title: BAG2 Condensates Couple Proteostasis to CD8 + T Cell Surveillance

city: Santa Barbara

middle: Paul

last: Longhini

state: California

address: 6139 Biological Sciences II

department: Neuroscience Research Institute

institute: University of California, Santa Barbara

summary: Protein aggregation, impaired degradation, and immune activation are central hallmarks of many neurodegenerative diseases, yet how these processes are coordinated remain unclear. Here we identify a new class of phase-separated proteostasis organelles, termed immune degradation condensates (IDCs), composed of BAG2 assemblies. Inflammatory cues drive the formation of BAG2 IDCs, which are enriched in immunoproteasome components, major histocompatibility complex class I (MHC-I) peptide-loading machinery, and chaperones associated with the endoplasmic reticulum (ER). These assemblies redirect proteostatic cargo from centrosomal aggregation pathways to immune-specialized sites, coupling substrate clearance to antigenic peptide production and enhancing CD8⁺ T cell engagement. Using a cellular model of aggregation-prone Tau, we show that BAG2 IDCs capture pathological Tau fibrils at ER–microtubule interfaces and process them into antigenic peptides, thereby reducing the abundance of the aggregation-prone PHF6 motif. We term this system the Proteostasis-Associated Immune Relay (PAIR), establishing IDCs as critical hubs with potential implications for multiple disease states.

overall_design: RNA-seq profiling of polyA capture from H4 cells, H4 cells stably expressing mClover3-0N4R-P301L Tau and H4 Cells stably expressing mClover3-0N4R-P301L Tau and harboring tau aggregates seeded by jR2R3 P301L mini fibril.

first: Marie

middle: C

last: Almeida

first: Daniel

last: Carrettiero

first: Kenneth

middle: S

last: Kosik


title: Examination of DNA methylation in untransformed and transformed pancreatic progenitor organoids (POs) [EPIC Methyl Capture]

status: Public on Apr 24 2026

city: New York

first: Wilfred

last: Wong

state: NY

address: 430 E 67th St

country: USA

institute: Memorial Sloan Kettering Cancer Center

type: Methylation profiling by high throughput sequencing

summary: We established a human pluripotent stem cell (hPSC)-derived pancreatic progenitor organoid (PO) culture that provides the cellular plasticity for PDAC modeling and supports robust gene editing. Through the combinatorial expression of oncogenic KRAS and deletion of multiple tumor suppressor genes (TSGs)，we successfully recapitulated the transcriptional hallmarks of initial malignant transformation and progression of PDAC in POs in vitro. Moreover, these POs exhibited distinct histopathology from preneoplastic pancreatic intraepithelial neoplasia (PanIN) and moderately differentiated to poorly differentiated PDAC upon orthotopic transplantation. Further chromatin accessibility profiling unveiled 1) a progressive loss of pancreatic lineage program during disease development, accompanied by repression of TET1, 5hmc marking and hypermethylation of essential pancreatic lineage transcription factors and 2) an emergence of trans-lineage/malignant feature, associated with the opening of AP-1 motif enriched chromatin regions. Gene perturbation screening identified FOSL2, FOS, and JUNB as pro-malignancy AP-1 factors during malignant transformation of POs. Notably, inhibition of ERK, a regulator of AP-1, not only reversed AP-1 levels and malignant feature in transformed POs, but also derepressed TET1 and its associated chromatin regions. Thus, our de novo PDAC POs faithfully model the disease development and reveal distinct but concerted mechanisms that drive the cellular plasticity in PDAC. The comprehensive validation of this model against clinical datasets approves its potential for discovery of therapeutic targets and biomarkers for preventive screening in the future.

overall_design: Examination of duplicates of PO samples using EPIC Methyl Capture

first: Xian

last: Zhang

first: Heng

last: Pan

first: Christina

last: Leslie

first: Danwei

last: Huangfu


title: AP-1 factor binding and histone status in transformed KCP pancreatic progenitor organoids (PO) [CUT&RUN]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Examination of AP-1 factor binding and histone activation (H3K27Ac) in KCP POs by CUT&RUN


title: Differential Regulation of Retinoic Acid Metabolism in Fanconi Anemia

status: Public on Apr 08 2026

city: KINGSTON

first: NIALL

middle: GEORGE

last: HOWLETT

state: RI

address: 120 FLAGG ROAD

department: CELL AND MOLECULAR BIOLOGY

institute: UNIVERSITY OF RHODE ISLAND

type: Expression profiling by high throughput sequencing

summary: The goal of this study was to analyze differential gene expression patterns between nontransformed FA-D2 (FANCD2-/-) and FANCD2-complemented Fanconi anemia patient skin fibroblasts

overall_design: Quadruplicate biological replicates of nontransformed FA-D2 (FANCD2-/-) and FANCD2-complemented Fanconi anemia patient skin fibroblasts were harvested for RNA-seq analysis. Sequencing libraries were prepared using NEBNext Ultra II RNA library prep kit. Sequencing libraries were clustered on a single lane of a flowcell and loaded onto an Illumina HiSeq 4000 instrument. Samples were sequenced using a 2 x 150 bp paired-end configuration at 60 million reads per sample.

first: Niall G.

last: Howlett

first: Justin L.

last: Blaize


title: Effect of CSDE1 knockout in RAW264.7 cells on gene expression following SARS CoV-2 RNA stimulation

status: Public on Apr 07 2026

city: Jinan

first: zheng

last: yi

address: 07 Wenhua xi road, Jinan, Shandong

country: China

institute: Shandong  University

summary: RIG-I-like receptors (RLRs)-mediated antiviral innate immunity is critical for restricting RNA viral infection. The liquid-liquid phase separation (LLPS) is crucial for fine-tuning cellular signaling transduction, but whether RLR signaling is under the regulation of LLPS remains largely enigmatic. In this study, we identify the RNA-binding protein cold shock domain containing E1 (CSDE1) as a novel negative regulator of RLR signaling to promote viral immune evasion. The deficiency of CSDE1 in macrophages results in increased expression of type I interferon and ISGs following RNA viral infection. Mice with macrophage conditional knockout of CSDE1 are less susceptible to RNA viral infection. CSDE1, with multivalent CSD motifs, forms bio-molecular condensates with long single stranded RNA (ssRNA). The LLPS of CSDE1 sequesters viral RNA from recognition by RLRs to inhibit RLR signaling. Notably, virus-activated TBK1 kinase mediates the phosphorylation of CSDE1 to disturb its LLPS. Consequently, phosphorylation of CSDE1 relieves its suppression of RLR signaling. Intriguingly, LLPS of CSDE1 promotes the condensation of the SARS-CoV-2 nucleocapsid (N) protein and is critical for the anti-interferon activity of the N protein. Repression of CSDE1 condensation with screened compound abrogates the CSDE1 LLPS and subsequent replication of SARS-CoV-2. Overall, our study delineates a novel regulatory mechanism of RLR signaling transduction by phosphorylation-modulated LLPS of CSDE1, indicating that targeting the LLPS of CSDE1 is a promising strategy for RNA viral infection treatment.

overall_design: gene expression in RAW264.7 cells with or without CSDE1 following SARS CoV-2 viral RNA (S RNA) stimulation

first: Yi

last: Zheng

first: Xuejing

first: Chengjiang

last: Gao


title: Histone chaperones ASF1s control germination by repressing PRX69

city: Yangling

first: Su

middle: Ying

last: Pei

state: Shaanxi

address: No. 3 Taicheng Road

department: College of Life Sciences and Institute of Future Agriculture

institute: Northwest A&F University

summary: Seed germination is a critical developmental decision that integrates hormonal and epigenetic signals. While physiological dormancy has been extensively studied, the molecular basis of physical dormancy—mediated by structural barriers such as the seed coat (testa)—remains poorly understood. Here, we investigate the role of Arabidopsis ASF1 histone chaperones in germination, revealing their function in altering chromatin structure to regulate testa penetrability. The asf1a1b double mutant exhibits significantly reduced germination rates, independent of ABA or GA levels. Using RNA-seq, we identified PRX69, a peroxidase implicated in testa hardening regulation, as markedly overexpressed in asf1a1b seeds. Genetic suppression of PRX69 partially rescues the asf1a1b germination defect. Additionally, by ChIP assays, we show that ASF1 proteins directly bind PRX69. Finally, loss of ASF1s disrupts H3.3 incorporation, reduces total H3 occupancy, and increases chromatin accessibility at PRX69, which is associated with RNA polymerase II enrichment. These findings establish ASF1-mediated H3.3 dynamics as a critical epigenetic mechanism controlling physical dormancy by repressing PRX69-driven testa hardening. Our research provides new insights into the interplay between epigenetic regulation and physical dormancy in plants.

overall_design: RNA-Seq profiling was performed on freshly harvested seeds, harvested within 24 hours of wildtype Columbia-0 and asf1a1b mutants.

first: Israel

last: Ausin

first: Yafei

last: Wang

first: Fan

last: Yang

first: Yingpei

last: Su

first: Zhipeng

last: Gong

first: Qin

last: Hu


title: The GET Pathway Modulates Azole Susceptibility through Sterol Metabolic Remodeling and Protein Trafficking in Filamentous Fungi

status: Public on Apr 23 2026

city: Beijing

first: Shuting

last: Ye

address: No.1 Beichen West Road, Chaoyang District,

institute: Institute of Microbiology, Chinese Academy of Sciences

summary: Azole antifungals are widely used to control fungal infection, yet resistance mechanisms beyond drug efflux and target modification remain insufficiently understood. Here, we identified the Guided Entry of Tail-anchored proteins (GET) pathway as a conserved regulator of azole susceptibility in Neurospora crassa and Aspergillus fumigatus. Deletion or dysfunction of the core GET components Get-3 or Get-4 confers resistance to multiple azoles without impairing hyphal growth or sporulation. Mechanistically, GET deficiency neither reduced intracellular accumulation nor altered drug efflux and target expression or total ergosterol levels. Instead, GET-deficient strains displayed significantly reduced accumulation of the toxic sterol intermediate 14α-methyl-3,6-diol under azole stress, indicating a potential bypass of azole-induced sterol toxicity. Proximity labeling and functional validation indicated that GET deficiency perturbs the trafficking of multiple azole-resistance-associated proteins, including the key tail-anchored protein transporter Emp-47 and mitochondrial Cox subunits Cox-4 and Cox-15, which deletion enhanced azole resistance. Transcriptomic and functional analysis further revealed that GET disruption altered the expression of some azole resistance-associated genes, which involve in membrane transport, metabolism, and cell wall organization, independent of canonical stress pathways. In this study, a total of 17 new genes that modulate azole susceptibility were identified. Collectively, our findings uncover a non-classical mechanism of azole resistance mediated by GET-dependent protein trafficking and metabolic adaptation, conserved across filamentous fungi.

overall_design: To thoroughly investigate mechanism of get-3 and get-4, we sequenced the transcriptome of get-3 and get-4 mutants treated with or without Ketoconazole.


