by SRCAP and H2A.Z

type: Methylation profiling by high throughput sequencing

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

first: Susanna

last: Dalla-Longa

first: Cédric

first: Devin

last: Assenheimer

first: J Christof

last: Gebhardt


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (EM-Seq)

overall_design: Enzymatic-Methyl Sequencing in two replicates in mESC depleted for 4h for SRCAP


title: Improving anti–CTLA-4 therapies through peptide masking and fragment crystallizable nonfucosylation: preclinical characterization of three novel antibodies

status: Public on Jan 05 2026

city: Redwood City

first: Amy

last: Jhatakia

address: 700 Bay Road

institute: Bristol Myers Squibb

summary: Background  The anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) monoclonal antibody, ipilimumab, has shown clinical benefit across multiple tumor types, both as monotherapy and in combination with nivolumab or chemotherapy. However, not all tumors respond, and peripheral effects can lead to immune-related adverse events. We characterized three novel anti–CTLA-4 antibodies: peptide-masked (PROBODY ® conditionally activatable therapeutic [PB]), nonfucosylated (NF), and combined NF- PB (BMS-986288).  Results  NF demonstrated greater T-cell priming and antitumor activity than both ipilimumab and the unmasked PB antibody in cell-based assays and mouse models. Whereas the intact PB antibody showed minimal CTLA-4 binding and peripheral immune activation, unmasking restored its functional activity to levels comparable with those of ipilimumab. Unmasked anti–CTLA-4 NF-PB retained the effectiveness of anti–CTLA-4 NF, and both molecules demonstrated more profound antitumor activity, increased effector memory T-cell response, and prolonged survival in mouse models compared with ipilimumab. Anti–CTLA-4 NF-PB demonstrated reduced peripheral immune responses than anti–CTLA-4 NF or ipilimumab in non-human primates and patients with solid tumors.  Conclusion  Anti–CTLA-4 NF-PB has enhanced antitumor activity, efficacy, and reduced peripheral activity in preclinical models, and has the potential to provide therapeutic benefit in solid tumors.

overall_design:
To capture the T-cell repertoire changes with anti–CTLA-4 treatment in the SEB hCTLA-4 mouse model, whole blood T-cell receptor (TCR) sequencing was performed using the Adaptive Mouse TCRb Immunosequencing platform (Adaptive Biotechnologies, RRID: SCR_018558). Whole blood samples were collected (at pretreatment, day 3, and day 6) in Paxgene tubes, and DNA was isolated using DNeasy Blood & Tissue Kit (Qiagen, Cat# 69504). For data analysis, GLIPH2 was utilized to analyze the local clustering of TCR sequences and to investigate the impact of SEB-specific TCRB motifs. All the TCR sequences from pretreatment samples were used as the reference panel, and sequences from day 3 and day 6 samples were utilized as the input panel. Additionally, all singleton and doubletons (TCR sequences with a count of one and two, respectively) were removed from both the reference and input panels. TurboGLIPH, an R implementation of GLIPH2, was configured and run with the following (default) parameters: sim_depth = 100, min_seq_length = 7, cluster_min_size = 2, and motif_length = (2, 3, 4). After clustering, the resulting cluster list was filtered so that only clusters with clones originating from at least two mice and a Fisher score >0.05 were kept. After filtering the clustering, each clustered clone was first linked back to the mouse/sample from which it originated and then tracked across the remaining samples for that mouse. The number of mice that fell into each treatment group across all days was counted and then plotted for each cluster outputted from GLIPH2. Each point represents how many clones were present for that cluster on a specific day for that treatment group.

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Adaptive Biotechnologies does not release raw data.
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first: Xin

last: Sun

first: Alessandra

last: Vaccaro

first: Michael

last: Wang

first: Mohammed

last: Nasser

first: Anandaroop

last: Mukhopadhyay

first: Neha

last: Gupta

first: Kyeongah

last: Kang

first: Wei

last: Hu

first: Courtni

last: Newsome

first: Cheuk Hong

last: Leung

first: John

last: Le

first: Mona

last: Yazdani

first: Haiping

last: Guo

first: Lili

last: Chen

first: Monika

last: Pradhan

first: Heather

middle: Y

last: Lin

first: Remie

last: Mandawe

first: Felix

last: Findeisen

first: Jack

last: Lohre

first: Leslie

first: Yun

last: Wei

first: Joshua

last: Dobroff

first: Shaun

last: O'Brien

first: Ke

last: Xu

last: Hammell

first: Karen

last: Price

last: Engelhardt

first: Mark

last: Selby

first: Alan

last: Korman

first: Nicholas

last: Wilson

first: Tina

last: Cascone


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (Mnase-Seq)

first: David

last: Suter

overall_design: MNase-Seq in triplicates in mESC in control condition or depleted for 4h for SRCAP, Mnase digestion was performed with 2 different concentrations : High (100 U/mL) or Low (6.25 U/mL)

first: Armelle

last: Tollenaere

first: Enes

last: Ugur

first: Cedric

last: Deluz

first: Heinrich

last: Leonhardt


title: Modulating AP-1 enables CAR-T cells to establish an intratumoral stem-like reservoir and overcomes resistance to PD-1 blockade

first: Shivani

last: Srivastava

overall_design: Single cell RNAseq profiling of lung tumors isolated from KP-ROR1 mice: 1) left untreated; 2) treated with cyclophosphamide (Cy) and ROR1 CAR-T cells (SS78); or 3) treated with Cy and cJun.ROR1 CAR-T cells (SS95). Tumors were isolated 9 or 30 days post-treatment, with N=3 mice per group. For analysis of T cells, CD8+ cells were enriched from lung tumor cell suspensions. For TME analysis, total live cells were sorted from lung tumor cell suspensions. ROR1 CAR-T and cJun.ROR1 CAR-T cell infusion products (IP) were also sequenced.

first: Andrew

last: Snyder


title: Comparative transcriptome analyses highlight distinct pathogenetic mechanisms for pleuropulmonary blastoma and congenital pulmonary airway malformations II

city: Québec

first: Lucie

last: Jeannotte

state: QC

address: 2260, boulevard Henri Bourassa

department: Biologie moléculaire, Biochimie médicale & Pathologie

institute: Université Laval

type: Non-coding RNA profiling by high throughput sequencing

summary: Pleuropulmonary blastoma (PPB) and congenital pulmonary airway malformations (CPAM) are two rare cystic lung diseases occurring in childhood. PPB can evolve from a low-grade epithelial cyst lesion to a high-grade sarcoma with poor prognosis, while CPAM usually has a favorable non-tumorous outcome. Clinical similarities complicate diagnosis and may delay appropriate care. PPB is associated with DICER1 mutations that disturb miRNA biogenesis, altering the miRNA repertoire. Conversely, KRAS mutations are detected in CPAM, but their implication remains unclear. To decipher the mechanisms underlying these diseases, we undertook a comprehensive analysis of molecular variations in CPAM and PPB lung lesions using genome-wide RNA-seq and miRNA-seq assays. Each pathology displayed a distinct expression profile revealing a unique etiology. CPAM presented misexpression of bronchial epithelial markers correlating with KRAS mutation, while changes in expression of distal lung epithelial and mesenchymal markers were PPB-specific. PPB also exhibited abnormal gain of expression of developmental transcription factors likely due to perturbed Polycomb Repressive Complex 2 (PRC2) activity. Overexpression of miR-323a-3p, which targets the PRC2 subunit EED, correlated with decreased EED expression. Together, these observations propose a PPB pathogenetic mechanism connecting DICER1 mutations and altered miRNA profile to defective PRC2 activity, misexpression of developmental transcription factors and cancer.

overall_design: Bulk miRNA-seq analysis was carried out on 3 PPB and 4 control lung specimens to identify differentially expressed miRNAs.

