title: CD8+ T cells are primed by cDC1 and exacerbate tau-mediated neurodegeneration

city: SAINT LOUIS

first: Hao

last: Hu

state: MO

address: 4370 Duncan Ave

department: Neurology

institute: Washington University School of Medicine

summary: There are changes in adaptive immunity in Alzheimer’s disease (AD) and increases in activated CD8+ T cells in brain correlate with tau pathology. However, which cells mediate T cell priming in tau-mediated neurodegeneration remains unclear. In different conditions such as cancer, viral infections, and autoimmune diseases outside the CNS, conventional type-1 dendritic cells (cDC1) perform antigen cross-presentation to prime CD8+ T cells4,5. We demonstrate that tauopathy mice deficient in cDC1 or cross-presentation are markedly protected against tau-mediated neurodegeneration and display a selective decrease in brain CD8+ T cell infiltration and glial reactivity. The remaining CD8+ T cells showed an antigen inexperienced status with less clonal expansion, indicating suboptimal T cell priming. We confirm that brain derived antigens are presented in secondary lymphoid tissues to prime CD8+ T cells. Our study identifies cDC1 cells as critical for CD8+ T cell priming outside the CNS. This priming is required for a large increase of activated CD8+ T cells in the brain which promotes tau-mediated neurodegeneration.

overall_design: For single nucleus RNA-sequencing (snRNA-seq), mouse brains were collected dissected to isolate the hippocampal regions. The brain slices were mechanically minced with surgical scissors. Nuclei were purified and further sorted with AF647-anti-NeuN (to isolate neuronal nuclei; Cat# ab190565) AT 1:1000 (v:v) and PE-anti-PU.1 (to isolate microglia nuclei; Cat# 57800S) at 1:50 (v:v).

first: Carisa

last: Zeng

first: Maxim

middle: N

last: Artyomov

first: Jason

last: Ulrich

first: David

last: Holtzman


title: A Panel of Differentially Methylated Putative Imprinting Control Regions Associated with Hepatocellular Carcinoma

status: Public on Jun 30 2026

city: RALEIGH

first: Dereje

last: Jima

state: NC

address: 850 Main Campus Drive

department: CHHE

country: USA

institute: NCSU

summary: Site-specific 5-methylcytosine levels measured in mixed blood leukocytes have been used as surrogate for inaccessible tissues and associated with hepatocellular carcinoma (HCC) risk. However, findings are difficult to replicate as methylation patterns at many of these sites do not always correlate with those in liver tissue. An exception is methylation at imprinting control regions (ICRs), which regulate the monoallelic expression of imprinted genes, a developmentally critical process requiring parental allele-specific DNA methylation that is consistent across cell types. Aberrant methylation of several ICRs have been linked to advanced liver disease or HCC.   We aim to create a DNA methylation-based risk stratification panel to improve early detection and triaging of patients before the onset of HCC in those at increased risk.  From whole genome bisulfite sequencing (WGBS) of mixed leukocyte-derived DNA of HCC cases and controls, 1,519 regions were significantly differentially methylated. This list was augmented with a compendium of 3,275 HCC-, cirrhosis-, and fibrosis-associated differentially methylated regions (DMRs) identified from primary literature on PubMed, for a total of 4794 unique DMRs. Filtering these DMRs with a published list of ICRs revealed 97 ICRs within these liver disease-associated DMRs, 21 of them previously characterized and 76 novel. Of these ICRs, 46 replicated in an independent case-control comparison using the novel Illumina custom Imprintome Methylation array. Limited sample sizes notwithstanding, this comprehensive analysis supports the use of altered DNA methylation of ICRs for HCC risk stratification from readily accessible tissue, blood.

overall_design: The ‘Human Imprintome Methylation array’, an Illumina Infinium HTS iSelect Custom BeadChip, was designed to capture the Imprintome which comprises 1,488 genomic sequences predicted to function as ICRs based on their methylation profiles in human brain, liver, kidney, sperm and oocytes.(Jima et al., 2022) This array contains 22,819 probes (704 control probes and 22,115 CpG probes, of which 10,438 CpG probes target unique CpG sites). Among the CpG probes, 9,757 probes are associated with 1,088 of the 1,488 candidate ICRs; see Carreras-Gallo et al. (2024) for additional details.  Additional cgBackground probes enabled background-normalization. Leukocytes isolated from whole blood of 30 HCC cases and 35 otherwise healthy controls were measured on the Human Imprintome Methylation array. The raw IDAT file produced from the array were processed using the openSesame function in the Sesame R package(39). We processed the arrays with the Sesame preprocessing code “0CDB” that applies a non-linear dye bias correction and background subtraction using the noob method (Norm-Exp out of band signal), which deconvolves out-of-band fluorescent signal from true signal. The beta values are calculated by the ratio of the methylated signal to unmethylated signal for each probe. These processing steps produced a beta measurement for each probe and patient, along with a corresponding Sesame signal detection p-value that is used as a quality score. Signal detection p-values were assigned using the pOOBAH method (P-value with out-of-band (OOB) array hybridization). Probes that did not map to a CpG site in the Imprintome were discarded, and any remaining probes were also discarded if their signal detection p-value exceeded 0.2 for more than 10% of samples measured. For cases where multiple probes targeted the same CpG site, we averaged the beta values to produce beta measurements for each CpG site and participant.

first: Annie

last: DiFrank

first: Bruce

last: Corliss

first: James

middle: J

last: Park

middle: A

last: Skaar

middle: D

first: Michael

last: Cowley

first: Susan

middle: K

last: Murphy

first: Andrew

last: Lui

first: Cynthia

last: Moylan

first: Cathrine

last: Hoyo


title: Runx1 is a mediator of fibrotic activation and fibrotic memory in lung fibroblasts

city: Rochester

first: Aditya

last: Bhagwate

state: MN

address: 200 1st Street SW

institute: Mayo Clinic

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Runx1 emerged as a transcription factor that was potentially regulating fibroblast activation and memory following intratracheal bleomycin injury. In order to examine this, fibroblasts were lineage traced and collected following bleomyicn induced fibrosis at the peak fibrotic time point, Day 14, and at the time of fibrotic recovery, Day 56. Runx1 ChIPseq was performed to assess Runx1 binding in regions of genes known to be associated with fibrosis.

overall_design: ChIPseq of Runx1 binding in GFP+ fibroblasts that were isolated from Col1a2-CreERT;mTmG mouse lungs. Cells were collected at Day(D)14 or D56 following delivery of intratracheal bleomycin.

first: Rachel

middle: M

last: Gilbert

first: Dakota

middle: L

last: Jones

first: Daniel

last: Tschumperlin


title: PRL2 Promotes Leukemogenesis through Inhibiting the p53 Tumor Suppressor Signaling Pathway in Leukemia-initiating Cells

city: Chicago

first: Yan

last: Liu

state: IL

address: 303 E. Superior Street, Lurie 5-107, Northwestern University

department: Department of Medicine

institute: Northwestern University

type: Expression profiling by high throughput sequencing

summary: MLL-rearranged (MLL-r) acute myeloid leukemia (AML) is an aggressive subtype of leukemia characterized by poor prognosis, frequent relapse, and resistance to conventional therapies. These challenges highlight the urgent need for novel therapeutic targets. The phosphatase of regenerating liver (PRL) family proteins, also known as protein tyrosine phosphatase 4A (PTP4A), have been identified as oncoproteins in various human cancers. Among the three PRL family members (PRL1, PRL2, and PRL3), PRL2/PTP4A2 has been shown to play important roles in both normal and malignant hematopoiesis. Previous study found that PRL2 is highly expressed in MLL-r AML, but its role in leukemogenesis remains poorly understood. To understand how PRL2 promotes MLL-AF9-driven AML, we performed RNA-Seq analysis to compare gene expressions in PRL2+/+ and PRL2-/- LICs expressing MLL-AF9. Comparative analysis revealed significant changes in gene expression associated with p53 pathway activation upon PRL2 loss. This dataset provides a valuable resource for understanding the molecular mechanisms underlying PRL2 function in MLL-r AML and may support future efforts to identify novel therapeutic targets.

overall_design: Embryonic day 14.5-16.5 fetal liver cells, which known to be enriched for hematopoietic stem and progenitor cells (HSPCs), were collected from pregnant female mice. Prl2+/+ and Prl2-/- fetal liver cells were transduced with a retroviral vector expressing MLL-AF9 (MSCV-MLL-AF9-IRES-GFP). Following transduction, GFP+ cells were sorted to enrich for successfully transduced populations. These MLL-AF9+ GFP+ Prl2+/+ and Prl2-/- cells were defined as leukemia-initiating cells (LICs). RNA-seq was then performed on sorted LICs from each genotype. Comparative transcriptomic analysis was performed to identify gene expression differences between Prl2+/+ and Prl2-/- LICs, with a focus on pathways altered by PRL2 deficiency during MLL-AF9-driven leukemogenesis.

first: Michihiro

last: Kobayashi

first: Shiyu

last: Xiao


title: Microdystrophins Partially Rescue Duchenne Muscular Dystrophy Deficits in iPSC-Cardiomyocytes

city: Irvine

first: Asuka

last: Eguchi

state: CA

address: 845 Health Sciences Road

department: Physiology & Biophysics

institute: University of California, Irvine

summary: Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by the lack of dystrophin. Dilated cardiomyopathy is the leading cause of death in DMD patients. Smaller variants of dystrophin, called microdystrophins, amenable to packaging into adeno-associated virus (AAV), have shown to be effective in improving skeletal muscle function in animal models; however, the functional benefit of these microdystrophins in the DMD heart remains unclear. To determine the efficacy of microdystrophin gene therapy, we compared three microdystrophin variants in DMD cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs). We used three DMD lines of different genetic backgrounds and benchmarked against healthy isogenic controls expressing full-length dystrophin. DMD iPSC-cardiomyocytes exhibit hallmarks of disease, including arrhythmia and poor viability compared to healthy isogenic controls. In parallel, we tested a dystrophin variant, called minidystrophin, which is larger than the microdystrophins. We validated dystrophin expression and compared transcriptional profiles by bulk RNA sequencing. For morphological analysis, we performed immunohistochemistry of cardiac troponin on fixed cells. To test the functional benefit of the transgenes, we performed calcium imaging with a ratiometric calcium indicator as well as viability assays. Our results show that the microdystrophins partially rescue disease phenotypes; however, the results are variable among genetic backgrounds. None of the gene therapies altered the global transcriptional profile of the DMD iPSC-CMs to resemble a healthy profile. Minidystrophin significantly improved cell viability of DMD iPSC-CMs in two of three lines of different genetic backgrounds. Our findings suggest that microdystrophins may have limited efficacy in DMD cardiomyocytes and that the delivery of larger dystrophin variants may be necessary to delay the onset of cardiac complications.

overall_design:
RNA-Seq profiling of DMD iPSC-CMs treated with microdystrophin or minidystrophin gene therapy. Control iPSC-CMs and iPSCs were included in the study. An empty vector control was used for DMD iPSC-CMs and Control iPSC-CMs. Profiling was conducted on Day 30 of differentiation.

