title: Nascent chain misfolding slows translation and stimulates co-translational mRNA decay

city: Baltimore

first: Jeff

last: Coller

state: MD

address: 725 N Wolfe St

institute: Johns Hopkins University

summary: Ribosome dynamics during mRNA translation elongation regulate mRNA stability. Yet, codon usage, a known regulator of ribosome transit, cannot fully explain transcriptome-wide decay rates. Here, we demonstrate that nascent polypeptide folding modulates elongation rates, with Zuotin (Zuo1) serving as an essential mediator. Using reporter constructs and RNA sequencing, we show that Zuo1 is essential for the selective destabilization of transcripts encoding co-translationally misfolded proteins. This process is independent of codon optimality but relies on co-translational mRNA decay factor Not5, which detects slowed ribosomes. Ribosome profiling reveals that global protein misfolding induces Zuo1-dependent ribosome stalling. 35S labeling confirms that nascent peptide misfolding directly slows elongating ribosomes in a Zuo1-dependent manner. These findings highlight Zuo1 as a pivotal mediator linking nascent peptide folding to ribosome dynamics and thereby mRNA stability, unveiling a novel mechanism of mRNA regulation driven by protein products. Furthermore, this work expands Not5’s role beyond codon optimality sensing.

overall_design: RNA-seq profiling of wild-type, zuo1, and not5 S288C yeast grown at room temperature, treated with L-azetidine-2-carboxylic acid (AZC) or vehicle (sterile water, as control) for 45 minutes.

first: Suhee

last: Chang

first: Ryan

last: Kawalerski

first: Sophie

last: Martin


title: Cardiac fibroblast deletion of PTBP1 modulates the profibrotic response by alternative splicing.

status: Public on Jun 01 2026

city: Chapel Hill

first: Shea

middle: N

last: Ricketts

state: NC

address: 111 Mason Farm Road

department: Pathology and Laboratory Medicine

country: USA

institute: UNC Chapel Hill

type: Expression profiling by high throughput sequencing

summary: In this project we investigate the role of RNA binding protein PTBP1 in cardiac fibrosis through the conditional deletion of PTBP1 in mouse cardiac fibroblasts. We isolated cardiac fibroblasts from Ptbp1fl/fl mice, deleted PTBP1 with Adenoviral-Cre, and stimulated cardiac fibroblasts with TGFb to perform deep RNA sequencing studies on the cardiac fibroblast to myofibroblast transformation.

overall_design: RNAseq profiling of PTBP1 depleted cardiac fibroblasts with wildtype controls with and without profibrotic stimulation via TGFb. RNA was isolated with Qiagen RNeasy Plus Mini Kit according manufacturers protocol. Three independent biological replicates were used for each experimental group and deep sequencing studies were performed to quantify transcript expression and alternative splicing isoform abundance.

first: Li

last: Qian


title: Yap/Taz function as new mediators of FGF signaling in neural crest-derived cranial suture mesenchymal cells [RNA-seq]

city: Houston

first: Jun

last: Wang

state: TX

address: 6431 Fannin Street

department: Department of Pediatrics  MSB.3.236B

institute: The University of Texas Health Science Center at Houston

summary: Cranial suture mesenchymal cells (SMCs), housed by the cranial suture, are required to maintain suture homeostasis and contribute to cranial bone growth, repair, and regeneration. Although their roles in craniofacial development are well-studied, how their functions are orchestrated by intricate signaling networks remain largely unknown. The Fibroblast growth factor (FGF) signaling pathway is a fundamental pathway involved in multiple key cell processes, including stem cell pluripotency and differentiation, and contributes extensively to cranial suture development and homeostasis, yet their precise roles in SMCs are still limited. Neural crest cells (NCCs), a multipotent stem cell population, greatly contribute to craniofacial and suture development, while a big knowledge gap remains regarding the molecular regulation of NCC-derived SMCs. Using NCC-derived SMCs from the frontal sutures of mice as a model, we identified the Hippo signaling downstream effectors, Yap/Taz, as novel mediators of FGF signaling in NCC-derived SMCs. Our data demonstrated that the activation of FGF signaling inhibited osteogenesis in NCC-derived SMC while enhancing their stemness and proliferation by promoting Yap nuclear translocation through pERK1/2, which could be reversed by Yap/Taz deficiency or pERK1/2 inhibition. Additionally, we uncovered a novel interaction between Yap and pERK1/2, and our data suggested that pERK1/2 promote Yap nuclear translocation by phosphorylating Yap at the S128 site to modulate Yap chromatin occupancy on related key Yap targets. Collectively, our data provided the first evidence that FGF signaling regulates the balance between stemness and osteogenesis of NCC-derived SMCs through Yap/Taz. These findings reveal a novel molecular mechanism in NCC-derived SMCs, advancing our understanding of stem cell biology and opening a new avenue for exploring diagnostic and therapeutic methods for craniofacial-related diseases

overall_design: RNA-seq profiling of wildtyoe O9-1 neural crest cells and their knockdown derivatives (siY/T) at d2.5 and d5 of osteobalst differenitation.

first: Zhao

last: Xiaolei

first: Tang

last: Li

first: Chen

last: Xiaotong

first: Wang

last: Jun


title: Yap/Taz function as new mediators of FGF signaling in neural crest-derived cranial suture mesenchymal cells [CUT&Tag]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: The Cleavage Under Targets and Tagmentation (CUT&Tag)-seq of Yap, H3K4me3 and IgG in nuclei of O9-1 neural crest cells with siRNA-induced knockdown of Yap and Taz and FGF2 ligand treatment.


title: Glucagon-like peptide-1 receptor agonist prevents pulmonary fibrosis following acute COVID-19 infection associated with type 2 diabetes

city: Hong Kong

first: Ming

last: Yue

address: 21 Sassoon Road, Pokfulam

country: China

institute: The University of Hong Kong

summary: Post-acute sequelae of COVID-19 (PASC) posts a major health burden after SARS-CoV-2 infection. Although type 2 diabetes (T2D) is associated with PASC, the mechanism of T2D-mediated PASC in lung remains elusive. Here we found that people with T2D (PWT2D) exhibited significantly upregulated fibrosis-related genes in monocytes, which correlated positively with pulmonary fibrosis-related biomarkers up to 3 months after acute SARS-CoV-2 infection. Using db/db mice to model human T2D, we found consistently that SARS-CoV-2 infection resulted in upregulation of fibrosis-related genes in lung macrophages and persistent pulmonary fibrosis. Moreover, the macrophage-depletion demonstrated that proinflammatory macrophages in db/db mice were determinants for inducing the pulmonary fibrosis post-infection. Importantly, the anti-T2D glucagon-like peptide-1 receptor agonist (GLP-1RA) reprogramed macrophage responses to SARS-CoV-2 by normalizing fibrosis-related genes, significantly reducing the pulmonary fibrosis in a glucose-independent manner. These findings demonstrated that SARS-CoV-2-induced proinflammatory macrophages are detrimental factors in T2D-mediated PASC, which can be prevented by GLP-1RA.

overall_design: Infected bone marrow-derived macrophages (BMDM) isolated from db/+ and db/db mice by SARS-CoV-2 (MOI: 1) in the presence of ctrl-Fc or GLP1-Fc.

first: Runhong

last: Zhou

first: Qing

last: Shen

first: Zhiwei

last: Chen


title: Single cell transcriptome of Clec3b-lineage cells in fracture callus and uninjured muscle

city: New York

first: Ugur

last: Ayturk

state: NY

address: 533 East 70th St.

institute: Hospital for Special Surgery

summary: Clec3b-expression marks interstitial muscle cells. We performed single cell RNA-seq on Clec3b-lineage cells obtained from the upper hindlimb of mice, before and after femoral fracture.

overall_design: Male Clec3b.creERT; Ai14.R26.tdTomato mice (n=3) were subjected to stabilized femoral fracture surgery on their right leg, 2 weeks after tamoxifen induction. Femoral bone and muscle specimens were collected separately from the intact and injured limbs 3 weeks after surgery. tdTomato+ cells were purified from pooled intact and fracture specimens using flow cytometry and processed for 10X single cell RNA-seq.

first: Jacob

last: Moore

first: Ezgi

last: Aydin

first: Kristin

last: Gebauer


title: Adrenal-derived factors drive progression of sclerotic prostate cancer  in bone

status: Public on May 31 2026

city: Gothenburg

first: Malin

last: Hagberg Thulin

address: Vita straket 11

department: Institute of medicine

country: Sweden

institute: University of Gothenburg

summary: Bone metastasis is a leading cause of death in prostate cancer (PC) patients. Although androgen‐deprivation therapy (ADT) combined with novel androgen‐targeted agents constitutes the cornerstone of systemic treatment, its efficacy is limited. We investigated the adrenal contribution in promoting progression of castration-resistant PC (CRPC) within bone using a preclinical intratibial xenograft model (VCaP, 22Rv1, and LNCaP cells). Mice underwent orchiectomy (ORX) to mimic ADT, with or without adrenalectomy (ORX+ADX) to eliminate adrenal contribution. A significant increase in bone mineral density (BMD) was observed in tumor-grafted tibiae in ORX-treated mice compared to controls (p<0.001), indicating a strong tumor-induced sclerotic response. In contrast, ORX+ADX reduced tumor take rate by approximately 50% and decreased tumor-induced BMD by over 80% (p<0.001). Transcriptomic analysis revealed that ADX downregulated tumor-induced transcripts in bone by over 90%, including osteogenic (Lox, Sparcl1, Bmp2, Postn, Col1a1) and pro-angiogenic (Bmper, Pecam-1, Esam) signatures. Additionally, BMP, PI3K/Akt and ERK1/2 signaling pathways were associated with the tumor-induced bone response. Both high serum progesterone and intratumoral levels of dihydrotestosterone (DHT) were associated with the sclerotic bone phenotype. ADX markedly reduced intratumoral DHT and downregulated glycolytic genes (HK2, PFK2, LDHA) and secretory proteins expressed by the tumor, including Stanniocalcin 2, potentially mediating paracrine effects in the sclerotic bone response. Altogether, these findings highlight the critical role of adrenal- dependent androgen synthesis, particularly via progesterone, in driving the sclerotic CRPC in bone. Our findings suggest that a comprehensive blockade of adrenal contribution is essential to prevent the sclerotic bone response associated with CRPC.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq profiling of VCaP intratibial xenografts in Balb/c nude mice subjected to orchiectomy (ORX) to model androgen deprivation therapy (ADT), with or without adrenalectomy (ORX+ADX) to ablate adrenal steroid contributions.

first: Matti

last: Poutanen


title: Observe the role of AQP1 gene overexpression in the RENCA cell line

city: Dalian

first: Shuo

last: Pang

address: No. 9, West Section of Lushun South Road

department: Urology

institute: The First Affiliated Hospital of Dalian Medical University

summary: Aquaporin-1 (AQP1) has been implicated in tumor progression, including cell migration, invasion, and angiogenesis in various cancers, but its specific role in renal clear cell carcinoma remains incompletely understood. To investigate the transcriptomic changes associated with AQP1 overexpression in renal cancer, we generated stable AQP1-overexpressing RENCA cells (a murine renal cell carcinoma cell line) and corresponding negative control cells using lentiviral transduction. Two weeks post-transduction, total RNA was extracted from three biological replicates per group and subjected to paired-end high-throughput RNA sequencing (RNA-seq).  This dataset provides transcriptome profiles comparing AQP1-overexpressing RENCA cells to negative control cells, aiming to identify differentially expressed genes, pathways, and potential mechanisms by which AQP1 influences renal cancer biology. The data may facilitate further studies on AQP1 as a therapeutic target or biomarker in renal clear cell carcinoma.