first: Josselin

last: Guéno

first: Nicolas

last: Houde

first: Kim

last: Landry-Truchon

first: Béatrice

last: Frenette

first: William

middle: D

last: Foulkes

first: Christophe

last: Delacourt


title: Microbiome-Derived Indole-3-lactic Acid Attenuates Cutibacterium acnes–Induced Inflammation via the Aryl Hydrocarbon Receptor Pathway

city: Seoul

first: Young In

last: Lee

state: Seoul

address: Yonsei-ro 50-1

department: Scar Laser and Plastic Surgery Center

country: South Korea

institute: Yonsei Cancer Hospital

summary: Acne vulgaris is a chronic inflammatory dermatosis where conventional therapies of-ten face limitations in efficacy and safety, necessitating the development of microbi-ome-targeted interventions. This study investigated the immunomodulatory potential of microbiome-derived tryptophan metabolites as a novel therapeutic strategy for Cutibacterium acnes-induced inflammation, focusing on the aryl hydrocarbon receptor (AHR) pathway. We evaluated indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), and indole-3-propionic acid (IPA) in comparison to tapinarof, utilizing C. ac-nes-stimulated human epidermal keratinocytes and a C. acnes-induced acne mouse model. In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including TNF-α, IL-1β, and COX2, whereas IAA demonstrated limited ef-ficacy. In vivo, ILA treatment exhibited superior therapeutic activity, markedly reduc-ing inflammatory cell infiltration, epidermal hyperplasia, and IL-1β expression. Tran-scriptomic analysis confirmed that ILA attenuates inflammatory signaling (e.g., IL-17 and TNF pathways) while upregulating AHR-responsive genes such as CYP1A1 and CYP1B1. Collectively, these findings establish ILA as a potent postbiotic that mitigates cutaneous inflammation through selective activation of the AHR. Future studies should prioritize the clinical translation of ILA-based topical fomulations, with rigorous evaluation of their efficacy and safety in well-designed human trials, to support their development as a non-antibiotic therapeutic alternative for acne management.

overall_design: RNA-seq profiling of primary human epidermal keratinocytes in untreated control, Cutibacterium acnes-stimulated, and four different treatment groups (indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), indole-3-propionic acid (IPA) and tapinarof(TAPI))

first: Sang Gyu

first: Nam Hao

last: Chau

first: Seoyoon

last: Ham

first: Yujin

last: Baek

first: Ngoc Ha

last: Nguyen


title: Thromboxane receptor activation in dendritic cells mitigates sepsis by suppressing S100a8/a9-mediated neutrophil recruitment

city: Tianjin

first: Ying

last: Yu

address: 22 Qixiangtai Road, Heping District

institute: Tianjin Medical University

summary: Dendritic cells (DCs) regulate both innate and adaptive immunity during sepsis. Prostaglandins (PGs), small lipid molecules derived from arachidonic acid via COX enzymes, are crucial regulators of immune homeostasis and inflammation. However, their role in sepsis pathogenesis remains poorly defined. In this study, we identified a significant negative correlation between DC depletion and disease severity in patients with sepsis. Thromboxane (TX) A2 receptor (TP) expression was markedly reduced in blood DCs of patients with sepsis. Patients with low DC-TP expression exhibited an increased blood neutrophil count and a worsening of disease severity. In murine models of sepsis induced by cecal ligation and puncture and lipopolysaccharide challenge, DC-specific TP deficiency exacerbated sepsis by promoting S100a8/a9-mediated neutrophil recruitment, and subsequently neutrophil extracellular trap (NET) formation and lung injury. Genetic and pharmacological inhibition of S100a8/a9-TLR4 axis protected TP-deficient mice from fatal sepsis. Mechanistically, TP signaling suppressed S100a8/a9 expression in DCs via PKCδ-Stat1 signaling, thereby restricting neutrophil infiltration and NETs formation. Finally, the targeted activation of TP in DCs using the nanodrug, DCpep-U-46619, effectively alleviated sepsis-induced lung injury in mice. These findings established TP as a critical immunoregulatory receptor in DCs, highlighting its potential as a therapeutic target for sepsis.

overall_design: Splenic CD45+ immune cells from TPflox/flox and TPflox/floxCD11cCre mice subjected to cecal ligation and puncture (CLP) were sorted for droplet-based single-cell RNA-seq (10x Genomics platform).

first: Ronglu

last: Du


title: Age-independent and targetable transcription factor networks regulate CD8+ T cell senescence in aging humans

city: Piscataway

first: Ricardo

middle: Iván

last: Martínez Zamudio

state: New Jersey

address: 675 Hoes Lane West

department: Pharmacology

institute: Rutgers Biomedical and Health Sciences | Rutgers-Robert Wood Johnson Medical School

summary: Aging impairs immunity in part through the accumulation of CD8+ T cells with senescence features, including a pro-inflammatory transcriptome and impaired proliferative capacity. Using senescent cell isolation coupled with multiomic profiling, we defined the epigenetic regulation of CD8+ T cell senescence in healthy younger and older humans. We discovered that the transition to senescence was controlled by chromatin state-specific transcription factor (TF) networks whose composition was largely insensitive to donor age. These TF networks mediated widespread enhancer remodeling, causing repression of genes essential for proliferation as well as upregulation of inflammatory and secretory pathways. Inhibition of AP1, KLF5, or RUNX2 modulated the transcriptional output and partially restored the blunted transcriptional response to stimulation of senescent CD8+ T cells. Our data also revealed CD8+ T cell senescence gene signatures predictive of response to CAR-T cell therapy in diffuse large B cell lymphomas. Overall, our study defines the gene regulatory mechanisms of senescence in human CD8+ T cells, provides a resource for the interrogation of CD8+ T cell senescence in disease, highlights TF network perturbation as a viable strategy to manipulate the senescence state of CD8+ T cells, and reveals senescent CD8+ T cell gene signatures as valuable prognostic tools for immunotherapy outcome.

overall_design: Cut&Tag profiling of H3K4me1, H3K27me3, H3K27ac and IgG control of SA-ßGal-low and SA-ßGal-high CD8+ T cells isolated from the peripheral blood from 3 younger donors.

first: Paolo S

last: Turano

first: Elizabeth

last: Akbulut

first: Hannah K

last: Dewald

first: Themistoklis

last: Vasilopoulos

first: Patricia

last: Fitzgerald-Bocarsly

first: Utz

last: Herbig

first: Ricardo Iván

last: Martínez-Zamudio


title: RNA catabolism restricts ERV expression and functionalization [WGBS]

first: Ivan

last: Marazzi

summary: Endogenous retroviruses (ERVs) are remnants of ancient parasitic viral integrations and comprise a sizable portion of the genome in most organisms. Deregulated expression of ERVs in human is associated with a plethora of disease conditions, such as cancer and neurodegeneration. Epigenetic mechanisms silence most ERVs by generating a local repressive environment (heterochromatin) to prevent their expression. However, the mechanisms controlling the fate of ERVs residing in euchromatic regions of the genome (e.g. MERVL elements) are not well understood. Here, by integrating multidimensional epigenetic and genomic analyses, we demonstrate that silencing of euchromatic MERVL elements is achieved via transcription-coupled RNA degradation. Disrupting RNA catabolism promotes RNAPII elongation from MERVL promoters, increases MERVL expression and exonization, creating novel chimeric gene isoforms, and directing embryonic stem (ES) cells toward a terminal undifferentiated state. Our results indicate that RNA catabolism is a core regulatory module of gene networks that safeguards cell identity and potency, restricts MERVL functionalization and suppresses gene birth.

overall_design: Bisulfite-Seq of mESCs and EpiLCs, in both Exosc3 cKO and control genotypes.

first: Denis

last: Torre

first: Yesai

last: Fstkchyan

last: Marrazi


title: Mechanistic basis of gene regulation by SRCAP and H2A.Z (ATAC-Seq)

first: David

last: Suter

overall_design: ATAC-Seq in mESC depleted for 2, 4, 6 or 8h t for SRCAP or for 1h and sorted for earlyG1 or lateG1 phase

first: Armelle

last: Tollenaere

first: Enes

last: Ugur

first: Cedric

last: Deluz

first: Heinrich

last: Leonhardt


title: Comparative transcriptome analyses highlight distinct pathogenetic mechanisms for pleuropulmonary blastoma and congenital pulmonary airway malformations I

first: Lucie

last: Jeannotte

overall_design: To characterize the global transcriptional changes occurring in pleuropulmonary blastoma (PPB) and congenital pulmonary airway malformations (CPAM), we applied bulk RNA sequencing (RNA-seq) to lung lesions from 4 PPB human patients, 4 CPAM human patients and  lung from 4 human controls.