Grant ID: 964697
Grant Title: Microdystrophin Design for the Treatment of Dystrophin-Deficient Cardiomyocytes
Grantee: Asuka Eguchi
Funding source: Muscular Dystrophy Association

first: Abiageal

middle: R

last: Keegan

first: Adriana Fernanda

middle: G

last: Gonzalez

first: Rongruo

last: Zhang

first: Hung

last: Doan

first: Sofía

middle: I

last: Torres-Bigio

first: Fiona

last: Lau

first: Kaulen

last: Ly

first: Elaine

middle: C

last: Lai

first: Leahlyn

last: Mamuyac

first: Sriram

last: Bhimaraju

first: Abhishree

last: Mishra

first: Michelle

last: Polen

middle: S

last: Ortiz

first: Jay

middle: H

last: Lam


title: Translational Control of Splicing Factors Directs Hematopoietic Stem Cell Fate [RNA-Seq]

city: Warsaw

first: Vladyslava

last: Liudkovska

address: Flisa 6

country: Poland

institute: IMol Polish Academy of Sciences

summary: The transition of hematopoietic stem cells (HSCs) from quiescence to differentiation is essential for homeostasis. While transcriptomic control of this process has been extensively studied, the diversity of mRNA isoforms during exit from quiescence remains unexplored. Here, we identify a translationally regulated splicing program governing hematopoietic fate decisions. Splicing factors involved in branch point recognition show dynamic protein-level regulation during HSC differentiation. Among them, Sf1 is translationally controlled via a conserved, structured 5′ UTR. Disrupting translation regulation of Sf1 skews differentiation toward stem cell and erythroid programs. Sf1-dependent alternative splicing affects 5′ UTRs of hematopoietic and DNA damage response genes, altering their translation and impairing DNA damage resolution. These findings reveal an unrecognized link between translational control of spliceosome components, alternative splicing, and HSC fate decisions.

overall_design: RNA-seq of primary ex vivo-expanded murine hematopoietic stem and progenitor cells (HSPCs) with and without translational control of Sf1. Samples with CRISPR-Cas9-mediated deletion of nucleotides 51–100 in the Sf1 5′ UTR (del) are compared to unedited control cells.

first: Sandra

last: Binias

first: Bartosz

last: Wojtas

first: Maciej

last: Cieśla


title: HTZ-1/H2A.Z expression sustains transcriptional programs that regulate Caenorhabditis elegans lifespan

city: Bonn

first: Daniele

last: Bano

state: NRW

address: Venusberg Campus 1/99

country: Germany

institute: DZNE, German Center for Neurodegenerative Diseases

summary: This study was performed to investigate the contribution of HTZ-1/H2A.Z to transcriptional programs regulated by insulin/IGF-1 signaling.

overall_design: RNAseq analysis of adult wildtype, daf-2(e1370), daf-16(mu86);daf-2(e1370), htz-1(bon101), daf-2(e1370);htz-1(bon101) and daf-16(mu86);daf-2(e1370);htz-1(bon101) mutant Caenorhaditis elegans.

first: Beijia

last: Xie

first: Enzo

last: Scifo

first: Yiru

last: Wang

first: Antonia

last: Piazzesi

first: Elena

last: De-Domenico

first: Stefan

last: Paulusch

first: Marc

last: Beyer


title: ARID1A terminates gastric regeneration to prevent cancer

city: Mississauga

first: Ho Sung

last: Rhee

state: ON

address: 3359 Mississauga Rd

department: Cell and Systems Biology

country: Canada

institute: University of Toronto

summary: Exposed constantly to environmental challenges, the stomach undergoes highly reversible cycles of regeneration and recovery. Although abnormal activation of regeneration is known to be associated with cancer, the mechanisms underlying tissue restoration remain unclear. Our single-cell gene expression and chromatin analysis defined cell state dynamics during regeneration and recovery, identifying the Brahma-related gene 1(BRG1)/BRM-associated factor (BAF) chromatin remodeling complex during recovery. Strikingly, deletion of AT-rich interaction domain 1A (Arid1a), a subunit of the BAF complex and the second most frequently mutated gene in gastric cancer, impaired recovery across multiple murine injury models, resulting in a persistent regenerative state. Integrative analyses combining single-cell multiome and chromatin immunoprecipitation sequencing (ChIP-seq) demonstrated that the BAF complex recruits lineage-specific transcription factors such as MIST1 and estrogen related receptor gamma (ERRγ) to regulate enhancers of recovery genes. Notably, deletion of Trp53 in the unresolved regenerative state caused by Arid1a loss is sufficient to drive cancer development and invasion, revealing the epigenetic mechanisms bridging gastric regeneration, recovery, and cancer.

overall_design: Examination of ChIP-seq profiles of mouse stomachs treated with tamoxifen by deep sequencing

first: Adrian

last: Loe

first: Alyssa

last: Ialongo

first: Tae-Hee

last: Kim


title: Transcriptome Analysis Reveals Sex Disparities in Recurremt and Non-Recurrent Papillary Thyroid Cancer (PTC)

city: Iowa City

first: Zhijie

last: Li

state: IA

address: 285 Newton Road

institute: University of Iowa

summary: RNA-seq was used to profile the transcriptomes of 16 patients (8 with non-recurrence and 8 with recurrence). Transcriptome analysis showed that sex differences in gene expression from thyroid cancer patients with and without recurrence. Gene Set Enrichment Analysis (GSEA) revealed TNFa signaling pathway was differentially regulated between male and female patients, providing insights into the complexity of gene expression changes underlying sex disparities.

overall_design: In total, 16 formalin-fixed, paraffin-embedded tissue sections (5 female patient tumor with non-recurrence, 5 female patient tumor with recurrence, 3 male patient tumor with non-recurrence, 3 male patient tumor with recurrence) were collected and prepared for RNA-seq

first: Jeremy

last: Chang

first: Guillermo

last: Ng Yi

first: Victoria

last: Deters

first: Ronald

last: Weigel

first: Anna

last: Beck


title: Reciprocal genetic screens identify epigenetics factors controlling epidermal cell activation. [seCLIP]

city: Turin

first: Andrea

last: Lauria

address: Via Accademia Albertina, 13

department: Life Sciences and Systems Biology

country: Italy

institute: University of Turin

summary: In adult tissues, in response to injury or to the acquisition of a mutational landscape, epithelial stem cells leave their homeostatic state and become activated. To identify the epigenetic factors involved in this process we performed pooled genetic screens integrated with two transcriptional read out systems. These revealed a network of factors including Kmt5c (Suv420h2), Ehmt2 and Cbx3. Through a series of omics and cellular functional assays we discovered their functional role at the cellular and molecular level. In particular we identified a multi-layered control of gene expression, dependent by Cbx3, ranging from transcriptional regulation to mRNA localization.

overall_design: Direct RNA targets of Cbx3. Single-end enhanced (se)CLIP of Cbx3 in mouse keratinocytes.

first: Carlotta

last: Duval

first: Giacomo

last: Donati


title: Genetic landscape of an in vivo protein interactome

city: Montreal

middle: W R

last: Serohijos

state: QC

address: 5155 Chem. de la Rampe

department: Department of Biochemistry

institute: University of Montreal

summary: The dynamics of protein-protein interaction (PPI) networks accurately map environmental perturbations to their molecular consequences in cells, but how and to what extent PPIs are modulated by genome-wide genetic variation is unknown. If a PPI network integrates both genetic and environmental effects to phenotype, then probing it could help define biochemical mechanisms underlying complex polygenic traits. Here, using inbred strains of the yeast Saccharomyces cerevisiae with ~12,000 single-nucleotide polymorphisms (SNPs) spread across the genome at a density of ~1 SNP/kb, we identified genomic loci that significantly modulate 61 in vivo PPIs. In contrast to mRNA expression and protein abundance that are primarily affected by SNPs local to the gene (in “cis”), PPIs are dominantly affected by SNPs far (in “trans”) from the gene locus of the interacting protein pair. Consistent with the small-world characteristic of PPI networks, these trans-acting SNPs, although distant in the genome, are enriched in genes that are neighboring nodes in the PPI network. We likewise discovered several SNPs in cryptic non-coding RNAs and post-transcriptional regulators (3' UTRs) with, counterintuitively, larger PPI-modulating effects than SNPs within protein-coding regions. Finally, we inferred known and novel mechanisms of action for four yeast and human drugs.

overall_design: To investigate the effecto of genome-wide genetic variations on protein-protein interactions, we constructed yeast libraries contains chromosomal barcode for identifying genetic variants. We measured these strains' fitness based on the barcode frequency after DFHR-PCA assay by using NGS.

first: Savandar

last: Besse

first: Tatsuya

last: Sakaguchi

first: Louis

last: Gauthier

first: Zahra

last: Sahaf

first: Rini

last: Ravindran

first: Lidice

last: Gonzalez

first: Xavier

last: Castellanos-Girouard

first: Cassandre

last: Clairmeont

first: Nazli

last: Koçatug

first: Olivier

last: Péloquin

first: Chloé

last: Matta

first: Julie

last: Hussin

first: Stephen

middle: W

last: Michnick


title: Immune Checkpoint Molecules as Biomarkers of Outcomes in Staphylococcus aureus Bone Infections

first: Gowrishankar

last: Muthukrishnan

state: New York

address: 665-G, 601 Elmwood Ave

department: Orthopaedics, Center for Musculoskeletal Research

institute: University of Rochester Medical Center

summary: Staphylococcus aureus prosthetic joint infections (PJIs) are considered incurable.  Unfortunately, clinical diagnostics to guide conservative vs. aggressive surgical treatment of PJI patients are not evidence-based. Developing clinical biomarkers are crucial for defining immunopathogenesis of PJIs.  PJI in humanized mice is characterized by increased infection, bone osteolysis, and large numbers of proliferating CD3+/Tbet+ cells adjacent to purulent abscesses in the bone marrow. Multi-omics studies in a humanized NSG-SGM3 BLT PJI mouse indicated the role of human T cells where 1) human T cells are remarkably heterogenous in gene expression and numbers, 2) human Th1/Th17 exists as a mixed population of activated, progenitor-exhausted, and terminally-exhausted cells which exhibit increased expression of immune checkpoint proteins (LAG3, TIM-3) 2-weeks post-infection. Moreover, these proteins are upregulated in the serum and the bone marrow of S. aureus PJI patients.  A multiparametric nomogram combining high serum immune checkpoint protein levels with low proinflammatory cytokine levels (IFN-g, IL-2, TNF-α, IL-17) revealed that TIM-3 was highly predictive of adverse outcomes in PJI patients (AUC=0.89). Hence, T cell impairment in the form of immune checkpoint expression and exhaustion could be a functional biomarker for S. aureus PJI disease outcome, and checkpoint blockade may benefit PJI patients.

overall_design: Humanized Mice were subjected MRSA transtibial implant-associated osteomyelitis with MRSA-infected implants and sterile implants. Two weeks post-surgery, humanized mice were sacrificed, bone marrow cells were isolated and flow-sorted to human CD3 T cells and CD19 B cells.

