title: A novel truncating variant c.1222dupC in RBM20 causes cardiomyopathy through haplo-insufficiency.

city: Heidelberg

first: Maarten

last: van den Hoogenhof

address: Eppelheimer Str. 8,

institute: Institute of Experimental Cardiology

summary: RBM20 is a cardiac splicing factor responsible for splicing of several cardiac genes such as TTN, TRDN, RyR2, PDLIM1, and CAMK2D. Mutations in RBM20 are a major cause of familial dilated cardiomyopathy (DCM), and lead to missplicing of RBM20 target genes. Here, we describe a novel pathogenic truncating mutation, RBM20 c.1222dupC, identified in a patient with mitral valve prolapse and late onset familial DCM. This mutation introduces a premature termination codon and generates a truncated protein of ~55 kDa in vitro. Splicing assays demonstrated complete loss of activity and no dominant-negative effect on WT RBM20. Overexpression in NRCMs revealed that the truncated protein localized to both cytoplasm and nucleus, partially co-localizing with WT RBM20, despite lacking the RS and RRM domains. To model the patient’s condition, we generated heterozygous c.1222dupC iPSC-derived cardiomyocytes. Western blot analysis of endogenous RBM20 revealed a strong reduction in RBM20 protein level. RT-PCR revealed splicing defects in canonical RBM20 targets, and RNA-sequencing identified widespread splicing abnormalities, including in established RBM20 targets (TTN, RyR2, CAMK2D, and CACNA1G). Together, these findings establish RBM20 c.1222dupC as a pathogenic truncating variant that causes DCM primarily through haploinsufficiency.

overall_design: RNA sequencing of WT and DupC+/– hiPSC cardiomyocytes.


title: Comprehensive mass spectrometry screening-derived atlas of HDAC inhibitors reveals histone specific acetylation changes [ChIP-seq]

status: Public on Mar 18 2026

city: St. Louis

first: Rashmi

last: Karki

address: 660 S. Euclid Ave

country: USA

institute: Washington University in St. Louis

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Histone deacetylases inhibitors (HDACi) have emerged as valuable therapeutics in cancer and other diseases, yet their effect on histone post-translational modification remains incompletely characterized. Here, we applied quantitative mass spectrometry and high throughput sequencing to systematically profile site-specific histone modification changes in response to a panel of HDAC inhibitors. This platform enabled mapping of histone modification changes across hundreds of sites including low abundant histone marks. Furthermore, integrative analysis of ChIP-seq and RNA-seq identified genome wide binding site for a low-abundant histone mark H2A.Z acetylation in HeLa cells and MDA-MB-231 breast cancer cells, highlighting the role of H2A.Z acetylation in regulating gene expression through various biological pathways and specific genes involved in tumor suppressor pathways. Our findings provide a functional resource for identification and quantification of epigenetic changes and transcriptional regulation of histone H2A.Z acetylation upon pharmacological perturbation

overall_design: ChIP-seq of histone H2A.Z K4+K7+K11 acetylation (H2A.Zac) in HeLa and MDA-MB-231 cells treated with Entinostat (1µM) for 24h. Controls were treated with DMSO. Two replicates were included for  each conditions.

first: Francisca

middle: N

last: Vitorino

first: Richard

middle: M

last: Searfoss

first: Joanna

middle: K

last: Lempiäinen

first: Cheryl

last: Arrowsmith

first: Benjamin

middle: A

last: Garcia


title: Unconventional role of HMGCS1 in driving pathogenic-Th17 cell immunity and autoimmune diseases

city: Wuhan

first: Jie

last: Sun

state: Hubei

address: Donghu Road, No. 115

department: MRI

country: China

institute: Wuhan university

type: Expression profiling by high throughput sequencing

summary: Identifying factors controlling pathogenic-Th17 cells is of importance, for their vital role in inflammation and immune-pathology. While intricate ER stress signals have been implicated in T cell biology, its role in Th17 cells remain poorly understood. Here, we demonstrated that HMGCS1, a cholesterol biosynthesis precursor enzyme, was highly induced by inflammatory cytokines and preferentially expressed by pathogenic-Th17 cells in vitro and in vivo. HMGCS1 specifically dictated pathogenic-Th17 cell differentiation and augmented autoimmune diseases. Nonetheless, HMGCS1 role in pathogenic-Th17 cells was independently of cholesterol metabolism but necessitated its catalytic Cys129 residue. Notably, HMGCS1 leveraged IRE1a-XBP1s-dependent ER stress response which was essential for pTh17 cell generation and pathogenicity by transcriptionally activating Rorc loci. Mechanistically, HMGCS1 located to the ER membrane, where it bound and stabilized IRE1a protein via restraining IRE1a interaction with K48-linked ubiquitination-dependent E3 ligase MARCH5. Of note, interfering HMGCS1 and ER stress impeded pathogenic-Th17 immunity and mitigated autoimmune diseases. Therefore, our work reveals a non-canonical axis wherein HMGCS1 sustains ER stress to license pTh17 cell differentiation during autoimmune responses.

overall_design: Naive CD4+ T cells, which were purified from spleen and lymph nodes, were cultured under pTh17  polarization conditions from WT and HMGCS1 cKO Mice,and with or without 1 uM Hymeglusin for 2 days. Then, RNA was extracted from the pTh17 cells.

first: Bing

last: Wu


title: Integrative genomic, phylogenetic, and transcriptomic analyses reveal temperature-responsive transient receptor potential (TRP) genes in Pacific abalone Haliotis discus hannai

city: Gangneung-city

first: Young Chang

last: Sohn

address: Jukheon-gil 7

country: South Korea

institute: Gangneung-Wonju National University

summary: Temperature profoundly influences the physiology, survival, and distribution of marine ectotherms, including mollusks. Transient receptor potential (TRP) channels are conserved thermosensory proteins in metazoans, yet their evolutionary diversification and functional roles in gastropod mollusks remain unclear. In this study, we present a comprehensive phylogenetic classification and expression analysis of TRP-like channel genes in Pacific abalone (Haliotis discus hannai). Through the extensive mining of genome and transcriptome datasets, we identified 49 TRP-like genes and categorized them into nine families from two major groups: Group 1 (TRPA, TRPC, TRPM, TRPN, TRPS, TRPV, and TRPVL) and Group 2 (TRPP and TRPML), along with two unclassified TRP-like genes. Phylogenetic analysis incorporating sequences from lophotrochozoans, choanoflagellates, fungi, and green algae outlined a lineage-specific TRP-like gene expansion in mollusks. Spatial expression profiling revealed distinct tissue-specific patterns: TRPC-, TRPM-, and TRPP-like genes were enriched in sensory organs (i.e., the eyes and tentacles), whereas TRPM- and TRPV-like genes were expressed predominantly in respiratory and metabolic tissues (i.e., the gills and hepatopancreas). Under acute thermal stress, RNA sequencing and real-time quantitative PCR identified several thermoresponsive TRP paralogs, including TRPA1- and TRPV-like genes, exhibiting distinct transcriptional regulation. These results elucidate the evolutionary complexity and functional diversification of TRP channels in marine gastropods, and highlight the potential role of these molecules in thermal sensing and adaptation. This study provides a molecular framework for understanding TRP-mediated environmental responses in mollusks, contributing to broader insights into marine invertebrate resilience under climate change.

overall_design: RNA-seq profile of Pacific abalone TRP genes in eyes, tentacles, gills, and hepatopancreas under acute thermal stress (9 and 27 degree C),

first: Mi Ae

last: Kim


title: In vitro butyrate modifies epigenetic and immune pathways in peripheral mononuclear cells from children with neurodevelopmental disorders associated with chromatin dysregulation

city: Westmead

first: Brian

middle: S

last: Gloss

state: NSW

address: 176 Hawkesbury Rd

department: Scientific Platforms

country: Australia

institute: Westmead Institute of Medical Research

summary:
Pathogenic DNA variants in chromatin-related genes cause an important minority of neurodevelopmental disorders (NDDs). Epigenetic mechanisms, including chromatin regulation, are associated with the etiopathogenesis of NDDs. Therapeutic strategies targeting chromatin dysregulation, such as histone deacetylase inhibition with butyrate, show promise; however, its effects remain poorly understood.

We performed single-cell RNA sequencing (scRNA seq) on 101,539 peripheral immune cells from four children with functionally impairing NDDs (median age 11.2 years, IQR = 3.5 years; 3 females): three with de novo pathogenic variants in chromatin-related genes (KMT2D, CHD7, and MECP2), and one without a monogenic diagnosis (non-monogenic), compared with  two sex-matched healthy controls (median age 12.5 years, IQR = 0.94 years; 1 female). Patient cells also underwent scRNA seq sequencing after in vitro butyrate treatment.

Untreated patient cells showed dysregulation of ribosomal and immune pathways compared to controls. Specifically, KMT2D, CHD7, and the non-monogenic patients exhibited downregulation of ribosomal pathways, and upregulation of immune pathways. In contrast, the MECP2 patient displayed upregulation of ribosomal pathways and mixed regulation of immune pathways. Butyrate treatment largely reversed these pathways, normalizing ribosomal and immune pathways in KMT2D, CHD7, and non-monogenic patient cells, with partial effects in MECP2. Overall, butyrate induced up-regulation of ribosome, GTPase, cytoskeletal, mitochondrial pathways, and down-regulation of epigenetic (histone, transcription factors) and immune pathways.

We propose that chromatin dysregulation is associated with a common RNA signature involving ribosomal pathways and immune dysregulation. Butyrate is a potential modulator of epigenetic and immune dysregulation in NDDs associated with chromatin dysregulation.

overall_design: single-cell RNA sequencing on peripheral immune cells from four children with functionally impairing NDDs (mean age 11 years; 3 females) and two age-matched healthy controls (mean age 14 years; 1 female), both untreated and butyrate-treated.

first: Jessica

middle: P

last: Hayes

first: Velda

middle: X

last: Han

first: Brooke

last: Keating

first: Hiroya

last: Nishida

first: Erica

last: Tsang

first: Ruwani

last: Dissanayake

first: Xianzhong

last: Lau

first: Shekeeb

last: Mohammad

first: Shrujna

last: Patel

first: Russell

middle: C

last: Dale


title: Transcriptomic insights into unisexual flower development in Cannabis sativa: conserved MADS-box networks and divergent developmental programs

city: Rehovot

first: Leor

last: Eshed-Williams

address: Herzl 229

country: Israel

institute: Hebrew University of Jerusalem

summary: Cannabis sativa, a member of the Cannabaceae family, is predominantly a dioecious species, producing male and female flowers on separate individuals. Although sex determination follows a heterogametic XY system, considerable plasticity in sex expression is evident. To investigate the gene regulatory networks underlying male and female flower development, we performed transcriptomic profiling of shoot apices from vegetative male and female inflorescences at one and three weeks following floral induction. Our analysis identified key MADS-box genes associated with floral organ specification and revealed that cannabis flower development largely conforms to the canonical ABCDE model

overall_design: mRNA-seq profiling of cannabis apical shoot tips from vegetative, female flowering weeks 1 and 3 and male flowering weeks 1 and 3 plants

last: Eshed Williams


title: Sex and life experience shape locus coeruleus pretangle tau pathology

city: St. John's

first: Touati

last: Benoukraf

state: NL

address: Craig L. Dobbin Genetics Research Centre,

department: Faculty of Medicine, Division of BioMedical Sciences

country: Canada

institute: Memorial University of Newfoundland

summary: The locus coeruleus (LC) is the earliest site of tau pathology in Alzheimer’s disease (AD), yet how modifiable environmental factors influence its vulnerability, particularly in a sex-specific manner, remains unclear. Using a rat model expressing pseudophosphorylated human tau (htauE14) in the LC, we show that tau accumulation induces anxiety-like behavior, cognitive deficits, and tau spread, shaped by sex and life history. Early-life enrichment attenuated tau propagation, reduced neuroinflammation, and increased hippocampal BDNF expression, while late enrichment reduced anxiety and improved learning. In contrast, late-life stress exacerbated LC degeneration. Single-nucleus RNA sequencing revealed female-biased transcriptional dysregulation in hippocampal excitatory neurons and glia cells following htauE14 expression. Environmental exposures drove distinct cell type-specific transcriptomic signatures: early stress further disrupted mitochondrial and synaptic programs, whereas early enrichment conferred transcriptional stability. These findings position the LC as a sexually dimorphic and environmentally sensitive node of early AD vulnerability and highlight the preventive potential of early-life interventions.