first: Josselin

last: Guéno

first: Nicolas

last: Houde

first: Kim

last: Landry-Truchon

first: Béatrice

last: Frenette

first: William

last: Foulkes

first: Christophe

last: Delacourt


first: Ricardo

last: Martínez Zamudio

overall_design: RNA-seq profiling of SA-ßGal-low and SA-ßGal-high CD8+ T cells isolated from the peripheral blood from 3 younger donors. The cells were electroporated with control and small interfering RNAs targeting JUN, KLF5 and RUNX (2  siRNAs per TF) and left either untreated or stimulated with anti-CD3/anti-CD28 antibodies for 16h prior to collection for RNA isolation.

first: Paolo S

last: Turano

first: Elizabeth

last: Akbulut

first: Hannah K

last: Dewald

first: Themistoklis

last: Vasilopoulos

first: Patricia

last: Fitzgerald-Bocarsly

first: Utz

last: Herbig

last: Martínez-Zamudio


overall_design: RNA-seq profiling of SA-ßGal-low and SA-ßGal-high CD8+ T cells isolated from the peripheral blood from 3 younger donors. The cells were then plated in the presence of IL2 20U/mL and DMSO or 30µM of the respective inhibitors: SR128662, T5224 or CADD522. Cells were cultured for 3 days and subsequently collected for RNA extraction.

first: Ricardo Iván


overall_design: ATAC-seq profiling of SA-ßGal-low and SA-ßGal-high CD8+ T cells isolated from the peripheral blood from 4 younger (20s) 4 older (55+) donors.


title: Gene expression of three ivermectin selected resistant Caenorhabditis elegans strains compared to the susceptible N2 strain

city: Toulouse

first: Rémy

last: Betous

address: 23 Chemin des Capelles

department: Animal Health

country: France

institute: INRAE

summary: Ivermectin (IVM) is a cornerstone of nematode control. However, its efficacy is increasingly compromised by emerging resistance in targets parasites. Here, we investigated these mechanisms in three independently evolved Caenorhabditis elegans lineages exposed to stepwise ivermectin selection. Remarkably, these populations, although distinct, converged over time to a comparable and stabilized high level of IVM resistance. RNAseq analysis across lineages revealed a conserved enrichment for ciliary/neuronal pathways including genes expressed in amphid/phasmid, indicating remodeling of the chemosensory/ciliary network as resistance intensifies. All resistant lines also converged on the dye-filling defective (Dyf) phenotype that emerged during selection at stages coinciding with sharp gains in ivermectin tolerance, implicating amphid structure/function in the establishment of durable resistance. Our results support a two-phase associative model in which early PGP-mediated tolerance precedes the emergence of ciliary/amphidial signatures and a Dyf phenotype during selection that durably reduces susceptibility.

overall_design: RNA-seq profiling of three ivermectin-selected resistant Caenorhabditis elegans  strains and of the wild-type N2 strain at the  L4 stage

first: Claire

last: Naylies

first: Yannick

last: Lippi


overall_design: ATAC-seq profiling of SA-ßGal-low and SA-ßGal-high CD8+ T cells isolated from the peripheral blood from 3 younger donors. The cells were then plated in the presence of IL2 20U/mL and DMSO or 30µM of the respective inhibitors: SR128662, T5224 or CADD522. Cells were cultured for 3 days and subsequently collected for nuclei isolation and tagmentation.


overall_design: RNA-seq profiling of SA-ßGal-low and SA-ßGal-high CD8+ T cells isolated from the peripheral blood from 4 younger (20s) 4 older (55+) donors. These samples were analzyed in conjunction with previously published samples from accession GSE169009. From this accession, FASTQ files were downloaded and processed as detailed below in 'data processing step'.


title: Blood-based epigenetic instability linked to human aging and disease [longitudinal_AML]

city: Toronto

first: Sagi

last: Abelson

address: 661 University Avenue

institute: Ontario Institute for Cancer Research

summary: The abundance, dynamics, and context-dependent heterogeneity of DNA methylation, where a pattern considered abnormal in one cell type may be normal in another, complicate the identification of early methylation changes that drive or signal disease development. This complexity can obscure early markers of increased disease risk, making it challenging to detect and intervene in disease processes at their inception. Here, we report 31,744 CpG sites exhibiting highly consistent methylation profiles in the blood of young, healthy individuals. We assess alterations at these epigenetically stable loci in 8,886 individuals across 29 diverse cohorts, including those with hematological cancers (n = 3,159), cardiovascular complications (n = 2,788), and healthy controls (n = 2,939). Our findings reveal methylation pattern disruption in myeloid and lymphoid malignancies, correlating with clonal burden dynamics and mutation frequency throughout leukemia treatment. In non-cancer cohorts, we observe that methylation levels at epigenetically stable loci become increasingly variable with age, a shift linked to higher cardiovascular disease risk and lower survival rates. This study highlights DNA methylation instability as a blood-based biomarker for both hematological cancer and cardiovascular disease and uncovers a mechanistic link between methylation dynamics and the expansion of maladaptive hematopoietic clones.

overall_design: Longitudinal samples from 14 AML patients were analyzed using the Infinium MethylationEPIC array. Bone marrow was sampled from four patients at four different time points, and peripheral blood was sampled from another ten patients at three different time points.

first: Steven

last: Chan

first: Mark

last: Minden


title: Adiponectin Modulates the Diurnal Hepatic Transcriptome and Energy Metabolism in Male Mice

city: Lübeck

first: Leonardo

last: de Assis

address: Marie Curie

country: Germany

institute: University of Lübeck

summary: Adiponectin is an adipocyte-derived hormone with insulin-sensitizing and lipid-lowering effects. Its expression and circulating levels show pronounced variation across the day, which opens the possibility that adiponectin influences metabolic programs in target tissues, such as the liver in a time-of-day dependent manner. To test this, we compared liver circadian transcriptome profiles (with sampling at 4-hour intervals) between adiponectin-deficient (ADQ-KO) and wild-type (ADQ-WT) mice. Adiponectin loss led to tonic (i.e., time independent) transcriptional changes in the liver with 1,393 differentially expressed genes (518 up- and 875 downregulated). These included upregulation of chromatin and RNA processing pathways and downregulation of immune and mitochondrial metabolic genes. At the same time, circadian analysis identified a marked reprogramming of transcriptome rhythms in ADQ-KO livers with changes in MESOR (n = 3,369 transcripts), amplitude (n = 386), and phase of gene expression (n = 603). Genes associated with mitochondrial respiration and fatty acid metabolism showed reduced rhythm amplitude and MESOR, whereas glycolytic genes exhibited increased MESOR. One of the identified adiponectin candidate targets and a master regulator of hepatic metabolism, Hif1a, was further studied by functional assays in hepatocytes. Pharmacological adiponectin receptor activation promoted glycolysis and mitochondrial respiration under normoxia, but these effects were attenuated under hypoxia mimicry, consistent with HIF1a-dependent interference. These findings suggest adiponectin as a regulator of liver circadian metabolism, modulating both the timing and magnitude of energy-related gene expression programs, potentially in part through a HIF1a-mediated mechanism.

overall_design: Three- to eight-month-old male ADQ-WT and ADQ-KO mice (B6;129-Adipoqtm1Chan/J; JAX strain 008195) on a C57BL/6J background were group-housed under a 12-hour light, 12-hour dark (LD, ~300 lux in the light phase) cycle at 22 ± 2 °C and a relative humidity of 60 ± 5 % with ad libitum access to standard chow and water. Mice were culled by cervical dislocation at 4-hour intervals, tissues were kept on dry ice and stored at −80 °C. Animal experiments were ethically approved by the Animal Health and Care Committee of the Government of Schleswig-Holstein and in line with international guidelines for the ethical use of animals. Data were reported according to the ARRIVE guidelines. For each timepoint, a total of 3 – 4 mice were used.