first: Motoo

last: Saito

first: Alex

last: Grier


title: Targeting neurodevelopmental miR132-3p promotes neuroprotection and axon regeneration after optic nerve injury in mice

status: Public on Jun 29 2026

city: Farmington

first: Jacob

last: Brady

state: Connecticut

address: 263 Farmington Avenue

department: Neuroscience

institute: UConn School of Medicine

summary: Micro-RNA (miRNA) miR-132 regulates the axonal elongation-to-branching switch in central nervous system (CNS) neurons during maturation, which coincides with the mammalian developmental loss of CNS projection neurons’ intrinsic axon growth capacity. However, it is unknown whether experimental targeting of miR-132 in mature CNS neurons could activate elongation/regeneration of the axons severed by an injury. Here, we characterized miR-132 5p and 3p arm expression during maturation of a prototypical CNS projection neuron, the retinal ganglion cell (RGC), and then tested whether miR-132 arm-specific knockdown (KD) in the RGCs activates elongation/regeneration of axons severed by optic nerve crush (ONC) injury in vivo. We identified the miR132-3p arm as developmentally-upregulated in the RGCs and found that its KD modestly but significantly promoted RGC axon-regeneration and survival. We also gained insights into the miR132-3p KD-regulated biological processes by transcriptomic profiling of the treated injured RGCs, which showed enrichment of a developmental gene network for formation of axonal projections. Thus, neuronal miR132-3p plays a role in axon regeneration after optic nerve injury, and future studies should investigate the underlying mechanisms.

overall_design: Optic nerve surgeries and intravitreal injections were carried out on mice of both sexes 8-12 weeks of age (average body weight 20-26 g) under general anesthesia. The viruses included adeno-associated virus serotype 2 (AAV2) vectors expressing anti-miR132-3p (sequence: 5′-CGACCATGGCTGTAGACTGTTA-3′, against the targeted sequence: 5′-TAACAGTCTACAGCCATGGTCG-3′) and scrambled control (sequence: 5’-TCGAGGGCGACTTAACCTTAGG-3’) shRNAs (titers ~1 × 1013 GC/mL; VectorBuilder, Inc.). Both viral vectors co-expressed an mCherry reporter of transduction. Viruses (2 μl per eye) were injected intravitreally, avoiding injury to the lens, in 8-week-old mice, which were randomly assigned to experimental or control conditions, 2 weeks prior to ONC surgery. It is standard protocol to inject AAV2 two weeks prior to ONC, because this lead time allows sufficient time for transduction and expression of the shRNAs in RGCs at the time of ONC. For bulk-mRNA-seq of injured adult RGCs transduced with AAV2 (~40% transduction efficiency) expressing anti-miR132-3p or scramble-control shRNAs, the RGCs were Thy1-immunopanned from single cell retinal suspension (from 10 post-ONC retinas per condition) and FACS’ed for mCherry+ cells. Approximately, 5,000 RGCs (for each of the 2 replicates per condition) were collected by FACS and RNA was isolated immediately using the Quick-RNA Microprep Kit (ZR1050, Zymo Research). For mRNA-seq, cDNA libraries were prepared using polyA-selected RNA (TruSeq RNA Library Prep Kit, Illumina), paired reads sequenced 100 bp from each end on HiSeq 2000 Sequencer (Illumina).

first: Ephraim

middle: F

last: Trakhtenberg


title: Tandem bispecific IL-7 receptor agonist antibody

city: 달성군

first: Jun-Kook

last: Park

state: 대구광역시

address: 대구광역시 테크노북로

country: South Korea

institute: DGIST

summary: Interleukin-7 (IL-7) is essential for T cell immunity, but the therapeutic application of existing IL-7 therapies is limited by narrow therapeutic window and suboptimal pharmacokinetics. To address this, we engineered a fully human tandem bispecific antibody, TB4, that functions as a potent IL-7 receptor (IL-7R) agonist by cross-linking the IL-7Rα and γc subunits. In primary human T cells, TB4 exhibited potent bispecific binding and induced sustained STAT5 signaling, a feature potentially associated with its slow antibody internalization rate. TB4 promoted T cell survival and the preferential expansion of CD4⁺ memory T cells. Notably, transcriptomic analysis revealed that TB4 induces a unique transcriptional signature enriched in genes associated with antiviral and innate immune responses, distinguishing it from native IL-7. These findings highlight TB4 as a promising IL-7R agonist with the potential to act as a subset-specific T cell immunomodulator, shaping both the expansion and functional profile of T cells.

overall_design: To define the molecular programs driven by TB4 and to distinguish them from those of IL-7, we performed bulk RNA-sequencing (RNA-seq) on CD3+ T cells isolated from human PBMCs treated for 14 days.

first: Inseong

last: Jung

first: Kyungmoo

last: Yea


title: CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation

city: New York

first: Viviana

middle: I.

last: Risca

state: NY

address: 1230 York Ave, Box 176

department: Laboratory of Genome Architecture and Dynamics

institute: The Rockefeller University

summary: Cellular senescence consists of regulated phenotypes associated with permanent exit from the cell cycle in response to stressors such as genomic instability. The consequences of senescence go beyond individual cells due to the senescence associated secretory phenotype (SASP), which can induce inflammation in neighboring cells. Some cancers respond to CDK4/6 inhibitors (CDK4/6i) with a senescence-like phenotype in the absence of extensive DNA damage. We asked how the SASP and the transcriptional regulatory profile triggered by CDK4/6i-driven arrest compares to the canonical NF-κB-regulated SASP triggered by DNA damage. We profiled the dynamics of transcriptional regulation in response to the CDK4/6i, palbociclib, and the DNA damaging agent, doxorubicin. We found upregulation of NF-κB driven-SASP genes was shared across both drugs, although delayed in CDK4/6i, coinciding with slower enhancer activation and epigenetic changes. ATM/ATR inhibition did not affect CDK4/6i-induced NF-κB nuclear localization, suggesting an alternative upstream activator. Inhibiting NF-κB suppressed the expression of SASP genes without reversing stable arrest, pointing to SASP manipulation as a potential therapeutic strategy and providing insights into controversies regarding cell cycle arrest-driven SASP.

overall_design: We profiled the dynamics of DNA damage-induced and DNA damage-independent senescence using a patient-derived liposarcoma cell line model (LS8817) known to be responsive to CDK4/6i. Using RNA-seq, ATAC-seq and CUT&Tag, we compared the temporal evolution of CDK4/6i- and doxorubicin-induced senescence over a 28-day time course of the CDK4/6i, palbociclib (Palbo), and a 21-day time course of doxorubicin (Doxo); we used a slightly shorter period for Doxo as doxorubicin-induced geroconversion occurs at a more rapid pace. This duration of treatment is long enough for progression through geroconversion in vitro to occur. We mapped out shared and distinct transcriptional regulatory networks, including those involved in the regulation and output of the senescence-associated secretory phenotype (SASP), in response to CDK4/6i and doxorubicin over time.  We also performed a similar experiment in MCF7 breast cancer cells, where we profiled the gene expression dynamics over 21 days of 100nM palbociclib + 10nM fulvestrant treatment.  We performed a separate experiment comparing CDK4/6i to doxorubicin induced senescence in MCF7 cells. MCF7 cells were treated with 100 nM doxorubicin (treated for 48 hours, followed by drug washout), 1 uM palbociclib or 100 nM palbociclib + 10 nM fulvestrant. Cells were harvested at day 14, day 21 and day 18 respectively, since treatment started. RNA extraction was done using the Quick-RNA Microprep Kit (Cat# R1050, Zymo Research, Irvine, California). Total RNA was sent to PlasmidSaurus for single-end RNA sequencing.  Samples are to be added to GSE295260

first: Joanna

last: Yeung

first: Justin

last: Rendleman

first: Lauren

last: Anderson Westcott

first: Arnold

last: Ou

first: Matthew

last: Pressler

first: Nicole

last: Pagane

first: Irene

last: Duba

first: Ria

last: Hosuru

first: Bat-Ider

last: Tumenbayar


title: Macrophage-exacerbated viral lung injury and mechanical overdistension-driven bacterial superinfection replicated in a human lung chip

status: Public on Jun 28 2026

city: Boston

first: Yuncheng

last: Man

state: MA

address: 201 Brookline Ave

institute: Wyss Institute, Harvard University

summary: Patients with severe influenza-induced lung injury exhibit disrupted alveolar barrier and persistent viral load, accompanied by hyperinflammation, immune cell recruitment, and risk of bacterial superinfection. These complications are often exacerbated in patients undergoing mechanical ventilation. Leveraging an immune-competent human lung alveolus-on-a-chip (Lung Chip) lined by human pulmonary alveolar epithelium co-cultured with monocyte-derived macrophages and interfaced with lung microvascular endothelium, we show that monocyte-derived macrophages play a central role in driving key hallmarks of severe influenza, including activated cell death programs. Physiological strain mimicking breathing motions supported alveolar homeostasis, whereas pathological strain analogous to mechanical ventilator-induced lung overdistension promoted secondary Pseudomonas aeruginosa infection. Computational gene network analysis combined with experimental validation identified SIRT1 as a key modulator of inflammation and susceptibility to bacterial superinfection, which can be mitigated using pharmacological SIRT1 activators. Together, these findings underscore the importance of incorporating macrophages into preclinical models of viral lung injury and establish an integrated workflow combining human Organ Chips and computational approaches for gaining insights into biophysical and molecular disease drivers while facilitating the identification of therapeutic targets and candidate countermeasures.

overall_design: Single-cell RNA-seq analysis of the human Lung Chip for cell composition validation


overall_design: Bulk RNA-seq profiling of human primary alveolar epithelial cells and macrophages interfaced with human primary lung microvascular endothelial cells that were cultured in human Lung Chips under indicated conditions.


title: Loss-of-function of ALDH3B2 transdifferentiates human pancreatic duct cells into beta-like cells

status: Public on Jun 27 2026

first: Jonathan

last: Dreyfuss

address: 1 Joslin Pl

department: Bioinformatics & Biostatistics Core

institute: Joslin Diabetes Center

summary: Replenishment of pancreatic beta cells is a key to the cure for diabetes. Beta cell regeneration is achieved predominantly by self-replication, especially in rodents, but it was also shown that pancreatic duct cells can transdifferentiate into beta cells. How pancreatic duct cells are transdifferentiated and whether we can manipulate transdifferentiation to replenish beta cell mass is not well understood. Using a genome-wide Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) screen, we found that loss-of-function of Aldehyde dehydrogenase family 3 member B2 (ALDH3B2) was sufficient to transdifferentiate human pancreatic duct cells into functional beta-like cells. The transdifferentiated cells had substantially increased expression of beta cell marker genes, secreted insulin in response to glucose, and lowered blood glucose to near normal when transplanted into streptozotocin (STZ)-induced diabetic mice for 6 weeks. Our study identifies a gene that could potentially be targeted in human pancreatic duct cells to replenish beta cell mass for diabetes therapy.

overall_design: Following NTC or ALDH3B2 lentiviral infection, the human pancreatic duct cells were isolated by fluorescence-activated cell sorting (FACS) and analyzed using scRNA-sq.

first: Peng

last: Yi

first: Jian

last: Li


title: Neocentromeres fail to maintain DNA methylation boundaries, driving CENP-A drift, instability, and chromosome missegregation

status: Public on Jun 26 2026

city: Pittsburgh

first: Megan

last: Mahlke

state: Pennsylvania

address: 5115 Centre Ave

institute: UPMC

summary: Centromere identity is specified by CENP-A, a histone H3 variant that epigenetically defines centromere position. How CENP-A is maintained at one location in rapidly evolving centromeric DNA is unknown. Using single-cell derived clones of human cell lines, we demonstrate heterogeneity in CENP-A position within cell populations at neocentromeres and a native centromere. CENP-A heterogeneity is accompanied by heterogenous DNA methylation patterns, with DNA methylation shifting according to CENP-A position. We demonstrate centromere epigenetic plasticity over extended proliferation, with native centromeres maintaining stable DNA methylation boundaries, but neocentromeres exhibiting DNA methylation instability, boundary loss and increased missegregation. Finally, we show that neocentromeres are more sensitive to DNA methylation inhibition than native centromeres, and that this inhibition is accompanied by expanded CENP-A-enriched domains and increased missegregation. This study supports a role for DNA methylation boundaries in maintaining centromere position, stability and function and highlights the intrinsic instability of DNA methylation at neocentromeres.