overall_design: Nuclei were isolated from the dissected frozen hippocampus of six experimental groups; AAV-GFP, AAV-htauE14, early stress + AAV-htauE14 (eSTR), early enrichment + AAV-htauE14 (eER), late stress + AAV-htauE14 (lSTR), late enrichment + AAV-htauE14 (lER), and analyzed for single nuclei RNA sequencing (snRNA-seq).

first: Zia

last: Hasan

first: Qi

last: Yuan


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma [RNAseq_tumor]

city: Singapore

first: Jason

middle: Yongsheng

last: Chan

address: 30 Hospital Blvd

country: Singapore

institute: National Cancer Centre Singapore

summary: Introduction: Brincidofovir (BCV) is a novel nucleoside phosphonate analogue with unique dual anti-viral and anti-tumor properties. Methods: Activity of BCV was evaluated in forty-four cell-line models, including T/NK-NHL (n=25) and B-cell lymphoma (BCL, n=19), as well as their respective NOD/SCID mice xenograft models (NK/T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, TP63-rearranged anaplastic large cell lymphoma, and MYC/BCL2-rearranged diffuse large B-cell lymphoma). Potential in vivo immunogenic effects were examined in a syngeneic EL4-C57BL/6 murine lymphoma model. Results: BCV demonstrated potent anti-tumor activity in vitro across the majority of cell-lines regardless of EBV positivity, with IC50 values within clinically-achievable human plasma concentrations (2 µg/ml) in 17/25 (68.0%) T/NK-NHL and in 13/19 (68.4%) BCL. In vivo treatment via intraperitoneal BCV (IP, 40mg/kg, 2X per week) significantly inhibited tumor growth in all xenograft models when compared to vehicle control. Notably, RNAseq analysis demonstrated BCV downregulated MYC and MYC-target pathways in T/NK-NHL models. Further mechanistic studies showed that BCV evoked S-phase cell cycle arrest, replication stress, DNA damage and apoptosis, while also triggering STING pathway-mediated interferon responses, PD-L1 expression and immunogenic cell death. In the syngeneic EL4-C57BL/6 model, BCV in combination with anti-PD1 significantly inhibited tumor growth and triggered an immune reaction characterized by highest scores for adaptive immune response, cytokines/chemokines & receptors, cytotoxic cells, dendritic cells, NK CD56dim cells and neutrophils (NanoString Immunology Panel). Conclusions: Taken together, these results demonstrate a novel role of BCV in the treatment of lymphoma, and suggest potential for combination with checkpoint immunotherapy.

overall_design: RNAseq profiling of lymphoma tumor tissue

first: Jason Yongsheng


title: PTPN2 deficiency amplifies interferon signaling and impairs functional maturation of human stem cell-derived islets [scRNA-seq]

city: Anderlecht

first: Valerie

last: Vandenbempt

state: Vlaams-Brabant

address: Lenniksebaan 808

country: Belgium

institute: Université Libre de Bruxelles

summary: Background: Protein tyrosine phosphatases (PTPs) play key roles in b-cell function and diabetes development. PTPN2 is a candidate gene for type 1 diabetes (T1D) that negatively regulates the JAK/STAT signaling. However, the impact of PTPN2 deficiency on the differentiation and functionality of human stem cell-derived somatic metabolic cells remains unclear.  Methods: PTPN2 expression in b cells from T1D organ donors and during the differentiation of human stem cell-derived islets (SC-islets) was evaluated in single-cell RNA-Sequencing data. Moreover, we differentiated CRISPR-Cas12a genome-edited PTPN2-deficient H1 human embryonic stem cells (H1-hESCs) into SC-islets, and sc RNA-Seq was performed. The maturation and functionality PTPN2 deficient SC-islets were assessed by implantation under the kidney capsule of NOD-SCID mice. Results: scRNA-Seq analysis showed that PTPN2 expression was increased in b cells from recently diagnosed T1D and decreased in long-standing T1D organ donors, compared with controls. Conversely, we found that PTPN2 expression was decreased at early stages of SC-islet differentiation and reconstituted at later stages, suggesting a developmental dynamic. CRISPR/Cas12-mediated gene editing was used to generate PTPN2-knockout human embryonic stem cells. PTPN2 deficiency exacerbated interferon-induced inflammatory signaling in stem cells and differentiated somatic metabolic cells. Interestingly, PTPN2 deficiency increased hedgehog signaling and reduced SC-islet differentiation efficiency in vitro. In addition, PTPN2-knockout SC-islets exhibited reduced glycemic control after implantation in vivo, mediated by reduced cell endocrine identity and enhanced interferon signaling. Conclusions: Our study postulates a key role of PTPN2 in preserving b-cell function during inflammatory and metabolic stress in SC-islets.

first: Javier

last: Negueruela

first: Francisco

last: Ribeiro-Costa

first: Mariana

last: Nunes

first: Leonardo

last: Traini

first: Sema Elif

last: Eski

first: Wadsen

last: Saint-Pierre-Wijckmans

first: Stéphane

last: Demine

first: Nicolas

last: Baeyens

first: Hazem

last: Ibrahim

first: Luciano

middle: G

last: Martelotto

first: Sumeet Pal

last: Singh

first: Alessandra

last: Cardozo

first: Esteban

last: Gurzov


title: 6-Hydroxydopamine promotes antitumor immunity through macrophage remodeling beyond sympathetic ablation

city: Beijing

first: Jialin

last: Yu

address: Chinese Institute for Brain Research, Beijing(CIBR), Bldg.3, NO.9, YIKE Rd, Zhongguancun Life Science Park, Changping District, Beijing, China

institute: CIBR

summary: Chronic stress activates the sympathetic nervous system (SNS) and has been linked to cancer progression, yet the role of SNS in cancer remains controversial. To investigate sympathetic regulation of cancer, we use genetic, pharmacological (6-hydroxydopamine, 6-OHDA) and surgical sympathetic ablation in a transgenic mouse model of breast cancer. Although all methods effectively deplete sympathetic nerves, only 6-OHDA, a neurotoxin targeting catecholaminergic neurons, suppresses tumor growth. Mechanistically, 6-OHDA promotes monocyte recruitment and their differentiation into pro-inflammatory CD64⁺Sca-1⁺ macrophages (MoMacs) through type I interferon signaling. These MoMacs function as antigen-presenting cells, stimulating type 1 T helper (TH1) cells to combat tumor growth. Depletion of MoMacs abolishes both TH1 response and 6-OHDA’s tumor-suppressive effect. Conversely, genetic sympathectomy fail to alter immune infiltration, distinguishing 6-OHDA's immune-modulatory effect from sympathetic ablation. Our findings reveal an unexpected off-target effect of 6-OHDA that suppresses tumor growth by modulating the immune microenvironment, which is independent of sympathetic ablation.

overall_design: PyMT mice were treated with vehicle or 6-OHDA at 6 to 7 weeks of age, and total tumor immune cells were collected 2 weeks after treatment.

first: Hao

last: Zhang

first: Meiyao

last: Li

first: Wei

last: Shi


title: Lung scRNA-seq reveals chronic inflammation and emphysemous phenotype in mice with Osteogenesis Imperfecta

city: Los Angeles

first: Jennifer

last: Zieba

state: CA

address: 615 Charles E. Young Dr.

institute: University of California, Los Angeles

summary: Osteogenesis imperfecta (OI), or brittle bone disease, is a rare congenital disorder characterized by bone fragility and increased fracture incidence. Genetic and allelic heterogeneity underlie the phenotypic spectrum of OI and yet all forms commonly feature early mortality stemming from pulmonary complications, the molecular cause for which has not been resolved. Using single-cell RNAseq, we identified novel molecular and cellular mechanisms underlying the lung abnormalities observed in our Col1a1Aga2/+ (Aga2) mouse, which recapitulates a moderate form of OI.

overall_design: Lung cells from wild type and Aga2 mice were isolated from whole lung samples at postnatal day 5 and 28 and analyzed using scRNAseq.

first: Roya

last: Bagheri

first: Alex

last: Kot

first: Jorge

last: Martin

first: Davis

last: Wachtell

first: Sereen

last: Wong

first: Maeve

last: Mungovan

first: Caroline

last: Wight

first: Deborah

last: Krakow


title: Identification of immune reconstitution and hematopoiesis restoration in bone marrow of multiple myeloma patients with high-dose melphalan following auto-HSCT by scRNA-seq

city: Tianjin

first: Lina

last: Zhao

address: Huan-Hu-Xi Road

institute: Tianjin Medical University

summary: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal expansion of plasma cells in the bone marrow (BM). The high-dose chemotherapy following autologous hematopoietic stem cell transplantation (auto-HSCT) is a mainstay therapy for MM. However, effect of therapy on reconstitution of both immune and hematopoietic stem and progenitor cell (HSPCs) in BM of MM patients is pooly understood. In this study, we investigated the significance of that using single-cell RNA sequencing (scRNA-seq). The scRNA-seq data of bone marrow mononuclear cells (BMMCs) from three MM patients with high-dose melphalan following auto-HSCT were integrated these data with scRNA-seq profiles from three newly diagnosed MM patients and three healthy donors. Our data showed that the malignant plasma cells in BM were strongly reduced to 0.09% in the MM group with therapy relative to 22.03% in control MM group. Notably, the proportions of pre-B cells, T cells, natural killer (NK) cells, and HSPCs were significantly elevated to 0.97%, 61.01%, 10.81% and 2.32% in BM of MM groupwith therapy relative to 0.10%, 27.34%, 7.17% and 0.46% in control MM group, indicating a robust reconstitution of both immune and HSPCs. The transcriptional landscape of HSPCs demonstrated functional restoration, with the enrichment of pathways involved in immune activation and multilineage differentiation. Pseudotime analysis revealed the distinct plasma cell trajectories and a notable downregulation of the unfolded protein response (UPR) pathway following by the treatment. Our findings provide a new insight into the comprehensive understanding of single-cell atlas in BM of MM by the therapy.

overall_design: The scRNA-seq was performed on freshly isolated BMMCs from three MM patients with high-dose melphalan following auto-HSCT to generate high-resolution transcriptomic profiles.

first: Qian

first: Yaling

last: Wang

first: Hongfeng

last: Yuan

first: Qiaomei

last: Cai

first: Li

last: Lin

first: Shuang

last: Gao

first: Lin

last: Chen

first: Zhiying

first: Jing

last: Ma

first: Su

last: liu

first: Zeng

last: Cao

first: Yufei

first: Shihui

first: Pan

last: Lv

first: Huihui

first: Guowen

first: Guang

last: Yang

first: Xiaodong

first: Yafei


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma [RNAseq_DLBCLcelllines]

first: Jason

last: Chan

overall_design: RNAseq profiling of lymphoma cell lines

first: Jason Yongsheng


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma [RNAseq_KAI3_NKS1_posttreatment]

overall_design: RNAseq profiling of lymphoma cell lines with or without treatment with brincidofovir at low (100ng/ml) and high doses (1000ng/ml).


