title: Insulator BEAF32 regulates expression of tissue-specific genes and piRNA source loci in the Drosophila ovaries [small RNA-seq]

summary: Background: Insulators are the multifunctional DNA binding proteins that perform architectural functions and regulate gene transcription. Although insulators have a well-established role in genome organization, it is still unclear how insulator proteins affect the control of tissue-specific processes. Drosophila insulator BEAF32 (Boundary Element-Associated Factor of 32 kD) is a component of chromatin complexes found in the open chromatin regions containing promoters of housekeeping genes. BEAF32 knockout impairs oogenesis and female fertility suggesting its specific functions during oogenesis Results: To get a better understanding of BEAF32 roles in oogenesis, we first examined its ovarian binding targets and discovered an enrichment of its localization sites in the promoters of both housekeeping and tissue-specific genes. Differential expression gene analysis revealed that BEAF32 knockout resulted in abnormal activation of non-ovarian tissue-specific genes in the ovaries, implying that BEAF32 regulates tissue-specific patterns of gene expression. Among upregulated genes there were not only BEAF32-associated genes suggesting direct and indirect mechanisms of BEAF32-mediated expression control. We discovered that BEAF32 occupied many ovary-specific gene promoters and acted as a positive regulator of the cell-cycle regulatory kinase Polo expression. To reveal the possible role of BEAF32 in the pathway mediated by Piwi-interacting RNAs (piRNAs) we performed an analysis of ovarian small RNAs in the BEAF32 null mutants and revealed a strong decrease in the production of piRNAs from the 3R subtelomeric region. Our data suggest that BEAF32-containing chromatin complex located upstream of the subtelomeric repeats preserves transcriptional and chromatin integrity of this domain in the germline. BEAF32 was also found upstream of flamenco, a largest piRNA source locus in the follicular cells, and is required for the cell-specific transcription of the flam locus. Conclusions: These findings suggest that BEAF32 represses the ectopic expression of developmental and tissue-specific genes in the ovaries. BEAF32 regulates polo kinase and other oogenesis-related genes. BEAF32 insulators have been revealed to play a specific ovarian role in the maintenance of piRNA-producing loci. Our results provide strong support for the importance of BEAF32 insulator protein in determining the proper landscape of tissue-specific gene expression and locus-specific function realization.

overall_design: Deep-sequencing of small RNAs (19-30 nt) of Drosophila melanogaster ovaries


title: Insulator BEAF32 regulates expression of tissue-specific genes and piRNA source loci in the Drosophila ovaries [ChIP-seq]

status: Public on Aug 06 2025

city: Moscow

first: Anastasiya

last: Kobelyatskaya

address: Vavilov str, 32

country: Russia

institute: Engelhardt Institute of Molecular Biology, RAS

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Deep-sequencing of chromatin immunoprecipitated genomic DNA on Drosophila melanogaster ovaries

first: Alla

last: Kalmykova


title: RNA-seq data of dry and imbibed seeds in Arabidopsis thaliana Col - 0 and odr1 - 2 mutant

city: Shenzhen

first: Ling

last: Ding

address: No 7,Pengfei Road,Dapeng District

country: China

institute: Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences

type: Expression profiling by high throughput sequencing

summary: This study aims to explore the transcriptomic differences in dry seeds and seeds after 6 - hour imbibition between wild - type Arabidopsis thaliana Col - 0 and the odr1 - 2 mutant.

overall_design: Transcriptome sequencing was performed on 12 samples, including three biological replicates each of dry seeds and 6 - hour imbibition seeds from Arabidopsis thaliana Col - 0 and the odr1 - 2 mutant.


title: IRF4 dose-dependently controls peripheral Treg cell differentiation and homeostasis by modulating chromatin accessibility in mice

city: Hamburg

first: Michael

last: Spohn

address: Martinistr. 52

department: Bioinformatics Core

country: Germany

institute: UKE Hamburg

summary: FoxP3+ regulatory T (Treg) cells restrict excessive immune responses and immunopathology as well as reactivity to self or environmental antigens and thus are crucial for peripheral immune tolerance. The transcription factor Interferon Regulatory Factor 4 (IRF4) controls differentiation and function of T cells. In Treg cells, IRF4 is required for peripheral activation and maturation to effector Treg (eTreg) cells with enhanced suppressive function. However, the mechanisms of Treg cell regulation by IRF4 are not fully understood. Here, we analyze the role of IRF4 in differentiation and maintenance of Treg cells using IRF4-deficient mice and a T cell transfer model, that allows Irf4 inactivation in peripheral T cells. We demonstrate that loss of one Irf4 allele already results in impaired eTreg cell differentiation and decreased Treg cell homeostasis, indicating that IRF4 controls peripheral Treg cell differentiation in a dose dependent mode. Peripheral Irf4 inactivation was also associated with enhanced production of inflammatory but also inhibitory cytokines by Treg cells. ATAC sequencing of Treg cells after mutation of one or both Irf4 alleles revealed regions with altered accessibility in genes involved in Treg cell function. In the FoxP3 gene, Irf4 inactivation resulted in reduced ATAC signals in the promoter region and in the conserved non-coding sequence (CNS) 2, required for stability of FoxP3 expression in peripheral Treg cells in response to TCR stimulation. IRF4 deficient Treg cells also displayed a reduction in open chromatin in several Treg cell specific super enhancers, mainly located in proximity to potential IRF4 binding sites. In conclusion, our results demonstrate that IRF4 controls peripheral Treg cell differentiation and homeostasis in a dose dependent manner.

overall_design: Rag1-/- mice were reconstituted with T cells from Irf4+/fl × CreERT2 and Irf4-/fl × CreERT2 donor mice. After 4-5 weeks, recipients were treated with tamoxifen to induce recombination, and after further 5 weeks, recipients were infected with LmOVA. Eight days after infection, Irf4+/fl × CreERT2 donor cells with recombination (GFP+) and without recombination of the Irf4fl allele (GFP-) as well as Irf4 /fl × CreERT2 donor cells with recombination (GFP+) and without recombination of the Irf4fl allele (GFP-) were sorted and analyzed by single cell ATAC sequencing.

first: Leonie Caroline

last: Voß

first: Constantin

last: Schmidt

first: Aenne

last: Harberts

first: Peter

last: Bradtke

first: Alina

last: Borchers

first: Stefanie

last: Fertig

first: Joanna

last: Schmid

first: Christian

middle: F

last: Krebs

first: Friederike

last: Raczkowski

first: Hans-Willi

last: Mittrücker

first: Friedrich

last: Koch-Nolte


title: Multi-omics analysis unveiled fibroblast-mediated pathogenesis in male genital lichen sclerosus

city: Chengdu

first: Lede

last: Lin

state: Sichuan

address: No.37 Guoxue Lane, Wuhou District, Chengdu, Sichuan, P. R. China

institute: West China Hospital of Sichuan University

summary: Male genital lichen sclerosus (MGLSc), a chronic inflammatory dermatological condition, has been recognized for its profound implications on the quality of life among males. The exact etiological factors behind this prevalent condition remained largely enigmatic. In this research, we employed a multi-omics strategy to identify and elucidate the underlying histological biomarkers and the fundamental pathogenesis associated with MGLSc. Generally, a comprehensive cell atlas of MGLSc disease was constructed, highlighting a pronounced increase in T cells coupled with a remarkable reduction in keratinocytes within the MGLSc samples. Further insights elucidated the enhanced crosstalk between fibroblasts and T cells via the collagen-CD44 axis, and between fibroblasts and keratinocytes through the APP-CD74 signaling pathway. This molecular dialogue was implicated in the immune infiltration and hyperkeratosis observed in the dermal-epidermal layer of MGLSc. Subsequently, we integrated single-cell RNA sequencing data with genome-wide association study findings to explore the cell type-specific genes predisposing to the development of MGLSc. The analysis underscored the pivotal role of GAS1, which was enriched in fibroblasts and implicated in the pathogenesis of MGLSc progression. Collectively, we highlighted the critical role of fibroblasts in initiating MGLSc onset, generating interactions with T cells and keratinocytes, and eliciting the classical histological features of MGLSc.

overall_design: In this study, we conducted single-cell RNA sequencing (scRNA-seq) analysis of 9 foreskin samples (3 normal, 3 paraLS, 3 LS) to delineate the cell atlas of normal and LS tissues.

first: Yu

last: Liu

first: Xiaocheng

last: Wang

first: Kun

first: Banghua

last: Liao

first: Shiqian

last: Qi

first: Liang

last: Zhou


title: SETDB1 Regulate Cell State Maintenance and Cell Fate Differentiation in DG

city: Shanghai

first: Yunli

last: Xie

state: Shanghai

address: 131 Dong'an Road, Shanghai

department: Institutes of Brain Science

institute: Fudan University

summary: In this study, we explored the function of histone methyltransferase SETDB1 in the development of the mouse dentate gyrus (DG). We discovered that a critical role of Setdb1 in steering the early development path of DG NSCs towards adult neural stem cells and astrocytes destinies. In an effort to delineate the exact molecular mechanisms of aberrant postnatal NSCs and astrocytes caused by Setdb1-deleted NSCs, we utilized a suite of techniques including RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) and Setdb1-Flag Cleavage Under Targets and Tagmentation (CUT&Tag) in both wild-type (WT) and Setdb1-deficient DG samples. Combination of transcriptome and epigenome analysis indicate that COX6B2 as a key target of SETDB1 for regulating maintenance of early postnatal NSCs and differentiation of astrocytes. Taken together, our results highlight the importance of transcriptomic and chromatin landscapes for metabolic reprogramming and identify a exquisite mechanism underlyling the cell state maintenance and cell fate differentiation.

overall_design: For all experiments, cells isolated from wild type and Setdb1 cKO mice were collected from mouse dentate gyrus (DG). Single cell sequencing library were prepared using 10x Genomics Chromium Single Cell 3`v3 assays.

first: Yunyun

last: Huang

first: Yue

last: Zhu


title: Very long-chain ceramides in skeletal muscle associate with systemic insulin resistance independent of obesity

city: Camperdown

first: Søren

last: Madsen

state: NSW

address: D17 Charles Perkins Centre – School of L, The University of Sydney

country: Australia

institute: University of Sydney

summary: Lipids are bioactive signaling molecules implicated in tissue-specific and whole-body insulin resistance, with ceramides and diacylglycerols (DAGs) as prominent species. Their precise roles remain unclear. Here, we leverage natural genetic variation in 399 male Diversity Outbred Australia (DOz) mice fed chow or a high-fat diet to examine the relationship between muscle lipids and insulin sensitivity. Fat mass was significantly associated with 55% of muscle lipid features and whole-body insulin sensitivity, with DAGs enriched in this association. To disentangle adiposity and muscle lipid contributions, we used: (1) linear models correcting lipid features for fat mass, and (2) insulin sensitivity quartiles within adiposity bins. Both approaches identified very long-chain ceramides, not DAGs, as linked to insulin resistance. RNA sequencing and proteomics from the same muscles associated these ceramides with cellular stress, mitochondrial dysfunction, and protein synthesis regulation. Meanwhile, DAGs correlated with leptin gene expression, suggesting an adipocyte, rather than myocyte, origin. These findings highlight very long-chain ceramides as key muscle lipids associated with insulin resistance, independent of adiposity.