overall_design: ChIP-seq and CUT&RUN for CENP-A was performed in PD-NC4, IMS13q, and BBB single-cell derived clones and subclones isolated form young and 12-months-old populations.

first: Angela

last: Enriquez

first: Yael

last: Arbely


title: RNA-seq of MDA-MB-231 with BCSC state sorting (A-BCSCs vs Q-BCSCs via SDorm system) and ENO1 silencing (siENO1 vs siNC)

city: Dalian city

first: Yujie

last: Zeng

state: Liaoning province

address: No. 9, West Section, Lvshun South Road

department: Institute of Cancer Stem Cell

country: China

institute: Dalian Medical University

summary:
Quiescent breast cancer stem cells (Q-BCSCs) can switch to an activated state (A-BCSCs). We established a dual-reporter system for stemness and quiescence (NANOG-EGFP + H2B-mCherry pulse-chase) to isolate A-BCSCs and Q-BCSCs from MDA-MB-231 cells. Strand-specific poly(A) RNA-seq was performed to compare A-BCSCs vs Q-BCSCs (n=3 per group). In a second dataset, ENO1 silencing (siENO1) was compared with a non-targeting control (siNC) in unsorted MDA-MB-231 cells (n=2 per group). Processed data are provided as separate experiment-specific gene-level matrices rather than a single unified matrix because different Ensembl gene annotation releases were used for quantification in the two experiments. For the A-BCSCs vs Q-BCSCs dataset, counts and FPKM matrices together with a matching gene annotation table are provided. For the siENO1 vs siNC dataset, counts and FPKM matrices together with a matching gene annotation table are provided.
Previous reports have identified NANOG as a key stemness factor in tumor cells. Based on this, we established a stable fluorescent reporter system in MDA-MB-231 cells via lentiviral transduction, in which EGFP is driven by the NANOG promoter and expressed upon NANOG activation. To validate whether this system faithfully reflects cellular stemness, NANOG-EGFP positive and negative cells were sorted by FACS and subsequently analyzed by RNA-seq. Our results showed that the NANOG-EGFP positive population was enriched for stemness-related gene pathways, confirming that this reporter system can effectively indicate tumor cell stemness

overall_design:
Cell line: MDA-MB-231 (female; breast; ATCC HTB-26). Datasets: (1) BCSC state sorting using a dual-reporter system for stemness and quiescence: A-BCSCs (activated) vs Q-BCSCs (quiescent), with 3 biological replicates per group (6 samples total). (2) ENO1 silencing in unsorted MDA-MB-231 cells: siENO1 vs siNC, with 2 biological replicates per group (4 samples total). Library preparation: strand-specific poly(A) mRNA-seq; paired-end 150 bp; Illumina NextSeq 2000. Processed data are deposited as separate gene-level matrices for the two experiments, with matching gene annotation tables, because different Ensembl annotation releases were used for quantification. The A-BCSCs vs Q-BCSCs dataset was quantified using Homo sapiens Ensembl release 94 annotation. The siENO1 vs siNC dataset was quantified using Homo_sapiens.GRCh38.110 annotation.
RNA-seq profiling data from FACS-sorted NANOG EGFP-positive versus NANOG EGFP-negetive MDA-MB-231 cells.

first: Shuai

last: Liu

first: Yunfeng

last: Ma

first: Zhijie

last: Hou

first: Dekang

last: Lv

first: Junxiu

last: Huang

first: Yaqi

last: Gong

first: Ruijun

last: Feng

first: Zihan

last: Wang

first: Ran

last: Sui

first: Dan

first: Yameng

last: Wu

first: Nuo

last: Chen

first: Mingzhi

last: Yao

first: Ying

last: Shan

first: Yuan

first: Yuesheng

first: Jinsong

last: Yan

first: Fei

last: Peng

first: Quentin

first: Jie

last: Xu


title: Insights From Genetic Predisposition to Pathogenicity of Myopia Development in Guinea Pigs

city: Baton Rouge

first: Sujoy

last: Ghosh

state: LA

address: 6400 Perkins Rd

institute: Pennington Biomedical Research Center

summary: The global prevalence of myopia is increasing, expected to affect nearly half the world's population by 2050. High myopia, impacting 2.7% globally, poses risks of severe vision loss and public health concerns. Myopia's cause is believed to be a mix of genetic and environmental factors leading to excessive eye elongation. This study focuses on understanding myopia's development by comparing albino and pigmented guinea pigs, with albinos showing higher spontaneous myopia incidence. The research uniquely investigates both genomic and proteomic aspects across different eye tissues in these animals, aiming to uncover the biological mechanisms behind myopia susceptibility and development, particularly in albino guinea pigs.

overall_design: 3 tissues (retina, choroid, sclera) X 3 strains (albino hyperopic, AH; albino myopic, AM; pigmented hyperopic, PH) X 4 replicates per tissue per strain

first: Susan

last: liqin

first: Lijin


title: Elevated Ozone Activates Maternal Immunity to Drive Offspring IgG-Mediated Anaphylaxis through IgG Glycosylation Reprogramming

city: Taiyuan

first: Xiaoyun

state: Shanxi

address: Wucheng Road 92, Xiaodian District

institute: Shanxi University

summary: The global burden of allergic diseases has reached alarming proportions and environmental factors exert a strong influence. Ozone (O3), with escalating pollution levels, has emerged as a critical and pressing environmental challenge worldwide and elicits pervasive oxidative stress among population. Epidemiological studies have linked prenatal oxidative stress to offspring allergy susceptibility, while existing evidence lacks causality.To address these gaps, correlation between hematological abnormalities in the retrospective mother-infant cohort and the daily O3 level was analyzed. Gestational MIA was induced via O3 exposure at environmentally relevant concentrations from embryonic day 9.5 (E9.5) onward, allowing for an in-depth examination of how neonatal IgG glycosylation is programmed.Using transcriptomic sequencing technologies, we further analyzed the subsequent effects on inflammatory pathways. Utilizing established allergic challenge models, long-term immune consequences in offspring were systematically evaluated, with a specific focus on elucidating the mechanistic role of glycosylated IgG in predisposing MIA progeny to allergic reactions.

overall_design: Comparative analysis of gene expression profiles in the lungs of offspring mice at different developmental stages (postnatal day 14 [PND14] and PND56) following maternal exposure to filtered air (control group) versus ozone (0.5 ppm) during pregnancy, based on RNA-seq data.

first: Zhihua

first: Yuchai

last: Tian

first: Xiaomin

last: Liang

first: Mudan

first: Huizhen

last: Zhu

first: Jiyue

last: Zhang

first: Yangcheng

last: Hu

first: Bin

last: Li

first: Pannan

first: Xiaotong

last: Ji

first: Huifeng

last: Yue

last: Sang


title: Mechanisms of MCM2-7 loading and initial DNA melting near base-pair resolution

city: London

first: LMS

last: Bioinformatics Core

address: Hammersmith Hospital Campus, Du Cane Road

department: Bioinformatics Core

country: United Kingdom

institute: MRC London Institute of Medical Sciences

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

overall_design: Refer to individual Series


title: Single-cell RNA sequencing of ovarian CD45+ immune cells from gonadotropin-treated and untreated mice

status: Public on Jun 24 2026

city: Burlington

first: Seth

last: Frietze

state: VT

address: 149 Beaumont Avenue

department: Biomedical and Health Sciences

institute: University of Vermont

summary: CD45+ immune cells were isolated from ovaries of adult female C57BL/6J mice treated with gonadotropin (n=5) or saline control (n=5). Individual mice were labeled with TotalSeq-B hashtag antibodies, pooled by treatment group, and subjected to 10x Genomics Chromium single-cell RNA sequencing. Hashtag oligonucleotide libraries were used for sample demultiplexing. The dataset was generated to characterize ovarian immune cell populations and their response to gonadotropin-induced hormonal stimulation.

overall_design: Female C57BL/6J mice (10–12 weeks old) received gonadotropin treatment (n=5) or saline control (n=5). Ovaries were harvested 48 hours later and dissociated into single-cell suspensions. CD45+ viable leukocytes were isolated by flow cytometric sorting. Individual samples were labeled with unique TotalSeq-B hashtag antibodies and pooled within treatment groups. Gene expression and hashtag oligonucleotide libraries were generated using the 10x Genomics Chromium Single Cell 3' v3 platform and sequenced on an Illumina HiSeq 2500. Hashtag libraries were used for sample demultiplexing and assignment of individual cells to their originating mouse. Processed data consist of the combined cell-by-gene expression matrix and associated cell metadata.

first: Dimitry

last: Krementsov

first: Tia

last: Brodeur


title: Deformability screening identifies NUDT5 as a mediator of cellular mechanobiology

city: Los Angeles

first: Angelina

last: Flores

state: California

address: 610 Charles E Young Dr. East

department: Integrative Biology and Physiology

institute: University of California, Los Angeles

summary: How cells deform, sense, and respond to mechanical cues drives physiological and disease processes ranging from development to cancer metastasis; however, unbiased approaches to identify mechanical mediators are lacking. We screened 1280 compounds to identify modulators of cancer cell deformability using a cellular filtration assay and identified 92 compounds that significantly reduced deformability of ovarian cancer cells; top hits also reduced migration and invasion. Connectivity mapping of the top 21 compounds identified NUDT5 (Nudix hydrolase 5) as a predicted mechanical mediator; transcriptomic analyses implicated NUDT5 in mechanobiology and metabolic processes. We confirmed that NUDT5 mediates intracellular ATP and cellular mechanical behaviors, including morphology and deformability. In ovarian cancer, increased NUDT5 levels were associated with higher tumor stage and worse patient survival; NUDT5 inhibition reduced migration and colony formation in vitro and peritoneal tumor burden in mice. These findings establish deformability-based screening as a platform for discovering mechanical mediators and identify NUDT5 as a therapeutic target in ovarian cancer.

overall_design: Bulk RNA sequencing was performed on OVCAR-5-Cisplatin resistant (OVCAR-5-CisR) cells 48 h after si-RNA-mediated NUDT5 knockdown

first: Jennifer

last: Soto

first: Amy

last: Rowat


title: Transcriptome profiling of ovaries in aged mice administered additional Samul-tang-associated compounds

status: Public on Jul 06 2026

city: Busan

first: Haeseung

last: Lee

address: 63 Beon-gil 2, Busandaehag-ro, Geumjeong-gu

department: College of Pharmacy

institute: Pusan National University

summary: Samul-tang (SM) is a traditional multi-ingredient treatment widely used in clinical practice for women's health and reproductive disorders. Despite its therapeutic benefits, the complexity of its mechanisms of action due to the combination of multiple compounds has limited its research integration into modern pharmacological science. To address this challenge, we identified 28 herbal compounds as major ingredients in SM and generated transcriptome data from the mice ovaries after administrating with individual ingredients. This dataset aims to provide insights into the mechanisms of action of SM and to aid in the identification of effective ingredient combinations.