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma [RNAseq_PTCLcelllines]


title: Pesco-vegetarian food components synergistically promote ferrroptosis in colonocytes to reduce colon cancer risk [bulkRNA-seq]

city: College Station

first: Destiny

last: Mullens

state: Texas

address: 2253 TAMU

department: Nutrition

institute: Texas A&M University

summary: To assess the utility of diet modulation as a promising avenue to modulate ferroptosis in the colon, we examined the combinatorial effect of n-3 vs. n-6 polyunsaturated fatty acids (PUFA) and highly fermentable vs. poorly fermentable fiber on ferroptosis induction in preclinical models and healthy human adults. In vitro treatment of immortalized mouse colonocytes with docosahexaenoic acid, a n-3 PUFA enriched in fish oil, and butyrate, a short chain fatty acid generated by colonic microbial fermentation of fiber, reduced cell viability and interactively (P < 0.05) increased lipid peroxidation, a key biomarker for ferroptosis, compared to counterpart treatments. Addition of the ferroptosis inhibitor, ferrostatin-1, significantly blocked the combined effects of docosahexaenoic acid and butyrate on colonocyte lipid oxidation and cell death in vitro. In vivo treatment of mice fed fish oil and highly fermentable fiber (pectin) vs. control, corn oil (contains n-6 PUFA) and poorly fermentable fiber (cellulose) significantly (P < 0.05) promoted lipid peroxidation and the induction of ferroptosis transcriptional networks exclusively in colonic epithelial cells. In addition, as part of a randomized controlled crossover pilot study in humans, supplemental fermentable fiber (35 g/d soluble corn fiber) and fish oil (6 g/d n-3 PUFA) upregulated intestinal ferroptosis related gene expression, as compared to similar doses of maltodextrin plus corn oil. Our findings demonstrate that dietary fish oil and fermentable fiber act synergistically to induce ferroptosis in colonocytes. These important and often overlooked interactions between diet and the gut microbiome help to explain the anti-cancer benefit of the pesco-vegetarian diet.

overall_design: RNAseq of colonocytes harvested from mice fed either a corn oil/cellulose diet or fish oil/pectin diet.

first: Yang-Yi

last: Fan

first: Michael

middle: L

last: Salinas

first: Laurie

last: Davidson

first: Jennifer

last: Goldby

first: Ivan

middle: V

last: Ivanov

first: Arul

last: Jayaraman

first: James

middle: J

first: Lisa

last: Levy

first: Meredith

last: Hullar

first: Sandi

last: Navarro

first: Johanna

middle: W

last: Lampe

first: Robert

last: Chapkin


title: Pesco-vegetarian food components synergistically promote ferrroptosis in colonocytes to reduce colon cancer risk [scRNA-seq]

overall_design: Mice fed either corn oil/cellulose diet or fish oil/pectin diet.

last: Cai


title: PTPN2 deficiency amplifies interferon signaling and impairs functional maturation of human stem cell-derived islets [BulkRNA_Stemcells]

first: Valerie

last: Vandenbempt

overall_design: RNA sequencing on stem cells with or without PTPN2 under IFNg treatment

first: Javier

last: Negueruela

first: Francisco

last: Ribeiro-Costa

first: Mariana

last: Nunes

first: Leonardo

last: Traini

first: Sema Elif

last: Eski

first: Wadsen

last: Saint-Pierre-Wijckmans

first: Stéphane

last: Demine

first: Nicolas

last: Baeyens

first: Hazem

last: Ibrahim

first: Luciano

last: Martelotto

first: Sumeet Pal

last: Singh

first: Alessandra

last: Cardozo

first: Esteban

last: Gurzov


title: PTPN2 deficiency amplifies interferon signaling and impairs functional maturation of human stem cell-derived islets [ATAC-Seq]

overall_design: ATAC sequencing on stem cells with or without PTPN2 under IFNg treatment


title: The E3 ubiquitin ligase mechanism specifying targeted microRNA degradation

city: Cambridge

first: Lianne

middle: Wang

last: Blodgett

address: 455 Main St

institute: Whitehead Institute/MIT

type: Non-coding RNA profiling by high throughput sequencing

summary: MicroRNAs (miRNAs) associate with Argonaute (AGO) proteins to form complexes that down-regulate target RNAs, including messenger RNAs from most human genes. Within each complex, the miRNA pairs to target RNAs, and AGO provides effector function while also protecting the miRNA from cellular nucleases. Although much is known about miRNA-directed gene regulation, less is known about how miRNAs themselves are regulated. One pathway that regulates miRNAs involves unusual targets called ‘trigger’ RNAs, which reverse the canonical regulatory logic and instead down-regulate miRNAs. This target-directed miRNA degradation (TDMD) is thought to require a cullin–RING E3 ligase because it depends on the cullin protein CUL3 and other ubiquitylation components, including the BC-box protein ZSWIM8. ZSWIM8 is required for murine perinatal viability and for destabilization of most short-lived miRNAs, which suggests biological importance of TDMD. Here, biochemical and cellular assays establish AGO binding and polyubiquitylation by the ZSWIM8–CUL3 E3 ligase as the key regulatory steps of TDMD, and thereby define a unique cullin–RING E3 ligase class. Cryogenic electron microscopy analyses show ZSWIM8 recognizing distinct AGO and RNA conformations shaped by pairing of the miRNA to the trigger. Specificity of AGO ubiquitylation is established through generalizable RNA–RNA, RNA–protein and protein–protein interactions. The substrate features recognized by the E3 ligase do not conform to a conventional degron but instead establish a two-RNA-factor authentication mechanism for specifying a protein ubiquitylation substrate.

sample_organism:
Drosophila melanogaster
Mus musculus

platform_organism:
Drosophila melanogaster
Mus musculus

overall_design: Small-RNA sequencing of ZSWIM8-knockout and control cell lines following immunoprecipitation of AGO-bound small RNAs. Samples include knockout and control Drosophila S2 cells and contact-inhibited mouse embryonic fibroblasts (MEFs).

first: Jakob

last: Farnung

first: Elena

last: Slobodyanyuk

first: Peter

middle: Y

last: Wang

first: Daniel

middle: H

last: Lin

first: Susanne

last: von Gronau

first: Brenda

last: Schulman

first: David

last: Bartel


title: Frailty impairs skeletal muscle resilience to downhill running stress in aged female mice

city: Boston

first: Boston University

last: Microarray and Sequencing Resource

state: MA

address: 72 East Concord Street, E631

department: Microarray and Sequencing Resource

institute: Boston University

summary: Frailty is a clinical syndrome marked by diminished physiological reserve and function. While skeletal muscle dysfunction is central to frailty, most preclinical models focus on basal function and overlook responses to physiological stress. Here, we examined the impact of frailty on skeletal muscle resistance and resilience to stress using a physiologically relevant model of downhill running stress. Female C57BL/6 mice (n=47; >17 months) were stratified into frail or robust groups by phenotyping and further randomized to undergo two bouts of downhill running or remain cage sedentary. Twenty-four hours later, contractile function was assessed ex vivo in the extensor digitorum longus (EDL) and soleus muscles. RNA was extracted from the gastrocnemius of randomly selected samples and analyzed by RNA sequencing. Despite comparable specific tetanic force, frail mice exhibited greater fatiguability and impaired recovery kinetics in the EDL following running stress. RNA sequencing revealed divergent transcriptional signatures in robust and frail mice in response to running, including upregulation of mitochondrial bioenergetic and complex assembly pathways in robust mice and downregulation in frail mice. These data demonstrate that the stress of downhill running unmasks latent impairments in the skeletal muscle of frail mice, and that mitochondrial dysfunction and/or redox imbalance may be potential contributors to reduced muscle resilience. Overall, our results highlight the importance of incorporating physiological stress paradigms to uncover frailty-associated muscle impairments and suggest that dynamic measures of stress responses may serve as more sensitive functional indicators of frailty than baseline muscle properties alone.

overall_design: Female C57BL/6 mice (n=47; >17 months) were stratified into frail or robust groups by phenotyping and further randomized to undergo two bouts of downhill running or remain cage sedentary (total of 4 independent groups). RNA was extracted from the gastrocnemius at this time point was analyzed by RNA sequencing.

first: Grant

middle: R

last: Laskin

first: LaDora

last: Thompson


title: Medicinal Cannabis Plant Extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in paediatric acute-onset neuropsychiatric syndrome

first: Brian

last: Gloss

summary: Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction. This open-label trial investigated the safety and efficacy of NTI164, a cannabis-derived medicinal formulation rich in cannabinoids (minimal tetrahydrocannabinol), at 20 mg/kg/day for 12 weeks in 14 children with chronic-relapsing PANS (mean 12.1 years, females 29%). Clinical assessments demonstrated significant improvements with NTI164 in disease severity, emotional regulation, anxiety, OCD, ADHD symptoms, and overall quality of life (all p<0.05). Cytokine and multi-omics analyses, including transcriptomics, proteomics, phosphoproteomics, and DNA methylation, revealed baseline dysregulation in epigenetic (chromatin remodelling, methylation, histone modifications, transcription factors), ribosomal, immune, and signalling pathways in PANS versus controls. These abnormalities were significantly modified following NTI164 treatment. These results suggest NTI164 has broad epigenetic and immune modulatory effects, modifying baseline immune cell abnormalities in PANS. While further controlled studies are warranted, NTI164 shows promise as a novel therapeutic for PANS.

overall_design: scRNA-seq in 4 children with PANS at baseline and after 12 weeks of NTI164 treatment and 4 age- and sex-matched healthy controls

first: Brooke

last: Keating

first: Velda

last: Han

first: Hiroya

last: Nishida

first: Nader

last: Aryamanesh

first: Lee

last: Marshall

first: Xianzhong

last: Lau

first: Ruwani

last: Dissanayake

first: Suat

last: Dervish

first: Mark

middle: E

last: Graham

first: Shekeeb

last: Mohammad

first: Manoj

last: Kanhangad

first: Michael

last: Fahey

first: Shrujna

last: Patel

first: Russell

last: Dale


title: Identification of gene signature in mock and miR-625-3p-transfected ovarian cancer cells

city: Houston

first: Chi Lam

last: Au Yeung

state: TX

address: 1515 Holcombe Blvd

institute: The University of Texas MD Anderson Cancer Center

summary: Advanced-stage high-grade serous ovarian cancer (HGSC) is a disease that is difficult to manage due to its heterogeneous clinical behavior. No reliable prediction of response to chemotherapy is currently available and the overall survival rate remains poor. Herein, we sought to determine the molecular mechanisms by which microRNAs (miRNAs) confer chemoresistance in ovarian cancer and to demonstrate the efficacy of targeting miRNAs to sensitize HGSC to cisplatin treatment. An miRNA signature for intrinsic chemoresistance was identified. Amongst all the downregulated miRNAs in the chemo-refractory samples, only miR-625-3p was associated with poorer overall survival and progression-free survival rates. Further functional studies showed that overexpression of miR-625-3p significantly decreased cisplatin resistance in ovarian cancer cells both in vitro and in vivo. SSX2IP was confirmed to be the direct gene target of miR-625-3p and its upregulation abrogated miR-625-3p-mediated cisplatin resistance by enhancing exosomal export of cisplatin in ovarian cancer cells. These findings provided a new paradigm for intrinsic cisplatin resistance acquisition by HGSC cells, which will be crucial for developing new treatment strategies for ovarian cancer based on upregulation of miR-625-3p or downregulation of SSX2IP to enhance cisplatin sensitivity and improve patient survival rates.