overall_design: All samples are from quadriceps muscle from DOz mice fed chow diet ~18-20 weeks old.

first: David

middle: E

last: James


title: The transcription factor MtHAC-1 plays a dual role in regulating the production of cellulase and xylanase in Myceliophthora thermophila

city: Auckland

first: Yapeng

last: Lai

address: 55 Wellesley Street East,  Auckland Central

department: School of Science

country: New Zealand

institute: Auckland University of Technology

summary:
Background: Filamentous fungi produce large quantities of extracellular enzymes, such as cellulase and xylanase, to degrade polysaccharides derived from plant biomass. This process is controlled by a complex network of transcription factors (TFs). However, the regulatory mechanisms of cellulase and xylanase gene expression are poorly understood.
Results: In this study, we reveal that the bZIP transcription factor Mthac-1 exerts dual regulatory effects on the production of cellulase and xylanase in the filamentous fungus Myceliophthora thermophila. The absence of Mthac-1 caused a reduction in cellulase and xylanase activities, as well as decreased protein secretion during the early phase of cultivation in Avicel medium, compared with the wild-type (WT) strain. However, in the middle and late stages, enzyme activities and protein secretion were noticeably enhanced by the deletion of Mthac-1. Additionally, the loss of Mthac-1 led to severe growth defects on sloid media containing various carbon sources, characterized by few hyphae branching and reduced conidiation. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis showed that Mthac-1 dynamically regulates the expression of major cellulase genes. Furthermore, electrophoretic mobility shift assays (EMSAs) demonstrated that Mthac-1 directly binds to the promoter regions of the β-glucosidase gene bgl1 (MYCTH_66804), cellobiohydrolase gene cbh1 (MYCTH_109566), endoglucanase gene egl2 (MYCTH_86753), xylanase gene xyn1 (MYCTH_112050), and the crucial regulatory gene xyr1 (MYCTH_2310145), exhibiting higher binding affinity for xyn1 and xyr1. Notably, comparative transcriptomic analysis indicated that Mthac-1 also plays an important role in the expression of 26S proteasome-encoding genes under cellulolytic conditions.
Conclusions: Mthac-1 functions as a dual regulator of cellulase and xylanase production by regulating the expression of major cellulase and xylanase genes, as well as the key transactivator gene Mtxyr1, via direct promoter binding. Our work provides new insights into the regulatory mechanisms underlying cellulase and xylanase gene expression and has potential applications in fungal strain engineering in biorefinery industries.

sample_organism: Thermothelomyces thermophilus ATCC 42464

overall_design: The transcription factor MtHac-1 regulates cellulase and xylanase production in M. thermophila. To comprehensively clarify the regulation of MtHac-1, we conducted transcriptional profiling analysis of the WT and ΔMthac-1 strains cultured on Avicel for 48 h after transferring from glucose.

first: Juan

first: Gang

first: Donnabella C

last: Lacap-Bugler


title: Integrative Assessment of RNA-seq and IHC: Linking Tumor Biomarkers and Microenvironment

city: Waltham

first: Ekaterina

last: Postovalova

address: 95 Sawyer Road

country: USA

institute: BostonGene Corporation

summary: This study aimed to assess the correlation between RNA sequencing (RNA-seq) and immunohistochemistry (IHC) in detecting key cancer biomarkers across solid tumors, and then, to establish RNA-seq thresholds that accurately reflect clinical IHC classifications. Expression levels of nine biomarkers—ESR1, PGR, AR, MKI67, ERBB2, CD274, CDX2, KRT7, and KRT20—were analyzed in 365 formalin-fixed, paraffin-embedded samples from breast, lung, gastrointestinal, and other solid carcinomas. Correlations between RNA-seq data and IHC scores were determined using Spearman’s correlation coefficients, with RNA-seq cut-offs established to distinguish positive from negative IHC scores. The results revealed strong correlations for most biomarkers, with coefficients ranging from 0.53 to 0.89. RNA-seq thresholds were confirmed across internal and external cohorts, demonstrating high diagnostic accuracy (up to 98%) and precision in identifying biomarker expression levels. The analysis also highlighted the influence of tumor microenvironment and purity, particularly in the moderate correlation 0.63 observed for PD-L1. Our study demonstrates that RNA-seq can serve as a robust complementary tool to IHC, offering objective and high-throughput biomarker assessment. The RNA-seq thresholds established provide a reliable method for determining biomarker positivity, supporting the integration of RNA-seq in clinical diagnostics to enhance precision, especially where tumor purity and microenvironment factors are significant.

overall_design:
FFPE tissue blocks from 365 patient samples formed the internal cohort (Supplementary Table 1). For 313 patients, FFPE blocks from the clinical program were provided initially and used for RNA-seq. For 52 patients, tissue samples were originally provided as fresh frozen tissue (FF) specimens (were purchased from Cureline Tissue Bank (Brisbane, CA)), which were used for RNA-seq directly.

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

last: Kushnarev

first: Danil

last: Stupichev

first: Suren

last: Davitavyan

first: Kirill

last: Kriukov

first: Basavaraja

middle: U

last: Shanthappa

first: Anna

last: Butusova

first: Sofia

last: Menshikova

last: Belozerova

first: Arina

last: Tkachuk

first: Olga

last: Khatenkova

first: Linda

last: Balabanian

first: Jochen

middle: K

last: Lennerz

first: Funda

last: Meric-Bernstam

first: Alexander

last: Bagaev


title: Gene expression profiles  of WT and epithlial GSDMD ko mouse intestine [scRNA-seq]

city: hangzhou

first: Qianzhou

last: Yu

address: 866 Yuhangtang Road

institute: Zhejiang University

summary: The small intestine (SI) is the first site of absorption for life-sustaining nutrients and a gateway for external pathogens and toxins. Diet enables the host to initiate the SI absorptive machinery, while maintaining the barrier activity and a strict immune homeostasis.

overall_design: To uncover the role of epithelial GSDMD in SI physiology, we conditionally deleted Gsdmd in intestinal epithelial cells by generating Villin-cre+; Gsdmdf/f (GsdmdΔIEC) mice

first: Di

last: Wang


title: Gene expression profiles  of WT and epithlial GSDMD ko mouse intestine [bulk RNA-seq]


title: AMF30a Promotes Survival and Function of Human Corneal Endothelial Cells by Regulating TGF-β/ROCK/HIPPO Pathway

city: Seoul

first: Young joo

last: Shin

state: Seoul

address: 665-3 shiheungdaero, Shinkwan2dong

country: South Korea

institute: Hallym University

summary: Purpose: Corneal endothelial cells (CECs), located in the innermost layer of cornea, are crucial for maintaining its transparency. Peptidylarginine deiminase 2 (PAD2) is an enzyme responsible for catalyzing the post-translational modification of arginine into citrulline, a process known as citrullination. In this study, we investigated the effect of AMF30a, PAD2 inhibitor, on survival and function of CECs. Methods: Cultured human CECs (hCECs) were treated with AMF30a, followed by treatments with or without AMF30a under transforming growth factor-beta (TGF-β). Cells were cultured from donor corneas and analyzed for viability (CCK-8), proliferation (BrdU assay), cytotoxicity (LDH assay), and oxidative stress (DCF-DA). Adhesion and morphology were evaluated via crystal violet staining and imaging software. Western blot and immunofluorescence identified protein expression and localization. RNA sequencing revealed differentially expressed genes, with functional enrichment via GO analysis. Results: AMF30a enhanced cell viability, proliferation, and adhesion while reducing cytotoxicity and oxidative stress. Morphological analysis revealed reduced cell size and elongation factor, indicating structural changes. AMF30a modulated the HIPPO signaling pathway by increasing YAP phosphorylation and reducing its nuclear translocation, while downregulating ERK1/2 activation. Transcriptome analysis identified differentially expressed genes (DEGs) associated with AMF30a treatment, highlighting pathways related to GPCR signaling and protein targeting. Additionally, AMF30a counteracted TGF-β-induced effects, including increased oxidative stress, citrullination, and ROCK/HIPPO signaling activation, thereby promoting cell cycle progression and reducing senescence. Conclusion: PAD2-mediated citrullination is essential for TGF-β/ROCK/HIPPO signaling pathway. AMF30a promoted the proliferation and protected against TGF-β-induced senescence in hCECs, suggesting that PAD2 plays a significant role in the survival and function of hCECs. Thus, AMF30a may be a promising therapeutic strategy for hCEC diseases.

overall_design: RNA-seq profiling of corneal endothelial cells with or without AMF30a

first: Young Joo


title: A distinct response to gas vesicle collapse in native, but not heterologous expression hosts

city: HOUSTON

first: George

last: Lu

state: Texas

address: 6500 Main St

department: Bioengineering

institute: Rice University

summary: Microbial gas vesicles (GVs) are genetically encodable protein microbubbles that have seen a rapid rise in biomedical interest for their applications as acoustic reporter genes and handles. Unlike artificial microbubbles, their nonlinear response to increasing ultrasound pressure enables modes of imaging with increased contrast and signal. Beyond a characteristic threshold pressure, GVs collapse akin to breaking ballons and release the internal air, an effect that has been used to induce cavitation and distinguish them from background signals. In contrast to the biomedical utility, little is known about the physiological consequences of GV collapse. Here, we demonstrate that GV collapse in a natively GV-positive cell – Dolichospermum flos-aquae – has a distinct transcriptional response, which may be linked to reports of GV recovery post collapse. Conversely, the collapse of GVs in heterologous expressors such as E. coli does not reproduce this behavior. We attempt to provide an initial investigation into the underlying mechanism. Our findings support the existence of a cellular homeostasis mechanism that responds to GV collapse and highlight the importance of the cellular environment in supporting efficient GV assembly and in sensing GV collapse, a feature unique to native GV-producing microbes.

overall_design: Cultures of the Cyanobacteria Dolichospermum flos-aquae were grown in triplicates and subjected to sonication before isolation of RNA, followed by RNAseq analysis. Control cells were not subjected to sonication instead. The RNAseq data is intended to display the transcription-level response to collapse of gas vesicles in D. flos-aquae

first: Manuel

last: Iburg

middle: J


title: A lung cancer specific BACH1 transcriptional signature for identifying novel BACH1 inhibitors [ChIP-Seq]

city: Gothenburg

first: Volkan

last: Sayin

address: Medicinaregatan 1F

department: Department of Surgery

country: Sweden

institute: University of Gothenburg

summary: The transcription factor BACH1 is a transcriptional repressor with a central role regulating oxidative stress and anti-inflammatory pathways, emerging as a promising therapeutic target for multiple conditions, including neurodegenerative disorders, ischemia-reperfusion injuries, sickle cell disease and cancer. In the field of cancer BACH1 has gained significant attention, with BACH1 overexpression correlating with poor prognosis and metastasis across various cancer types; however, despite this increasing relevance of BACH1, no universal pro-metastatic mechanism or transcriptional signature for BACH1 has been identified which is a major limitation for this growing field. To fill this gap, in this study we performed RNA-Seq coupled with ChIP-Seq in BACH1 proficient and deficient lung cancer cells and identified a set of common BACH1 directly regulated genes, which we thoroughly validated in a large panel of cancer cells. This novel lung cancer BACH1 transcriptional signature is highly sensitive and specific to BACH1 perturbations (both genetic and pharmacological) and does not respond to NRF2 modulation, underscoring its specificity. This signature not only represents a robust surrogate for BACH1 activity, but we also provide evidence of its potential value as a tool to i) identify novel BACH1 inhibitors; and ii) provide insights into BACH1’s pro-metastatic role.

