title: ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis through Symbiotic Adhesion and Reverse Migration

status: Public on May 19 2026

first: Ling

last: Wu

summary: Analyses of neutrophils of pan human cancers revealed an ICAM1high subset enriched in the tumor microenvironment, mMurine triple negative breast cancer (TNBC) models recapitulate this observation. ICAM1high neutrophils exhibited enhanced capacity of cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion confers mutual advantages on both cell types. In contrast, cancer cells of mesenchymal-like phenotypes are thwarted by neutrophils due to decreased cell adhesion and elastase resistance. These nearly opposite effects drive the evolution toward a dichotomy of neutrophil-enriched, epithelial-like versus macrophage-enriched, mesenchymal-like ecosystems. The ICAM1high neutrophils are known for reverse migration (from tissue to circulation). The adhesive and reverse migratory properties together mediate metastatic intravasation. These observations were verified in a subset of human TNBCs that unexpectedly enrich in non-Hispanic European patients. Thus, we demonstrated a co-evolution through which neutrophils sculpt phenotypes and metastatic behaviors of TNBC, which may preferentially occur in patients of certain race/ethnicity.

overall_design: 2208L tumor cells were injected to the mammary fat pad of the Balb/c mice. The tumor was collected when its diameter reached 1cm and was disociated. ICAM1high and ICAM1low neutrophils were sorted by flow cymetry.

first: Xiang

last: H.-F. Zhang


title: Nanoparticulate Immunoactive Complex (IMAX) for local chemoimmunotherapy: From murine models to pilot canine study.

city: West Lafayette

first: Sagar

middle: M

last: Utturkar

state: IN

address: 201 S University St

department: Institute for Cancer Research

country: USA

institute: Purdue University

type: Expression profiling by high throughput sequencing

summary: A nanoparticulate IMmunoActive compleX (IMAX) was developed for local treatment of locatable and accessible tumors. This was used  to treat naturally-occuring cancers in dogs. Several naturally-occuring canine cancers resemble the same disease in humans.

overall_design: Three dogs with naturally-occuring cancer were treated with IMAX. RNAseq data are being submitted on longitudinal tumor samples collected from the dog pre- and post-treatment.

first: Deepika

last: Dhawan

first: Marejka

last: Shaevitz

first: Meaghan

last: Broman

first: Yeo

last: Yoon

first: Knapp

last: Deborah


title: Inflammatory reprogramming of immature oligodendrocytes perturbs myelination and neurodevelopment in a dual-hit model of preterm brain injury

city: Chongqing

first: Xueling

last: Ma

state: chongqing

address: Zhongshan 2nd Road, No.136

country: China

institute: Children's hospital of Chongqing Medical University

summary:
Background: Preterm infants are highly susceptible to white matter injury, in part due to exposure to perinatal inflammation and/or hypoxia. These insults dis_x0002_rupt oligodendrocyte (OL) lineage maturation, leading to impaired myelination and neurodevelopmental deficits; however, the underlying mechanisms remain incompletely understood.
Methods: A dual-hit rat model was established to recapitulate key features of preterm brain injury. Myelination, behavior, and brain function and structure were assessed. The early developmental trajectory of immature OLs was tracked, and the cells were isolated for transcriptomic profiling.
Results: The dual-hit model exhibited delayed myelination, accompanied by long-term behavioral abnormalities, reduced hippocampal functional connectivity, and decreased hippocampal gray matter volume. A marked surge in immature OL death was observed around postnatal day 9. Transcriptomic profiling at this developmentally vulnerable time point revealed pronounced inflammatory reprogramming within immature OLs.
Conclusions: Perinatal inflammation combined with postnatal hypoxia delays myelination and leads to persistent behavioral and brain structural and functional alterations, with immature OLs loss and inflammatory reprogramming emerging as potential drivers of preterm brain injury.

overall_design: A perinatal dual-hit injury model was established by intraperitoneal injection of lipopolysaccharide (LPS, 200 μg/kg, i.p.) into pregnant dams at embryonic day 18.5 (E18.5), followed by postnatal intermittent hypoxia exposure of offspring from postnatal day 3 to postnatal day 11 (P3–P11; 8 ± 1% O2 for 2.5 h/day). The uploaded datasets include two independent cohorts. Cohort 1 consisted of bulk RNA-seq analysis of whole brain tissue collected at postnatal day 11 (P11). Cohort 2 consisted of SMART-seq analysis of O4+ immature oligodendrocytes isolated from brain tissue at postnatal day 9 (P9) by fluorescence-activated cell sorting (FACS).

first: Wen

last: Jia

first: Xingdao

last: Zhang

first: Yuan

last: Shi


title: DNA-damage dependent association of Orc6 to ISWI during S-phase modulates chromatin remodeling [CUT_and_RUN]

city: Urbana

first: Supriya

last: Prasanth

state: IL

address: 601 S Goodwin Ave # C409

department: Department of Cell and Developmental Biology

institute: University of Illinois Urbana-Champaign

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The human Origin Recognition Complex subunit 6 has recently garnered significant attention because of its dispensability in the licensing of origins. The loss of human Orc6 doesn’t impact MCM loading in vivo, while in vitro reconstitution experiments have demonstrated that MCM loading can occur without Orc6, but could be stimulated upon the addition of Orc6. We recently reported an unexpected role for hOrc6, in promoting S-phase progression post pre-RC assembly and DNA damage response (DDR). Using CUT&RUN to map the binding of Orc6 genome-wide, we find that Orc6 is present at replication origins and at sites of DNA damage during S-phase. Upon encountering oxidative damage in S-phase, Orc6 associates with chromatin remodelers, SMARCA1/SNF2L, also a component of the replication fork. Loss of Orc6 shows enhanced genome-wide association of SMARCA1 to Orc6-bound sites, concomitant with chromatin remodeling at these sites supporting the model that Orc6 is a negative regulator of SMARCA1 and constrains its localization. Upon DNA damage, enhanced association of Orc6 to SMARCA1 prevents chromatin remodeling activity in order to halt replication progression. We propose that during S-phase, Orc6 is a barrier factor, which limits the activity of chromatin remodelers at replication and repair sites.

overall_design: CUT&Run of SMARCA5 was done in early S-phase-synchronized U2OS cells with presence or absence of Orc6 or/and H2O2-induced oxidative damage. CUT&Run of SMARCA1 was done in early S-phase-synchronized U2OS cells with absence of Orc2. CUT&Run of Orc6 was only done in cells with Orc6 presence.

first: Dazhen

last: Liu

first: Mohit

last: Mishra

first: Alvaro Gonzalo

last: Hernandez


title: Symbiotic Adhesion of Neutrophils and Epithelial-like Cancer Cells Shapes the Tumor Microenvironment and Promotes Metastasis [2]

city: Houston

state: TX

address: One Baylor Plaza

department: Breast Center

institute: Baylor College of Medicine

summary: Neutrophils play complicated roles in tumor progression. Examination of several murine triple negative breast cancer (TNBC) models revealed nearly opposite impact of neutrophils on epithelial-like vs. mesenchymal-like cancer cells (ECCs vs. MCCs). Interaction with ECCs upregulates ICAM1 in neutrophils, a feature that also distinguishes tumor-infiltrating neutrophils from other neutrophils in human. Direct adhesion between ECCs and neutrophils, especially the ICAMhigh subpopulation, promote the survival of each other – forming a symbiotic relationship. In contrast, MCCs are thwarted by neutrophils due to decreased cell adhesion and elastase resistance. The ICAM1high neutrophils are known for reverse migration to circulation. The adhesive and reverse migratory properties of ICAM1high neutrophils mediate intravasation of metastatic seeds. These observations were verified in a subset of human TNBCs that unexpectedly enrich non-Hispanic European patients. Thus, we demonstrated a co-evolution through which neutrophils sculpt phenotypes and metastatic behaviors of TNBC, which may preferentially occur in patients of certain race/ethnicity.

overall_design: ICAM1high and ICAM1low tumor infiltrating neutrophils from PyMT-N bearing C57/B6 mice were FACS sorted sequenced


title: Diminished transcriptional activity and splicing changes drive gene length-biased rewiring in the aging transcriptome (RNA-Seq)

status: Public on May 31 2026

city: Chicago

first: Ali

last: Shilatifard

address: 320 E Superior St

department: Department of Biochemistry and Molecular Genetics

institute: Northwestern University Feinberg School of Medicine

summary: Transcription by RNA polymerase II (RNAPII), which is essential for protein-coding gene expression and cellular function, is increasingly understood to become dysregulated with aging. Here, we use a multi-modal approach to comprehensively characterize age-dependent changes in RNAPII-mediated transcription in both mouse and human tissues. Short-read total RNA sequencing (RNA-seq) to profile nascent transcription reveals a global reduction in overall transcriptional activity/frequency in aged tissues, without apparent change in elongation rates. Transcriptomic analysis reveals a shift toward preferential expression of short genes in aged tissues, with notable upregulation of short stress-response genes and downregulation of long neurodevelopmental genes in the aged mouse brain. These results are recapitulated by analysis of total RNA-seq data from human tissues. Leveraging long-read RNA-seq, we determine that the representation of aberrant mono-exonic and intron-retention splice isoforms is increased in the aged mouse brain. Finally, we characterize the composition of RNAPII transcriptional machinery, finding that interactions between RNAPII and the Mediator complex are decreased in the chromatin of aged mouse liver and brain. Collectively, these analyses provide insight for future aging studies and reveal potential transcriptional control targets for anti-aging drug development.

overall_design: Gene expression profiling analysis of the whole brain, liver, and kidney using data obtained from total RNA-seq

first: Saeid

last: Parast

first: Madhurima

last: Das

first: Marta

last: Iwanaszko


title: Mitochondrial metabolism and epigenetic crosstalk drive the SASP (RNA-Seq)

city: La Jolla

first: Peter

middle: D.

last: Adams

state: CA

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: Senescent cells drive age-related tissue dysfunction largely through the persistent activation of the senescence-associated secretory phenotype (SASP). Here, we identify key mitochondrial metabolic pathways, including the mitochondrial citrate carrier (SLC25A1) and ATP-citrate lyase (ACLY), as critical regulators of the SASP. These pathways fuel histone acetylation at SASP gene loci, promoting their expression. Targeted inhibition of SLC25A1 or ACLY suppresses SASP expression without affecting cell cycle arrest, underscoring their potential as selective therapeutic targets for mitigating age-related inflammation. Furthermore, pharmacological inhibition of SLC25A1 reduces systemic inflammation and extends healthspan in aged mice. Our findings suggest that disrupting metabolic reprogramming in senescent cells offers a promising strategy to ameliorate aging-associated pathologies.

overall_design: mRNA profile of proliferative or senescent fibroblasts induced by irradiation (Sen(IR)) treated with two different mitochondrial transporter inhibitors (CTPI2 and UK5099)

first: Helene

last: Martini

first: João

middle: F

last: Passos


title: Mitochondrial metabolism and epigenetic crosstalk drive the SASP (ChIP-seq)

overall_design: Chromatine Immunoprecipitation DNA sequencing (ChIP-seq) for histone variants H3K27ac and H3 totale in two type of experiments: 1) proliferative, senescent and senescent cells upon mitochondrial clearance (IMR90 Parkin) 2) Proliferative, Senescent and Senescent cells treated with SLC25A1 inhibitor (CTPI2) in MRC5

first: Aaron

last: Havas

first: Rabi

last: Murad

first: Xue

last: Lei

first: Rebecca

middle: A

last: Porritt

middle: D


title: DNA-damage dependent association of Orc6 to ISWI during S-phase modulates chromatin remodeling [ATAC-Seq]

overall_design: ATAC-seq in early S-phase-synchronized U2OS cells with presence or absence of Orc6 or/and H2O2-induced oxidative damage.