overall_design: Total RNAs from mock or miR-625-3p-transfected A224 cells were extracted using a TRI reagent (Molecular Research Center). Purified RNA samples were amplified, labeled, and hybridized onto Affymetrix GeneChip Human Genome U133 Plus 2.0 microarrays (Affymetrix Inc., Santa Clara, CA, USA) according to the manufacturer’s protocol. The arrays were then washed and stained using the Affymetrix Fluidics Station 450 (Affymetrix Inc.). The arrays were scanned by the Cancer Genomics Laboratory at MD Anderson using a GeneChip Scanner 3000 7G (Affymetrix Inc.).

first: Tetsushi

last: Tsuruga

first: Tsz Lun

last: Yeung

first: Samuel C

last: Mok


title: CD371-Targeted CAR T-cells Secreting Interleukin-18 Exhibit Robust Expansion and Clearance of Refractory Acute Myeloid Leukemia

city: New York

first: Xiaoli

last: Mi

state: NY

address: 408 East 69th Street, 408-18

institute: Memorial Sloan Kettering Cancer Center

summary: Success of chimeric antigen receptor (CAR) T-cell therapy in lymphoid malignancies has not yet been recapitulated in acute myeloid leukemia (AML). We developed CAR T-cells targeting CD371 with a mutated CD28 costimulatory domain to limit T-cell exhaustion, and constitutive interleukin-18 secretion to enhance immune function (CD371/SAVVY/IL-18 CAR). We initiated a phase I trial (NCT06017258), successfully manufactured and administered CD371/SAVVY/IL-18 CAR T-cells in 5 patients with relapsed/refractory AML, and observed expansion following a single infusion of 3x104 or 3x105 CAR T-cells/kg; three patients refractory to ≥5 lines of therapy and post-allogeneic transplant exhibited AML clearance. Single-cell analyses revealed that circulating CAR T-cells in responders included predominantly cytotoxic CD8+ effector T-cells 2 weeks post-infusion while co-existing NK-cells expressed markers of activation. This pilot study highlights the activity of low-dose IL-18 “armored” CAR T-cells against refractory AML and their potential to promote CAR T-cell cytotoxicity and innate endogenous anti-tumor immunity.

overall_design: Given the CAR T cell expansion and changes in serum cytokines seen in each patient, we studied the phenotypic evolution of CAR T cells expanding in vivo in parallel with circulating immune cells and malignant blasts. We performed 5’-based CITE-seq on sorted lymphocyte and myeloid subsets on the end of production product (EOP) and longitudinal peripheral blood samples from each patient.

middle: B

last: Geyer

first: Susan

last: DeWolf

first: Kenyon

last: Weis

first: Brian

last: Shaffer

first: Briana

last: Cadzin

first: Devin

last: McAvoy

first: Zoe

last: Katsamakis

first: Rachel

last: Lorenc

first: Alexander

middle: M

last: Lewis

first: Brianna

last: Gipson

first: Adriana

last: Cuibus

first: Narina

middle: N

last: Girotra

first: Erin

last: Burns

first: Jasmine

last: Um

first: Sarah

last: Yoo

first: Pallavi

last: Galera

first: Kinga

last: Hasszu

first: Jagrutiben

last: Chaudhari

first: Xiuyan

last: Wang

first: Qianqian

last: Lin

first: Kevin

last: Curran

first: Jae

last: Park

first: David

last: Scheinberg

first: Marcel

last: van den Brink

first: Omar

last: Abdel-Wahab

first: Renier

last: Brentjens

first: Anthony

middle: F

last: Daniyan


title: Targeting WWP2 to restore mitochondrial OXPHOS integrity―a novel strategy to attenuate acute kidney injury to chronic kidney disease transition

city: Nanjing

first: Mengqiu

last: Miao

state: Jiangsu

address: Children's Hospital of Nanjing Medical University

summary: Analysis of kidney from transgenics depleted for renal tubular WW domain containing E3 ubiquitin protein ligase 2 (WWP2)  then established a kidney unilateral ischemia reperfusion (UIR) injury in mice induce acute kidney injury (AKI) to chronic kidney disease (CKD) transition.  Results provide insight into the role of WWP2 activation in AKI-to-CKD transition.

overall_design: WWP2fl/fl mice (WT) and proximal tubule conditional WWP2-knockout mice (WWP2 PTCKO) on a C57BL/6J background were generated.WT mice and WWP2 PTCKO mice (male, 8 weeks old) were randomly divided into four groups: WT Sham group, WT UIR group, WWP2 PTCKO Sham group and WWP2 PTCKO UIR group (n=6-8 per group).And we aim to explore the function of WWP2  in UIR induced AKI-to-CKD transition and explore the possible machanisms.


title: Medicinal cannabis plant extract (NTI164) modifies epigenetic, ribosomal, and immune pathways in Paediatric Acute-onset Neuropsychiatric Syndrome

first: Nader

last: Aryamanesh

address: 214 Hawkesbury Rd

department: Bioinformatics

institute: CMRI

summary: Paediatric Acute-onset Neuropsychiatric Syndrome (PANS) is a syndrome of infection-provoked abrupt-onset obsessive-compulsive disorder (OCD) or eating restriction. This open-label trial investigated the safety and efficacy of NTI164, a cannabis-derived medicinal formulation rich in cannabinoids (minimal tetrahydrocannabinol), at 20mg/kg/day for 12 weeks in 14 children with chronic-relapsing PANS (mean 12.1 years, females 29%). Clinical assessments demonstrated significant improvements with NTI164 in disease severity, emotional regulation, anxiety, OCD, ADHD symptoms, and overall quality of kife (all p<0.05). Cytokine and multi-omic analyses, including transcriptomics, proteomics, phosphoproteomics, and DNA methylation revealed baseline dysregulation in epigenetic (chromatin remodelling, methylation, histone modifications, transcription factors), ribosomal, immune, and signalling pathways in PANS versus controls. These abnormalities were significantly modified following NTI164 treatment. These results suggest NTI164 has broad epigenetic and immune modulatory effects, modifying baseline immune cell abnormalities in PANS. While further controlled studies are warranted, NTI164 shows promise as a novel therapeutic for PANS.

overall_design: Open-label clinical trial. Patients vs control, and patients pre- and post-treatment (NTI164).

first: Brooke

last: Keating

first: Velda

last: Han

first: Hiroya

last: Nishida

first: Lee

last: Marshall

first: Brian

last: Gloss

first: Xianzhong

last: Lau

first: Ruwani

last: Dissanayake

first: Suat

last: Dervish

first: Mark

last: Graham

first: Shekeeb

last: Mohammad

first: Manoj

last: Kanhangad

first: Michael

last: Fahey

first: Shrujna

last: Patel

first: Russell

last: Dale


title: Association between environmental contaminant TBOEP and hepatic metabolism

city: Changzhou

first: Shuai

last: Chen

address: 68 Gehu Rd, Wujin District

institute: The Affiliated Changzhou NO.2 People’s Hospital of Nanjing Medical University

summary: tris(2-butoxyethyl) phosphate (TBOEP) is a common organophosphorus compound widely used in industrial production as a plasticizer and flame retardant. In recent years, studies have shown that TBOEP may pose potential threats to human health, particularly its association with liver metabolic function has attracted widespread attention. The liver, as the most important metabolic organ in the human body, plays a crucial role in detoxification, synthesis, and decomposition of various biomolecules. After entering the human body, TBOEP is mainly metabolized and detoxified by the liver. However, TBOEP and its metabolites may interfere with the normal function of the liver, leading to metabolic disorders. Research has shown that TBOEP exposure may affect the activity of enzymes in the liver, such as the cytochrome P450 enzyme system, which plays an important role in drug metabolism and endogenous substance synthesis. Long-term exposure to TBOEP may also lead to liver inflammation and fatty degeneration, further affecting liver metabolic function. In addition, TBOEP may also affect liver metabolic pathways by influencing gene expression. For example, TBOEP exposure may activate or inhibit genes related to lipid metabolism, glucose metabolism, and oxidative stress, thereby altering the metabolic state of the liver. These changes not only affect the function of the liver itself but may also have a chain reaction on the health of other organs and systems through the interaction of the systemic metabolic network. In summary, as an environmental pollutant, the potential impact of TBOEP on liver metabolic function cannot be ignored. Future research needs to further explore the toxicological mechanisms of TBOEP and its long-term effects on human health in order to develop effective prevention and intervention measures to protect public health.

overall_design: Once the AML12 cells reached confluency, they were stimulated with 20 μM TBOEP for 48 hours


title: Gene expression profiling of murine osteosarcoma NHOS cells with/without IL10RB transfection

city: Tokyo

first: Chie

last: Kudo-Saito

address: 5-1-1 Tsukiji, Chuo-ku

department: Department of Immune Medicine

country: Japan

institute: National Cancer Center Research Institute

summary: To investigate the effect of IL10RB expression in cancer cells, IL10RB(low) NHOS cells were transfected with a plasmid vector pCMV6-ENTRY encoding murine il10rb (NHOS-TR) or the empty vector as mock control (NHOS-mock), and compared the differences in gene expressions between them.

overall_design: RNA-sequencing of murine osteosarcoma NHOS cells with/without IL10RB transfection


title: Transcriptome-Proteome analysis of human naive and memory B cell subsets reveal isotype and subclass-specific phenotypes

city: Amsterdam

first: Arie Johan

last: Hoogendijk

address: Plesmanlaan 125

country: Netherlands

institute: Sanquin Research

summary: Antibodies produced by B cells aid in recognition and clearance of pathogens and is the cornerstone of vaccination strategies. Humans produce nine different antibody isotypes and their effector functions differ according to the type of antigen and route of exposure. Phenotypic variation between isotype-swithched B cell subsets is expected but not studied in detail. To obtain a molecular definition of isotype-defined B cell identity, we performed proteomics and transcriptomics on isotype-defined populations of human naive and memory B cells (MBCs): CD27-IgM+IgD+, CD27+CD38lo/-IgM+IgD+, CD27+CD38lo/-IgM+IgD-, and IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4 MBCs (CD27+CD38lo/-Ig+). Combined proteome and transcriptome analysis revealed that mRNA and protein expression profiles segregate separate isotype-defined B cell subsets according to their differentiation status. mRNA and protein expression levels correlated reasonably well for many genes. IgG4+ MBCs were most distinct from naive B cells. Besides a distinct expression profile of cytokine and Fc receptors, we identified a high expression of IgE-coding mRNA in IgG4-switched B cells. SDR16C5 was identified as uniquely upregulated in IgG4-switched B cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for isotype-defined populations of human naive and memory B cells (MBCs): CD27-IgM+IgD+, CD27+CD38lo/-IgM+IgD+, CD27+CD38lo/-IgM+IgD-, and IgA1, IgA2, IgG1, IgG2, IgG3, and IgG4 MBCs (CD27+CD38lo/-Ig+)

first: Jana

last: Koers

first: Arie

first: Simon

last: Tol

first: Floris

last: van Alphen

first: Ninotska

last: Derksen

first: Maartje

last: van den Biggelaar

first: Theo

last: Rispens


title: Effect of overepression of HK1 in hepatocellular carcinoma cells

city: xiamen

first: feng

last: deyi

state: xiamen

address: Xiamen University

institute: xiamen university

summary: Hexokinase (HK), accountable for the phosphorylation of glucose, catalyzes the initial step of glucose metabolism. The HK family encompasses four members (HK1-4) in mammals, and HK1 exhibits the highest affinity for glucose. We found that overexpression of HK1 in Huh7 cells not only promoted the glycolysis pathway but also increased the pathway of asparagine N-linked glycosylation.

overall_design: Overexpressing HK1 in Huh7 cells, then control cells and HK1-overexpressing Huh7 cells were collected for RNA-sequencing.