overall_design: To identify BACH1-regulated genes in lung cancer cells and develop a transcriptional signature specific to BACH1

first: Donika

last: Klenja

first: David

last: Walker

first: Kevin

middle: X

last: Ali

first: Maureen

last: Higgins

first: Angana

last: Patel

first: Dorota

last: Raj

last: Creelman

first: Charlotte

last: McDowald

first: Tomasz

last: Wenta

first: Erik

last: Lekholm

first: Clotilde

last: Wiel

middle: I

first: Laureano

last: de la Vega


title: A lung cancer specific BACH1 transcriptional signature for identifying novel BACH1 inhibitors

first: Anna


title: High-Fat Diet Driven Post-Operative Colon Cancer Recurrence is Dependent upon Genetic Susceptibility to Deoxycholic Acid

city: Chicago

first: Mohammad Amin

last: Bayat Tork

state: IL

address: 929 East 57th Street

department: Biochemistry and Molecular Biophysics

institute: University of Chicago

summary: The development of postoperative recurrence following surgical resection of colorectal cancer remains a major obstacle. While a high-fat diet is a risk factors for the development of recurrence studies that examine the molecular mechanism by which diet drives postoperative tumors have been lacking. Here, using a murine model that mimics postoperative tumor formation, we show that the tumorigenic influence of a high-fat diet strongly depends on the genetic backbone of the tumor cells. We identify deoxycholic acid as a major contributor to the promotion of tumor recurrence. We recapitulate the deoxycholic acid effect on the proliferation of tumoroids and identify the tumoroid response to the transcriptome expression and to transfer RNA abundance, modification, and charging. The integrated analysis of mRNA and tRNA sequencing results reveals enhanced decoding of codons in proliferation-promoting genes. Our results provide a new understanding of associating diet, tumor genetics, and a translation regulation mechanism in colorectal cancer recurrence.

overall_design: RNA-seq profiling of Organoid cells KPN (villinCreER KrasG12D/+ Trp53fl/fl Rosa26N1icd/+) and AKPT (villinCreER Apcfl/fl KrasG12D/+ Trp53fl/fl TrgfbrIfl/fl) at 48 h after Deoxycholic Acid(DCA) treatment in comparison with untreated cells.

first: Ryan

last: Morgan

first: Zitong

last: Lin

first: Claire

last: Wild

first: Luke

middle: R

last: Frietze

first: Sihao

last: Huang

first: Meejeon

last: Roh

first: Colin

last: Steele

first: Tao

last: Pan

first: Benjamin

middle: D

last: Shogan


title: High-Fat Diet Driven Post-Operative Colon Cancer Recurrence is Dependent upon Genetic Susceptibility to Deoxycholic Acid [tRNA-seq]

summary: The development of postoperative recurrent tumors or metastasis following surgical resection of colorectal cancer remains a major obstacle to colon cancer cure. While a high-fat diet is a risk factor for the development of recurrence, studies that examine the molecular mechanism by which diet drives postoperative tumors have been lacking. Here, using a murine model that mimics postoperative tumor formation, we show that the tumorigenic influence of a high-fat diet strongly depends on the genetic backbone of the primary tumor cells. We identify deoxycholic acid as a major contributor to the promotion of tumor recurrence only when the primary cancer cell line has an APC-driving, but not with an KRAS-driving mutation. We recapitulate the deoxycholic acid effect on the proliferation of tumoroids and identify the tumoroid response to the transcriptome expression and transfer RNA abundance, modification, and charging. The integrated analysis of mRNA and tRNA sequencing results reveals enhanced decoding of codons in proliferation-promoting genes. Our results provide a new understanding of how both diet and tumor genetics together lead to postoperative colorectal cancer recurrence.


title: A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region

city: New Orleans

first: Surjyadipta

last: Bhattacharjee

state: Louisiana

address: 2020 Gravier Street, Suite D, 8th floor

department: Neuroscience Center of Excellence

institute: LSU Health, New Orleans

summary: Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP’s limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund’s adjuvant (CFA)-induced inflammatory pain against no treatment and vehicle controls.

overall_design: Multiome sequencing (snRNA and snATAC) of PAG following CFA induced pain treated with analgesic drugs ApAP or SRP-001 compared to control and CFA induced pain with no treatment to determine genetic and epigenetic changes with analgesic treatment

first: Hernan

middle: A

last: Bazan

first: Brian

middle: L

last: Giles

first: Scott

last: Edwards

first: Nicolas

middle: G


title: Single-cell RNA-sequencing of HNSCC-infiltrating T cells

city: Houston

first: William

last: Hudson

state: TX

address: 1 Baylor Plaza

department: Molecular and Cellular Biology

institute: Baylor College of Medicine

summary: This study examines the T cell landscape in head and neck squamous cell carcinoma (HNSCC) using single-cell RNA sequencing combined with T cell receptor and protein profiling. By analyzing tumor-infiltrating T cells from 28 patients, we identified diverse T cell subsets, characterized their transcriptional states, and mapped their clonal dynamics. These findings provide a detailed view of the immune microenvironment in HNSCC and offer insights into T cell-mediated immunity and potential targets for immunotherapy and are patient-matched to PBMC TCR sequencing and Xenium spatial transcriptomics in separate GEO submissions.

overall_design: T cells (CD45+CD3+) were sorted from 28 patients with head and neck and squamous cell carcinoma (HNSCC) using a Cytek Aurora Cell Sorter. Cells originating from each patient were labeled with one Totalseq-C human hashtag antibody (BioLegend). Four patient samples with distinct hashtags were pooled and loaded into one well of a GEM-X microfluidics chip (10x Genomics). 16 GEM-X reactions were performed, run on two independent GEM-X microfluidics chips. Pools 1-7 were replicated on both chips, and two pools (pool 8 and pool 16) were each run on one chip. Hashes used for each patient and the patient composition of each pool are described in the patient_matrix.txt supplementary file. Hashtag sequences are as follows:  Hashing antibody sequences: hashtag 1 - GTCAACTCTTTAGCG; hashtag 2 - TGATGGCCTATTGGG; hashtag 3 - TTCCGCCTCTCTTTG; hashtag 4 - AGTAAGTTCAGCGTA.  Gene expression (GEX), T cell receptor (TCR), and CITE-seq libraries were generated for each pool according to the manufacturer's instructions.  For gene expression libraries, processed files include the aggregated gene expression and CITE-seq matrix from CellRanger. aggregation.csv lists the order of aggregation. A cloupe file of processed gene expression data for use in 10x Genomics' Loupe Browser software is also included. For T cell receptor (TCR) libraries, processed files for each sample are the folder output by cellranger vdj for each sample.  After completion of the study, one patient (patient #10) received a final diagnosis of ameloblastoma.

first: Hudson

last: William

first: McCord

last: Kelli


title: IFN-γ induced the formation of foamy macrophages by CD40 signaling control during Mycobacterium abscessus pulmonary infection

city: shanghai

first: Xianwei

last: Wu

address: No.725 South Wanping Road

department: Institute of Respiratory Diseases

institute: Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

summary: Transcriptome sequencing was performed to identify genes that might be responsible for the formation of a large number of lipid droplets with a combination of IFN-γ pretreatment and M. abscessus infection

overall_design: For transcriptome sequencing analysis of BMDM (2.5×106/well), cells were plated on 6 well glass bottom plate. Media was changed to either BMDM media, or BMDM media with 6.25 ng/mL recombinant murine IFN-γ (Novoprotein, Suzhou, China). After overnight IFN-γ pretreatment, BMDM were infected with M. abscessus at an MOI of 10. Following the 2-hour phagocytosis period, media was changed and IFN-γ was added again at 6.25ng/mL to all IFN-γ pre-treated wells. 48 hours post-infection, discard the supernatant and wash twice with sterile PBS. Total RNA was extracted from BMDM cells using TRIzol (Invitrogen, Carlsbad, California, USA) according to manual instruction.

first: Shaoyan

last: Zhang

first: Ya

last: Feng

first: Jiajun

last: Chen

first: Li

last: Tian

first: Hai

last: Lou

first: Liping

last: Wang

first: Ben

last: Su

first: Xing

first: Lei

last: Qiu

first: Dingzhong

first: Wei

last: Sha

first: Zhenhui

last: Lu


title: T cell receptor sequencing of HNSCC patient and healthy donor peripheral blood

summary: This dataset comprises TCR-seq data from peripheral blood CD4+ and CD8+ T cells of head and neck squamous cell carcinoma (HNSCC) patients and healthy donors. Viable peripheral blood mononuclear cells (PBMCs) were sorted into CD45+CD3+CD4+ (CD4+ T cells) and CD45+CD3+CD8+ (CD8+ T cells) subsets, and RNA was isolated using the Qiagen AllPrep DNA/RNA Micro kit. TCR libraries were prepared with the SMART-Seq Human TCR-seq with UMIs kit (Takara Bio) and sequenced on an Illumina NovaSeq X Plus platform. This dataset includes samples from 27 tumor patients and five healthy donors (HDs).  The study aims to investigate the phenotype, function, and spatial localization of T cells in HNSCC patients. This peripheral blood dataset focuses on characterizing circulating immune determinants of anti-HNSCC immunity and linking circulating T cell clones to those identified in patient-matched tumor scRNA-seq data.

overall_design: CD4+ and CD8+ T cells were sorted from PBMCs of 27 HNSCC patients and 5 healthy donors (HDs). RNA was isolated and TCRs were sequenced using the SMART-Seq Human TCR-seq with UMIs kit from Takara Bio.

first: Kelli

last: McCord

first: Sean

last: Hyslop


title: Non-Mutated Human Tau Stimulates Alzheimer’s Disease-Relevant Neurodegeneration in a Microglia-Dependent Manner

last: Cao

address: 6431 Fannin Street

institute: The University of Texas Health Science Center at Houston

summary: The accumulation of abnormal, non-mutated tau protein is a key pathological hallmark of Alzheimer’s disease (AD). Despite its strong association with disease progression, the mechanisms by which tau drives neurodegeneration in the intact brain remain poorly understood. Here, we selectively expressed non-mutated or mutated MAPT in neurons across the brain and observed neurodegeneration in the hippocampus, especially associated with non-mutated human tau. Single-nuclei RNA sequencing confirmed a selective loss of hippocampal excitatory neurons and revealed the upregulation of neurodegeneration-related pathways in the affected populations. The accumulation of phosphorylated tau was accompanied by cellular stress in neurons and reactive gliosis in multiple brain regions. Notably, the lifelong absence of microglia significantly and differentially influenced the extent of neurodegeneration in the hippocampus and thalamus. Therefore, our study established an AD-relevant tauopathy mouse model, elucidated both neuron-intrinsic and neuron-extrinsic responses, and highlighted a critical role for microglia in modulating tau-driven neurodegeneration.