first: Liu

last: Dazhen

first: Mishra

last: Mohit

first: Hernandez

last: Alvaro Gonzalo


title: Effects of T cell–specific IL-21 isoform expression on gene expression in mammary epithelial cells.

status: Public on May 18 2026

city: Yamagata

first: Junji

last: Yokozawa

address: 2-2-2 Iida-Nishi

department: Department of Immunology

country: Japan

institute: Yamagata University Faculty of Medicine

summary: Interleukin-21 (IL-21) is a pleiotropic cytokine produced by CD4⁺ T cells that critically regulates the differentiation and functions of various adaptive and innate immune cells. In this study, to investigate the chronic effects of IL-21 on gene expression in mammary epithelial cells (MECs), MECs were isolated from 10-week-old transgenic mice expressing a membrane-bound IL-21 isoform specifically in T cells (IL-21isoTg) and subjected to RNA sequencing analysis, followed by comparison with wild-type controls. IL-21isoTg MECs showed marked upregulation of genes associated with mammary gland development and lactation and Spp1.

overall_design: RNA-seq analysis of mammary epithelial cells from 10-week-old female wild-type BALB/c mice and BALB/c transgenic mice expressing the IL-21 isoform specifically in T cells.

first: Risako

last: Yamaguchi

first: Hironobu

last: Asao


title: Methylation Mesa define functional regulatory elements for targeted gene activation

city: Boston

first: Mahmoud

middle: Adel

last: Bassal

state: Massachusetts

address: 3 Blackfan Circle

department: Hematology and Oncology

institute: Beth Israel Deaconess Medical Center

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Spleen and brain T cells in Toxoplasma gondii infection- scRNA-seq, CITE-seq and TCRab

first: Liang

last: Yang

state: MA

address: 77 Avenue Louis Pasteur

department: Pathology

institute: Harvard Medical School

summary: This study is part of the immgenT Open Source Project, specifically IGT59, which characterizes activated CD4 and CD8 T cells in the spleen and brain during Toxoplasma gondii infection at 9 dpi (peak infection in the spleen) and 23 dpi (chronic phase with brain cysts). Splenocytes from uninfected controls were also profiled. It includes a spleen control at baseline (6-8-week-old C57BL/6J mouse).

overall_design: Female C57BL/6NCrl mice were infected orally with 10 ME49 T. gondii cysts. Cells were isolated from spleen or brain tissue after mechanical dissociation, using defined gating strategies: CD45+ CD5+ B220- CD4+ CD44+, CD45+ CD5+ B220- CD8a+ CD44+, and CD45+ CD5+ B220- CD4+ CD44+ AS15-Tet+. Spleen samples were collected at 9 and 23 dpi, while brain samples were collected only at 23 dpi. T cells were profiled using single-cell RNA sequencing (10x Genomics), combined with CITE-seq (TotalSeq C) and paired TCR α/β sequencing. Samples were pooled using hashtags

first: Melanie

last: Vacchio

first: Alexander

last: Clark

first: Ian

last: Magill

first: David

last: Zemmour

first: Christophe

last: Benoist

first: Rémy

last: Bosselut


title: BCMA CAR promoter choice drives a highly effective GZMK+ transcriptional program

city: New York

first: Sneha

last: Mitra

state: New York

address: 1265 York Ave

institute: Memorial Sloan Kettering Cancer Center

summary: Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are FDA-approved BCMA-directed CAR T cells for multiple myeloma. The increased efficacy of cilta-cel compared to ide-cel may be related to its unique nanobody binding domain, but the constructs also differ in their use of EF1α and MND promoters, respectively, to drive CAR expression. To elucidate the basis of cilta-cel’s superior efficacy, we analyzed CAR T cells from 87 patients (50 cilta-cel, 37 ide-cel) using flow cytometry and single-cell multi-omics. Cilta-cel showed a 10-fold higher peak expansion and greater persistence, driven by an inflammatory GZMK⁺ T cell subset marked by EOMES expression and motif accessibility, but not exhaustion profile. Animal modeling revealed that the EF1α promoter (cilta-cel) rather than binder recapitulated increased tumor control, enhanced expansion and GZMK transcriptional profile compared to the MND promoter (ide-cel). Cilta-cel’s efficacy is therefore linked to EF1α-driven GZMK⁺ transcriptional trajectory that supports both persistence and effector function.

overall_design: Multi-omic DOGMA-seq assessment was performed on peripheral blood mononuclear cells collected from ide- and cilta-cel treated patients. Cells were sorted for live, CD3+, and CAR+ cells from 13 patients at early (days 7-14), intermediate (days 25-35), and late (days 60-90 post-infusion) timepoints. Cells were hashed and batched to preserve identity and ensure similar frequencies of cells from both cilta- and ide-cel treated patients.

first: Herrera

last: Kevin

first: Mitra

last: Sneha

first: Sun

last: Yuqing

first: Lucero

last: Kimberly

first: Singh

last: Kristin

first: Chen

first: Takizawa

last: Meril

first: Shah

last: Gunjan

first: Giralt

last: Sergio

first: Park

last: Jae

first: Usmani

middle: Z

last: Saad

first: Chaligne

last: Ronan

first: de Stanchina

last: Elisa

first: Mailankody

last: Sham

first: Leslie

middle: S

last: Christina

first: Perica

last: Karlo


title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while preserving gut microbiota homeostasis [mouse lung macrophages]

city: beijing

first: lu

last: z

state: - 选择 -

address: beijing

institute: institution of microbology

summary: Staphylococcus aureus (SA) remains a global health threat due to its increasing drug resistance and intracellular persistence, which compromise the efficacy of conventional antibiotics. Host-directed therapy (HDT) has emerged as a promising alternative by modulating host immunity. With the multi-targeting and immunomodulatory properties, Traditional Chinese Medicine (TCM) monomers represent ideal candidates for HDT. However, their ability to promote host immunity-mediated SA clearance remains largely unexplored. Here, we identified triptolide as a compound that facilitates intracellular clearance of SA and MRSA. Mechanistic studies revealed that triptolide directly binds to the X‑linked inhibitor of apoptosis protein (XIAP) to inhibit XIAP-caspase interaction, thereby releasing caspase inhibition and inducing apoptosis. Moreover, treatment with triptolide reduced bacterial loads and alleviated lung inflammation in mice infected with SA and MRSA, concurrently maintaining microbiota homeostasis and improving metabolic function. Taken together, these findings establish triptolide as a promising lead compound for the development of HDT against SA and MRSA infections.

overall_design: triptolide, and from lung macrophages of mice infected with SA or MRSA treated with PBS, triptolide, triptolide combined with SM-164, or methicillin

first: Zehui

last: Lei

first: Jing

last: Wang

first: Cui Hua

last: Liu


title: Plasma and Extracellular Vesicle small RNAs sequencing -severe Traumatic Brain Injury Patients,polytrauma patients and healthy controls

city: Frankfurt am Main

first: Cora

middle: Rebecca

last: Schindler

address: Theodor-Stern-Kai 7

country: Germany

institute: Goethe University

type: Non-coding RNA profiling by high throughput sequencing

summary: This study aimed to compare plasma- and extracellular vesicles (EVs)-associated microRNAs (miRNAs) signatures in patients with severe TBI, polytrauma and healthy controls.

overall_design: For profiling circulating miRNAs, blood samples were collected ≤3 and at 48 hours after admission. Plasma samples of n=15 patients with severe isolated TBI (AISHead ≥4, all other AIS ≤1), n=15 Patients with polytrauma (ISS ≥16, AISHead= 0) and n=15 age- and sex-matched healthy controls were pooled (n=5/ pool) and subjected to next-generation sequencing (NGS).

first: CR

first: L

last: Leppik

first: I

last: Schaible

last: Kraemer


title: Triptolide clears Staphylococcus aureus infection by targeting XIAP to induce host apoptosis while preserving gut microbiota homeostasis [iBMDMs]

overall_design: iBMDMs infected with SA and treated with DMSO


title: NR5A2 controls gene expression and chromatin contacts of essential circadian metabolic genes in the liver

status: Public on May 27 2026

city: Mexico City

first: Mayra

last: Furlan-Magaril

state: Mexico City

address: Circuito exterior s/n

department: Molecular Genetics

country: Mexico

institute: IFC-UNAM

summary: Circadian regulation of gene expression relies on the coordinated action of core clock components, tissue-specific transcription factors, and epigenetic mechanisms, including dynamic enhancer–promoter interactions. Although rhythmic chromatin looping has been described in the liver, the transcription factors that mediate these temporal interactions remain poorly defined. Here, we identify the nuclear receptor NR5A2 as a key regulator of circadian enhancer–promoter communication in the mouse liver. We show that NR5A2 protein levels fluctuate over the 24-hour cycle, peaking around Zeitgeber time 0 (ZT0). Genome-wide analysis reveals that NR5A2 preferentially binds H3K27ac-enriched enhancer regions, many of which engage in chromatin looping with promoters of metabolic genes. High-resolution 4C-seq analyses demonstrate that promoters of Elovl5 and Ppp1r3c dynamically interact with NR5A2- and H3K27ac-enriched enhancers in a time-dependent manner, with maximal interactions at ZT0 and reduced contacts at ZT12. Pharmacological inhibition of NR5A2 in vivo leads to alterations in hepatic glycogen and cholesterol accumulation, attenuates the rhythmic expression of circadian metabolic genes, including Ppp1r3c, Cyp8b1, and Elovl5, and disrupts enhancer–promoter contact frequencies at the Elovl5 locus. Together, our findings provide in vivo evidence that NR5A2 integrates circadian and metabolic regulation by modulating enhancer–promoter chromatin interactions, thereby shaping rhythmic liver gene expression.

overall_design: 4C-seq experiments from mouse liver tissues at opposite times during the day. Experimental conditions include WT, Vehicle, and SR1848-treated samples. For each condition, two biological replicates were conducted

first: Abraham

last: Román-Figueroa

first: Juan Carlos

last: Gómora-García

first: Luis

last: Tenorio-Hernández

first: Rosario

last: Pérez-Molina

first: Karina

last: Jácome-López


title: Transcriptome-guided development of a fibrosis-reversal compound reduces skin scarring and allows regeneration via mitochondrial uncoupling [RNA-seq]

city: Beijing

first: Ruilin

last: Xu

address: No.5 Yiheyuan Road, Haidian District, Beijing, P.R. China

institute: Peking University

summary: Skin scarring impairs function and aesthetics. Current therapies show limited efficacy and cause iatrogenic dermal disruption (e.g., triamcinolone acetonide, a first-line corticosteroid for keloids), with topical medications demonstrating inferior outcomes. Through transcriptome-guided evaluation, we develop FR-1 (fibrosis-reversal compound 1), a small molecule that reverses fibrosis in vitro by inhibiting fibroblast proliferation, suppressing α-SMA, and remodeling the ECM via collagen downregulation and MMP1 induction. In a murine linear excisional wound model, daily topical FR-1 application progressively reduces scar area. Notably, unlike triamcinolone acetonide, FR-1 avoids skin atrophy and hair follicle damage. Comprehensive safety evaluations, druggability and skin permeation assessments, and studies utilizing patient-derived keloid ex vivo explants and in vivo xenografts demonstrate its translational potential. Mechanistically, FR-1 induces mitochondrial uncoupling, lowering ATP levels in profibrotic myofibroblasts. Other uncouplers similarly attenuate fibrosis. This work identifies a topical small molecule that attenuates scarring, highlighting the therapeutic potential of mitochondrial uncouplers in resolving fibrosis.