overall_design: Paired-end RNA sequencing was performed on total RNA from three biological replicates each of murine RENCA renal cell carcinoma cells with stable lentiviral-mediated AQP1 overexpression and negative control cells, two weeks post-transduction.

first: Jianbo


title: Targeting the Calcineurin Homologous Protein 1 (CHP1)-Transmembrane Protein 87A (TMEM87A) Mechanosensing Complex: A Druggable Vulnerability in Metastatic Ovarian Cancer

city: Shanghai

first: Mingzhu

last: Jin

state: Shanghai

address: PuJian Rd 160

institute: Renji Hospital, Shanghai Jiao Tong University School of Medicine

summary: Bulk RNA-seq was performed to investigate transcriptomic changes upon CRISPR-mediated knockout of CHP1 or TMEM87A in OVCAR8 human ovarian cancer cells (in vitro), and to assess the effect of gluconate treatment versus PBS control in an OVCAR8-NSG orthotopic tumor model (in vivo). Three independent biological replicates were profiled per condition.

overall_design: Three experimental groups were profiled by bulk RNA-seq: (1) OVCAR8 cells stably expressing sgNC (non-targeting control, n=3) vs sgCHP1 (CHP1 knockout, n=3); (2) OVCAR8 cells stably expressing sgNC (non-targeting control, n=3) vs sgTMEM87A (TMEM87A knockout, n=3); (3) OVCAR8-NSG orthotopic tumors treated with PBS (vehicle control, n=4) vs gluconate (n=4). All samples were sequenced by paired-end 150 bp RNA-seq (polyA selection) on Illumina NovaSeq 6000.

first: Hengan

last: Liu

first: Wen

last: Di


title: Spatially resolved, integrated single-cell multiomic profiling of the transcriptome and epigenomic targets in frozen tissue sections

city: Rochester

first: Yuanhang

state: MN

address: 200 1ST ST SW

institute: Mayo Clinic

summary: We present a spatial Trekker–CUT&Tag multiome protocol that combines direct spatial barcoding of a frozen tissue section with subsequent single-cell multiome analysis. This approach enables integrated single-cell and spatial profiling of histone H3K27ac modification and gene expression, revealing mechanistic and anatomical cell-type organization across the tissue.

overall_design: Mouse brain tissue was Mounted onto the Trekker barcode tile for spatial barcoding. Tissue dissociation and nuclei isolation was performed. CUT&Tag tagmentation with H3K27ac was performed on isolated nuclei. Single cell barcoding of tagmented nuclei and pre-amplification of barcoded DNAs was performed. Library preparation was constructed for CUT&Tag, gene expression, and spatial barcode followed by next generation sequencing.

first: Ting

last: Zhang

first: Saba

last: Farassati

first: Alejandro

last: Quiroz

first: Tamas

last: Ordog

first: Jeong-Heon

last: Lee


title: The ER Anchoring and Abundance of the EEF1B Complex is Affected by Tissue Specific Alternative EEF1D Spicing

city: Sendai

first: Masaki

last: Hosogane

state: Miyagi

address: 2-1 Seiryo-machi, Aoba-ku

country: Japan

institute: Tohoku university

summary: The EEF1B complex plays a central role in translation elongation by reactivating EEF1A for delivery of aminoacyl-tRNAs to the ribosome. Among its components, EEF1D undergoes alternative splicing to produce one long and several short isoforms, each with distinct N-terminal domains and tissue-specific expression patterns. Although the short isoforms are broadly expressed, their functional significance has remained unclear. In this study, we show that short EEF1D isoforms containing exon 5 interact with endoplasmic reticulum (ER)-resident scaffold protein KTN1 and RRBP1, thereby anchoring the EEF1B complex to the ER. Mass spectrometry of FLAG-tagged EEF1D identified these interactions, and deletion of exon 5 disrupted ER anchoring, resulting in diffuse cytoplasmic localization of the EEF1B complex. In exon 5 knockout mice, this altered localization was accompanied by reduced EEF1B subunit abundance in multiple tissues, including liver, although global protein synthesis rates remained unaffected. These findings uncover an ER-anchoring mechanism controlled by alternative splicing that shapes the spatial organization and abundance of the elongation machinery in vivo.

overall_design: Ribo-seq together with RNA-seq (for normalization of Ribo-seq reads) of Eef1d exon 5 knockout Hepa1-6 cells.


title: MicroRNA-200 family inhibits sebaceous gland fate specification by disrupting SOX9 function [Spatial Transcriptomics]

city: Chicago

first: Arpan

last: Das

state: IL

address: 303 E Chicago Ave

department: Pathology

institute: Northwestern University

summary: Hair follcile (HF) are known as mini-organs because of their cycling capability. They also provide an excellent system to study the developmental timeline of these appendages, regulated by multiple factors. However, how another skin appendage, sebaceous gland (SG), associated with the HFs gets specified from the HF-cells is largely unknown. Here using an integrated method we demonstrate how SOX9+ early progenitor cells regulate the fate specification of the SG.

overall_design: Mouse dorsal skin at P3 stage were fixed using FFPE protocol and then sectioned and analyzed using 10X Visium v1 FFPE ST.

first: Rui

last: Yi


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

first: Ali

last: Shilatifard

address: 320 E Superior St

department: Department of Biochemistry and Molecular Genetics

institute: Northwestern University Feinberg School of Medicine

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

overall_design: Cleavage under targets and release using nuclease (CUT&Run) of Med23 and Ser2P in mouse liver

first: Saeid

middle: M

last: Parast

first: Madhurima

first: Marta

last: Iwanaszko


title: MicroRNA-200 family inhibits sebaceous gland fate specification by disrupting SOX9 function [scRNA-seq]

overall_design: Total dorsalskin from mice of P3 was dissociated with dispase for 1 hour at 37C and the epidermis (Epi) was peeled off and treated with trypsin for 8 min at 37 C. The dermal layer (Der) that contains the HFs was treated with collagenase for 1 hour at 37C followed by trypsinization for 8 min at 37C. Single cell suspesion was obtained by mixing Epi and Der to a ratio of 30:70 and  loaded onto 10x Genomics single cell transcriptome profiling platform.


title: MicroRNA-200 family inhibits sebaceous gland fate specification by disrupting SOX9 function [scATAC-seq]

overall_design: Total dorsalskin from mice of E18 was dissociated with dispase for 1 hour at 37C and the epidermis (Epi) was peeled off and treated with trypsin for 8 min at 37 C. The dermal layer (Der) that contains the HFs was treated with collagenase for 1 hour at 37C followed by trypsinization for 8 min at 37C. Single cell suspesion was obtained by mixing Epi and Der to a ratio of 80:20 and  loaded onto 10x Genomics single cell ATAC-seq profiling platform.


title: The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart

status: Public on May 29 2026

first: Richard

last: Lutze

address: 111 Mason Farm Rd

department: MHI

institute: University of North Carolina at Chapel Hill

summary: Trametinib (Trm) is a highly selective MEK inhibitor that potently and persistently abrogates ERK1/2 activation. Trm initially was used to treat BRAF V600E-mutated melanoma but its FDA-approved indications are expanding rapidly. Trm generally is well tolerated but it can cause dose-limiting cardiomyopathy and heart failure. Here we characterize a mouse model of Trm cardiotoxicity using complementary in vitro approaches to show that Trm induces mitochondrial dysfunction in cardiomyocytes and some cancer cell types. In vivo, Trm caused contractile dysfunction within 3 days and heart failure within 2 weeks. High resolution respirometry using isolated cardiac mitochondria revealed that Trm compromises oxidative metabolism, in part through blunted activity of Electron Transport System Complexes. Trm-mediated mitochondrial injury led to the release of mitochondrial Damage-Associated Molecular Patterns including mitochondrial DNA in both mice and humans, triggering activation of canonical innate immune pathways including cGAS-STING. In multiple rodent and human cardiomyocyte platforms, Trm diminished mitochondrial respiratory capacity at nanomolar concentrations but this lesion was reversed by expression of a phosphomimetic STAT3-S727 construct. We also found that Trm induced mitochondrial dysfunction in some but not all cancer cell lines, identifying a previously unrecognized effect that could contribute to Trm’s anti-cancer efficacy.

overall_design: RNA-seq profiling of hearts from 12-16 week old WT female FVB mice treated with vehicle or Trametinib (3mg/kg) for 14 days, once daily.


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

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

overall_design: Refer to individual Series


title: MicroRNA-200 family inhibits sebaceous gland fate specification by disrupting SOX9 function [Cut&Run]

overall_design: Dorsal skin samples from three P3 animals with Krt14-H2BGFP allele were first digested with Dispase for an hour and epidermal cells were peeled off. Remaining dermal fraction with HFs were then digested with Collagenase IV for 90 mins at 37C. Krt14-H2BGFP/Hoechst-lo cells were then sorted and used for Sox9 Cut-&-Run library preparation.


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

overall_design: Chromatin immunoprecipitarion of DNA-sequencing (ChIP-seq) for Pol2


title: AGO1 and AGO2 immunoprecipitation / small RNA seq from Arabidopsis thaliana stems adjacent to Cuscuta campestris haustoria

city: University Park

first: Michael

middle: J

last: Axtell

state: PA

address: 280 Mueller Lab

department: Biology

institute: Pennsylvania State University

type: Non-coding RNA profiling by high throughput sequencing

summary: The obligate parasitic plant Cuscuta campestris delivers trans-species microRNAs (miRNAs) into host plants to silence host mRNAs. Here, the genetic requirements for biogenesis, movement, and function of these miRNAs were investigated. Primary miRNA transcript accumulation precedes mature miRNA accumulation by 24 to 48 hours. Trans-species miRNAs accumulate in host tissues a short distance from the site of parasite attachment. Trans-species miRNAs require C. campestris but not host Dicer-Like 1 (DCL1) for accumulation. These miRNAs specifically avoid Argonaute (AGO) loading in C. campestris tissue where they instead accumulate as miRNA/miRNA* duplexes. After arrival and short-distance spreading in host tissues, they are loaded onto host AGO proteins including AGO1 and AGO2. This study clarifies the transcription, dicing, delivery, and function of C. campestris trans-species miRNAs. We propose that selective avoidance of self AGO-loading is a mechanism to facilitate high rates of delivery of these "export only" miRNAs to host tissues.

overall_design: PAGO1::3XHA-AGO1 / ago1-36 (-/-)28 and pAGO2::3XHA-AGO2 / ago2-1 (-/-)29 plants were grown in long day conditions (16 hours light / 8 hours dark) until the inflorescence stems reached at least 15 centimeters. Three-day-old C. campestris seedlings were attached to the inflorescence stem, with ten10 attachments per plant. C. campestris was allowed to establish and grow for ten10 days. C. campestris tissue was then peeled away and the A. thaliana stem tissue beneath each attachment site was collected. Approximately 400 such stem segments were pooled for each biological replicate.