title: Pulmonary fibroblast activation during Aspergillus fumigatus infection enhances lung defense via immunomodulation and tissue remodeling [scRNA-seq]

city: Columbus

first: Jose

middle: P

last: Guirao-Abad

state: OH

address: 2255 Kenny Rd

department: Emergency Medicine

institute: Ohio State University

summary: Aspergillus fumigatus is the etiologic agent of invasive aspergillosis, a life-threatening fungal pneumonia that is initiated by the inhalation of conidia (spores) into the lung. If the conidia are not cleared, they secrete large quantities of hydrolytic enzymes and toxins as they grow, resulting in extensive damage to pulmonary tissue. Stromal fibroblasts are central responders to tissue damage in many organs, but their functional response to pulmonary injury caused by A. fumigatus has not been explored. In this study, we employed cell lineage tracing, targeted cell ablation, and single-cell RNA sequencing to monitor the dynamics of fibroblast behavior upon exposure to A. fumigatus in both immunocompetent and immunosuppressed hosts. The results demonstrate that a subset of pulmonary fibroblasts becomes activated in an immunocompetent host in response to a challenge with A. fumigatus conidia, acquiring a gene expression program reflecting the acquisition of new immunomodulatory properties as well as enhanced extracellular matrix (ECM)-secreting ability. Remarkably, through targeted ablation of fibroblasts that express the profibrotic activation marker periostin, we demonstrate that the progression of an invasive A. fumigatus infection in an immunosuppressed host is accelerated by the absence of periostin lineage cells and is accompanied by severe alveolar hemorrhage and angioinvasion. These findings uncover a novel protective role for fibroblasts in limiting the severity of A. fumigatus-induced pulmonary injury and emphasize the importance of the pulmonary stroma in host defense against this invasive fungal infection.

overall_design: Immunocompetent mice were exposed to either a single inoculum of conidia or a mock inoculation with saline. The stromal cell population was then isolated from total lung cells on days 1 and 7 post-inoculation by flow cytometry, excluding the non-stromal population based on expression of CD31, CD45 and EpCAM. The resulting stromal cell population was then subjected to a single-cell transcriptome analysis.

first: Shannon

last: Shearer

first: Jon

last: Bowden

first: Daniel

middle: A

last: Kasprovic

first: Christina

last: Grisham

first: Mustafa

last: Ozdemir

first: Elliot

last: Lowe

first: Michael

last: Tranter

first: Yunguan

first: David

last: Askew

first: Onur

last: Kanisicak


title: Behavioral flexibility and gut microbiome as potential predictors of oral oxycodone self-administration

status: Public on Apr 03 2026

city: Stratford

first: Elizabeth

last: West

state: NJ

address: 2 Medical Center Dr

department: Neuroscience

institute: Rowan University School of Osteopathic of Medicine

summary: Prescription opioids such as oxycodone have been widely used in the United States and have contributed to the ongoing opioid epidemic. While many individuals limit use to prescribed contexts, a subset transitions to misuse and, in some cases, to illicit opioid use. Identifying behavioral and biological factors that predict this vulnerability is critical for improving prevention and intervention strategies. Here, we investigated whether individual differences in behavioral flexibility and gut microbiome composition are associated with future oxycodone intake using a translationally relevant model of oral oxycodone self-administration in male and female Long-Evans rats. We established a model in which distinct intake phenotypes emerged, characterized by animals with high versus low oxycodone consumption. Behavioral flexibility, assessed using a contingency degradation task, was associated with oxycodone intake, identifying it as a potential behavioral biomarker of vulnerability. In parallel, oral oxycodone exposure altered gut microbiome composition, and microbiome features were associated with both behavioral flexibility and drug-taking behavior. These findings support a framework in which individual differences in opioid intake arise from the interaction of pre-existing behavioral traits and biological states, including gut microbiome composition which provides a foundation for identifying predictive biomarkers and developing individualized strategies to mitigate risk for opioid misuse.

overall_design: 16s rRNA sequencing of fecal samples from water exposed (control) and oxycodone exposed adult male and female Long-Evans rats at Pre (prior to self-administration) and Post (last days of self-administration, range: days 19 to 21) timepoints

first: Claire

middle: M

last: Corbett

first: Alexis

middle: E

last: O'Shall

first: Mark

last: Niedringhaus


title: Inherent Specificity and Variation Sensitivity as Quantitative Metrics for RBP Binding

city: Cleveland

first: Soon Yeul

last: Yi

address: CWRU Wood Research Building W127A, 2109 Adelbert Rd,

department: Biochemistry

institute: Case Western Reserve University

summary: Interactions between RNAs and RNA binding proteins (RBPs) regulate gene expression in eukaryotic cells. RNA-RBP affinity measurements in vitro reveal diverse binding preferences, yet approaches to directly compare motif specificities across RBPs are lacking. Here, we introduce two quantitative metrics: inherent specificity, which measures how selectively an RBP distinguishes its strongest binding motif from all possible motifs, and variation sensitivity, which assesses tolerance to single nucleotide variations within a preferred motif. Analyzing high-throughput sequencing datasets, we compared these metrics across 100 RBPs in vitro and 27 RBPs in cells, finding a strong correlation between in vitro and cellular measurements for RBPs that bind RNA independently of local structural context. Through RNA binding domain swap CLIP experiments between low-specificity RBM25 and high-specificity HNRNPC, we demonstrated that sequence specificity can be measurably transferred between protein contexts. Using these insights, we developed mathematical models to understand how inherent specificity and mutational sensitivity shape competitive RBP binding in ways not predicted by affinity alone. These models reveal that low-specificity RBPs can functionally enhance the specificity of high-specificity RBPs by occupying non-target sites. Overexpression of low-specificity RBM25 in cells recapitulates this effect, sharpening HNRNPC binding toward its preferred target motifs. Together, this work establishes inherent specificity and variation sensitivity as a quantitative basis for modeling how RBPs compete for RNA targets, complementing affinity-based descriptions of RNA-RBP interactions.

overall_design: To test whether a low-specificity RBP can focus the binding of a high-specificity RBP toward its preferred target sites in cells, we performed competition CLIP. HEK293 cells stably expressing V5-tagged wildtype or mutant RBM25 under doxycycline-inducible control were used. In these cells, both V5-RBM25 (via V5 IP) and endogenous HNRNPC (via anti-HNRNPC IP under V5-RBM25 overexpression) were profiled by CLIP-seq. To assess the contribution of endogenous HNRNPC tetramerization, V5-HNRNPC CLIP (wildtype and mutant) was performed with and without siRNA-mediated knockdown of endogenous HNRNPC. UV crosslinking and immunoprecipitation followed by high-throughput sequencing (CLIP-seq) was performed to compare binding profiles across all conditions.

first: Joseph

last: Luna

first: Soon

first: Sashi

last: Singh

first: Rohan

last: Krishna

first: Vidusha

last: Kothwela


title: Salmonella SopB suppresses post-transcriptionally regulated cytokine  release to reduce early tissue inflammation and delay disease progression

status: Public on Apr 06 2026

city: Aachen

first: Kaiyi

last: Zhang

address: Pauwelsstraße 30

department: Medicine Microbiology

country: Germany

institute: Uniklinik RWTH Aachen

summary: Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) manipulates cellular processes through the translocation of effector molecules into the host cell cytosol. Using a recently established neonatal S. Typhimurium infection model, we provide functional insights into how Salmonella outer protein B (SopB) suppresses early mucosal tissue inflammation and prolongs host survival. Mechanistically, SopB prevents a disintegrin and metalloprotease 17 (ADAM17) activation, plasma membrane translocation and the release of membrane-bound TNFa from enterocytes and reduces epithelial secretion of IL-18 via mTOR-controlled secretory autophagy. This abolishes the early epithelial transcriptional response and reduces immune cell recruitment and programmed cell death-mediated mucosal barrier disruption delaying disease progression. The immunosuppressive effect of SopB is independent of the C-terminally encoded phosphatidylinositol phosphatase and phosphotransferase activity but requires an intact N-terminal domain. Thus, SopB suppresses the early, post-transcriptional regulation of epithelial cytokine release in an inositol phosphatase-independent manner likely promoting pathogen transmission.

overall_design: Tnfr1 ko mice are infected on day 1 after birth with 100 CFU wild-type or SopB-deficient S. Tm. (both strains are provided by Prof. Michael Hensel at Osnabrück Univerisity, Germany). Enterocytes (IECs) were isolated from total small intestinal tissues using a previously established EDTA-based protocol at d1p.i. (Lotz et al., 2006). RNA was isolated from the epithelial cell pellet or homogenized intestinal tissue using TRIzol® according to manufacturer’s recommendations. The RNA samples were handed in to Genomics Core Facility at UKA.

first: Nour

last: Diab

first: Matthias

last: Schmitz

first: Mathias W.

last: Hornef


title: SAM68 is a crucial post-transcriptional regulator of cardiogenesis

status: Public on Apr 02 2026

city: Barcelona

first: Elias

last: Bechara

address: Dr Aiguader 88

country: Spain

institute: CRG

summary: RNA-binding proteins (RBPs) of the STAR family play important roles in mammalian development, yet their precise contributions to lineage specification remain incompletely understood. Here, using CRISPR–Cas9 knockout models combined with multi-omics approaches, we investigate the roles of two STAR proteins, SAM68 and QKI, in mouse embryonic stem cells (mESCs). Both RBPs contribute to mESC proliferation, self-renewal, and efficient differentiation into cardiomyocytes. Our data support a role for QKI in the regulation of cardiac differentiation programs. In addition, our analyses reveal a previously underappreciated contribution of SAM68 to cardiomyocyte specification, acting through multiple post-transcriptional mechanisms. Despite belonging to the same protein family, SAM68 and QKI regulate largely distinct post-transcriptional programs during differentiation. Specifically, SAM68 modulates alternative splicing and promotes the biogenesis of a subset of cardiac-enriched circular RNAs through binding to intronic regions flanking back-splice sites and association with NF90/110. In addition, SAM68 associates with untranslated regions of key differentiation-related transcripts, including Gata4 mRNA, a key transcription factor regulating cardiogenesis, and likely functions in complex with other RNA-binding proteins to regulate these transcripts. Together, these findings identify SAM68 as a regulator of multiple RNA processing pathways contributing to cardiomyocyte differentiation and provide insight into how STAR proteins shape post-transcriptional gene regulatory networks during early development.

overall_design: Sam68 iCLIP2 experiment using E14 cells at Day0, Day3 and Day10 of differentiation. The experiment was performed as 5 replicates per time point.

first: Laura

last: Broglia

first: Sarah

last: Wolf

first: Melina

last: Klostermann

first: Kathi

last: Zarnack

first: Gian Gaetano

last: Tartaglia


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [CosMx]

city: La Jolla

first: Peter

middle: D.

last: Adams

state: CA

address: 10901 North Torrey Pines Road

department: Cancer Genome and Epigenetics Program

institute: Sanford Burnham Prebys Medical Discovery Institute

summary: Age-associated functional decline is partly driven by progressive chromatin degeneration. Conversely, maintenance of chromatin integrity preserves cell identity and promotes healthy aging, albeit through different mechanisms in proliferating and non-proliferating cells. However, whether tissue regeneration with its associated cell proliferation can rescue defects in epigenetic maintenance in otherwise non-proliferative cells remains unclear. The histone chaperone HIRA deposits the histone variant H3.3 in a DNA replication–independent manner, leading to its accumulation in aging, non-proliferating cells. Here, we show that hepatocyte-specific loss of HIRA causes loss of cell identity, metabolic dysfunction, and accelerated fibrotic pathology with age. Transcriptomic and epigenomic analyses indicate that HIRA–H3.3 preserves chromatin integrity and sustains transcription of highly expressed genes. Partial hepatectomy, associated with induced proliferation, restores cell identity with compensatory deposition of canonical histones H3.1/2. Together, these results demonstrate that HIRA-mediated H3.3 deposition is essential for safeguarding cell identity and tissue function during aging of non-proliferating cells, but this function can be rescued by tissue regeneration with associated cell proliferation.