overall_design: Keloid fibroblasts were treated with various small molecules in KF medium  (10% FBS DMEM, 2% penicillin-streptomycin, 1% ITS, and 20 ng/ml bFGF) for 2 days and analyzed using  DRUG-seq2 or bulk RNA-seq

first: Chunye

last: Chen

first: Jiahao

last: Wu

first: Jun

last: Chi

first: Zhangrui

first: Yi

first: Xincao

last: Zhong

first: Xiaoying

last: Lin

first: Zhongya

last: Song

first: Yang

first: Yong

last: Yang

first: Weiqiang

last: Tan

last: Zhao


title: Cattle and human organoids recapitulate the trans-species transmission of H5N1 2.3.4.4b virus and reveal cross-reactive neutralizing antibodies in humans

city: Hong Kong

first: Jie

last: Zhou

address: 102 Pokfulam Road, Pokfulam, Hong Kong

department: Microbiology

country: Hong Kong

institute: The University of Hong Kong

summary: The unexpected circulation of clade 2.3.4.4b H5N1 influenza viruses in dairy cattle and the transmission to diverse mammalian species poses a pandemic risk. We sought to explore cattle and human respiratory susceptibility to the 2.3.4.4b H5N1 virus. We establish long-term expandable cattle airway and mammary organoids. The 2.3.4.4b H5N1 virus exhibits high replicative fitness in cattle mammary organoids, recapitulating its remarkable mammary tropism. The virus also replicates robustly in cattle airway organoids, suggesting an underrecognized respiratory component in ongoing outbreaks. Interestingly, human airway and nasal organoids are highly susceptible to the 2.3.4.4b H5N1 virus. Yet, a novel organoid-based neutralization assay reveals that N1 antibodies in human sera had cross-neutralizing activity against the 2.3.4.4b H5N1 and ancestral H5N1-VN1194 viruses. The cross-neutralization, exclusively manifested in the organoid-based assay, is enhanced after seasonal influenza vaccination and diminished after depleting N1-specific antibodies. Therefore, cross-neutralizing N1 antibodies are likely limiting zoonotic infection by H5N1 viruses in humans.

sample_organism:
Homo sapiens
Bos taurus

platform_organism:
Homo sapiens
Bos taurus

overall_design: To characterize the cellular response in human airway and nasal organoids with the infection of H1N1, H5N1, CH5N1, we infected human airway and nasal organoids, cattle airway organoids. Three biological replicates of mock-treated, HRV-C infected, HRV-C infected with CYT387 treatment airway and nasal organoids were harvested for RNA extraction using RNAeasy Mini Kit (Qiagen, Cas.74106).After a quality check with Bioanalyzer, RNA specimens were applied to library preparation by KAPA mRNA HyperPrep Kit. In brief, Poly-A containing mRNA was collected by using poly-T oligo-attached magnetic beads. The purified mRNA was fragmented to 200 ~ 300 bp by incubating at 94°C for 6 min in the presence of magnesium ions. The fragmented mRNA was then applied as a template to synthesize the first-strand cDNA by using random hexamer-primer and reverse transcriptase. In the second strand cDNA synthesis, the mRNA template was removed and a replacement strand was generated to form the blunt-end double-stranded (ds) cDNA. The ds cDNA underwent 3’ adenylation and indexed adaptor ligation. The adaptor-ligated libraries were enriched by 15 cycles of polymerase chain reaction (PCR). The libraries were denatured and diluted to optimal concentration. Illumina NovaSeq 6000 was used for Pair-End 151bp sequencing. Sequencing reads were assigned to individual samples. Each sample had an average throughput of 4.6 Gb and a total throughput of 54.8 Gb.Quality control of raw fastq data was carried out by FastQC v0.11.7 (http://www.bioinformatics.babraham.ac.uk/projects/fastqc/) and fastp [PMID: 30423086]. Then clean reads were aligned to the UCSC GRCh38 reference and the Rhinovirus C3 strain genome (GenBank: OK161378.1) using Hisat2 v2.2.1 [PMID: 31375807]. HTSeq v0.6.1 [PMID: 25260700] was used to generate raw read count for each gene. Differential expression analysis was performed using DESeq2 [PMID: 25516281]. Genes with log2|fold change| > 1 and adjusted p-value < 0.05 were considered significantly different. Volcano plot was generated using EnhancedVolcano R package (https://github.com/kevinblighe/EnhancedVolcano). Heatmaps of gene expression levels were constructing using the pheatmap R package (https://cran.r-project.org/web/packages/pheatmap/index.html). Gene set enrichment analysis (GSEA) was performed using fgsea R package (https://github.com/ctlab/fgsea).

first: Cun

last: Li

first: Yifei

last: Yu

first: Zhixin

last: Wan

first: Jianpiao

last: Cai

first: Jingjing

last: Huang

first: Xiaoxin

last: Zhu

first: Jiali

first: Wei

last: Xue

first: Ying

first: Manchun

last: Chiu

first: Qiaoshuai

last: Lan

first: Shuxin

last: Zhang

first: Zijun

first: Yidong

first: Yuhong

last: Liu

first: Pui

last: Wang

first: Shaofeng

last: Deng

first: Ming

last: Yue

first: Longchao

first: Keshan

first: Mengmeng

first: Jieshi

first: Wen-kang

last: Wei

first: Xiang

last: Gao

first: Lin

first: Hin

last: Chu

first: Gang

first: Honglin

first: Kwok Yung

last: Yuen

first: Richard

last: Webby


title: Loss of O-Antigen Due to wbbL Mutations is Common and Associated with Increased Mortality in Escherichia coli Bloodstream Infections

city: Durham

first: Joshua

last: Parsons

state: NC

address: 203 Research Dr

institute: Duke University

summary: Escherichia coli bloodstream infections are common and associated with high mortality. A key feature of E. coli is the lipopolysaccharide (LPS) O-antigen, which contributes to immune evasion during invasive infection. We analyzed serial E. coli isolates from patients with relapsed bacteremia and identified frequent disruption of O-antigen synthesis due to mutations in wbbL, resulting in a rough LPS (R-LPS) phenotype. E. coli with rough LPS isolates were more serum sensitive and less pathogenic in mice. Despite this apparent attenuation, 11 of 66 (18%) E. coli sequence type 131 bloodstream isolates in our cohort lacked O-antigen and were associated with significantly worse clinical outcomes, including septic shock and mortality. Using a recurrent bacteremia model, we show that R-LPS isolates partially evade protective immunity generated against smooth-LPS E. coli, highlighting the importance of host immune context in invasive disease.

overall_design: RNAseq profiling of PBMCs from three healthy donors treated with heat killed E. coli with smooth LPS, rough LPS or PBS for 4 hours

first: Kaleb

middle: J

last: Tyson

first: Amanda

last: Velez

first: Blake

last: Hanson

first: Jianping

last: Jiang

first: Kuan-Yi

last: Lu

first: Felicia

last: Ruffin

first: Granger

last: Sutton

first: Lauren

last: Brinkac

first: Thomas

middle: H

last: Clarke

first: Yazhong

last: Tao

first: Derrick

middle: E

last: Fouts

first: Mark

last: Adams

first: Sanjay

last: Khandelwal

first: Cesar

last: Arias

first: Vance

middle: G

last: Fowler

middle: T

last: Thaden

first: Brian

middle: P

last: Conlon

middle: B


title: Transcriptome-guided development of a fibrosis-reversal compound reduces skin scarring and allows regeneration via mitochondrial uncoupling [DRUG-seq2]

first: Ruilin

last: Xu

overall_design: Keloid fibroblasts were treated with various small molecules in KF medium  (10% FBS DMEM, 2% penicillin-streptomycin, 1% ITS, and 20 ng/ml bFGF) for 2 days and analyzed using  DRUG-seq2 or bulk RNA-seq.

first: Chunye

last: Chen

first: Jiahao

last: Wu

first: Jun

last: Chi

first: Zhangrui

first: Yi

last: Wang

first: Xincao

last: Zhong

first: Xiaoying

last: Lin

first: Zhongya

last: Song

first: Yang

last: Liu

first: Yong

last: Yang

first: Weiqiang

last: Tan

last: Zhao


title: High resolution mapping of erythroid niches in mice using subcellular spatial transcriptomics

first: Xu

last: Han

address: 303 E Chicago Avenue

institute: Northwestern University

summary: Like hematopoiesis, erythropoiesis requires erythroid niches nurturing and support. We performed subcellular spatial transcriptomics to reveal the erythroid niches in mice. Our results identified novel erythroblastic island macrophage marker in mouse during development and stress.

overall_design: Diverse hematopoietic organs including embryonic 13.5 days fetal liver, embryonic 14.5 days fetal liver, bone marrow including P8 bone marrow and bone marrow from 89 weeks old wild type mice, and spleen from wild type mice were used for the analysis. Spleen from the PHZ treated mice was also used for the analysis. These samples were analyzed using subcellular spatial transcriptomics.        "

first: Peng

last: Ji


title: High resolution mapping of erythroid niches in human using subcellular spatial transcriptomics

summary: Like hematopoiesis, erythropoiesis requires erythroid niches nurturing and support. We performed subcellular spatial transcriptomics to reveal the erythroid niches in human. Our results identified novel erythroid niches in human during development and stress.

overall_design: Formalin-Fixed Paraffin-Embedded (FFPE) blocks of diverse human hematopoietic organs including embryonic 16 weeks (gestational age, GA) fetal liver, adult bone marrow from healthy donor and MDS patient were used for the analysis. These FFPE block samples were analyzed using spatial transcriptomics.


title: Spatial mapping reveals erythroid niches in human during development and stress

summary: Like hematopoiesis, erythropoiesis requires erythroid niches nurturing and support. We performed spatial transcriptomics to reveal the erythroid niches in human. Our results identified novel erythroid niches in human during development and stress.

overall_design: Formalin-Fixed Paraffin-Embedded (FFPE) blocks of diverse human hematopoietic organs including embryonic 12 weeks and 16 weeks (gestational age) fetal liver, adult bone marrow from healthy donors and MDS patients were used for the analysis. These FFPE block samples were analyzed using spatial transcriptomics.


title: The MYB-related Transcription Factor MYPOP acts as a Selective Regulator of Cancer Cell Growth

city: Mainz

first: Federico

last: Marini

address: Obere Zahlbacher Strasse 69

department: Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI)

institute: University Medical Center - Mainz

summary: The MYB-related transcription factor and partner of profilin (MYPOP or p42POP) is a ubiquitously expressed and understudied protein, recently discovered in restricting oncogenic human papillomaviruses (HPV) and suggested as a tumor suppressor. In this study, we investigate the role of MYPOP on cancer cells.  At supra-physiological levels, induced by both plasmid DNA- and messenger RNA-mediated gene transfer, MYPOP emerges as a potent tumor growth inhibitor, capable of inducing cancer cell death while sparing normal cells. Using HPV-transformed cervical cancer cells and normal human epidermal keratinocytes, cell behavior assessments as well as transcriptome analysis revealed MYPOP's specific anti-proliferative and death-inducing impact on cancer cells. We found MYPOP capable of silencing viral and human oncogenes including E6, E7, and MYC, and of triggering the release of the cancer-killing cytokine interleukin-24. Extending our research to murine Mypop, we observed anti-proliferative effects in mouse melanoma and colorectal cancer cells. Collectively, our findings underscore MYPOP's potential as a selective tumor suppressor in both human and mouse cancer cells, opening a promising avenue for future in vivo studies.