title: Trans-kingdom, rapid, affordable Purification of RISCs (TraPR) enrichment of small RNAs from Cuscuta campestris in vitro haustoria and flanking host stems of Arabidopsis thaliana

sample_organism:
Arabidopsis thaliana
Cuscuta campestris

platform_organism:
Arabidopsis thaliana
Cuscuta campestris

overall_design: Host-induced haustoria were established on A. thaliana inflorescence stems for ten days under far-red light enriched conditions. Each inflorescence stem supported approximately ten attachments. Stems were excised above and below each attachment site, avoiding inclusion of C. campestris tissue. Each stem segment measured approximately 2-3 millimeters in length. For each biological replicate, 30 to 40 stem segments (~80 milligrams total) were pooled. For in vitro haustoria, a total of 60 to 70 C. campestris seedlings were used to induce approximately 50 milligrams of in vitro haustorial tissue for each biological replicate.


title: Small RNA-seq from the parasitic plant Cuscuta campestris during infestation of Nicotiana benthamiana

sample_organism:
Nicotiana benthamiana
Cuscuta campestris

overall_design: N. benthamiana  host plants were grown under long-day conditions (16 hours light / 8 hours dark) and watered weekly with a fertilizer supplement for four to five weeks prior to parasite attachment. C. campestris seeds were scarified in sulfuric acid for one hour, with gentle swirling every 20 minutes to ensure even exposure. After scarification, seeds were placed on moist tissue paper folded into a Petri dish and incubated at 30°C under long-day conditions supplemented with far-red light for 2.5 to 3 days. Sprouted parasite seedlings were attached to N. benthamiana petioles by placing with surgical tape. Specimens were allowed to attach a grow for approximately 10 days after attachment before harvesting. Total RNA was extracted and sRNA-seq libraries were constructed and analyzed.


title: USP18 impacts on platinum-resistance in ovarian cancer cells by modulating DNA repair

city: Milano

first: Paola

last: Perego

address: via Amadeo 42

country: Italy

institute: Fondazione IRCCS Istituto Nazionale dei Tumori

summary: Aims: Deubiquitinases (DUBs) are proteases with emerging roles in cancer progression and therapy resistance, yet their contribution to drug resistance in ovarian cancer remains underexplored. Ovarian cancer patients often fail to benefit from platinum-based therapy, highlighting the need to identify novel factors involved in drug resistance. To this end we performed a CRISPR/Cas9 screen targeting DUB family to identify genes essential for platinum- resistant ovarian carcinoma cell survival. Methods: A CRISPR/CAS9 DUB knockout screen was performed on IGROV-1 parental and platinum-resistant ovarian carcinoma cells. Preclinical pharmacology approaches were also applied. Results: We identified USP18 as a survival factor in platinum-resistant ovarian cancer cells. USP18 expression was elevated at the mRNA and protein levels across five platinum-resistant cell lines. Knockdown and CRISPR/CAS9 editing of USP18 sensitized cells to cisplatin, coinciding with impaired repair of cisplatin-induced DNA damage. RNA-seq of USP18 RNA interfered and edited cells revealed the modulation of pathways including DNA repair. A peptide-based USP18 inhibitor suppressed growth of resistant cells, supporting its role in sustaining the growth of platinum-resistant cells. Conclusion: We identified USP18 as a novel mediator of platinum resistance in ovarian cancer, through modulating DNA repair. Targeting USP18 may offer a therapeutic strategy to improve outcomes in platinum-resistant ovarian cancer.

overall_design: (1) RNA-seq of USP18 knockdown (KD) in IGROV-1/Pt1, PEO4, and A2780CO cells: untransfected or transfected with negative control siRNA, siRNAb, or siRNAc. (2) RNA-seq of USP18 knockout (CRISPR/Cas9) (KO) in IGROV-1/Pt1 cells: control, wild type clones (C7, E10), KO clones (C2, C14)

first: Cristina

last: Corno

first: Mathilde

last: Robin

first: Diego

last: Tosi


title: Early-life stress alters chromatin modifications in VTA to prime stress sensitivity

city: Princeton

first: Catherine

middle: Jensen

last: Pena

state: NJ

address: Washington Road

department: Neuroscience

institute: Princeton University

summary: Early-life stress increases sensitivity to subsequent stress, which has been observed at behavioral, neural activity, and gene expression levels. However, the molecular mechanisms underlying such long-lasting sensitivity are poorly understood. We tested the hypothesis that persistent changes in transcription and transcriptional potential were maintained at the level of the epigenome, through changes in chromatin. We used a combination of bottom-up mass spectrometry, viral-mediated epigenome-editing, RNA-sequencing, patch clamp electrophysiology of dopamine neurons, and behavioral quantification in a mouse model of early-life stress, focusing on the ventral tegmental area (VTA), a dopaminergic brain region critically implicated in motivation, reward learning, stress response, and mood and drug disorders. We found that early-life stress alters histone dynamics in VTA, including enrichment of histone-3 lysine-4 monomethylation — associated with open chromatin and primed or active enhancers — and the H3K4 monomethylase Setd7. Mimicking early-life stress through postnatal overexpression of Setd7 and enrichment of H3K4me1 in VTA sensitizes transcriptional, physiological, and behavioral response to adult stress, while knocking down Setd7 ameliorates the impact of ELS. These findings link early-life stress experience to long-term stress hypersensitivity within the brain's dopaminergic circuitry, providing a mechanism by which early-life stress increases risk for mood and anxiety disorders later in life.

overall_design: Setd7 was overexpressed in mouse ventral tegmental area (VTA) at P14; VTA tissue punches were taken for bulk RNA-sequencing in adulthood with or without exposure to adult social defeat stress.

first: Julie-Anne

last: Balouek


title: A dish-to-biobank framework links β-cell nutrient-stress programs to genetic and dietary risk for Type 2 Diabetes

status: Public on May 28 2026

city: New York City

last: Hu

address: 430 East 67th Street

department: Developmental biology

institute: Sloan Kettering Institute

summary: Type 2 diabetes (T2D) arises from genetic susceptibility and chronic metabolic stress, but whether these converge on shared molecular programs in human populations remains unclear. Here, we develop a dish-to-biobank framework linking controlled β-cell perturbation to population-scale disease genetics through the circulating plasma proteome, and apply it to T2D. scRNA-seq of human stem cell–derived islets under factorial glucose and palmitate exposure identifies their combination (glucolipotoxicity) as the condition eliciting the strongest SC-β cell transcriptional response, with glucolipotoxicity-upregulated genes uniquely enriched for T2D heritability, monogenic diabetes genes, and rare-variant burden signals. CRISPR knockout of β-cell identity regulators PAX6 and PDX1 aligns with this program, establishing convergence of environmental and genetic perturbations on a shared disease-relevant state. We then used the plasma proteome as an accessible population-scale readout of these experimentally defined β-cell stress programs, scoring 45,956 UK Biobank White British participants. We define heritable stress signatures that associate with refined carbohydrate and saturated fat intake, and undergo trans-tissue genetic regulation, with a subset of variants showing diet-dependent effects. Together, these findings establish glucolipotoxicity as a genetically anchored model of β-cell dysfunction and provide a generalizable framework for linking controlled cellular perturbations to human disease genetics at population scale.

overall_design: A single differentiation of XM001 was performed; at stage 6 day 14 the resulting SC-islet pool was divided into six aliquots, each assigned to one nutrient-stress condition and treated independently for 72 h. The 4 primary nutrient stress conditions were (i) 8 mM glucose + BSA vehicle control (Cayman Chemical, 29556), (ii) 8 mM glucose + 1 mM BSA-conjugated palmitate (Cayman Chemical, 29558), (iii) 33 mM glucose + BSA vehicle control, and (iv) 33 mM glucose + 1 mM BSA-conjugated palmitate. Additionally, we included 2 secondary stress experiments comprising 8 mM glucose (no BSA) and 33 mM glucose (no BSA).  After 72 h of treatment, SC-islets were dissociated into single cells, collected and cryopreserved in Bambanker cell freezing medium (Fujifilm, 302-14681). On the day of scRNA-seq library preparation, frozen cells were thawed at 37°C , resuspended in PBS containing 2% BSA and then incubated with Live/Dead Fixable Violet Dead cell stain (Invitrogen, L34955) in FACS buffer for 15 minutes at room temperature. Live cells were sorted by FACS and loaded onto the Chromium Controller with a targeted collection of 10,000 cells per reaction (10x Genomics Chromium Single Cell 3′ Reagent Kit v3.1 User Guide). cDNA and sequencing libraries were prepared according to the manufacturer’s instructions and sequenced on NovaSeq 6000 platform.

first: Xianming

last: Wang

first: Berk

last: Turhan

first: Kushal

last: Dey

first: Danwei

last: Huangfu


title: RNA seq analysis comparing uninfected to MCPyV-infected 2D monolayer or 3D spheroids

city: Hershey

first: Hyun Jin

last: Kwun

address: 500 University Drive

department: Microbiology and Immunology

institute: Penn State Milton S. Hershey Medical Center

summary: Human tumor virus infections account for ~10% of the world’s cancer cases. However, studies on the life cycle of small DNA tumor viruses have been hampered primarily due to the lack of virus culture systems that allow for robust replication and high-level infection in host cells. Thus, studies involving Merkel cell polyomavirus (MCPyV), a human oncogenic polyomavirus, infections primarily rely on utilizing quasiviruses, virions produced through the artificial complementation of the viral genome with exogenous MCPyV proteins. However, recombinant quasiviruses might not fully reflect the native MCPyV virions or infection conditions. To mimic the natural skin infection of MCPyV, we developed a simple and efficient method for producing MCPyV virions derived from primary human dermal fibroblasts without the requirement for exogenous MCPyV protein supplementation using a 3D spheroid culture system. Here, we found that the 3D spheroid microenvironment enabled the production of MCPyV virions and their release into the supernatant that were packaged inside of extracellular vesicles (EVs) from natural host cells. This demonstrates that the physical properties within the skin structure influence how MCPyV establishes a unique infectious life cycle by avoiding host immune surveillance. We propose the use of 3D spheroids as a novel cell culture system to recapitulate the MCPyV life cycle and establish a skin infection, a feature which has been challenging to accomplish in the field.

overall_design: Mock- or MCPyV-infected human neonatal dermal fibroblast were cultured as a monolayer or as a 3D spheroid. Samples were harvested 4 days after infection for RNA Seq Analysis.

first: Alexander

last: Pham


title: Lineage tracing reveals photoreceptor precursor cell subpopulations that contribute to murine retinogenesis

city: Philadelphia

first: Katherine

last: Uyhazi

state: Pennsylvania

address: 422 Curie Blvd

institute: University of Pennsylvania

summary: Cell-based therapies hold great promise for treating late-stage retinal degenerative diseases. However, photoreceptor cell transplantation has been limited by poor cellular integration, suggesting that an ideal population of donor cells has not yet been defined. Here, we utilized single-cell RNA-sequencing to assess the heterogeneity of photoreceptor precursor cells during murine retinal development. Subgroup analysis revealed three transcriptionally and spatially distinct populations of Crx+ cells from postnatal day 2-6 retinas which are consistent with early (Dll1+), intermediate (Neurod4+), and late (Prom1+) photoreceptor precursor cells. Lineage tracing with subpopulation-specific Cre mice showed that Dll1+, Neurod4+, and Prom1+ cells all generate photoreceptor cells but exhibit a spectrum of developmental plasticity. Transcriptomic analysis revealed that homologous CRX+ subpopulations are present in maturing human retinal organoids. These findings highlight the heterogeneity of neonatal photoreceptor precursor cells, and could help inform future strategies to isolate an optimal population of cells for retinal regeneration.