title: Sucrose-Activated TOR and phyA Signaling Alleviates Shade-Mediated Inhibition of Leaf Development in Arabidopsis

city: Shanghai

first: Lin

last: Li

address: 2005 Songhu Road,Yangpu District

department: school of life sciences

institute: Fudan University

summary: Shade can trigger shade avoidance responses with increasing the elongation of stem-like organs at the expense of leaf development. We report that exogenous sucrose alleviates shade-induced inhibition of leaf development through a mechanism dependent on both the TOR complex and phyA. To investigate the function of sucrose and phyA, we performed RNA-Seq of wild type Col-0 and phyA-211 with sucrose treatment under shade.

overall_design: 10-day-white-light grown seedlings were treated with 30 mM sorbitol or 30 mM sucrose in 1/2 MS liquid medium under shade for 6 h, and the leaf portions were harvested for RNA extraction.

first: Jiayu

last: Wang


title: Intermittent Fasting Reprograms Chromatin Accessibility to Modulate Gene Expression in Brain and Muscle

city: Melbourne

first: Yibo

last: Fan

state: VIC

address: Science Dr, Bundoora VIC 3083

institute: La Trobe University

summary: Intermittent fasting (IF), a dietary regimen that mimics the natural feeding patterns observed across diverse organisms—from single-celled life to mammals—is thought to activate systemic survival responses and confer health benefits. However, the molecular mechanisms underlying these effects remain poorly understood. In this study, we utilized ATAC-Seq and RNA-Seq to investigate how IF influences chromatin accessibility and gene expression in brain and muscle tissues of mice, compared to ad libitum feeding. Our results reveal that IF induces significant changes in chromatin accessibility, modulating pathways related to metabolism, ribosome function, HIF-1 signaling, and glycolysis. Motif analysis identified tissue-specific transcription factors enriched in IF-regulated regions, including Sp1, Mef2a, NeuroD2, Banp, and NFIA in the brain, and SMAD4, TCF4, STAT5B, NKX3-1, and ZEB2 in muscle. Integrative analysis of ATAC-Seq and RNA-Seq data demonstrated that IF upregulates 50 genes and downregulates 15 in the cortex, while upregulating 31 genes and downregulating 10 in muscle. These gene expression changes are linked to pathways associated with neuroprotection and enhanced muscle function, offering mechanistic insights into the health benefits of IF. Our findings underscore the role of IF-induced chromatin remodeling in driving adaptive gene regulation.

overall_design: Male mice were divided into two groups: Ad Libitum (AL) and 16:8 fasting (IF) (n=8 per group). After 4 months on their respective dietary regimens, mice were sacrificed, and tissues from the cortex and muscle were harvested, prepared, and subjected to ATAC-seq and RNA-seq analyses

first: Xiangyuan

last: Peng

first: Thiruma

last: Arumugam


title: KPPC parental and sgCCR2 line grown under culture conditions

city: St Louis

first: Kian-Huat

last: Lim

state: MO

address: 4566 Scott Avenue

department: Oncology

institute: Washington University Medical school

summary: We treated KPPC parental and sgCCR2 line grown under tissue culture conditions 48 hours

overall_design: Bulk RNAseq analysis

first: Vikas

last: Somani


title: snRNAseq of diffuse leptomeningeal glioneuronal tumors

city: Toronto

first: Cynthia

last: Hawkins

state: ON

address: 555 University Ave.

department: Pediatric Laboratory Medicine

institute: The Hospital for Sick Children

summary: As part of a larger study on disseminated pediatric low-grade gliomas, we performed scRNAseq on two diffuse leptomeningeal glioneuronal tumors (DLGNT), one of which remained low-grade, and the other of which underwent high-grade transformation. Using this data, we compared the cellular pathway activation of each tumor, identifying a subpopulation of highly proliferative tumor cells in the transformed sample, which had elevated MAPK pathway activity and depressed p53 pathway activity.

overall_design: Two snap frozen tissue specimens were used from brain tumor resections. One sample (DLGG038) represents a DLGNT that remained low grade, while the other (DLGG181) is a sample that underwent progression to a high-grade neoplasm.

first: Adrian

last: Levine


title: Developmental systesms drift in dorsoventral patterning is linked to transitions to autonomous development in Annelida

city: London

first: Allan

last: Carrillo-Baltodano

address: Mile End

department: School of Biological and Behavioural Studies

country: United Kingdom

institute: Queen Mary University of London

summary: The Bone Morphogenetic Protein (BMP) pathway is the ancestral signalling defining the dorsoventral axis in bilaterally symmetrical animals. However, Spiralia, a large bilaterian clade including molluscs and annelids, uses the Fibroblast Growth Factor pathway and ERK1/2 as the ancestral cue to establish their posterodorsal side. How this profound change in axial patterning evolved and what it implied for BMP’s developmental role remains elusive. Here, we studied four annelid species and combined disruption of the BMP and Activin/Nodal pathways with transcriptomics and blastomere deletions to demonstrate that BMP is ancestrally downstream of ERK1/2 and promotes dorsoventral development in Spiralia. Importantly, this signalling hierarchy is lost in annelids that secondarily transitioned into a maternally controlled, autonomous development. While some, like Capitella teleta, use Activin/Nodal, the annelid Platynereis dumerilii relies on BMP to establish dorsoventral polarity only in the head. Unexpectedly, this divergence in upstream axial regulators implied extensive rewiring of downstream targets, as inferred by comparing C. teleta and Owenia fusiformis. Our data clarify the ancestral BMP’s axial role in Spiralia, unveiling a potential causal link between parallel shifts to autonomous cell-fate specification in early development and the emergence of developmental system drift, a pervasive yet poorly understood phenomenon in animal embryogenesis.

overall_design: We generated bulk RNA-seq in the annelid Owenia fusiformis grown in laboratory conditions,  treated with DMH1 and SB435421 (BMP and Nodal/Activin antagonists) and zBMP4 and Activin-A recombinant protein, and compared to DMSO treated control samples.

first: Allan M

first: Emmanuel

last: Hailot

first: Steffanie M

last: Meha

first: Imran

last: Luqman

first: Artenis

last: Pashaj

first: Yun-Ju

last: Lee

first: Tsai-Ming

last: Lu

first: David KE

last: Ferrier

first: Stephan Q

last: Schneider

first: Jose M

last: Martín-Durán

first: Jimena

last: Montagne


title: Integration of functional precision oncology to immune contexture predicts immunotherapies strategies for mucosal melanomas.

city: Verona

first: Marzia

last: Rossato

state: Italy

address: Strada Le Grazie,15

department: Department of Biotechnology

country: Italy

institute: University of Verona

summary: Mucosal melanomas (MM) arise from mucosal melanocytes at various anatomical sites. These tumors are rare, highly aggressive, and often associated with poor outcomes. Current treatments, including immune checkpoint inhibitors, show limited efficacy in advanced disease. Compared to cutaneous melanomas, there is a lack of data on the immunogenicity and IFN-γ sensitivity of MM. In this study, we examine these features in sino-nasal melanoma (SN-MM) cell lines and clinical samples using microscopy and functional genomics. Microscopic analysis reveals that most SN-MM tumors are immune "desert" with few tumor-infiltrating lymphocytes (TILs), a characteristic linked to poor prognosis. Additionally, SN-MM tumors are CD274/PD-L1 negative. SN-MM cell lines express transcripts for melanocytic and cancer testis antigens. They also show normal surface expression of IFN-γ receptors (IFNGR) and maintain the integrity of the IFNGR/JAK/STAT signaling pathway. Transcriptomic and proteomic analyses demonstrate that SN-MM cell lines, as a group, respond to IFN-γ by upregulating genes involved in immune recognition and antigen presentation. In 60% of SN-MM lines, IFN-γ also induces cytotoxic and anti-proliferative effects, the release of CXCL10 and upregulation of CD274/PD-L1. The remaining SN-MM cell lines, characterized by poor differentiation, show refractoriness to these effects, likely due to post-transcriptional regulation. These findings suggest that combining functional precision oncology with immune context analysis could refine our understanding of immune escape mechanisms in MM and improve patient stratification for immune therapies.

overall_design: Bulk RNA-Seq analysis of five sino-nasal mucosal melanoma cell lines, treated or not with IFN-γ (100 ng/mL) for 4 hours.

first: Matilde

last: Monti

first: Sara

last: Picinoli

first: Anna

last: Bozzola

first: Marco

last: Ferrari

first: Mattia

last: Bugatti

first: Irene

last: Pezzali

last: Carlomagno

first: Giada

last: Carta

first: Matteo

last: Orlandi

first: Giacomo

last: Lora

first: Luisa

last: Benerini Gatta

first: Francesco

last: Missale

first: Giorgia

first: Marcello

last: Manfredi

first: Veronica

last: De Giorgis

first: Emilio

last: Marengo

first: Mario

last: Turri-Zanoni

first: Piero

last: Nicolai

first: Francesca

last: Consoli

first: Davide

last: Lombardi

first: Paolo

last: Martini

first: William

last: Vermi


title: Integrated clinical and molecular landscape of disseminated pediatric low-grade glioma

first: Cynthia

last: Hawkins

summary: Pediatric-type low-grade gliomas (PLGG) are the most common central nervous system (CNS) tumor in children. Many are indolent and have excellent outcomes, however a major cause of morbidity and mortality can occur when tumors spread throughout the CNS. To better understand this rare and difficult-to-treat entity, as well as the underlying processes driving dissemination in CNS tumors, we assembled a large international cohort (n=269) of patients with disseminated PLGG with detailed clinical and molecular characterization. We identified three subgroups of patients based on the temporal and spatial distribution of dissemination. Tumors with diffuse leptomeningeal spread and those occurring in infants had the worst clinical outcomes. The genetics overlapped substantially with those in non-disseminated PLGG, suggesting that non-genetic mechanisms are an important contributor to dissemination. Therapeutically, targeted MAPK-pathway inhibition was more effective than conventional chemotherapy as first or second-line treatment. In sum, this clinical cohort increases our understanding of this rare disease, provides insights for improving patient care, and directs future study.

overall_design: We aimed to understand the methylation profiles of pediatric low-grade gliomas. Formalin-fixed paraffin embedded (FFPE) tissue from 97 surgical specimens were profiled using Illumina Infinium EPIC arrays.

first: Adrian

last: Levine

first: Uri

last: Tabori


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma [RNAseq_NKTCLcelllines]

city: Singapore

first: Jason

last: Chan

address: 30 Hospital Blvd

institute: National Cancer Centre Singapore

summary: Introduction: Brincidofovir (BCV) is a novel nucleoside phosphonate analogue with unique dual anti-viral and anti-tumor properties. Methods: Activity of BCV was evaluated in forty-four cell-line models, including T/NK-NHL (n=25) and B-cell lymphoma (BCL, n=19), as well as their respective NOD/SCID mice xenograft models (NK/T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, TP63-rearranged anaplastic large cell lymphoma, and MYC/BCL2-rearranged diffuse large B-cell lymphoma). Potential in vivo immunogenic effects were examined in a syngeneic EL4-C57BL/6 murine lymphoma model. Results: BCV demonstrated potent anti-tumor activity in vitro across the majority of cell-lines regardless of EBV positivity, with IC50 values within clinically-achievable human plasma concentrations (2 µg/ml) in 17/25 (68.0%) T/NK-NHL and in 13/19 (68.4%) BCL. In vivo treatment via intraperitoneal BCV (IP, 40mg/kg, 2X per week) significantly inhibited tumor growth in all xenograft models when compared to vehicle control. Notably, RNAseq analysis demonstrated BCV downregulated MYC and MYC-target pathways in T/NK-NHL models. Further mechanistic studies showed that BCV evoked S-phase cell cycle arrest, replication stress, DNA damage and apoptosis, while also triggering STING pathway-mediated interferon responses, PD-L1 expression and immunogenic cell death. In the syngeneic EL4-C57BL/6 model, BCV in combination with anti-PD1 significantly inhibited tumor growth and triggered an immune reaction characterized by highest scores for adaptive immune response, cytokines/chemokines & receptors, cytotoxic cells, dendritic cells, NK CD56dim cells and neutrophils (NanoString Immunology Panel). Conclusions: Taken together, these results demonstrate a novel role of BCV in the treatment of lymphoma, and suggest potential for combination with checkpoint immunotherapy.

