title: Quorum sensing regulator LsrR modulates resistance to oxidative stress by interfering with sulfate assimilation in avian pathogenic Escherichia coli

city: Shanghai

first: Lan

middle: fang

last: Kong

address: 518 Ziyue Road, Shanghai

institute: Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences

summary: Prokaryotes and eukaryotes endogenously generate the gaseous molecule hydrogen sulfide (H2S), which has been identified as a novel signaling molecule. Bacterial H2S plays a protective role against reactive oxygen species (ROS) and antibiotic-induced cellular damage. Endogenous H2S can be produced by the assimilation pathway of sulfate and thiosulfate in Escherichia coli. The transcription regulator LsrR influences various bacterial characteristics. The results of the present study revealed that avian pathogenic E. coli (APEC) lacking LsrR exhibited increased H2S production and enhanced tolerance to oxidative stress. Transcriptome sequencing revealed the upregulation of genes related to the sulfate assimilation pathway after the deletion of lsrR. Further investigation demonstrated that LsrR, acts as a transcriptional repressor, binds directly to the promoter region of cysPUWAM and interacts with both CysJ and CysN, thereby inhibiting exogenous sulfate assimilation and decreasing the oxidative stress resistance of APEC. Additionally, the absence of lsrR facilitated the survival of APEC94 in macrophage RAW264.7 cells. Our findings suggest that LsrR represses resistance to oxidative stress in APEC by interfering with the sulfate assimilation pathway and provide valuable insights into host‒pathogen interactions.

overall_design: RNA-seg profiling of wild type APEC94 cells and lsrR deletion mutant(APEC94ΔlsrR) at the stable mid-exponential (mid-log) phase.

first: Lanfang

first: Chuntian

last: Tu

first: Xiangjun

last: Song

first: Yang

first: Zhihao

first: Zhaoguo

first: Wenyan

last: Fan

first: Lianhua

last: Nie

first: Wei

last: Jiang

first: Xiangan

last: Han


title: Integrated Transcriptomics and Metabolomics Analyses Revealed that Phenylpropanoid Metabolism Regulates the Complex Salt-alkali Tolerance in Allium mongolicum

status: Public on Feb 08 2026

city: Hohhot

first: Zhenyu

last: Cao

state: Inner Mongolia

address: No. 306, Zhaowuda Road

country: China

institute: Inner MongoliaAgricultural University

type: Expression profiling by high throughput sequencing

summary: Allium mongolicum, a xerophytic industrial plant native to the Mongolian Plateau, demonstrates notable stress resistance, though its salt-alkali tolerance mechanisms remain poorly understood. This study integrates physiological assessments, transcriptomics, metabolomics, and full-length transcriptome analyses to uncover its adaptive mechanisms under salt-alkali stress.A comprehensive full-length transcriptome was constructed under these conditions, comprising 30,117 non-redundant genes, alongside significant trends observed in the activities of antioxidant enzymes and key enzymes in the phenylpropanoid pathway. Combined transcriptomic and metabolomic analyses identified key genes and metabolites in the phenylpropanoid pathway as central to salt-alkali tolerance. WGCNA further highlighted critical genes, such as AmCOMT1, AmHSP18, and AmPPL7, with functional validation of AmCOMT1 and AmHSP18 confirming transcriptome reliability. The salt tolerance function of AmCOMT1 has been validated through overexpression in plants, and the binding interaction with AmERF4 has also been confirmed.A proposed model suggests A. mongolicum mitigates salt-alkali stress via reactive oxygen species scavenging, osmotic regulation, and structural support, providing valuable insights for breeding salt-tolerant crops and enhancing its agricultural applications.

overall_design: In this study, plump and similarly sized seeds of Allium mongolicum were used for germination on paper. The germination conditions were set at 20°C in the dark for 7 days, after which seeds with good germination status were selected and transplanted into pots filled with substrate soil. The cultivation conditions were established at 25°C with 12 hours of light and 12 hours of darkness, maintaining a humidity of 70%. After 45 days of seedling growth, the seedlings were transferred to 1/2 Hoagland nutrient solution for an additional 7 days, followed by exposure to composite saline-alkali stress treatment. The composition of the saline-alkali solution was NaCl:Na2SO4:NaHCO3:Na2CO3 = 1:9:9:1, the total salinity concentration is 150 mmol/L, with treatment durations of 0 hours (control group CK), 24 hours (T24), 48 hours (T48), and 72 hours (T72). Under this salinity composition(Hou et al., 2023), the expression of salt-related genes significantly increased. For each treatment group, 20 seedlings were randomly selected to obtain root samples, which were immediately frozen in liquid nitrogen for further experiments.


title: RNA-seq of the brain and spinal cord of NTDs fetal mice at day 9.5

city: Taiyuan

first: lu

last: li

address: Xinjian South Road, Yingze District

institute: Shanxi Medical University

summary: To investigate the genes exprsssion change  in the brain and spine at E9.5 days in the folate-deficient NTDs mouse model, we established NTDs mouse model and normal mouse model.

overall_design: Male and female CD-1 mice were fed on low-folate diet for more than 8 weeks. Sexually matured individuals were mated overnight; vaginal plug was detected at 8:00 am in the following morning and was designated as E0.5 day. NTDs mouse models were  induced by intraperitoneal injection with 1.5 mg/kg of MTX (Sigma–Aldrich, USA) on E7.5. On E9.5, pregnant mice were euthanized by cervical dislocation, and the phenotypes of the fetuses were observed under a microscope. All samples with NTDs clinical manifestations were collected for experiments.We then performed gene expression profiling using data from four different RNA-seq.

first: Lu

last: Li

first: Jianting

first: Wenbin

last: Ren

first: Zhihua


title: Reversibility of Nuclear and 3D Genomic Changes in Non-Cancerous Fibroblasts After Constricted Migration

status: Public on Feb 07 2026

city: Knoxville

first: Rachel

middle: Patton

last: McCord

state: TN

address: 309 Mossman Bldg. 1311 Cumberland Ave

department: BCMB

country: USA

institute: University of Tennessee

summary: Metastatic cancer cells and healthy fibroblasts must traverse constrictive spaces to reach secondary sites. After passing through multiple constrictions, cancer cells often experience stable changes to their nucleus morphology, 3D genome structure, and migratory phenotype. Here, we investigate whether fibroblasts (BJ-5ta), which are non-cancerous and have an inherent ability to migrate to fulfill roles in wound repair, likewise experience nuclear and 3D genomic changes with constricted migration. We find that BJ-5ta cells do not get progressively better at migrating with sequential attempts but do experience nuclear deformations and 3D genome alterations at the compartment level after constricted migration. Transient compartment shifts spatially rearranged genes associated with preparation for and response to migration. Unlike the stable changes associated with long term phenotype changes in cancer cells, however, the nucleus deformations recovered back to unmigrated levels following proliferation and cell movement. Some compartment changes persist and might influence responses to future stimuli, but most 3D genome changes revert to the unmigrated state after cell proliferation. Our study shows that non-cancerous migratory cells are not more robust against alterations caused by constricted migration but can recover from the ones that do arise more readily than cancer cells.

overall_design: The 3D genome structure of BJ-5ta cells was analyzed using chromosome conformation capture (Hi-C) in the following experimental conditions: standard culture conditions, starvation (overnight in serum-free media) followed by 24 hours exposure to Fibroblast Growth Factor, 1 round of constricted migration through 5 micron pores, 1 round of constricted migration followed by 96 hours of recovery, or 5 rounds of constricted migration with recovery time in between each round.

first: Christopher

last: Playter

first: Samuel

middle: J

last: Benson

first: Renata

last: Dos Reis Marques

first: Preston

last: Young

first: Timothy

last: Simmons

first: Kathryn

last: Perry

first: Amanda

middle: K

last: Swets

middle: P


title: scRNA-seq data of spleen immune cells from Vehicle- and Glutoborin-treated mice [replicate experiment]

city: Beijing

first: Weixuan

last: Wang

address: No. 38 Xueyuan Road, Haidian District

institute: Peking University

summary: To determine whether Glutoborin exerts its immunomodulatory effects by disrupting interactions between MZMs and MZBs, we performed scRNA-seq to analyze the immune microenvironment of spleens from Pb-infected mice treated with Vehicle or Glutoborin.

overall_design: Mice were intraperitoneally injected with 1 × 10⁴ iRBCs, and on days 2 and 4 post-infection Vehicle and Glutoborin were administered. On day 5 post-infection spleens from both group were collected to isolate lymphocytes. CD45+ cells were then sorted by flow cytometry for subsequent single-cell sequencing analysis

first: Xin

last: Sun

first: Dan

last: Lv


title: SND1-Tudor Recognition of Methylated S6K2 Regulates Pancreatic Homeostasis

city: Houston

first: Bin

last: Liu

state: TX

address: 1515 Holcombe BLVD

department: epigenetics and molecular carcinogenesis

institute: University of Texas MD Anderson Cancer Center

summary: Staphylococcal nuclease and Tudor domain containing 1 (SND1) is a multifunctional protein with four SN domains and a Tudor domain that recognizes symmetric dimethylarginine (SDMA) modifications. Although highly enriched in the pancreas, its role in this tissue remains unclear.  Here, we show that loss of SND1 SDMA-reader activity—via knockout or a Y766L point mutation in the Tudor domain—leads to reduced S6 phosphorylation. Mechanistically, SND1 binds SDMA-modified arginines within the C-terminal glycine- and arginine-rich (GAR) motif of S6K2, a kinase also highly expressed in the pancreas. To evaluate the functional relevance of this interaction, we generated S6k2 RK mice carrying lysine substitutions at the GAR arginines, which abolished SND1 recognition. Transcriptomic profiling revealed a strong overlap in dysregulated genes and pathways—including the unfolded protein response and metabolic programs between Snd1 KI and S6k2 RK pancreata. These findings define a methylation-dependent SND1-S6K2 signaling axis as a critical regulator of pancreatic homeostasis.

overall_design: S6k2 RK, Snd1 KI, and the WT littermate mice (8-week old, n=3 per group) were euthanized via CO₂ inhalation. The pancreas was rapidly collected and snap-frozen in liquid nitrogen. Frozen tissues were ground into a fine powder, and appropriate amounts were transferred into 1.5 mL Eppendorf tubes for submission to Admera Health for standard RNA sequencing.

first: Yalong

first: Mark

middle: T

last: Bedford


title: The role of Senp1 in  regulating  CD8+ T cells activation

first: Cen

last: Jiang

address: 227 South Chongqing Road

institute: Shanghai Jiao Tong University

summary: To better understan the role of Senp1 in regulating CD8+ T cells activation, we performed a transcriptional analysis (RNA-seq) to compare gene expression patterns between wild type and Senp1-deficient naïve CD8+ T cells or activated by anti-CD3/CD28.

overall_design: Senp1 WT/CKO naïve CD8+ T cells were isolated and stimulated with anti-CD3 (5 μg/ml) and anti-CD28 (1 μg/ml) for 48 h  or not for RNA extraction.