overall_design: Neurosensory retinas were harvested from wild type mice at ages embryonic day (E) 14, E16, postnatal day (P) 0, P3, and P6. Cell suspensions were prepared by papain dissociation and FACS purification, and samples were then profiled by single-cell RNA-sequencing.

first: Joseph

last: Yano

middle: E


title: A Novel CRYBB2 Splicing Mutation Is Associated with Lens Extracellular Matrix Remodeling and Vascular Alterations in Congenital Cataract

city: Chengdu

first: Xing

last: Wei

state: --- Select One ---

address: No. 20, Section 3, Renmin South Road

institute: West China Second University Hospital

summary: Purpose: We identify the genetic cause of autosomal dominant congenital cataract in a large family and to define how a CRYBB2 splice-site variant perturbs lens development and associated ocular phenotypes. Methods: Whole-exome sequencing and Sanger sequencing were used for variant identification and segregation. Wild-type (WT) or mutant CRYBB2 was expressed in lens epithelial cells to assess splicing and downstream transcriptional changes by RNA sequencing and qRT-PCR. Extracellular matrix (ECM) organization and cell–matrix interactions were examined by immunostaining and adhesion assays. In zebrafish, crybb2 disruption was evaluated using lens structural assays, hyaloid vasculature imaging in Tg(flk1:EGFP) larvae, tracer distribution assays, and mRNA rescue. Single-cell RNA sequencing at 48 hpf was performed to profile lens and vascular populations and infer pathway-level changes. Results: We identified a novel CRYBB2 splice-site variant in affected members of a family with congenital cataract, consistent with an association with the disease in this pedigree. The variant disrupted normal splicing and was associated with altered βB2-crystallin–linked transcriptional programs and ECM homeostasis, including changes in collagen IV/laminin deposition and impaired cell–matrix adhesion. In zebrafish, crybb2 disruption caused lens fiber cell differentiation defects and was accompanied by abnormal hyaloid vascular patterning and altered tracer distribution around the lens; these phenotypes were partially improved by crybb2 mRNA rescue. Single-cell transcriptomic analyses suggested coordinated changes in ECM and junction/adhesion-related pathways across lens and vascular compartments, consistent with a lens-associated, non-cell-autonomous influence on adjacent vasculature. Conclusions: A novel CRYBB2 splice-site mutation is associated with autosomal dominant congenital cataract and disrupts lens homeostasis with accompanying changes in hyaloid vascular remodeling. These findings expand the pathogenic spectrum of CRYBB2 and support a model in which lens abnormalities are associated with altered lens–vascular interactions during development.

overall_design:
Single-cell RNA sequencing was performed on zebrafish embryos at 48 hours post fertilization (hpf) from wild-type and Crybb2 mutant groups. Approximately 200 embryos per group were dissociated into single-cell suspensions and processed using the 10x Genomics Chromium platform. Libraries were generated using the Chromium Single Cell 3’ Reagent Kit (v3.1) and sequenced on an Illumina NovaSeq 6000. Raw data were processed with Cell Ranger (v6.0.1) against the zebrafish GRCz11 reference genome, and downstream analyses were conducted using Seurat (v4.1.0).

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The table below lists GEO accessions reused/reanalyzed for this study.
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first: Jing

first: Yanyun

first: Cong

last: Zhou

first: Zhaoyi

last: Chen

first: Shanling

last: Liu

first: Huaqin

last: Sun

first: Bin

first: Lin

last: Zhang


title: Depletion of endothelial KLF4 drives age-related neurovascular dysfunction and neuropsychiatric impairment [ChIP-Seq]

city: Providence

first: Tapatee

last: das

state: RI

address: 11 Almuni Ave ,Apt# 16,

department: mcb

institute: Brown University

summary: Brain aging is associated with neurovascular uncoupling, blood-brain barrier (BBB) dysfunction, neuroinflammation, and cognitive decline. Brain endothelial cells are essential for maintaining BBB integrity and neurovascular homeostasis and are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because endothelial KLF4 expression declines with aging, we investigated whether endothelial KLF4 depletion contributes to age-associated neurovascular dysfunction and neuropsychiatric impairment.

overall_design: RNA Polymerase II ChIP-seq was performed on purified brain endothelial chromatin from endothelial-specific Klf4 knockout (EC-K4KO) and WT Cre mice to profile active transcriptional programs associated with endothelial aging and neurovascular dysfunction. Integration with ATAC-seq and RNA-seq datasets identified actively transcribed chromatin regions linked to inflammatory, stress-response, and senescence-associated pathways.

first: Matasha

last: Dhar

first: Edwin

last: Vázquez-Rosa

first: Kalyani

last: Chaubey

first: Emiko Miller

last: Sofia Corella

first: Suwarna

last: Chakraborty

first: Sunil

last: Tripathi

last: Das

first: Xudong

last: Liao

first: Mohamed

last: Alkassem Alosman

first: Hua Fang

last: Yeojung Koh

first: Preethy

middle: S

last: Sridharan

first: Kathryn

last: Franke

first: Coral

last: Cintrón-Pérez

first: Adrian

first: Taylor

last: Tomco

first: Vidya

last: Indrakumar

first: Phoebe

last: Rubin

first: Justin

middle: G

last: Pieper

first: Luke

middle: A

last: Ashiku

first: Min-Kyoo

last: Shin

first: Xinmiao

last: Tang

first: Roshan

last: Padmanabhan

first: Margaret

last: Flanagan

first: Rajan

last: Jain

first: Bradley

middle: D

last: Winters

first: Brigid

last: Wilson

first: Bindu

last: Paul

first: Mukesh

middle: K

first: Andrew


title: Depletion of endothelial KLF4 drives age-related neurovascular dysfunction and neuropsychiatric impairment [scRNA-seq]

first: Tapatee

last: das

overall_design: Single-cell RNA sequencing was performed on brain cells isolated from young and aged endothelial-specific Klf4 knockout (EC-K4KO) and WT Cre mice to characterize transcriptional alterations associated with endothelial KLF4 depletion and neurovascular aging. Endothelial cell clusters demonstrated inflammatory, senescence-associated, and blood-brain barrier dysfunction signatures associated with loss of endothelial KLF4.Single-cell suspensions were prepared from mouse brains followed by droplet-based single-cell RNA sequencing. Endothelial cell populations were identified using Seurat clustering and analyzed for differential gene expression associated with endothelial KLF4 depletion and aging.

first: Matasha

last: Dhar

first: Edwin

last: Vázquez-Rosa

first: Kalyani

last: Chaubey

first: Emiko Miller

last: Sofia Corella

first: Suwarna

last: Chakraborty

first: Sunil

last: Tripathi

last: Das

first: Xudong

last: Liao

first: Mohamed

last: Alkassem Alosman

first: Hua Fang

last: Yeojung Koh

first: Preethy

first: Kathryn

first: Coral


title: Depletion of endothelial KLF4 drives age-related neurovascular dysfunction and neuropsychiatric impairment [ATAC-seq]

summary: Omni-ATAC sequencing was performed on purified brain endothelial nuclei from young and aged endothelial-specific Klf4 knockout (EC-K4KO) and WT Cre mice to investigate chromatin accessibility changes associated with endothelial aging and neurovascular dysfunction. Endothelial KLF4 loss induced chromatin remodeling enriched for inflammatory, stress-response, and senescence-associated pathways.

overall_design: Purified endothelial nuclei isolated from mouse brain tissue were subjected to Omni-ATAC sequencing to assess genome-wide chromatin accessibility changes associated with endothelial KLF4 depletion and aging.

last: Sridharan

last: Franke

last: Cintrón-Pérez

first: Adrian

first: Taylor

last: Tomco

first: Vidya

last: Indrakumar

first: Phoebe

last: Rubin

first: Justin

last: Pieper

first: Luke

last: Ashiku

first: Min-Kyoo

last: Shin

first: Xinmiao

last: Tang

first: Roshan

last: Padmanabhan

first: Margaret

first: Rajan

first: Bradley

first: Brigid


title: Peripartum-associated heart failure develops independently of RHOT proteins

status: Public on May 27 2026

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

country: Germany

institute: HCI - Helmholtz Centre for Infection Research

summary: The present study investigates whether the expression of RHOT1 and RHOT2 proteins is required for pregnancy-associated adaptations in the maternal heart.

overall_design: Mice with tamoxifen-inducible, cardiomyocyte-selective deletion of Rhot1 and Rhot2 (iRhot1/2-KO; genotype: Rhot1lox/lox Rhot2lox/lox αMHC-MCM+/-) and controls (genotype: Rhot1lox/lox Rhot2lox/lox) were mated after the induction of gene deletion by tamoxifen administration at 7-9 weeks of age. Left ventricular tissue was analyzed after three to five consecutive pregnancies and nursing periods. iRhot1/2-KO and control mice expressing Rhot1 and Rhot2 were sacrificed 1 or 2 days post delivery (indicated as time point delivery; D) or at the end of the nursing period, 18 to 21 days post-delivery (indicated as time point postpartum; PP). Age-matched nulliparous (NP) iRhot1/2-KO mice and age-matched mice expressing Rhot1 and Rhot2 served as controls. Six samples per group were analyzed.

first: Christian

last: Riehle


title: Growth arrest of Mycobacterium tuberculosis in acidic environments enhances their survival of antibiotic treatment

city: Boston

first: Eun Seon

last: Chung

state: MA

address: 136 Harrison Ave

institute: Tufts University

summary: The ability of Mycobacterium tuberculosis (Mtb) bacilli to adapt to host microenvironments by changing growth behaviors promotes population-level survival against host and drug stressors. However, we have a poor understanding of how Mtb’s growth behaviors change at a single-cell level as the population responds to host environmental cues. Here we show that Mtb adapts to acidic conditions by increasing the proportion of bacteria in a growth-arrested state rather than uniformly slowing the growth rate of the entire population. Bacteria in the growth-arrested subpopulation were more tolerant to treatment with ethambutol. Clinical strains in both neutral and acidic conditions have a higher proportion of bacteria in the growth-arrested state, suggesting that growth arrest is a bet-hedging mechanism that is important during infection. The PhoPR two-component system is thought to be a master regulator that enables Mtb to adapt to and survive acidic pH stressors, but we show that it is a partial regulator of the non-growing bacterial subpopulation and that other transcriptional regulators are involved. Our study demonstrates that non-growing subpopulations of Mtb provide fitness benefits and are an active adaptation to environmental cues and not a passive consequence of stressors.

overall_design: Mtb strains were adapted to either pH 5.9 or pH 7.0 for one or four days prior to RNA extraction. Briefly, Mtb were initially cultured in standard growth medium consisting of 7H9 broth (ThermoFisher; DF0713-17-9), 0.2% glycerol, 10% OADC (0.5 g/L oleic acid, 50 g/L albumin, 20 g/L dextrose, and 0.04 g/L catalase), and 0.05% Tween-80, and then subcultured once before pH adaptation. Once the bacterial cultures reached an OD₆₀₀ ≈ 0.5, they were diluted to an OD₆₀₀ of 0.05 in standard growth medium buffered to either pH 5.9 or pH 7.0 and incubated for one or four days before RNA extraction.