overall_design: HeLa cells transfected with GFP-empty vector (ctrl), compared to HeLa cells transfected with GFP-Mypop

first: Johannes

last: Strunk

first: Annekathrin

last: Ludt

first: Matthias

last: Klein

first: Barbara

last: Schroers

first: Luise

last: Florin


title: Spatial mapping reveals erythroid niches in mice during development and stress

summary: Like hematopoiesis, erythropoiesis requires erythroid niches nurturing and support. We performed spatial transcriptomics to reveal the erythroid niches in mice. Our results identified novel erythroblastic island macrophage marker in mouse during development and stress.

overall_design: Diverse hematopoietic organs including embryonic 13.5 and 14.5 days fetal liver, postnatal 8 days bone marrow, adult bone marrow and adult spleen from wild type and C1qa knockout mice were used for the analysis. Then these organ samples were analyzed using spatial transcriptomics.


title: CMPK2 restricts Mycobacterium tuberculosis replication and regulates macrophage gene expression

status: Public on May 15 2026

city: Dallas

first: Michael

last: Shiloh

state: Texas

address: 5323 Harry Hines Blvd

institute: UT Southwestern

summary: Host cell metabolic pathways influence innate immune responses to intracellular pathogens, but the contribution of nucleotide metabolism to antimicrobial defense remains incompletely defined. Here, we identify the mitochondrial nucleoside monophosphate kinase CMPK2 as a regulator of macrophage responses to Mycobacterium tuberculosis (Mtb). Using a targeted genetic screen of candidate host factors, we found that depletion of CMPK2 enhances intracellular Mtb replication in human macrophages. This phenotype was confirmed using both shRNA-mediated knockdown and CRISPR-Cas9-mediated knockout approaches. CMPK2 expression increased following macrophage activation and Mtb infection. Transcriptomic profiling revealed that loss of CMPK2 is associated with broad alterations in gene expression, including reduced expression of genes linked to innate immune and inflammatory responses early after infection. In contrast, myeloid-specific deletion of Cmpk2 in mice did not significantly alter bacterial burden or survival following aerosol Mtb infection, indicating that the contribution of CMPK2 to host defense is context dependent. Together, these findings identify CMPK2 as a host factor that limits Mtb replication in human macrophages and shapes innate immune gene expression programs.

overall_design: THP1 WT and CMPK2 KO cells were plated in 6-well plates (2*10ˆ6) and infected with Mtb (MOI of 5) or left uninfected. Uninfected cells were harvested immediately after infection of other samples. After 4 or 24 hrs of infection, samples were lysed using TRIzol and RNA was isolated using phenol & the Qiagen RNeasy Mini Kit, followed by bulk RNA-sequencing.

first: Neff

last: John


title: Inhibition of programmed cell death-1 in cytotoxic CD8+ T cells exacerbates pressure overload-induced cardiac injury

status: Public on May 22 2026

city: Harbin

first: Mingming

last: Wu

state: Heilongjiang

address: 23 Youzheng St

department: Departments of Cardiology

institute: The First Affiliated Hospital of Harbin Medical University

summary:
Background: The use of anti-programmed cell death 1 (PD-1) antibody increases heart failure (HF) risk in cancer patients with pre-existing cardiovascular conditions. However, the underlying mechanism remains incompletely understood.
Methods: To evaluate the effects of anti-PD-1 antibody on transverse aortic constriction (TAC)-induced cardiac remodeling and HF, anti-PD-1 antibody-treated mice, T cell-, myeloid-, and CD8+ T cell-specific PD-1 knockout (KO) mice, and C-X-C motif chemokine receptor 3 (CXCR3) KO and granzyme B (GZMB) KO mice combined with flow cytometry, western blotting, immunofluorescence staining, pharmacological approaches, and bulk RNA-sequencing analyses were used.
Results: Administration of anti-PD-1 antibody, T cell-, or CD8+ T cell-specific PD-1 deletion, but not myeloid-specific PD-1 KO, aggravated TAC-induced cardiomyopathy and HF in mice. Mechanistically, PD-1 blockade or deletion increased myocardial infiltration of CXCR3+ CD8+ T cells, which led to GZMB/perforin-mediated impairment of cardiomyocyte mitochondrial complex I to exacerbate TAC-induced cardiac injury and HF. Notably, TAC-enhanced chemotaxis, between cardiac fibroblasts (CF)-derived CXCL9/CXCL10 and CXCR3+ CD8+ T cells, was a driving force for recruiting CXCR3+ CD8+ T cells under the conditions of PD-1 blockade or deletion. The worsened TAC-induced cardiomyopathy caused by anti-PD-1 antibody or T cell-specific PD-1 deletion was rescued by genetic deletion or pharmacological blockade of GZMB and CXCR3.
Conclusions: Anti-PD-1 antibody administration enhances myocardial infiltrated CXCR3+ CD8+ T cells under TAC condition via CXCL9/CXCL10-mediated chemotaxis. These CD8+ T cell-released GZMB impairs mitochondrial complex I and causes cardiomyocytes apoptosis in a perforin-dependent manner, exacerbating TAC-induced cardiomyopathy and HF. CXCL9/CXCL10-CXCR3+ CD8+ T cell axis may represent a promising target for combating anti-PD-1 antibody-associated cardiotoxicity.

overall_design:
Following anti-PD-1 antibody therapy, PBMCs from patients with therapy-associated cardiac injury (diagnosed as “possible myocarditis”) and control patients without signs of cardiac injury were isolated by density gradient centrifugation and analyzed using scRNA-seq.
UPDATE
[Jun-23-2026] The organism was corrected from Mus musculus to Homo sapiens.

first: Zhiren

last: Zhang


title: RNA seq - comparing  ingB mutant to AF293 - Genetic mechanisms of azole tolerance

status: Public on May 24 2026

city: Hanover

first: Sandeep

last: Vellanki

address: 1 Rope Ferry Rd

institute: Geisel school of medicine at Dartmouth

summary: The Inhibitor of Growth domain proteins are conserved in all eukaryotes. Here we show that loss of ING domain protein (IngB) results in tolerance to azoles in vitro and in vivo. To determine the underlying mechanism, we performed a RNA seq comparing ingB mutant biofilms to the reference strain AF293. We found that loss of ingB results in primarily upregulation of genes involved in iron starvation response and dowregulation of genes in mevalonate and ergosterol biosynthesis pathway,

overall_design: 10^5 conidia per ml of each strain were cultured in Glucose minimal media for 16 hrs at 37℃, 5% CO2. The RNA was extracted and was submitted to sequencing.

first: Robert

last: Cramer


title: Cx43-mediated mitochondrial transfer from MSCs mitigate oxidative stress-inflammation interplay in IRI-AKI via PGC1a activation

status: Public on May 25 2026

city: Palo Alto

first: Avnesh

last: Thakor

state: California

address: 3155 Porter Dr

department: Radiology

institute: Stanford Medicine

summary: Ischemia Reperfusion Injury-related Acute Kidney Injury (IRI-AKI) is a significant clinical challenge characterized by interrupted blood flow to the kidneys, leading to substantial complications such as prolonged hospital stays, chronic kidney disease, and increased mortality rates. Current management strategies are limited to supportive care, underscoring the need for targeted therapies. This study investigates the potential of Mesenchymal Stromal Cells (MSCs) to transfer functional mitochondria to damaged renal cells via gap junctions, specifically connexin 43 (Cx43), in a clinically relevant surgical model of IRI-AKI. We conducted a time-course analysis to identify critical time points for mitochondrial dysfunction and the optimal therapeutic window for MSC administration, comparing the reno-protective effects of bone marrow-derived MSCs (BM-MSCs) and umbilical cord-derived MSCs (UC-MSCs) in both in vivo and in vitro models. Additionally, we explored the activation of mitochondrial biogenesis and dynamics signaling pathways, particularly PGC1α, to assess the restoration of mitochondrial homeostasis in IRI-AKI, and its potential to disrupt the oxidative stress-inflammation axis, paving the way for precision therapies in treating IRI-AKI.

overall_design: In the current study, we studied the effect of human bone marrow and umbilical cord derived MSC in preventing IRI-AKI, using temporal profile to idenitfy corerct therapeutic window

first: Ganguly

last: Abantika

first: Wang

last: Jing

first: Regmi

last: Shobha

first: Primevera

last: Rosita

first: Chetty

last: Shashank

first: Levitte

last: Steven

first: Ramasamy

last: Paulmurugan


title: CRISPR interference screens in ALK+ anaplastic large cell lymphoma cell culture (SU-DHL-1) under treatment with therapies used in peripheral T-cell lymphoma treatment

city: Chapel Hill

first: Jacob

middle: C

last: Pantazis

address: 116 Manning Drive

department: Pharmacology

summary: The following are raw Illumina sequencing files for 14-day genome-wide CRISPR interference screens conducted in a T-cell lymphoma cell culture. This submission contains the results of two sets of genome-wide screens conducted at the University of North Carolina at Chapel Hill School of Medicine, in the lab of Adam Palmer. SU-DHL-1 cells stably expressing dCas9-KRAB (Addgene # 110820) were transduced with pCRISPRi-v2 genome-wide library (Addgene #84832) and treated for 14-days with either pralatrexate, romidepsin, oxaliplatin, gemcitabine, or bortezomib. Deposited here are the raw high-throughput sequencing files, and the processed gene tables with phenotype scores, generated using the CRISPR interference screen data analysis pipeline originally published by Max Horlbeck from the lab of Jonathan Weissman.

overall_design: CRISPR interference competent SU-DHL-1 cells were grown to high density in a large volume and transduced at a target multiplicity of infection of 0.3 with the hCRISPRi genome-wide guide RNA library. The culture was selected with puromycin treatment for seven days, at which point a T0 sample of 80M cells was taken and frozen. In the first set of CRISPR screens, SU-DHL-1 cells were treated for 13 days with 5 nanomolar pralatrexate, 5 nanomolar romidepsin, 20 nanomolar gemcitabine, 2 micromolar oxaliplatin, or 0.1% DMSO as an untreated control. In the second CRISPRi screen, SU-DHL-1 cells were treated with either 10nM bortezomib or 0.1% DMSO as an untreated control for fourteen days. Following treatment, genomic DNA was extracted from 80M cells from each treatment condition, and PCR was used to amplify single guide RNA sequences and add Illumina adapters and indices to all amplicons. Amplicons were gel extracted, and samples from each screen condition were pooled and sequenced by NextSeq2000. The first set of screens were sequenced at the University of North Carolina High-Throughput Sequencing Facility, while the second bortezomib was sequenced at Novogene Corporation. Sequencing results were then processed, with phenotype scores generated and reflected in processed data files for each drug treatment screen, reflecting differences in guide RNA abundance between treated and untreated conditions. These outputs were used for downstream biomarker analysis to identify determinants of drug sensitivity in lymphoma.