title: Transcriptome changes in human PSC-derived cardiomyocytes induced by doxorubicin II

city: Kyoto

first: Tomoya

last: Kitani

address: 465 Kajii-cho Kawaramachi-Hirokoji Kamigyo-ku

country: Japan

institute: Kyoto Prefectural University of Medicine

summary: Doxorubicin (DOX) is one of the most effective chemotherapeutic agents for various types of cancers. However, DOX often causes cardiotoxicity referred to as DOX-induced cardiomyopathy (DIC). In this experiment, transcriptome changes induced by doxorubicin were examined in  human PSC-derived cardiomyocytes.

overall_design: Global gene expression changes were examined using RNA-seq in human PSC-derived cardiomyocytes with 1 μM doxorubicin or DMSO control treatement for 24h.


title: A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [Methylation array]

city: Memphis

first: Paul

middle: A.

last: Northcott

address: 262 Danny Thomas Place

department: Developmental Neurobiology

institute: St. Jude Children's Research Hospital

type: Methylation profiling by genome tiling array

summary: Mouse tumor methylation profiling by MouseMethylation Beadchips (MM285) platform

overall_design: The study utilizes the MouseMethylation Beadchips (MM285) platform, focusing on the epigenetic profiling of mouse tumors. We compare PB GEM models to human PB methylation profiles.

first: Brian

last: Gudenas

middle: A


title: A Wnt7a-Hoxa13 pathway for Müllerian duct fusion at the body midline for uterine morphogenesis

summary: During embryonic development, the Müllerian ducts and adjacent mesenchyme differentiate into the tissues of the oviducts, uterus, cervix, and upper vagina. Variations in the fusion process can alter typical uterine morphology, correlating with an increased incidence of infertility, high-risk pregnancy, and miscarriage. We show that Wnt7a is required for Müllerian duct fusion at the body midline to generate the bipartite uterus of the mouse. Wnt7a null female mice form Müllerian ducts, but the ducts do not fuse at the midline resulting in a duplex reproductive tract (two separate uterine horns, two cervices, and two vaginas). Spatial transcriptome analysis of Wnt7a null and control fusion regions identified a downregulation of Hoxa13 in Wnt7a-null mesenchyme compared to wild type. Reduction in Hoxa13/HOXA13 is associated with didelphic uterine formation. These studies identify a Wnt7a-Hoxa13 genetic pathway that regulates uterine morphology.

overall_design: Spatial transcriptomics is an approach that quantifies gene transcripts at specific locations in tissues. We used the NanoString GeoMx® Digital Spatial Profiling transcriptomic platform to analyze wild-type and Wnt7a null embryos at E13.5 (prior to Müllerian duct fusion) and E14.5 (at apposition of the two Müllerian ducts at the body midline with initial basement membrane breakdown) at the region of Müllerian duct fusion at the body midline. Three biological replicates for each genotype and time point were analyzed for a total of 12 biological replicates. Laminin immunofluorescence was used to identify Regions of Interest (ROI). ROI1 was the Müllerian duct epithelial cells (MDE), and ROI2 was the Müllerian duct mesenchymal cells (MDM) adjacent to the Müllerian ducts for a total of 24 ROIs.

first: Richard

middle: R

last: Behringer

first: Diana

last: Machado


title: Peripheral blood mononuclear cells single-cell landscape of newly diagnosed NK/T cell lymphoma patients

first: Xiaozhen

last: Liang

address: Life Science Research Building 320 Yueyang Road, Xuhui District

institute: Shanghai Institute of Materia Medica Chinese Academy of Sciences

summary: Natural killer/T cell lymphoma (NKTCL) is a rare and aggressive form of non-Hodgkin's lymphoma associated with Epstein-Barr Virus (EBV) infection.The recent advancement of multi-omics technologies has significantly enhanced our understanding of NKTCL disease biology, including genetics, transcription landscape, variations of EBV strain, and microenvironments. Emerging evidence suggests that immunoprofiling of peripheral blood mononuclear cells (PBMCs) is associated with the treatment response of cancer patients and can be used to guide clinical trials and therapy. In this study, we utilized single-cell RNA sequencing (scRNA-seq) to comprehensively characterize the phenotypic landscape of PBMCs in newly diagnosed patients with NKTCL. This research offers a valuable peripheral blood-based signature for newly diagnosed NKTCL, which could be a crucial resource for further investigations into the pathogenesis of NKTCL and the optimization of therapeutic regimens.

overall_design: scRNA-seq profiling of PBMCs from healthy donors and newly diagnosed NKTCL patients

first: Rong

last: Tao

first: Ran

last: Jia

first: Chuanxu


title: Pharmacological elevation of lactate alleviates sepsis via histone lactylation-induced IL-10 production

city: shanghai

first: qian

last: fang

address: No. 3, Pan Shan Road

institute: Changhai Hospital

summary: Despite that lactate accumulation is deemed to be a marker of severe sepsis, lactate-driven histone lactylation induces transcription of homeostatic genes. Thus, the biological roles of lactate in sepsis remain unknown. Here, we report that amlexanox, an anti-inflammatory drug, improves survival, mitigates multiorgan dysfunction, and suppresses inflammatory infiltrates in endotoxemia and sepsis. Mechanistically, amlexanox elevates intracellular lactate to enhance histone lactylation of IL10 gene promoter and IL-10 production to alleviate sepsis. Blocking IL-10 receptor nearly abrogates therapeutic effect of amlexanox, and inhibiting lactate production abrogates amlexanox-induced IL-10. Amlexanox treatment significantly downregulates gene expression of electron transport chain, indicating it elevates lactate level by breaking aerobic respiration. Importantly, in vivo sodium lactate administration improves survival in endotoxemia. Our study clarifies that elevating lactate-mediated histone lactylation plays a protective role in sepsis, and amlexanox is a potential drug for sepsis.

overall_design: To investigate the mechanisms that amlexanox ameliorates sepsis, RNA-sequencing analysis of peritoneal lavage cells from amlexanox and vehicle treated CLP mice were performed.


title: Multicellular origins of ovarian inflammaging [Spatial Transcriptomics]

city: Kansas City

first: Anna

middle: M

last: Galligos

state: KS

address: 1000 E 50th Street

institute: Stowers Institute for Medical Research

summary: Age-dependent reproductive decline has become a significant global health concern as the average maternal age at first birth increases. Fertility loss associated with reproductive aging is driven in part by alterations to ovarian composition and function, dysregulation of folliculogenesis and increased inflammatory signaling. Our understanding of the molecular changes underlying ovarian aging has been expanded by single cell and spatial transcriptomic studies, which identified infiltration of immune cells as a feature of ovarian aging. However, the function of these age-associated immune cells and their potential contributions to the inflammaging phenotype remains unclear. In this study we integrate single cell and spatial transcriptomics to define changes in the composition and intercellular signaling in the aging mouse ovary. We identify specific macrophage and T cell subpopulations that increase with age and are key sources of pro-inflammatory signaling in old ovaries. Further, we predict bidirectional signaling between these pro-inflammatory cells and granulosa cell populations that may impair follicular growth and development while promoting immune cell recruitment. These findings provide new insights into the mechanisms that drive ovarian inflammaging.

overall_design:
Spatial transcriptomics was performed on histological sections of whole ovaries isolated from 2 month old and ~14 month old C57BL6/J female mice.
Slide-seq

first: Joseph

last: Varberg

first: Wei-Ting

last: Yueh

first: Aubrey

last: Converse

first: Seth

last: Malloy

first: Fatimah

last: Aljubran

first: Francesca

middle: E

last: Duncan

first: Jennifer

middle: L

last: Gerton


title: High-frequency recurrence index for predicting multiple recurrences in non-muscle-invasive bladder cancer (Discovery cohort)

city: Yuseong-gu

first: Seung Woo

last: Baek

state: Daejeon

address: Gwahak-ro 125

country: South Korea

institute: Korea Research Institute Biology & Biotechnology

summary: Non-muscle invasive bladder cancer (NMIBC) has a recurrence rate of more than 50% after transurethral resection (TUR) and Calmette-Guérin (BCG) treatment. This study aimed to develop a high-frequency recurrence index (HfRI) to predict multiple recurrences in NMIBC patients and guide personalized treatment strategies. In this study, we analyzed transcriptome data (Discovery cohort) of 45 high-risk NMIBC patients who received intravesical BCG treatment, including patients with >=2 recurrences, to identify genes significantly associated with high-frequency recurrence and construct a signature. In addition, we validated the predictive performance using transcriptome data of 94 patients (Discovery cohort).

overall_design: A validation cohort of 45 NMIBC patients from Chungbuk National University Hospital is RNAseq transcriptome data produced for high-frequency recurrence of NMIBC.

first: Seung-Woo

first: Young-Joon

last: Byun


title: A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [ATAC-seq]

first: Paul

last: Northcott

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Pineoblastoma is a clinically aggressive childhood brain tumor composed of distinct molecular subgroups with divergent driver genes, demographics, and clinical outcomes. To identify developmental origins and mechanisms governing disease pathogenesis, we derive single-cell transcriptomes from pineal parenchymal tumors, aligning malignant cells with developmental counterparts to retrace cellular origins. Integrative computational analyses map pineoblastoma origins to transient, cycling pinealocyte progenitors during development. Lineage-specific perturbation of suspected drivers in the early pineal gland yields preclinical models representative of consensus molecular subgroups. Multi-omic characterization of patient tumors and these models uncovers a tumor-associated photoreceptor signature (TAPS) common to pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this signature within respective cellular origins establishes a developmental basis for molecular similarities between entities. Photoreceptor signature constituents are selective dependencies across these anatomically distinct central nervous system malignancies, motivating future studies evaluating developmentally encoded programs of malignancy as potential therapeutic liabilities.

overall_design: Chromatin accessibility profiling of PB-Rb1 mouse models and normal pineal gland.


title: Real-time quantitative PCR analysis of intestine of gilthead seabream

city: Almería

first: Alba

last: Galafat Díaz

state: Almería

address: Carr. Sacramento s/n

country: Spain

institute: University of Almería

summary: Anterior intestines were processed to extract RNA using the Total RNA Kit I (ENZA, Omega Bio-Tek), incorporating a Dnase tratment with the DNA free Kit (Rnase-Free Dnase I Set, Omea Bio-tek). Reverse transcription was performed using the RevertAid First Strand cDNA Synthesis Kit (Thermo Scientific #K1691). Real-time 1PCR amplifications were conducted in duplicates using a BIO-RAD CFX connect system (Bio-Rad Laboratories, Hercules) on 384-well-plates.

overall_design: qPCR gene epression profiling. The intestines of four fish per tank were used and treated separately as indicated in the summary.

first: A

last: Barany

first: J

last: Martos-Sitcha


title: Gene expression response in sulfur-starved pine seedlings subjected to a sulfate pulse

city: Malaga

first: Rafael

last: Cañas

address: Facultad de Ciencias, Campus de Teatinos

department: Biología Molecular y Bioquímica

institute: Universidad de Málaga

summary: This study analyzed changes in gene expression in the organs (needles, cotyledons, stem, and roots) of maritime pine seedlings 24 hours after being watered with 0.5 mM potassium sulfate. Seedlings one month after germination were watered for three months with 0.3 mM KNO3 once a week to induce sulfur starvation. Control seedlings were watered with 1 mM KCl. This work was funded by the Spanish Agencia Estatal de Investigación (AEI), grant number PID2024-156791NB-I00.