overall_design: To establish a model of tau pathology in vivo, we inoculated neonatal C57BL/6J mice at post-natal day 0 with AAV vectors containing one of three forms of human MAPT transcript: the first with an early STOP codon preventing translation of tau protein which served as a control virus (AAV-STOP), the second expressing full-length 2N4R wild-type human tau (AAV-Tau). The AAVs were delivered bilaterally into the intracerebroventricular spaces. To investigate molecular changes in neuronal populations during pathology induced by wild-type human tau expression, we performed single-nucleus RNA sequencing (snRNA-seq) on pooled hippocampi from animals receiving AAV-STOP or AAV-Tau at 6 weeks of age (N=3 per group).

first: Ethan

last: Roy

first: Qiang

first: Kexin

last: Huang

first: Sanming

last: Li


title: Loss of SETD8 remodels enhancer chromatin accessibility to eliminate t(8;21) leukemia stem cells by mitochondrial homeostasis reprogramming [RNA-seq]

city: changchun

first: yongwei

last: su

address: 2699 qianjin street

institute: Jilin university

summary: Leukemic stem cells (LSCs) are at least partially responsible for relapse and resistance in patients with t(8;21) acute myeloid leukemia (AML), while the intricate regulatory network governing LSC stemness is yet to be fully elucidated. Chromatin accessibility remodeled by epigenetic alterations represents a defining hallmark of LSCs, endowing them with enhanced survival and self-renewal capacities, which may offer potential therapeutic opportunities for intervention. Here, we show that SETD8, a lysine methyltransferase that monomethylates lysine 20 of histone H4 (H4K20me1), is essential for the maintenance of stemness in t(8;21) AML LSCs. Genetic deletion or pharmacological inhibition of SETD8 impairs the survival and self-renewal of LSCs in retroviral AML1-ETO9a-driven t(8;21) AML mice and primary t(8;21) AML CD34+ cells. Mechanistically, SETD8 promotes the expression of Ras homolog family member T1 (RHOT1), a mitochondrial outer membrane protein, by increasing chromatin accessibility at the enhancer region, thereby reprogramming mitochondrial homeostasis. These findings improve our understanding of the gene regulation through chromatin accessibility remodeling and establish a link between histone lysine methylation and mitochondrial homeostasis, suggesting a potential strategy for eliminating LSCs in t(8;21) AML.

overall_design: RNA-seq in Kasumi-1 cells after SETD8 knockout by CRISPR/Cas9.

first: Yongwei

first: Shuyi

first: Jingfeng

last: Zhou

last: Yu


title: Site-Specific HPV18 Integration Facilitates Cervical Carcinogenesis through metabolic reprogramming-Induced dysfunction of the SpHK1/S1P/S1PR1 pathway

city: Hangzhou

first: Wang

last: Hui

state: Zhejiang

address: First of Xueshi road

department: Department of Gynecological Oncology

institute: Women’s Hospital, School of Medicine, Zhejiang University

summary: The integration of high-risk human papillomavirus (HR-HPV) into specific loci of the human genome is a pivotal event in cervical carcinogenesis. However, how HPV integration contributes to malignant transformation remains unclear. Here, we utilized the CRISPR/Cas9 system established an 8q24 site-specific HPV18 gene knock-in cell model. We discovered that HPV18 knock-in resulted in a global alteration of the genome's topologically associating domain (TAD) structure and up-regulation of cancer-related genes in HaCaT cells, leading to malignant transformation. Furthermore, the IL-17 signaling pathway and S100A8/A9 genes were found to be significantly up-regulated in the HPV18 knock-in cell line, as well as K14-HPV transgenic mice and cervical cancer clinical database. Metabolic reprogramming of the HPV18 knock-in cell line, particularly the up-regulation of glycolysis, facilitated glycerolipid synthesis and Sphingosine-1-phospate(S1P) secretion. The increased secretion of S1P and activation of the S1P receptor 1(S1PR1) signaling pathway induced the expression of S100A8/A9 and cytokines. Inhibition of the S1P/S1PR1 signaling pathway down-regulated the expression of S100A8/A9 and suppressed the growth of HPV18 knock-in cell line and cervical cancer patient derived Xenograft. These findings provide novel insights into the molecular mechanisms underlying cervical carcinogenesis and identify potential therapeutic targets for its treatment.

overall_design: We employed CRISPR/Cas9 gene editing combined with homologous end repair for the establishment of stable 8q24 site-specific HPV18 gene knock-in cell lines using HaCaT as the parent. The HPV-KI cells were treated with 2-DG, FSG67, W146 and JTE013 to explore the metabolic proramming in HPV-KI/HaCaT

last: Liming

first: Li

last: Xiaomin

first: Ren

last: Ci

first: Liu

last: Liting

first: Yuan

last: Zan

first: Huang

last: Yafei


title: Site-Specific HPV18 Integration Facilitates Cervical Carcinogenesis through metabolic reprogramming-Induced dysfunction of the SpHK1/S1P/S1PR1 pathway-part2

first: Liming

last: Wang

first: Xiaomin

first: Ci

last: Ren

first: Liting

last: Liu

first: Zan

last: Yuan

first: Yafei

first: Hui


title: Loss of SETD8 remodels enhancer chromatin accessibility to eliminate t(8;21) leukemia stem cells by mitochondrial homeostasis reprogramming [ATAC-seq]

first: yongwei

overall_design: ATAC-seq in Kasumi-1 cells after SETD8 knockout by CRISPR/Cas9.

last: Su


title: Next Generation Sequencing Facilitates Quantitative Analysis of  Spleenic T-DC Transcriptomes in mouse T cell acute lymphoblastic leukemia

city: Tianjin

first: cui

last: xiaoxi

address: 288 Nanjing Road

institute: Peking Union Medical College

summary: The aim of this study is to uncover the functional and phenotypic diversity of N-mDCs from normal mice, as well as T-DCs and T-mDCs from mice with T-cell acute lymphoblastic leukemia

overall_design: Compare Transcriptomes of Normal-mDCs, T-DCs and T-mDCs.

first: Guoguang

last: Zheng

first: Lina

first: Xiaoxi

last: Cui


title: REL deregulation stands as a primary hit for AID-imprinted B-cells along the germinal center competition

city: Limoges

first: Nathalie

last: Faumont

address: Rue Bernard Descottes

department: Centre de Biologie et de Recherche en Santé

country: France

institute: Université e Limoges

summary: In diffuse large B-cell lymphomas (DLBCLs), gains and amplifications of the 2p15-16 region, which always encompass the REL gene, are mostly restricted to the germinal center (GC) B-cell DLBCL subtype (GCB-DLBCL) for which c-Rel is the pivotal Rel/NF-kB subunit. While REL also plays a key role in the GC reaction, its contribution to GCB-DLBCLs remains unclear. At the transcriptomic and phenotypic level, we demonstrate that dysregulation of REL at the GC B-cell stage promotes GC B-cell expansion and favors both class-switch recombination and plasma cell differentiation. Additionally, although REL overexpression was neutral on post-GC memory B-cell differentiation, it did confer a long-term competitive advantage allowing for GC persistence and continuous recirculation of REL-overexpressing B-cells. Functionally, REL enhanced the protection against apoptosis in the early steps of GCB differentiation. Additionally, mRNA IGHV dominance was increased in REL-overexpressing B-cells and clonal expansion could be detected at the DNA level in some cases.

overall_design: To understand the role of REL in the very first steps of GCB transformation, i.e when B-cells with deregulated REL are competing with other B-cells during chronic antigenic stimulation, we have created a dual-color mouse that allows to induce REL in a limited pool of AID-imprinted B-cells after immunization and to differentially stain AID-imprinted B-cells cells that overexpress REL or not.

first: Karima

last: Ferhat

first: Dilara

last: Sensoy

first: Ophélie

last: Téteau

first: Jean

last: Feuillard


title: Loss of SETD8 remodels enhancer chromatin accessibility to eliminate t(8;21) leukemia stem cells by mitochondrial homeostasis reprogramming [CUT&Tag (H4K20me1)]

last: su

overall_design: CUT&Tag of H4K20me1 in Kasumi-1 cells after SETD8 knockout by CRISPR/Cas9.

first: Yongwei

first: Shuyi

last: Li

first: Jingfeng

last: Zhou

first: Li

last: Yu


title: Loss of SETD8 remodels enhancer chromatin accessibility to eliminate t(8;21) leukemia stem cells by mitochondrial homeostasis reprogramming [CUT&Tag (H3K27ac)]

overall_design: CUT&Tag of H3K27me1 in Kasumi-1 cells after SETD8 knockout by CRISPR/Cas9.


title: IRE1alpha cancer mutants diiferentially regulate Rho family GTPases

city: University Park

first: Adam

middle: Bleier

last: Glick

state: PA

address: 108 AVBS Building

department: Department of Veterinary and Biomedical Sciences

institute: Pennsylvania State University

summary: IRE1alpha is a multi-domain, ER-transmembrane protein that can mediate the Unfolded Protein Response (UPR). Here, we show that cancer-specific mutations in IRE1alpha can differentially activate the Rho family GTPases to mediate  tumor promoting events in mouse keratinocytes.

overall_design: To investigate the roles of cancer-relevant mutations in IRE1alpha during skin carcinogenesis, we generated multicellular spheroids (MCS) of immortalized mouse keratinocytes line C57-T inducibly expressing wildtype (WT) or cancer-relevant IRE1alpha mutations for 24h using doxycycline. We pooled 30 spheroids per cell line per replicate, extracted total cellular RNA, which was used for differential gene expression profiling by RNA-Seq to identify genes potentially regulated by IRE1alpha. Biological triplicates were generated and processed for all conditions. Samples were compared against the parent C57-T cells.

first: Mogre

last: Saie

first: Robinson

last: Lily

first: Sethia

last: Komal

first: Rimal

last: Bipin

first: Son

last: Jeongin

first: Pacifico

last: Christian

first: Santy

last: Lorraine

first: Patterson

last: Andrew

first: Glick

last: Adam Bleir


title: Synergism 1 between RUNX1 and PHF6 mutations in leukemogenesis [scRNAseq]

city: Taipei City

first: Chi-Yuan

last: Yao

address: No.7, Chung Shan S. Rd.

department: Hematology

country: Taiwan

institute: National Taiwan University Hospital

summary: RUNX family transcription factor 1 (RUNX1) mutated acute myeloid leukemia (AML) has now been formally classified as AML with myelodysplasia-related gene mutations, and considered to predict adverse prognosis. In addition, mutations of RUNX1 and plant homeodomain finger gene 6 (PHF6) frequently co-occurred and conferred particularly adverse clinical outcomes. Becasue the pathological effects of these combined mutations remained understudied, we sought to address this topic through genetically modified mouse models. We found that Phf6 knockout and RUNX1 double-mutated bone marrow (BM) cells displayed significantly higher engraftment capacity, and recipient mice transplanted with double-mutated BM cells developed AML with significantly shortened survival. We also discovered that the multipotent progenitors (MPPs) were the main cell subpopulation responsible for double-mutated BM cell-induced leukemia. Our findings highlighted the synergistic leukemogenic potential of Phf6 and RUNX1 mutations in vivo, and provided evidence for possible underlying molecular mechanisms.

overall_design: We transduced vectors carrying the RUNX1-S291fs mutation (with GFP) into wild-type (WT) and Phf6 knockout (KO) mouse BM cells, and then sorted GFP+ cells, which were transplanted into recipient mice. Eight-week post-transplant, we sorted for GFP+Lin- cells from recipient mice bone marrow for scRNA-seq.