first: Jacob Christopher

first: Amy Elizabeth

last: Pomeroy

first: Adam Christopher

last: Palmer


title: A GPS2-like protein interacts with HOS15 and HDA6 to form a repressor complex that regulates ABA signaling and drought adaptation in Arabidopsis

city: Seoul

first: Nassem

last: AlBakri

address: Gwangjin-gu

department: Biomedical Science and Engineering

country: South Korea

institute: Konkuk University

summary: Plants rely on chromatin-mediated transcriptional control to fine-tune stress responses, yet the evolutionary conservation and functional adaptation of repressor complexes remain incompletely understood. Here, we identify GPS2-like protein (GPL; AT3G47850) as the missing component of the plant equivalent of the animal NR–co-repressor complex. GPL interacts with HOS15, PWR, and HDA6/HDA9 to form a chromatin repressor module that suppresses abscisic acid (ABA)–responsive genes. Loss-of-function gpl-mutants exhibit ABA hypersensitivity and enhanced drought tolerance, while overexpression confers ABA insensitivity. Mechanistically, GPL promotes histone H3K9 deacetylation and dimethylation at stress-responsive loci and stabilizes HOS15 to ensure its nuclear retention. Global RNA-seq revealed widespread de-repression of ABA-responsive transcriptional networks in gpl-mutants. Under stress, ABA destabilizes the GPL–HOS15 complex, releasing repression and activating defense genes. These findings establish GPL as the plant homolog of GPS2 and reveal that the GPL–HOS15 repressor complex acts as a chromatin-mediated rheostat to dynamically balance growth and drought adaptation. Our work provides mechanistic insight into stress-responsive chromatin remodeling and identifies GPL as a potential target for engineering climate-resilient crops

overall_design: RNA sequencing was performed on Col-0 (wild type) and gpl-1 (mutant) under both normal conditions and ABA treatment.

first: Zein Eddin

last: Bader

last: Albakri


title: Multi-omics analysis reveals sex-specific etiology of human muscle weakness following musculoskeletal injury

city: Lexington

first: Christopher

last: Fry

state: Kentucky

address: 900 S. Limestone

institute: University of Kentucky

summary: Background: Musculoskeletal injuries comprise a growing source of disability worldwide, and the recovery of muscle strength following injury is a critical determinant of patient reported outcomes. Females experience exacerbated muscle atrophy, poorer outcomes, and higher re-injury rates, necessitating a comprehensive interrogation of sex-specific skeletal muscle differences. Our purpose in the current study was to perform an unbiased transcriptomic profiling of muscle samples to identify putative sex-specific molecular targets to enhance recovery in patients who underwent anterior cruciate ligament reconstruction (ACLR).  Methods: We performed cellular phenotyping, bulk and single nucleus RNA-sequencing on muscle biopsy samples obtained from thirty-six participants (18M, 18F). Muscle samples were obtained from the ACLR and contralateral limb with follow-up tissue collection of the injured limb also occurring at seven days and four months post-ACLR. Transcriptomic analyses illuminated putative molecular mechanisms through which sex influences muscle recovery following acute injury. Results: Females exhibited greater muscle atrophy relative to males at 4 months post-ACLR compared to the uninjured limb. Bulk and single nucleus paired-limb transcriptomic analyses revealed the emergence of sex-specific myonuclear signaling cascades that demonstrate impaired reactive oxygen species scavenging in females. Females exhibited attenuated SOD2 expression that was associated with increased indices of oxidative stress and protein damage. Within females, angiogenesis signaling was also impaired and associated with capillary rarefaction after reconstructive surgery. Conclusions: These findings reveal inherent sex-based differences in muscle pathology that likely necessitate unique clinical treatments following musculoskeletal injury.

overall_design: Differential gene expression was calculated comparing male vs. female ACLR limbs. Raw Healthy samples from GSE211681 were included for differential gene expression analysis.

first: Alexander

middle: R

last: Keeble

first: Allison

middle: M

last: Owen

first: Nicholas

last: Thomas

first: Sara

last: Gonzalez-Velez

first: Camille

last: Brightwell

first: Tyler

last: Barnes

first: Douglas

last: Long

first: Phillip

last: Kern

first: Caitlin

last: Conley

first: Austin

middle: V

last: Stone

first: Darren

middle: L

last: Johnson

first: Yuan

last: Wen

first: Brian

last: Noehren


title: Defining the role of fibroblasts in skin expansion

city: Modena

first: Elena

last: Enzo

state: Modena

address: 100, Via Glauco Gottardi, Centro di Medicina Rigenerativa

department: Interdepartmental Centre for Stem Cells and Regenerative Medicine (CIDSTEM)

country: Italy

institute: Unimore

summary: Stretch-mediated tissue expansion is commonly used to grow extra skin for reconstructive surgeries. To ensure harmonious growth, the two main skin compartments, the epidermis and the dermis, must both expand in a coordinated manner. Although the epidermal response has been previously described, it remains unclear how fibroblasts, the main supporting cell type, respond to stretching in vivo. Here we map the transcriptional response of the entire skin during stretch-mediated tissue expansion, and we describe the fibroblast response to stretching in vivo. We show an increase in fibroblast volume accompanied by changes in organisation. We demonstrate that stretching forces fibroblasts to exit their quiescent state and restart proliferation. Concurrently, fibroblasts reduce collagen production and upregulate extracellular matrix remodelling factors, adopting a more embryonic-like program. Because embryonic fibroblasts are widely used as feeder layers to support the expansion of epidermal stem cells for clinical application, we leveraged this model to show that a low collagen state enhances epidermal stem cell self-renewal, thereby coordinating epidermal and dermal responses during skin expansion. These findings provide valuable insights to guide the design of in vivo stretch-mediated tissue expansion protocols and the production of in vitro skin grafts for clinical application.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Primary keratinocytes were cultured on lethally irradiated 3T3-J2 fibroblast feeder layers prepared as standard-quality feeders (SQ-FL; control) or low-quality feeders (LQ-FL; stressed). SQ-FL feeders were used within 24 h after plating, whereas LQ-FL feeders were maintained for 4 days after plating before keratinocyte seeding. Keratinocytes grown under each condition were collected after 5 days for single cell analysis, with two independent biological replicates per group (SQ-FL, n=2; LQ-FL, n=2).

first: Caroline

last: Aguilera Stewart

first: Ceyhun

last: Alar

first: Gaia Andrea

last: Gozza

first: Leslie

last: Bargsted

first: Ioanna

last: Kaklamanou

first: Maria Pia

last: Polito

first: Giulia

last: Bergamini

first: Lorenzo

last: Tagliazucchi

first: Andrea

last: Alessandrini

first: Maria Paola

last: Costi

first: Alejandro

last: Sifrim

first: Mariaceleste

last: Aragona


title: Integrated biomarker and treatment correlates of prognosis in infant medulloblastoma: Multi-national retrospective cohort studies

status: Public on May 29 2026

city: Newcastle upon Tyne

first: Ed

last: Schwalbe

address: Ellison Place

department: Natural Sciences

country: United Kingdom

institute: Northumbria University

type: Methylation profiling by genome tiling array

summary: This dataset spans two studies which investigate the clinico-pathology and molecular features of infant medulloblastoma, defined as children aged <5 years at diagnosis. Both abstracts follow. Background  Infant medulloblastoma (iMB; <3-5-years old at diagnosis) is a major challenge in paediatric oncology. The favourable-risk SHH iMB molecular group with desmoplastic histology (40% of iMB) is commonly spared upfront craniospinal irradiation (CSI) to avoid neurocognitive side-effects. However, clinical studies of the remaining non-WNT/non-SHH iMB group (~60% of iMBs) have not been undertaken, and it is currently considered uniformly high-risk. Understanding the potential for its biological subclassification and clinical stratification is an essential goal towards improved outcomes. This study therefore aimed to directly compare different therapeutic approaches in non-WNT/non-SHH iMB and determine relationships between outcomes and clinico-molecular features.  Methods  We assembled a global cohort of non-WNT/non-SHH iMBs (n=375). Inclusion criteria was a principal non-WNT/non-SHH MB classification (Group 3 or Group 4); confidence score >0.8) using DNA methylation array-based classification. The survival cohort (n=313) was defined by availability of complete progression-free (PFS) and overall (OS) survival data. Using these cohorts, we characterised their molecular pathology, treatments received, and relationships to outcomes, principally PFS.  Findings  The total collected cohort (n=375) comprised 262 males and 110 females, with a median age of 3.0 (IQR 2.53-4.0) years.  Molecular group 3 tumours (iMBGrp3) predominated (n=246, 66%), primarily molecular subgroups 2 (n=75; 32%), 3 (n=46; 19%) and 4 (n=98; 42%). Regimens incorporating upfront CSI were most common (54% of patients); such patients had significantly better PFS than those treated with focal or no radiotherapy (5-year PFS; CSI, 57.9%; Focal-radiotherapy, 35.3%; No radiotherapy, 26.8%; p<0.001), and equivalent PFS to CSI-treated non-infant patients.   Upfront chemotherapy -only approaches were used in 33% (66/199) of iMBGrp3; high-dose (HIGH-DOSE) chemotherapy produced better survival rates (45.7%, 5-year PFS) than intraventricular methotrexate-based (21.1%, 5-year PFS) or standard-dose (11%, 2-year PFS) chemotherapy (p=0.003).   Subgroup 4 represents a novel chemo-sensitive iMB group, with 64.3% 5-year PFS using high-dose -chemotherapy-only and with evidence of rescue post-relapse. MYC-amplified iMBGrp3 ( subgroup2/3) have dismal prognosis (0% 2-year overall survival (OS)), with rapid progression regardless of treatment. Remaining  subgroup 2/3 patients treated with Chemotherapy-only had 30% 5-year PFS, showed some evidence of post-relapse rescue, and could be randomised to test alternative therapeutic strategies.  Interpretation  Non-WNT/non-SHH iMB outcomes are associated with specific biomarkers and therapy received. Capturing this ‘real-world’ experience identifies favourable ( subgroup 4) and very-high-risk ( subgroup 2/3-MYC) patient groups, providing a critical foundation for first biomarker-driven iMBGrp3 clinical trials.   Background   Medulloblastoma in infants (iMB; <5 years) presents the challenge of achieving cure while minimizing deleterious cranio-spinal irradiation (CSI)-associated late-effects.  Non-randomised Phase-II studies have examined upfront CSI omission and chemotherapy intensification for favourable-risk desmoplastic/nodular (DN) tumours associated with the SHH molecular group (iMBSHH).  Comparison of these therapies in large molecularly-defined iMBSHH cohorts, alongside investigations of prognostic biomarkers in therapy-specific context, is urgently required to define future therapeutic strategies.  Methods   A multi-national cohort of molecularly and clinically-annotated iMBSHH (n=267), not previously reported in clinical trials, was assembled. We investigated molecular pathology, upfront treatments, and relationships to outcome, in this ‘real-world’ setting.  Findings   iMBSHH patients treated upfront with intensified chemotherapy-only regimens (n=132) based on intraventricular methotrexate (IVT-MTX; 5-year progression-free survival (PFS), 72.6%) or high-dose (HD; 73.0%) therapy, achieved (PFS) outcomes comparable to upfront CSI-based regimens (n=49; 74.0%)(p=0.51). Lower-intensity standard-dose chemotherapy-only regimens were inferior (SD; 48.4% PFS)(p=0.006). Rescue was common post-relapse after IVT-MTX/HD protocols and translated into 5-year overall survival (OS) of 85.6% and 88.6%, respectively. iMBSHH encompassed SHH-1 (38%), SHH-2 (47%) and SHH-3 (14%) WHO subgroups. In CSI-naïve iMBSHH, SD associated with worse PFS in SHH-1 (p=0.001), but not SHH-2. Non-DN/MBEN histology (21.2% of iMBSHH) conferred worse PFS in upfront CSI-treated and SD (p<0.001 and p=0.003, respectively) groups. Metastatic disease only associated with prognosis with upfront IVT-MTX-only therapies (p=0.013), while established high-risk features of non-infant MBSHH (TP53-mutation, LCA-histology, MYCN-amplification) only associated with poor prognosis in older SHH-3 (7/7 relapsed). Finally, CSI-naïve PFS findings were validated in a re-evaluation of smaller historical trials cohorts.  Interpretation   iMBSHH outcomes and prognostic biomarkers are therapy-dependent. Non-metastatic iMBSHH treated with HD or IVT-MTX chemotherapy-only have equivalent favourable outcomes, independent of histology and subgroup. With outcomes established, clinical trials must now focus on quality-of-life following different intensified approaches, to identify kindest curative strategies.