first: William

middle: C

last: Johnson

first: Bree

middle: B

last: Aldridge


title: Altered miRNA cargo of endometrial extracellular vesicles in endometriosis: potential implications for pregnancy outcomes

city: Valencia

first: Alba

last: Bas Rivas

state: Valencia

address: Fernando Abril Martorell

department: IVIRMA Global Research Alliance- IVI Foundation

country: Spain

institute: IIS La Fe

summary: Study question: Is the miRNA cargo of extracellular vesicles (EVs) secreted by the eutopic endometrium from women with endometriosis involved in its pathogenesis and related infertility? Summary answer: Data suggest that EVs secreted by primary endometrial epithelial cells from women with endometriosis transport an altered miRNA cargo that modulates biological processes related to endometriosis pathogenesis and pregnancy disorders. Main results and the role of chance: EVs had a mean size of 171 nm and expressed the EV protein markers CD63, CD9, and CD81. TEM corroborated EV cup-shaped morphology. Principal Component Analysis (PCA) revealed differentiated behavior between groups. miRNA-seq showed 8 significantly differentially expressed miRNAs (FDR<0.05), 6 downregulated and 2 upregulated. Among which hsa-miR-1290, hsa-miR-1246, hsa-miR-4516, hsa-miR-191-5p, hsa-miR-335-5p, hsa-miR-12136 and hsa-miR-3065-5p had previously been described as related to gestational complications or endometriosis pathogenesis. These miRNAs targeted 3,964 genes and GO enrichment analysis of these miRNA target genes identified 789 biological processes in endometriosis (FDR<0.05) involved in embryo development and developmental growth, immune system function and angiogenesis, which are important for embryo-maternal tolerance and nutrition; and mesenchymal-epithelial and epithelial-mesenchymal transitions, that are crucial for embryo invasion. KEGG pathway analysis revealed 32 deregulated pathways (FDR<0.05), including PI3K-Akt pathway involved in pathogenesis of preeclampsia.

overall_design: A prospective descriptive study was performed, in which endometrial organoids  were derived from biopsies of eutopic endometrium from endometriosis (ENDO-GESTorg) and healthy women (CONTROL-GESTorg) and erentiated into the gestational phase by supplementation with pregnancy hormones .Conditioned medium was collected from ENDO-GESTorg (n= 16) and pooled in 4 different pools (n= 4 patients/pool), while conditioned medium was collected from CONTROL-GESTorg (n=15) and pooled in 3 different pools (n= 5 patients/pool), and EVs were isolated by ultracentrifugation method.miRNAs were extracted, and miRNA-seq was performed. Target genes of significantly differentially expressed miRNAs were obtained from mirDIP and miTARBase, and functional enrichment analysis was performed with G Profiler.


title: Nutrient-responsive and DAF-16/FoxO target H1 histone HIL-1 promotes resistance to starvation and bacterial pathogens in Caenorhabditis elegans

city: Durham

first: Kinsey

last: Fisher

address: 124 Science Drive

institute: Duke University

summary: Insulin/IGF-1 signaling (IIS) mediates metabolic and developmental acclimation to stressful conditions including starvation. The transcription factor DAF-16/FoxO actuates many of the physiological effects of reduced IIS, yet the specific contributions of DAF-16 target genes to stress resistance remain poorly understood. We explore the function of C. elegans H1 linker histone variant hil-1/H1.0, a DAF-16 target that is upregulated during starvation. The HIL-1 sequence is divergent from the other eight annotated C. elegans H1 variants, and the others are not so highly responsive to nutrient availability and DAF-16 activity, suggesting distinct function. Using knock-in reporters, we find that HIL-1 is expressed ubiquitously in nuclei of L1 and dauer larvae during starvation, but that expression is largely undetectable in fed larvae. Disrupting hil-1 activity through mutation or auxin-inducible degradation led to reduced growth after extended L1 starvation, revealing reduced starvation resistance. RNA-seq of hil-1 mutants showed that hil-1 affects expression of relatively few genes. However, hil-1 activates genes involved in the innate immune response, Pseudomonas aeruginosa infection, and components of the nipi-3/TRIB1 immunity pathway. hil-1 mutants display compromised survival upon exposure to P. aeruginosa under reduced IIS, and genes activated by hil-1 promote resistance to P. aeruginosa. Together these results suggest that DAF-16/FoxO activates transcription of hil-1 during starvation to promote resistance to starvation and pathogens. We demonstrate conditional regulation of an H1 histone, and we reveal a novel mechanism for how IIS promotes stress resistance by identifying a histone variant that connects nutrient sensing to immunity.

overall_design: RNA-seq of starved (12 hrs after hatch) wild type (N2), hil-1(gk229) and hil-1(tm1442)

first: Rojin

last: Chitrakar

first: Ryan

last: Baugh


title: Restraint of melanoma progression by cells in the local skin environment

status: Public on May 26 2026

city: New York

first: Yilun

last: Ma

state: New York

address: 1300 York Ave.

institute: Weill Cornell Medicine

summary: Keratinocytes, the dominant cell type in the melanoma microenvironment during tumor initiation, exhibit diverse effects on melanoma progression. Using a zebrafish model of melanoma and human cell co-cultures, we observed that keratinocytes undergo an Epithelial–Mesenchymal Transition (EMT)-like transformation in the presence of melanoma, reminiscent of their behavior during wound healing. Surprisingly, overexpression of the EMT transcription factor Twist in keratinocytes led to improved overall survival in zebrafish melanoma models, despite no change in tumor initiation rates. This survival benefit was attributed to reduced melanoma invasion, as confirmed by human cell co-culture assays. Single-cell RNA-sequencing revealed a unique melanoma cell cluster in the Twist-overexpressing condition, exhibiting a more differentiated, less invasive phenotype. Further analysis nominated homotypic jam3b-jam3b and pgrn-sort1a interactions between Twist-overexpressing keratinocytes and melanoma cells as potential mediators of the invasive restraint. Our findings suggest that EMT in the tumor microenvironment (TME) may limit melanoma invasion through altered cell-cell interactions.

overall_design: Melanoma and adjacent skin were dissected from adult zebrafish (mitfa:BRAFV600E; tp53-/-; mitfa-/-; mpv17-/-) with keratinocyte-specific empty vector (CTRL) or twist1a/twist1b overexpression (TWIST), and eGFP+ keratinocytes and tdTomato+ melanoma cells were isolated by FACS and analyzed by scRNA-seq.


title: Ago2 loss restores sensitivity to immune checkpoint inhibitors in immunorefractory lung cancer [RNA-seq vitro]

city: Paris

first: Enzo

last: Poirier

address: 26 Rue d'Ulm

department: U932 - Immunity and Cancer

country: France

institute: Institut Curie

summary: One of the first-line treatments for advanced non-small cell lung cancer (NSCLC) are immune checkpoint inhibitors (ICI), which activate the antitumor immune response. Despite their success, ICI remain ineffective in many patients, highlighting the need for strategies to overcome resistance. Most efforts have focused on promoting immune cell infiltration into refractory tumors to improve ICI efficacy. In this work, we mobilize this approach by focusing on Argonaute 2 (Ago2), a pivotal member of the RNA interference pathway. Using two murine models of immunorefractory NSCLC, we demonstrate that tumoral Ago2 suppresses interferon signaling, leading to poor immunogenicity and failure of ICI therapy. Genetic deletion of Ago2 in cancer cells restores interferon signaling and supports immune infiltration of the tumor. Consequently, whereas wild-type tumors are resistant to ICI, tumors devoid of Ago2 become sensitive to treatment. In NSCLC patients treated with ICI, high Ago2 expression and a low interferon signature in tumors correlates with reduced survival. Ago2 is thus a driver of the immunorefractory phenotype observed in NSCLC and may represent a therapeutic target when aiming to sensitize patients to ICI.

overall_design: RNA-seq profiling of wild-type and Ago2KO LLC cells grown in vitro. 4 replicate/group.

first: Dario Pasquale

last: Anobile

first: Layla

last: Barbar

first: Emile

last: Maucotel

first: Alexis

last: Cornec

first: Valeria

last: Manriquez

first: Wilfrid

last: Richer

first: Jordan

last: Denizeau

first: Christine

last: Sedlik

first: Charlie

last: Bories

first: Elodie

last: Couderc

first: Renaud

last: Leclere

first: Judith

last: Sobas

first: Emeline

last: Papillon

first: Rafael

last: Mena Osuna

first: Jimena

last: Tosello-Boari

first: Marianne

last: Burbage

first: Eliane

last: Piaggio


title: CD4/CD8 ratio is associated with structural reorganization of vaccine-induced immune responses in people living with HIV

city: Bunkyo

first: Yoko

last: Tabe

state: Tokyo

address: 3 Chome-1-3 Hongo

institute: Juntendo University

summary: Background: Despite effective antiretroviral therapy and sustained viral suppression, people living with HIV (PLWH) continue to exhibit persistent immune activation and low-grade inflammation. Although the CD4/CD8 ratio is routinely monitored as a marker of immune health, the mechanisms underlying residual immune dysregulation remain incompletely understood. Methods: Peripheral blood mononuclear cells from PLWH and HC were collected before and one month after two doses of mRNA vaccination and analyzed by single-cell RNA sequencing with paired TCR profiling. Differential gene expression (DGE) and protein–protein interaction (PPI) network analyses were performed, and node degree distributions were compared among groups. TCR and bulk BCR repertoires were analyzed, and neutralizing antibody responses were assessed. PLWH were stratified by CD4/CD8 ratio. Results: Stratification by CD4/CD8 ratio revealed distinct immune states in PLWH. Differential genes from the normal CD4/CD8 ratios showed focused transcriptional activation with coordinated chemokine-associated communication, whereas those with low CD4/CD8 ratios exhibited broad transcriptional dysregulation and structural reorganization of gene-expression networks. This network signature was characterized by altered PPI topology and significantly increased monocyte-specific node degree, independent of overall transcriptional complexity. Repertoire analyses demonstrated clonal skewing and reduced clonotype diversity in the low CD4/CD8 ratio group, consistent with impaired immune coordination. Conclusion: Vaccine-induced immune responses in PLWH are shaped by network-level organization associated with CD4/CD8 ratio–defined immune states. Low CD4/CD8 ratio group showed increased monocyte-specific PPI connectivity and clonal imbalance, suggesting altered vaccine-induced response dynamics not captured by conventional clinical markers.

overall_design: Peripheral blood mononuclear cells (PBMCs) were collected from two primary patient cohorts: people living with HIV (PLWH) and healthy controls (HC). For each participant, longitudinal samples were obtained at two distinct time points: pre-vaccination (before vaccination) and post-vaccination (one month after receiving two doses of mRNA vaccination). To assess structural reorganization of vaccine-induced immune dynamics, the PLWH cohort was further stratified based on clinical CD4/CD8 ratios (normal vs. low). Individual samples were processed for multi-omic single-cell analysis, including single-cell RNA sequencing (scRNA-seq / GEX) for transcriptomics and paired single-cell immune repertoire profiling for T-cell receptors (TCR) and B-cell receptors (BCR).

first: Faith Jessica

last: Paran

first: Mizue

last: Saita

first: Rieko

last: Oyama

first: Namiko

last: Nomura

first: Kaori

last: Saito

first: Abdullah

last: Khasawneh

first: Pei

last: Gao

first: Songling

last: Li

first: Hendra Saputra

last: Ismanto

first: Noriyo

last: Nagata

first: Naoko

last: Iwata

first: Yasushi

last: Okazaki

first: Tadaki

last: Suzuki

first: Kazuhisa

last: Takahashi

first: Yuki

last: Uehara

first: Daron

last: Standley

first: Toshio

last: Naito


title: Ago2 loss restores sensitivity to immune checkpoint inhibitors in immunorefractory lung cancer [RNA-seq vivo]

first: Enzo

last: Poirier

overall_design: RNA-seq profiling of wild-type and Ago2KO LLC tumors implanted subcutaneously in syngeneic immunocompetent mice. Tumor sampling was performed at day 12 post-engraftment. 4 mice/group.

