title: Stage and Cultivar Specific Regulation of Cannabinoid in Hemp: An Integrated Omics Perspective

city: Chuncheon

first: Prakash

last: Basnet

state: Gangwon-do

address: Department of Agriculture and Life Industry, Kangwon National University, Bldg. Asangwan Rm.424, 1 K

department: Agriculture and Life Industries

institute: Kangwon National University

summary: we employed integrated transcriptomic and metabolomic analyses to elucidate the molecular basis of cannabinoid biosynthesis during early and late flowering stages in two hemp cultivars, CBG-Ambit and CBG-Limonene. A total of 338 differentially expressed genes (DEGs) were identified at the early stage (ES), while 342 at the late stage (LS) between CBG-Ambit (Amb) and CBG-Limonene (Lim) cultivars. Additionally, 1342 DEGs were identified between the early and late stages of Ambit, whereas 1152 DEGs among early and late stages in Limonene. Key candidate genes including cytochrome P450 78A9 (CYP78A9), 3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (HMGCR1), auxin transporter-like protein 2 (LAX2), myrcene synthase (MyrS), terpene synthase 29 (TS-29), geranylpyrophosphate: olivetolate geranyltransferase (GPP),  ABSCISIC ACID-INSENSITIVE 5-like protein 7 isoform X1 (ABI5), MYB transcription factor 1, histone-lysine N-methyltransferase (SUVH6), TIFY 10A, tetraketide alpha-pyrone reductase 2 (TPKR2), ethylene-responsive transcription factor (ERF109), berberine bridge enzyme-like 8 (BBE8) and monoterpene synthase (MTS1), were implicated as central regulators of CBD biosynthesis and conformed by RT-qPCR. Functional enrichment (GO and KEGG) analysis demonstrated that these genes are concentrated in secondary metabolic processes, oxidoreductase activity, and transcriptional regulation, highlighting their central roles in cannabinoid and terpenoid biosynthesis. Along with ultra-performance liquid chromatography-mass spectrometry (UPLC-MS), metabolomic profiling further showed increased accumulation of CBDA and CBGA in late stage.

overall_design: Identification of differentially expressed genes in early and late stage of CBG-Ambit and CBG-Lim for cannabinoid biosynthesis

first: Ik-Young

last: Choi

first: Taeyoung

last: Um

first: Sevin

last: Lee

first: Beom-Soon

first: Grace

last: Lachica

first: Kyoungcheul

last: Park


title: ZDHHC13 Modulates Tumor Microenvironment Interactions to Suppress Melanoma Metastasis [RNA-Seq]

status: Public on Sep 23 2025

city: Cleveland

first: Shuyang

last: Chen

state: OH

address: 9500 Euclid Ave

country: USA

institute: Cleveland Clinic

type: Expression profiling by high throughput sequencing

summary: This dataset supports a study investigating the role of ZDHHC13 in melanoma development. Using bulk RNA sequencing and 10x Genomics single-cell RNA sequencing, we analyzed how ZDHHC13 influences tumor progression and the tumor microenvironment. These data provide insights into the transcriptomic changes associated with ZDHHC13 activity in melanoma and serve as a resource for understanding gene expression dynamics in both tumor cells and surrounding immune components.

overall_design: For bulk RNA sequencing, we engineered B16F10 murine melanoma cells to stably overexpress ZDHHC13 using a lentiviral vector. RNA was extracted from both ZDHHC13-overexpressing and control (empty vector) B16F10 cells for transcriptomic profiling to assess the direct effects of ZDHHC13 on tumor cell gene expression.

first: Hongjin

last: Li


title: The Effect of Methyl Donors in a Murine Model of MASLD in a Multidisciplinary Study.

city: guadalajara

first: angel

middle: omar

last: vazquez

address: SIERRA MOJADA 950

country: Mexico

institute: IBMMTG

summary: Addressing the challenge of Metabolic Dysfunction Associated Steatotic Liver Diseases (MASLD), this study assesses the efficacy of methyl donor supplementation in a C57BL/6J mouse model, hypothesizing its potential to mitigate disease symptoms through epigenetic and metabolic pathways.  In the liver, global DNA methylation was quantified and the transcriptome was analyzed using dual-channel microarrays.  An increased DNA methylation, normalization in the expression of lipid-related genes, and hypermethylation of lipogenic genes were observed in methyl donnors supplemental mice (MET).