overall_design: To obtain RNA-seq data of ovaries treated with compounds of Samul-tang, mice were randomly divided into groups of three. Aged mice(38 weeks old) were orally administered either distilled water containing 0.5% Dimethyl sulfoxide (DMSO; D2650; Sigma-Aldrich) or each of the 28 single compounds at a dose of 5 mg/kg, five times a week for four weeks. After four weeks of compound administration, a post-ovulatory state was induced by intraperitoneal injection of 5 IU PMSG followed 48h later by 5 IU hCG. Ovaries were collected 16-18h after hCG administration and immediately preserved in liquid nitrogen for RNA sequencing.

first: Sooseong

last: You

first: Hyejin

last: Shin


title: Human amygdala-like telencephalic organoids from Pluripotent Stem Cells

status: Public on Jun 25 2026

city: New haven

first: Woo Sub

last: Yang

state: CT

address: 10 Amistad St, Room 214j

institute: Yale University

summary: The amygdala, a key region in the limbic system, is central to regulating emotion, memory, stress, and social behaviors. However, studying its functions has been challenging due to the lack of reliable in vitro models. Here, we developed amygdala-like telencephalic organoids (hATOs) from pluripotent stem cells, recapitulating the cellular composition, molecular features, and functional properties of the amygdala.

overall_design: The scRNA-seq analysis was performed on amygdala organoids at Day 40 and Day 80, while the RNA-seq analysis was conducted on Day 81 amygdala organoids derived from sample sets with Angelman syndrome patients or healty control iPSCs and 24h cortisol treatment.and RNA-seq for hypothalamic organoid with or without BMP4 at D80


title: Genome-wide mapping of DNA G-quadruplexes in Trypanosoma brucei chromatin reveals enrichment in coding regions and transcription start sites [RNA-seq]

first: Marco

last: Di Antonio

address: 82 Wood Lane

department: Chemistry

institute: Imperial College London

summary: G-quadruplexes (G4s) are non-canonical DNA structures formed in guanine-rich sequences that are proposed to act as regulatory elements in trypanosomatid parasites, including Trypanosoma brucei, the causative agent of African sleeping sickness. However, their functional roles remain poorly understood, largely due to limited knowledge of their genomic distribution. Herein, we performed in silico analyses across 64 trypanosomatid species uncovering high degree of variability in G4 prevalence and species-specific patterns. We generated the first chromatin-based, genome-wide G4 map in T. brucei using G4 chromatin immunoprecipitation followed by sequencing (G4 ChIP-Seq), revealing enrichment within gene-associated regions, including coding DNA sequences (CDSs), and transcription boundaries such as transcription start sites (TSSs) and transcription termination sites (TTSs). This pattern diverges markedly from previous genome-wide G4 maps in humans, suggesting that G4s may play roles unique to trypanosome biology. To investigate their functional relevance, we profiled the transcriptome of T. brucei upon treatment with the G4-stabilizing ligand PhenDC3. PhenDC3 induced targeted transcriptional perturbation of genes bearing G4s, particularly those located within CDSs and TSSs. Altogether, our findings highlight a distinctive role for G4s in regulating gene expression in T. brucei and support their potential as therapeutic targets in the treatment of African sleeping sickness.

overall_design: Differential gene expression analysis was performed on RNA-sequencing data from T. brucei 427 bloodstream form parasites following 4-hour co-culture with 2× EC₅₀ concentrations of PhenDC3, CX-5461, or BMH-21, alongside an untreated control. Each condition was assessed in four biological replicates.

first: Ludovica

last: Monti

first: Genta

last: Firth

first: Joana

last: Correia Faria

first: John

last: Kelly

first: Gem

last: Flint

first: Silvia

last: Galli

first: Thomas

middle: E

last: Maher

first: Htay

last: Mon Aye


title: Genome-wide mapping of DNA G-quadruplexes in Trypanosoma brucei chromatin reveals enrichment in coding regions and transcription start sites [ChIP-seq]

overall_design: ChIP-seq was performed to map the genomic distribution of DNA G-quadruplex (G4) structures in Trypanosoma brucei 427 bloodstream form parasites. Seven samples are provided, including 5 G4-ChIP repeats, and 2 input DNA control.


title: Synovial Fluid and Serum MicroRNA Signatures in Equine Osteoarthritis

status: Public on Jun 23 2026

city: Wien

first: Andreas

middle: B

last: Diendorfer

address: Leberstraße 20

country: Austria

institute: TAmiRNA GmbH

type: Non-coding RNA profiling by high throughput sequencing

summary: The aim of this study was to identify differentially expressed microRNAs (miRNAs) in serum and synovial fluid (SF) samples of control horses and those with osteoarthritis (OA), to identify potential candidates for biomarkers of disease. Total RNA was extracted from serum and SF samples of control (n=4) and OA (n=9) horses, and sequenced. Differential expression analysis, pathway analysis and miRNA target prediction were performed. A group of six miRNAs (eca-miR-199a-3p, eca-miR-148a, eca-miR-99b, eca-miR-146a, eca-miR-423-5p and eca-miR-23b) were selected for validation in an independent cohort (serum, n=46; SF, n=88). The effect of clinical variables on miRNA expression was also assessed. Sequencing analyses found 43 and 23 differentially expressed miRNAs in serum and SF samples, respectively. Pathway analysis showed miRNA were involved in inflammatory disease/response and associated with OA pathways. miRNA expression in serum was strongly associated with the horses’ workload, while age had a pronounced influence on miRNA expression in SF. Distinct patterns of miRNA differential expression were observed in serum and SF samples from horses with OA compared to controls. miR-199a-3p and miR-148a warrant further investigation as potential biomarkers of equine OA. Further characterization of these molecular changes could provide novel insights into the mechanisms of early OA.

overall_design: small RNA seq of equine synovial fluid and serum from horses with osteoarthritis and control horses, to identify differentially expressed microRNAs.

first: Catarina

last: Castanheira

first: Sarah

last: Taylor

first: Eva

last: Skiöldebrand

first: Luis

last: Rubio-Martinez

first: Matthias

last: Hackl

first: Peter

last: Clegg

first: Mandy

middle: J

last: Peffers


title: Immune-dominated cellular heterogeneity and stromal plasticity in keloid infiltrating and hypercellular zones revealed by single-cell RNA sequencing

city: Beijing

first: Cao

last: Yuchen

address: Thirty-three Badachu Road, Shijingshan District, Beijing, P.R. China

institute: Chinese Academy of Medical Sciences and Peking Union Medical College

summary: Background Keloids are aggressive fibroproliferative disorders characterized by a sclerotic core and an actively invading margin, yet the cellular and molecular basis of this spatial heterogeneity remains poorly understood. The roles of immune-stromal crosstalk in driving peripheral invasion have not been systematically dissected. Methods Paired infiltrating and hypercellular zones were collected from anterior chest keloids of four patients. Single‑cell RNA sequencing was performed on 128,678 cells after rigorous quality control. Unbiased clustering, differential gene expression analysis, pseudotime trajectory reconstruction, and cell-cell interaction profiling were applied to compare the landscapes of cell composition, function, and differentiation/development trajectories between the two zones. Results The hypercellular zone was dominated by extracellular matrix‑producing myofibroblasts, whereas the infiltrating zone was enriched in mononuclear phagocytes and endothelial cells, exhibiting a loose collagen architecture permissive for cellular invasion. Infiltrating zone fibroblasts adopted an immunomodulatory, inflammatory cancer‑associated fibroblast‑like phenotype, while macrophages displayed a type I interferon signature and immunoglobulin‑mediated activation, indicating a chronic  inflammatory state with features reminiscent of certain autoimmune conditions. Langerhans cells followed a three‑stage developmental trajectory from a stress‑responsive to a terminal NF‑κB‑driven effector state, orchestrating neutrophil and Th17 cell recruitment via chemokine and cytokine networks, with significant enrichment of the IL‑17 signaling pathway. Endothelial cells at the margin underwent endothelial‑to‑mesenchymal transition, and Schwann cells exhibited phenotypic plasticity, mirroring aggressive tissue remodeling. Conclusions In the context of this spatially resolved analysis, this study redefines the keloid margin as an immunology‑dominated niche characterized by profound cellular and spatial heterogeneity that is associated with features that could drive peripheral invasion. These findings suggest a shift of the paradigm of keloid pathogenesis from a fibroblast‑centric model to an immune‑driven integrated landscape in this cohort and provide a theoretical foundation for keloid precision therapies and zone‑specific biomarkers for treatment response and disease monitoring.

overall_design: Paired infiltrating and hypercellular zones were collected from anterior chest keloids of four female patients (aged 18-60). Single-cell RNA sequencing was performed using the Singleron Matrix Single Cell Processing System. Transcriptional profiles of the two zones were compared to dissect the spatial cellular heterogeneity and immune microenvironment.

first: Yuchen

last: Cao

first: Li

last: Duan

first: Dongxian

last: Lin

first: Yue

last: Liu

first: Mingzi

last: Yang


title: Sp8 and Sp6 regulatory functions in the limb bud ectoderm

city: Santander

first: Marian

last: Ros

address: 22nd Albert Einstein St.

country: Spain

institute: IBBTEC-CSIC-SODERCAN

summary: Sp8 and Sp6 are two closely related Sp genes expressed in the limb ectoderm, where they regulate proximo-distal and dorso-ventral patterning. Genetic studies in mice have shown that they act in a dose-dependent manner, with Sp8 exerting a substantially stronger effect than Sp6. Here, we integrate ChIPmentation-seq and RNA-seq analyses to elucidate their genome-wide regulatory networks and mechanisms of action. Our results show that Sp8 has a dual mode of action either directly binding GC-rich motifs or indirectly binding AT-rich motifs through Dlx. In contrast, Sp6 primarily acts through AT-rich motifs, likely via interaction with cofactors such as Dlx5. Both factors regulate key components of the Wnt, FGF, and BMP signaling pathways, central to limb patterning, and display both cooperative and independent roles. We further show that Sp8 and Sp6 can form homo- and heterodimers, as well as interact with Dlx5, revealing a complex regulatory network. Our findings provide molecular insight into limb morphogenesis and have potential implications for understanding congenital limb malformations.

overall_design:
Genome-wide analysis of Sp8 and Sp6 gene regulatory networks in the mouse limb bud ectoderm at E10.5 by ChIP-seq of Sp8 flagged/flagged for Sp8 and WT for Sp6 respectively and RNA-seq of WT and KO embryos at E10.5 and WT and double KO embryos at E9.75
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The table below lists GEO accessions reused/reanalyzed for this study.
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first: Alejandro

last: Castilla-Ibeas

first: Sandra

last: Moreu

first: Rocio

last: Pérez-Gómez

first: Laura

last: Galán

first: Victor

last: Campa

first: Juan

last: López-Giménez

first: Álvaro

last: Rada-Iglesias

middle: A


title: Organoid modeling of lung branching morphogenesis and epithelial lineage specification [BLO scRNA-seq]

city: Guangzhou

first: Ruifang

last: Zhang

state: Guangdong

address: Haizhu District

institute: Guangzhou Laboratory

summary: In this study, multi-level branching lung organoids (BLOs) were generated from primary tip epithelial cells. Single-cell RNA sequencing demonstrated that BLOs comprise proximal airway and distal alveolar epithelial cell populations, faithfully modeling the developmental trajectory of distal lung epithelial lineages in vitro.