overall_design: One month after germination, the seedlings were watered for three months with 0.3 mM KNO3 once a week to induce sulfur deficiency. The pine seedlings were then divided into two groups. The first control group (C) was watered with 1 mM KCl, while the second experimental group (S) was watered with 0.5 mM K2SO4. Twenty-four hours after watering, samples were taken from four organs: needles, cotyledons, stems, and roots. Each of these was immediately frozen in liquid nitrogen. Three biological replicates were obtained by grouping samples from 13-14 seedlings. Total RNA was isolated from the samples. The 24 samples were sequenced on an Illumina NovaSeq 6000 as paired reads of 150 bp in length.

first: Javier

last: Canales

first: Juan

middle: C

last: Aledo

first: Francisco

last: Cantón


title: Lanthanide-dependent methanol dehydrogenase XoxF confers a competitive advantage for occupancy of Medicago sativa nodules by Sinorhizobium meliloti.

city: Kalamazoo

first: Enish

last: Pathak

state: MI

address: 1903 W Michigan Ave

department: Biological Sciences

institute: Western Michigan University

summary: The recent discovery of the lanthanide(Ln)-dependent methanol dehydrogenase (MDH) XoxF has expanded the spectrum of bacteria recognized for methylotrophic metabolism. Many bacteria, including rhizobia, have long escaped being categorized as methylotrophs because they exclusively produce XoxF-type Ln-dependent MDH and entirely lack the long-studied calcium-dependent MDH MxaFI. We report that the XoxF-type Ln-dependent MDH encoded by the smb20173 gene is the sole MDH that supports methylotrophic growth of Sinorhizobium meliloti. The Ln that consistently supported growth of S. meliloti in minimal media with methanol included lanthanum, cerium, praseodymium, and neodymium. Based on genome, whole-transcriptome, and mutant phenotype analyses, we propose a metabolic model for Ln-dependent methylotrophy in S. meliloti wherein oxidation of one-carbon compounds such as methanol generates the reducing power needed to assimilate carbon via the Calvin-Benson-Bassham cycle. By investigating how these newfound insights about Ln reshape our understanding of the methylotrophic capabilities of rhizobia, we explored how methanol produced by plants has the potential to create a nutritional niche in the rhizosphere. Using a Medicago sativa (alfalfa) nodule occupation assay, we found that the xoxF mutant strain was outcompeted by the wild-type strain only when Ln were available, suggesting that Ln-dependent methylotrophy is a potential nutritional mediator of the rhizobia-legume symbiosis.

overall_design: Differential gene expression of Sinorhizobium meliloti when grown in the presence or absence of Lanthanides.

first: Olivia

middle: N

last: Walser

first: Angel

middle: I

last: Banuelos

first: Silvia

last: Rossbach


title: An EGFR Co-amplified Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-driven gene programs

city: Chicago

first: Shi-yuan

last: Cheng

state: Illinois

address: 303 E. Superior Street, The Robert H. Lurie Cancer Center

institute: Northwestern Univeristy

summary: EGFR amplification at extrachromosome DNAs (ecDNAs) is a major driving mutation in glioblastoma (GBM).  However, targeting EGFR for GBM treatments remain unsatisfied. Here we identify a de novo long non-coding RNA (lncRNA) that is co-amplified with EGFR which we named hidden EGFR long non-coding downstream RNA (HELDR). HELDR is a GBM-specific lncRNA that promotes tumorigenicity independent of EGFR expression and signaling. HELDR globally binds genomic DNA and recruits a transcription co-activator p300 to the promoter of KAT7. p300-induced H3K27ac at KAT7 promoter enlists other co-transcription factors, activating KAT7 transcription. KAT7 induces H3K14ac H4K12ac that activate the transcription of KAT7-targeting gene programs critical for GBM malignancy. Targeting KAT7 synergistically enhances therapeutic effects of targeting EGFR for GBM treatment. These results not only reveal the role of HELDR in EGFR-driven GBM malignancy, but also provide strong rationale to characterize the roles of lncRNAs co-amplified with driver oncogenes at ecDNAs in human cancers.

overall_design: GSC11 and GSC34 cell lines

first: Xiaozhou

last: Yu

first: Bo

last: Hu

first: Shi-Yuan


title: A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies

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

overall_design: Refer to individual Series


title: Isoliensinine promotes the clearance of senescent vascular smooth muscle cells by natural killer cells [VSMC]

city: Nanjing

first: po

last: hu

state: jiangsu

address: 栖霞区 南京中医药大学 B3-F106（栖霞仙林校区）

institute: 南京中医药大学

summary: Atherosclerosis (AS) is an age-related disease whose incidence increases with advancing age. During disease pathogenesis, vascular smooth muscle cells (VSMCs) undergo senescence within the plaques and secrete senescence-associated secretory phenotype (SASP) factors, which contributes to the development and destabilization of atherosclerotic plaques. As key effector cells of the innate immune system, natural killer (NK) cells can specifically recognize and eliminate senescent cells; however, their role in inhibiting AS progression and the underlying mechanisms remain unclear. Isoliensinine (IsoL) is a bisbenzylisoquinoline alkaloid extracted from lotus plumule, which exerts anti-inflammatory and immunomodulatory effects. Studies have shown that IsoL can effectively enhance the immune clearance of tumor cells by NK cells, suggesting that this compound may also have the potential to inhibit AS progression by regulating the recognition and elimination of abnormal target cells by immune cells.

overall_design: This submitted sample set includes human aortic vascular smooth muscle cell samples from different experimental groups. The experimental groups consist of the hydrogen peroxide-induced cellular senescence group and the isoliensinine treatment group, with biological replicates set up for all groups.

first: XiaoNi

last: Ma


title: An EGFR Co-amplified Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-driven gene programs [KAT7]

overall_design: GSC17 (Control and KAT7 KD)


title: Safety and efficacy of neoadjuvant radiotherapy and immunotherapy in the treatment of esophageal squamous cell carcinoma

city: Hefei

first: Shuanghu

last: Yuan

address: No. 17 Lujiang Road

department: Department of Radiation Oncology,

institute: The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China

summary:
Background: Immunotherapy has been employed in the neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma. To assess the feasibility of neoadjuvant radiotherapy combined with immunotherapy (NRIT), this study compares the efficacy and effectiveness of neoadjuvant chemoradiotherapy combined with immunotherapy (NICRT) and NRIT, while also exploring the underlying mechanisms of NRIT.
Methods:This study retrospectively analyzed a cohort of 64 patients diagnosed with locally advanced esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant therapy followed by esophagectomy between January 2019 and September 2023. Of these, 26 patients received neoadjuvant radiotherapy and immunotherapy (NRIT), while 38 patients were treated with neoadjuvant chemoradiotherapy (NICRT). The final analysis included pathological complete response (pCR), major pathological response (MPR), tumor regression grade (TRG), the rate of positive lymph node pCR, toxicity, surgical outcomes, postoperative complications, disease-free survival (DFS), and overall survival (OS). Additionally, paraffin-embedded tissue sections obtained before and after neoadjuvant NRIT were subjected to whole-exome sequencing, transcriptome sequencing, and immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) analysis.
Results: There was no significant difference in the rates of MPR and PCR (28.95% vs 30.77%, P=0.873), TRG classification (P=0.338), surgical outcomes, or postoperative complications (P=0.148), as well as overall survival (OS) and disease-free survival (DFS) between the NICRT and NRIT groups. However, a notable difference was observed in grade 3 or higher adverse events during treatment, with the NICRT group experiencing a higher incidence (34.21% vs 7.69%, P = 0.017) and severe hematological toxicity (23.68% vs 0.00%, P = 0.008). In the NRIT group, patients with high CPS scores demonstrated improved pathological responses. Pre-treatment genomic analyses indicated no differences in tumor mutation burden (TMB), somatic mutations, and copy number variations between MPR and non-MPR patients post-surgery. Transcriptome analysis revealed a significant number of differentially expressed genes in patients before and after treatment, closely associated with key pathways related to immunity. Following treatment, MPR patients exhibited a marked upregulation of the type I interferon response and the MHC class I antigen presentation pathway. Additionally, the number of B cells and monocytes increased, while non-MPR patients showed a significant downregulation of dendritic cells (DCs) after treatment, alongside the activation of various immune cells, including CD8 naïve cells, NK cells, and B cells.
Conclusion: There was no significant difference between the NRIT group and the NICRT group regarding pathological response, surgical outcomes, postoperative complications, and survival analysis; furthermore, NRIT demonstrated a better safety profile compared to NICRT during treatment. Additionally, the mechanism of action of NRIT has been elucidated through a comprehensive analysis of genomic, transcriptomic, immunohistochemical, and other methods in conjunction with clinical results, thereby establishing NRIT as a neoadjuvant treatment that is both effective and safe.

overall_design: Patients receiving NRIT were subjected to whole-exome sequencing, RNA sequencing, and immunohistochemistry (IHC) analysis of programmed death-ligand 1 (PD-L1) on paraffin-embedded tissue sections obtained before and after treatment. The RNA sequencing included 14 pretreatment samples (RNA1-14) and 15 post-treatment samples (RNA15-29).

first: Shuming

last: Shi

first: Hao

last: Zhou

first: Li

last: Li

first: Gongjun

last: Wang

first: Dexian

last: Zhang

first: Changxing

last: Feng


title: Early-stage idiopathic pulmonary fibrosis is characterized by bronchoalveolar accumulation of SPP1+ macrophages

city: Bonn

first: Jiangyan

address: Carl-Troll-Str. 31

country: Germany

institute: University of Bonn

summary: Patients affected by idiopathic pulmonary fibrosis (IPF), a progressive chronic and eventually fatal lung disease with unknown causes, suffer from delayed diagnosis due to the lack of predictive markers for disease development. Prior studies focused on the cellular and transcriptomic changes found in lung tissue during established, often terminal, lung disease. In clinical routine, bronchoscopy is applied for diagnosis and staging of suspected IPF affected individuals, thus providing us with a clinically applicable window, to study the cellular and transcriptional changes within affected individuals. Here we study a patient collective consisting of 11 IPF affected individuals and 11 healthy controls. We investigate their single cell transcriptomic profile alongside their cellular surface phenotype of alveolar-resident immune cells. Single cell transcriptional analysis reveals early accumulation of SPP1+ macrophages (SPP1+M) within the alveolar space as an early cellular sign of IPF, in the absence of a decline in lung function. Early-stage IPF accumulated SPP1+M were characterized by high expression of lipid storage and handling genes, accumulation of intracellular cholesterol and expression of proinflammatory cytokine expression. In silico developmental trajectory analysis revealed that SPP1+M are likely derived from monocytes. Finally to confirm the clinical diagnostic value of SPP1+ M we developed a flow cytometry panel to rapidly identify and test for the presence of SPP1+ M in bronchoalveolar lavage samples and confirm our observation in an independent validation cohort. Taken together, we show that SPP1+ M are associated with early IPF pathogenesis in the absence of an obvious decline in lung function, thus providing a clinically valuable markers for easy diagnosis of early IPF in clinical practice.

overall_design: Cells isolated from BALF samples from patients or control subjects were analyzed by scRNA sequencing.