overall_design: CosMx Spatial Molecular Imager (SMI) was used to profile spatial gene expression in HIRA hepatocyte-specific knockout (KO) and control mouse livers. HIRA fl/fl C57BL/6 mice were injected with AAV8-TBG-Cre at 6 months of age to achieve hepatocyte-specific HIRA deletion (KO, n=3). Wildtype C57BL/6 mice injected with AAV8-TBG-Cre served as controls (n=3). Mice were aged for an additional 12 months post-injection and livers were collected at 18 months of age. Spatial transcriptomic profiling was performed on FFPE liver sections using the NanoString CosMx SMI platform (6 samples total; 3 biological replicates per group).

first: Rouven

last: Arnold

first: Christina

middle: H

last: Shi

middle: D


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [ATAC-seq]

overall_design: ATAC sequencing was used to study the chromatin accessibility changes of HIRA KO livers in mice. We used female wildtype mice injected with AAV8 Tbg-Cre (control)  and HIRA fl/fl C57BL/6 mice injected with AAV8 Tbg-Cre (KO mice). Mice were injected at 6 months and then aged for an additional 12 months. Chromatin accessibility analysis was performed using data obtained from bulk-ATAC seq of 4 samples (2 independent replicates per experimental group).

first: Xue

last: Lei

first: Rabi

last: Murad


title: Transcriptome analysis of breast tumour tissue and adjacent normal

status: Public on Apr 21 2026

city: London

first: Eleni

last: Maniati

address: John Vane Science Centre, Charterhouse Square

department: Barts Cancer Institute

country: United Kingdom

institute: Queen Mary University of London

summary: Patients with cancer that respond to immunotherapy benefit from prolonged and possibly indefinite progression free survival. Response rates vary across cancer types, with solid carcinomas generally being the poorest responders at between 10-20 %. Understanding the differences between responders (the 10- 20%) and non-responders (the 80-90%) could identify ways to improve response rates. In this project we investigate transcriptome changes in breast cancer tissue which may help understanding the differences in treatment responses.

overall_design: Tumour (n = 34)  and non-tumour (n = 6)  tissues (≥2cm away from the tumour) were collected from patients with localised or locally advanced TNBC (T1-3, N0-2, M0) eligible for mastectomy +/- neoadjuvant treatment and analysed by RNASeq.

first: Eleanor

middle: J

last: Tyler

first: Oliver

last: Pearce


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during liver aging

type: Methylation profiling by genome tiling array

summary: Age-associated functional decline is partly driven by progressive chromatin degeneration. Maintenance of chromatin integrity preserves cell identity and promotes healthy aging, but through different mechanisms in proliferating and non-proliferating cells. However, specific mechanisms of chromatin maintenance and their compensatory capacity in proliferating and non-proliferating cells are undefined. The histone chaperone HIRA deposits the histone variant H3.3 in a DNA replication-independent manner, leading to its accumulation in aging, non-proliferating cells. Here, we show that hepatocyte-specific loss of HIRA causes loss of cell identity, metabolic dysfunction, and accelerated fibrotic pathology with age. Transcriptomic and epigenomic analyses indicate that HIRA-H3.3 preserves chromatin integrity and sustains transcription of highly expressed genes, including cell identity genes. Partial hepatectomy, associated with induced proliferation, restores identity of HIRA knockout livers with compensatory deposition of canonical histones H3.1/2. Together, these results demonstrate that HIRA-mediated H3.3 deposition is essential for safeguarding cell identity and tissue function during aging of non-proliferating cells, but this function can be rescued by tissue regeneration and associated cell proliferation.

overall_design: DNA methylation profiling was used to study the epigenetic changes of HIRA KO livers in mice. We used female wildtype C57BL/6 mice injected with AAV8-Tbg-Cre (control) and female HIRAfl/fl C57BL/6 mice injected with AAV8-Tbg-Cre (KO). Mice were injected at 6 months and then aged for an additional 12 months. DNA methylation analysis was performed using the Illumina Infinium Mouse Methylation BeadChip on 8 samples (4 independent replicates per experimental group).


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [RNA-Seq]

overall_design: RNA sequencing was used to assess the effect of liver regeneration on the transcriptomic defects caused by HIRA loss in the livers of mice. HIRA was deleted using two independent approaches: Cre-mediated deletion in HIRAfl/fl C57BL/6 mice injected with AAV8-Tbg-Cre (with wildtype C57BL/6 mice injected with AAV8-Tbg-Cre as controls), and CRISPR-mediated deletion in wildtype C57BL/6 mice injected with AAV8-Tbg-saCas9-sgRNA-HIRA (with wildtype C57BL/6 mice injected with AAV8-Tbg-saCas9-sgRNA-Rosa26 as controls). Male mice were injected at 6 months of age, and partial hepatectomy was performed 4 weeks post-injection to induce liver regeneration. In a paired design, the resected liver tissue served as the pre-regeneration sample and the remaining liver was collected 5 days post-resection as the post-regeneration sample, such that each mouse served as its own control. Gene expression analysis was performed using data obtained from bulk RNA-seq of 16 samples (4 groups: control before regeneration, control after regeneration, HIRA KO before regeneration, HIRA KO after regeneration; 4 independent replicates per group, 2 from each deletion approach).


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [RNA-Seq HIRAKO_1Y]

overall_design: RNA sequencing was used to study the transcriptomic changes of HIRA KO livers in mice. We used male and female wildtype mice injected with AAV8 Tbg-Cre (control 1), HIRA fl/fl C57BL/6 mice injected with AAV8 Tbg-MCS (control 2) and HIRA fl/fl C57BL/6 mice injected with AAV8 Tbg-Cre (KO mice). Mice were injected at 6 months and then aged for an additional 12 months. Gene expression analysis was performed using data obtained from bulk-RNA seq of 18 samples (3 independent replicates per experimental group).


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [RNA-Seq 2]

overall_design: RNA sequencing was used to study the transcriptomic changes of HIRA KO livers across a timecourse in mice. We used female wildtype C57BL/6 mice injected with AAV8-Tbg-saCas9-sgRNA-Rosa26 (control) and female wildtype C57BL/6 mice injected with AAV8-Tbg-saCas9-sgRNA-HIRA (KO). Mice were injected at 6 months of age and livers were harvested at 3 weeks and 6 months post-injection. Gene expression analysis was performed using data obtained from bulk RNA-seq of 20 samples (5 independent replicates per experimental group).


title: Pulmonary fibroblast activation during Aspergillus fumigatus infection enhances lung defense via immunomodulation and tissue remodeling [RNA-Seq]

first: Jose

last: Guirao-Abad

overall_design: Immunocompetent PostnLin mice were administered a single inoculum of A. fumigatus conidia to induce fibroblast activation and Pdgfrα-GFP mice were given a mock inoculation with saline. The induced PostnLin cells and the resident Pdgfrα-GFP fibroblasts were then isolated on day 7 post-inoculation by sorting tdTomato+ or GFP+ cells. Total RNA was extracted from the two populations and bulk RNA-Seq was performed to compare the transcriptional profile of A. fumigatus-induced PostnLin cells to that of Pdgfrα+ resident fibroblasts.

first: Shannon

last: Shearer

first: Jon

last: Bowden

first: Daniel

last: Kasprovic

last: Grisham

first: Mustafa

last: Ozdemir

first: Elliot

last: Lowe

first: Michael

last: Tranter

first: Yunguan

last: Wang

first: David

last: Askew

first: Onur

last: Kanisicak


title: A hPSC-Derived Progressive Pancreatic Ductal Adenocarcinoma Model Reveals Dual Pathways in ERK-Driven Cellular Plasticity

status: Public on Apr 20 2026

first: Wilfred

last: Wong

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

overall_design: Refer to individual Series


title: Alveolar Macrophages Undergo a Postnatal Transition from a Hyperphagocytic and Proinflammatory Profile to a Tolerogenic Profile

status: Public on Apr 19 2026

city: He Fei

first: Yu

last: Hang

address: 宿松路

institute: 合肥综合性国家科学中心大健康研究院

summary: Alveolar Macrophages (AMs) are crucial for lung immunity and homeostasis. While the ontogeny of AMs is well characterized, their postnatal phenotypic and functional maturation remains unclear. Here, we developed a bronchoalveolar lavage (BAL) protocol across key developmental stages and systematically analyzed age-dependent changes in AMs. AM numbers increased with age, acquiring a mature phenotype alongside alveolar maturation.BAL-recovered AMs decreased in size and increased in roundness from day 3 onward and revealed distinct gene expression profiles across different ages. Functionally, phagocytic capacity peaked in 3-day-old mice. Furthermore, AMs from all ages beyond day 1 showed lower basal inflammatory cytokine expression and an attenuated response to LPS, indicating a postnatal transition toward a tolerant phenotype. The transition from a hyper-phagocytic, pro_x0002_inflammatory neonatal profile to a tolerogenic adult phenotype underscores the intrinsic adaptation of AMs to the immunotolerant microenvironment of the mature lung. Our study provides a comprehensive kinetic profile of postnatal AM development.

overall_design: Bronchoalveolar lavage fluid (BALF) was collected from mice at postnatal days 1, 3, 7, 21, and 49 (D1, D3, D7, D21, D49). AMs were pooled from 3-6 mice per time point. 1.5×10⁴ AMs were resuspended in 50 μL of DMEM medium supplemented with 10% fetal bovine serum and seeded into a 384-well untreated plate.The cells were then stimulated with lipopolysaccharide (LPS) at a concentration of 400 ng/mL (purchased from InvivoGen, catalog number tlrl-b5lps) or treated with LPS-free medium (served as control). After 4 hours of incubation, AMs from  were collected for subsequent RNA sequencing (RNA-seq) analysis.

first: Hang

last: Yu

first: Shengwen

last: Shang

first: Qing

last: Xu

first: Jiabing

last: Tong

first: Jian

first: Fengqi

last: Li


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [CUT&Tag]

first: Peter

last: Adams

overall_design: CutnTag was used to study the epigenetic changes of HIRA KO livers in mice. We used female wildtype mice injected with AAV8 Tbg-Cre (control 1),  and HIRA fl/fl C57BL/6 mice injected with AAV8 Tbg-Cre (KO mice). Mice were injected at 6 months and then aged for an additional 12 months. Histone modification distribution analysis was performed for H3.3, H3K27ac, and H3K36me3 using data obtained from of 6 samples (3 independent replicates per experimental group).

first: Rouven

last: Arnold

first: Xue

last: Lei


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging [RNA-Seq H33KO_3wks]

overall_design: RNA sequencing was used to study the transcriptomic changes of H3.3 KO livers in mice. We used male wildtype mice injected with AAV8 Tbg-Cre (control 1), H3f3afl/fl_H3f3bfl/fl C57BL/6 mice injected with AAV8 Tbg-MCS (control 2) and H3f3afl/fl_H3f3bfl/fl C57BL/6 mice injected with AAV8 Tbg-Cre (KO mice). Mice were injected at 6 months and then aged for an additional 3 weeks. Gene expression analysis was performed using data obtained from bulk-RNA seq of 10 samples (n = 3 for both of the controls, n = 4 for the KO).


title: HIRA-mediated H3.3 deposition preserves hepatocyte cell identity during non-proliferative liver aging

overall_design: CutnTag for H3.3 was performed to validate antibody specificity. We used a H3f3afl/fl; H3f3bfl/fl C57BL/6 mouse injected with AAV8-Tbg-Cre (H3.3 double KO) and a wildtype C57BL/6 control injected with AAV8-Tbg-Cre. Mice were injected when they were 6 months old and aged for an additional 3 weeks before tissue collection. Gene regulatory analysis was performed using data obtained from CutnTag of 2 samples (n = 1).