middle: V

first: Henrik

last: Oster


title: Tet2 modulates ER stress responses, β cell death, and autoimmunity in diabetes [scTCR-seq]

city: Farmington

first: Madhav

last: Kothari

state: CT

address: 10 Discovery Drive

institute: The Jackson Lab

summary: In previous studies, we showed that Tet2 controls the responses of beta cells to inflammation in a model of autoimmune Type 1 diabetes, but the specific cell types affected by Tet2  loss in islets was not clear and the molecular mechanisms responsible for the autoimmune responses and beta cell death were unknown. We found that Tet2-deficient islets have fewer islet infiltrating lymphocytes beginning 8-10 weeks after bone marrow transplant, reduced activation of CD8+ T cells, and greater CD8+ T cell repertoire diversity. Transcription factor finding motifs for interferon responses factors and inflammatory signaling molecules were enriched in Tet2-responsive cis-regulatory elements across all KO islet endocrine cells, but we observed beta cell-specific enrichment of TFs modulating homeostatic or ER stress response pathways. To confirm the effects of TET2 in human islets, we induced ER stress with brefeldin A or thapsigargin and inhibited TET2 with Bobcat 339. Pharmacologic TET inhibition reduced expression of ER stress response genes, inflammatory responses, and stress-induced beta cell death. We conclude that Tet2(TET2) can regulate ER stress responses involved in beta cell killing in autoimmune/inflammatory settings.

overall_design: scRNA-seq, snATAC-seq and scTCR-seq of islets from NOD and Tet2KO NOD mice of 10-13 weeks of age

first: Jinxiu

last: Rui

first: Romy

last: Kursawe

first: Mahsa

middle: N

last: Barkestani

first: Romi

last: Genosar

first: Pamela

last: Clark

first: Michael

last: Stitzel

first: Kevan

middle: C

last: Herold


title: Spatial single cell transcriptomic analysis of a lineage-traceable mouse model of DICER1 Syndrome informs tumor developmental hierarchy [RNA-Seq]

city: Vancouver

first: David

last: Huntsman

state: BC

address: 675 W 10th Ave

department: Molecular Oncology

institute: BC Cancer Research Centre

summary: DICER1 syndrome predisposes children and young adults to tumor development across various organs. Most of these cancers are sarcomas, which uniquely express the RNase IIIb domain-deficient form of DICER1 and exhibit histological and molecular similarities regardless of their anatomical origins. To uncover their cellular origin and developmental hierarchy, we established a lineage-traceable genetically engineered mouse model allowing for controlled activation of Dicer1 mutations in Hic1+ mesenchymal stromal cells. This resulted in the development of renal tumors closely mirroring human DICER1 sarcoma histologically and molecularly. Spatial single-cell transcriptomics analysis revealed that a Hic1+Pdgfra+Dpt+Pi16+ fibroblastic progenitor population, corresponding to universal fibroblasts of steady-state kidneys, exhibits the capability to undergo rhabdomyoblastic differentiation or transition into proliferative sarcomatous cells. Investigation of patient samples identified analogous cell states and developmental trajectories. This study uncovers a fibroblastic origin for DICER1 sarcoma and provides a faithful model for future mechanistic and translational investigation.

overall_design:
Hic1+ mesenchymal cells were obtained from Hic1CreERT2/CreERT2:Rosa26LSL-tdTomato and
Hic1CreERT2/CreERT2:Dicerfl/fl-D1693N;Rosa26LSL-tdTomato GEMM mice 4 weeks post tamoxifen treatment, which occurred when mice were 3-weeks-old. Following collection, cells were enriched for tdTomato+ cells via FACS. The resulting cell populations were grown in either Mesencult media or DMEM/F12 media with 10% FBS. Passaged cells were isolated and examined via bulk RNA-seq.

first: Felix

middle: K

last: Kommoss

first: Joyce

last: Zhang

first: Branden

last: Lynch

first: Shary

last: Chen

first: Janine

last: Senz

first: Yana

last: Moscovitz

first: Lesley

middle: A

last: Hill

first: Wilder

last: Scott

first: Jonathan

last: Bush

first: Kenneth

first: Andrew

last: Roth

first: Andreas

last: von Diemling

first: William

last: Foulkes

first: Gregg

middle: B

last: Morin

last: Underhill

first: Yemin

last: Wang


title: Tet2 modulates ER stress responses, β cell death, and autoimmunity in diabetes [scRNA-seq]

first: Madhav

last: Kothari

first: Jinxiu

last: Rui

first: Romy

last: Kursawe

first: Mahsa

last: Barkestani

first: Romi

last: Genosar

first: Pamela

last: Clark

first: Michael

last: Stitzel

first: Kevan

last: Herold


title: MicroRNA-146a protects against Hepatocellular Carcinoma through suppression of CCL5

city: Salt Lake City

first: Ryan

last: O'Connell

state: UT

address: Emma Eccles Jones, Medical Research Building, 15 North Medical Drive East

department: Pathology, Microbiology & Immunology

institute: University of Utah

summary: The microRNA miR-146a regulates several aspects of chronic inflammation, including the Hepatocellular Carcinoma (HCC) risk factor hepatosteatosis. Here, we find that loss of miR-146a leads to significantly increased tumor burden in a mouse model of HCC. Notably, this miR-146a-/- phenotype is most pronounced in females, who are typically not sensitive to this model. Mechanistically, we identified increases in dysfunctional CD8+ T-cells that express high levels of CCL5 and resemble Taa cells, as well as elevated levels of myeloid cells that resemble monocytic myeloid-derived suppressor cells (M-MDSCs), a class of myeloid cells that suppress tumor immunity. Deletion of Ccl5 from miR-146a-deficient mice returned tumor growth and the aberrant myeloid cell population to wild-type (WT) levels. Surprisingly, deletion of Ccl5 did not rescue the gross metabolic phenotype observed in miR-146a-/- mice subjected to HCC induction, indicating independent roles for miR-146a in its regulation of HCC and metabolic disease. Taken together, this work reveals a critical host protective role for miR-146a in HCC through suppression of CCL5, providing an impetus for targeting these pathways as a means to combat HCC. Further, the correlations with disease and Taa cells suggest that aging may increase HCC risk through the accumulation of Taa cells.

overall_design: CD45 positive immune cells from C57BL/6 mice either WT or mutant for mir146 and/or Ccl5, and maintained under different diet and carcinogen conditions to young or aged timepoints, were purified from liver cell suspensions by FACS and processed for scRNAseq analysis using a 10x Genomics platform and a Novaseq 6000.

first: Morgan

last: Nelson

first: Liam

last: O’Malley

first: Soh-Hyun

last: Lee

first: Kaylyn

last: Bauer

first: Arevik

last: Ghazaryan

middle: W

last: Tang

first: Chad

last: VanSant-Webb

first: Van

last: Tran

first: Colton

last: Hernandez

first: Benjamin

last: Battistone

first: Amber

last: Thibeaux

first: June

last: Round

first: Micah

last: Drummond

first: H

last: Ekiz

first: Kimberley

last: Evason

first: Warren

middle: P

last: Voth

last: O’Connell


title: Miconazole attenuates  LPS-induced lung inflammation by modulating alveolar macrophage polarization  through the regulation of lipid metabolism

city: Hangzhou

first: Yicheng

last: Xie

address: 3333 Binsheng Rd

institute: Children’s Hospital Zhejiang University School of Medicine

summary: Miconazole (MCZ), an antifungal agent with anti-inflammatory potential, was evaluated in a lipopolysaccharide (LPS)-induced mouse model of lung inflammation.MCZ reduced inflammatory cell infiltration, suppressed the expression of inflammatory factors, and alleviated lung injury.Single-cell RNA sequencing revealed that MCZ decreased pro-inflammatory alveolar macrophages (AM1) and increased anti-inflammatory AM2 subsets, accompanied by a shift from lipid synthesis to lipid catabolism.MCZ also disrupted the interactions between inflammatory cells in vitro and regulated the polarization of macrophages by promoting the expression of CD206 and reducing the expression of CD86 and PLIN3.These findings highlight MCZ as a potential therapeutic agent for pulmonary inflammation via lipid metabolic reprogramming and immune modulation.