first: Jake

last: Thomas

first: Jessica

last: Haub

first: Carmen

last: Pizarro

first: Miaomiao

first: Leonie

last: Biener

first: Matthias

last: Becker

first: Lili

first: Theodore

middle: S

last: Kapellos

first: Wolfgang

last: Schulte

first: Joachim

last: Schultze

first: Jan

last: Hasenauer

first: Dirk

last: Skowasch

first: Andreas

last: Schlitzer


title: An EGFR Co-amplified Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-driven gene programs [ChIRP]

first: Shi-yuan

last: Cheng

overall_design:
GSCs, ChIRP experiment, include input, even group, and odd group
Please note that, for HELDR_KD* samples, differential binding analysis was conducted using the DiffBind R package, in which BAM files were imported and even/odd probe sets were treated as biological replicates.

first: Xiaozhou

last: Yu

first: Bo

last: Hu

first: Shi-Yuan


title: Multiomics assessment of lung adenocarcinoma subtypes defined through tumor purity-adjusted DNA methylation

city: Lund

first: Johan

last: Staaf

address: Medicon Village

department: Laboratory Medicine

country: Sweden

institute: Lund University

summary: Molecular subtypes of lung adenocarcinoma (LUAD) with varying prognosis and characteristics have been proposed based on one or two-dimensional studies but are not yet implemented into clinical routine. Epigenetic modifications in cancer cells are independent of sequence variants, directly linked to gene and genome regulation, and thus provide important information to guide subclassification efforts. We performed in-depth epigenomic profiling of 95 primary LUAD samples from a Swedish discovery cohort with comprehensive clinicopathological, epigenomic, genomic, transcriptomic, proteomic, and metabolomic data. Not all samples have all omics data, and data have been deposited at different timepoints. Here we include DNA methylation values for 13 LUAD samples. In this project, we subdivided the 95 samples into four epigenetic subtypes, or epitypes, reflecting distinct tumor cell methylation states. Resulting epitypes were contrasted based on clinicopathological and molecular features, and our main findings were validated in two additional primary tumor cohorts totaling over 700 samples.

overall_design: DNA methylation data were generated from 13 lung adenocarcinoma samples to complement lung tumor data already available from other sample series.

first: Deborah

middle: F

last: Nacer


title: RNA-seq of OT-I cells co-cultured with vehicle, TANs or TAMos under OVA257-264 stimulation

first: Zeliang

last: Yang

address: No.38 Xueyuan Road,Haidian

institute: Peking University Health Science Center

summary: To explore the effects of tumor-associated monocytes (TAMos) on T cell transcriptional landscape, we conducted RNA transcriptome profiling of OT-I cells co-cultured with vehicle, tumor-associated neutrophils (TANs), or TAMos derived from the spleens of LLC tumor-bearing mice in response to OVA257-264 peptides.`

overall_design: We sorted TANs (CD11b+Ly6G+Ly6Clow) or TAMos (CD11b+Ly6G-Ly6Chigh) from the spleens of LLC tumor-bearing mice and incubated them with OT-I cells under OVA257-264 stimulation for 48 hr. Then activated T cells were purified, followed by RNA isolation and sequencing.

first: Yuxin

last: Yin


title: Acetate supercharges xylose metabolism in Rhodotorula toruloides

city: Urbana

first: Christopher

middle: V.

last: Rao

state: IL

address: 600 S Mathews Ave

department: Chemical and Biomolecular Engineering

institute: University of Illinois

summary: To confirm the transcriptional mechanism of xylose gene activation in Rhodotorula toruloides is principally determined by acetate and not other factors, like nitrogen content. RNA-Seq was conducted to understand xylose pathway metabolism. Ultimately, we used new-found understanding in RNA-Seq to engineer R. toruloides better.

overall_design: Nitrogen = {0.1 ammonium sulfate and 0.375 g/L yeast extract, 5 g/L ammonium sulfate}, acetate = {0 g/L, 2 g/L}, time = {48 hr, 64 hr, 88 hr}

first: Joshua

last: Ye

first: Sujit

last: Jagtap

first: Hyun

middle: G

last: Koh

first: Thanh

middle: Q

last: Pham

first: Yong

last: Jin

first: Chris

middle: V

first: Diya

last: Kamath


title: Multicellular origins of ovarian inflammaging

first: Anna

last: Galligos

overall_design: RNA-sequencing conducted on single-cell suspensions of whole ovaries  from 2 month old  and ~14 month old C57BL6/J female mice.

first: Joseph

last: Varberg

first: Wei-Ting

last: Yueh

first: Aubrey

last: Converse

first: Seth

last: Malloy

first: Fatimah

last: Aljubran

first: Francesca

last: Duncan

first: Jennifer

last: Gerton


title: scRNA-seq of endocrine pancreatic lineages in Isl1CKO mouse model

city: Vestec

first: Valéria

last: Fabríciová

address: Průmyslová 595

country: Czech Republic

institute: Institute of biotechnology CAS

summary: To understand the pathophysiology of diabetes and to develop more effective treatments, we need to unravel how pancreatic endocrine lineages are generated. ISL1 transcription factor has important role in differentiation, maturation and maintenace of endocrine cells.  Eliminating ISL1 in mouse pancreatic endocrine progenitors leads to the diabetic phenotype with altered islet architecture. To evaluate effects of lacking transcription factor on molecular level we performed single cell transcriptomics.

overall_design: We created conditional knockout mouse model using Cre-loxP system. Isl1CKO mutants carry genotype Neurod1 Cre/+; Isl1 f/f and mice with genotype Neurod1 Cre/+; Isl1f/+ do not show any phenotype and are used as controls. TdTomato fluorescent protein is used as reporter. 9 days old (P9) pups were sacrificed and pancreases were dissected. 6 samples from each genotype were pooled together. FACSed tdTomato+ cells were loaded to 10x Chromium Next GEM Single cell 3' Reagents kit v.3.1.

first: Pavel

last: Abbafy

first: Valeria

last: Fabriciova

first: Romana

last: Bohuslavova

first: Eva

last: Rohlova

first: Zuzana

last: Berkova

first: Frantisek

last: Saudek

first: Gabriela

last: Pavlinkova


title: An EGFR Co-amplified Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-driven gene programs [HELDR]

first: Shi-yuan

last: Cheng

overall_design: GSCs (Control vs HELDR KD or Control vs ASO-HELDR)

first: Xiaozhou

last: Yu

first: Bo

last: Hu

first: Shi-Yuan


title: An EGFR Co-amplified Long Noncoding RNA HELDR Promotes Glioblastoma Malignancy through KAT7-driven gene programs [Long-reads, GBM6]

overall_design: GBM6, long-reads RNA-seq


title: RNA sequencing of naïve T cells, central memory T cells and effector memory T cells derived from mouse spleens

city: Beijing

first: Zeliang

last: Yang

summary: To explore the relationship between OT-I cells co-cultured with tumor-associated monocytes (TAMos) and conventional T cell subsets, we conducted RNA transcriptome profiling of naïve T cells, central memory T cells, and effector memory T cells from mouse spleens.

overall_design: We sorted naïve T cells, central memory T cells, and effector memory T cells from mouse spleens, followed by RNA sequencing.

first: Yuxin

last: Yin


title: A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [bulkRNA-seq]

first: Paul

last: Northcott

summary: Pineoblastoma is a clinically aggressive childhood brain tumor that segregates into molecularly distinct subgroups. Mechanisms governing pineoblastoma pathogenesis, including developmental origins, remain poorly defined. Herein, we resolved the cellular composition of pineoblastoma and other pineal parenchymal tumors at single-cell resolution, aligning malignant cells with pineal gland development to retrace cellular origins. Integrative computational analyses mapped divergent pineoblastoma subgroups to cycling progenitors of the pinealocyte lineage. Lineage-specific perturbation of suspected drivers provoked the generation of genetically accurate preclinical models representing distinct molecular subgroups, while uncovering an oncogenic photoreceptor program conserved across pineoblastoma, retinoblastoma, and Group 3 medulloblastoma. Transcriptional activity of this program was acquired from cellular origin, incriminating photoreceptor identity as a common developmental vulnerability, substantiated as a strong dependency. Illuminated through multidisciplinary analysis of an uncommon, heterogeneous pediatric brain tumor, these advances motivate future studies evaluating developmentally encoded transcriptional programs of malignancy as potential therapeutic liabilities in clinically challenging entities.

overall_design: Transcriptome profiling by bulk RNA-seq of the developing pineal gland and mouse pineal tumor models.

first: Brian

last: Gudenas


title: ATAC-seq of OT-I cells co-cultured with vehicle or TAMos under OVA257-264 stimulation

summary: To characterize the regulation of tumor-associated monocytes (TAMos) on the epigenetic map of T cells, we conducted the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) of OT-I cells co-cultured with vehicle or TAMos derived from the spleens of LLC tumor-bearing mice in response to OVA257-264 peptides.

overall_design: We purified TAMos (CD11b+Ly6G-Ly6Chigh) from the spleens of LLC tumor-bearing mice and incubated them with OT-I cells under OVA257-264 stimulation for 48 hr. Then activated T cells were sorted by FACS, and used for ATAC-seq.


title: Synergistic Effects of Retinol and Retinyl Palmitate in Alleviating UVB-Induced DNA Damage and Promoting the Homologous Recombination Repair in Keratinocytes

city: SHENZHEN

first: JIANGMING

last: ZHONG

address: Shennan rd 9996, 518000, Shenzhen, Guangdong, P.R. China.

institute: Shenzhen Hujia Technology Co., Ltd.

summary: Ultraviolet B (UVB) rays are a type of ultraviolet radiation emitted by the sun, primarily responsible for skin photodamage. These rays mainly affect the epidermis, leading to direct damage to DNA and contributing to skin cancer development. Retinol and its derivatives are effective in combating skin aging and photodamage, but they often cause skin intolerance, limiting their use despite their potent effects. Therefore, investigating optimal compositions of retinoids is essential to enhance their efficacy against photodamage. In this study, we aimed to investigate the synergistic effects of retinol (ROL) and retinyl palmitate (RPalm) in alleviating UVB-induced DNA damage in human keratinocytes (HaCaT). Applying the ROL+RPalm combination after UVB exposure in HaCaT cells significantly reduced inflammation and apoptosis while promoting collagen synthesis compared to individual treatments with ROL or RPalm. Through bulk mRNA sequencing, we identified that the biological function of the ROL+RPalm synergy is primarily directed toward mediating DNA damage repair. Using comet assays, Western blotting, immunofluorescence, and flow cytometry, we demonstrated the anti-DNA damage effects of ROL+RPalm in HaCaT cells and reconstructed human epidermis. We further elucidated that the molecular mechanism underlying the ROL+RPalm combination involves the activation of RARβ, which subsequently triggers the ATM-CHK2-p53 signaling pathway and increases the expression of homologous recombination (HR)-associated repair genes. This combination presents a potential therapeutic strategy for UVB-induced photodamage and emphasizes the synergistic effects of ROL and RPalm in alleviating UVB-induced DNA damage.

overall_design: RNA-seq profiling of HaCaT (Human Keratinocyte) cells subjected to UVB irradiation. After UVB irradiation with the addition of ROL or Rpalm or ROL+Rpalm, we wanted to investigate whether ROL or Rpalm or ROL+Rpalm had the ability of anti-photodamage in HaCaT (Human Keratinocyte) cell, especially in DNA repair. Then we performed gene expression profiling analysis using data obtained from RNA seq of 5 different treated ways (control group, UVB treated group, UVB and ROL co-treated group, UVB and Rpalm co-treated group, UVB and ROL with Rpalm co-treated group)in Hacat cell.