first: Dario Pasquale

last: Anobile

first: Layla

last: Barbar

first: Emile

last: Maucotel

first: Alexis

last: Cornec

first: Valeria

last: Manriquez

first: Wilfrid

last: Richer

first: Jordan

last: Denizeau

first: Christine

last: Sedlik

first: Charlie

last: Bories

first: Elodie

last: Couderc

first: Renaud

last: Leclere

first: Judith

last: Sobas

first: Emeline

last: Papillon

first: Rafael

last: Mena Osuna

first: Jimena

last: Tosello-Boari

first: Marianne

last: Burbage

first: Eliane

last: Piaggio


title: Co-Treatment with Empagliflozin and Pirfenidone Improves Cardiac Functions and Reverses Hypertrophic Remodeling in Heart Failure with Preserved Ejection Fraction in a Two-Hit Rat Model

city: Kepala Batas

first: Jun Jie

last: Tan

state: Penang

address: Bertam

department: Advanced Medical and Dental Institute

country: Malaysia

institute: Universiti Sains Malaysia

summary: Heart failure with preserved ejection fraction (HFpEF) is a life-threatening condition that affects more than half of all heart failure patients. Sodium-glucose cotransporter-2 inhibitor (SGLT2i) showed promising improvements in cardiovascular death or heart failure among HFpEF patients. This study aimed to test if cotreatment of Empagliflozin and Pirfenidone can improve the therapeutic outcome HFpEF by addressing the underlying cardiac fibrosis. We induced HFpEF in Sprague-Dawley rats using N-nitro-L-arginine methyl ester and a high-fat diet for 5 weeks, then treated them with EMPA, PFD, or both (EMPA+PFD) for 4 weeks. Echocardiography showed that EMPA+PFD significantly improved left ventricular ejection fraction (LVEF, p<0.0001), fractional shortening (FS, p=0.0427), stroke volume (SV, p=0.0019), and cardiac output (CO, p=0.0016) compared to the untreated group. These improvements were superior to PFD treatment alone (LVEF, p = 0.0131; CO, p = 0.040) and were absent in the EMPA group. Also, the late diastolic transmitral flow velocity and isovolumic relaxation time were much better with EMPA+PFD (p<0.0001) than with EMPA or PFD alone. PFD alone greatly reduced cardiac fibrosis in the subendocardial region. However, when EMPA and PFD were combined, the amount of fibrosis was significantly reduced in both the subendocardium (p<0.0001) and myocardium (p=0.0140). Myocyte cross-sectional area was significantly lower in both PFD-treated and EMPA+PFD-treated groups (p<0.001). However, only the EMPA+PFD group showed a significant reduction in left ventricular weight index (p = 0.0008), while the EMPA-treated group did not show these effects. Greater exercise capacity in HFpEF rats after EMPA+PFD treatment reflected the improvement in cardiac function, outperforming both EMPA and PBS-treated control. In conclusion, cotreatment with PFD and EMPA improves cardiac functions and reverses hypertrophic remodeling, suggesting a better strategy for treating HFpEF. Further investigation to decipher the cellular changes in ventricular CM may provide insights into the mechanism underlying the benefit of treatment combinations.

overall_design: The 24-week-old Sprague-Dawley rats (300-350g) were used in this study. Prior to commencement of any experiments under constant temperature (20-25℃), humidity (50%-65%), 12h light/dark cycle with unrestricted access to food and water. HFpEF were induced using NG-nitro-L-arginine methyl ester (L-NAME, GA11233, Glpbio, 0.5g/L, dissolved in drinking water, adjust PH to 7.4) and high-fat diet (HFD, 60% kilocalories from lard, (D12492, Teklad), for 5 weeks. Control rats were not fed L-NAME in their drinking water. Confirmation of the HFpEF characteristics in rats was performed after 5 weeks. Then, the established HFpEF rats were then randomized to receive daily oral Empagliflozin (EMPA, 0.35g/kg/d, Aladdin), Pirfenidone (PFD, 0.3g/kg/d, Aladdin), or a combination of both EMPA and PFD in phosphate-buffered saline (PBS) through gavage feeding, for 4 weeks. HFpEF rats administered with PBS were served as untreated control. All groups contained n=16 with equal amounts of male and female rats. The hearts were harvested, and total RNA was isolated using the TRIzol reagent. RNA quality was assessed with an Agilent 2100 bioanalyzer and the RNA quantification was performed using the NanoDrop 2000 Spectrophotometer System. The sequencing data were uploaded to the Galaxy web platform and were pre-processed at the public server at usegalaxy.org

first: King-Hwa

last: Ling

first: Zhikun

last: Guo

first: Jun


title: Sex-specific impact of brain estrogen deficiency on the hippocampal transcriptome changes and memory deficits in brain-specific aromatase knockout mouse models

city: Chicago

first: Hong

last: Zhao

address: 303 E Superior St

department: Obstetrics and Gynecology

institute: Northwestern University

summary: Background: Nearly two-thirds of Americans with Alzheimer's disease (AD) are women, however, the molecular mechanisms underlying this sex difference in AD vulnerability remain unclear. Prior research has reported that women with AD have lower brain estrogen. Yet, how estrogen deficiency modulates this sex difference in AD is not well understood. Aromatase, the key enzyme for estrogen biosynthesis, is expressed in both neurons and astrocytes of the brain, with high levels in the hippocampus. To explore the underlying mechanism of estrogen deficiency in sex-specific AD vulnerability, we generated mouse models with brain-specific aromatase knockout (bArKO) and whole-body total aromatase knockout (tArKO).  Method: We performed a series of memory and behavior tests including spontaneous alternation, social interaction, and tail suspension tests on 6- and 19-month-old bArKO and tArKO mice with both sexes (n=10/group). Hippocampus tissues from these mice (n=3~4) were collected for bulk RNA-seq and qPCR. Serum and tissue estrogen were measured using liquid chromatography-mass spectrometry.  Result: Aromatase deletion decreased brain estrogen levels in bArKO mice and circulating and brain estrogen levels in tArKO mice. Impairments of spatial working memory and social interaction behavior were found in 19-month-old female bArKO and tArKO mice. Female tArKO mice also displayed depression-like behavior at 6- and 19-month-old. Bulk RNA-seq showed differentially expressed genes associated with glia and neurons (e.g., Tenm4, Col1a1, Ogn, Dcn, Slc17a6, and Ccn2) in aged female bArKO mice.  Conclusion: Our findings provide novel mechanisms that link estrogen deficiency to sex-specific transcriptome changes in the hippocampus and memory loss in aged female mice. Future studies will focus on defining impact of estrogen signaling deficiency on AD mouse models and identifying druggable targets to inform the development of new therapeutic strategies for the prevention and treatment of AD.

overall_design: Hippocampus tissues from  6- and 19-month-old bArKO and tArKO mice (n=3~4) were collected for bulk RNA-seq

first: Natalie

last: Piehl

first: Ariel

last: Halle

first: Guadalupe

last: Rodriguez

first: Andrea

last: Locci

first: Stacy

last: Kujawa

first: Caroline

last: Haywood

first: John

middle: V

last: Coon

first: Tianming

last: You

first: Hongxin

last: Dong

first: Serdar

last: Bulun


title: Uncoupling the TFIIH Core and Kinase Modules Leads to High CTD Serine 5 Phosphorylation Throughout Transcription

city: Montreal

first: Francois

last: Robert

state: QC

address: 110 av des Pins Ouest

country: Canada

institute: IRCM

summary: TFIIH is a transcription initiation factor for RNA polymerase II (RNApII). This multi-subunit complex comprises two modules that are physically linked by the Tfb3 (MAT1 in metazoans). The Core Module carries two DNA-dependent ATPases that unwind DNA, not only for transcription but also nucleotide excision repair. The Kinase Module phosphorylates the C-terminal domain (CTD) of RNApII subunit Rpb1 to facilitate the transition of initiation complexes to elongation.  Yeast Tfb3 can be split into two parts to uncouple the TFIIH modules, and resulting cells are viable but slow-growing. Chromatin immunoprecipitation shows that Core, but not Kinase, is properly recruited to promoters. Surprisingly, instead of the normal promoter-proximal peak, CTD phosphorylation is now spread throughout transcribed regions.

overall_design: RNApII (Rpb1), CTD Ser5P, Tfb1 and Kin28 chromatin immunoprecipitation (ChIP-seq) in wild type and three split Tfb3 cells with corresponding Inputs were paired-end sequenced. A small amount (10%) of chromatin from S. pombe cells was spiked in all samples prior to the immunoprecipitation for normalization. All data are from two independent biological replicates, for a total of 40 ChIP-seq samples.

first: Gabriela

last: Giordano

first: Robin

last: Buratowski

first: Celia

last: Jeronimo

first: Christian

last: Poitras

first: Stephen


title: Fucoidans are senotherapeutics that enhance SIRT6-Dependent DNA repair

status: Public on May 25 2026

city: Minneapolis

first: Lei

middle: Justan

last: Zheng

state: Minnesota

address: 312 Church St. SE

institute: University of Minnesota

summary: Aging is marked by the accumulation of senescent cells (SnCs), which contribute to tissue dysfunction and age-related diseases. Senotherapeutics, including senolytics which specifically induce lysis of SnCs and senomorphics, which suppress the senescence phenotype, represent promising therapeutic interventions for mitigating age- related pathologies and extending healthspan. Using a phenotypic-based senescent cell screening assay, we identified fucoidans, a class of sulfated polysaccharides derived from brown algae and seaweed, as novel senotherapeutics. In particular, fucoidan from Fucus vesiculosus (Fucoidan-FV) displayed potent senomorphic activity in different types of SnCs, reduced senescence in multiple tissues in aged mice, and extended healthspan in a mouse model of accelerated aging. Fucoidan-FV also enhanced the deacetylation and mono-ADP-ribosylation (mADPr) activity of SIRT6 and improved DNA repair and reduced senescence, in part, through SIRT6-dependent pathways. In addition, Fucoidan-FV downregulated genes associated with inflammation, Wnt signaling, and ECM remodeling pathways in SnCs and increased expression of genes involved with DNA repair. These findings support the translational potential of fucoidans as novel senotherapeutics that also are able to improve SIRT6-mediated DNA repair.

overall_design: RNA-seq profiling of WT and Senescent Mouse Embryonic Fibroblasts, both untreated and treated with Fucoidan.