overall_design: Male ICR mice, aged 6-8 weeks, were purchased from Shanghai SLAC Laboratory Animal Co., Ltd. Lung tissue samples from all mice in the LPS group and the LPS + MCZ group   (LPS + 1 mg/kg MCZ) were collected and pooled for analysis. The left lower lobe of the lung was rapidly excised, placed in cold PBS, and cut into small fragments.

first: Jian

last: Shen


title: Villification of the intestinal epithelium is driven by Foxl1

city: Philadelphia

first: Klaus

last: Kaestner

state: PA

address: 3400 Civic Center Blvd

department: Perelman School of Medicine

institute: University of Pennsylvania

summary: The primitive gut tube of mammals initially forms as a simple cylinder consisting of the endoderm-derived, pseudostratified epithelium and the mesoderm-derived surrounding mesenchyme. During mid-gestation a dramatic transformation occurs in which the epithelium is both restructured into its final cuboidal form and simultaneously folded and refolded to create intestinal villi and intervillus regions, the incipient crypts. Here we show that the mesenchymal winged helix transcription factor Foxl1, itself induced by epithelial hedgehog signaling, controls villification by activating BMP and PDGFRa as well as planar cell polarity genes in epithelial-adjacent telocyte progenitors, both directly and in a feed- forward loop with Foxo3. In the absence of Foxl1-dependent mesenchymal signaling, villus formation is delayed, the separation of epithelial cells into mitotic intervillus and postmitotic villus cells impaired, and the differentiation of secretory progenitors blocked. Thus, Foxl1 orchestrates key events during the epithelial transition of the fetal mammalian gut.

overall_design: Single-cell RNA sequencing (scRNA-seq) was performed to investigate the role of the winged helix transcription factor Foxl1 in orchestrating villus formation during mouse fetal gut development. Proximal half of the small intestines were isolated from embryonic day 15.5 (E15.5) Foxl1-CreERT2-tdTomato mice, and single-cell suspensions were prepared using enzymatic digestion followed by FACS enrichment of live cells. Libraries were generated using the 10x Genomics Chromium Single Cell 3' v2 platform, with a target of ~5,000 cells per sample. The goal was to characterize Foxl1-dependent gene regulatory networks in mesenchymal telocyte progenitors and their impact on epithelial-mesenchymal cross talk and developmental signaling pathways. Comparative analyses were performed between control (heterozygous) and Foxl1-null (homozygous) embryos to define how loss of Foxl1 alters transcriptional programs essential for intestinal villification.

first: Guoli

last: Zhu

first: Jonathan

last: Schug

first: Deeksha

last: Lahori


title: The effect of pentafactor (M5) treatment on the transcriptome of keratinocyte cell line HaCaT

city: Shiyan

first: Qin

last: Shanshan

address: Renmin Road 30, Maojian District

institute: Institute of Basic Medical Sciences, School of Basic Medical Sciences, Hubei University of Medicine

summary: HaCAT cells were treated with pentafactor (M5) to construct a psoriasis cell model, which was used to study the pathogenesis of psoriasis at the in vitro level. This study aimed to explore the genes activated by pentafactor (M5) treatment.

overall_design: Pentafactor (M5) consists of five cytokines: IL-1α (10 μg/L), IL-17 (10 μg/L), IL-22 (10 μg/L), TNF-α (10 μg/L), and Oncostatin M (10 μg/L). It can induce the proliferation and inflammation of keratinocytes. Its impact on the transcriptome of keratinocytes is mainly reflected in promoting the expression of inflammation-related genes, cell proliferation-related genes, and activating specific signaling pathways

first: Shanshan

last: Qin

first: Dandan

last: Li


title: Tumor Acidosis Remodels the Glycocalyx to Control Lipid Scavenging and Ferroptosis

city: Umea

first: Silvia

last: Remeseiro

state: Vasterbottens lan

address: Johan Bures vag 12, MBC-huset

department: Umea Centre for Molecular Medicine

institute: Umea University

summary: Cancer cell adaptation to metabolic stress remains a major barrier to effective therapy. Here, we identify a chondroitin sulfate (CS)-enriched glycocalyx in the acidic microenvironment of human glioblastoma (GBM) and CNS metastases. Integrated analyses of patient GBM tumors and in vitro and in vivo models reveal that CS-glycocalyx encapsulation provides a physical barrier to lipid scavenging and mitigates lipid-induced toxicity in acidosis. Mechanistically, HIF and TGFβ signaling converge to induce CS biosynthesis and dynamically reprogram syndecan-1 glycosylation from heparan sulfate (HS) to CS, limiting lipid particle uptake. Dual inhibition of CS biosynthesis and diacylglycerol-O-acyltransferase 1 (DGAT1), which blocks lipid storage, triggers uncontrolled lipid peroxidation and ferroptotic cell death. These findings uncover a stress-adaptive glycan program that insulates tumor cells from lipotoxic stress. Disrupting this glyco-metabolic barrier selectively sensitizes GBM cells in the lipid-rich, acidic microenvironment and reveals a therapeutic vulnerability that may be leveraged to overcome metabolic resilience in aggressive tumors.

overall_design: Two biological replicates (500,000 cells each) were prepared for each of the following U87MG-derived conditions for HIF1α CUT&RUN sequencing (targeting 25 million reads per replicate): NA cells (U87MG cultured at pH 7.4) AA cells (U87MG cultured at pH 6.4) Ctrl cells (U87MG cultured in serum-free media at pH 7.4) DMOG-treated cells (U87MG treated with 0.5 mM dimethyloxalylglycine at pH 7.4) In addition, CUT&RUN was performed using IgG provided in the CUT&RUN Assay Kit (Active Motif, #53180, version 47) to serve as a control for normalization and peak calling in the HIF1α datasets.

first: Anna

last: Bång-Rudenstam

first: Chaitali

last: Chakraborty

first: Itzel

last: Nissen

first: Mattias

last: Belting


title: MECOM: A novel player in AR-driven Treatment Resistant Castration-Resistant Prostate Cancer

city: Buffalo

first: Remi

last: Adelaiye-Ogala

state: New York

address: 875 Ellicot Street

department: Department of Medicine

institute: University at Buffalo

summary: Reprogramming of the androgen receptor (AR) cistrome is associated with disease progression, and advanced castrate-resistant prostate cancers (CRPC) tend to rely on a reprogrammed/non-canonical AR signaling that is addictive to AR signaling inhibitor (ARSI) resistance. We identified EVI1, an oncogenic nuclear transcription factor, EVI1 coded by MECOM, as a novel AR-recruited co-activator for non-canonical signaling. MECOM is exclusively overexpressed CRPC and enzalutamide-resistant CRPC and interacts with AR in the nucleus. MECOM knockdown cells exhibited decreased proliferation and critical cell survival transcriptional programs, suppressed super-enhancer (SE) activity, and affected non-canonical AR signature profiles. Intriguingly, MECOM overexpression is vulnerable to PARP inhibitors regardless of DDR or HRR gene mutation status. These insights uncover the mechanistic role of MECOM in AR reprogrammed cistrome and its vulnerability. More importantly, this study suggests that MECOM overexpression may be another biomarker that could significantly broaden the use of PARP inhibitors beyond those with HRR gene mutations.

overall_design:
RNA-Seq Profiling of wild type LREX, C42B-ER, CWR-R1 cells and their knockdown derivatives(ShMECOM).
CHIP-Seq Profiling on AR and H3K27ac pull downs on various cell lines LREX, C4-2BER and CWR-R1 wild type and ShMECOM knock down conditions.