overall_design: DNA methylation profiles of 646 medulloblastoma from children <5 years old at diagnosis were generated from IDATs from previously published studies (GSE85212 (n=175), GSE93646 (n=136) and GSE130051 (n=70) as detailed in the reanalysis_samples.xlsx) and newly derived fresh-frozen and formalin-fixed paraffin-embedded material using the Illumina 450k and EPIC methylation microarray platforms.

first: Edward

first: Steven

last: Clifford


title: HDAC4 myonuclear reprogramming underlies denervation and weakness following musculoskeletal trauma

first: Alexander

middle: Romano

last: Keeble

state: KY

address: 900 S Limestone st

summary: Muscle weakness following joint injury contributes to substantial functional deficits and disability. The molecular etiology of prolonged muscle atrophy and weakness following knee ligament injury remains undefined, limiting our understanding of the inceptive events underlying poor functional recovery. We studied the muscle transcriptome in men and women in response to ligament injury and surgical reconstruction, revealing substantial injury- and reconstructive surgery-dependent changes, with sustained increases in genes associated with neuromuscular junction remodeling. We identified histone deacetylase 4 (HDAC4) as one of the most upregulated targets in muscle following both injury and reconstruction, and multi-omics integration of HDAC4 ChIP-sequencing and RNA-sequencing revealed a coordinated repression of genes associated with metabolism and contractile function following injury. We further applied single nucleus RNA-sequencing and uncovered aberrant neuromuscular signaling and myonuclear reprogramming. Our multi-omics and single-nucleus transcriptome analyses demonstrate unique myocellular and neuromuscular adaptations that could explain persistent functional deficits following acute musculoskeletal injury.

overall_design:
Differential gene expression was calculated comparing Injured vs. Healthy limbs and 7d post-Sx vs. Healthy limbs. Raw Healthy and Injured samples from GSE211681 were included for differential gene expression analysis.

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

first: Nicholas

last: Thomas

first: Allison

last: Owen

first: Camille

last: Brightwell

first: Christine

last: Latham

first: Megan

last: Graham

first: Kelsey

middle: A

last: Reeves

first: Jensen

last: Goh

first: Sara

last: Gonzalez-Velez

first: Douglas

last: Long

last: Harrison

first: Phillip

last: Kern

first: Gregory

last: Hawk

first: Caitlin

last: Conley

first: Jean

last: Fry

first: Austin

last: Stone

first: Katherine

last: Thompson

first: Darren

last: Johnson

first: Yuan

last: Wen

first: Brian

first: Christopher


title: 3-Hydroxypropionic acid converts inflammatory macrophage glycolysis into mitochondrial oxidation through GAPDH carboxyethylation

status: Public on May 14 2026

city: Xi'an

first: Wu

last: Kefei

institute: Air Force Military Medical University

summary: Macrophages dynamically reprogram their metabolic states in response to environmental stimuli, thereby exerting distinct immune functions. In our preliminary study, a gut microbiota-derived metabolite 3-hydroxypropionic acid (3-HPA) is increased in chronic inflammation and generates cysteine carboxyethylated neoantigens. However, the role of such metabolite-induced modification in regulating the function of macrophages remains obscure. Here, we show that 3-HPA alleviates inflammation in a mouse model of sepsis and inhibits the macrophage inflammatory response. Mechanistically, 3-HPA induces glyceraldehyde-3-phosphate dehydrogenase (GAPDH) carboxyethylation, which promotes GAPDH degradation via the ubiquitin-proteasome pathway, thereby suppressing its enzymatic activity and expression to inhibit glycolysis. Concomitantly, reduced GAPDH activity elevates the NAD+/NADH ratio, which enhances mitochondrial oxidation by upregulating arginine biosynthesis and the TCA cycle pathway. All above, our research reveals the mechanism by which GAPDH carboxyethylation mediates metabolic reprogramming and regulates inflammation during inflammatory macrophage activation.

overall_design: RNA-seq profiling  of  LPS-stimulated THP-1 macrophages with or without 3-HPA pretreatment.

first: Kefei

last: Wu

first: Yankun

last: Jia

first: Qi

last: Lin

first: Huanyu

last: Lu

first: Yue

last: Zhai


title: Neolecta irregularis secuence data.

city: Murcia

first: Samanta

last: Hernandez-Garcia

address: Campues de Espinardo, Murcia

department: Bioquimica y Biologia Molecular A

country: Spain

institute: Universidad de Murcia

summary: Analisis of the RNA extracted from the fungi Neolecta irregularis, a living fossil fungus. It is a specie of particular evolutionary interest because occupies an intermediate position between yeast and fungi.

overall_design: Total RNA obtained from two independent specimens of N. irregularis. Samples were obtained from the Denver Botanic Garden (Denver, CO, USA) under catalog numbers DBG-F-033461 and DBG-F-031510.

first: Pedro

last: Martínez-Rodríguez

first: Fernando

last: Gandía-Herrero


title: Single-cell transcriptome analysis of bronchoalveolar lavage in SARS-CoV-2 Omicron severe patients

city: Nanjing

first: Han-Bing

last: Chen

address: No. 87, Dingjiaqiao Road, Gulou District

institute: School of Medicine, Southeast University

summary: To delineate the single-cell transcriptional landscape of the lungs in severe patients infected with the Omicron variant of SARS-CoV-2, we performed single-cell RNA sequencing on bronchoalveolar lavage fluid samples collected within 24 hours of ICU admission.

overall_design: Intact live cells were obtained from the bronchoalveolar lavage fluid  of two severe COVID-19 cases infected by the Omicron variant, and single-cell RNA sequencing (scRNA-seq) was subsequently conducted.

first: Chao

last: Gao

first: Jie

last: Chao

first: Hai-Bo

last: Qiu


title: ICAM1high Neutrophils Sculpt Tumor Evolution and Metastasis through Symbiotic Adhesion and Reverse Migration

city: Houston

first: Xiang

last: Zhang

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: Analyses of neutrophils of pan human cancers revealed a ICAM1high subset enriched in the tumor microenvironment, Murine triple negative breast cancer (TNBC) models recapitulate this observation. ICAM1high neutrophils exhibited enhanced capacity of cell-cell adhesion specifically with tumor cells retaining epithelial features, and this adhesion confers mutual advantages on both cell types. In contrast, cancer cells of mesenchymal-like phenotypes are thwarted by neutrophils due to decreased cell adhesion and elastase resistance. These nearly opposite effects drive the evolution toward a dichotomy of neutrophil-enriched, epithelial-like versus macrophage-enriched, mesenchymal-like ecosystems. The ICAM1high neutrophils are known for reverse migration (from tissue to circulation). The adhesive and reverse migratory properties together mediate metastatic intravasation. These observations were verified in a subset of human TNBCs that unexpectedly enrich non-Hispanic European patients. Thus, we demonstrated a co-evolution through which neutrophils sculpt phenotypes and metastatic behaviors of TNBC, which may preferentially occur in patients of certain race/ethnicity.

overall_design: 2208L tumor cell line were injected into mouse mammary gland, after four weeks, the tumor were harvested and send for scRNA-Seq.

first: Yang

first: Ling

last: H-F Zhang


title: Botulinum Neurotoxin A Signaling in Pain Modulation within Human Sensory Neurons

city: Richardson

first: Katherin

last: Gabriel

address: 2811 N Floyd Rd.

institute: University of Texas Dallas

summary: Botulinum Neurotoxin A1 (BoNT/A1) is an effective treatment for chronic migraines, but its direct mechanism of action on human sensory neurons has not been tested. While rodent studies on dorsal root ganglion (DRG) and trigeminal ganglion (TG) show that BoNT/A1 inhibits neurotransmission, including calcitonin gene-related peptide (CGRP) release, by cleaving SNAP-25, only one previous study has assessed its effect on human DRG neurons . The objective of this study was to understand the mechanism of action of BoNT/A1 in human sensory neurons and assess, using RNA sequencing, the transcriptomic consequences of BoNT/A1 treatment. Using DRGs obtained from organ donors   the expression of key targets, including SNAP25, SV2C, & CALCA, was validated by mining existing transcriptomic datasets as well as immunohistochemistry. Cultured dissociated human DRG neurons treated with BoNT/A1 were used to examine cleavage of SNAP25, release of CGRP and transcriptomic changes after BoNT/A1 treatment. SV2C was found to be widely expressed in human DRG neurons in a pattern that completely overlapped with CGRP expression. Consistent with this finding, BoNT/A1 disrupted SNARE protein complexes in human DRG neurons as demonstrated by SNAP-25 cleavage in most somatosensory neurons and a reduction in capsaicin-evoked CGRP release, indicating impaired vesicle fusion. Moreover, Bulk RNA sequencing experiments revealed downregulated expression of a large subset of genes responsible for neurotransmitter and neuropeptide release from neurons suggesting a novel mechanism through which BoNT/A regulates neurotransmission. These results provide new insight into the molecular mechanisms by which BoNT/A may exert its pain-relieving effects in humans.

overall_design: Primary human dorsal root ganglion cultures that were treated with either Vehicle or BoNT/A1

first: Kali

last: Hankerd

first: Paulino

last: Barragan-Iglesias

first: Steve

last: McGaraughty

first: Edwin

last: Vazquez-Cintron

first: Theodore

last: Price

first: Lance

last: Steward

first: Amy

middle: D

last: Brideau-Andersen


title: Bulk RNAseq of sorted fibroblasts from a mouse model of stretch-mediated skin expansion

city: København

first: Mariaceleste

last: Aragona

address: Blegdamsvej 3B

country: Denmark

institute: University of Copenhagen

summary: Using an in vivo mouse model of stretch-mediated skin expansion, we have performed bulk RNAseq on control (CTRL) skin fibroblasts and expanded (EXP) skin fibroblasts at 3 time points: day 1, day 2 and day 4. Stretch-mediated expansion is used in reconstructive and cosmetic surgeries to produce extra skin, however the mechanisms behind it are not well understood. Here we investigate the transcriptional changes occurring in fibroblasts upon expansion. We find downregulation of many extracellular matrix genes, including collagens, and upregulation of genes related to mitosis and sterol biosynthesis.