first: Yueh-Chwen

last: Hsu

first: Wen-Chien

last: Chou


title: Depot-dependent transcriptomic profile of human adipose tissue macrophages

city: Badalona

first: Lauro

last: Sumoy

state: Barcelona

address: Ctra. Can Ruti, Camí de les escoles s/n

department: High Content Genomics and Bioinformatics

country: Spain

institute: IGTP

summary:
Macrophages from visceral and subcutaneous white adipose tissue (vWAT and sWAT, respectively) can have opposing roles in the systemic metabolic changes associated with obesity.
We evaluated the gene expression in CD11b positive macrophage cells from vWAT and sWAT and in the whole adipose depots.

overall_design: A Clariom D-based transcriptomics analysis was performed in macrophages magnetically separated from vWAT and sWAT from patients with obesity (Cohort 1; N = 11). The experimental design for hybridization processing included 4 batches of 9-11 samples each with balancing among different batches between the two compared conditions: vWAT and sWAT.

first: Marjorie

last: Reyes-Farias

first: Pablo

last: Fernández-García

first: Patricia

last: Corrales

first: Lorena

last: González

first: David

last: Navarro-Sanagustin

first: Andrea

last: Soria-Gondek

first: Silvia

last: Pellitero

first: Jordi

last: Tarascó

first: Pau

last: Moreno

first: María

last: Galán

first: Ester

last: Martínez

first: Francesc

last: Villarroya

first: Rubén

last: Cereijo

first: Laura

last: Herrero

last: Sánchez-Infantes


title: Hepatocellular Carcinoma Escapes Immune Surveillance through Deceiving Thymus into Recalling and Killing Peripheral Activated CD8+ T Cells

city: Fuzhou

first: Qiao

middle: ting

last: Hu

state: Fujian

address: 420 Fuma Road, Jin'an District

department: Medical oncology

institute: Fujian medical University

summary: BACKGOUND & AIMS: The role of thymic epithelial cells (TECs) in elimination of self-reactive T cells through presentation of self-antigens is well-established. However, it remains unclear whether TECs can effectively clear hepatocellular carcinoma (HCC)-reactive T cells by presenting HCC-associated antigens. METHODS: HCC nodules and thymuses were harvested from spontaneous and in situ transplanted tumors. Differentially expressed proteins or genes in the aforementioned tissues were determined using liquid chromatograph mass spectrometer (LC-MS) and mRNA transcriptomic sequencing (mRNA-seq). Cell death in histological tissue sections was detected and quantified through the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique. Specific protein expression and immune phenotype were evaluated by multiplex immunofluorescence staining and flow cytometry. RESULTS: In comparison to normal thymuses, there is a significant increase in CD8+ T cell death within the thymuses of HCC model mice. Notably, a substantial portion of these dead cells are peripheral activated T cells homing to the thymus. Mechanistically, TECs did not express tumor-associated antigens by themselves, instead, they captured antigens from HCC cells for antigen presentation. Thymus-homing tumor antigen-specific T cells-initiated activation-induced T cell death (AICD) when they recognized the same antigen presented by TECs. Thymectomy suppressed HCC tumor by redistributing CD8+ T cells into the tumor focus. Importantly, instead of thymectomy, adenosine monophosphate activated protein kinase (AMPK) activator and C-C chemokine receptor type 7 (CCR7) antagonist dramatically decreased immune escape while effectively restrained HCC through curtailing the thymus homing of peripheral activated CD8+ T cells. CONCLUSION: Our findings suggest that HCC deceives thymus into recalling and killing peripheral activated CD8+ T cells. Pharmacological blocking thymus homing of CD8+ T cells via AMPK activation and CCR7 antagonism would be an attractive and promising strategy for HCC prevention and treatment.

overall_design: To investigate the impact of hepatocellular carcinoma (HCC) on thymic gene expression and biological function, we established a diethylnitrosamine (DEN) combined with carbon tetrachloride (CCl4)-induced HCC model in C57BL/6J mice. We then obtained HCC and thymus samples for mRNA sequencing analysis.

first: Qiaoting

first: Xuefeng

last: Wang

first: Ting

last: Xu

first: Xiaojun

last: Cai

first: Yangkai

last: Ou


title: ER-phagy and proteostasis defects create a pre-malignant injury state in Kras-mediated tumourigenesis (RNA-Seq)

city: Edinburgh

first: Carla

last: Salomo Coll

address: Crewe Rd S

department: Institute of Genetics and Cancer - CRUK Scotland Centre

country: United Kingdom

institute: University of Edinburgh

summary: Pancreatic acinar cells are surprisingly resistant to pre-malignant transformation by the mutant Kras oncogene. Here, reporter mice show that an early, transcriptionally-mediated effect of Kras activation is downregulation of ER-phagy. Subsequently, stochastic failure of ER-phagy correlates with pre-malignant transdifferentiation into acinar-ductal metaplasia (ADM). Genetic perturbation of ER-phagy, combined with proteomics and transcriptomics, reveals endogenous injury, micro-inflammation and ADM across the acinar epithelium. Phenotypically, this occurs alongside intra-acinar formation of distinctive insoluble aggregates of ER proteins, including the injury marker REG3B. Mechanistically, REG3B is shown to bind to the ER-phagy receptor CCPG1 to facilitate degradation. Strikingly, spatial transcriptomics shows that oncogenic Kras also drives this cell state in a highly stochastic fashion, again characterised by protein aggregation, partial ductal identity, evidence of injury and propensity for ADM. Importantly, expression of insoluble mutant REG3B shows that protein aggregate formation directly engenders this state. Pancreatic cancer can thus arise from stochastic proteostatic defects that are both made probable by, and co-operate with, oncogenic Kras.

overall_design: To investigate the transcriptional effect of loss of ER-phagy in murine pancreatic acinar cells, Ccpg1 was floxed in KC mice (LSL-KrasG12D; Pdx1-Cre). RNA was extracted from pancreata of 10-week-old mice, 8 KC Ccpg1+/+ an 8 KC Ccpg1ΔPanc. Differential gene expression analyses were performed using data from bulk mRNA-Seq.

first: Simon

last: Wilkinson


title: ER-phagy and proteostasis defects create a pre-malignant injury state in Kras-mediated tumourigenesis (Spatial transcriptomics)

overall_design: Four FFPE tissue samples from 10-week-old KC mice (LSL-KrasG12D; Pdx1-Cre) were analysed by NanoString GeoMX Digital Spatial Profiling. A total of 5 different cell populations were identified based on morphology markers (REG3A/B, Amylase, PanCK) and geographic component.


title: Dauricine regulates SAT1 to induce ferroptosis and overcome osimertinib resistance in Non-small cell lung cancer

city: Guangzhou

first: 碧莹

last: 门

address: 广东省广州市白云区广州大道北1838号南方医科大学

institute: 南方医科大学

summary: Targeted tyrosine kinase inhibitors (TKIs) play a crucial role in the treatment of lung cancer; however, nearly all patients face the challenge of TKI resistance. Unraveling the molecular mechanisms of TKI resistance and effectively addressing it is a pressing clinical issue. We have successfully established a third-generation TKI-resistant lung cancer cell line and organoids, and identified batatasin alkaloid from 302 traditional Chinese medicines as capable of effectively overcoming osimertinib resistance. Our scientific hypothesis posits that batatasin alkaloid improves osimertinib resistance by modulating ACSL1 to influence lipid peroxidation-induced ferroptosis. This project aims to utilize various lung cancer models to elucidate the relationship between osimertinib resistance and ferroptosis in lung cancer, uncover the specific molecular mechanisms by which batatasin alkaloid regulates ACSL1, and explore the feasibility of batatasin alkaloid in improving osimertinib resistance. This project will unveil novel molecular mechanisms of TKI resistance in lung cancer and explore the application of traditional Chinese medicine in overcoming resistance to targeted therapy for lung cancer.

overall_design: To investigate the difference in the efficacy of DAC and OSI when administered alone versus when administered simultaneously,our experimental design was divided into four groups:  control, osimertinib(OSI), Dauricine(DAC), Dauricine and osimertinib(DAC+OSI)


title: Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth [RNA-seq]

city: Denver

first: Pluto

last: Bio

state: CO

address: 3575 Ringsby Ct Suite 414

institute: Pluto Bio

summary: Posterior fossa molecular subtype A (PFA) ependymoma occurs in young children and is the deadliest subtype of pediatric ependymoma. High-risk subtypes with chromosome 1q+ and/or 6q- exhibit significantly poorer outcome compared to wild-type PFA. However, 50% of wild-type PFA patients relapse and there is a high risk of gaining chromosome 1q at recurrence. We previously found constitutively active NF-kB, through loss of LDOC1, led to chronic IL-6 secretion and an overall immunosuppressive tumor microenvironment in the higher risk wild-type PFA ependymoma subset (PFA1). In this study, we delineate the mechanistic consequences of LDOC1 loss in PFA1, using our PFA ependymoma in vitro and in vivo models under normoxia and hypoxia conditions. We noted chromatin compaction by H3K27me3 at the LDOC1 loci results in loss of LDOC1 gene expression. Restoration of LDOC1 was sufficient to reduce proliferation, NF-kB signaling and significant decrease in IL-6 secretion. Furthermore, tumors implanted with LDOC1- transduced cells in vivo were out competed by non-transduced cells, suggesting loss of LDOC1 is required for PFA tumor growth. These findings shed further light on the biology of PFA1 ependymoma and the role LDOC1 loss has on the tumor and immunobiology of high risk pediatric ependymoma.

overall_design: EPN cell lines were grown in normoxia (5%O2) or hypoxia (2% O2) for 72hrs.

first: Graziella

last: Ribeiro de Sousa

first: Annaliese

last: Calzadilla

first: Enrique

last: Grimaldo

first: Andrew

middle: M

last: Donson

first: Lays

last: Martin Sobral

first: Kendra

last: Jones

first: Tian

last: Liu

first: Vladimir

last: Amani

first: Sujatha

last: Venkataraman

first: Nathan

last: Dahl

first: Jean

last: Mulcahy Levy

first: Tzu

last: Phang

first: Rajeev

last: Vibhakar

first: Todd

last: Hankinson

first: Michael

last: Handler

first: Elvis

last: Terci Valera

first: Nicholas

last: Foreman

first: Andrea

last: Griesinger


title: Epigenetic methylation chip analysis of childhood PFA ependymoma cell lines cultured in normoxia versus hypoxia

city: Aurora

department: Pediatrics

institute: CU Anschutz Medical Campus

type: Methylation profiling by genome tiling array

summary: DNA methylation analysis was perfomed using Infinium EPIC Methylation BeadChip platform on 12 PFA ependymoma cell lines samples. Idat files were batch normalized and background corrected using default settings of the R package ChAMP to obtain GpG methylation beta values for analysis of differentially methylated GpG regions on the LDOC1 locus.

overall_design:
Bisulphite converted DNA from the 12 samples were hybridised to the Illumina Infinium EPIC Methylation Beadchip