last: Adelaiye Ogala

first: Surendra

last: Gulla

first: Tej

last: K Sharma

first: Ephraim

last: Gardner

first: Chennan

first: Sean

last: Colligan

first: Cha

last: Xue

first: Shreya Shyam

last: Sundar

first: Brian

last: Capaldo

last: E. Bard

first: Tobi

last: Ogunbowale

first: Abbas

last: Jawadala

first: Min

last: Ma

first: Adam

last: Sowalsky

first: Kathleen

last: Kelly

first: Roberto

last: Pili

first: Jun

last: Qu

first: David

last: J VanderWeele


title: Antigen-selected gut IgA is generated from IgG1 germinal center B cells (BCR)

city: New Haven

first: Hailong

last: Meng

address: 300 George Str

institute: Yale University

summary: Determine whether IgA B cells are derived from IgE B cells during allergy; understand whether IgE and IgA B cells induced during allergy share clonal relationships in the gut.

overall_design: C57Bl/6 WT or GC Fate Reporter (S1PR2CreERT2 Rosa-lsl-tdTomato) mice orally immunized with OVA+CT to generate OVA-specific IgA B cells. In one experiment, WT OVA-specific B cells from MLN, PP, and LP were sequenced for transcriptomes and BCRs. In another experiment OVA-specific B cells from GC Fate Reporter mice were separated based on tdTomato staining (tdTomato+=GC; tdTomato-=nonGC) and sequenced from MLN, PP, and LP.

first: Emily

last: Siniscalco

first: Gisela

last: Gabernet

first: Stephanie

last: Eisenbarth

first: Steven

last: Kleinstein


title: Genetic rescue of mitochondrial complex I reverses metabolic defects in circadian mutant mice

city: Chicago

first: Joseph

last: Bass

state: IL

address: 303 E Superior St, Lurie 7-220

institute: Northwestern University

summary:
We used single nuclei RNA-seq to compare gene expression from adipocyte circadian mutant mice +/- expression of the yeast NADH dehydrogenase (NDI1).

We used RNA-sequencing of fractionated adipocytes from the visceral white adipose tissue of control mice, mice lacking the circadian clock activator Bmal1, and mice lacking the mitochondrial complex I subunit Ndufs2.

overall_design:
Visceral white adipose tissue (WAT) was isolated from 3-month old male mice and was homogenized, followed by filtering and centrifugation to isolate nuclei. Nuclei were then analyzed for single nuclei RNA-sequencing with 10X genomics.

Bulk RNA-seq: Visceral white adipose tissue (WAT) was isolated from 3-month old male mice and was digested with collagenase followed by differential centrifugation to float the adipocytes. The adipocyte fraction was then homogenized followed by RNA isolation, library preparation, and sequencing.

first: Chelsea

last: Hepler

first: Nathan

last: Waldeck

first: Joe


title: miRNA expression of upcyte human hepatocytes treated with valproate (VPA) 4mM, fatty acids (OP) 0,6 mM or vehicle (PBS)

city: Valencia

first: Ramiro

middle: Jover

last: Atienza

state: Valencia

address: Avenida Fernando Abril Martorell, 106.

department: Experimental Hepatology Unit

country: Spain

institute: IIS Hospital La Fe

summary:
Valproate (VPA) has been the first line, most-frequently prescribed anti-epileptic drug in children for the past 50 years. VPA causes, in some patients, idiosyncratic hepatotoxicity, which very often presents with hepatic steatosis. Experimental studies also support that VPA has a high potential to induce steatosis
The aims of this study are to demonstrate VPA-induced triglyceride (TG) accumulation in cultured human upcyte hepatocytes, to identify miRNAs that are deregulated by VPA and associated with TG levels in these cells, and to test these miRNAs, as potential non invasive biomarkers, in plasma of paediatric epileptic patients on VPA, to identify those with a potential risk of liver steatosis

overall_design: Human upcyte hepatocytes were exposed to subcytotoxic VPA concentrations. Hepatocytes increased intracellular TGs by 27% and 45% after 2 and 4 mM VPA for 24 h. The profiling of cellular miRNAs after 4 mM VPA by microarray analysis identified 43 deregulated human miRNAs

first: Jover Atienza

last: Ramiro

first: Soluyanova

last: Polina

first: Moro Castaño

last: Erika

first: Marco-Hernandez

last: Ana V.

first: Castell

last: Jose V.


title: Effect of SOD1K123R mutation on gene expression in nucleus pulposus cells treated with lactate.

status: Public on Jan 04 2026

city: Chongqing

first: Yuyao

last: Zhang

address: No.83, Xinqiao Zhengjie, Shapingba District

institute: Xiqiao hospital

summary: Among musculoskeletal disorders, intervertebral disc degeneration (IVDD) is the primary cause of discogenic pain and associated disability and productivity loss in the workforce worldwide.Oxidative stress is an important inducing and aggravating factor of intervertebral disc degeneration. We found that lactate could induce the lactylation of SOD1 lysine 123 in nucleus pulposus cells, which impaired the antioxidant ability of the enzyme. Therefore, we mutated lysine (Lys) to arginine (Arg) at residue 123 of SOD1 in nucleus pulposus cells to eliminate the lactylation at residue 132 and investigated the underlying mechanism by RNA sequencing.

overall_design: After knocking down SOD1 in nucleus pulposus cells, RNA-seq was performed after transfection of wild-type SOD1 and K123R mutant SOD1 with 10 mM lactate for 7 days

first: Yu

last: Zhai

first: Lin

last: Chen

first: Minghan

last: Liu

first: Changqing

last: Li


title: Highly dynamic dural sinuses support meningeal immunity

city: Bethesda

first: Kory

middle: R

last: Johnson

state: MD

address: 35/GF-127, 9000 Rockville Pike

department: DIR IT & Bioinformatics

institute: NINDS/NIH

summary: The central nervous system (CNS) is surrounded by three interconnected membranes referred to as the meninges, which host a diverse immune network1-3. Situated within the skull-interfacing dura mater are venous sinuses, which are large veins thought to serve predominantly as passive blood drains for the brain and skull4,5. However, these structures also represent an important neuroimmune interface6-8. Here, we sought mechanistic insights into this interface using intravital microscopy, revealing that the dural sinuses and associated endothelial cells are a highly dynamic surface that constantly restructures to modulate blood flow, fluid movement, and immune surveillance. Specifically, we demonstrate that sinuses are not passive drains but instead constrict and dilate under RAMP1-dependent smooth muscle control similar to arteries. In addition, the murine superior sagittal sinus is bifurcated into an upper and lower chamber, both comprised of specialized, highly fenestrated endothelial cells that allow the movement of fluids, macromolecules, and microbes between the sinus lumen and leukocyte-rich perisinus space. To protect this permeable interface, sinus endothelial cells (SECs) continually open and close their boundaries in a RAMP2-dependent manner. Transcranial RAMP2 antagonism impeded SEC boundary dynamics and immune cell movement along the sinus wall during steady state and after systemic viral infection. Interference with SEC dynamics during viral infection disrupted local antiviral immunity and facilitated pathogen entry into the meninges. These findings demonstrate that dural sinuses are dynamic venous drains with specialized SECs designed to control fluid movement and support both steady state immune surveillance and antiviral immunity.

overall_design: Pooled cells representing lower sagittal sinus ("SINUS") and rostral-rhinal hub ("HUB") in mouse were prepared for single cell RNA sequencing and sequenced to an average of 35,000 reads per cell.

first: Kelly

last: Monaghan

first: Nagela

last: Zanluqui

first: Yijun

last: Su

first: Nicole

last: Peterkin

first: Jared

middle: S

last: Rosenblum

first: Jiamin

first: XiaoYang

last: Wang

first: Harshad

last: Vishwasrao

first: Lawrence

last: Latour

first: Dorian

last: McGavern


title: Effect of HIF-1alpha knockout in gene expression profile of osteosarcoma cells in vivo.