first: Jiangming

last: Zhong

first: Ling

last: Liang

last: Zhao

first: Jing

last: Wang

first: Peng

last: Shu


title: Single-cell transcriptome profiles of Drosophila melanogaster olfactory projection neurons at 12 hours after puparium formation (h APF)

status: Public on Feb 06 2026

city: Stanford

first: Yunming

last: Wu

state: CA

address: 327 Campus Drive, Bass biology building, rm334

department: Biology

institute: Stanford University

summary: Neurons in the nervous system exhibit remarkable wiring specificity that underlies the specialized functions of defined cell types. In the fruit fly (Drosophila melanogaster) olfactory system, olfactory receptor neurons (ORNs) expressing the same receptor project to a specific type of projection neuron (PN) within a glomerulus in the antennal lobe. This precise glomerular map is essential for odorant detection and serves as a premier model for studying how neuronal wiring specificity emerges. A key remaining question is how specific PNs establish this map by tiling their receptive fields—the prospective glomeruli—with high specificity and no redundancy. In this study, we profiled the single-cell transcriptomes of PNs between 12 and 18 hours after puparium formation (12–18h APF), a critical window when PNs sort their dendrites into specific regions to form a prototypic map. These data complement existing datasets from 0h, 24h, 48h APF, and adults, providing a comprehensive transcriptional profile of PN development.

overall_design: Single-cell RNA-seq of Drosophila melanogaster olfactory projection neurons at 12h APF using Smart-seq2. To be comparable with the previous 0 h, 24 h, 48 h APF, and adult data, the experiment is done with the same protocol.

first: Kenneth

middle: K

last: Wong

first: Hui

last: Ji


title: Transcriptomic profiling of miR-18a CRISPR knockout melanoma identifies genes associated with therapy resistance and T cell killing

city: Tianjin

first: Wanyi

last: Xiao

address: West Huan-Hu Rd, Ti Yuan Bei, Hexi District Tianjin

institute: Tianjin Medical University Cancer Institute and Hospital

summary: In melanoma, the knockout of miR-18a not only leads to resistance to monotherapy with BRAF inhibitors but also to combined therapy with BRAF and MEK inhibitors. This resistance is achieved by promoting the expression of YAP in the Hippo pathway. Additionally, the knockout of miR-18a results in high expression of THBS1-CD47, which causes T cell tolerance. miR-18a is regulated by hnRNPA1, and patients with low expression of miR-18a and hnRNPA1 have poorer Event-Free Survival (EFS).

overall_design: Bulk RNA sequencing was performed to compare transcriptomic changes between wild-type and miR-18a knockout melanoma cells under vemurafenib treatment or CD8+ T cell co-culture. Biological replicates were included for each experimental condition.


title: Single-cell transcriptomic profiling reveals the heterogeneity of miR-18a-mediated resistance to targeted therapy and immunotherapy in melanoma

overall_design: Single-cell RNA sequencing was performed on miR-18a knockout, vemurafenib-resistant, and CD8+ T cell–resistant melanoma cells to characterize transcriptional heterogeneity and cell state changes. Cells were processed using the 10x Genomics platform, and biological replicates were included.


title: A tumor-associated photoreceptor signature unifies distinct central nervous system malignancies [scRNA-seq]

city: Memphis

address: 262 Danny Thomas Place

institute: St. Jude Children's Research Hospital

overall_design: Transcriptome profiling by scRNA-seq in the developing pineal gland from the Crx-GFP mice across eleven developmental  timepoints (E11-P21).


title: Effect of KIFC1 knockdown on gene expression in H146 small-cell lung cancer cells

city: Bunkyo-ku

first: Natsuki

last: Nakagawa

state: Tokyo

department: Respiratory Medicine

institute: The University of Tokyo

summary: To investigate the function of KIFC1 in small-cell lung cancer, we established the H146 cell line in which KIFC1 was knocked down using siRNA. We then performed gene expression profiling analysis using RNA-seq data obtained from control siRNA-treated cells and KIFC1-depleted cells.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for NCI-H146 cells following siRNA-mediated knockdown of KIFC1 compared with control siRNA treatment.

first: Hiroaki

last: Ikushima

first: Masanori

last: Kawakami


title: High-frequency recurrence index for predicting multiple recurrences in non-muscle-invasive bladder cancer (Validation cohort)

city: Yuseong-gu

first: Seung Woo

last: Baek

institute: Korea Research Institute Biology & Biotechnology

summary: Non-muscle invasive bladder cancer (NMIBC) has a recurrence rate of more than 50% after transurethral resection (TUR) and Calmette-Guérin (BCG) treatment. This study aimed to develop a high-frequency recurrence index (HfRI) to predict multiple recurrences in NMIBC patients and guide personalized treatment strategies. In this study, we analyzed transcriptome data (Discovery cohort) of 45 high-risk NMIBC patients who received intravesical BCG treatment, including patients with >=2 recurrences, to identify genes significantly associated with high-frequency recurrence and construct a signature. In addition, we validated the predictive performance using transcriptome data of 94 patients (Validation cohort).

overall_design: A validation cohort of 94 NMIBC patients from Chungbuk National University Hospital is RNAseq transcriptome data produced for high-frequency recurrence of NMIBC.

first: Seung-Woo

first: Young-Joon

last: Byun


title: Gene expression differences between LPS, anti-CD36 Abs, or LPS plus anti-CD36 Abs treated RAW264.7 cells.

first: Weixuan

address: No. 38 Xueyuan Road, Haidian District

institute: Peking University

summary: To comprehensively analyze the transcriptome of macrophages treated with LPS, anti-CD36 Abs, or LPS plus anti-CD36 Abs, respectively, we employed RNA sequencing (RNA-seq) assay

overall_design: We performed gene expression profiling analysis using data obtained from RNA-seq of LPS (50ng/mL),purified anti-CD36 Abs, or LPS plus anti-CD36 Abs treated RAW264.7 cells.

first: Xin

last: Sun

first: Dan

last: Lv


title: miRNA-18a screened based on CRISPR can regulate targeted therapy resistance and T-cell killing in melanoma

overall_design: A pooled CRISPR-Cas9 knockout screen targeting human miRNAs was performed in A375 melanoma cells to identify regulators of vemurafenib resistance and CD8+ T cell–mediated cytotoxicity. Cells stably expressing Cas9 were transduced with a lentiviral sgRNA library at low MOI and selected with puromycin. Genomic DNA was collected at baseline (Day 0) and after drug treatment or T cell co-culture, followed by PCR amplification and next-generation sequencing of sgRNA cassettes. Biological replicates were included for each condition.


title: The role of BAF60C in type 2 diabetes——scRNA-seq

city: Hangzhou

first: Zhuoying

last: Yang

address: Yuhangtang Road

institute: Zhejiang University

summary: This research identify reduced expression of BAF60C in diabetic islets and demonstrate that altered β-cell BAF60C levels strongly influence metabolic homeostasis. Genetic loss of BAF60C in β-cells exacerbates hyperglycemia and islet dysfunction under metabolic stress, whereas β-cell–specific restoration of BAF60C produces protective effects. These findings establish BAF60C as an important regulator of β-cell integrity and disease progression in T2D.

overall_design: We used scRNA-Seq to assess islets isolated from beta-cell-specific ablation (BcBKO) mice.  Islets for scRNA-Seq data were isolated from flox/flox and BcBKO Pdx1-cre mice, then dissociated into single cells for sequencing. You can find detailed information on sample collection and data analysis pipeline in our manuscript.


title: Lipid metabolism dysregulation in solar lentigo: a multi-system-level analysis reveals membrane instability and energy homeostasis disruption

city: Seoul

first: Soonhyo

last: Kwon

address: 892 Dongnam-ro, Gangdong-gu

institute: Kyung Hee University Hospital at Gangdong

summary: Solar lentigo is a common hyperpigmented skin condition caused by chronic ultraviolet exposure, primarily affecting photoaged skin. While previous investigations focused on inflammatory and melanogenic mechanisms, the comprehensive role of lipid metabolism in pathogenesis remains unclear. We aimed to investigate systemic alterations in lipid metabolism and their contribution to solar lentigo development. We performed comprehensive analysis of RNA sequencing data from solar lentigo lesions and control skin samples (n=7 per group) using metabolic flux simulations, gene co-expression networks, and protein-protein interaction analysis. These multi-system approaches were integrated to identify coordinated alterations in lipid metabolic pathways. Solar lentigo samples exhibited coordinated inhibition of fatty acid elongation, acetyl-CoA carboxylase activity, and sphingolipid biosynthesis, alongside impaired cholesterol synthesis via reduced squalene epoxidase and 7-dehydrocholesterol reductase activity. Compensatory upregulation of phospholipid synthesis enzymes and dihydroceramide desaturases was observed. Pathway disruption and altered calcium signaling, indicating aberrant cellular energy metabolism and membrane integrity. These findings demonstrate that solar lentigo pathogenesis involves systematic lipid metabolism dysregulation beyond melanogenesis, causing membrane instability, energy homeostasis disruption and redox imbalance. The identification of specific metabolic bottlenecks reveals novel targets for lipid-based therapeutic approaches in pigmentary diseases.

overall_design:
The dataset comprised paired tissue samples from solar lentigo lesions and adjacent normal skin obtained from seven patients.

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

first: Man

last: Kim


title: The role of BAF60C in type 2 diabetes ——ATAC-seq

overall_design: We used ATAC-Seq to assess islets isolated from beta-cell-specific ablation (BcBKO) mice,  which elaborates the changes in chromatin accessibility.  Islets for ATAC-Seq data were isolated from flox/flox and BcBKO Pdx1-cre mice. You can find detailed information on sample collection and data analysis pipeline in our manuscript.


title: Effect of cross sex hormones on gene expression in Mattek reconstructed vaginal tissue model

city: Boston

first: Robin

middle: R.

last: Ingalls

state: MA

address: 650 Albany St, EBRC 610

department: Infectious Disease

institute: Boston Medical Center

summary: It is estimated that more than one million people in the United States identify as transgender.  Despite recent increased visibility, transgender individuals remain marginalized and subject to health disparities, and are underrepresented in biomedical research.  Our central hypothesis is that gender affirming hormone therapy in transgender men leads to a dysregulated innate immune microenvironment and impaired barrier function of the vaginal mucosal compartment. we will conduct transcriptomic studies to identify the gene expression profile of the testosterone dominant vagina to identify changes in the immunologic signaling pathways that could negatively impact host-pathogen interactions.  We conducted transcriptomic studies using RNA sequencing to identify the gene expression profile of the testosterone dominant vagina in comparion to the estradiol dominant vagina and vaginal tissue without sex hormone exposure to identify changes in the immunologic signaling pathways that could negatively impact host-pathogen interactions in this compartment in transgender men.