overall_design: Following surgery, involving the subcutaenous insertion of expanders, control or expanded skin was dissected and digested into single cells. Fibroblasts were isolated via fluorescence-activated cell sorting (FACS) via exclusion of vasculature, hematopoietic, melanocyte and epithelial cells (cells expressing CD31, CD45, CD117 and EpCAM, respectively) and then inclusion of CD34+ and PDGFRα+ fibroblast cells. Live cells were detected based on negative DAPI staining.

first: Caroline

last: Aguilera Stewart


title: scRNAseq of stretch-mediated skin expansion in mouse

summary: Using an in vivo mouse model of stretch-mediated skin expansion, we have performed scRNAseq (10x Genomics) on control (CTRL) skin and expanded (EXP) skin at 3 time points: day 1, day 2 and day 4. Stretch-mediated expansion is used in reconstructive and cosmetic surgeries to produce extra skin, however the mechanisms behind it are not well understood. This study represents the first full skin scRNAseq study of in vivo stretch-mediated skin expansion.

overall_design: Following surgery, involving the subcutaenous insertion of expanders, control or expanded skin was dissected and digested into single cells. Live cells were isolated via fluorescence-activated cell sorting (FACS) for DAPI negative cells.

first: Ceyhun

last: Alar

first: Alejandro

last: Sifrim


title: CDK2 Inhibition Exerts RB-Independent Antitumor Activity in CDK4/6 Inhibitor-Resistant HR+/HER2- Breast Cancer

city: Boston

first: Hanjun

last: Lee

address: 77, Avenue Louis Pasteur

department: Department of Genetics

institute: Harvard Medical School

summary: Intrinsic and acquired resistance to CDK4/6 inhibitors (CDK4/6i) is a critical challenge in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). CDK2 inhibitors (CDK2i) show promise in this context, with several currently under early-phase clinical evaluation. Here, by analyzing tumor and liquid biopsies from patients treated with the selective CDK2i PF-07104091, we observed that PF-07104091 monotherapy achieved disease stabilization in a cohort of CDK4/6i-resistant HR+/HER2- MBC patients. Notably, responses were observed irrespective of RB expression and phosphorylation, whereas non-progressive disease appeared more frequently among patients whose tumors retained wild-type TP53. Studies in established and patient-derived cell lines further substantiated that the growth suppressive effects of CDK2i were independent of RB status in CDK4/6i-resistant models. CDK2i activity reduced DNA replication rate, increased DNA damage, and inhibited mitotic entry, with growth inhibition dependent on p53 expression. These findings indicate that CDK dependency shifts from CDK4/6 toward CDK2 as cells transition from CDK4/6i-sensitive to CDK4/6i-resistant state. The distinct mechanisms of CDK2i and CDK4/6i support enhanced synergistic activity in HR+/HER2- MBC with acquired resistance to CDK4/6i therapy.

overall_design: RNA-seq for patient-derived HR+ metastatic breast cancer cell lines before and after resistance to palbociclib

first: Ioannis

last: Sanidas


title: Residual p53 in HPV positive cervical cancer cells has gain of function properties

status: Public on May 13 2026

city: Trieste

first: Silvano

last: Piazza

address: localita' Padriciano 99

institute: ICGEB

summary: Human papillomavirus (HPV)-positive cervical cancer cells retain residual p53 despite E6-mediated degradation. To investigate whether this residual p53 has gain-of-function properties, CRISPR/Cas9 was used to generate p53 knockout HeLa clones and compare them with a WT control clone. RNA-seq profiling identified transcriptomic changes associated with loss of residual p53.

overall_design: We performed RNA sequencing analysis of the p53 KO clones to understand the transcriptomic profiles and pathways that may be affected by the loss of this residual p53. Clone A was used to represent p53 KO samples, while Clone D was used as a WT control.

first: Sannia

last: Farrukh

first: Nezka

last: Kavcic

first: Giulia

last: Canarutto

first: Lawrence

last: Banks


title: CRISPR-mediated engineering of bovine satellite cells for AGS-compatible cultivated meat

first: Grace

middle: Elizabeth

last: Kenney

address: 104 Manning Dr

institute: University of North Carolina-Chapel Hill

summary: Alpha-gal Syndrome (AGS) is a potentially life-threatening allergy caused by an IgE-mediated immune response to galactose-α-1,3-galactose (alpha-gal), a carbohydrate epitope present in most mammalian meats. Currently, strict avoidance of mammalian meat remains the primary management strategy for affected individuals, and alpha-gal–free beef is not commercially available. Here, we leverage cultivated meat as a biotechnology platform to address this unmet clinical need by engineering alpha-gal–free bovine muscle cells. Using CRISPR/Cas9 genome editing, we disrupted GGTA1, the gene encoding α1,3-galactosyltransferase, in immortalized bovine satellite cells. High-efficiency editing produced clonal GGTA1 knockout cell lines harboring a homozygous frameshift mutation. Flow cytometry and immunofluorescence confirmed loss of the alpha-gal epitope, while bulk RNA-seq indicated minimal disruption of global gene expression and preserved myogenic differentiation capacity. Importantly, lysates from GGTA1 knockout cells elicited substantially reduced basophil activation in assays using plasma from a patient with AGS, indicating reduced basophil activation consistent with reduced allergenic potential. Together, these findings establish a proof of concept for engineering AGS-compatible cultivated meat and demonstrate the potential of cultivated meat technologies to address human health challenges.

overall_design: RNAseq profiling of wild-type and CRISPR/Cas9 GGTA1 knockout immortalized bovine satellite cells at day 0 and day 3 of differentiation.

first: Susan

last: D’Costa

first: Shailesh

middle: K

last: Choudhary

first: Jacqueline

last: Shine

first: Brian

last: Diekman

first: Scott

last: Commins

first: Douglas

last: Phanstiel


title: Lineage tracing of soma-to-primordial germ cell-like conversion in human tumor cell line

city: Shanghai

first: Jing

last: Li

address: 12 Middle Urumqi Road

department: Department of Laboratory Medicine

institute: Huashan Hospital, Shanghai Medical College,  Fudan University

summary: Identifying the origin of tumor-initiating ability is critical for targeted therapies. While early primordial germ cells (PGCs) inherently possess this ability, our previous study indicated that soma-to-PGC-like conversion (SPLC) facilitates its acquisition in mouse breast tumor cells.

overall_design: This study reports evidence of SPLC activation in the human hepatic tumor cell line HL7721, where tumor cells spontaneously exhibit sequential developmental stages, progressing from somatic tumor cells through intermediate stages to PGC-like and late germ cell-like stages. Knocking out PGC specification inducers (ACVR1, SMAD5, PRDM1, or SOX17) or fate-maintaining genes (NANOG or DDX4) suppressed both SPLC and tumor initiation. Collectively, our findings suggest that SPLC might be activated in human tumor cells, serving as a potential pathway for gaining tumor-initiating ability that involves human PGC-related pathways. These results demonstrate that the acquisition of PGC-like fate in somatic cells drives tumor malignant progression, providing a potential paradigm for targeted cancer therapy.


title: SRP orchestrates protein biogenesis beyond initial ER-membrane targeting

city: Heidelberg

first: Ilgin

last: Kotan

address: Im Neuenheimer Feld 329

institute: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH)

summary: The Signal Recognition Particle (SRP) is crucial for targeting nascent proteins to the endoplasmic reticulum (ER). However, its range of substrates and point of engagement during targeting, and hence full biological impact remain unclear. Here, we examined SRP interactions with the nascent proteome of S. cerevisiae during translation and membrane targeting. SRP binds effectively to transmembrane domains (TMDs) as they emerge from the ribosomal tunnel, but not to most cleavable signal peptides. We identify nascent chain features that promote SRP binding, allowing to develop a predictive algorithm. We show SRP performs a role in triaging nascent ER proteins into distinct targeting routes and downstream maturation processes. Furthermore, ribosomes frequently dissociate from the membrane before completing translocation, allowing the chaperone Ssb to assist folding of emerging cytosolic domains. Ribosomes translating multipass membrane proteins are retargeted through repeated SRP interactions with internal TMDs, emphasizing collaboration between SRP and chaperones in membrane protein biogenesis.

overall_design: Ribosome profiling (RP) data from S. Cerevisiae based on sequencing 30 nucleotide long ribosome protected mRNA footprints from all ribosomes or a selected set of ribosomes. For SeRP, SRP-bound ribosomes were co-IPed pulling on N- or C-terminally GFP tagged Srp54. RP libraries were prepared from the IPed ribosomes, and in parallel from all ribosomes (total translatome). For soluble-RP, the soluble subset of ribosomes were isolated via fractionation in a detergent-free cell lysate. RP libraries from the soluble fraction of ribosomes was prepared in parallel to a total translatome. This experiment was performed in WT, srp54(delta), Ssb(delta), snd1(delta), and get5 yeast strains. For soluble-RP with PK treatment, prior to the fractionation step, lysates were treated with proteinase K to digest nascent chains. For collided disome libraries, disomes in RNase treated cell lysates were collected by sucrose gradient fractionation. 60 nucleotide footprints were sequenced to enrich for collided disomes in WT and srp54(delta) strains.

first: Sabrina

last: Sartori

first: Rudra

last: Bose

first: Bernd

last: Bukau

first: Günter

last: Kramer


title: SEX-DEPENDENT TYPE I INTERFERON SIGNALING EXACERBATES ALZHEIMER'S PATHOLOGY

status: Public on May 12 2026

city: San Joan d'Alacant

first: Jose

last: Lopez-Atalaya

address: Av Ramon y Cajal s/n

department: Instituto Neurociencias

institute: CSIC-UMH

summary: Alzheimer’s disease (AD) disproportionately affects women, but the biological basis for this sex difference remains unclear. Using transcriptomic profiling of postmortem human AD brain tissue, we identified a sex-specific enrichment of interferon-alpha (IFN-α) signaling pathways in females. This immune signature was recapitulated in APP/PS1 transgenic mouse models, where female mice exhibited greater amyloid pathology, neuroinflammation, and neurodegeneration compared to males.

overall_design:
Bulk RNA-seq was performed on hippocampal tissue from 6-month-old mice on a C57BL/6 background, including wildtype controls and APPswe/PSEN1dE9 (APP/PS1) transgenic mice, which express a chimeric human/mouse amyloid precursor protein with the Swedish mutation and human presenilin 1 lacking exon 9 under the mouse prion promoter. To investigate the role of interferon signaling, APP/PS1 mice were crossed with Rela conditional knockout mice to generate APP/PS1 x Rela-cKO animals, modeling AD with amplified interferon responses. Additionally, a subset of APP/PS1 mice were treated with the cGASâ??STING inhibitor C-176, administered intraperitoneally every other day from 3 to 6 months of age, while corresponding vehicle-treated groups were included as controls. Selected animals from each group underwent behavioral testing prior to tissue collection.
Bulk RNA-seq was performed on hippocampal tissue from 3-month-old C57BL/6 mice, including vehicle-treated wild-type controls and poly(I:C)-treated mice. Poly(I:C), a synthetic double-stranded RNA analog that mimics viral infection, was used to induce interferon signaling. Treatments and vehicle solutions were administered intraperitoneally, and hippocampal tissue was collected 24 hours after administration for RNA extraction.