overall_design: RNAseq profiling of lymphoma cell lines

first: Jason Yongsheng


title: Exploring Mechanism of Action of Abemaciclib in Breast Cancer Through Circulating Chromatin Fragment

city: Grand Forks

first: Motoki

last: Takaku

state: ND

address: W221 Biomedical Sciences 1301 N. Columbia Road

institute: University of North Dakota

summary: Cell free DNA (cfDNA) analysis has a large potential for cancer patient diagnosis. Given the evidence that cfDNA partially preserves chromatin architecture of tumor cells, it potentially allows the detection of tumor responses after therapeutic treatment. In this study, we aimed to detect the responses of abemaciclib, a potent cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6 inhibitor), in metastatic recurrent breast cancer patients through cfDNA analysis. Our results suggest that cfDNA can be used as a valuable marker to monitor cancer burden, cancer responses to drug treatment, and sensitivity against therapeutic reagents. cfDNA concentrations purified from serum are significantly higher in cancer patients compared to healthy donors, suggesting that a significant portion of the cfDNA originates from tumors in our samples. The cfDNA concentrations are also significantly decreased after abemaciclib treatment. The sequencing analysis of cfDNAs revealed a higher enrichment of cfDNAs at open chromatin regions and differentiated the cfDNA enrichment patterns between abemaciclib treated and non-treated samples. Altered cfDNA signals are frequently associated with the genes that are involved in apoptosis and CDK4/6 related pathways. Finally, the differentially enriched region analysis also detected the differences in abemaciclib cases that could be treated long-term and cases that had an exacerbation after short-term treatment. In conclusion, this research enhances our understanding of the biology of abemaciclib and provides new insights into CDK4/6 inhibitor’s action in metastatic breast cancer.

overall_design: Cell-free DNAs (cfDNAs) were isolated from metastatic luminal breast cancer patients and healthy donors. The study was designed to monitor the impact of abemaciclib using cDNAs. cfDNA enrichment patterns were analyzed at accessible chromatin regions defined by ATAC-seq. Differentially enriched regions were identified between abemaciclib-treated and non-treated samples.  Comparative analysis was performed to identify treatment-responsive genomic regions. Finally, gene ontology analyses provided insights into the biological processes affected by abemaciclib, revealing potential biomarkers for monitoring tumor response and therapeutic sensitivity.

first: Mamoru

last: Takada

first: Sakuntha

middle: D

last: Gunarathna

first: Regina

last: Nguyen

first: Muhan

last: Yu

first: Hideyuki

last: Yamada

first: Takeshi

last: Nagashima

first: Hiroshi

last: Fujimoto

first: Junta

last: Sakakibara

first: Hiroto

last: Yamamoto

first: Mayumi

last: Iida

first: Tsutomu

last: Kawaguchi

first: Otsuka

last: Masayuki


title: Effect of AMP-dT on lymph node immune response in rhesus macaque

first: Martin

middle: P

last: Steinbuck

state: Massachusetts

address: 451D Street, Ste 501

department: Research

institute: Elicio Therapeutics

summary: Adjuvants are immuno-activators capable of shaping the magnitude and quality of antigen-specific immune responses induced by subunit immunization. Presently, there is an acute need for effective adjuvants that safely induce durable and balanced humoral and cellular responses. Here, we engineered a class of Amphiphile (AMP)-modified, immunostimulatory DNA-adjuvants designed for targeted delivery to lymph nodes and enhanced stimulation of TANK-binding kinase 1 (TBK1)-mediated danger-sensing pathways to generate strong adaptive immunity and long-term memory with potent recall potential. AMP-DNA adjuvants induced robust interferon type-I (IFN-I)-driven inflammatory environments in mouse and non-human primate (NHP) lymph nodes, leading to significantly enhanced cytokine secretion by polyfunctional CD8+ and CD4+ T cells in multiple tissues, as well as strongly elevated TH1-associated and neutralizing antibody responses, in the absence of systemic toxicity. These results demonstrate that AMP-modification enables lymph node-targeted DNA-adjuvants to potently activate IFN-I-signaling to generate substantial cellular and humoral responses crucial for vaccine efficacy.

overall_design: 1 group of two NHP (non-human primates) was injected with AMP-dT vaccine (SARS-CoV2-RBD with AMP-dT). Their immune responses within the draining iguinal lymph nodes at 24h and 48h post immunization were compared to baseline responses prior to immunization.

first: Lisa

middle: K

last: McNeil

first: Peter

middle: C

last: DeMuth

first: Lochana

last: Seenappa


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma [RNAseq_PTS1_posttreatment]

first: Jason

middle: Yongsheng

last: Chan

overall_design: RNAseq profiling of lymphoma cell lines with or without treatment with brincidofovir at low (100ng/ml) and high doses (1000ng/ml).

first: Jason Yongsheng


title: DHX9 sustains hematopoietic stem cell function in cooperation with H3 acetylation [CUT&Tag]

city: Hefei

first: Minhui

last: Shi

state: Anhui

address: University of Science and Technology of China

department: Division of Life Sciences and Medicine

summary: We identify DHX9 as critical regulator for HSCs maintenance and it's associated with H3 acetylation, particularly at K27. To elucidate the mechanisms underlying the role of Dhx9 deficiency and H3K27ac in hematopoiesis, we performed CUT&Tag on lineage nagative cells from DHX9 hematopoietic cell-specific conditional knockout mice(cKO) and those from WT mice.

overall_design: Chromatin immunoprecipitation DNA-sequencing (CUT&Tag) for DHX9 as well as H3K27ac in  lineage nagative cells from Dhx9f/f mice (WT) or Dhx9f/f;MX1 mice (cKO).

first: Huaiping

last: Zhu

first: MengQing

last: Gao


title: DNMT3B Regulates Cis-Regulatory Chromatin and Cell Cycle Programs in Acute Myeloid Leukemia

city: Little Rock

first: Samrat

last: Roy Choudhury

state: AR

address: 13 Children's Way, Arkansas Children's Research Institute

institute: University of Arkansas for Medical Sciences

type: Methylation profiling by genome tiling array

summary: Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML), often driven by dysregulated DNA methyltransferases. To investigate the epigenomic impact of DNMT3B inhibition, we treated KG1A AML cells with Nanaomycin A (NanA), a selective DNMT3B inhibitor, and performed genome-wide DNA methylation profiling using the Illumina MethylationEPIC v2.0 array. Following 48-hour exposure to NanA (50 nM), differentially methylated CpG sites were identified, with the majority exhibiting moderate hypomethylation (±25% Δβ-value). These changes were enriched in promoter and gene body regions and overlapped with regions of altered chromatin accessibility. The resulting dataset provides a high-resolution view of DNMT3B-dependent methylation dynamics in AML and serves as a resource for understanding the epigenetic consequences of targeted methyltransferase inhibition.

overall_design: To examine the effects of DNMT3B inhibition on the DNA methylation landscape in AML, we treated KG1A cells with Nanaomycin A (NanA; MedChemExpress, HY-103397), a selective DNMT3B inhibitor. Cells were seeded at a density of 1×10⁶ per condition and treated with 50 nM NanA or DMSO (vehicle control) for 48 hours. Following treatment, genomic DNA was isolated using the AllPrep DNA/RNA (Qiagen) according to the manufacturer’s protocol. Genome DNA was bisulfite converted and genome-wide DNA methylation profiling was performed using the Illumina Infinium MethylationEPIC v2.0 BeadChip array. Three biological replicates were included for each condition (NanA-treated and DMSO control). Raw IDAT files and processed β-values were submitted to GEO. Differential methylation analysis was performed using standard pipelines with a Δβ threshold of ≥10% and FDR-adjusted p-value < 0.05.

last: Choudhury


title: Role of DNMT3B in enhancer-transcriptional activities in molecular subtypes of acute myeloid leukemia.

first: Kimberly

last: Stephens

address: 4301 W. Markham St Slot 510

department: Neuroscience

summary: Aberrant epigenetic regulation is a hallmark of acute myeloid leukemia (AML). Here, we investigated the molecular consequences of DNMT3B inhibition in KG1A cells, a model of immature AML, using an integrative multi-omics approach combining RNA-seq, Illumina EPIC DNA methylation arrays, ATAC-seq, and TMT-based quantitative proteomics.

overall_design: Treatment with Nanaomycin A, a selective DNMT3B inhibitor, led to marked transcriptional changes, including upregulation of differentiation- and apoptosis-associated genes and downregulation of stemness programs. These transcriptional shifts were accompanied by widespread promoter hypomethylation, frequently overlapping with regions of increased chromatin accessibility. Notably, several differentially accessible regions coincided with differentially methylated CpGs, indicating coordinated epigenetic remodeling. Proteomic profiling revealed significant changes in protein abundance, some of which aligned with alterations at the transcript and methylation levels. Functional enrichment highlighted pathways involved in chromatin organization, transcriptional regulation, and cell cycle control. Collectively, our findings demonstrate that DNMT3B inhibition drives coordinated epigenetic and transcriptional reprogramming in AML cells, supporting its potential as a therapeutic epigenetic modulator.


title: Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers [nanopore]

city: Saskatoon

first: Franco

last: Vizeacoumar

state: Saskatchewan

address: 4D40 Health Sciences Building, 107 Wiggins Road

institute: University of Saskatchewan

summary: Tumor heterogeneity presents a major clinical challenge. Reactivation of telomerase (hTERT) is a near-universal hallmark of cancer, yet direct inhibition of hTERT has shown limited therapeutic benefit. To uncover tractable telomerase-related vulnerabilities, we applied a synthetic dosage lethality (SDL) strategy to identify genes required only when hTERT is overexpressed. We performed genome-wide CRISPR/Cas9 and shRNA screens across multiple isogenic cell line pairs differing in hTERT expression. From these datasets, 100 high-confidence candidates were prioritized and validated using an arrayed in vitro CRISPR screen and a pooled in vivo CRISPR screen across diverse cancer models, non-malignant cells, and patient-derived organoids. Through this pipeline, we identified FTSJ3, an RNA 2′-O-methyltransferase, as a top SDL target of hTERT. Depletion of FTSJ3 selectively impaired the viability of hTERT-positive cancer cells while sparing normal cells. Mechanistically, FTSJ3 installs 2′-O-methylation on the telomeric RNA TERRA, a modification essential for TERRA stability and function. Loss of FTSJ3 destabilizes TERRA, disrupts recruitment of the histone methyltransferase SUV39H1, and diminishes H3K9 trimethylation and HP1 assembly at sub-telomeric regions. This breakdown of repressive telomeric chromatin leads to genome instability and apoptosis specifically in hTERT-positive cells. These findings highlight SDL as a powerful strategy for uncovering telomerase-dependent liabilities and establish FTSJ3 as a central regulator of telomere stability in telomerase-active cancers. Targeting FTSJ3 enzymatic activity offers a promising therapeutic entry point, acting upstream of TERRA to eliminate telomerase-driven malignancies selectively.