overall_design: RNA-seq profiling of Mattek EpiVaginal reconstructed tissues grown for 1 week without hormone or with 10 nM estradiol, 150 nM testosterone, or 15 nM DHT


title: Adaptive immune responses to vaccination reflect social status at first exposure in rhesus macaques

city: Chicago

first: Joao

last: Barroso-Batista

address: The University of Chicago, KCBD room 9220E, 900 E 57th Street

institute: The University of Chicago

summary: Social gradients are consistently associated with variation in health outcomes, including infectious disease. However, distinguishing between social gradients in antigen exposure versus susceptibility remains challenging. Here, we use a nonhuman primate model for chronic social stress to investigate how social status influences the influenza vaccine-induced adaptive immune response. We manipulated the social status of female rhesus macaques to test the response to influenza antigens in naïve individuals and after secondary exposure. Higher social status at the time of first exposure, but not at the time of secondary exposure, predicted stronger antibody responses to both exposures. Social status also drove gene expression differences for adaptive immune pathways, and genes that predict the magnitude of the antibody response overlap with those linked to social status. Thus, social gradients shape the adaptive immune response in a temporally dependent manner, with particular sensitivity at the time of initial antigen exposure.

overall_design: RNA-seq profiling of PBMCsfrom rhesus macaques before (day 0) and 1, 3 or 7 days following influenza vaccination

first: C. Ryan

last: Campbell

first: Luis B.

last: Barreiro

first: Jenny

last: Tung


title: Snail1 Induced Suppression of Proliferation via EGR1, FOXO1, and CEPBg Creates a Vulnerability for Targeting Apoptotic and Cellular Senescence Pathways [ChIP-Seq]

city: Tucson

first: Jack

last: Tran

state: AZ

address: 1515 N. Campbell Avenue

department: Cancer Center

institute: University of Arizona

summary: The annual ~36,000 prostate cancer (PCa) deaths represent a large clinical unmet need and a call for deeper understanding of PCa metastasis. Epithelial-mesenchymal-transition (EMT) has been used to model metastatic behaviors in numerous cancers including PCa. One hallmark of EMT is cell cycle suppression, but how EMT impacts PCa proliferation remains unclear primarily due to the lack of appropriate models. Methods: We transiently induced expression of Snail1 (SNAI1), an EMT driver expressed in PCa, at physiological levels in three PCa cells lines, C4-2B, 22Rv1, and DU145. We used RNA-seq, ChIP-Seq, bioinformatics, qRT-PCR, shRNA, and immunoblotting to identify mechanisms of Snail1-driven inhibition of proliferation. Results: Snail1 suppressed proliferation and the G2/M cell cycle progression, without affecting cell death. Mechanistically, Snail1 upregulated expression of CEBPg, ERG1, FOXO1, cyclin G1, p21, stress genes SESN3 and SOD3, apoptotic programmers Puma, Bax, and Noxa, and senescence-related laminB1, and downregulated Ki67, cyclins A2 and B2. ChIP-Seq data identified Snail1 direct binding to p21, cyclin B2 and G1, EGR1, and CEPBg promoters. EGR1 induced FOXO1 and EGR1 was required for Snail1-induced SOD3 and Puma, and suppression of Caspase 3 to prevent apoptosis. The EGR1/FOXO1 axis induced BAX, Noxa, and SESN3. CEBPg was required for Snail1 induction of Lamin B1 to block Snail1-induced senescence. Conclusions: We identified three new major downstream targets of Snail1 that improve our understanding of the role of EMT in limiting stress signaling, apoptosis, and senescence during cell cycle suppression to create a vulnerability for therapeutic targeting.

overall_design: Snail1-6SA-FLAG plasmid vector, or mCherry control was transiently transfected into C4-2B or DU145 prostate cancer cells and incubated in 2% CSS phenol-red free media for 2 days. Cells were then harvested per ChIP-seq kit and protocol per Cell-Signaling-Technologies, for downstream chromatin immunoprecipitation and high throughput sequencing. Snail1-chromatin was then immunoprecipitated with anti-FLAG antibody. Column-purified DNA was then submitted to Novogene for ChIPseq sequencing.

first: Cynthia

last: Miranti

first: Samyukta

last: Sundaram

first: Sukitrti

last: Shivpuri

first: Hunain

last: Khawaja


title: Phase II proof-of-concept study of durvalumab and cediranib with and without olaparib in recurrent ovarian cancer

city: Frederick

last: Chen

state: MD

address: 8560 Progress Drive

institute: Frederick National Laboratory

summary: We report the efficacy and translational research findings of durvalumab, olaparib, and cediranib (D+O+C) and durvalumab plus cediranib (D+C) from the recurrent epithelial ovarian cancer (EOC) cohort within a single center, multi-arm, non-randomized, multi-cohort phase I/II trial (NCT02484404). Sixty-eight patients were enrolled (39 in D+O+C, 29 in D+C). The objective response rate (ORR) was 19.4% (95% CI, 9.5-43.5) for D+O+C and 29.6% (95% CI, 13.8-46.9) for D+C. Median progression-free survival (PFS) was 4.5 months in both arms, with each arm including four exceptional responders (PFS ≥ 12 months). Pre- and on-treatment biopsies and blood samples were collected for pre-specified transcriptomic and immunophenotypic profiling; signature analyses and preclinical studies were exploratory. We identified distinct transcriptional signatures associated with clinical outcomes. Baseline tumors from exceptional responders and patients with clinical benefit (partial response or stable disease [SD] with PFS ≥ 4 months) demonstrated strong enrichment of immune activation and metabolic pathways. Conversely, tumors with no clinical benefit (NCB; progressive disease or SD with PFS < 4 months) exhibited upregulation of vascular adaptation and cytoskeletal remodeling pathways. The correlation between immune, metabolic, and NCB signatures and clinical outcomes within each arm was independent of prior platinum response. These findings support proof-of-concept clinical activity of D+O+C and D+C and identify molecular signatures with potential predictive value in subsets of recurrent EOC.

overall_design: Pre-treatment biopsies for RNAseq were available for 31 patients in the D+O+C arm (21 CB including 4 exceptional responders, and 10 NCB) and 24 in the D+C arm (14 CB including 3 exceptional responders, and 10 NCB). Paired pre- and on-treatment biopsies were available for 11 and 9 patients in the D+O+C and D+C arms, respectively. RNAseq was performed on tumor biopsies to characterize gene expression profiles. RNA samples were pooled and sequenced on NovaSeq Xplus 1.5B using Illumina® Stranded Total RNA Prep, Ligation with Ribo-Zero Plus and paired-end sequencing.

first: Huang

last: Tzu-Ting


title: Snail1 Induced Suppression of Proliferation via EGR1, FOXO1, and CEPBg Creates a Vulnerability for Targeting Apoptotic and Cellular Senescence Pathways [RNA-Seq]

overall_design: Prostate cancer cell line model C4-2B is stably transduced with inducible Cumate-Snail1 and tetON-shAR(androgen receptor) plasmid vectors. Cells were incubated in 2% CSS phenol-red free RPMI1640 media. Cells were pretreated for 2 days with 4.5ug/ml cumate or H2O control. After the 2 days, further treatments were further stratified to a total of 4 groups to either induce Snail1 and or AR-knockdown:  control+control, cumate+veh, cumate+dox. The described treated were done for 4/6 days. At the end of 4/6 days, cells were harvested in trizol lysis reagent for downstream total RNA isolation. Total RNA was isolated using standard alcohol precipitation. Isolated total RNA were submitted to NOVOGENE for next generation, selective for mRNA.


title: Glycine Promotes Cardiomyocyte Proliferation and Cardiac Regeneration via the GCN2/AKT Axis

city: Chongqing

first: feng

last: wang

address: #10 Changjiang Branch Road

department: Department of Cardiology, Daping Hospital

institute: The Third Military Medical University

summary: While glucose–lipid metabolic remodeling is a major driver of cardiomyocyte proliferative decline, the role of amino acid metabolism in cardiac generation remains poorly understood. Here, we identify glycine as a previously unrecognized pro-proliferative metabolic regulator in mammalian cardiomyocytes. Notably, exogenous glycine supplementation significantly enhanced cardiomyocyte proliferation in both neonatal and adult models, while also demonstrating enhanced efficacy in promoting cardiac repair following myocardial infarction. Mechanistically, glycine activated PI3K–AKT signaling through the amino acid sensor GCN2 and weakened the GCN2–AKT association, thereby facilitating AKT phosphorylation and enabling cardiomyocyte cell cycle re-entry. To address the pharmacokinetic limitations of free glycine administration, specifically its high peak concentration and suboptimal biodistribution profiles, we developed a cardiac-targeted liposomal nanoformulation (LNP@glycine) that exhibited enhanced myocardial accumulation efficacy, reduced dosing requirements, and further improved therapeutic efficacy. Collectively, our findings reveal glycine as a novel metabolic regulator of heart regeneration and highlight a translatable strategy that integrates amino acid-specific metabolic modulation with precision targeted delivery for ischemic heart disease.

overall_design: In primary rat cardiomyocytes, treat with 10 mM glycine or PBS for 24 hours, then perform transcriptome sequencing on total RNA.


title: Single-cell and spatial profiling reveal cDC2A-CXCL13+ CD8+ T-epithelial cell crosstalk and cytotoxicity through TNFRSF9 in cutaneous and mucosal lichen planus

city: Ann Arbor

first: Poulami

last: Dey

address: 1301 Catherine St

institute: Michigan Medicine

summary: Lichen planus (LP) is a chronic inflammatory disease of the skin and mucous membranes, marked by T cell infiltration and keratinocyte apoptosis. However, its immune microenvironment remains poorly understood. Using single-cell RNA sequencing, spatial transcriptomics, and proteomics on samples from 28 patients and 18 healthy controls, we identify elevated interferon (IFN) and cytotoxic signatures in CXCL13+CD8+ T cells in both cutaneous and mucosal LP, but not in lichen planopilaris. T cells expressing TNF and IFNG are spatially linked to epithelial cells through ligand-receptor interactions, correlating with inflammation. We identify cDC2A cells as key contributors, proximal to CXCL13+CD8+ T cells, serving as a major source of IL-15. CXCL13+CD8+ T cells express TNFRSF9 (4-1BB), which enhances their cytotoxic responses in the skin. In summary, our data reveal a critical role for cDC2A in driving CXCL13+CD8+ T –epithelial cytotoxicity in cutaneous and mucosal LP through TNFRSF9.

overall_design: To investigate changes in cell-type composition and transcriptional profiles in lesional skin, mucous membranes, and scalp tissue from patients with lichen planus, compared with healthy control skin.

first: Johann

last: Gudjonsson

first: Lam

last: Tsoi


title: Dietary Glutamine Supplementation Mitigates Age-Associated Cardiac Decline  by Restricting H3K27me3

city: London

first: Joseph

last: Burgoyne

state: Please select...

address: The Rayne Institute, St Thomas' Hospital

country: United Kingdom

institute: King's College London

summary: Epigenetic alterations are central drivers of cardiovascular aging, with histone modifications regulating gene expression through chromatin remodeling and changes in DNA accessibility. However, the mechanisms underlying these epigenetic shifts in the aging heart remain poorly defined. Here, we identify an age-associated accumulation of the repressive histone mark H3K27me3 in the myocardium of mice and humans, implicating this modification in myocardial aging. Elevated H3K27me3 was associated with impaired glutamine metabolism, driven by reduced expression of the amino acid transporter SLC1A5. Clinically, low circulating glutamine levels correlated with increased heart failure incidence, and genetic variants in SLC1A5 were linked to heightened cardiovascular disease risk. Mechanistically, elevated myocardial H3K27me3 suppressed cardiomyocyte autophagy and induced metabolic reprogramming, thereby promoting age-related myocardial dysfunction. Dietary glutamine supplementation in aged mice reduced H3K27me3 accumulation and improved myocardial function. Collectively, these findings identify a novel epigenetic mechanism underlying cardiac aging and highlight the glutamine–SLC1A5 axis as a potential therapeutic target for preserving myocardial function with age.