first: Gerard

last: Iniesta

first: Marina

last: Guillot

first: Verónica

last: López

last: López-Atalaya


title: snRNAseq analysis of PAH liver

city: Minneapolis

first: Kurt

last: Prins

state: MN

address: 2231 6th St Se

institute: University of Minnesota

summary: We evaluated the effect of PAH on the cellular landscape of the liver in human samples

overall_design: Control and PAH patient liver samples had nuclei isolated and were analyzed by single nucleus RNAseq

middle: W


title: Identification of novel candidate neural genes for diet-induced obesity in outbred heterogeneous stock rats

status: Public on May 11 2026

city: London

first: Richard

last: Mott

address: Gower St

department: Genetics, Evolution and Environment

institute: University College London

summary: Obesity is in large part a brain disease that is caused by genetics, the environment (e.g., diet) and their interactions.  Identifying genes in the brain that interact with diet to influence obesity is not possible in humans.  The goal of this study was to use outbred heterogeneous stock (HS) rats to identify genetic loci for diet-induced obesity followed by RNAseq in the ventromedial hypothalamus (VMH) to identify candidate causal genes. We measured multiple metabolic traits (including fat and lean mass, fasting glucose, insulin, and lipids, glucose tolerance, food intake and activity levels) after long-term consumption of a low-fat (LFD) or high-fat diet (HFD) in 2000 HS rats, split equally be sex and diet. Rats were genotyped using low-coverage whole genome sequencing. RNAseq was run in the VMH of a sub-set of 400 HS rats split equally by sex and diet. We used linear mixed models to detect physiological and expression quantitative trait loci (pQTLs and eQTLs, respectively) in the full dataset and separately by diet and sex.  Genes with cis-eQTLs that overlapped pQTLs were assessed as candidate causal genes through mediation analysis. We also identified VMH genes differentially expressed by diet in both sexes, followed by pathway analysis. We identified 47 pQTLs where seven mapped multiple traits, 11 were diet-specific and 13 were sex-specific. We identified nine candidate causal genes, including Pcare, Rbks, Mpv17 and Gpn1 within a pleiotropic pQTL for multiple adiposity traits on rat chr. 6 and Tnsfs9 within a pQTL for fat pad weight on rat chr. 9. We also identified Ccdc77 as a candidate gene within a LFD-specific pQTL for activity levels and Rtel1 and Polr3k within a male-specific pQTL for fatty liver.  Genes involved in extracellular matrix and inflammation were dysregulated by diet, particularly in females, while males on HFD showed upregulation of several addiction pathways. This work demonstrates the importance of accounting for diet and sex in genetic studies for obesity and identifies novel candidate genes as neural regulators of diet-induced obesity and related traits.

overall_design: We measured gene expression in the ventromedial hypothalamus of 400 heterogeneous stock rats representing both sexes, of which half were fed a high-fat diet and the remainder a normal diet. The data deposited here are the raw data and inferred expression levels. We analysed these data to identify genes that were differentially expressed depending on sex, diet and sex*diet interaction. The data were also combined with obesity-related phenotypes measured on the same animals to identify causal mediators of these traits.

first: Thu

last: Le

first: Teresa

last: Mcgee

first: Osborne

last: Seshie

first: Trangdai

last: Bui

first: Gina

last: Giorgio

first: Angela

last: Beeson

first: Benjamin

last: Johnson

first: Gracie

last: Ang

first: Oksana

last: Polesskaya

first: Abraham

last: Palmer

first: William

last: Valdar

first: Leah

last: Solberg Woods


title: Single-cell RNA sequencing of intratumoral CD45+ Immune cells in a murine cancer model under chronic unpredictable mild stress (CUMS)

city: New York

first: Julia

last: Brown

address: 413 E 69th Street, 1252A

institute: Weill Cornell Medicine

summary: We performed single-cell RNA sequencing (scRNA-seq) of intratumoral CD45+ Immune cells from mice subjected to chronic unpredictable mild stress (CUMS) or control conditions. Cells were multiplexed using hashtag oligonucleotides (HTO1-HTO4, TotalSeq-C) and sequenced using the 10x Genomics 5-prime Gene Expression + Feature Barcode + B cell receptor (BCR) V(D)J workflow (Well 3). This dataset contains GEX profiles of intratumoral B cells from 4 samples (2 conditions x 2 biological replicates; 29,456 cells total). BCR V(D)J sequencing data (IGH/IGK/IGL; 1,107 contigs from 604 B cells) from the same tumor well are also provided. The raw files contain additional unrelated, unlabeled samples as the sequencing was done in multiplex for multiple projects; the processed files reference only the samples used for this study.

overall_design: Intratumoral CD45+ cells were collected from control and CUMS-treated mice. Cells were hashtagged (HTO1-HTO4, TotalSeq-C, BioLegend) and loaded into a single 10x Genomics Chromium well (Well 3: Tumor Control replicates 1-2 on HTO1-HTO2; Tumor CUMS replicates 1-2 on HTO3-HTO4). HTO demultiplexing was performed using Seurat HTODemux (margin > 1.499). Cell type annotation was performed using SingleR with Lee2021 B cell reference markers. Processed H5 files contain GEX raw counts only (HTO features removed), subsetted to high-confidence intratumoral singlets per sample.

first: Hilal

last: Bashir

first: Melody

middle: Y

last: Zeng


title: Integrated transcriptomic and metabolomic analysis of the snap bean pod fiber mutant (bfm) identifies candidate genes associated with pod wall fiber accumulation

city: Harbin

first: Kanhui

last: Mo

address: 74 Xuefu Road, Nangang District

institute: Heilongjiang University

summary: Snap bean is a widely planted legume vegetable crop in the world, with tender pods as its edible organ. In the actual production process, excessive fiber content in bean pods can lead to a deterioration in their taste after cooking, seriously affecting their edible quality. In order to better study the mechanism of fiber formation in bean pod walls, we selected a bean pod fiber mutant (bfm) from the bean mutant library.

overall_design: Fiber content determination, cytological observation, transcriptome and metabolome analysis were performed on the pod walls of mutant bfm and its wild-type at different developmental stages.

first: Zhuang

last: Sun

first: Guojun

last: Feng

first: Dajun

last: Liu

first: Taifeng

last: Zhang

first: Zhishan

last: Yan

first: Chang


title: Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover

city: Moscow

first: Denis

last: Maksimov

address: Leninskie Gory

country: Russia

institute: MSU

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

overall_design: Refer to individual Series


title: Regulation of chromatin dynamics by a calcium-dependent nucleoskeleton

city: Milan

first: Santo

last: Diprima

state: MI

address: Via Olgettina 58

department: COSR

institute: San Raffaele Hospital

summary: Growth factors selectively activate calcium signaling pathways in the cell nucleus, which in turn regulate gene transcription and other intra-nuclear events, but the specific way this is accomplished is not entirely understood. The present study shows that growth factors increase inositol 1,4,5-trisphosphate (IP3) in the nucleus, which in turn releases calcium from intranuclear IP3 receptors (ITPRs), which then leads to transient assembly of an actin nucleoskeleton that associates with intranuclear MYH9. Mass spectrometry suggests that much of the MYH9 cargo consists of components of the gene transcription machinery, while chromatin immunoprecipitation identified a number of specific genes that associate with the myosin in response to stimulation with growth factors. Together, these findings suggest that growth factors initiate gene transcription by transiently assembling an actin nucleoskeleton that works with MYH9 to bring specific genes to the transcription machinery.

overall_design: ChIP-Seq of MYH9 experiments were conducted in EGF-stimulated cells expressing either a control adenovirus (mRFP) or with the IP3-NLS.

first: María Jose

last: González Armijos

first: Michele Angela

last: Rodrigues

first: Dejian

last: Zhao

first: Thais

last: Fernandes Bassani

first: Clara

last: Couto Fernandez

first: Emma

last: Kruglov

first: Michael

last: H. Nathanson

first: Dawidson Assis

last: Gomes


title: RNA sequencing of HeLa cells overexpression CHIKV structural protein TF and 6K

status: Public on May 10 2026

city: Jinan

first: Junwen

last: Luan

state: Shandong

address: 6699#of Qingdao street

department: Basic medical and clinical medicine

institute: ShanDong first medical university

summary: The analysis indicates that overexpression of tf leads to the upregulation of genes related to endoplasmic reticulum stress, and KEGG analysis also identified pathways related to endoplasmic reticulum stress in biological metabolism.

overall_design: To analyze the changes of gene transcription levels induced by the overexpression of TF and 6K compared to the GFP control group: HeLa cells were transfected with GFP, GFP-TF, GFP-6K for 24 hours, then cells were collected to extract the total RNA using TRIzol. 1 μg total RNA was used for following library preparation. The poly(A) mRNA isolation was performed using Oligo(dT) beads. The mRNA fragmentation was performed using divalent cations and high temperature. Priming was performed using Random Primers. First strand cDNA and the second-strand cDNA were synthesized. The purified double-stranded cDNA was then treated to repair both ends and add a dA-tailing in one reaction, followed by a T-A ligation to add adaptors to both ends. Size selection of Adaptor-ligated DNA was then performed using DNA Clean Beads. Each sample was then amplified by PCR using P5 and P7 primers and the PCR products were validated. Then libraries with different indexs were multiplexed and loaded on an Illumina HiSeq/ Illumina Novaseq/ MGI2000 instrument for sequencing using a 2x150 paired-end (PE) configuration according to manufacturer’s instructions.

first: Shengnan

last: Wang

first: Leiliang


title: RNA-seq of SRR2KO

status: Public on May 09 2026

city: Burjassot

first: Antonio

last: Jordan

state: Valencia

address: Doctor Moliner 50

institute: Universitat de Valencia

summary: Stem cell maintenance and lineage commitment in the nervous system require precise regulation of transcription factors, among which SOX2 plays a central role. Its expression is controlled by multiple enhancers, including the Sox2 regulatory region 2 (Srr2), located downstream of the Sox2 locus. To dissect the role of Srr2 during neural development, we generated a CRISPR-Cas9 mouse model harboring a targeted deletion of this enhancer. We find reduced SOX2 in SEZ/SGZ niches and diminished ASCL1/OLIG2 progenitors, accompanied by fewer neurons and oligodendrocytes in vitro. Paired bulk RNA-seq and ATAC-seq at two defined transitions as 2 DIV (proliferation) and 2+1 DIV (early commitment) show that Srr2 loss causes widespread chromatin compaction during proliferation (6,393 DARs; 6,319 less accessible) that phenocopies wild-type differentiation, while accessibility largely converges by 2+1 DIV. Multi-omic integration reveals 115 neurogenic genes with persistent promoter closure and reduced induction at the transcriptional level in mutants, consistent with failure to activate proneural programs upon early differentiation. In vivo, SEZ cells of Srr2del/del mice exhibit lower SOX2 and FOXG1, fewer ASCL1/OLIG2 progenitors, and reduced neuronal and oligodendroglial markers. Together, our results uncover Srr2 as a critical enhancer of Sox2, required for establishing a chromatin environment permissive to neural differentiation, and underscore the importance of non-coding regulatory elements in controlling stem cell fate.

overall_design: 3 DIV proliferating WT and SRR2KO neurospheres and WT and SRR2KO NPs at the onset of differentiation (2+1 DIV) were harvested for RNA extraction. Between 2 and 3 biological replicates per condition and genotype.

first: Sara

last: Cruces-Salguero

first: Ana

last: Domingo-Muelas

last: Jordán-Pla

first: Jose

last: Morante-Redolat

first: Robin

last: Lovell-Badge

first: Isabel

last: Farinas

first: Verónica

last: Moncho-Amor