title: Regulation of Cyclic Lipopeptide Orfamide A Biosynthesis in Pseudomonas protegens by the Gac-Rsm-LuxR Cascade

status: Public on Apr 01 2026

city: Suzhou

first: Chenjie

state: Jiangsu

address: Xiyuan road 279

institute: Suzhou Polytechnic Institute of Agriculture

summary: Orfamide A, a lipopeptide produced by Pseudomonas protegens Pf-5, is a key determinant of its biocontrol properties. In this study, we investigated the regulatory interactions among the GacS/A two-component system, small RNAs (sRNAs), repressor proteins, and two LuxR-type transcription factors in orfamide A biosynthesis. We found that GacS/A indirectly regulates orfamide A production by enhancing transcription of three sRNAs (RsmX, RsmY and RsmZ). RsmY and RsmZ synergistically relieve repression by RsmA and RsmE, while RsmX plays a lesser role, likely counteracting only one repressor. LuxR-type transcription factors LuxR1 and LuxR2, which positively regulate orfamide A synthesis, are directly repressed by RsmA and RsmE via binding to their 5′ untranslated regions, linking them to the Gac-Rsm signaling cascade. We further demonstrate that LuxR2 activates luxR1 expression, which in turn facilitates orfamide A production by binding to the promoter of the orfamide A biosynthetic gene cluster. Importantly, we show that this entire regulatory cascade operates in the rhizosphere and directly influences biocontrol efficacy. These findings provide a comprehensive understanding of the Gac-Rsm-LuxR pathway in orfamide A biosynthesis and offer valuable insights for the development of biocontrol agents based on Pseudomonas strains.

overall_design: RNA-seq profiling of wild-type Pf-5 and  ΔgacA mutant at 12 h of culture time.


title: Time-course transcriptome data of Actinoplanes sp. SE50/110 during the whole process of acarbose fermentation

city: Shanghai

first: Feifei

last: Cai

address: 800 Dongchuan RD. Minhang District, Shanghai, China

institute: Shanghai Jiao Tong University

summary: Metabolic engineering for high-value compounds like acarbose, a type 2 diabetes drug, requires systematic understanding of metabolic regulation. Here, we integrated multi-dimensional systems biology approach in Actinoplanes sp. SE50/110, a non-model bacterium producing acarbose. First, we reconstructed a substantially enhanced genome-scale metabolic model (iASE1267), which features an expanded set of genes, metabolites, and reactions, providing improved metabolic coverage. The model demonstrated high quality  with a MEMOTE  (metabolic model test suite) evaluation score of 80%, and showed significantly better phenotype simulation under various conditions. By using dual-objective OptRAM in-silico strain design approach on iASE1267 model, we identified two sets of static engineering strategies, overexpression of the 1-epi-valienol-1,7-diphosphate 1-adenylyltransferase AcbR and repression of an adenylosuccinate lyase; overexpression of a dTDP-glucose 4,6-dehydratase and repression of a 4-(cytidine 5'-diphospho)-2-methyl-D-erythritol kinase. Further, the dynamic flux pattern of time-course metabolic models revealed key time-dependent metabolic valves, L-aspartate oxidase (ASPO1), pyruvate carboxylase (PC), and pyruvate kinase (PYK). Additionally, we uncovered a core transcription-metabolism network by utilizing static modification sites as boundary markers, and identified two global negative transcriptional factors (TFs) within this network. Both the two TFs and the four metabolic genes have been experimentally validated with enhanced acarbose titer by 18–23%. This study establishes a framework linking static/dynamic modeling with transcriptional networks to decode metabolic-regulatory mechanisms in non-model bacteria, offering generalizable strategies for optimizing valuable microbial products.

overall_design: Transcriptome data encompassed 11 sampling points (8, 16, 20, 24, 32, 40, 48, 52, 56, 64,72 hr) over the whole 72-h fermentation period from Actinoplanes sp. SE50/110 ΔtreY cultured in fermentation medium.

first: Linquan

last: Bai

first: Zhuo


title: Expanding the droplet-based microfluidic single-cell toolbox with a cost-effective full-length total RNA sequencing technology

city: Jerusalem

last: Sun

address: Hebrew University, Givat Ram campus

department: Biochemistry department

country: Israel

institute: The Hebrew University of Jerusalem

summary: We developed sc-rDSeq, a high-throughput single-cell full-length total RNA sequencing technology and validated its performance using human cancer cell line, showed benchmarking against traditional scRNAseq method inDrops. sc-rDSeq was further applied in a drug resistance study on NSCLC lines treated with EGFR inhibitors Gefitinib and Osimertinib.

overall_design: We have developed a high-throughput single-cell full-length total RNA sequencing technology, sc-rDSeq. First, we validated its performance with the non-small cell lung cancer (NSCLC) cell line PC9. Both sc-rDSeq and inDrops were applied to PC9 cells for comparison purpose. We then conducted a drug resistance study using PC9 and another NSCLC cell line, HCC827. These cells were treated with 1 μM of two different EGFR inhibitors, Gefitinib and Osimertinib, for 9 days, with the medium containing fresh drugs replaced every three days. Cells that remained adherent were profiled using sc-rDSeq. Control cells treated with an equivalent concentration of DMSO were also analyzed. Raw data were aligned in multiple rounds to exclusively map to total RNA. Reads were first mapped to the whole genome, then counted with different GTF files in each round. Only reads that failed to align proceeded to the next round. The alignment order was short RNA, long RNA exons, long RNA introns, and pseudogenes. Single cell matrix obtained from each round were combined in downstream analysis.

first: Oren

last: Ram


title: DYRK1A enhances antitumor immunity in type 1 conventional dendritic cells via mTORC1 activation

city: Xiamen

first: Hongjiao

last: Wang

address: xiangannanlu

institute: xiamen university

summary: Type 1 conventional dendritic cells (cDC1s) play an integral role in mediating immune responses and maintaining homeostasis, yet the molecular mechanisms underlying their functions remain poorly understood. In this study, we identify dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) as a key kinase that responds to TLR and growth factor stimulation, acting as an essential regulator of cDC1 function. Genetic ablation of Dyrk1a specifically in cDC1s impairs antitumor immunity and accelerates tumor progression in murine models. Mechanistically, DYRK1A mediates the phosphorylation of the mTORC1 inhibitor TSC2 at serine 540, triggering the degradation of TSC2 and promoting the mTORC1 signaling in cDC1s. Notably, Tsc2 deletion in Dyrk1a-deficient cDC1s remarkably restores their antitumor immune functions. Furthermore, DYRK1A-mediated mTORC1 signaling in cDC1s positively correlates with effector T-cell responses across multiple human cancers. Our findings highlight a critical role for the DYRK1A-TSC2-mTORC1 signaling pathway in regulating cDC1 functions in antitumor immunity, offering potential strategies to improve cancer immunotherapy.

overall_design: For tumor-infiltrating DC sequencing, the DCs (CD3-CD19-NK1.1-Ly6C-Ly6G-F4/80-Siglec-CD11c+MHCII+) were purified from tumor tissues of B16-F10 tumor-bearing Dyrk1a+/+-Cd11c-cre mice and Dyrk1a fl/fl-Cd11c-cre mice (day 13 after tumor cell inoculation).


title: Differential gene expression drives cell-cycle-dependent transition from monopolar to bipolar growth in fission yeast

status: Public on Mar 31 2026

city: Chestnut Hill

first: Maitreyi

last: Das

state: MA

address: 140 Commonwealth Ave

department: Biology

institute: Boston College

summary: In S. pombe, cells transition from monopolar to bipolar growth in a cell cycle-dependent manner. To investigate this, we performed RNA-seq analysis of the cell-cycle mutant cdc10-129 to identify distinct gene expression patterns in G1 versus G2 phase. Our analysis identified upregulation of the pheromone- and stress-response pathways in G1/S-arrested cells and cell wall organization genes in G2 cells. Protein interaction networks identified a spk1-byr2-ste11 stress-response hub in G1/S. in agreement we find that cells spk1 are precociously bipolar. We propose that pheromone-response pathways block bipolarity until nutrient-rich conditions downregulate these pathways, enabling cell cycle progression and bipolar transition.

overall_design: RNA seq profiling of wild-type (WT) and cdc10-129 mutant at 25°C, 36°C for 4 hours, and 150 minutes after release to 25°C. The experiment was perfromed in triplicate.

first: Samridhi

last: Pathak


title: Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis [RNA-Seq]

city: New York

first: Rohit

last: Chandwani

address: 413 East 69th St, BRB 1360G

department: Surgery

institute: Weill Cornell Medicine

summary: Inflammation in the context of pancreatic injury drives acinar-to-ductal metaplasia (ADM), a cell state that can be hijacked by mutant Kras to drive the formation of pancreatic cancer. ADM has been described alternatively to bear progenitor features, but the extent to which lineage reversion is a broad feature of the response to injury and early tumorigenesis – particularlyacross the different mutant Kras alleles – remains poorly understood. Herein we implement novel Ptf1a-tdTomato mice to characterize early and late pancreatic progenitors to serve as benchmarks that define cell fate decisions in the context of inflammatory injury and initiation. In so doing, we define ADM as a mixed-lineage transcriptomic and epigenetic state, harboring ductal features but also featuring a lineage reversion to a late progenitor program. By contrast, while inducible mutant Kras alone is able to induce oncogenic gene expression, it does little to alter chromatin in the absence of injury. The most frequent Kras mutant alleles – G12D, G12V, and G12R – display differential cooptation of the injury-induced mixed-lineage state, with mutant KrasG12D able to form ADM and PanIN more robustly than either KrasG12V or KrasG12R. In particular, KrasG12R fails to promote phenotypic transformation on its own or even in concert with inflammatory injury. Whereas KrasG12Dand injury induce enhancer reprogramming at AP-1 chromatin and a lineage reversion to resemble early progenitors, KrasG12Rcan initiate but not sustain the key cell-intrinsic transcriptional and epigenetic programs characteristic of neoplasia. In KrasG12R we identify a decrease in Rac1 signaling, not AKT activation, as the key molecular defect. Together, these data demonstrate that the PDAC-associated Kras variants are not functionally equivalent and distinctly drive lineage reversion and epigenetic reprogramming, such that allele-specific approaches will be essential to therapeutic targeting in pancreatic cancer.

overall_design: Characterization of bulk RNA via RNA-seq of cells from the developing and mature pancreas (including early & late progenitor, adult ductal, adult lineage-traced acinar and acinar-derived cells) exposed to caerulein (or saline as control) and/or mutant Kras (G12D, G12V, G12R).

first: David

last: Falvo

first: Adrien

last: Grimont

first: Paul

last: Zumbo


title: The Chromatin Remodeler, Mit1, Enables the Propagation of the Histone Modification, H3K9me [RNA-seq]

city: Waltham

first: Kaushik

last: Ragunathan

address: 415 South St

institute: Brandeis University

summary: Chromatin structure dynamically regulates the balance between DNA accessibility and compaction, which is essential for controlling gene expression in eukaryotic cells. ATP-dependent chromatin remodelers are key effectors in this process, modulating nucleosome positioning to establish either open or repressive chromatin states. The CHD family of remodelers exhibits diverse roles in transcriptional regulation, yet the mechanisms by which they contribute to transcriptional silencing remain incompletely understood. In Schizosaccharomyces pombe, the CHD remodeler Mit1 functions within the SHREC complex to enforce heterochromatin formation, but its precise mode of action is unclear. Here, we directly tether Mit1 to an ectopic chromatin locus and demonstrate that Mit1 recruitment induces transcriptional gene silencing and nucleates broad domains of H3K9 methylation in a manner dependent on the Clr4 methyltransferase. This silencing requires Mit1’s remodeling activity but does not involve direct physical interaction with Clr4, indicating that Mit1 remodels chromatin to create a substrate favorable for Clr4 function. Furthermore, we find that enables the formation of de novo heterochromatin domains genome-wide. Our findings uncover a novel feedback mechanism whereby CHD-family remodelers initiate stable heterochromatin formation through chromatin remodeling that promotes methylation-based silencing, revealing new insights into the interplay between nucleosome dynamics and epigenetic gene regulation.