overall_design: A model using male C57BL/6J mice was used, divided into three groups: normal diet (ND, n=8), high-fat and high-sugar diet (HF, n=8) for 18 weeks, and a third group with HF diet for 10 weeks followed by 8 weeks of supplementation with methionine, choline, betaine, folate, cobalamin, and ZnSO4 (MET, n=8). At sacrifice, liver samples were collected and processed to obtain DNA, which was then subjected to bisulfite conversion following the manufacturer's protocol (Zymo Research). Subsequently, methylation was evaluated using the Infinum Mouse Methylation BeadChip Array (Illumina) following the manufacturer's instructions

first: Vazquez-Esqueda

last: Angel

first: Rosas-Campos

last: Rebeca

first: Escutia-Gutiérrez

first: García-Bañuelos

last: Jesus

first: Galicia-Moreno

last: Marina

first: Christian

last: Monroy-Ramirez

first: Jorge

last: Gutiererz-Cuevas

first: José

last: Navarro-Partida

first: Armendáriz-Borunda

last: Juan

first: Sandoval-Rodríguez

last: Ana


title: KANSL3 directs transcriptional programs essential for hepatic metabolism and differentiation [RNA-seq]

city: Freiburg

first: Asifa

last: Akhtar

address: Stuebeweg 51

department: Chromatin Regulation

country: Germany

institute: Max Planck Institute of Immunobiology and Epigenetics

summary: Understanding the molecular mechanisms governing liver homeostasis and disease progression is essential for advancing therapeutic strategies for chronic liver diseases and hepatocellular carcinoma, with emerging evidence highlighting the pivotal role of epigenetic regulation in these progressive types of diseases. Here, we show that hepatic deletion of the epigenetic regulator KANSL3 initiates a series of pathological changes leading to early-onset chronic liver disease. The absence of KANSL3 leads to biliary hyperplasia and early hepatic fibrosis. We identify KANSL3 as a master regulator of core hepatocyte gene expression through its regulation of histone acetylation, which significantly alters transcriptional networks in the liver. Single-cell RNA sequencing (scRNA-seq) analysis of Kansl3 liver knockout (LKO) animals reveals a marked shift in liver cellular composition following Kansl3 depletion. We show that the hepatic epithelial cells of Kansl3 LKO mice and Kansl3-depleted ductal organoids exhibit impaired differentiation into mature hepatocytes, uncovering the importance of KANSL3 in hepatic cell fate decisions. Ultimately, chronic loss of KANSL3 induces significant changes in the liver microenvironment, promoting a premalignant state characterized by an immunosuppressive environment linked to hepatocellular carcinoma (HCC) progression. These results highlight KANSL3 as a crucial regulator of liver homeostasis and a promising target for drug discovery.

overall_design: Liver RNA-seq: Comparison of total RNA expression in whole liver tissue isolated from 3-week-old (P21) control liver and Kansl3 LKO mice. Organoid RNA-seq: Time-course mRNA expression analysis of ductal organoids generated from neonatal livers undergoing hepatocyte differentiation in vitro. Comparison of control (iWT) and Kansl3-iKO organoids, depletion of Kansl3 was induced by 4OHT treatment at day 3 for 48hrs. Hepa16 RNA-Seq: mRNA expression analysis in Hepa 1-6 HA-dTAG-KANSL3 cells upon degradation of KANSL3. Hepa 1-6 HA-dTAG-KANSL3 cells were treated for 24hrs with either dTAG-NEG control compound or dTAG13 to rapidly degrade KANSL3. 72hrs prior to the treatment cells were induced with the lentiviral pCHDblast MCSNard empty vector (EV) and selected with Blasticidine.