overall_design: We generated multi-level branching lung organoids (BLOs) from primary tip epithelial cells and analyzed their transcriptional profiles using single-cell RNA sequencing (scRNA-seq).


title: RNA-seq study using Karpas422 xenograft tumors after vehicle or PRC2 inhibitor C36 treatment

city: Shanghai

first: Wei

last: Qi

state: Shanghai

address: B514, L Building

department: School of Life Science and Technology

institute: ShanghaiTech University

summary: Polycomb Repressive Complex 2 (PRC2) is the conserved methyltransferase depositing mono-, di-, and tri- methylation (H3K27me1/me2/me3) on the lysine 27 of histone H3 and thereby represses gene transcription. EZH2 is the catalytic subunit of the histone methyltransferase Polycomb Repressive Complex 2 (PRC2), and EZH2 somatic gain-of-function (GoF) mutations are lymphoma-drivers. Therefore, EZH2/PRC2 is a critical target for cancer drug development. In the present study, we characterized a small molecule inhibitor of PRC2, C36, and demonstrated its novel allosteric inhibitory mechanism from biochemical and structural perspectives. C36 efficiently inhibits H3K27 trimethylation and specifically prevents the expression of PRC2 target genes in human tumor cell lines and xenograft tumor model. And through transcriptomic and proteomic studies critical pathways regulated by PRC2 inhibition were elucidated in B cell lymphoma.

overall_design: We established the Karpas422 xenograft model in mice, and obtained the expression profiles of Karpas422 xenograft tissues after treatment with vehicle or 40 mg/kg C36 for 28 days (twice a day).

first: Dongdong

first: Chenyang

last: Qin

first: Yang

last: An


title: CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation [CUT&Run]

status: Public on Jun 22 2026

first: Viviana

last: Risca

address: 1230 York Ave, Box 176

institute: The Rockefeller University

summary: Cellular senescence consists of regulated phenotypes associated with permanent exit from the cell cycle in response to stressors such as genomic instability. The consequences of senescence go beyond individual cells due to the senescence associated secretory phenotype (SASP), which can induce inflammation in neighboring cells. Some cancers respond to CDK4/6 inhibitors (CDK4/6i) with a senescence-like phenotype in the absence of extensive DNA damage. We asked how the SASP and the transcriptional regulatory profile triggered by CDK4/6i-driven arrest compares to the canonical NF-κB-regulated SASP triggered by DNA damage. We profiled the dynamics of transcriptional regulation in response to the CDK4/6i, palbociclib, and the DNA damaging agent, doxorubicin. We found upregulation of NF-κB driven-SASP genes was shared across both drugs, although delayed in CDK4/6i, coinciding with slower enhancer activation and epigenetic changes. ATM/ATR inhibition did not affect CDK4/6i-induced NF-κB nuclear localization, suggesting an alternative upstream activator. Inhibiting NF-κB suppressed the expression of SASP genes without reversing stable arrest, pointing to SASP manipulation as a potential therapeutic strategy and providing insights into controversies regarding cell cycle arrest-driven SASP.

overall_design: We profiled the dynamics of DNA damage-induced and DNA damage-independent senescence using a patient-derived liposarcoma cell line model (LS8817) known to be responsive to CDK4/6i. Using RNA-seq, ATAC-seq, and CUT&Tag, we compared the temporal evolution of CDK4/6i- and doxorubicin-induced senescence over a 28-day time course of the CDK4/6i, palbociclib (Palbo), and a 21-day time course of doxorubicin (Doxo); we used a slightly shorter period for Doxo as doxorubicin-induced geroconversion occurs at a more rapid pace. This duration of treatment is long enough for progression through geroconversion in vitro to occur. We mapped out shared and distinct transcriptional regulatory networks, including those involved in the regulation and output of the senescence-associated secretory phenotype (SASP), in response to CDK4/6i and doxorubicin over time.

first: Joanna

last: Yeung

first: Justin

last: Rendleman

first: Lauren

last: Anderson Westcott

first: Arnold

last: Ou

first: Matthew

last: Pressler

first: Nicole

last: Pagane

first: Irene

last: Duba

first: Ria

last: Hosuru

first: Bat-Ider

last: Tumenbayar


title: Comparative transcriptomics of maize B73 and ZmCCD8 mutant under nitrogen and water stress

city: Legnaro

first: Leonardo

last: Buzzicotti

state: Italy PD

address: Vle dell'Università, 16

institute: Università di Padova

summary: Strigolactones (SLs) modulate multiple aspects of plant development and stress physiology. This study investigated the role of SLs in maize adaptation to nutrient and water limitation by comparing the root transcriptomes of an SL-biosynthesis mutant (zmccd8) and the wild type (WT).

overall_design: Seedlings of the Zea mays L. inbred line B73 and the zmccd8::Ds insertional mutant (in the B73 genetic background) were grown in vermiculite for four weeks under controlled growth-chamber conditions. Plants were subjected to three growth regimes: (i) control (optimal nutrient and water supply), (ii) nitrogen deficiency, and (iii) water stress. For each genotype and treatment, three independent biological replicates were used, yielding a total of 18 samples. Roots were harvested and used for subsequent transcriptomic analyses.

first: Silvia

last: Quaggiotti


title: Vanin-1 deficiency enhances host tolerance to influenza infection by modulating cellular redox status

city: Seoul

first: Jun Young

last: Hong

address: 50, Yonsei-ro, Seodaemun-gu

department: Systems Biology

institute: Yonsei University

summary: Host survival during infection depends on the balance between pathogen resistance and tissue tolerance mechanisms. Although resistance pathways are well-characterized, the molecular determinants of host tolerance remain poorly understood. Here we demonstrate that vanin-1, an ectoenzyme known for its role in vitamin B5 metabolism, unexpectedly regulates host tolerance during influenza infection through modulation of cellular redox status. Mice lacking vanin-1 showed enhanced survival following lethal influenza infection without alterations in viral burden, immune responses, or tissue pathology. While vanin-1 deficiency impairs vitamin B5 metabolism, neither vitamin B5 supplementation nor deficiency affected survival during infection, indicating a vitamin B5- independent mechanism. RNA sequencing analysis revealed enhanced expression of antioxidant pathway genes in vanin-1-deficient mice, with Nrf2 serving as a key upstream regulator. Mechanistically, vanin-1-deficient mice maintained higher glutathione levels during infection and showed reduced lipid peroxidation, suggesting protection against oxidative stress-induced cell death. Importantly, pharmacological inhibition of glutathione synthesis abolished the survival advantage in vanin-1-deficient mice, while glutathione supplementation protected wild-type mice from lethal infection. Our findings reveal an unexpected role for vanin-1 in regulating host tolerance through antioxidant pathways and identify a potential therapeutic target for enhancing survival during severe viral infections.

overall_design: Three replicates of lung tissues of control or infected with influenza virus strain A/WSN/33 from wild type and Vanin-1 KO mice at day 8 post infection

first: Jin Soo

last: Joo

first: Ruslan

last: Medzhitov


title: Characterization of human M2-like (TGFbeta/IL10) vs M0 monocyte-derived macrophages

status: Public on Jun 21 2026

city: Redwood City

first: Douglas

middle: V.

last: Faget

state: CA

address: 200 Cardinal Way, Ste 300

institute: Pheast Therapeutics

summary: Peripheral human monocytes from different human donors were differentiated into M2-like (TGFbeta/IL10) or M0 and analyzed by RNAseq.

overall_design: Monocytes were thawed rapidly in a 37°C water bath, washed in pre-warmed macrophage media containing IMDM media (Fisher Scientific, cat. #31980097) 10% human serum (Gemini Bio, cat. #100-512), and 1% Pen-Strep (Gibco, cat. #15140-122). Alternatively, monocytes were differentiated into macrophages by supplementation with X-Vivo 15 media (Lonza, cat. #BE02-053Q), 50 ng/mL of human M-CSF (R&D Systems, cat. #216-MC-025/CF) and 1% Pen-Strep. Cells were pelleted for 5 minutes at 400×g and 4°C. Pellets were resuspended in macrophage media and cells were seeded on to non-TC treated 15 cm2 bacterial Petri dishes (Sigma, P5856). Cells were maintained in culture at 37°C with 5% CO2 for 7 days. Media was refreshed after 7 days in culture. For M0 macrophages, no additional components were added to the media. For M2-like macrophages, TGF- (R&D Biosystems, cat. #240-B/CF) and IL-10 (R&D Biosystems, cat. #1064-ILB) were added at a final concentration of 50 ng/mL to the macrophage media. Respective medias were refreshed every 48 hours for an additional week to polarize the macrophages. After macrophage differentiation, total RNA was isolated using Qiagen RNeasy® 96 Kit following the manufacturer's instructions. Isolated RNA sample quality was assessed by High Sensitivity RNA Tapestation (Agilent Technologies Inc., California, USA) and quantified by AccuBlue® Broad Range RNA Quantitation assay (Biotium, California, USA). Paramagnetic beads coupled with oligo d(T)25 are combined with total RNA to isolate poly(A)+ transcripts based on NEBNext® Poly(A) mRNA Magnetic Isolation Module manual (New England BioLabs Inc., Massachusetts, USA). Prior to first strand synthesis, samples are randomly primed (5´ d(N6) 3´ [N=A,C,G,T]) and fragmented based on manufacturer’s recommendations. The first strand is synthesized with the Protoscript II Reverse Transcriptase with a longer extension period, approximately 40 minutes at 42⁰C. All remaining steps for library construction were used according to the NEBNext® Ultra™ II Directional RNA Library Prep Kit for Illumina® (New England BioLabs Inc., Massachusetts, USA). Final libraries quantity was assessed by Qubit 2.0 (ThermoFisher, Massachusetts, USA) and quality was assessed by TapeStation D1000 ScreenTape (Agilent Technologies Inc., California, USA). Final library size was about 430bp with an insert size of about 300bp. Illumina® 8-nt dual-indices were used. Equimolar pooling of libraries was performed based on QC values and sequenced on an Illumina® NovaSeq Platform (Illumina, California, USA, RRID:SCR_016387) with a read length configuration of 150 PE for 40M PE reads per sample (20M in each direction). FastQC (version v0.12.1, RRID:SCR_014583) was employed to check the quality of raw reads. Trimmomatic (version v0.39, RRID:SCR_011848) was applied to cut adaptors and trim low-quality bases with default setting. STAR package (version 2.7.10b, RRID:SCR_004463) was used to align the reads via the human GRCh38.p14 (Release 113) genome reference. The package of Picard tools (version 3.0.0, RRID:SCR_006525) was applied to mark duplicates of mapping. StringTie (version 2.2.1, RRID:SCR_016323) was used to assemble the RNA-Seq alignments into potential transcripts. HTSeq (version 2.0.3) (RRID:SCR_005514) was used to count mapped reads for genomic features such as genes, exons, promoters, gene bodies, genomic bins, and chromosomal locations. DESeq2 (version 1.40.2) (RRID:SCR_015687) was employed to process the differential gene expression analysis with raw read counts of samples as input.