overall_design: RNA-seq of tetrmit1, tetrmit1k587a, and tetrmit1_clr4oe (in triplicate)

first: Melissa

last: Seman

first: Alexandria

last: Latuda

first: Fenting

last: Huang

first: Agnisrota

last: Mazumder

first: Luca

last: Wolfstadter

first: Sigurd

last: Braun


title: Molecular dynamics driving phenotypic divergence among KRAS mutants in pancreatic tumorigenesis [ATAC-Seq]

overall_design: Characterization of bulk chromatin accessibility via ATAC-seq of cells from the developing and mature pancreas (including early & late progenitor, adult ductal, adult lineage-traced acinar and acinar-derived cells) exposed to caerulein (or saline as control) and/or mutant Kras (G12D, G12V, G12R).


title: RNA-seq profiling of P2 rat neonatal atrial myocytes transfected with non-targetting (control) and Pitx2c (KD) siRNA.

city: Saskatoon

first: Michelle

last: Collins

address: 107 Wiggins Rd

department: Anatomy, Physiology and Pharmacology

country: Canada

institute: University of Saskatchewan

summary: Genome wide association studies have identified numerous cardiac transcription factors in association with atrial fibrillation. Amongst these transcription factors, the paired-like homeodomain transcription factor 2 (PITX2) is the strongest genetic risk variant associated with atrial fibrillation. However, the downstream mechanisms of PITX2 are not completely understood. Here, we explore the role of PITX2 in oxidative metabolism and stress as a unifying mechanism of arrhythmogenesis. To identify PITX2 mechanisms, we performed transcriptomic analysis to identify gene expression changes in Pitx2c-deficient neonatal rat atrial myocytes. We identify oxidative phosphorylation as the top dysregulated pathway and direct transcriptional targets lie in mitochondrial electron transport chain complexes I and IV. Using the Seahorse Extracellular Flux Analyzer, we identified a functional decrease in oxidative metabolism in Pitx2c-deficient cardiomyocytes. As electron transport chain complexes I and IV may generate reactive oxygen species (ROS) under mitochondrial dysfunction, we quantified mitochondrial specific ROS using MitoSOX and observed an increase in mitochondrial specific ROS in Pitx2c-deficient cardiomyocytes. We additionally assessed spontaneous cardiomyocyte calcium cycling using Fluo-8AM and observed an increased frequency of pro-arrhythmogenic mechanisms including early and delayed afterdepolarizations as inferred through calcium traces. Further, we identified sarcomere disassembly including a potential role of PITX2 in regulating Titin, where Pitx2c-deficient cardiomyocytes display Titin mis-localization within the sarcomeres. To assess whether ROS drives these phenotypes, we treated neonatal rat atrial myocytes with N-acetylcysteine, a potent ROS scavenger, and observed decreased early and delayed afterdepolarizations, as well as restoration of Titin localization.

first: Andy

last: Kim

first: Sébastien

last: Gauvrit

first: Frederick

last: Vizeacoumar


title: Neurotranscriptomics of mutualistic cleaning in Labroides dimidiatus

status: Public on Apr 16 2026

city: Austin

first: Rebecca

middle: L

last: Young

state: TX

address: 2415 Speedway #C0930, Patterson Lab 607A

institute: University of Texas at Austin

summary: Despite the astonishing diversity of life, evolutionary biologists have documented numerous instances where species converge in how they behave, look, and function. Given the importance of happenstance in evolution, it is often assumed that mechanisms driving independent evolution of similar phenotypes (convergence) are distinct; yet recent discoveries suggest that conserved genomic mechanisms can underlie convergent traits. Here, we generate forebrain transcriptomes from six sympatric Labridae wrasses that vary in mutualistic cleaning behavior and apply differential gene expression, co-expression, and phylogenetic comparative analyses to address three questions. First, do neurotranscriptomes vary among species with distinct cleaning behavior? Second, do species that have independently evolved facultative cleaning share neurotranscriptomic patterns? Third, are transcriptomic signatures linked to facultative cleaning also expressed in obligate cleaners? We identify shared neurotranscriptomic patterns in the repeated evolution of facultative cleaning, including 25 novel candidate genes. We then find that transcriptomic patterns associated with facultative cleaning are shared in our focal obligate cleaner species, with more genes than expected by chance with concordant expression patterns in obligate and facultative cleaners. Our results illuminate the neuromolecular basis of cooperative behavior and demonstrate the predictive potential of comparative transcriptomics to unravel the mechanistic underpinnings of the repeated evolution of complex phenotypes.

overall_design: Transcriptome profiling of a forebrain section taken from the obligate cleaner Labroides dimidiatus using 3'tag-seq.

first: Hans

last: Hofmann

first: Redouan

last: Bshary

first: Chelsea

last: Weitekamp

first: Zegni

last: Triki

first: Yiheng

last: Su

first: Abigail

middle: G

last: Beman

first: Matthew

last: Petershack


title: Adhesion-Related Macrophages Regulate Metabolic Homeostasis through CAV-1 Dependency

city: Changsha

first: Hu

last: Wanyu

address: 长沙市芙蓉区人民中路139号

institute: 中南大学湘雅二医院

summary: The significance of adipose tissue macrophages (ATMs) in regulating adipose tissue function is well-established. However, our investigation revealed a previously overlooked subpopulation of macrophages adhered to adipocytes, which we term adhesion-related macrophages (ARMs). We developed an approach to isolate ARMs and compared them with SVF macrophages (SMs). Our findings demonstrate that ARMs constitute the predominant expanded subpopulation of ATMs during obesity, ARMs acquire adipocyte mRNA through direct adhesion to adipocytes, thereby enhancing their lipid processing capacity. Notably, ARMs can be characterized by a key functional marker, Caveolin-1. Genetic ablation of Caveolin-1 in macrophages significantly diminishes ARM abundance, disrupting their adhesion capacity and lipid content, leading to adipocyte hypertrophy, adipose tissue expansion, and impaired glucose homeostasis. Reintroducing ARMs from lean mice into eWAT mitigate obesity-induced insulin resistance. Our study uncovers ARM as a potential therapeutic target for obesity-induced insulin resistance and opening avenues for identifying similar paradigms in other tissues and diseases.

overall_design: By using ATAC sequencing, the differences between ewat adhesion-related macrophages (ARM) and SVF macrophages (SM) in mice under obesity conditions (8 weeks of HFD) were compared.

first: Wanyu

last: Hu

first: Xiyan

last: Liao

first: Limin

last: Xie

first: Xiaoxiao

last: Sun

first: Luodi

last: Jing

first: Qin

last: Zeng

first: Hongwei

last: Jiang


title: Comparative transcriptomics reveals differences in cortical cell type organization between metatherian and eutherian mammals [snRNA-Seq]

city: Los Angeles

first: Joshua

last: Trachtenberg

address: 635 Charles E. Young Dr. South, Room 503

department: Neurobiology

institute: University of California-Los Angeles

summary: The neocortex supports mammalian cognition through a conserved columnar architecture, but variation in the transcriptomic organization of cortical columns across deep mammalian divergences has not been directly examined. We used single-nucleus RNA sequencing and spatial transcriptomics to compare primary visual cortex in marsupial (opossum) and placental (mouse) mammals. Major neuronal subclasses and laminar architecture were broadly conserved, but intratelencephalic (IT) neurons differed markedly. Opossum IT neurons exhibited more generalized, overlapping transcriptomic identities with a continuous spatio-transcriptomic gradient between superficial (L2/3) and deep (L5) IT populations, whereas mouse IT neurons showed sharper transcriptomic distinctions and greater spatial confinement, consistent with increased specialization. Mouse cortex also displayed reduced PV interneuron density and redistribution of perineuronal nets, suggesting altered constraints on cortical plasticity. These findings demonstrate that substantial variation in intracortical circuit organization exists across deeply diverged mammalian lineages, identifying IT neurons as a principal axis of evolutionary divergence in the neocortical column.

overall_design: Primary visual cortical tissue from both hemispheres was collected from two opossums, pooled by animal (biological replicates), and used to generate nuclear suspensions. Nuclei were stained with Draq5 and purified with fluorescence-aided sorting (FANS) to remove excess debris. Each nuclear suspension was then used to generate two transcriptomic libraries (library replicates) for a total of four nuclear transcriptomic libraries.

middle: T

first: Ryan

last: Gorzek


title: Comparative transcriptomics reveals differences in cortical cell type organization between metatherian and eutherian mammals [Stereo-seq]

sample_organism:
Mus musculus
Monodelphis domestica

platform_organism:
Mus musculus
Monodelphis domestica

overall_design: Cortical tissue (coronal slices) from both hemispheres of an opossum and mouse was extracted and flash-frozen in OCT using a multi-embedding strategy that resulted in four hemispheres of primary visual cortex per section. The Stereo-seq pipeline was then performed on one 10-µm section (excluding optimization of tissue permeabilization) from each species.


title: Intestinal epithelial and immune cell responses to Vibrio cholerae and IL22 therapy at single-cell resolution

city: Boston

first: Yuko

last: Hasegawa

address: 181 Longwood Ave.

institute: Brigham and Women's Hospital

summary: Vibrio cholerae colonizes the small intestine and causes acute severe diarrhea. Knowledge of intestinal cell responses and innate immune defenses to infection with the cholera pathogen is limited. We defined the epithelial and lamina propria immune cell transcriptional responses to experimental cholera using single-cell RNA sequencing using the infant mouse model of V. cholerae infection. Infection increased the abundance of an enterocyte subtype that highly expressed defense-associated functions, as well as the production of Il22 from ILC3 cells. An IL22 Fc-fusion protein markedly limited V. cholerae intestinal colonization and protected mice from diarrhea and death. IL22 treatment induced expression of vibriocidal Reg3b and elevated the abundance of secretory lineage cells that produce Muc2, impairing V. cholerae association with epithelial cells.

overall_design: We performed single-cell RNA-seq using 10X Genomics Chromium Next GEM Single Cell 3' Reagent Kits v3.1 on epithelial and lamina propria immune cells of P5 infant mouse (2.5-3.5 g of body weight) small intestine at 16 hours post-infection. For IL22Fc treated epithelial single-cell RNA-seq, P4 infant mice were administered with 20 mg of IL22Fc intraperitoneally and returned to their dam. After 36 hours, infant mice were euthanized and cells were isolated from SI. We pooled cells in the same group of mice (n=3-4). Live Epcam+ or CD45+ cells were sorted by FACS.