overall_design: RNA-seq profiling of heart tissue from young and aged mice. Also CUT&RUN-seq of H3K27me3 from young and aged mouse cardiac tissue.

first: Cassy

last: Le


title: Analysis of peripheral blood transcript and protein expression across adult systemic lupus erythematosus (SLE) and adult dermatomyositis (DM) patients, each compared to respective healthy matched control subjects.

city: Durham

first: James

last: Ward

state: NC

address: 111 TW Alexander Dr

department: Integrative Bioinformatics

institute: NIEHS

summary:
The study interrogates SLE and DM gene expression measurements across three platforms: Affymetrix transcriptomics, SomaLogic proteomics, and Rules Based Medicine (RBM) proteomics. Patients are matched 1:1 with healthy donor subjects by age, ethnicity, and sex. DM patients are matched 1:3 with SLE patients by the same criteria. All patients have been treated for at least one year, and represent patients receiving standard treatment care for the respective diseases. The data posted contain SLE patients in support of the paper Distinct Interferon and Intracellular Signaling Signatures in Systemic Lupus Erythematosus and Dermatomyositis by Integrative Transcriptomic and Proteomic Analysis.
Dermatomyositis (DM) patient consent requires controlled access, as a result the equivalent DM data are deposited in dbGaP Study Accession phs003270.v1.p1.

overall_design: Affymetrix transcriptomics data are provided for 41 SLE patients and 41 SLE_Control matched healthy controls. SomaLogic SOMAscan proteomics array data are provided for 34 SLE patients, 34 matched healthy controls. Rules Based Medicine (RBM) proteomics array data are provided for 34 SLE patients, and 34 matched healthy controls, using the same 34 samples as with SomaLogic proteomics data.

first: Mythri

last: Ambatipudi

first: Zerai

last: Manna

first: Adam

last: Schiffenbauer

first: Michael

last: Smith

first: Saifur

last: Rahman

first: Frederick

middle: W

last: Miller

first: Mariana

middle: J

last: Kaplan

first: Jian-Liang

last: Li

first: Kerry

last: Casey

first: Sarfaraz

last: Hasni

first: Lisa

last: Rider


title: The role of BAF60C in type 2 diabetes——RNAseq

first: Zhuoying

last: Yang

overall_design: We used RNA-Seq to assess the effects of different treatment in mouse islets, containing RNA-Seq from islets isolated from beta-cell-specific ablation (BcBKO) mice, REG3B treated mice, WT mice, which elaborates the changes in transcriptional networks.  Islet RNA-Seq data from flox/flox and BcBKO Pdx1-cre mice were fed with chow diet or HFD for 3M. You can find detailed information on sample collection and data analysis pipeline in our manuscript.


title: Characterisation of thyroid 8505 cells treated with CUET (RNA-Seq)

city: Detroit

first: Moray

last: Campbell

address: 4100 John R

institute: Barbara Ann Karmanos Cancer Institute, Detroit , Michigan, US

summary: In this study, we examined the impact of copper diethyldithiocarbamate (Cu(DDC)2), a metabolite of the FDA-approved drug disulfiram, on thyroid cancer cells. Mechanistically, Cu(DDC)2  targets valosin containing protein (VCP) – a key regulator of proteostasis – as well as inducing potent transcriptional responses.

overall_design: Thyroid cancer 8505C cells were treated with Cu(DDC)2 (250 nM, 24 hours) versus vehicle (DMSO). RNA-Seq libraries were prepared at the Next Generation Sequencing Facility (Genomics Birmingham Genomics Service, University of Birmingham).Sequencing libraries prepared with the TruSeq Stranded Total RNA kit (Illumina Inc), from 1ug total RNA. Alignment of raw sequence reads to the human transcriptome (hg38) was performed via Rsubread and transcript abundance estimates were normalized and differentially expressed genes (DEGs) identified using a standard edgeR pipeline.

first: Christopher

last: McCabe

first: Martin

last: Read


title: Tumor matrix proteoglycan accumulation and processing alters T cell effector function and the response to immunotherapy in oligometastatic colorectal cancer

city: Madison

first: Huy

last: Dinh

state: WI

address: 1111 Highland Avenue

institute: University of Wisconsin-Madison

summary: Versican (VCAN) is an immunoregulatory extracellular matrix proteoglycan that when cleaved by ADAMTS proteases releases an immunostimulatory fragment, versikine. Here, we confirm that VCAN accumulates within colorectal cancers (CRCs) and inhibits T cell trafficking/effector function. VCAN is heavily proteolyzed in a subset of CRCs (VCAN proteolytic predominant (VPP)), leading to enhanced T cell infiltration. This phenotype was found to be more common in oligometastatic CRCs. A phase 1b clinical trial examined the safety/efficacy of the sequential combination of stereotactic body radiotherapy and pembrolizumab in patients undergoing resection of their microsatellite stable oligometastatic CRCs. The primary endpoint was met with a 1-year recurrence free survival (RFS) of 60%. Of those enrolled, 40% of cancers had the VPP phenotype, which was associated with improved RFS and overall survival. The VPP phenotype was associated with improved circulating T cell effector function, which was enhanced with study treatment. Clinical trial information: NCT02837263.

overall_design: PBMCs from trial participants were stored, prepared for sequencing, and then profiled using 10X Genomics fixed single-cell RNA sequencing according to the 10x genomics user guide CG000527 Rev E. Single cells were captured and barcoded using the 10X Chromium controller using its 3’ or 10X Flex (probe- based) whole transcriptome kits. Gel Bead-In EMulsions (GEMs) were prepared, followed by cDNA amplification and size-based cleanup. Final libraries were sequenced using NovaSeq and NovaSeqX platforms to target at least 20k reads per cell.

first: Dustin

last: Deming

first: Sean

last: Krau

first: Joshua

last: Brand

first: Katherine

last: Johnson

first: Daniel

last: Abbott

first: Jeremy

last: Kratz

first: Anita

last: Turk

first: Philip

last: Emmeric

first: Evie

last: Carchman

first: Sam

last: Lubner

first: Noelle

last: LoConte

first: Nataliya

last: Uboha

first: Somak

last: Chaudhuri

first: Ruchi

last: Shah

first: Anna

last: Field

first: Elizabeth

first: Cheri

last: Pasch

first: David

last: Kim

first: Sharon

last: Weber

first: Charles

last: Heise

first: Elise

last: Lawson

first: Cristina

last: Sanger

first: Kristina

last: Matkowskyj

first: Fotis

last: Asimakopoulos

first: Jens

last: Eickhoff

last: Bassetti


title: Loss of Angiopoietin-2 leads to region-specific brain malformations and blood-brain barrier leakage

city: Stockholm

first: Michael

last: Vanlandewijck

address: Blickagången 6

department: Department of Medicine

institute: Karolinska Institute

summary: Angiopoietin-2 (ANGPT2) is known to destabilize vascular barriers in most peripheral organs; however, its role in the brain vasculature remains poorly understood. To investigate its physiological function within the brain vasculature, we analyzed constitutive Angpt2 knockout (KO) mice in adulthood. We show that loss of ANGPT2 leads to region-specific vascular malformations and blood-brain barrier (BBB) dysfunction, resulting in differential permeability to 1 kDa and 70 kDa fluorescent tracers. Notably, overt vascular malformations appeared only in select brain regions that allowed leakage of both tracers. These malformations were characterized by dilated, intertwined, and sprouting endothelial cells, surrounded by reactive perivascular cells, along with high levels of astrocyte- and neuron-derived vascular endothelial growth factor A (VEGFA) and elevated expression of the vascular receptors VEGF receptor 2 (KDR) and neuropilin 1 (NRP1). Other cortical areas without obvious malformations exhibited significant leakage of the 1 kDa tracer. We also demonstrate that different cell types take up the tracers after passing the BBB. Our findings identify ANGPT2 as an important factor involved in the regulation of cerebrovascular architecture, barrier integrity, and endothelial–parenchymal interactions, and uncover surprising differences in the leakage patterns and cellular uptake of two widely used BBB tracers.

overall_design: For scRNA-seq, the cerebrums were collected and the microvascular fragments were isolated as previously described by Bjornholm et al (Cell Rep Methods 2023, PMID: 37056377) with minor modifications prior 10x Genomics scRNA-seq.

first: Weihan

last: Li

first: Elisa

last: Vázquez-Liébanas

first: Chanaelle

last: Fébrissy

first: Florent

last: Sauvé

first: Jianhao

last: Wang

first: Doğan

last: Sayıner

first: Pia

last: Buslaps

first: Amanda

last: Norrén

first: Liqun

last: He

first: Marie

last: Jeansson

first: Lars

last: Muhl

first: Maarja

last: Andaloussi Mäe


title: Targeting lymphatic vessels enhances bone regeneration by augmenting osteoclast activity in mouse models of amputation

city: Dallas

first: Sneha

last: Korlakunta

address: 6000 Harry Hines Blvd

department: Surgery

institute: UT Southwestern Medical Center

summary: Although mammals generally demonstrate limited regenerative capacity compared with amphibians, the digit tip retains remarkable regenerative potential, providing a useful model to study successful mammalian regeneration. This process involves coordinated immune cell activity, vascular remodeling, and tissue reconstruction, yet the molecular checkpoints controlling regenerative versus fibrotic outcomes remain poorly understood. In mammals, regeneration of the digit tip (P3) proceeds through myeloid cell migration, early osteoclast-mediated osteolysis of the distal bone, and subsequent blastema-mediated regeneration. Here we test the hypothesis that lymphatic vessels regulate regenerative capacity by modulating local immune cell dynamics and osteoclast function. Using a lymphatic system–specific reporter line, we discovered that lymphatic vessels grow toward the nail region from the ventral side of the digit during quiescence and after amputation. These lymphatics closely surround, but do not invade, the native or regenerated bone. Unexpectedly, genetic, pharmacological, and surgical inhibition of lymphangiogenesis accelerated early osteolysis through enhanced transition of myeloid cells to osteoclasts, resulting in faster and more robust regeneration. These findings reveal a mechanism linking lymphatic vessel, immune regulation, and bone remodeling, suggesting that targeted manipulation of lymphatics dynamics may enhance regenerative outcomes after musculoskeletal injury.

overall_design: 1. P3 digits were isolated after dietary administration of SAR131675 (a well-characterized inhibitor for VEGFR3),30 mg/ Kg chow (30ppm) for 8 days with diet matched controls. 2. P3 digits were isolated after lymph node removal (LNR) on one extremity with sham controls.