city: Tokyo

first: Takatsune

last: Shimizu

address: 2-4-41, Ebara, Shinagawa-ku

department: Pathophysiology

institute: Hoshi University

summary: To explore in vivo changes in gene expression of osteosarcoma cells upon depletion of HIF-1alpha we performed RNAseq analysis using Mock control AXT cells and HIF-1alpha KO AXT cells. HIF1alpha was knocked out using CRISPR-Cas9 with two different target sequences. KO1-1 and KO1-2 cells are derived from target sequence#1:5’- AGATGTGAGCTCACATTGTGGGG -3’ (exon3) and KO2 cells are from  #2:5’-GCTAACAGATGACGGCGACATGG-3’ (exon5). AXT cells were established from BMSCs of Ink4a/Arf null mouse by overexpressing human c-MYC (Shimizu T, et al. Oncogene, 2010).

overall_design: 2x10^6 Mock control cells and HIF-1alpha KO cells emmbedded in matrigel were inoculated into C57BL/6scid mice and harvested tumors next day. Tumors were disrupted using a BioMasher (Nippi, Tokyo, Japan) and total RNA was extracted.


title: Antigen-selected gut IgA is generated from IgG1 germinal center B cells (GEX)

first: Hailong

last: Meng

first: Emily

last: Siniscalco

first: Gisela

last: Gabernet

first: Stephanie

last: Eisenbarth

first: Steven

last: Kleinstein


title: Mouse myocardial infarction

city: Harbin

first: Feiyong

last: Xu

state: Heilongjiang Province

address: 157 Baojian Road, Nangang District, Harbin City, Heilongjiang Province

department: College of Pharmacy

institute: Harbin Medical University

summary: Cardiac ischemia-reperfusion (I/R) injury is a leading cause of disability and mortality worldwide, but the underlying mechanism remains largely unknown. Despite the emerging recognition of circular RNAs (circRNAs) as pivotal regulators in cardiac development and disease, their roles in cardiac I/R injury have yet to be thoroughly investigated. In this study, we identified a circRNA, named circArhgap26, which was regulated by m6A-modification.

overall_design: All mice were treated with sham operation and myocardial infarction for 1 Day (n=3 per group).  Arraystar arrays were performed according to the manufacturer's directions on RNA extracted from cardiac tissue. Total RNA was extracted from each sample using TRizol Reagent according to the protocol from manufacturer. RNA quantity and quality were measured by NanoDrop ND-1000. RNA integrity was assessed by standard denaturing agarose gel electrophoresis. Arraystar Mouse mRNA and ncRNA Microarray V3.0 is applied for the global profiling of mouse lncRNAs and protein-coding transcripts. About 35,923 lncRNAs and 24,881 coding transcripts can be detected by our third-generation mRNA and lncRNA microarray.

first: Mingyu

last: Zhang


title: Clariom D Pico gene array of acidosis adapted and control PANC1 pancreatic cancer cells

city: Lund

first: Mattias

last: Belting

address: Barngatan 4

department: Department of Clinical Sciences, Division of Oncology

institute: Lund University

summary:
In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors.
We used microarrays to evaluate transcriptional signature of adaptation to acidosis (pH 6.4) in PANC1 pancreatic cancer cells.

overall_design: PANC1 pancreatic cancer cells were adated to acidic condition (pH 6.4) or not (non-adapted= control) during 10 weeks. In total 6 samples (2 types of samples in three biological replicates) underwent RNA extraction with RNAeasy mini kit, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige. Gene expression profile obtained from acidosis-adapted PANC1 pancreatic cancer cells was compared to the profile of non-adapted control cells.

first: Anna

last: Bång-Rudenstam

first: Myriam

last: Cerezo-Magaña

first: Marton

last: Horvath

first: Hugo

last: Talbot

first: Emma

last: Gustafsson

first: Stevanus

last: Jonathan

first: Chaitali

last: Chakraborty

first: Itzel

last: Nissen

first: Kelin

last: Gonçalves de Oliveira

first: Axel

last: Boukredine

first: Sarah

last: Beyer

first: Julio

last: Enriquez Perez

first: Maria

last: C Johansson

first: Lena

last: Kjellén

first: Emil

last: Tykesson

first: Anders

last: Malmström

first: Toin

last: H van Kuppevelt

first: Karin

last: Forsberg-Nilsson

first: Jeffrey

last: Esko

first: Silvia

last: Remeseiro

first: Johan

last: Bengzon

first: Valeria

last: Governa


title: Tet2 modulates ER stress responses, β cell death, and autoimmunity in diabetes [snATAC-seq]

first: Madhav

last: Kothari

first: Jinxiu

last: Rui

first: Romy

last: Kursawe

first: Mahsa

last: Barkestani

first: Romi

last: Genosar

first: Pamela

last: Clark

first: Michael

last: Stitzel

first: Kevan

last: Herold


title: Clariom D Pico gene array of primary GBM cells grown as 3D (LD⁺) spheroid cultures or 2D (LD⁻) cultures

first: Mattias

last: Belting

summary:
In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors.
We used microarrays to evaluate transcriptional signature realted to 3D (LD⁺) cultures compared to 2D (LD⁻) cultures from primary glioblastoma (GBM) cell line.

overall_design: Primary cell cultures derived from three independent GBM patients were grown in 3D (LD⁺) and 2D (LD⁻) cultures. In total 18 samples (6 types of samples in three biological replicates) underwent RNA extraction with AllPrep DNA/RNA Micro Kit for RNA, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige. Gene expression profiles obtained from  3D (LD⁺) cultures were compared to the profile  2D (LD⁻) cultures for each primary cell line.

first: Anna

last: Bång-Rudenstam

first: Myriam

last: Cerezo-Magaña

first: Marton

last: Horvath

first: Hugo

last: Talbot

first: Emma

last: Gustafsson

first: Stevanus

last: Jonathan

first: Chaitali

last: Chakraborty

first: Itzel

last: Nissen

first: Kelin

last: Gonçalves de Oliveira

first: Axel

last: Boukredine

first: Sarah

last: Beyer

first: Julio

last: Enriquez Perez

first: Maria

last: C Johansson

first: Lena

last: Kjellén


title: Photorespiration is linked to DNA methylation by formate as a one-carbon source [BiSulfite-seq]

city: Neuherberg

first: Martin

last: Groth

address: Ingolstädter Landstr. 1

department: Institute of Functional Epigenetics

institute: Helmholtz Munich

summary: DNA methylation is a key epigenetic modification regulating genome organization, stability, and gene expression. Stable DNA methylation critically relies on methyl groups provided through folate-mediated one-carbon (C1) metabolism, yet the origin and regulation of C1 supply remain elusive. Here we demonstrate that photorespiration serves as a major C1 source for DNA methylation in Arabidopsis. We show that C1 from formate, a photorespiratory byproduct, is incorporated into 5-methyl-cytosine via the reductive cytosolic folate pathway. This occurs predominantly during the day, negatively regulating serine utilization as alternative C1 source. Consequently, suppression of photorespiration under elevated CO₂ levels alters the DNA methylation landscape, an effect exacerbated when regulation of C1 metabolism by the formate-dependent pathway is impaired. Thus, our findings link the fundamental metabolic process of photorespiration to epigenetic stability, highlighting how rising atmospheric CO₂ levels can induce DNA methylation changes.

overall_design: BS-seq analysis of Arabidopsis thaliana wild type compared to mthfd1 (m), thfs (t) single, and mt double mutants under long day (LD) conditions (8 samples in total); BS-seq analysis of mT-cr23 and mt-cr20 CRISPR-Cas9 lines (4 samples in total); BS-seq analysis of wild type and m under LD compared to short day (SD) conditions (8 samples in total); BS-seq analysis of wild type and m under high CO2 (3000 ppm) compared to control CO2 (410 ppm) conditions (8 samples in total); mRNA-seq analysis of wild type compared to mthfd1 (m), thfs (t) single, and mt double mutants under long day (LD) conditions (12 samples in total); and mRNA-seq analysis of wild type and m under high CO2 (3000 ppm) compared to control CO2 (410 ppm) conditions (12 samples in total).