first: Masataka

last: Suzuki

first: Hailong

last: Zhang

middle: K

last: Waldor


title: The Chromatin Remodeler, Mit1, Enables the Propagation of the Histone Modification, H3K9me

status: Public on Mar 30 2026

first: Kaushik

last: Ragunathan

overall_design: Chromatin immunoprecipitation sequencing (ChIP-seq) for H3K9me2 and H3K9me3

first: Melissa

last: Seman

first: Alexandria

last: Latuda

first: Fenting

last: Huang

first: Agnisrota

last: Mazumder

first: Luca

last: Wolfstadter

first: Sigurd

last: Braun


title: Identification of host lncRNAs that impact Venezuelan equine encephalitis  virus replication

city: Albuquerque

first: Steven

last: Bradfute

state: NM

address: 1 University of New Mexico

institute: University of New Mexico Health Sciences Center

summary: Venezuelan equine encephalitis virus (VEEV) causes encephalitis in humans and equids, and there are no vaccines or therapeutics available for humans. In recent years, non-coding RNAs have emerged as critical regulatory factors affecting different cellular pathways. Specifically, long non-coding RNAs (lncRNAs) have been identified  as regulators of antiviral pathways during various viral infections; however, their role in  regulating VEEV infection has not been assessed. Here we show differential expression of several lncRNAs in primary mouse target cells infected with a vaccine strain of VEEV (TC-83) but not a pathogenic strain (TrD). Among the differentially expressed genes (DEGs), suppressing lncRNA small nucleolar RNA host gene 15 (Snhg15) resulted in about a 7-fold increase in VEEV TC-83 replication in primary mouse a strocytes. Knockdown of Snhg15 during VEEV TC-83 infection resulted in thesuppression of ten genes including Irf1, Junb, Atf3, Relb, Pim1, Hbegf, Ccl5, Ankrd33b, and H2-K2, all of which were also increased during TC-83 infection when the expression of Snhg15 increased in primary mouse astrocytes. Most of these genes are involved inantiviral responses. KEGG pathway analysis confirmed the suppression of both pattern recognition receptor and inflammatory pathways after in Snhg15 knockdown. These data are the first to identify lncRNA responses in encephalitic alphavirus infection and demonstrate important roles for these overlooked RNAs on VEEV infection.

overall_design: Total RNA sequencing was used to profile lncRNA gene expression in primary mouse  astrocytes and neurons in reponse to VEEV Trinidad donkey (TrD) and VEEV TC-83  infections. The gene expression profiles of VEEV TrD and VEEV TC-83 at 16hpi and 24hpi were compared to those of uninfected cells.

first: Mahgol

last: Behnia

first: Chunyan

last: Ye

first: Kim

last: Somfleth

first: Olufunmilola

last: Oyebamiji

first: Kathryn

last: Brayer

first: Yan

last: Guo

first: Scott

last: Ness

first: Ram

last: Savan

middle: B


title: Identification of host lncRNAs that impact Venezuelan equine encephalitis virus replication

summary: Venezuelan equine encephalitis virus (VEEV) causes encephalitis in humans and equids, and there are no vaccines or therapeutics available for humans. In recent years, non-coding RNAs have emerged as critical regulatory factors affecting different cellular pathways. Specifically, long non-coding RNAs (lncRNAs) have been identified as regulators of antiviral pathways during various viral infections; however, their role in regulating VEEV infection has not been assessed. Here we show differential expression of several lncRNAs in primary mouse target cells infected with a vaccine strain of VEEV (TC-83) but not a pathogenic strain (TrD). Among the differentially expressed genes (DEGs), suppressing lncRNA small nucleolar RNA host gene 15 (Snhg15) resulted in about a 7-fold increase in VEEV TC-83 replication in primary mouse astrocytes. Knockdown of Snhg15 during VEEV TC-83 infection resulted in the suppression of ten genes including Irf1, Junb, Atf3, Relb, Pim1, Hbegf, Ccl5, Ankrd33b, and H2-K2, all of which were also increased during TC-83 infection when the expression of Snhg15 increased in primary mouse astrocytes. Most of these genes are involved in antiviral responses. KEGG pathway analysis confirmed the suppression of both pattern recognition receptor and inflammatory pathways after in Snhg15 knockdown. These data are the first to identify lncRNA responses in encephalitic alphavirus infection and demonstrate important roles for these overlooked RNAs on VEEV infection.

overall_design: Total RNA sequencing was used to profile lncRNA gene expression in primary mouse astrocytes and neurons in reponse to VEEV Trinidad donkey (TrD) and VEEV TC-83 infections. The gene expression profiles of VEEV TrD and VEEV TC-83  at 16hpi and 24hpi were compared to those of uninfected cells.


title: Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of Fragile X mice and identifies EPAC2 as a therapeutic target

first: Anand

last: Suresh

address: 650 CHARLES E YOUNG DR S, MED RECEIVING CHS, RM 76-200C

department: Neurology

institute: University of California Los Angeles

summary: Symptoms of Fragile X Syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance. Here, we leverage cell type specific mRNA sequencing to profile molecular alterations of cortical excitatory (Camk2) and inhibitory (Pvalb) neurons in Fmr1 knockout (KO) mice, integrating transcriptomic results with circuit and behavioral readouts to prioritize novel therapeutic targets. We uncovered significant genotype-by-cell interactions for differential gene expression in Camk2a and Pvalb translatomes, and, strikingly, the underlying signaling pathways were often altered in opposite directions. Among the 184 DEGs that were concordantly dysregulated across both cell types, only Rapgef4 (Epac2; upregulated in Fmr1 KO) was also an FMRP target, brain-enriched and associated with neurodevelopmental disorders. Treatment of Fmr1 KO mice with a specific EPAC2 antagonist restored cortical circuit function and ameliorated multiple behavioral phenotypes. Thus, EPAC2 should be considered as a potential target for therapy in FXS.

overall_design: Young adult (P70-100) PV-Cre-Rpl22HA/HA and Camk2a-Cre-Rpl22HA/HA, WT or Fmr1 KO mice were used for the Ribotag RNA-seq experiments.

first: Nazim

last: Kourdougli

first: Toshihiro

last: Nomura

first: Jessie E

last: Buth

first: Soledad

last: Miranda-Rottmann

first: Carlos A

last: Sanchez-Leon

first: Michelle W

last: Wu

first: Sofia M

last: Nelson

first: Lauren T

last: Wall

first: Anne T

last: Tran

first: Roberto

last: Araya

first: Anis

last: Contractor

first: Michael J

last: Gandal

first: Carlos

last: Portera-Cailliau


title: Dysbiotic Microbiota-Induced Ammonium Stress Drives Intestinal Barrier Dysfunction and MASH Progression: The Therapeutic Promise of DT-109

city: Xi'an

first: Pengxiang

last: Qu

address: 76 Yanta West Road, Xi’an, Shaanxi

institute: Xi'an Jiaotong University

summary: The prevalence of metabolic dysfunction-associated steatohepatitis (MASH) continues to rise annually. This study explores the link between intestinal microbial dysbiosis and MASH development. Three livers from each group were selected for single-cell RNA sequencing (scRNA-seq) in Cynomolgus monkeys.

overall_design: Two group male monkeys were fed MASH diet for 10 months, then the monkeys were randomized to receive orally (gavage) DT-109 at 150 mg/kg body weight/day or equivalent volume of H2O for 5 additional months on the MASH diet. Six male monkeys were fed chow diet during the 15 months.


title: Sperm sncRNA networks are synchronized by a coordination between adverse childhood experiences (ACE) and current stress

city: Aurora

first: Nickole

last: Moon

state: CO

address: 12700 East 19th Avenue, RC2, Rm 9480

institute: University of Colorado

type: Non-coding RNA profiling by high throughput sequencing

summary: Reproductive fitness is impacted by sperm RNA composition, including that of small noncoding RNA (sncRNA). Our previous studies found that elevated perceived stress significantly altered dynamically expressed sncRNA and increased sperm motility. However, the lasting influence of stressors earlier in life, such as adverse childhood experiences (ACE), and its interaction with current stress on sperm sncRNA remain unclear. Therefore, in a longitudinal human cohort we examined differential sncRNA and co-expression networks associated with perceived stress and ACE. Utilizing computational modeling, we identified significant time-dependent interactions between ACE and perceived stress that altered both sncRNA levels and subtype coordination. Such changes across sncRNA are likely to significantly alter genes important for reproductive outcomes, reflecting a synchronized strategy by which current and past environments may impact the next generation. Evolutionarily, this specificity may preserve sncRNA modules essential for species survival while allowing refined changes in stress-responsive pathways for intergenerational fitness.

overall_design: Repeated sampling longitudinal human cohort study (1 semen sample provided per month). Single end analysis, therefore only R1 fastq files were used for analysis, therefore, only R1 files are provided and the paired end section is not completed.

first: Caio

last: Braga

first: Alyssa

last: Jeng

first: Arthur S.

last: Feltrin

first: Rachel

last: Johnson

first: Mary D.

last: Sammel

first: Sergio N

last: Simões

first: David C.

last: . Martins-Jr

first: H.

last: Brentani

first: C. Neill

last: Epperson

first: Tracy L.

last: Bale


title: Photoactivatable CRISPR/Cas13d via upconversion nanoparticles for deep tissue RNA engineering and orthopedic therapy

status: Public on Mar 29 2026

city: tianjin

first: miaomiao

last: gao

address: tianjin

country: Algeria

institute: tianjin university

summary: To overcome the limited tissue penetration of blue light, we engineer polyethylenimine-functionalized upconversion nanoparticles (UCNPs-PEI) that serve dual roles as gene carriers and photon transducers, converting tissue-penetrating near-infrared (980 nm) to blue light (470 nm). The UCNPs-PEI@paCas13d system achieves precise spatiotemporal control of RNA targeting within bone tissue in vivo. In a murine steroid-associated osteonecrosis model, NIR-activated paCas13d achieves robust TET3 knockdown, disrupting the TET3-5hmC-PTEN axis that drives glucocorticoid-induced osteocyte apoptosis. This targeted intervention prevents bone deterioration, with treated mice showing preserved trabecular architecture, enhanced bone volume, and favorable shifts in bone turnover markers, while maintaining systemic glucocorticoid efficacy. Our platform combines the programmability of CRISPR/Cas13d with non-invasive optical control, offering a versatile approach for treating diseases requiring localized RNA modulation while minimizing systemic effects.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for HEK293T cells transfected with non-targeting control or ANXA4-targeting paCas13d

first: Jie

last: Zhao

first: Jun

last: Jiao

first: Miaomiao

last: Gao

first: Jingyu

last: Zhang

first: Jinbin

last: Pan

first: Xinlong

last: Ma


title: Compare the transcriptomic effects of FK228 and Class I HDACs YF mutants overexpression

status: Public on Mar 28 2026

first: Hang

last: Ruan

address: 199 Ren'ai Road

department: IBMS

institute: Soochow University

summary: To compare the transcriptomic effects of FK228 and Class I HDACs YF mutants overexpression and to characterize their inter-dependency, we performed RNA-seq in AML12 cells in the above-mentioned 4 groups: control, FK228, YF overexpression, and FK228 + YF overexpression.

first: Zheng

last: Sun

first: Chaitra

last: Rai

first: Leng

last: Han

first: Wenbo

last: Li


title: Compare the loci-specific histone acetylation on the chromatin of FK228 and Class I HDACs YF mutants overexpression

summary: To compare the H3K27ac effects of FK228 and Class I HDACs YF mutants overexpression and to characterize their inter-dependency, we performed ChIP-seq in AML12 cells in the above-mentioned 4 groups: control, FK228, YF overexpression, and FK228 + YF overexpression.