last: Zhang

first: Osama

last: Elsallabi

first: Carolina

last: Soto-Palma

first: Josh

last: Bartz

first: Rahagir

last: Salekeen

first: Wandi

last: Xu

first: Kyooa

last: Lee

first: Brian

last: Hughes

first: Borui

first: Abdalla

last: Mohamed

first: Sara

middle: j

last: McGowan

first: Luise

last: Angelini

first: Ryan

last: O'Kelly

first: Seyed

last: Biashad

first: Eric

last: Hillpot

first: Francesco

last: Morandini

first: Andrei

last: Seluanov

first: Vera

last: Gorbunova

first: Xiao

first: Laura

last: Niedernhofer

first: Paul

last: Robbins


title: Integrated omics-based mechanistical insights into a membrane-targeting antibacterial

status: Public on May 22 2026

city: Leuven

first: Haitham

last: Abdallah

address: Herestraat

department: Microbiology and Immunology and Translpantation

country: Belgium

institute: KU Leuven

summary: The continuous risk of antibiotic resistance development underscores the demand for new agents with mechanisms distinct from existing antibacterial drugs. Here, we investigated HSI#6, a small-molecule antibacterial previously identified as a SecA activator, using integrated omics and functional assays. HSI#6 exhibits broad-spectrum bacteriostatic activity and acts through a dual-phase mechanism: transient activation of SecA-dependent secretion followed by membrane perturbation and global stress reprogramming. Time-resolved transcriptomics and proteomics revealed early activation of envelope stress regulons (Cpx, Rcs, Pho), efflux systems, and oxidative stress pathways, followed by suppression of ribosome biogenesis and central metabolism. Comparative analysis and biomarker-based principle component analysis (PCA) positioned HSI#6 within the envelope stress mechanistic space, closely aligned with membrane-active antibiotics yet displaying a distinct signature. Adaptive laboratory evolution (ALE) combined with whole-genome sequencing (WGS) revealed compensatory mutations in topoisomerase 1A gene (topA) and transcriptional regulators, without adaptive resistance emerged even under prolonged selection pressure. These findings establish HSI#6 as a mechanistically unique antibacterial targeting membrane homeostasis with low resistance potential.

sample_organism:
Escherichia coli K-12
Escherichia coli O127:H6

overall_design: RNA-seq profiling of E.coli BW25113 and Enteropathogenic E.coli treated with new antimirobials (active and inactive and DMSO) and whole genome sequencing of  BW25113 ΔtolC

last: Sedky

first: Mohamed

last: Hamed

first: Kurt

last: Vermeire

first: Joost

last: Schymkowitz

first: Spyridoula

last: Karamanou

first: Anastassios

last: Economou


title: ATML1-GIR1-TPL transcriptional repression module controls glucosinolates and giant cells in Arabidopsis thaliana sepals

city: Manhattan

first: Kathrin

last: Schrick

state: KS

address: 116 Ackert Hall

institute: Kansas State University

summary: Glucosinolates (GSLs) are sulfur- and nitrogen-containing secondary metabolites that serve as defense compounds in Arabidopsis and other members of the Brassicales. Although the enzymatic pathway that produces GSLs is well-studied, the upstream mechanisms that control their tissue-specific synthesis are poorly understood. We identified a novel repression module that transcriptionally regulates GSL levels in sepals, the modified leaves that protect reproductive tissues within the floral bud. GLABRA2 (GL2) INTERACTING REPRESSOR1 (GIR1) interacts directly with Arabidopsis thaliana MERISTEM LAYER1 (ATML1), an HD-Zip IV transcription factor known to be required for giant cell formation in the sepal epidermis. This interaction requires a predicted zinc finger of GIR1 and the C-terminal START adjacent domain (STAD) of ATML1. The gir1 loss-of-function mutants exhibit excess giant cells, in contrast to atml1 mutants which lack giant cells, supporting the role of GIR1 as a negative regulator of ATML1. We confirmed that GIR1 interacts with TOPLESS (TPL) and TOPLESS-RELATED (TPR) corepressors that recruit chromatin remodelers, and coimmunoprecipitation demonstrated that GIR1 acts as an adaptor protein between ATML1 and TPL/TPR. RNA sequencing revealed that numerous genes involved in GSL biosynthesis, including the key transcriptional regulator MYB29, are upregulated in gir1 mutants. Consistent with the transcriptomic data, chemical analysis revealed that gir1 mutants display elevated GSL levels in sepals. Mass spectrometry imaging confirmed high GSL accumulation in gir1 sepals compared to wild type and atml1. Overall, our findings uncover a previously unrecognized link between cell expansion and GSL metabolism and suggest strategies for engineering plants with cell-type specific GSL profiles.

overall_design: Stage 12 unopened flowers were dissected to obtain 200 sepals (from 50 buds) for each genotype (Wild type of ecotype Col-0, atml1-3, and gir1-1) in triplicate. Samples were frozen in liquid nitrogen prior to RNA extraction using the QIAGEN RNeasy Plant Mini Kit. RNA quality evaluation, cDNA library construction, and Illumina sequencing were performed by Novogene (Sacramento, CA).

first: Lauren

last: Apprill


title: Interferon-Stimulated Neutrophils Impair Breast Cancer Response to Immunotherapy and Disrupt Immunological Memory

city: Houston

first: Xiang

last: Zhang

address: One Baylor Plaza

institute: Baylor College of Medicine

summary: Despite durable remissions observed in a subset of cancer patients treated with immunotherapy, the majority remain unresponsive, underscoring the need for predictive biomarkers and novel therapeutic targets. In this study, we integrated single-cell RNA sequencing, spatial transcriptomics, and conditional knockout mouse models to uncover a conserved neutrophil interferon (IFN)-stimulated gene signature that predicts responsiveness to anti-PD1 therapy. We demonstrate that early reductions in neutrophil abundance and neutrophil IFN responses are strongly associated with therapeutic efficacy, while the spatial exclusion of neutrophils from tertiary lymphoid structures emerges as a hallmark of successful treatment. Furthermore, our findings reveal that neutrophil IFN signaling is pivotal in mediating resistance to therapy and in impairing the development of durable immunological memory. These findings offer insights into the interplay between neutrophil IFN signaling and adaptive immunity, providing a foundation for developing bloodborne biomarkers and combinatorial strategies to enhance the efficacy of immune checkpoint blockade therapy.

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

first: Yang

last: Gao

last: H-F Zhang


title: Transcriptional landscape of mouse adipose tissue transfected with LHX8 siRNA

status: Public on May 21 2026

city: Debrecen

first: Tamás

last: Röszer

address: Nagyerdei krt. 98.Gyermekklinika

department: Pediatrics

country: Hungary

institute: University of Debrecen

summary: We have studied the role of LHX8 (Lim Homeobox 8) in adipocyte development. Mouse 3T3-L1 adipcoytes were used for our analyses. Cells were cultured in high glucose DMEM, supplemented with 10% FCS, 1% glutamine and 1% penicillin/streptomycin. Cells were grown to reach 70-80% confluence, and transfected with a siRNA silencer to decrease Lhx8 mRNA expression. Turbofectamine was used for cell transfection. Total RNA was isolated 48h post-transfection and used for subsequent NGS analysis.

overall_design: Samples are labeled as vehicle and siRNA groups. Vehicle group was treated with Turbofectamine. Our aim was to identigy differentially expressed genes (DEGs) in the cell cultures transfceted with Lhx8 siRNA.

first: Röszer

last: Tamás


title: Schisandrin B exhibits anti-proliferative effects by inducing ferroptosis in pancreatic cancer

city: Qingyuan

first: Fengjin

last: Li

state: Guangdong

address: NO.21 Yinquan North Road

institute: The Affiliated Qingyuan Hospital of Guangzhou Medical University

summary: Pancreatic cancer (PC) is a lethal malignancy of the digestive system with an extremely low survival rate. Schisandrin B (Sch B) has demonstrated novel pre-clinical antitumor activity in several animal tumor models. However, it remains unclear whether Sch B exerts antitumor effects in PC. The molecular mechanisms underlying the antitumor properties of Sch B were explored using RNA sequencing.

overall_design: RNA-seq profiling of PANC-1 cells treated with Sch B (20 μM) or vehicle control (<0.1% DMSO) for 24 h.

first: Jiacai

last: Fu

first: Xiaowei

last: Lin

first: Yanting

last: Liu

first: Lu

last: Yang

first: Yuxin

first: Tieli

last: Peng

first: Ling

last: Qi


title: Transcriptomic profiling of A549 cells in response to dexamethasone, in the context of light-controlled GR degradation using novel GR-PhotoPROTACs

city: Zurich

first: Katharina

last: Gapp

address: Winterthurerstrasse 190

department: Health Science and Technology

country: Switzerland

institute: Swiss Federal Institue of Technology

summary: Glucocorticoid receptor (GR) signaling, activated by dexamethasone (Dex), induces a reversible dormancy state in non-small cell lung cancer (NSCLC) cells, contributing to therapy resistance. To enable precise modulation of GR activity, we developed photoswitchable PROTACs (PhotoPROTACs) incorporating arylazopyrazole scaffolds that allow reversible, wavelength-specific control of GR degradation. A549 lung carcinoma cells were incubated with the active (E-isomer) or inactive (Z-isomer) form of PhotoPROTAC KH-5-309 or KH-5-306 for 12 hours, with Dex added during the final 2 hours. RNA sequencing revealed that the E-isomer of KH-5-309 selectively disrupts GR-driven dormancy-associated gene expression, while the Z-isomer remains functionally inert. This dataset provides a resource for understanding GR-mediated dormancy and demonstrates the utility of light-responsive chemical tools for spatiotemporal control of stress hormone receptor signaling to disrupt cancer cell dormancy.

overall_design: RNA-seq profiling of A549 cells treated with the active (E-isomer) or inactive (Z-isomer) form of PhotoPROTAC KH-5-306 or KH-5-309 for 12 hours, with Dex added during the final 2 hours. As controls, A549 cells were treated with DMSO.

first: Robin

last: Scheuplein

first: Karina

last: Freitag

first: Chiara

last: Orlacchio

first: Bohan

first: Vincent

last: Fischer

first: Erick

last: Carreira


title: A temporal single-nucleus atlas of the hippocampus in temporal lobe epilepsy mice unveils neuroprotective IGF1+ microglia

city: Chongqing

first: Ran

last: Duan

address: 1 Youyi Road

institute: Ten Thousand Talent Plans for Young Top-notch Talents of Yunnan Province

summary: Epilepsy is a complex chronic disease characterized by intricate interactions between neurons and various types of glial cells during its pathogenesis. Understanding the molecular sequence of events underlying epilepsy onset and progression is critical for identifying molecular and cellular targets for therapeutic development. In this study, we aimed to reveal the dynamic cell-type-specific responses in TLE hippocampal tissue following KA induction, and identify cellular and molecular mechanisms that either promote or restrict epileptic seizures.

overall_design: To construct a temporal lobe epilepsy mouse model, stereotactic injection of kainic acid (KA) into the CA1 region of the hippocampus was performed in mice. Hippocampal tissues from the injection side were collected at three time points, including the latent phase (7 days after KA injection), chronic phase (28 days after KA injection), and late chronic phase (60 days after KA injection). To account for potential surgical effects, hippocampal tissues from mice injected with physiological saline (sham-operated group) were collected at the corresponding time points as controls. Single-nucleus RNA sequencing (snRNA-seq) was performed on these hippocampal tissues.

first: Fei

last: Xiao

first: Ziwei

last: Yuan

first: Yan

first: Xiaogang

last: Zhang

first: Liqin

last: Hu

last: Song

first: Yuan

last: Meng

first: Pingyang

last: Ke


title: Symbiotic Adhesion of Neutrophils and Epithelial-like Cancer Cells Shapes the Tumor Microenvironment and Promotes Metastasis [1] [coculture]

last: Wu

state: TX

department: Breast Center

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

overall_design: RNA sequencing of neutrophils from the bone marrow of C57/B6 wild type mice either cultured alone or in co-culture with PyMT-N or PyMT-M cells in low serum condition for 12 hours. Neutrophils from the co-culture groups were FACS sorted.