first: Jennifer Yinuo

last: Cao

first: Giovanni

last: Forcina


title: RNA Sequencing of S. aureus infected nmr-2(ok3324) and  wild type (WT) N2 C. elegans

city: Houston

first: Benson

last: Otarigho

state: Texas

address: 6767 Bertner Avenue

department: Department of Genetics

institute: The University of Texas MD Anderson Cancer Center

summary: While there is a significant understanding of how neurotransmitter signaling modulates the immune defense, there is still limited knowledge regarding the modulation of molecular immunity by glutamatergic signaling. This study investigates dysregulated genes and pathways in nmr-2(ok3324) mutants compared to WT animals after a 4-hour infection with S. aureus at 25°C

overall_design: RNA was extracted from synchronized L4 stage nmr-2(ok3324) and WT animals grown at 20 C using Qiagen extraction kits and following standard methods

first: Alejandro

last: Aballay


title: CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation

city: New York

first: Viviana

last: Risca

overall_design: We profiled the dynamics of DNA damage-induced and DNA damage-independent senescence using a patient-derived liposarcoma cell line model (LS8817) known to be responsive to CDK4/6i. Using RNA-seq, ATAC-seq and CUT&Tag, we compared the temporal evolution of CDK4/6i- and doxorubicin-induced senescence over a 28-day time course of the CDK4/6i, palbociclib (Palbo), and a 21-day time course of doxorubicin (Doxo); we used a slightly shorter period for Doxo as doxorubicin-induced geroconversion occurs at a more rapid pace. This duration of treatment is long enough for progression through geroconversion in vitro to occur. We mapped out shared and distinct transcriptional regulatory networks, including those involved in the regulation and output of the senescence-associated secretory phenotype (SASP), in response to CDK4/6i and doxorubicin over time.

first: Joanna

last: Yeung

first: Justin

last: Rendleman

first: Lauren

last: Anderson Westcott


title: CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation [CUT&Tag]

first: Arnold

last: Ou

first: Matthew

last: Pressler

first: Nicole

last: Pagane

first: Irene

last: Duba


title: Translational control by RPL22L1-specific ribosomes enhances DNA repair and chemoresistance

city: Hangzhou

first: Yu

last: Qian

state: Zhejiang

address: 866 Yuhangtang Rd

department: School of Medicine

institute: Zhejiang University

summary: Ribosome heterogeneity has emerged as a regulatory layer in gene expression, yet its biological roles in cancers remain poorly characterized. Here, we identify RPL22L1, a paralog of the ribosomal protein RPL22, as a key modulator of DNA damage response (DDR) in colorectal cancer cells. DNA damage induces RPL22L1 upregulation and ribosomal incorporation, forming RPL22L1-specific ribosomes. Ribosome profiling reveals that RPL22L1-containing ribosomes preferentially translate mRNAs with highly structured 5’ untranslated region (5’UTR). In particular, RPL22L1 enhances the translation of ATRX through a cap-independent mechanism. ATRX subsequently recruits DNA-PKcs to DNA damage sites, thereby enhancing the DNA repair capacity. RPL22L1 loss creates exploitable DDR vulnerabilities, sensitizing cancer cells to cisplatin and PARP inhibitors in vitro and in vivo. Collectively, these findings uncover a specialized ribosome-mediated translational program in DDR and highlight RPL22L1 as a potential therapeutic target in DDR-based cancer therapy.

overall_design: Ribo-seq was performed on RKO control, RPL22L1-knockdown, RPL22L1-overexpressing and RPL22L1-IP samples. RNA-seq was performed on RKO control and RPL22L1-knockdown cells.

first: Saisai

last: Wei

first: Wentao

last: Yu

first: Yilin

last: Shen

first: Ye

last: Wang

first: Tiezheng

last: Li

first: Jiaqi

first: Xiangwei

last: Gao

first: Xiujun

last: Cai


title: Vaccination elicits HIV broadly neutralizing antibodies in primates

city: La Jolla

first: Patrick

last: Madden

address: 9420 Athena Circle

department: Center for Vaccine Innovation

institute: La Jolla Institute for Immunology

summary: The high antigenic diversity of HIV has been a major obstacle to development of a broadly protective vaccine. Nevertheless, protective HIV broadly neutralizing antibodies (bnAbs) exist and have been proposed as templates for vaccine development1-6. Germline-targeting is a conceptually radical vaccine design approach to elicit bnAbs, aiming to prime rare bnAb-precursor B cells possessing pre-determined human genetic and structural features shared with template bnAbs, and then guide B cell affinity maturation to potent bnAb evolution with heterologous boosters7-11. Although the approach has shown promise in clinical12-17 and pre-clinical18-34 studies, it faces many immunological challenges and, to date, has not succeeded in generating bnAbs in humans or nontransgenic animals. Here, we report an adjuvanted protein germline-targeting vaccine tested in outbred nonhuman primates that successfully generated bnAb-class memory B cells and sera capable of neutralizing diverse HIV clinical isolates. bnAb clonal lineages were generated in ≥50% of animals, achieving up to 46% neutralization breadth compared to the reference bnAb. Vaccine-induced bnAbs exhibited precise structural mimicry of human bnAb interactions with HIV envelope (Env), matching the germline-targeting predictions. Furthermore, serum bnAb activity developed in 44% of animals; in the most striking instance serum bnAb titers reached levels expected to confer protection against diverse HIV isolates. These results demonstrate proof of principle that germline-targeting vaccines can reproducibly elicit prespecified classes of bnAbs to prespecified epitopes under endogenous conditions, supporting further optimization of this approach for HIV vaccine development.

overall_design: N332-GT5 epitope-specific B cells from PBMCs were isolated by fluorescence-activated cell sorting (FACS) and analyzed by scRNA-seq, including VDJ and GEX libraries, using the 10X Genomics platform. Samples were multiplexed using TotalSeq™-C hashtag antibodies (BioLegend).

first: Shane

last: Crotty

first: Jon

last: Steichen

first: William

last: Schief


title: Single-cell transcriptomic analysis reveals tumor-immune determinants of lymph node colonization and progression in thyroid cancer

status: Public on Jun 19 2026

first: Anthony

last: Nguyen

address: 8700 Beverly Blvd, Department of Radiation Oncology

institute: Cedars-Sinai Medical Center

summary: Lymph node (LN) metastases are a major driver of mortality across solid cancers, including thyroid carcinomas, which are known for high rates of nodal colonization. To elucidate the determinants of nodal spread, we isolated tumor-infiltrating leukocytes from primary thyroid tumors and matched metastatic LNs for single-cell RNA sequencing with validation by multiplex immunohistochemistry. Comparing the microenvironmental alterations between primary tumors and their LNs, we found that thyrocytes and tumor-associated macrophages downregulate the expression of multiple inflammatory cytokine receptors, including TNFRSF12A and CX3CR1, upon LN colonization. LNs were associated with the induction of regulatory T cells to suppress T cell-mediated cytotoxicity compared to matched primary tumors. Notably, tumor-infiltrating lymphocytes within LNs demonstrated increased expression of activation markers, including interleukin-7 receptor (IL7R). High LN expression of IL7R was significantly correlated with improved outcomes and can serve as a biomarker in this heterogeneous disease. Our findings on the dynamic equilibrium within LN metastases may offer conserved mechanisms for nodal colonization across solid tumors.

overall_design: Following CD45-positive selection, samples were diluted to 1000 cells/uL and processed according to the Single Cell 3’ v1 assay (10x Genomics) with a targeted 10,000 cell recovery. Gene expression libraries were prepared according to the Single Cell 3’ v1 protocol (10x Genomics) and were sequenced using paired-end 150bp reads on the Novaseq 6000 (Illumina) through the CSMC Applied Genomics, Computation & Translational Core. Demultiplexed fastq files for gene expression libraries were processed by Cellranger (v4.0.0, GRCh38-3.0.0) transcriptome reference).

middle: T

first: Stephen

last: Shiao

first: Allen

last: Ho


title: Integrated Transcriptomic and Functional Analysis Reveals Tissue-Specific Molecular Pathology in Adolescent Idiopathic Scoliosis

city: Gainesville

first: Darius

last: Ramkhalawan

address: 1200 Newell Drive

institute: University of Florida

summary:
Adolescent idiopathic scoliosis (AIS), the spontaneous development of a lateral spine curvature during puberty, is the most common pediatric spine disorder, affecting ~3% of children worldwide. As the underlying etiology remains unclear, AIS is treated purely symptomatically, initially by bracing and ultimately by highly invasive, costly surgeries.  Genome-wide association studies (GWAS) have identified numerous risk loci, but most are in non-coding regions, making it difficult to link them to a biological function. To address this, we performed a multi-tissue investigation to connect genetic risk to tissue-specific molecular pathology.
We conducted RNA sequencing on the primary tissues implicated in AIS—paravertebral muscle and spinal cartilage—from patients and unaffected controls. In paravertebral muscle, we identified differentially expressed genes (DEGs) enriched for pathways related to muscle structure, myogenesis, and metabolism. Key upregulated genes include the transcription factor EGR1 and structural components such as MYH1. In spinal cartilage, we found enrichment of genes related to TGF and FoxO signaling, as well as metabolic pathways. Notably, genes crucial for chondrocyte differentiation (e.g., SOX5 and SOX6) were significantly downregulated. We then examined genes at known GWAS loci and found that several risk-associated genes were differentially expressed in one or both tissues. To investigate the function of non-coding variants at these loci, we identified and validated several novel enhancer elements harboring AIS risk SNPs at the BCL2, ADGRG6, and BNC2 loci. We reveal distinct pathological signatures in muscle and cartilage and lay the foundation for connecting non-coding genetic risk to the dysregulation of key developmental and structural pathways.

overall_design: RNA-seq profiling of paraspinal muscle from AIS patients dissected from the concave and convex sides of the curve and paraspinal muscle from adult control patients.

first: Justin

last: Koesterich

first: Nadja

last: Makki


title: Rewiring Oncogenic Transcriptional Complexes with Domain-ALTeration Chimeras (DALTACs) in Prostate Cancer [ChIP-Seq]

status: Public on Jun 18 2026

city: Ann Arbor

first: Arul

last: Chinnaiyan

state: MI

address: 1500 East Medical Center Dr

department: MCTP

institute: University of Michigan

summary: Transcriptional addiction to the androgen receptor (AR) underlies metastatic castration-resistant prostate cancer (mCRPC), where AR maintains oncogenic enhancer programs through dynamic, domain-specific interactions with the lysine acetyltransferase p300 and associated cofactors. Here, we describe a mechanistically distinct therapeutic modality, Domain-ALTeration Chimeras (DALTACs), designed to rewire endogenous protein complexes by enforcing non-native domain–domain interactions rather than degrading or inhibiting individual components. Our first-in-class molecule, AR–p300 DALTAC-1, induces a synthetic proximity between the AR ligand-binding domain and the p300 bromodomain, thereby misconfiguring the native AR–p300 interface and locking the complex into a non-productive, transcriptionally inert state. DALTAC-1 triggers a profound “super-inhibitory” effect, suppressing AR-driven transcription and proliferation more potently than combined AR and p300 inhibition. Mechanistically, DALTAC-1 reprograms the substrate specificity of p300, extinguishing the enhancer-associated histone mark H2B N-terminal acetylation (H2BNTac) while inducing neomorphic acetylation of AR and SRC2/3, culminating in collapse of the AR neo-enhanceosome. Chromatin profiling revealed widespread redistribution of AR and p300 toward canonical palindromic AREs, coupled with attenuation of ERG/BRD4 recruitment and a near-complete loss of histone H2BNTac acetylation and RNA polymerase II loading at oncogenic AR/ERG neo-enhancers. Strikingly, DALTAC-1 exhibits exquisite lineage selectivity, displaying potent activity in AR-positive prostate cancer cells and patient-derived organoids while sparing AR-negative or non-prostate lineages. In multiple in vivo models, including castration-resistant and patient-derived xenograft tumors, DALTAC-1 induces deep and durable tumor regressions with favorable tolerability. Together, these findings establish DALTACs as a universally applicable strategy to rewire disease-defining protein complexes by altering their domain topology, expanding the conceptual and therapeutic landscape of induced proximity agents. The precision and lineage-selective action of DALTAC-1 highlight its strong translational potential for treating AR-driven prostate cancer

overall_design: VCaP cells were treated with 100nM DALTAC-1 or combination of p300 inhibitor and AR inhibitor for 1 or 3 hours. The AR, p300, FOXA1, ERG, BRD4, RNA-POL2, h2bk20ac, H3K27ac, CBP and PR ChIP-seq were conducted.