first: Meike

last: Wiese

first: Eray

last: Akbas

first: TzsHong

last: Tsang

first: Yidan

last: Sun

first: Kerstin

last: Ganter


title: Capicua refines mossy fiber–CA3 axon targeting in the late postnatal hippocampus

city: Edmotnotn

first: Qiumin

last: Tan

state: Alberta

address: 114 St and 87 Ave

department: Cell Biology

country: Canada

institute: University of Alberta

summary: Proper brain wiring relies on the precise distribution of axonal projections to specific subcellular domains of their target neurons. These spatially confined connections establish the anatomical foundation for neural circuit assembly. The mossy fiber (MF)–CA3 pathway in the hippocampus is an excellent system to study the mechanisms underlying lamina-specific connectivity. In rodents, MF projections develop postnatally and reach their mature configuration by the end of the second postnatal week. MF axons synapse on the proximal segments of the dendrites but avoid the somas of CA3 pyramidal neurons. As dentate gyrus granule neurons are continuously generated and integrated into the existing hippocampal circuit throughout the postnatal period and adulthood, the mechanisms that guide MF axons to achieve lamina-specific targeting of these later-born granule neurons remain unclear. Here, we show that deletion of the neurodevelopmental disorder-associated protein capicua (CIC) results in abnormal MF targeting in the mouse hippocampus. Notably, this defect emerges after the second postnatal week and persists into adulthood, distinguishing it from classical MF guidance defects, which typically manifest during the first postnatal week. We also demonstrate that this miswiring is due to CIC loss in dentate gyrus granule neurons rather than CA3 pyramidal neurons. Single-nucleus transcriptomics and trajectory analysis reveal a loss of a mature granule neuron subtype and dysregulation of axon guidance genes that are normally downregulated as granule neurons mature. Our findings uncover a previously unrecognized role for CIC in hippocampus development and offer insights into the regulation of lamina-specific MF connectivity in the postnatal brain.

overall_design: Three Cicflox/flox and three Emx1-Cre; Cicflox/flox mice (littermates, two males and one female for each genotype) at P19 were euthanized and their hippocampus micro-dissected. The dissected tissues were snap-frozen in liquid nitrogen until nuclei extraction for single-nuclei RNAseq. One hippocampus from each mouse was used for nuclei extraction.


title: Single cell sequencing analysis of control, photon- and proton- irradiated salivary gland organoids at day 7 and control salivary gland organoids at day 11

city: Groningen

first: Davide

last: Cinat

address: Hanzeplein 1

country: Netherlands

institute: University Medical Center Groningen

summary: The specific impact of different radiation types, such as photons and protons, and their effects on normal stem cell activity and tissue regeneration are unknown. In this study, we used a scRNA-seq approach to characterize our mouse salivary gland organoid model at day 7 and 11 and assess the effects of photon and proton irradiation on salivary gland stem/progenitor cells at day 7.

overall_design: Mouse salivary gland organoids derived from 4 different animals were irradiated at day 5 with either 7 Gy photons or 7 Gy protons (plateau). Non-irradiated (control), photon- and proton-irradiated organoids were collected at day 7 (2 days after irradiation) and pooled before the sequencing run. After trypsinization, propidium iodide (PI) was used to isolate live cells (PI negative) by flowrescence-activated cell sorting (FACS). Cells were then analysed using scRNA-seq. Fresh isolated submandibular salivary gland tissue was also included in the analysis together with non-irradiated 11-day old salivary gland organoids. 11-day salivary gland organoids were run separately.

first: Rob

middle: P

last: Coppes

first: Lara

last: Barazzuol


title: Induction of CDX2 as a differentiation therapy in colorectal cancers [CRC organoids]

city: La Jolla, CA 92093

first: Pradipta

last: Ghosh

state: CA

address: 9500 Gilman Drive (MC 0651)

department: Departments of Medicine and Cellular and Molecular Medicine

institute: University of California San Diego

summary:
Background: Lack of expression of the transcription factor CDX2 identifies a subset of poorly differentiated colorectal cancers (CRCs) that are associated with lower overall (OS) and disease-free (DFS) survival, independent of ethnicity, MSI status, or stage. CDX2 expression lowers risk of death and disease recurrence by ~50%. Induction of CDX2 as a therapeutic strategy is yet to be implemented in clinical practice.
Methods: We used a novel network-based computational model to identify and prioritize therapeutic targets that can robustly augment CDX2 expression and, consequently, differentiation. The top candidate with available clinical-grade pharmacophore was tested for efficacy in 3 models: CRC lines in vitro, xenografts in mice, and in prospective cohorts of CRC patient-derived organoids (PDOs; n = 23).
Results:  Our network-derived gene clusters reliably classified healthy and CRC tissues in diverse publicly available gene expression datasets (>10,000 human and >250 mouse samples). The target showed potent anti-cancer activity, induced crypt differentiation signatures in all models tested, and shifted the network in predictable ways. Effective pairing of therapy (IC50 of the target) and CDX2 expression (companion biomarker) was confirmed in an independent cohort of CRC PDOs. A multivariate analysis revealed KRAS mutation and high-CDX2 as key determinants of resistance to the target.
Conclusions: Induction of CDX2 expression by the target augments differentiation and shows potent anti-cancer effect on CRCs that lack CDX2 expression. This benefit of drug-biomarker pairing should be considered for confirmatory studies in randomized clinical trials.