overall_design: Nanopore sequencing for the TERRA Seq was performed on 2 models with and without FTSJ3 knockdown. Total of 4 samples

first: Jared

last: Price

first: Frederick

middle: S

first: Judy

last: Wong

first: Andrew

last: Freywald


title: KAT2B-Mediated Epigenetic Suppression of RAD51C Enhances Olaparib Sensitivity in Colorectal Cancer

city: Mannheim

first: Siche

last: Chen

address: Stockhornstrasse 55, 55

department: Dept. of Experimental Surgery - Cancer Metastasis

country: Germany

institute: Medical Faculty Mannheim, Ruprecht-Karls University of Heidelberg

summary: By blocking poly ADP ribose polymerase (PARP), olaparib prevents DNA damage repair, particularly in tumors that have a BRCA1/2 mutation or are BRCA-positive. Nevertheless, a Phase II study of 33 CRC patients receiving mono-Olaparib therapy revealed that some of these individuals still had resistance to Olaparib while having poor DNA damage repair. RAD51 reversion mutations are a frequent cause of resistance to PARP inhibitors in cancers that do not have BRCA mutations. Though little is known, a number of tactics have been studied when combining PARPi with other inhibitors. Here, we introduce the enzyme KAT2B as a protein involved in transcription that is connected to RAD51C, reducing the levels of RAD51C by lowering the acetylation of Histone H3 (H3K27) at the beginning of the RAD51C gene. Consequently, colorectal cancer cells become more vulnerable to Olaparib therapy. The H3K27ac binding domain is necessary for the transcription of RAD51C. We find that a subpopulation of tumor cells expressing RAD51C have reduced endogenous KAT2B expression. This expression leads to increased DNA damage accumulation and decreased PARPi resistance in RAD51C-expressing cells. According to our findings, RAD51C-expressing cells' RAD51C and PARPi responses are significantly regulated by KAT2B and histone acetylation. This information offers vital new understandings into the molecular requirements for focusing on BRCA-functional malignancies.

overall_design: Examination of DMSO-treated versus Olaparib-treated colorectal cancer cells from RKO cell line representing two treating types in culture.

first: Yue

last: Mi

first: Peiren

last: Xu

first: Jixiang


title: Preclinical activity of brincidofovir in Peripheral T-cell and NK/T-cell Lymphoma

summary:
Introduction: Brincidofovir (BCV) is a novel nucleoside phosphonate analogue with unique dual anti-viral and anti-tumor properties.
Results: BCV demonstrated potent anti-tumor activity in vitro across the majority of cell-lines regardless of EBV positivity, with IC50 values within clinically-achievable human plasma concentrations (2 µg/ml) in 17/25 (68.0%) T/NK-NHL and in 13/19 (68.4%) BCL. In vivo treatment via intraperitoneal BCV (IP, 40mg/kg, 2X per week) significantly inhibited tumor growth in all xenograft models when compared to vehicle control. Notably, RNAseq analysis demonstrated BCV downregulated MYC and MYC-target pathways in T/NK-NHL models. Further mechanistic studies showed that BCV evoked S-phase cell cycle arrest, replication stress, DNA damage and apoptosis, while also triggering STING pathway-mediated interferon responses, PD-L1 expression and immunogenic cell death. In the syngeneic EL4-C57BL/6 model, BCV in combination with anti-PD1 significantly inhibited tumor growth and triggered an immune reaction characterized by highest scores for adaptive immune response, cytokines/chemokines & receptors, cytotoxic cells, dendritic cells, NK CD56dim cells and neutrophils (NanoString Immunology Panel).
Conclusions: Taken together, these results demonstrate a novel role of BCV in the treatment of lymphoma, and suggest potential for combination with checkpoint immunotherapy.

overall_design:
35 samples analyzed
Methods: Activity of BCV was evaluated in forty-four cell-line models, including T/NK-NHL (n=25) and B-cell lymphoma (BCL, n=19), as well as their respective NOD/SCID mice xenograft models (NK/T-cell lymphoma, peripheral T-cell lymphoma, not otherwise specified, TP63-rearranged anaplastic large cell lymphoma, and MYC/BCL2-rearranged diffuse large B-cell lymphoma). Potential in vivo immunogenic effects were examined in a syngeneic EL4-C57BL/6 murine lymphoma model.


title: Pla2g12b is critical for intestinal lipid absorption and C129Y is a dominant negative mutation

city: Mineola

first: M. Mahmood

last: Hussain

state: New York

address: 101 Mineola Blvd.

department: Foundations of Medicine

institute: NYU Grossman Long Island School of Medicine

summary: Lipoprotein assembly in the small intestine and liver is critical for the transport of dietary and endogenous lipids. Pla2g12b has recently been shown to play a role in lipoprotein assembly in mice livers and zebrafish larvae. Pla2g12b knockout and mutant (MUT) mice with the C129Y missense mutation have low plasma cholesterol levels. However, the role of Pla2g12b in the intestine and the reason why C129Y mutation decreases plasma lipids are unknown. We observed that Pla2g12b expression was the highest in the duodenum. Furthermore, male and female chow fed 3-month-old MUT mice and wildtype (WT) mice expressed similar amounts of Pla2g12b protein and several genes in lipid metabolism. Nonetheless, the MUT mice had significantly lower plasma triglyceride (TG), cholesterol, HDL-C, LDL-C, apoB48, and apoB100 levels than WT mice. Several mechanisms for lower plasma lipids and lipoproteins in MUT mice were investigated. C129Y mutation had no effect on the expression of Pla2g12b and several other proteins necessary for lipid transport. Therefore, the low plasma lipid levels in MUT mice were neither due to the absence of Pla2g12b protein nor due to reductions in critical proteins in lipid transport. Next, we addressed the role of Pla2g12b in hepatic lipid mobilization and intestinal lipid absorption. MUT livers exhibited normal TG synthesis, defective TG secretion, and enhanced fat accumulation. MUT mice also showed defective intestinal fat absorption, intracellular lipid accumulation, and elevated fat excretion in the feces. We propose that Pla2g12b is critical for fat absorption and C129Y is a dominant negative mutation.

overall_design: We performed studies in  male Pla2g12b MUT and age matched control  C57BL/6 mice. Both Control and MUT mice were fed regular chow diet for 3-months.

first: Binu

last: Prakash

first: Sujith

last: Rajan

first: Bhargavi

last: Gangula

first: Thomas

last: Palaia

first: Chandana

last: Prakashmurthy

first: Pradeep

last: Kumar Yadav

first: Swati

last: Valmiki

first: Mahmood


title: A Course-Undergraduate Research Experience (CURE) to explore the effect of structural variants on gene expression in C. elegans balancers

city: Calgary

first: Tatiana

last: Maroilley

state: Alberta

address: Tarailo-Graovac

institute: University of Calgary

summary: Bioinformatics, a discipline at the crossroads of Biology and Computational Sciences, also referred to as Computational Biology, is nowadays widely spread in research programs. However, implementing any Bioinformatics projects requires the ability to comprehend biological concepts and apply computational approaches, and rare are the undergraduate programs offering such multi-disciplinary training. In addition, understanding the dynamic between Biology research projects and Bioinformatics analyses is challenging with no real-life experience. Course-based undergraduate research experience (CURE) courses are innovative programs that allow more students to acquire research experience and provide the perfect setting to introduce students to applied bioinformatics. As a part of the Bachelor of Health Sciences of the Cumming School of Medicine at the University of Calgary (Canada), a CURE applied bioinformatics was implemented in the Winter of 2023 to 2025. Students investigated the effect of structural variants (SVs, genetic variants larger than 50 bp) on gene expression in the model organism Caenorhabditis elegans (a hermaphrodite 1-mm long roundworm). The students detected and characterized SVs by analyzing genome and transcriptome sequencing data of C. elegans strains called balancers, as they are known to carry large genomic variations balancing regions of the genome by limiting recombination and allowing maintenance of lethal mutations. They used Galaxy, a public web-based supercomputing resource, but also a local High-Performance computing system, and R, to report different effects of SVs on gene expression and splicing. Students’ research explained the molecular mechanism behind the uncoordinated phenotype caused by the reciprocal translocation eT1(III;V) and uncovered unexpected effects on gene expression on an understudied gene. We evaluated the course’s impact on student learning journeys and showed that the CURE favored students’ understanding of the Bioinformatics field and fostered their research interest. We provide here guidelines to facilitate the CURE implementations to improve access for undergraduate students to bioinformatics research experiences.

overall_design: RNA-Seq (bulk) of the C. elegans strains BC986 and N2 to explore the effect of SVs of gene expression

first: Victoria

last: Barbosa

first: Rumika

last: Mascarenhas

first: Suzanne

last: Ferris

first: Catherine

last: Diao

first: David

last: Anderson

first: Maja

last: Tarailo-Graovac


title: Tumor-associated macrophage (TAM) polarizatoin in organoids

city: Fukuoka

first: Michitaka

last: Nakano

state: Fukuoka

address: 3-1-1, Maidashi, Higashi-ku

department: Department of Medicine and Biosystemic Sciences

institute: Kyushu University

summary: We performed polarization of organoid TAM toward M1- or M2- phenotyope by adding IFN-γ for M1- and IL-4 for M2- polarization. IFN-γ  treatment induced IFN-γ- and M1 macrophage related gene expressions, and  IL-4 induced IL-4 and M2 macrophage related gene expressions in organoid TAM.

overall_design: ALI clear cell renal cell carcinoma (ccRCC) organoids were cultured for day 8 after surgical resection. IFN-γ or IL-4 were added into the culture for 24 hours.

first: Lyong

last: Heo


title: Orgaonid modeling of tumor-assciated macrophages (TAM)

summary: We characterized TAM in human ALI tumor orgaonid that contains tumor cells and immune cells without artificial reconstitution. Organid TAM preserved subset diversity in single cell transciptome compared with fresh tissue. We found that anti-CD47 TAM targeted therapy induced phenotypic change of TAM from C1Q+ to SPP1+ TAM. T cell cytotoxicity related gene induction by anti-CD47 was prominent in clear cell renal carcinoma (ccRCC) organoids.

overall_design: TAM gene expression from fresh tumor tissues and air liquid intercace (ALI) organoids were analyzed using scRNA seq by FACS sorted immune cells or TAM population. Library were processed using 10X Genomics Chromium single cell 5' platform. ALI organoids were generated from clear cell renal cell carcinoma (ccRCC) and non-small cell lung cancer (NSCLC). ALI organoids were treated IgG1 isotype control and anti-CD47 for 8 days.


title: miR-34a deficiency in an animal model of Alzheimer's disease

city: Peoria

first: Ken-ichiro

last: Fukuchi

state: Illinois

address: One Illini Dr

department: Cancer Biology and Pharmacology

institute: University of Illinois College of Medicine

summary: To investigate the role of miR-34a in Alzheimer's disease, we have created an animal model of Alzheimer's disease with miR-34a deficiency.

overall_design: Comparative gene expression profiling analysis of RNA-seq data from miR-34a-sufficient and -deficient TgSwDI mice (an animal model of Alzheimer's disease).

first: Junling

last: Yang

first: Mark

last: Maienschein-Cline

first: Carlos

last: Martinez


title: Atypical memory B cells form a pre-plasmacellular reservoir for steady-state IgD responses to common nasopharyngeal antigens

city: Barcelona

first: Júlia

last: Perera-Bel

address: Doctor Aiguader, 88

department: MARData-BU

country: Spain

institute: Hospital del Mar Research Institute

summary: The human nasopharyngeal mucosa includes organized lymphoepithelial structures continually engaged in frontline immune responses to aerodigestive antigens. Advancing our understanding of these responses might lead to the development of new strategies for the prevention and treatment of common immune disorders such as allergies. Here we identified a hitherto elusive tonsillar subset of atypical IgD class-switched IgD+IgM- memory (IgD-ME) B cells that were clonally related to IgD+IgM− germinal center (IgD-GC) B cells and IgD-secreting IgD+IgM− plasma cells (IgD-PCs) but not anergic IgD+IgM− B cells. Consistent with their pre-plasmacellular properties, IgD-ME B cells served as preferential precursors of IgD-PCs over IgD-GC B cells. IgD antibodies from IgD+IgM− cells acquired reactivity to multiple oral, airborne and commensal antigens through a mutation-dependent pathway involving both innate and adaptive signals. Thus, IgD-ME B cells may form a ready-to-use pre-plasmacellular reservoir for steady-state IgD responses likely aimed at enhancing nasopharyngeal homeostasis.