first: Neda

last: Vishlaghi

first: Benjamin

last: Levi


title: In situ spatial transcriptomics reveal novel markers of the limbal stem cell niche and ocular surface epithelia

city: Kensington

first: Orazio

last: Vittorio

address: High St

department: School of Biomedical Sciences, Faculty of Medicine

country: Australia

institute: UNSW Sydney

summary: The mammalian cornea is endowed with stem cells (SCs) that have lifelong regenerative activity for its stratified epithelium. The niche for these cells is the limbus, and damage to this microstructure or its SCs results in a blinding disease known as limbal stem cell deficiency (LSCD). Despite the numerous studies that employ single-cell RNA sequencing, the identity of these cells remains an enigma principally because their spatial positioning is lost upon dissociation from their repository, and their gene expression is altered upon exposure to physical and chemical stressors during procurement. Herein, these adversities were avoided by conducting spatial transcriptomic screening directly on corneal, limbal and conjunctival tissues. Differentially expressed genes in the limbus included Krt16 and Nkiras1 among 6 others, which play a role in maintaining stemness, epithelial organization, immune surveillance, and tumor suppression. Krt16 was dynamically expressed in the developing limbus, correlated with slow-cycling label-retaining limbal epithelia and was induced during corneal injury; observations consistent with marking functional SCs. Additionally, we established Nkiras1 as a novel maker of neutrophils in the limbal SC niche, and Alox12e as a specific marker of conjunctival epithelia. Because current gold standard treatments for LSCD include SC transplantation, our data will inform future studies in delivering a more reliable standard therapy which incorporates an identifiable SC population to improve clinical outcomes.

overall_design: C57BL/6 male and female wild-type mice (n = 81) were obtained from Australian BioResources (Moss Vale, Sydney, Australia). They were housed under pathogen-free conditions in temperature-controlled rooms and given ad libitum access to standard chow and water. Eyes (n=3) were fixed in 4% paraformaldehyde (PFA) overnight. The superior nasal (SN) quadrant was dissected and paraffin-embedded. Sections (5µm) were mounted onto glass slides within a 35.3mm x 14.1mm area, dried at 58°C for 3 hrs, then subjected to the GeoMx DSP workflow (Bruker Spatial Biology, San Jose, CA). Prior to selecting ROIs, serial sections were stained with hematoxylin or double immunostained for K8 and K12 to identify tissue boundaries. ROIs included corneal, transitional (containing some limbus and cornea), limbal and bulbar conjunctival epithelia.

first: Lamia

last: Nureen

first: Antonietta

last: Salerno

first: Nick

last: Di Girolamo


title: SETD2 methyltransferase activity promotes correct transcription initiation and termination

city: Fukuoka

first: Takayuki

last: Nojima

state: Japan

address: Maidashi

department: Medical Sciences

institute: Kyushu University

summary: SETD2 is a methyltransferase responsible for depositing histone H3 lysine 36 trimethylation (H3K36me3). Loss of its enzymatic activity occurs in some cancers, including renal cell carcinoma. SETD2 mutations have been linked to delayed transcription termination, but have not been explored in depth. Here, using nascent transcriptomics in SETD2 knockout and patient-derived cells, we reveal a dichotomy in SETD2 functions depending on the affected protein-coding gene. The majority of genes, named class I, are dependent on SETD2 function for transcription initiation, yet terminate transcription in the usual locations. In contrast, for class II genes, corresponding to 15-25% of active protein-coding genes, transcription initiation is robust in absence of SETD2 activity; however, widespread transcriptional readthrough occurs. Defective termination following SETD2 loss/mutation is associated with increased cryptic transcription initiation and impaired 3′ pre-mRNA cleavage. Additionally, alternative polyadenylation upon SETD2 activity loss is highly cell type specific, and no relationship with transcription readthrough was observed. We demonstrate that methyltransferase activity of SETD2 stimulates proper initiation, prevents cryptic initiation and promotes efficient 3′ end processing, however it does so indirectly.

overall_design: POINTseq profiling U2OS parental cells and SETD2 KO cells.

first: Magda

last: Kopczyńska

first: Chihiro

last: Nakayama

first: Agata

last: Stępień

first: Shoko

last: Ito

first: Koshi

last: Imami

first: Michal

middle: R

last: Gdula

first: Kinga

last: Kamieniarz-Gdula


title: Stress-induced ADGRL4 orchestrates tumor dormancy and relapse via Gαs-YAP1 signaling and angiogenesis

city: Changsha

first: Xiaolong

last: Tang

state: Select State

address: No. 106, Fubuhe Road, Yuelu district,

institute: Hunan University

summary: Adhesion G protein-coupled receptors (aGPCRs), the second-largest GPCR family, remain poorly understood due to their structural complexity. Here, we identify the member ADGRL4 as a key orchestrator of tumor adaptation to stress. Cellular stress induces ADGRL4 expression via the canonical JNK-ATF2/c-Jun pathway. Elevated ADGRL4 suppresses tumor expansion and enforces a dormancy-like state, whereas its loss accelerates tumor growth and metastasis. Mechanistically, stress-induced shedding of the N-terminal fragment (NTF) activates the C-terminal fragment (CTF) of ADGRL4, which couples with Gαs to stimulate cAMP-PKA signaling and consequently suppress YAP1 activity. In the absence of ADGRL4, hyperactivated YAP1 forms a transcriptional complex with β-catenin, reprograming the extracellular matrix (ECM) signaling to bypass tumor dormancy and drive tumor expansion. Notably, stress-induced ADGRL4 exerts dual effects: while restraining tumor growth through dormancy enforcement, it simultaneously diminishes chemosensitivity and promotes angiogenesis, thereby heightening relapse risk. Thus, ADGRL4 emerges as a stress sensor that integrates YAP1 signaling with tumor angiogenesis to govern the balance between dormancy and relapse, providing mechanistic insight into therapy-induced tumor progression.

overall_design: RNA-seq profiling of control B16 (Con) cells and knockdown derivatives (KD1 and KD2) was conducted using three biological replicates per group.


title: Genome-scale perturb-seq in primary human CD4+ T cells reveals genes regulating T cell programs and human immune traits.

city: Palo Alto

first: Lattice

last: Data Coordination

address: 3165 Porter Drive

department: Genetics

institute: Stanford University

summary: CD4+ T cells orchestrate immune responses against infection and cancer, yet a comprehensive map of their gene regulatory networks has been lacking. Perturb-seq enables systematic mapping of such networks, but large-scale application in primary human T cells has been challenging. Here, we developed a scalable, probe-based Perturb-seq platform and performed genome-scale perturbations of all expressed genes across 22 million primary CD4+ T cells from four donors under three stimulation conditions. We demonstrate the utility of this dataset in three ways. First, we identify previously unrecognized regulators of the two important immune cytokines, IL-10 and IL-21. Second, we show that ex vivo perturbation signatures can model T cell states observed in population-scale atlases, revealing regulators of helper T cell polarization and T cell aging. Third, we leverage regulatory relationships to mechanistically explain gene–trait associations in immune-related diseases, nominating genes for uncharacterized immune functions. Thus genome-scale perturb-seq in primary human T cells provides a foundational resource for decoding immune variation in humans and reprogramming T cell states for next-generation precision therapies.

overall_design:
scRNA-seq of human CD4-positive, alpha-beta T cells with genome-wide CRISPR interference screen, resting and stimulated conditions from 4 donors.scRNA-seq of human CD4-positive, alpha-beta T cells with genome-wide CRISPR interference screen, resting and stimulated conditions from 4 donors.
bulk RNA-seq of human CD4-positive, alpha-beta T cells with CRISPR interference and T cell stimulation, 5 donors, 9 CRISPRi targets

first: Ronghui

last: Zhu

first: Emma

last: Dann

first: Jun

last: Yan

first: Justine

last: Reyes Retana

first: Ryunosuke

last: Goto

first: Reese

last: Guitche

first: Lillian

last: Petersen

first: Mineto

last: Ota

first: Brian

last: Shy

first: Jonathan

last: Pritchard

first: Alexander

last: Marson


title: Nutritional Genomics Uncovers Vitamin B3 Therapy as Curative for NAXD Disease

city: San Francisco

first: Ayushi

last: Agrawal

address: 1650 Owens St

institute: Gladstone Institutes

summary: Vitamins are essential metabolites that must be obtained from external sources. All 13 vitamins were identified in the early 1900s, a rich era of biochemistry. More recently, they are consumed indiscriminately. We introduce a new nutritional genomics framework that begins with a treatment and identifies all potential disease candidates. Using a genome-wide CRISPR screen at varying vitamin B3 levels, we nominated dozens of diseases for B3-based therapy. The top candidate was NAXD, a proofreading enzyme involved in correcting an aberrant form of NADH (NADHX). Mutations in NAXD cause severe neurodevelopmental disease, with no proven therapies. We created a new mouse model of disease, observing NADHX accumulation and NAD+ depletion in affected organs, leading to impaired serine biosynthesis. Low B3 diets worsened the disease, while B3 supplementation was curative, extending lifespan by more than 20-fold. This work introduces a new approach to nutritional genomics and precision vitamin therapies.

overall_design: Nuclei were isolated from frozen hemi brains of P5 mice across different genotypes and experimental treatments. All mouse pups were treated with either vehicle or 750 mg/kg Nicotinamide Riboside starting from postnatal day 0 until collection on postnatal day 5. Mice were perfused with PBS, and the left hemi-brains (excluding the olfactory bulb) were collected from both Control and NAXD KO mice (n = 4 per genotype per treatment group). We then employed a single-nucleus RNA sequencing approach on these isolated nuclei using the 10x Genomics GEM-X Flex Kit protocol, where samples first undergo fixation before Gene Expression library preparation. This single-nucleus RNA-seq experiment using the GEM-X Flex protocol is probe-based rather than using 3' capture. We randomized the samples being assigned to each mouse probe barcode and assigned to each GEM reaction.

first: Ankur

last: Garg

first: Adam

last: Turner

first: Skyler

last: Blume

first: Michela

last: Traglia

first: Reuben

last: Thomas

first: Ryan

last: Corces

first: Isha

last: Jain


title: Nerve Growth Factor (NGF) drives ILC2 pro-tumoral functions - bulk RNA sequencing of human TRKA+ and TRKA- ILC2s

city: Lausanne

first: Tania

last: Wyss

address: Rue du Bugnon 25A

country: Switzerland

institute: SIB Swiss Institute of Bioinformatics

summary: ILC2s are key regulators of tissue homeostasis and inflammation. In cancer, ILC2s can exhibit pro-tumoral functions by increasing the MDSC/T-cell ratio. Nevertheless, the upstream ILC2 triggers remain poorly defined. Here, we identify NGF as the driver of ILC2 pro-tumoral functions in bladder cancer patients. We show that ILC2s express the NGF receptor TrkA and respond to NGF by secreting type-2 cytokines. In the tumor microenvironment, NGF-producing mast cells accumulate and activate ILC2s to induce Tregs, ultimately fostering tumor growth. In patients, NGF levels inversely correlate with survival in ILC2-rich tumors, underscoring the clinical significance of this axis. In vivo administration of a selective TrkA inhibitor improves survival in orthotopic tumor-bearing animals and sensitizes them to immune checkpoint blockade (ICB). Overall, we identify NGF as a novel ILC2 activator that shapes pro-tumoral ILC2 functions. The blockade of TrkA+ ILC2s might represent a targetable strategy to improve survival, particularly in ICB-resistant patients.

overall_design: To uncover transcriptomic differences between TrkA+ and TrkA- ILC2s, we sorted these two subpopulations from PBMCs of three healthy donors and performed bulk RNAseq.

first: Maryline

last: Falquet

first: Sara

last: Trabanelli

first: Alejandra

last: Gomez-Cadena

first: Ziyang

last: Su

first: Camilla

last: Jandus