title: Immune-remodeling mRNAs expressing IRF8 or NIK generate durable anti-tumor immunity in multiple cancer models

city: Cambridge

first: Yann

last: Vanrobaeys

address: 500 Main Street, Building 76

institute: Massachusetts Institute of Technology

summary: Although immunotherapy has a subset of cancer patients, its broader efficacy remains limited, primarily due to an immunosuppressive tumor microenvironment characterized by insufficient numbers of functional tumor-specific T cells, antigen-presenting cells (APCs) and tumor-infiltrating lymphocytes. Here we engineer immune cells in the tumor microenvironment using lipid nanoparticles (LNPs) to deliver immune remodeling mRNAs (IR-mRNAs) encoding NF-κB inducing kinase (NIK) or interferon regulatory factor 8 (IRF8). These IR-mRNAs activate APCs in tumors, significantly increasing activated type 1 conventional dendritic cells, immunostimulatory cytokines, and priming anti-tumor CD8+ T cells. IR-mRNAs encapsulated in LNPs elicited durable antitumor responses in multiple syngeneic mouse tumor models via both intratumoral and intravenous delivery. Co-administration of IR- and OVA-mRNA elicited ~10-fold increase of antigen-specific CD8⁺ T cell responses, sustained long-term memory, and effectively prevented tumor growth in vaccinated mice. Additionally, adjuvanting influenza vaccines with IR-mRNAs enhanced the humoral response by 5-fold and the cellular response by ~15-fold, underscoring their potential as adjuvants for boosting adaptive immunity.

overall_design: We investigated how immune remodeling mRNAs modulate immature dendritic cells to acquire mature phenotypes capable of efficient T-cell priming, using flow cytometry and single-cell RNA sequencing (scRNA-seq)

first: Akash

last: Gupta

first: Riddha

last: Das

first: Kaelan

last: Reed

first: Taewon

last: Jeon

first: Quang Trung Chinh

last: Nguyen

first: Arnab

last: Rudra

first: Xinying

last: Ge

first: Suthathip

last: Trongjit

first: Robert

last: Langer

first: Ralph

last: Weissleder

first: Christopher

last: Garris

first: Daniel

last: Anderson


title: Distinct phases of immune system programming during ART-suppressed immunodeficiency virus infection

city: Beaverton

first: Benjamin

middle: N

last: Bimber

state: OR

address: 505 NW 185th Ave

summary: This project contains rhesus macaque immune cell single-cell RNA-seq data, from SIV/ART studies.

overall_design: These data are bulk immune cells from the indicated tissue, processed using the 10x genomics scRNA-seq platform. Cells were isolated from tissue biopsies or at necropsy at the indicated timepoints.


title: PrPC-facilitated cell signaling activates phospholipase Cɣ1 and triggers an Arc/Arg3.1 response in mouse neurons and human iPSC-derived neurons

status: Public on Apr 13 2026

city: La Jolla

last: Ojeda-Juarez

address: 9500 Gilman Dr. MC 0612

institute: UC San Diego

summary: Synapse loss is an early feature of prion disease, yet the underlying drivers are poorly understood. We recently found evidence of neuronal hyperactivity and synaptic loss in prion-infected mice. Herein we identified increased Arc/Arg3.1 in patients with prion disease, suggesting heightened neuronal activity also occurs in human prion-affected brain. To determine the signaling events initiated by prion aggregates (PrPSc), we developed a disease model in which human iPSC-derived excitatory neurons are stimulated with a PrPSc-mimetic antibody that binds cellular prion protein (PrPC). Within two hours, we detected an Arc/Arg3.1 response together with transcriptomic changes previously reported in prion-infected mice. We identified altered phosphorylation of PLC-γ1, ERK1/2, and EGFR as PrPC-triggered cell signaling events that accompany the Arc/Arg3.1. These results suggest that PrPC ligands, including PrPSc, trigger rapid signaling events linked to neuronal hyperactivity in human neurons, and indicate PLC-γ1 as a potential therapeutic target.

overall_design: 6 - 8 week-old iNs were treated with PBS, POM1 (33 nM), or IgG (33 nM) for 2 hours. Samples were lysed in RLT buffer and RNA isolated using the RNeasy Micro kit (Cat# 74004; Qiagen) following the manufacturer’s protocol. Total RNA was assessed for quality using an Agilent Tapestation 4200, and samples with an RNA Integrity Number (RIN) greater than 8.5 were used to generate RNA sequencing libraries using the TruSeq Stranded mRNA Sample Prep Kit (Illumina, San Diego, CA). Samples were processed following the manufacturer's instructions. Resulting libraries were multiplexed and sequenced with 100 base pair (bp) single reads (SR100) to a depth of approximately 25 million reads per sample on an Illumina NovaSeq X Plus. Samples were demultiplexed using bcl2fastq Conversion Software (Illumina, San Diego, CA). QC and RNA-seq were conducted at the IGM Genomics Center, University of California, San Diego, La Jolla, CA.

first: Gail

last: Funk

last: McClatchy

first: Emily

last: Richards

first: Alexander

last: Rajic

first: Katrin

last: Soldau

first: Michael

last: Geschwind

first: Xu

last: Chen

first: John

middle: R

last: Yates III

first: Steven

last: Gonias

first: Christina

last: Sigurdson


title: PD-1 Deficiency Exacerbates Mycobacterium abscessus Lung Infection via Dysregulated T Cell Responses

status: Public on Apr 14 2026

city: Chongqing

first: Xiaowen

last: Yu

address: No. 6, Panxi 7th Branch Road, Jiangbei District

department: Basic Research Laboratory of Traditional Chinese Medicine

institute: Chongqing Traditional Chinese Medicine Hospital

summary: A PD-1-deficient Mycobacterium abscessus -infected mouse model was established. The impact of PD-1 on bacterial clearance, immune cell activity, and metabolism was evaluated via colony counting, histopathology, flow cytometry, multiplex immunofluorescence and transcriptomics. We fonud that PD-1−/− mice exhibited increased susceptibility to MAB. Early infection showed elevated lung CD4⁺ T cells, reduced neutrophils, and higher blood cytokines (IFN-γ, IL-21, IL-6, IL-27).

overall_design: Transcriptomic Analysis of Immune Cell Recruitment and Functional Alterations in Pulmonary Tissues of Wild-Type and PD-1-Deficient Mice Following MAB Infection at 3, 7, and 14 Days Post-Infection

first: Lu

last: Huang


title: Transcriptome-based classification of resected pancreatic ductal adenocarcinoma enhances prognostic modelling accuracy of overall survival following adjuvant treatment

city: Amsterdam

first: Richard

last: Volckmann

state: Noord-Holland

address: van der Boechorststraat 6a

department: Laboratory of Experimental Oncology and Radiobiology

country: Netherlands

institute: msterdam UMC and University of Amsterdam

summary: In pancreatic ductal adenocarcinoma, patient outcomes after resection remain highly variable. Prognostic models are often inaccurate. Our study aimed to improve survival prediction by adding transcriptome-based classification to a validated prognostic model and applying it on a multicenter real-world cohort. Fresh-frozen tumor resection materials were obtained from the Dutch Pancreas Parel biobank. RNA was sequenced if tumor cellularity was >30%. The samples were classified using transcriptome-based classification. Survival differences between transcriptome-based subtypes were studied in patients treated with and without adjuvant chemotherapy. Both patients receiving neoadjuvant treatment (NAT) and patients undergoing immediate surgery were included. Samples of 461 patients were collected, of which 118 samples underwent RNA sequencing. Of those, 39.0% were of the basal-like subtype and 61.0% were of the classical subtype. The basal-like subtype became dominant after NAT (63.3%, p = 0.004). Adjuvant gemcitabine-treated patients with a classical tumor survived longer than those with a basal-like tumor (median overall survival (OS): 22.8 vs. 11.4 months; p < 0.001). In multivariable Cox regression, the classical subtype significantly associated with increased survival (hazard ratio = 0.38; p = 0.002) and adding transcriptome-based subtyping significantly improved the prognostic model (p = 0.002). Subtype and adjuvant treatment independently statistically significantly associated with OS. Transcriptome-based subtyping significantly adds to clinical variables in survival prediction after surgery. The independent associations for subtype and adjuvant treatment with OS indicate that subtypes are prognostic, but not predictive for OS with adjuvant treatment. The provided prognostic information could potentially support treatment decisions and serve as stratification factor.

overall_design:
Retrospective cohort study: Resection specimen of PDAC patients were collected, and selected for sufficient tumor cell percentage. Subsequently, RNA was isolated and submitted for RNA sequencing.

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

first: Marjolein

middle: F

last: Lansbergen

first: Vincent

last: Lanting

first: Paul

last: Manoukian

first: Marc

last: Besselink

first: Geert

last: Kazemier

first: Ignace

last: de Hingh

first: Mike

middle: S

last: Liem

first: Casper

last: van Eijck

first: Erwin

last: van der Harst

last: de Meijer

first: Ronald

last: van Dam

first: Martijn

middle: W

last: Stommel

first: Jan

last: Koster

last: Tanck

first: Arantza

last: Fariña

first: Joanne

last: Verheij

first: Frederike

last: Dijk

first: Johanna

last: Wilmink

first: Maarten

last: Bijlsma

first: Hanneke

last: van Laarhoven


title: ATR and PKMYT1inhibition re-sensitize a subset of TNBC patient-derived models to carboplatin and induce mitotic catastrophe

status: Public on Mar 27 2026

city: Montreal

first: Mark

last: Basik

address: 3755 Chem. de la Côte-Sainte-Catherine

institute: Lady Davis Institute

summary: Triple negative breast cancer (TNBC) is associated with poor prognosis and is mainly treated with chemotherapy-based regimens, often including carboplatin. Resistance to carboplatin is a common clinical issue that is either initially present or develops with treatment. Overcoming this resistance is a significant clinical challenge, which highlights the need for novel therapeutic strategies. We used a pooled shRNA screening approach with a chemoresistant TNBC patient-derived xenograft (PDX) cell (PDXC) line to identify targets whose knockdown would enhance the efficacy of carboplatin. This screening led to the identification of the ATR (ataxia telangiectasia and Rad3-related) gene as a key therapeutic vulnerability. Inhibiting ATR with BAY1895344 or AZD6738 re-sensitized carboplatin-resistant PDXCs and PDXs to carboplatin, resulting in an increase in DNA damage, and apoptosis. ATR inhibition prevents carboplatin-resistant cells from effectively engaging the S and G2/M checkpoints required for DNA repair, leading to mitotic catastrophe. We further identified that the addition of ATR inhibitors to carboplatin enabled FOXM1-targeted gene program leading to premature passage into mitosis. Moreover, targeting PKMYT1, a regulator of cyclin-dependent kinase 1 (CDK1) controlling the G2/M checkpoint, through knockdown or with the novel PKMYT1 inhibitor RP-6306, also enhanced carboplatin efficacy in our TNBC PDXC. Molecular factors associated with response to the ATR inhibitor/carboplatin combination included low RNA levels of PKMYT1. These results underscore the pivotal roles of ATR and PKMYT1 in mediating resistance to carboplatin in TNBC and support targeting these pathways to overcome carboplatin resistance in this disease.