overall_design: The primary aim of this study was to identify tonsillar IgD-ME B cells and characterize their phenotype, clonal architecture, transcriptional signatures, and reactivity properties. To address these questions and better understand the ontogeny and regulation of IgD responses, we combined standard and high-throughput approaches with sorting of 13 tonsillar B cell subsets, immunoglobulin gene repertoire analysis, cloning and expression of recombinant IgD mAbs, and reactivity analysis of these antibodies as well as native IgD pAbs from both healthy controls and patients with rare inborn errors of immunity. We first defined the topography, phenotype, transcriptional signatures, ultrastructural properties, and fundamental functions of tonsillar IgD-ME B cells as well as canonical IgG-ME and IgA-ME B cells by combining standard approaches with high-dimensional flow cytometry, RNA sequencing, and transmission electron microscopy. To further investigate the clonal architecture of IgD-ME B cells and their relationship with other tonsillar IgD class-switched B cell subsets, we performed high-throughput Ig gene sequencing, followed by clonal lineage and phylogeny analyses. Next, Ig cloning-expression technology, ELISA and bacterial flow cytometry were applied to assess the reactivity of secreted IgD to common nasopharyngeal antigens. Finally, total serum IgD from patients with rare inborn errors of immunity provided insights into the in vivo regulation of IgD responses. Experiments were performed 2-6 times at least in triplicate (where applicable) and showed excellent reproducibility.

first: Andrea

last: Cerutti

first: Martyna

last: Filipska


title: Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers [sequencing]

first: Franco

middle: J

last: Vizeacoumar

overall_design: Genome-wide CRISPR knock-out screen for synthetic dosage lethal interactions of telomerase-overexpressing cells. There are two model cells used and for each model there are 6 samples done in duplicates. Total of 24 samples.

first: Jared

last: Price

first: Frederick

first: Omar

last: Abuhussein

first: Judy

last: Wong

first: Andrew

last: Freywald


title: Cell fate specification during respiratory development requires ARID1A-containing canonical BAF complex activity

status: Public on Mar 17 2026

city: CINCINNATI

first: William

last: Zacharias

state: OH

address: 3333 BURNET AVE

institute: Cincinnati Children's Hospital Medical Center

summary: Mammalian lung development requires coordinated gene regulation to drive lung bud formation, branching morphogenesis, proximal-distal patterning, and epithelial specification. While key transcriptional and signaling regulators are known, the epigenetic regulators are less well studied. Here, we identify the canonical BAF complex as essential for lung epithelial development. Complete loss of BAF complex causes failure of lung formation, and selective deletion of ARID1A leads to loss of distal patterning and reduced alveolar type 1 (AT1) cell differentiation, with emergence of a highly proliferative cell state defined by joint activation of YAP and WNT signaling and loss of BMP response. Epigenomic analyses demonstrate broad failure of cell type-specific enhancer activation. Notably, exogenous BMP4 rescues distal differentiation in embryonic murine lung organoids, while YAP and WNT signaling require functional BAF complex. These data demonstrate a requirement for BAF complex activity during lung epithelial development and reveal a surprising differential specificity between signaling pathways.

overall_design: scRNAseq and scATACseq of ARID1A knockout respiratory endoderm and WT respiratory endoderm at E18.5

first: Zacharias

last: William J

first: Lee

last: Hyunwook


title: Ancestral Bisphenol A Exposure Induces Sexually Dimorphic Nonalcoholic Fatty Liver Disease Through Transgenerational Transmission of Sperm Gene Body CpG Island Methylation

city: Columbia

first: Ramji

last: Bhandari

address: 1200 University Ave

department: Division of Biological Sciences

institute: University of Missouri

type: Methylation profiling by high throughput sequencing

summary: Environmental exposures induce heritable disease through germline epigenetic alterations, yet how epimutations establish sex-biased metabolic disease in descendants remains unclear. We demonstrate that ancestral bisphenol A (BPA) exposure induces sexually dimorphic nonalcoholic fatty liver disease (NAFLD) in unexposed medaka fish offspring through stable sperm DNA methylation transmission. Females developed severe macrovesicular steatosis with 5,376 differentially expressed genes (DEGs), enrichment for human NAFLD signatures, dysregulated clinically validated biomarkers, and suppressed mitochondrial electron transport chain genes, whereas males showed attenuated microvesicular steatosis with only 306 DEGs. Promoter hypermethylation silenced key hepatic master regulators, HNF4A in females and SREBF1 in males. Whole‑genome bisulfite sequencing revealed twice as many differentially methylated regions (DMRs) in females versus males, enriched in exons, 3′ UTRs, and gene-body CpG-islands versus promoters, indicating non‑promoter‑centric regulation. Critically, 61 gene-body CpG-island DMRs persisted across F0 sperm, F1 sperm, and F2 livers, with mTOR signaling emerging uniquely in F2 liver consistent with nutrient-sensing dysregulation and lipogenesis, while Notch signaling was exclusively enriched in F2 females, aligning with fibrogenic progression. These findings establish gene-body CpG-island methylation as a principal conduit for sex‑specific transgenerational epigenetic inheritance linking ancestral BPA exposure to metabolic liver disease.

overall_design: Whole-genome bisulfite sequencing (WGBS) was performed on the sperm from three biological replicates of both BPA and control lineages of Medaka fish from the F0 and F1 generations. Additionally, WGBS was conducted on the liver tissue of three biological replicates of male and female Medaka fish from the F2 generation for both BPA and control lineages.

first: Sourav

last: Chakraborty

first: Santosh

last: Anand


title: Effect of AMP-dT on lymph node immune response in mouse

city: Boston

first: Martin

last: Steinbuck

overall_design: 3 groups of mice were injected with the following vaccines: mock control (SARS-CoV2-RBD without adjuvant), SOL dT (SARS-CoV2-RBD with dT), AMP-dT (SARS-CoV2-RBD with AMP-dT). 4 time points (2h, 6h, 24h, 72h) with 2 mice per time point.

first: Peter

last: DeMuth

first: Lochana

last: Seenappa

first: Erica

last: Palmer


title: Aging and the pathophysiology of pulmonary Mycobacterium avium complex (MAC) disease

city: TSUKUBA

first: Masashi

last: Matsuyama

state: IBARAKI

address: 1-1-1 AMAKUBO

department: respiratory medicine

institute: Tsukuba university

summary: We infected 18-month-old mice (old mice) and 9-week-old mice (young mice) with 1 × 10⁷ CFU of Mycobacterium avium via the respiratory tract for comparison analysis. Two months post-infection, both bacterial loads and mortality rates were significantly higher in old mice compared to young mice. RNA-seq analysis of lung tissues were performed.

overall_design: Total RNA from lung tissues was extracted using TRIzol with a homogenizer in 12 individual samples (3 from the lungs of the young mice treated with PBS, 3 from the lungs of the old mice treated with PBS, 3 from the lungs of the young mice infected with M. avium for 2 months, and 3 from the lungs of the old mice infected with M. avium for 2 months).

first: Sosuke

last: Matsumura

first: Chio

last: Sakai

first: Masayuki

last: Nakajima

first: Masafumi

last: Muratani

first: Nobuyuki

last: Hizawa


title: Reanalysis of ChIP-Seq of PRJEB5782

first: Parmit

middle: Kumar

last: Singh

state: MA

address: 450 Brookline Avenue

department: Department of Cancer Immunology and Virology

institute: Dana-Farber Cancer Institute

summary: In this reanalysis, 20 ERR series were reanalyzed for ChIp-Seq data.

overall_design:
Raw files were downloaded from ArrayExpress BioStudies (E-MTAB-2360) and aligned against the UCSC hg19 human genome using Bowtie2 with the parameters described in the original study (PMID: 24824428). The aligned files were filtered for unique alignments and converted to BAM format using SAMtools (version 1.3.1). Resulting BAM files were converted to BEDPE format with BEDtools, and columns 1, 2, 3, 7, 8, and 9 were selected. Significant peaks were identified using SICER. The following accession numbers served as input controls: ERR453856 for ERR453847, ERR453850 for ERR453858, ERR453846 for ERR453851, ERR453854 for ERR453857, ERR453852 for ERR453859, ERR453845 for ERR453853, ERR453848 for ERR453844, and ERR453849 for ERR453855.
Data processing: Raw paired-end sequences were trimmed for adaptor contamination using TrimGalore (v0.6.6) with the command: trim_galore --paired -a AGATCGGAAGAGCG --stringency 6 -e 0.1 -q 20 --length 20 --fastqc -o <output_folder> <read1.fastq> <read2.fastq> Trimming required a minimum 6 bp overlap between the read and adaptor and allowed up to 10% mismatches. Reads with low-quality bases (Phred score <20) or lengths <20 bp were removed. FastQC was used to generate quality reports for the trimmed reads. Trimmed reads were aligned to the hg19 genome using Bowtie2 (v2.3.4.3) with the following command: bowtie2 -p 8 -I 80 -X 500 --no-mixed -3 1 -x <hg19_index> -1 <read1_trimmed> -2 <read2_trimmed> -S <output.sam> Only properly paired reads with insert sizes of 80–500 bp were retained, and 1 bp was trimmed from the 3’ end prior to alignment. Unique alignments were filtered using Samtools (v1.3.1) with: samtools view -q 20 -F 1024 -o <output.bam> -b -h <input.sam> This retained reads with mapping quality ≥20 and removed PCR duplicates. BAM files were converted to BEDPE format using Bedtools (v2.27.1) via: bedtools bamtobed -bedpe -i <input.bam> > <output.bed> From the resulting BEDPE files, columns 1–3 and 7-9 were extracted to generate BED files containing genomic coordinates of aligned reads, which were used for peak calling with SICER (v1.1). SICER was run with the following command: sicer -t <treatment_plus.bed> -c <control_plus.bed> -s hg19 -w 200 -egf 0.85 -fdr 0.01 SICER scanned the genome in 200 bp windows, accounting for 85% mappable genome fraction, and called peaks at a false discovery rate <1%. ChIP-seq samples were analyzed using matched controls as follows: ERR453856 for ERR453847, ERR453850 for ERR453858, ERR453846 for ERR453851, ERR453854 for ERR453857, ERR453852 for ERR453859, ERR453845 for ERR453853, ERR453848 for ERR453844, and ERR453849 for ERR453855.


title: Epigenetic control of telomeric RNA maintains heterochromatin in telomerase-driven cancers

first: Franco

last: Vizeacoumar

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

overall_design: Refer to individual Series


title: DHX9 sustains hematopoietic stem cell function in cooperation with H3 acetylation [RNA-Seq]

first: Minhui

last: Shi

institute: University of Science and Technology of China

summary: To elucidate the mechanisms underlying the role of Dhx9 deficiency in hematopoiesis, we performed RNA sequencing on lineage nagative cells from DHX9 hematopoietic cell-specific conditional knockout mice(cKO) and those from WT mice.

overall_design: RNA-seq analyses on lineage nagative cells from Dhx9f/f;MX1 mice (cKO) in comparison with those from Dhx9f/f mice (WT).

first: Huaiping

last: Zhu

first: MengQing

last: Gao