first: Xiang


title: Diverse impact of neutrophils on cancer cells of different epithelial/mesenchymal phenotypes leads to distinct tumor microenvironment and metastatic behavior [3]

first: Ling

overall_design: Primary tumors of 2208L bearing balb/c mice were isolated. Circulating tumor cells were propagated from the peripheral blood of the matched mice.


title: ORCA-mediated Polycomb Repressive Complex stabilization maintains 3D-genome architecture and controls replication timing [NS-seq]

status: Public on May 20 2026

city: Urbana

first: Supriya

last: Prasanth

address: 601 S Goodwin Avenue

department: Cell and Developmental Biology

institute: University of Illinois Urbana Champaign

summary: Polycomb bodies, also called Polycomb group (PcG) protein complexes, are implicated in gene regulation, especially during development, differentiation, and during the maintenance of tissue-specific functions in multicellular organisms. Predominantly, in transformed cells, PcG bodies  form distinct nuclear foci, within which PcG-bound DNA is localized. These structures likely represent misregulated gene expression due to the loss of normal regulatory mechanisms, yet the molecular function of these bodies in cellular homeostasis remains unknown. Using TSA-Seq (Tyramide signal amplification), we provide the first-of-a-kind comprehensive view of the genomic regions, including specific centromeric and telomeric sites that are in proximity to the PcG bodies. Further, these regions are enriched for the repressive histone marks, H3K27me3, H3K9me3 and depleted for active marks, H3K4me3 consistent with a lack of accessible chromatin. We find high density of replication origins around PcG bodies, consistent with the replication factor, ORCA/LRWD1 localizing at these sites. ORCA interacts with the PRC complex, stabilizes the H3K27 methyltransferase, and facilitates the deposition of this histone mark at specific chromatin sites. Loss of ORCA impacts the chromatin organization around the PcG bodies, leading to decompaction of the repeat regions, and enhanced initiation from replication origins. Our results indicate that ORCA interacts with the PcG complex-bound chromatin and maintains a repressed heterochromatin environment to control the timing of replication origin firing.

overall_design: NS-seq involves sequencing to understand activated origins. We performed experiment in control and siORCA treated cells to see difference in origin activity.

first: Neha

last: Chetlangia

first: Bhushan

middle: L

last: Thakur

first: Christophe

last: redon

first: Oraya

last: Zinder

first: Lorinc

last: Pongor

first: YouJin

first: Darya

last: Asoudegi

first: Dazhen

last: Liu

first: Chris

last: Fields

first: Kannanganattu

first: Mirit

middle: I

last: Aladjem


title: H2BE113K mutation promotes breast cancer metastasis through modulating chromatin dynamics

city: hong kong

first: shiman

last: hu

address: dazhiroad

institute: city university of Hong Kong

summary: Cancer progression is driven by the accumulation of DNA mutations and aberrant gene regulation. Recent studies have demonstrated that multiple mutations in genes encoding histone H3 serve as drivers of tumorigenesis. However, the role and significance of various cancer-associated histone H2B mutations in cancer development remain largely unknown. Here, we investigate H2BE113K, a missense mutation of histone H2B predominantly found in breast cancer patients. Using MDA-MB-231 cells knockin with H2BE113K, we show that H2BE113K promotes colony formation in breast cancer. Of note, transcriptomic analysis reveals differential expression of genes in various cancer pathways in H2BE113K mutant cells. Intriguingly, the loci with elevated gene expression display increased chromatin accessibility and accompany with the enrichment of E113K mutant H2B. Importantly, the depletion of G3BP2, one of the H2BE113K target genes that has been implicated in breast cancer, reduces the colony formation phenotype in H2BE113K mutant cells. In addition, MMTV-PyMT breast cancer model crossbred with our H2BE113K knock-in mice results in elevated lung metastasis. Together, our findings provide critical insights in the mechanistic role of H2BE113K in gene regulation, chromatin function and breast cancer progression.

overall_design: We performed RNA-seq, ATAC-seq, and CUT&RUN to examine the effects of H2BE113K mutation both in vitro and in vivo

first: Shiman

first: Jiaxian

first: Jiaqi

last: Zhou

first: Tiantian

last: Qin

first: Jiaohua

last: Chen

first: Haiyun

last: Gan

first: Ming

last: Chan


title: The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation [small RNA-seq]

city: Zwijnaarde

first: Sophie

last: Janssens

address: Technologiepark 71

department: Inflammation Research Center

institute: VIB/UGhent

summary: Conventional type I dendritic cells (cDC1s) are characterized by their unique capacity to engulf and cross-present antigens from dead cells, in contrast to the closely related cDC2s. Recently, the engulfment of dead cells by cDC1s was found to initiate cDC1 homeostatic maturation and induction of cholesterol efflux pathways by inducing LXRb activity. cDC1s are uniquely characterized by high basal activity of IRE1, a sensor of the unfolded protein response (UPR). IRE1 activity in cDC1s is unconventional because it does not induce a typical UPR gene signature and hence the role of IRE1 in cDC1s remains enigmatic. Here we show that IRE1 activity is critical for the survival of homeostatically matured cDC1s, not cDC2s, after engulfment of apoptotic cells. Mechanistically, we found that IRE1 becomes activated by the influx of dead-cell derived cholesterol, explaining its cDC1 subset specific activation. Following activation, IRE1’s endonuclease activity degrades miRNA-92a in a process termed Regulated IRE1 dependent decay (RIDD). miRNA-92a targets Abcg1 mRNA which is an essential cholesterol efflux transporter in cDC1s. Thus IRE1, together with LXRß which drives the expression of Abcg1 mRNA, coordinates cholesterol efflux in cDC1s after efferocytosis. Loss of IRE1 leads to cholesterol toxicity and cell death of mature cDC1s after engulfment of dead cells. This could be rescued by blocking miRNA synthesis or by enforcing cholesterol efflux with reconstituted high density lipoprotein treatment. In conclusion, these data highlight the central role of the endoplasmic reticulum and IRE1 as a sensor of cholesterol influx, extending IRE1’s function beyond its canonical role in protein folding. Furthermore, they underscore the tight control of lipid metabolism during cDC1 maturation, uncovering a second pathway to coordinate cholesterol efflux.

overall_design: To investigate the role of Xbp1 and Ire1a in cDC1s, an Xbp1-deficient and an Ire1a-Xbp1 compound deficient mouse line were created. We then isolated splenic cDC1s from these mice and generated small RNA-seq data. Subsequently, comparative small RNA expression profiling analysis was performed between the genotypes.

first: Victor

last: Bosteels

first: Sandra

last: Maréchal

first: Eva

last: Cloots

first: Clint

last: De Nolf


title: The Exercise Hormone Irisin Mediates Neuroprotective Effects in a Mouse Model of Multiple Sclerosis

city: Boston

first: Pius

middle: Friedrich

last: Schlachter

state: Massachusetts

department: Cardiovascular Research Center CVRC

institute: Massachusetts General Hospital and Harvard Medical School

summary: Aerobic exercise has been considered a disease-modifying intervention in multiple sclerosis (MS) as it not only improves the physical fitness of people with MS but also ameliorates progressive neurological symptoms. However, the exact mechanisms are unknown, and currently, no drug is available that harnesses these therapeutic effects. The novel exercise hormone irisin, the secreted form of FNDC5 (fibronectin-domain III containing 5), is a prime candidate to mediate part of the neuroprotective exercise effects in MS as it is a crucial regulator of cognitive function in exercise, aging, and Alzheimer’s disease. Furthermore, irisin is neuroprotective in preclinical models of Alzheimer’s disease and Parkinson’s disease. Here, we show that voluntary wheel-running exercise leads to an ameliorated experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Peripheral delivery of irisin resulting in higher irisin plasma levels improves hippocampal and spinal cord clinical symptoms of EAE and reduces neurodegeneration. Interestingly, peripheral irisin does not alter peripheral and central immune response on a transcriptional level but induces neuroprotective gene programs in neurons, mainly associated with synapses and mitochondria. Accordingly, irisin and voluntary exercise resulted in a rescue of synaptic loss during EAE. Taken together, the exercise hormone irisin confers direct neuroprotective effects in an inflammation-driven neurodegenerative condition such as MS, thereby making it an attractive therapeutic target for MS.

overall_design: To determine how peripheral irisin impacts the gene expression in the spinal cord in an EAE model, we conducted bulk RNA sequencing on FACS-sorted NeuN-negative and NeuN-positive spinal cord cells isolated from EAE mice that were treated with either AAV8-GFP or AAV8-Irisin-FLAG.


title: ZNHIT1-dependent H2A.Z deposition at meiotic prophase I underlies pachytene gene expression and meiotic progression during male meiosis [KAS-seq]

city: Shanghai

first: Jiang

last: Yamei

address: Songhu Road

institute: Fudan University

summary: Accurate meiotic progression is important for gamete formation and the generation of genetic diversity. However, little is known about the identity of chromatin regulators that underlie mammalian meiosis in vivo. Here, we identify the multifaceted functions of the chromatin remodeler ZNHIT1 in governing meiosis. The expression of *Znhit1* gradually increases during the meiotic prophase, and *Znhit1* knockout in spermatocytes results in arrested pachytene development, impaired DNA double-strand break repair, and defective homologous recombination. Single-cell RNA sequencing and transcriptome analysis reveal that *Znhit1* loss dysregulates meiotic transcriptional programs at the pachytene stage. Chromatin immunoprecipitation data show that ZNHIT1 is needed for the incorporation of the histone variant H2A.Z into pachytene chromatin. Moreover, we found that H2A.Z cooperates with the transcription factor A-MYB to co-bind DNA elements and control gene activity. Our findings provide insights into the regulatory mechanisms governing meiotic progression and highlight ZNHIT1 as a critical regulator of meiotic progression.

overall_design: To uncover ZNHIT1-mediated modulation of nascent transcription, we profiled pachytene spermatocytes via KAS-seq.

first: Shenfei

last: Sun

first: Yamei

last: Jiang

first: Ning

first: Qiaoli

last: Zhang

first: Hongjie

last: Pan

first: Fujing

last: Huang

first: Xinna

first: Yuxuan

last: Guo

first: Xiaoyu

last: You

first: Kai

last: Gong

first: Wei

last: Wei

first: Hanmin

first: Zhenju

last: Song

first: Yuanlin

first: Xiaofang

last: Tang

first: Miao

last: Yu

first: Runsheng

last: Li

first: Xinhua

last: Lin


title: The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation

first: Sophie

last: Janssens

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

overall_design: Refer to individual Series

first: Victor

last: Bosteels

first: Sandra

last: Maréchal

first: Eva

last: Cloots

first: Clint

last: De Nolf


title: The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation [CITE-seq]

overall_design: We performed CITE-seq to compare homeostatic maturation of Xbp1-Ire1 compound deficient cDC1s with wild-type cDC1s within the spleen. Combining the measurement of the transcriptome and the surface epitopes of cDC1s facilitated a detailed analysis of the various stages cDC1s go through during this maturation process.


title: The unfolded protein sensor IRE1 is essential for homeostatic dendritic cell maturation [RNA-seq]

overall_design: To investigate the role of Xbp1 and Ire1a in dendritic cells, an Xbp1-deficient and an Ire1a-Xbp1 compound deficient mouse line were created. We then isolated cDC1s and cDC2s from the spleen of these mice and generated bulk RNA-seq data. Subsequently, comparative gene expression profiling analysis was performed between the genotypes for both cDC1s and cDC2s respectively.