overall_design: RNA-seq profiling of T-786 patient-derived xenograft cell untreated or treated for 24h with carboplatin (20uM), BAY1895344 (5nM), RP-6306 (100nM, carboplatin+BAY1895344 or carboplatin+RP-6306

first: Juliet

last: Guay

first: Hellen

last: Kuasne

first: Catherine

last: Chabot

first: Kathryn

last: Bozek

first: Yasamin

last: Majedi

first: Marguerite

last: Buchanan

first: Adriana

last: Aguilar-Mahecha

first: Eric

last: Bareke

first: Benjamin

last: Ulmer

first: Tim

last: Kong

first: Kangning

last: Yang

first: Minyan

last: Liao

first: Oluwadara

last: Elubute

first: Ruining

last: Guo

first: Anie

last: Monast

first: Geneviève

last: Morin

first: Sidong

last: Huang

first: Morag

last: Park


title: Single-cell characterization of anterior segment development in the mouse reveals the cell types, pathways, and signals driving formation of the trabecular meshwork and Schlemm's canal

city: New York

first: Revathi

last: Balasubramanian

address: 635 West 165th street

department: Ophthalmology

institute: Columbia University

summary: Morphogenesis of the anterior segment (AS) is crucial for healthy ocular physiology and vision but is only partially understood. The Schlemm's canal (SC) and trabecular meshwork (TM) are essential drainage tissues within the AS, and their proper development and function are critical for maintaining normal intraocular pressure; abnormalities in either tissue can result in elevated pressure and glaucoma. Here, we use single-cell transcriptomic profiling to provide high-resolution molecular detail of AS development with a particular focus on SC and TM. We report transcriptomes for ~130,000 single cells at key developmental stages from postnatal day 2 (P2) to P60. We provide the first annotation of cell types across these developmental stages and crucial information about dynamic changes in pathways/gene expression. Further, we trace developmental trajectories for TM cell and SC endothelial cell (SEC) subtypes and determine genes and signaling networks driving their specific cell fates. We demonstrate dynamic changes in signaling interactions between SC and the TM cells during their synchronized development. Collectively, our data lay a deep molecular foundation for AS development that will direct understanding of normal ocular physiology, glaucoma, and other AS conditions.

overall_design: Pregnant dams were checked daily between 9:00 AM and 12:00 PM for births. The date of birth was recorded as midnight of the day pups were first observed. Mice were collected at the following timepoints: P2.5, P4.5, P6.5, P10, P14, P21, and P60. For each timepoint, eyes from four animals (eight eyes total) were pooled per sample, and two samples were collected per age. All samples consisted of eight eyes, except for one P21 sample, which contained seven eyes due to exclusion of a severely microphthalmic eye. Sex was balanced at each timepoint. Sex was determined by anogenital distance at P21 and P60, and by genotyping at earlier ages. To standardize early timepoint collections, P2.5 and P6.5 harvests were conducted between 7:00–9:00 AM, while all other timepoints were collected between 9:00 AM–12:00 PM. Eyes were enucleated into fresh Dulbecco’s Modified Eagle Medium (DMEM; Gibco) and dissected in the same medium. All dissection tools and surfaces were treated with RNaseZap (Ambion). For dissection, the posterior segment was removed by cutting between the limbus and sclera, followed by lens removal. Finally, we made a small circular cut in the anterior cornea, removing the middle 1/3rd of the area (P2.5–P14), and the middle 2/3rds for P21 and P60. The iris was carefully removed at P21 and P60. The remaining anterior segment tissue (limbal strip) was minced and prepared for enzymatic digestion. Tissues were digested enzymatically (Papain Dissociation System; Worthington Biochemical Corporation) and single cells were loaded into 10× Chromium Single Cell Chips (detailed protocol in Balasubramanian et al.21). Single-cell libraries were generated according to the manufacturer’s protocol. Libraries were sequenced on the Ilumina Novaseq platform. Sequencing data were demultiplexed and aligned using Cellranger software (10× Genomics). Reads were aligned to the mouse mm10 genome.

first: Nicholas

last: Tolman

first: Taibo

last: Li


title: Histone deacetylase enzyme activity is not the universal anti-cancer target of HDAC inhibitors [RNA-seq_MC38]

city: Houston

first: Chaitra

last: Rai

address: ABBR 631C, 1 BAYLOR PLAZA

institute: Baylor College of Medicine

summary: As a family of anti-cancer drugs, histone deacetylase inhibitors (HDIs) show efficacies against a wide range of cancers, but their mechanism of action is unclear. Here, we performed unbiased bioinformatics analysis and found that genetic variants or expression levels of HDACs do not correlate with the carcinogenesis of most cancer types and do not predict cancer patient survival. Whole-genome CRISPR library screens did not identify HDACs as genes affecting cellular responses to HDIs such as SAHA or MS-275. Overexpression of dominant-negative, catalytically inactive Class I HDACs (HDAC1, 2, 3, and 8) caused a similar degree of histone hyperacetylation as Class I-specific HDI FK228 in cancer cell lines without similar anti-cancer effects, transcriptomic changes, or cellular responses to FK228. The anti-cancer effects of FK228 can be further dissociated from the histone hyperacetylation in an in-situ liver cancer mouse model. Importantly, chemical manipulations of several pan-HDIs abolished HDAC-inhibiting activity but retained the majority of anti-cancer effects in a mouse xenograft cancer model. These results suggest that HDAC enzyme activity is not a universal de facto target of HDIs for their anti-cancer efficacy. These findings have profound implications for understanding the pharmacodynamics of HDIs and developing next-generation compounds for this promising family of anti-cancer drugs.

overall_design: To investigate the anti-cancer effect of SAHA and SAA on MC38 mouse Xenograft model. The study has three groups control, SAHA and SAA. We performed gene expression profiling analysis using the data obtained from RNA-seq of four different groups.


title: Oligodendrocyte subtype imbalance and dysfunction contribute to motor deficits and Purkinje cell axonopathy in SCA1

status: Public on Mar 26 2026

city: New Haven

first: Changwoo

last: Lee

state: CT

address: 295 Congress

institute: Yale University

summary: Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease marked by progressive motor deficits and Purkinje cell (PC) degeneration, driven by polyglutamine expansion in ataxin-1. While oligodendroglial dysfunction precedes PC loss, its direct contribution toward SCA1 pathogenesis remains unclear. Here, using an oligodendroglia-specific SCA1 conditional knock-in mouse model, we demonstrate that mutant ataxin-1 in oligodendrocytes is sufficient to drive aspects of SCA1-related pathology, including dysregulated myelination, PC axonal shrinkage, and torpedo formation, ultimately impairing motor coordination. Cross-species single-nucleus RNA-sequencing reveals cerebellar oligodendrocyte subtypes with distinct gene expression and abundance dysregulation that contribute to demyelination. This, compounded by a progressive decline in the neuroprotective functions of a cerebellar-specific oligodendrocyte subtype, establishes a critical link between demyelination, axo-myelinic dysfunction, and axonal pathology in SCA1. Upstream transcriptional regulator analysis in oligodendroglia identifies TCF7L2 and HTT as key mediators of oligodendroglial dysfunction in SCA1, suggesting shared pathogenic mechanisms with other polyglutamine diseases. These findings position oligodendroglia as central players in SCA1 pathogenesis and underscore their essential role in supporting PC of axonal integrity.

overall_design: we performed snRNA-seq on the cerebella of OL-SCA1-cKI( SCA1fl/+; NG2-cre) mice and their SCA1fl/+ littermate controls at 30 weeks

first: Janghoo

last: Lim


title: Ribosome-associated RNA of cardiac endothelial cells purified from endothelial specific RiboTag mice

city: bad nauheim

first: Stefan

last: Günther

address: ludwigtr. 43

institute: MPI for heart and lung research

summary: To assess the expression levels of ribosome-associated RNAs of murine cardiac endothelial cells, hearts were collected from Cdh5-CreERT2;Rpl22tm1.1Psam mice (endothelial specific RiboTag) and ribosomes of endothelial cells containing HA-tagged RPL22 protein were immunoprecipitated. Then, RNA-seq was performed. The mice underwent coronary ligation 7 days before and only the remote healthy area of the heart was analyzed.

overall_design: Three biological replicates for RNA-seq of ribosome-associated RNA of cardiac endothelial cells.

first: Haruya

last: Kawase

last: Offermanns


title: Inactive b1-integrin acts as a cell junction-localized molecular scaffold for Angiopoietin2-TIE2-FOXO1 signaling [RNA-Seq]

status: Public on Mar 25 2026

city: Helsinki

first: Pipsa

last: Saharinen

address: Haartmaninkatu 8

country: Finland

institute: University of Helsinki

summary: Transcriptome profiling of lymphatic endothelial cells (LECs) treated with R&D angiopoietin-2 (rhAng2) for 3 or 6 hours to investigate early transcriptional responses.

overall_design: Lymphatic endothelial cells (LECs) were stimulated with multimeric Ang2 for either 3 h or 6 h. Control cells were treated with BSA for the corresponding time periods. Following stimulation, cells were collected for downstream scRNA-seq analysis.

first: Klaudia

last: Lewna

first: Shraman

last: Bohra

first: Keerthana

last: Ganesh


title: Bulk RNAseq in microglia from wild-type (WT) and Lactamase B (LACTB) enymatic dead (ED) mice (LACTB S162I).

status: Public on Mar 24 2026

first: Ruben

last: Gomez-Gutierrez

address: 1881 East Road

department: Therapeutics Discovery Division

institute: The University of Texas MD Anderson Cancer Center

summary: Our mendelian randomization analysis showed that lower expression of LACTB in myeloid cells might be protective for Alzheimer's Disease. We evaluated how microglial cells from LACTB enzymatic dead mice show transcriptional changes.

overall_design: RNA-seq profiling of microglia (iMGLs) from mice with enzymatic dead Lactamase B (LACTB ED) and wild-type (WT) controls.

first: Jiacheng

last: Ma

first: Kendra

last: Allton

first: Olivia

last: Calderon

first: Yaima

last: Lightfoot

first: Morgan

last: McReynolds

first: William

last: Ray


title: Inactive b1-integrin acts as a cell junction-localized molecular scaffold for Angiopoietin2-TIE2-FOXO1 signaling

summary: Transcriptome profiling of lymphatic endothelial cells (LECs) treated with multimeric angiopoietin-2 (Ang2) for 3 or 6 hours to investigate early transcriptional responses.


title: Beneficial impact of acquired AmpC β-lactamases on bacterial fitness and pathogenicity: a new paradigm

city: RENNES

first: Charlotte

last: Michaux

address: 2 avenue du Pr Leon Bernard

department: Inserm

country: France

institute: University of Rennes

summary: The study investigated the impact of acquired AmpC β-lactamases on global gene expression and cellular physiology in Enterobacterales. Isogenic Escherichia coli MG1655 strains carrying empty vector (p0) or plasmids encoding CMY-2, CMY-42, or CMY-145 β-lactamase variants were grown to mid-log phase in minimal M9 medium with kanamycin. Total RNA was extracted in three biological replicates, ribosomal RNA was depleted, and strand-specific libraries were sequenced. Reads were mapped to the E. coli K-12 reference genome and differential expression analysis was performed. Comparative transcriptomics revealed large gene expression changes associated with AmpC variant production, including consistent deregulation of genes involved in flagellar biosynthesis, motility, and additional metabolic functions. These RNA-seq data provide a transcriptomic framework to understand how distinct AmpC variants differentially reshape bacterial regulatory networks beyond β-lactam resistance.

sample_organism: Escherichia coli str. K-12 substr. MG1655

overall_design: RNA-seq profiling of wild-type Escherichia coli MG1655 with or within expression of different β-lactamase variants.

first: Otávio Hallal

last: Ferreira Raro

first: Andrea

last: Endimiani

first: Jorge

last: Lariosf

first: Claudia

last: Aldeia

first: Edgar

last: Campos-Madueno

first: Dimitri

last: Vanhecke

first: Patrice

last: Nordmann

first: Vincent

last: Cattoir

first: Laurent

last: Poirel