first: Jie

last: Luo

first: Sumit

last: Das

first: Eleanor

last: Young


title: Transcriptomic analysis of cancer-associated thrombosis in plasma EVs  from patients with advanced lung adenocarcinoma.

city: Pamplona

first: Josune

last: Orbe

address: Avenida Pio XII 55

institute: CIMA

summary: Venous thromboembolism (VTE) is a major contributor to morbidity and mortality in patients with advanced lung adenocarcinoma. Extracellular vesicles (EVs) are established mediators of the associated hypercoagulable state. We conducted a transcriptomic analysis of plasma EVs to identify molecular signatures specific to cancer-associated thrombosis (CAT) for refined risk stratification and therapeutic targeting. Methods: Plasma EVs from lung adenocarcinoma patients with (n=10) and without (n=11) VTE were analyzed by RNA-Sequencing. Differentially Expressed Genes (DEGs) were analyzed for pathway enrichment. Results: RNA-Seq identified 483 DEGs in VTE patients, with significant enrichment in pathways related to inflammation, neutrophil degranulation (NETs), and blood coagulation. Conclusion: Plasma EVs carry a potent, multi-cellular derived immuno-thrombotic mRNA signature that distinctly underlies CAT in lung adenocarcinoma.

overall_design: Extracellular vesicles isolated from plasma samples of patients with diagnosed locally advanced or metastatic lung adenocarcinoma. From this cohort, 10 patients who developed venous thrombosis during a 6-month follow-up period were selected, along with 11 patients matched for diagnosis, age, sex, and cancer stage who did not develop thrombosis during a 12-month follow-up period.

first: Ramon

last: Lecumberri


title: A genome-wide functional analysis of conserved intronic regions reveals essential roles for speckle-associated detained introns [CHyMErA]

city: Toronto

first: Ulrich

last: Braunschweig

state: Ontario

address: 160 College Street

department: Donnelly Centre

institute: University of Toronto

summary: Thousands of human introns harbour extended regions of high evolutionarily conservation that have not been previously characterized. A survey of these sequences reveals that they are associated with intron retention and enriched in genes that function in RNA processing, chromatin remodelling and neuronal biology. Using a dual CRISPR-Cas editing approach, we targeted 2,600 of these regions for deletion and observe that a subset of these perturbations affectaffects cell growth. Many of these ‘fitness’ sequences affect intron retention and or expression levels of their host genes. Deletions in nuclear speckle-associated retained introns in the FNBP4 and DDX5 genes are further linked to downstream effects on cell growth-related genes and intron retention, respectively. The DDX5 deletion additionally results in the accumulation of R-loops overlapping first introns in speckle-proximal genes. Overall, the results highlight multifactetedmultifaceted, critical roles of highly conserved intronic sequences in the control of gene regulation, R-loop resolution and cell growth.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design: Screens were performed in human HAP1 and RPE-1 cells by generating deletions in intronic regions using a dual-CRISPR system. Abundance of hybrid guide RNAs (hgRNAs) was assessed at infection and later time points to screen for changes in cell fitness. Screening was carried out either in untreated cells, cells treated with the CLK-1 inhibitor TG003 or DMSO as a control. Triplicate pools were split after infection for each treatment arm.

first: Shaghayegh

last: Farhangmehr

first: Mingkun

last: Wu

first: Syed

last: Nabeel-Shah

first: Kevin

last: Brown

first: Jason

last: Moffat

first: Benjamin

last: Blencowe


title: Stem Cells in Muscle Contractures of Children with Cerebral Palsy have Decreased Myogenic and Increased Fibrotic Transcripts

city: Davis

first: Madison

middle: W.

last: Stewart

address: 2121 Glacier Drive, Apt 56

institute: University of California, Davis

summary: Development of muscle contractures are common in Cerebral palsy (CP) and characterized by high muscle stiffness that limits function and mobility. The state of the cell types within muscle, particularly muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs), are largely unknown. The aim of this study was to leverage single cell RNA sequencing technology to determine how specific cell types are altered in contracture. CP MuSCs demonstrated significant upregulation of fibrotic genes (ACTA2) and down regulation of myogenic genes (MYF5) compared to typically developing MuSCs. The most dramatically up-regulated genes in FAPs in CP were also major fibrotic components (COL1A1). Interacting signals between FAPs, MuSCs, and immune cells, such as TNF signaling between macrophages and FAPs, were identified that support contracture progression. The study reveals specific genes and signals as therapeutic targets to reduce muscle contracture in children with CP.

overall_design:
Tissue from the gracilis muscle of three typically developing (TD) children and three children with cerebral palsy (CP) was dissociated and red blood cells were removed. Cells were then sequenced and analyzed using scRNA-seq.

***************************************************************
Raw files for human/patient samples are being made available in dbGaP (https://www.ncbi.nlm.nih.gov/gap/) for controlled access to the personally identifiable sequence data.
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first: Lin-Ya

last: Hu

first: Taryn

last: Loomis

first: Lizbeth

middle: M

last: De La Torre

first: Vedant

last: Kulkarni

first: Marie

last: Villalba

first: Jon

last: Davids

first: Yue

last: Wang

first: Lucas

last: Smith


title: Integrated transcriptome-metabolome analyses reveal regulatory networks underlying soluble solids accumulation in Capsicum chinense fruits

status: Public on Jun 17 2026

city: Viçosa

first: Wesley Elias

middle: Bhering

last: Barrios

email: wesley.barrios@ufv.br, wesb18@gmail.com

state: Minas Gerais

address: Ph. Rolfs, Av., UFV campus, Unidade de Crescimento de Plantas

department: Plant Biology

country: Brazil

institute: Universidade Federal de Viçosa

summary: The Capsicum genus shows remarkable phenotypic diversity, making it an excellent system to study non-climacteric fruit ripening. Unlike climacteric model species, such as tomato (Solanum lycopersicum), the regulatory networks linking transcriptome and metabolome to fruit quality traits remain poorly understood in non-climacteric crop species. To address this gap, we selected four contrasting C. chinense accessions and performed integrated transcriptomic and metabolomic analyses to investigate the regulation of total soluble solids (TSS) accumulation. We profiled 16,922 genes and 63 metabolic features across two fruit developmental stages (immature and mature), including sugars, organic acids, capsaicinoids, and other secondary metabolites. We identified more than 3,800 differentially expressed genes and detected strong correlations between gene expression and metabolite levels. Some metabolites, including chlorophylls, carotenoids, and starch, showed consistent temporal trends across genotypes, while others showed genotype-dependent variation. Our results demonstrate that pepper fruit ripening involves a transcriptional shift toward soluble sugar accumulation, characterized by upregulation of starch-hydrolyzing enzymes (CaAMY1/2, CaBAM1), invertases (CaINV1, CaCWINV3), sucrose synthase (CaSUS2), and the sugar transporter CaSWEET10, alongside downregulation of the starch biosynthetic gene CaSBE1. Among these, CaSUS2, CaSWEET10 and CaBAM1 emerged as key candidate regulators. These results suggest that coordinated starch degradation and sucrose transport primarily drive TSS increase, while secondary metabolism undergoes substantial changes during ripening but does not appear to be a major contributor to this process.

overall_design:
The experiment was conducted in a randomized block design, using five and three biological replicates per C. chinense accession for metabolite and RNA-seq analyses, respectively. Each biological replicate consisted of tissue from at least three homogeneous fruits harvested from the same plant.
Metabolite data were analyzed by two-way ANOVA (OLS) on log₂-transformed values, including genotype, stage (20 and 60 DAA), and their interaction. Estimated marginal means and Tukey’s HSD pairwise comparisons (statsmodels) were used, with significance at adjusted p < 0.05; group differences were summarized by compact letter display (CLD). For heatmap visualization, z-scores were calculated per metabolite from log₂ emmeans by centering on the grand mean and scaling by the standard deviation across groups, enabling comparisons across metabolites with different units (GC-MS peak areas and molar concentrations). All heatmap analyses were conducted in Python using NumPy, SciPy, Pandas, and statsmodels.
In the RNA-seq analysis, genes with FDR< 0.05 (Benjamini and Hochberg, 1995) and |log₂ fold change| ≥ 1 were considered differentially expressed. Metabolite–transcript Pearson correlation coefficients (PCC) were calculated in R version 4.3.0 (R Core Team, 2024), and correlograms were generated for 20 and 60 DAA, retaining only significant correlations (FDR ≤ 0.05). Genes were grouped by functional classification, and correlograms were plotted using ggplot2 from the gplots package (Wickham, 2011).

first: Acácio

last: Rodrigues-Salvador

first: Rebeca Patrícia

last: Omena-Garcia

first: Débora

middle: G

last: Gouveia

first: Caris dos Santos

last: Viana

first: Laise

last: Rosado-Souza

first: Pedro Marcus

middle: P

last: Vidigal

first: Diego

last: Riaño-Pachón

first: Federico

last: Scossa

first: Alisdair R.

last: Fernie

first: Wagner

middle: L

last: Araújo

first: Agustin

last: Zsögön

first: Adriano

last: Nunes-Nesi


title: Gene expression analysis of skin from Merkel cell sufficient and deficient B6 mouse models of Cutaneous Lupus Erythematosus

city: North Grafton

first: Jillian

last: Richmond

state: Massachusetts

address: 200 Westboro Road

department: Comparative Pathobiology

institute: Tufts Cummings School of Veterinary Medicine

summary: Cutaneous lupus erythematosus (CLE) is a chronic connective tissue disorder that primarily affects the skin. Many patients experience photosensitivity and itch. Recent work has demonstrated that Merkel cells in the skin are important for itch responses in alloknesis and sunburn-induced itch. We asked whether Merkel cells were important for skin inflammation in the context of CLE given the overlap of symptoms. To address this, we bred Merkel cell deficient mice to our adoptive T cell transfer CLE mouse model. Mice lacking half of their Merkel cells had increased skin disease scores compared to littermates and CLE controls regardless of TLR9 status. We deposit this microarray data examining gene expression in the skin of Merkel-deficient CLE mice versus other genetic controls.

overall_design: OT2 Th2 T cells were injected into CLE (rtTA+K5TGO+TLR9KO) recipients, littermate controls (rtTA- and/or K5TGO- TLR9KO) or CLE mice that had lost Merkel cells (Atoh1flox/wt K14Cre+ rtTA+K5TGO+TLR9KO). A portion of the skin was frozen and saved for RNA analysis at the first presentation of disease (approximately 3-4 weeks).  All extracted RNA samples were analyzed using NanoString mouse Immunology panel (C2269).