first: Valentin

last: Hankofer


title: Acidosis and hypoxia responsive gene expression profiles of U87MG glioblastoma cells

first: Mattias

last: Belting

summary:
In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors.
We used microarrays to evaluate transcriptional signature of acidosis adaptation, short-term acidosis (pH 6.4) or short-term hypoxia in U87MG GBM cells.

overall_design: U87MG GBM cancer cells were adapted to acidic condition (acidosis-adapted, pH 6.4) or not (non-adapted= control) during 10 weeks. Alternatively U87MG GBM cells were treated in short-term acidosis at pH 6.4 or 7.4 (pH control) or in short-term hypoxia, grown at normoxic (21% oxygen) or hypoxic (1% oxygen) conditions for 48 h. In total 18 samples (6 types of samples in three biological replicates) underwent RNA extraction with RNAeasy mini kit and was subjected to genome-wide transcriptional analysis with Illumina HumanHT-12 V3.0 expression beadchip. Gene expression profile obtained from acidosis-adapted U87MG GBM cells was compared to the profile of non-adapted control cells and gene expression profiles obtained from short-term acidic (pH 6.4) or hypoxic U87MG cells was compared their respective control samples.

first: Emil

last: Tykesson

first: Anders

last: Malmström

first: Toin

last: H van Kuppevelt

first: Karin

last: Forsberg-Nilsson

first: Jeffrey

last: Esko

first: Silvia

last: Remeseiro

first: Johan

last: Bengzon

first: Valeria

last: Governa


title: Clariom D Pico gene array of microdissected lipid droplet (LD)+ and LD- human GBM areas.

summary:
In this study, we aimed to elucidate the molecular underpinnings of metabolic adaptation in the stressed TME. LD accumulation has been well documented in glioblastoma (GBM), a prototypical high-grade brain malignancy characterized by severe acidosis, hypoxia, and metabolic heterogeneity. Unexpectedly, we observed a prominent enrichment of pathways related to glycocalyx remodeling in the LD-rich niche of patient tumors, particularly those involving CS biosynthesis and PG regulation. These findings prompted us to explore how glycan remodeling intersects with lipid metabolism in GBM and whether this interaction contributes to tumor stress adaptation. Our results highlight an acidosis-induced glycan program with potential as a metabolic vulnerability, offering new therapeutic avenues for targeting the lipid-stressed niche in aggressive tumors.
We used microarrays to evaluate transcriptional signature realted lipid droplet (LD)+ and LD- regions of patient glioblastoma (GBM) sections.

overall_design: Lipid droplet (LD)+ and LD- human GBM tumor areas were captured by laser capture microdissection (LCM), excluding vasculature and CD68⁺ immune cells. The samples were microdissected, underwent RNA extraction with AllPrep DNA/RNA Micro Kit for RNA, and hybridization on Affymetrix Clariom Human D Pico microarray cartrige.  2 samples in total  pooled from 5 patients: 1 for LD+/CD68- (LD+ cancer cell) and 1 for LD-/CD68- (LD- cancer cell) areas respectively. Gene expression profiles of LD+ GBM cancer cell areas were compared to the profile of LD- GBM cancer cell areas.

first: Anna

last: Bång-Rudenstam

first: Myriam

last: Cerezo-Magaña

first: Marton

last: Horvath

first: Hugo

last: Talbot

first: Emma

last: Gustafsson

first: Stevanus

last: Jonathan

first: Chaitali

last: Chakraborty

first: Itzel

last: Nissen

first: Kelin

last: Gonçalves de Oliveira


title: Caspofungin interferes with Candida albicans iron homeostasis

city: Oeiras

first: Catarina

last: Pimentel

state: Lisboa

address: Av. da República

department: MOSTMICRO

country: Portugal

institute: ITQB NOVA

summary: In this study we used a transcriptomic approach to determine whether caspofungin could impact iron homeostasis in Candida albicans, the most frequent cause of invasive candidiasis. Caspofungin affects iron homeostasis by inducing a high iron response. Caspofungin treatment leads to a downregulation of genes involved in iron uptake, while genes associated with iron storage and detoxification, as well as the transcription factor SFU1 that regulates the cell response to high iron, are upregulated.

overall_design: RNA-Seq of Candida albicans SC5314 cells exposed to FeSO4, caspofungin or both compounds was compared to untreated cells.

first: Andreia

last: Pedras


title: Photorespiration is linked to DNA methylation by formate as one-carbon source [RNA-seq]

first: Martin

last: Groth

first: Valentin

last: Hankofer


title: RNA-Seq analysis of roots of Stylosanthes guianensis in response to manganese toxicity

city: Haikou

first: Zhijian

last: Chen

email: jchen@scau.edu.cn, zjchen@catas.cn

address: Xueyuanlu 4

institute: Institute of Tropical Crop Genetic Resources, Chinese Academy of Tropical Agricultural Sciences

summary: Stylo (Stylosanthes guianensis) is an important tropical legume with superior tolerance to manganese (Mn) toxicity, which severely constrains plant growth especially in tropical acid soils. However, the underlying mechanisms of Mn tolerance in stylo remain largely unknown. SgUBC2, an ubiquitin-conjugating enzyme, has been documented to involved in Mn tolerance in stylo. RNA-seq analysis showed that overexpression of SgUBC2 resulted in changes in a variety of Mn-responsive gene expressions, including genes associated with antioxidant defense response, ion transporter and organic acid metabolism.

overall_design: In this study, the transgenic composite stylo plants overexpressing SgUBC2 (OX-SgUBC2) were generated by Agrobacterium rhizogenes-mediated hairy root transformation metood. The composite stylo plants transformed with the pFGC5941 binary vector (EV) was used as control. After verification of SgUBC2 transcripts in the hairy roots via RT-qPCR analysis, roots of OX-SgUBC2 and EV lines were harvested for RNA-seq analysis.


title: Spatial single cell transcriptomic analysis of a lineage-traceable mouse model of DICER1 Syndrome informs tumor developmental hierarchy [scRNA-seq]

city: Vancouver

first: David

last: Huntsman

address: 675 W 10th Ave

institute: BC Cancer Research Centre

summary: DICER1 syndrome predisposes children and young adults to tumor development across various organs. Most of these cancers are sarcomas, which uniquely express the RNase IIIb domain-deficient form of DICER1 and exhibit histological and molecular similarities regardless of their anatomical origins. To uncover their cellular origin and developmental hierarchy, we established a lineage-traceable genetically engineered mouse model allowing for controlled activation of Dicer1 mutations in Hic1+ mesenchymal stromal cells. This resulted in the development of renal tumors closely mirroring human DICER1 sarcoma histologically and molecularly. Spatial single-cell transcriptomics analysis revealed that a Hic1+Pdgfra+Mfap4+ fibroblastic progenitor population, corresponding to perivascular universal fibroblasts of steady-state kidneys, exhibits the capability to undergo rhabdomyoblastic differentiation or transition into proliferative sarcomatous cells. Investigation of patient samples identified analogous cell states and developmental trajectories. This study uncovers a fibroblastic origin for DICER1 sarcoma and provides a faithful model for future mechanistic and translational investigation.

overall_design: Control mice and mice bearing a tamoxifen inducible compound heterozygous Dicer1 -/D1693N  genotype (HDT) were treated with tamoxifen; both express tdTomato in Hic1+ cells. Kidney cells and renal tumor cells were collected at various intervals (range 1-15 months), isolated with fluorescence activated cell-sorting (FACS) for a tdTomato reporter and antibody depletion of EpCAM, CD45, CD31, CD11b, and F4/80. Isolated cells were then analyzed with scRNA-seq.

first: Felix

last: Kommoss

first: Joyce

last: Zhang

first: Branden

middle: J

last: Lynch

first: Shary

first: Janine

last: Senz

first: Yana

last: Moscovitz

first: Lesley

last: Hill

first: Ross

last: Scott

first: Jonathan

last: Bush

first: Andrew

last: Roth

first: Kenneth

first: Gregg

last: Morin

first: Andreas

last: von Diemling

first: Tully

last: Underhill

first: William

last: Foulkes

middle: G