***Processed data not provided***


title: Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth [CUT&RUN]

first: Pluto

last: Bio

first: Graziella

last: Ribeiro de Sousa

first: Annaliese

last: Calzadilla

last: Martin  Sobral

last: Terci  Valera


title: Spatial 3D genome organization controls the activity of bivalent chromatin during human neurogenesis

city: San Francisco

first: Mitchel

last: Cole

state: CA

address: 35 Medical Center Way

department: Neurological Surgery

institute: UCSF

summary: Subnuclear compartments including the nuclear lamina and speckles organize the genome in three-dimensional (3D) space and regulate gene expression. By studying the neurogenic cell lineage isolated directly from the human brain, we show that lamina association plays a dominant role in maintaining the lowly expressed, poised state of key developmental genes bivalent for H3K27me3 and H3K4me3. During neurogenesis, large regions of the genome relocate from the lamina to speckles, corresponding to enhanced resolution of bivalent chromatin to monovalent H3K4me3 and a ~7-fold increase in transcription. Using cell culture models of human neurogenesis, we confirm the bivalent state of lamina-associated genes and provide further evidence that lamina association contributes strongly to the low expression of bivalent genes independent of H3K27me3.  These data support a model in which spatial location of genomic regions in relation to subnuclear structures plays a dominant role in regulating the activity of chromatin state and lineage-specific gene expression.

overall_design: LaminB1 GO-CaRT followed by sequential ChIP (LaminB1 GO-CaRT.ChIP-reChIP) and H3K27me3/H3K4me3 CUT&RUN of iPSC-derived NPCs; LaminB1 CUT&Tag, H3K27me3/H3K4me3 CUT&Tag of iPSC-derived NPCs and iPSC-derived neurons (iN); LaminB1 GO-CaRT and H3K27me3/H3K4me3 CUT&RUN of ESC-derived NPCs treated with DMSO or EZH2 inhibitor, EPZ-6438; H3K27me3 CUT&RUN and LaminB1 GO-CaRT of HEK293T cells with or without Fab blocking

first: Chujing

last: Zhang


title: Genome-wide analysis of H3K27ac and RBPJ distribution in a human chronic B cell leukemia cell line.

city: Philadelphia

first: Tobias

last: Friedrich

state: Pennsylvania

address: 421 Curie Boulevard

institute: University of Pennsylvania

summary: The Notch signaling pathway regulates several processes including development and differentiation and its aberrant regulation leads to several diseases such as leukemia. Here, we investigated the genome-wide distribution of the transcription factor RBPJ and of the active histone mark H3K27ac in a human chronic B cell leukemia cell line called HG3.

overall_design: Human HG3 cells were analyzed by ChIP-Seq using an RBPJ-specific antibody or by CUT&TAG  using an antibody directed against H3K27ac.

first: Benedetto

last: Giaimo

first: Tilman

last: Borggrefe


title: Combustion products of burn pit constituents induce more changes in murine lungs with pre-existing asthma than naïve lungs

city: Chapel Hill

first: Lanazha

last: Belfield-Simpson

address: 125 Mason Farm Rd

institute: Univeristy of North Carolina at Chapel Hill

summary: ABSTRACT

overall_design: Gene expression profiling analysis was performed on RNA obtained from the lung of 1) HDM or PBS mice exposed to saline 2) HDM or PBS mice exposed to combustion products (CP). CP= a mixture consisted of  paper, plastic and  plywood burned under controlled combustion.

first: Jessica

last: Martin

first: Alessandra

last: Liveraghi-Butrico

first: Hong

last: Dang

first: Yong Ho

last: Kim

first: Matthew

last: McPeek

first: Ian

last: Gilmour

first: Claire

last: Doerschuk


title: Bulk RNA-seq of duodenal mucosa of potential Celiac disease with progression

city: St. Louis

first: Eric

last: Tycksen

state: Missouri

address: 4444 Forest Park Avenue

department: McDonnell Genome Institute

institute: Washington University in St. Louis School of Medicine

summary: Celiac disease (CeD) is an immune-mediated chronic enteropathy caused by gluten exposure in HLA-DQ2 and/or -DQ8 positive individuals. The hallmarks of CeD include increased intraepithelial lymphocytes and villous atrophy. Clinically, a small subset of individuals with elevated serum tissue transglutaminase antibody (TTG) concentrations but unremarkable duodenal mucosa at initial endoscopy may progress to CeD over time. We hypothesize that these rare CeD precursor cases can allow us to interrogate histologic and molecular signatures to predict those who subsequently develop CeD, and to study the final cascade into overt lesions in CeD.

overall_design: Formalin-fixed paraffin embedded (FFPE) duodenal biopsies were analyzed by bulk RNA-seq. Transcriptomes of duodenum from CeD precursor children were compared with those of children with CeD and children with normal duodenum and negative Celiac serology (negative control).

first: Changqing

last: Ma

first: Adina

last: Bard

first: Brian

last: Muegge

first: Phillip

last: Tarr

first: Lori

last: Holtz

first: Ta-Chiang

last: Liu


title: Spatial 3D genome organization controls the activity of bivalent chromatin during human neurogenesis [RNA-seq]

first: Mitchel

last: Cole

overall_design: RNA-seq of iPSC-derived NPCs and iPSC-derived neurons (iN); RNA-seq of ESC-derived NPCs treated with DMSO or EZH2 inhibitor, EPZ-6438

first: Chujing

last: Zhang


title: Gene epression analyses on pre- and post-treatment samples obtained from AML patients who respond or failed to respond to  Venetoclax/Decitabine treatment

city: Tokyo

first: Kotoko

last: Yamatani

address: Building A 6F, Hongo Bunkyo-ku 2-1-1

country: Japan

institute: Juntendo University

summary: To elucidate the underlying mechanisms of resistance to venetoclax and dexitabine combination therapy, we performed transcriptomic analysis of VEN/DEC pre- and post-treatment samples from AML patients enrolled in the DEC10-VEN clinical trial (NCT03404193). We have reported that AML cells from non-responders show a significant upregulation of the mRNA expression of the fatty acid metabolism activator PPARG (Peroxisome Proliferator-Activated Receptor γ) after VEN/DEC treatment.

overall_design: We investigated differentially expressed genes beween AML cells obtained from responders and nonresponders

first: Yoko

last: Tabe


title: Loss of LDOC1 by chromatin compaction in mesenchymal tumor cells is required for PFA1 ependymoma growth

first: Pluto

last: Bio

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

overall_design: Refer to individual Series


title: Hepatoprotective Effect of Nitrate Against Methotrexate-Induced Liver Injury by Activating Wnt/β-Catenin Signaling in Mice

city: beijing

first: Xin

last: Wen

address: awfa

institute: Capital Medical University

summary: Methotrexate (MTX) is an effectively used drug for certain forms of cancer and autoimmune diseases. However, its hepatotoxicity severely limits its clinical use which has no effective treatment but withdrawal. Therefore, further study is required to combat the liver injury associated with MTX. Nitrate, abundant in green vegetables, possesses diverse physiological roles including anti-inflammatory, antioxidant, and immunoregulation. This study investigated the preventive effect of nitrate on MTX-induced liver injury. The liver injury model in mice was induced by a single dose of MTX (20 mg/kg) injected intraperitoneally (i.p.). Administration of 2 mM nitrate in drinking water 5 days prior effectively mitigated MTX-elevated serum aminotransferases, attenuated hepatic pathological injury, reduced the level of hepatic apoptosis, and restored the proliferative capacity of hepatocytes. The molecular mechanism may involve the activation of the Wnt/β-catenin pathway. In this study, the hepatoprotective effect of nitrate on drug-induced liver injury (DILI) was identified for the first time, which provides a new idea for the prevention of drug-induced liver injury in clinical practice.

overall_design: To investigate the effect of nitrate on MTX-induced liver injury, the mice were given 2 mM nitrate water for 5 days, and a sigle dose of MTX (20mg/kg, i. p.) on day 5 and the liver were collected for analysis 24 h after the injection.

first: Ying

first: Songlin

last: Wang

first: Shaorong

last: Li


title: SETDB1 Orchestrates Metabolic Reprogramming to Regulate Cell State Maintenance and Cell Fate Differentiation

city: Shanghai

first: Yunli

last: Xie

address: 131 Dong'an Road, Shanghai

department: Institutes of Brain Science

institute: Fudan University

summary: In this study, we explored the function of histone methyltransferase SETDB1 in the development of the mouse dentate gyrus (DG). We discovered that a critical role of Setdb1 in steering the early development path of DG NSCs towards adult neural stem cells and astrocytes destinies. In an effort to delineate the exact molecular mechanisms of aberrant postnatal NSCs and astrocytes caused by Setdb1-deleted NSCs, we utilized a suite of techniques including RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) and Setdb1-Flag Cleavage Under Targets and Tagmentation (CUT&Tag) in both wild-type (WT) and Setdb1-deficient DG samples. Combination of transcriptome and epigenome analysis indicate that COX6B2 as a key target of SETDB1 for regulating maintenance of early postnatal NSCs and differentiation of astrocytes. Taken together, our results highlight the importance of transcriptomic and chromatin landscapes for metabolic reprogramming and identify a exquisite mechanism underlyling the cell state maintenance and cell fate differentiation.

overall_design: For all experiments, cells isolated from wild type and Setdb1 cKO mice were collected from mouse dentate gyrus (DG). Single cell sequencing library were prepared using 10x Genomics Chromium Single Cell 3`v3 assays. For bulk RNA-seq, dentate gyri were isolated from P7 mouse brains. Total RNA was extracted using Trizol reagent and applied for RNA sequencing. Setdb1-Flag Cleavage Under Targets and Tagmentation (CUT&Tag) in both wild-type (WT) and Setdb1-deficient DG samples. Assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) in both wild-type (WT) and Setdb1-deficient DG samples.

first: Yunyun

last: Huang

first: Yue

last: Zhu


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SSPDX.RNA-seq]

city: Richmond

first: Mikhail

last: Dozmorov

state: VA

address: 830 E Main St

department: Biostatistics

institute: Virginia Commonwealth University

summary: Synovial Sarcoma (SS) is driven by the SS18::SSX translocation event and is often diagnosed in patients under 30. In general, SS is refractory to chemotherapy and other therapeutic approaches. SS18::SSX does not directly bind to DNA. Instead, SS18::SSX alters ATP-dependent chromatin remodeling complex BAF (mammalian SWI/SNF complex) complexes away from a wild-type SS18-containing canonical (cBAF) complex towards a SS18::SSX-containing non-canonical (nc)BAF complex to drive a SS-specific transcription program with subsequent tumor formation. Small molecule targeted therapies are expanding beyond the kinome, providing additional tools to treat cancers that are not yet amenable to targeted therapies. Here, we demonstrate that SS18::SSX activates the SUMOylation program and SS are sensitive to the small molecule SAE1/2 inhibitor, TAK-981 (subasumstat). Mechanistically, we demonstrate TAK-981 de-SUMOylates the cBAF and Polybromo-associated BAF complex (PBAF) complex member, SMARCE1. The result of which is stabilization and restoration of cBAF complexes on chromatin, shifting away from the dominant SS18::SSX-ncBAF-complex driven transcriptome. This phenotypic shift is associated with DNA damage and cell death, resulting in tumor inhibition across both human and mouse SS tumor models. As such, TAK-981 combined with standard-of-care chemotherapy enhances induced synergistic activity through increased DNA damage, leading to tumor regressions. Targeting the SUMOylation pathway in SS restores cBAF complexes and blocks the SS18::SSX-ncBAF transcriptome, identifying a therapeutic vulnerability in SS, and positioning the in-clinic TAK-981 as a novel candidate to treat this refractory cancer.

first: Konstantinos

middle: V

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

first: Kun

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

last: Hill

first: Jamie

last: Slaughter

first: Mayuri

last: Shende

first: Madelyn

last: Lorenz

first: Mandy

last: Hinojosa

first: Benjamin

last: Belvin

first: Zhao

last: Lai

first: Sosipatros

last: Boikos

first: Angeliki

last: Stamatouli

first: Janina

middle: P

last: Lewis

first: Masoud

middle: H

last: Manjili

first: Kristoffer

last: Valerie

first: Renfeng

first: Ana

last: Banito

first: Andrew

last: Poklepovic

first: Jennifer

last: Koblinski

first: Trevor

last: Siggers

first: Kevin

middle: B


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [RNA-seq_HS-SY-II]

first: Mikhail

last: Dozmorov

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

last: Zhang

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

first: Jamie

middle: E


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SY18_ChIP-seq]

first: Mikhail

last: Dozmorov

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP seq) for SS18::SSX, SMARCA4, KDM2B and H3K27ac in SYO.1 and SYO.1 synovial sarcoma cell lines

first: Konstantinos

last: Floros

first: Carter

middle: K

first: Jinxiu

first: Kun

last: Hill

last: Slaughter

first: Mayuri

last: Shende

first: Madelynk

last: Lorenz

first: Mandy

last: Hinojosa

first: Benjamin

last: Belvin

first: Zhao

last: Lai

first: Sosipatros

last: Boikos

first: Angeliki

last: Stamatouli

first: Janina

last: Lewis

first: Masoud

last: Manjili

first: Kristoffer

last: Valerie

first: Renfeng

first: Ana

last: Banito

first: Andrew

last: Poklepovic

first: Jennifer

last: Koblinski

first: Trevor

last: Siggers

first: Kevin


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SYJHD_ChIP-seq]

first: Mikhail

last: Dozmorov

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP seq) for SS18::SSX, SMARCA4, KDM2B and H3K27ac in SYO.1 and SYO-1 synovial sarcoma cell lines

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

last: Zhang

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

first: Jamie


title: HDAC7 induction combined with standard-of-care chemotherapy provides a therapeutic advantage in t(4;11) infant B-ALL

first: Maribel

last: Parra

address: Ctra. de Can Ruti, Camí de les Escoles, s/n

department: Lymphocyte Development and Disease

institute: Josep Carreras Leukaemia Research Institute

summary: Infants diagnosed with acute lymphoblastic leukemia (B-ALL) and t(4;11) chromosomal rearrangements represent a subset of patients with poor therapeutic response. t(4;11) B-ALL cells exhibit low levels of HDAC7, which is essential for optimal B lymphocyte differentiation. Here, we show that HDAC7 silencing in this malignancy is mediated by epigenetic mechanisms involving the chromatin remodeler EZH2 and the KMT2A-AFF1 fusion protein. Remarkably, the menin inhibitor MI-538 restores HDAC7 expression, and this effect is enhanced by the addition of the class I HDAC inhibitor chidamide. This treatment drives leukemic pro-B cells towards a more differentiated and less malignant state, thereby impairing aberrant proliferation. In addition to reducing the malignant capacity of leukemic cells in vitro, addition of MI-538 and chidamide to standard chemotherapy shows promise in reducing the engraftment of t(4;11) pro-B-ALL cells in vivo and delaying relapse. Finally, the newly developed therapy increases the ex vivo glucocorticoid sensitivity of t(4;11) pro-B-ALL primary cells.

overall_design: SEM-K2 cells (derived from an infant diagnosed of MLL-AF4+ iB-ALL) were treated with MI-538 and Chidamide. These compounds are epigenetic drugs that impair the activity of KMT2A-AFF1 by blocking specific cofactors coactivators (Menin and class I HDACs). We have previously observed that the treatment with these compounds induces HDAC7 expression, which is a biomarker associated to an improved prognosis. In this RNAseq experiment we aim to compare the transcriptional profile of SEM-K2 cells treated with this combinatorial therapy with counterparts cells treated with DMSO (as vehicle).

first: Oriol

last: de Barrios

first: Mar

last: Gusi-Vives

first: Olga

last: Collazo

first: Ainara

last: Meler

first: Ingrid

last: Ocón-Gabarró

first: Paola

last: Romecín

first: Alba

last: Martínez-Moreno

first: Juan

last: Tejedor

first: Pauline

last: Schneider

first: Giovanni

last: Cazzaniga

first: Rolf

last: Marschalek

middle: W

last: Stam

first: Clara

last: Bueno

first: Pablo

last: Menéndez


title: Single-cell atlas of the leiomyoma microenvironment reveals hallmarks of myometrial vascular inflammation

city: Oxford

first: Adam

last: Cribbs

address: Windmill Road, Oxford, OX3 7LD, UK

institute: University of Oxford

summary: Uterine fibroids or leiomyoma are benign smooth muscle-derived tumours and are the most common pelvic uterine tumours of women in reproductive age. Large numbers of patients present with symptoms of heavy or prolonged menstrual bleeding, dyspareunia, pelvic pain, miscarriage, and infertility. The underlying causes are not understood; however it is hypothesized that fibroid-uterine interactions orchestrate clinical sequelae, mediated through the pseudocapsule, an anatomical entity that surrounds the myoma and separates it from normal myometrium. We here present a single cell atlas of the uterine pseudocapsule architecture by integrating single nuclei transcriptomics with highly multiplexed immunofluorescence imaging. The data suggest vascular inflammation leading to substantial infiltration of activated innate and adaptive immune cells in the pseudocapsule and we map fibroblast/stromal and endothelial cell activation states and interactions. The results advance our understanding of molecular events underlying leiomyoma pathology and provide novel insights into aberrant and actionable immunological processes occurring in the tumour microenvironment.

overall_design: Tissue samples obtained including endometrium and pseudocapsule from leiomyoma patients were applied for single-nuclei RNA sequnecing.

first: Chen

middle: Y

last: Wang

first: Martin

last: Philpott

first: Udo

last: Oppermann


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [RNA-seq_Utah]

first: Mikhail

last: Dozmorov

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

last: Zhang

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

middle: I

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

last: Hill

first: Jamie

last: Slaughter

first: Mayuri

last: Shende

first: Madelyn

last: Lorenz

first: Mandy

last: Hinojosa

first: Benjamin

last: Belvin

first: Zhao

last: Lai

first: Sosipatros

last: Boikos

first: Angeliki

last: Stamatouli

first: Janina

last: Lewis

first: Masoud

last: Manjili

first: Kristoffer

last: Valerie

first: Renfeng

first: Ana

last: Banito

first: Andrew

last: Poklepovic

first: Jennifer

last: Koblinski

first: Trevor

last: Siggers

first: Kevin


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [HS18_ChIP-seq]

first: Mikhail

last: Dozmorov

overall_design: Chromatin Immunoprecipitation DNA sequencing (ChIP seq) for SS18::SSX, SMARCA4, KDM2B and H3K27ac in SYO.1 and HS-SY-II synovial sarcoma cell lines

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

last: Zhang

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

first: Jamie

first: Madelynk

middle: R


title: PBMC gene expression profiles from vaccinated or non-vaccinated humans challenged with influenza viruses

city: Seattle

first: kathie

last: walters

state: WA

address: 401 Terry Ave N

institute: Institute for Systems Biology

first: Kathie-Anne

last: Walters

first: John

middle: C

last: Kash

first: Jeffery

last: Taubenberger


title: Spatial transcriptome landscape of systemic vasculitis

first: Kotaro

last: Matsumoto

address: 35, Shinanomachi, Shinjuku-ku

department: Division of Rheumatology, Department of Internal Medicine

institute: Keio University School of Medicine

summary: We screened vasculitis-specific molecules by combining the findings from serum proteome analysis and whole blood bulk RNA sequencing. We validated the results using immunohistochemical staining and spatial transcriptome analysis of their tissues. Finally, we elucidated the significant molecule to reflect the landscape of systemic vasculitis using trans-omics analysis.

overall_design: Expression profiling by high throughput sequencing

first: K

last: Suzuki

first: H

last: Yoshida

first: Y

last: Kaneko


title: Cell Delivery Agent as Drug. A Multitarget Agent Delivers an Antisense Oligonucleotide for Synergistic Activity in Myotonic Dystrophy Type 1

city: URBANA

first: Ullas

middle: Valiya

last: Chembazhi

state: Illinois

address: 600 S Mathews Avenue

department: Biochemistry

institute: UIUC

summary: Drug delivery vehicles are hoped to be inert, although many suffer toxicity issues that limit their use. In developing potential agents to treat myotonic dystrophy type 1 (DM1), we wondered if a delivery vehicle might be designed to be a direct acting drug. DM1 is an incurable neurodegenerative disease that originates from expanded (CTG)·(CAG) repeats in the 3'-UTR of the DMPK gene. The majority of drug discovery efforts have been focused on development of small molecules that inhibit MBNL1 protein sequestration by the expanded RNA transcript, r(CUG)exp. Antisense oligonucleotides (ASOs) have also been utilized to treat DM1. However, ASOs normally exhibit poor cell penetration so considerable effort has focused on their delivery. Herein, we report a series of multitargeting oligomeric ligands that have been developed to serve both as drug molecules and as antisense delivery vehicles for DM1. As a result of multivalency, the longer oligomers bound the target DNA and RNA with nanomolar affinities, in vitro, and exhibited improved disease outcomes in DM cell culture model and DM1 patient myotubes. The oligomers form polyplexes with a locked nucleic acid (LNA) CAG16 gapmer, facilitating its cell uptake in both HeLa cells and DM1 patient myotubes decreasing the level of toxic r(CUG)exp significantly. RNA-seq analysis indicated that the oligomeric ligand and its polyplex can rescue DM1 associated splicing defects and gene expression changes transcriptome-wide in DM1 patient myotubes.

overall_design: Evaluate the rescue of DM1 associated splicing defects and gene expression changes in DM1 patient myotube cultures upon treatment with a multitargeting oligomeric ligand and its polyplex with a locked nucleic acid (LNA) CAG16 gapmer.

first: Ke

last: Li

first: Auinash

last: Kalsotra

first: Steven

last: Zimmerman


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [SYATAC_ATAC-seq]

first: Mikhail

last: Dozmorov

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

first: Kun

last: Zhang

first: Jane

middle: L

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

first: Asha

first: Elsamani

middle: D

last: Hill

last: Slaughter

first: Mayuri

last: Shende

last: Lorenz

first: Mandy

last: Hinojosa

first: Benjamin

last: Belvin

first: Zhao

last: Lai

first: Sosipatros

middle: A

last: Boikos

first: Angeliki

last: Stamatouli

first: Janina

last: Lewis

first: Masoud

last: Manjili

first: Kristoffer

last: Valerie

first: Renfeng

first: Ana

last: Banito

first: Andrew

last: Poklepovic

first: Jennifer

last: Koblinski

first: Trevor

last: Siggers

first: Kevin


title: Comprehensive analysis of hypoxia-dependent expression of myelin-related genes in Schwann cells

city: Fukuoka

first: Yasuyuki

last: Ohkawa

address: 3-1-1 Maidashi

institute: Medical Institute of Bioregulation

summary: Schwann cells (SC) generate myelin sheath in the peripheral nervous system. Several specific genes have been identified in SC during development of peripheral nerves. Expression of these genes has been also found in SC of peripheral nerves after injury or in demyelinating disorders. However, it remains unclear how these genes regulate SC differentiation and peripheral myelination. Here, we show the hypoxia induced factor-1α (HIF-1α) involvement in the regulation of SC differentiation and myelination. We used ChIL-seq technology to understand the comprehensive HIF-dependent gene expression in SC during myelination.

overall_design: ChIL-seq for HIF1 alpha  in primary rat Schwann cells.

first: Yuka

last: Ujiie

first: Shuji

last: Wakatsuki

first: Toshiyuki

last: Araki


title: Human iPSC-derived cell grafts promote functional recovery by molecular interaction with stroke-injured brain

city: Los Angeles

first: Ruslan

last: Rust

address: 1501 San Pablo Street

institute: University of Southern California

summary: IPSC-NPC were transplanted in a mouse model of stroke. To dissect the molecular graft composition and identify graft-host interactions, single nucleus profiling of the cell transplants and host stroke tissue was performed. We identified graft differentiation preferentially towards GABAergic cells with remaining cells acquiring glutamatergic neuron, astrocyte, and NPC-like phenotypes. Interaction between graft and host transcriptome indicated that GABAergic cell grafts were primarily involved in graft-host communication through the regeneration-associated NRXN, NRG, NCAM and SLIT signalling pathways

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: IPSC-NPC were transplanted in mice one week after stroke. Nuclei from cell grafts and stroke-injured tissue were isolated and analysed using single nucleus RNAseq


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [HSJHD_ChIP-seq]

first: Mikhail

last: Dozmorov

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

last: Zhang

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

last: Hu

first: Vita

last: Kraskauskiene

first: Nayyerehsadat

last: Hosseini

first: Shanwei

last: Shen

first: Melissa

last: Inge

first: Kylie

last: Smith-Fry

first: Li

first: Afroditi

last: Sotiriou

first: Krista

last: Dalton

first: Asha

last: Jose

first: Elsamani

last: Abdelfadiel

first: Yanli

last: Xing

first: Ronald

last: Hill

first: Jamie

last: Slaughter

first: Mayuri

last: Shende

first: Madelynk

last: Lorenz

first: Mandy

last: Hinojosa

first: Benjamin

first: Zhao

middle: G


title: Targeting of SUMOylation leads to cBAF complex stabilization and disruption of the SS18::SSX transcriptome in synovial sarcoma [RNA-seq_SYO.1]

first: Mikhail

last: Dozmorov

first: Konstantinos

last: Floros

first: Carter

last: Fairchild Jr

first: Jinxiu

last: Li

first: Kun

last: Zhang

first: Jane

last: Roberts

first: Richard

last: Kurupi

first: Bin

first: Vita

first: Nayyerehsadat

middle: M

first: Madelyn

last: Belvin

last: Lai

first: Sosipatros

last: Boikos

first: Angeliki

last: Stamatouli

first: Janina

last: Lewis

first: Masoud

last: Manjili

first: Kristoffer

last: Valerie

first: Renfeng

first: Ana

last: Banito

first: Andrew

last: Poklepovic

first: Jennifer

last: Koblinski

first: Trevor

last: Siggers

first: Kevin


city: New York

first: John

last: Tuddenham

state: NY

institute: Columbia University

summary: Live single-cell RNA-sequencing data from ALS donors only. Single-cell RNA-sequencing data on CD45+ cells dissociated from autopsy tissue and surgical resections from ALS donors across a different series of brain regions.

middle: F

first: Marta

last: Olah

first: Vilas

last: Menon

first: Philip

last: De Jager


title: Microbiota promote enhanced CD39 expression in gd intraepithelial lymphocytes through the activation of TCR and IL-15 signaling.

status: Public on Aug 05 2025

first: Darwin

last: D'Souza

address: 1470 Madison Avenue

department: ImmunoBio

institute: Human Immune Monitoring Center

summary: Intraepithelial lymphocytes expressing the gd T cell receptor (gd IEL) provide continuous surveillance of the intestinal epithelium. We report that mice harboring a microbiota-specific hyperproliferative gd IEL (gdHYP) phenotype also upregulate the expression of the ectonucleotidase CD39, a marker of regulatory gd T cells. Enhanced TCR and IL-15 signaling correlates with a progression from a naïve-like CD39neg gd IEL to a more mature, tissue-adapted CD39hi IEL population. We find that TCRgd activation drives CD122-mediated CD39 upregulation on gdHYP IELs and increased mucosal IL-15 further amplifies CD39 expression in gdHYP IELs. Notably, CD39 induction requires sustained exposure to the gdHYP-associated microbiota. Increased IL-15 signaling prolongs IEL survival and enhances gdHYP IEL bioenergetic potential. Notably, CD39hi gd IELs produce less pro-inflammatory cytokine, which may explain the lack of histopathology in gdHYP mice. Overall, our study identifies a previously unappreciated mechanism by which an altered microbiota amplifies CD39 expression on gdHYP IELs, leading to the expansion of gd IELs with regulatory potential.

overall_design: CD3+ IELs were sorted from WT and gdHYP mice and stained with anti-CD39 antibody. CITEseq was performed.

first: Sara

last: Alonso

first: Karen

last: Edelblum


title: EET Reduction Contributes to Granulosa Cell Senescence And Endometriosis-Associated Infertility Via the PI3K/AKT/mTOR Signaling Pathway

city: Hangzhou

first: Xiang

last: Lin

state: Zhejiang province

address: No. 3 Qingchun East Road, Shangcheng District, Hangzhou, 310000, China

department: Assisted Reproduction Unit, Department of Obstetrics and Gynecology;

institute: Sir Run Run Shaw Hospital, Zhejiang University School of Medicine;

summary: Oxidative stress is involved in endometriosis (EM)-related infertility via various mechanisms, such as accelerating ovarian granulosa cell (GC) senescence, inhibiting ovulation, and interfering with lipid metabolism. In this study, we aimed to examine abnormal oxidative lipid levels and their related mechanisms in EM-associated infertility. Through liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis, we observed that epoxyeicosatrienoic acids (EETs), which have antioxidant and anti-senescence effects, had decreased levels in follicular fluid samples from EM patients. The EET levels were positively correlated with in vitro fertilization outcomes. Using qPCR and western blot experiments, we found elevated soluble epoxide hydrolase (EPHX2) expression levels in EM-GCs. This enzyme metabolizes EETs into dihydroxyeicosatrienoic acids (DHETs), explaining the decreased 14, 15-EET levels in EM patients. Lower 14, 15-EET concentrations led to decreased GC antioxidant capacity, reduced ATP production, reactive oxygen species (ROS) accumulation in oocytes, and abnormal cumulus-oocyte complex (COC) expansion, which ultimately resulted in decreased fertility. Inhibiting EPHX2 in vivo or in vitro could reverse these observed abnormalities by upregulating 14, 15-EET. Mechanistic studies showed that 14, 15-EET alleviated GC senescence and improved fertility by inhibiting excessive PI3K/AKT/mTOR signaling pathway activation in EM-GCs. Moreover, the PI3K/AKT/mTOR pathway inhibitor BEZ-235 significantly alleviated ROS-induced cell senescence and abnormal COC expansion. Further work showed that an oxidative stress-induced decrease in EZH2/H3K27Me3 histone methylation led to the elevated EPHX2 expression patterns in EM-GCs. In addition, the decreased 14, 15-EET levels led to ROS accumulation, decreased EZH2 enzymatic activity, less EPHX2/H3K27Me3 histone methylation, and increased EPHX2 protein expression levels, which further reduced 14, 15-EET levels as part of a vicious feedback loop. Using LC-MS/MS, viral infection, transcriptomic sequencing, knockout mice, and EM mouse model experiments, we elucidated the molecular mechanisms of 14, 15-EET in EM-associated infertility and the mechanism controlling its decreased levels.

overall_design: RNA sequencing (RNA-seq) and bioinformatics analysesRNA-seq were conducted in two distinct experimental phases. Firstly，to elucidate GC abnormalities in EM mice, we constructed EM mice models and performed RNA-seq analysis on freshly isolated mGCs obtained from the sham surgery group (Con-mGC, n=5) or EM group (EM-mGC, n=5) after ovulation induction. A total of 10 mice were used in this experiment, 5 sham surgery mice and 5 EM mice models.Secondly, freshly isolated mGCs from six EM model mice were randomly divided into two parts for in vitro culture: one part was cultured in DMEM/F12 with 5% FBS for 24 hours and the other was treated additionally with 100 nM 14, 15-EET for 24 hours. A total of six EM mice were used in this experiment and three paired biological replicates of mGCs were collected for RNA-seq. Detailed procedure were described in Supplementary Information.

first: Weijia

last: Gu

first: Xiaomei

last: Tong

first: Mengru

last: Lai

first: Yi

last: Zhang

last: Liu

first: Xiaoying

last: Jin

first: Chao

last: Li

first: Dong

last: Huang

first: Feng

last: Zhou

first: Yongdong

last: Dai

first: Songying


title: Genetic Control of tRNA-Derived Fragments Contributes to Cancer Risk

city: Wuhan

first: Bin

address: Donghu Road 115

institute: Department of Epidemiology and Biostatistics, School of Public Health; Wuhan University

summary: Transfer RNA-derived fragments (tRFs) are a class of small non-coding RNAs that have exhibited several functions in cancer. Recent studies have shown that mutations in tRNA genes can lead to global changes in tRF expression levels and may affect tRF function, highlighting the need to further elucidate the regulation and functions of tRFs in cancer. Here, we conducted a pan-cancer analysis of tRF quantitative trait loci (tRFQTLs), encompassing 16,703 genetic variants associated with tRF expression across 31 cancer types. A joint analysis of GWAS data revealed that tRFQTLs were preferentially enriched in cancer risk loci and colocalized with 106 GWAS variants, explaining a substantial portion of cancer heritability. Moreover, tRFs regulated by tRFQTLs were enriched in cancer-related pathways and correlated with drug response and immune infiltration. Notably, polygenic risk score models incorporating tRFQTLs improved high-risk population identification. Investigation of large-scale population cohorts revealed a tRFQTL, rs9461276, associated with colorectal cancer (CRC) risk. In biological assays, the rs9461276-C allele increased tRF-18-HSQS52D2 expression, which suppressed CRC malignant phenotypes. Mechanistically, tRF-18-HSQS52D2 bound to the 3'UTR of POU2F1, destabilizing the oncogenic transcript. Integrated RNA sequencing and ChIP-seq assays indicated that POU2F1 enhanced CRC cell proliferation by activating various pathological pathways associated with oxidative and glycolytic metabolism, mitotic stability, and cell cycle regulation. Finally, a database (Cancer-tRFQTL) was generated as a resource to support investigation into tRF-mediated mechanisms and genetic basis of tRF expression in human cancers. Overall, this study helps advance the understanding of tRFs in cancer pathogenesis.

overall_design: RNA-seq profiling of HCT116 cells with either POU2F1 knockdown (siPOU2F1) or non-targeting siRNA (sicontrol)

first: Hanting