overall_design: Eleven patient derived organoids representing the colorectal cancer were used in  this study. Standard cell biological, functional and phenotypic assays were used to assess the prodifferantiation and anticancer actions of the PF compound : 1) prodifferantiation induction, 2) cytotoxicity assay, 3)qPCRt , 4) RNA sequencing

first: Saptarshi

last: Sinha


city: Kansas City

first: Soumen

last: Paul

state: KS

address: Hemenway Building 3901 Rainbow Boulevard

department: Department of Pathology & Laboratory Medicine

institute: University of Kansas Medical Center

summary: Placenta is the vital reproductive organ of mouse, which is required for sustainable growth, protection, and nourishment of the fetus during gestation. It performs many crucial functions which include removal of waste products from the fetus, facilitation of the oxygen supply and nutrients to the fetus etc. Advances in the next generation sequencing technology, especially single cell transcriptional profiling, have provided the opportunity to explore the cell heterogeneity in mouse placenta. However spatial organization of these cell types and their functional mechanism, genes co-expression and regulations remain elusive yet. Visium Spatial 10x is a modern technology to study gene expression, where whole transcriptome analysis has been performed while taking account of their morphological context. This helps to gain a complete view of disease complexity, discover new biomarkers, identify novel cell types and developmental states. Along with it is used to identify spatiotemporal gene expression patterns and create map of the spatial organization of cell atlas. Placental tissue comprised of different cell types and are well organized display signature of developmental stages, along with their gene's expression. In this regard, exploring the new cell types and tracking their developmental trajectory is important to get insight into their role in spatial organizational context. Cellular functions and extensive interactions among cell types are unexplored taking consideration of spatial context in mouse placenta. It is required to explore the cell types, cell-to-cell communication which is essential for deciphering the regulation of placental development and functions. In this study, we have applied spatial transcriptomes for two developmental stages of mouse placenta E10.5 and E12.5 to explore the cell heterogeneity of the developing placenta. This work shows their significance by providing insight of tissue level identification cell types of clusters, identification of cell types of markers to get the significantly expressed genes in particular clusters. The arrangement of different cell types on tissue images are more informative to study the arrangement and cell differentiation in developmental stages. In conclusion, this study provides new insight into the development and functions of placenta.

overall_design: Spatial transcriptome analysis of mouse placenta in different developmental time points: E10.5, E12.5

first: Rajnish

last: Kumar

first: Ananya


title: A shift in PKM2 oligomeric state instructs adipocyte inflammatory potential

city: Cincinnati

first: Maria

middle: Eugenia

last: Fields

address: 3430 Burnet Ave

department: Gastroeneterology Hepatology and Nutrition

institute: Cincinnati Children's Hospital Medical Center

summary: Processes that promote white adipocyte inflammatory function remain underdefined. Here, we demonstrated that Type I interferons (IFN-Is) dependent skewing of adipocyte glycolysis, nicotinamide adenine dinucleotide (NAD+) utilization, and pyruvate kinase isozyme M2 (PKM2) function may contribute to increased systemic and tissue inflammation and disease severity in obesity. Notably, chemical and/or genetic inhibition of glycolysis, the NAD+ salvage pathway, or PKM2 restricted IFN-I dependent increase in adipocyte inflammatory cytokine production. Further, genetic, or small molecule targeting of PKM2 function in vivo was sufficient to reduce systemic and tissue inflammation and metabolic disease severity in obese mice, in an adipocyte PKM2-dependent manner. Lastly, white adipose tissue of individuals living with obesity and metabolic disease, compared to metabolically healthy individuals with obesity, showed an increase in expression of inflammatory and metabolic genes, while small molecule targeting of PKM2 function contributed to reduced IFN-I-driven inflammatory cytokine production by primary human adipocytes. Together, our findings invoke the IFN-I//PKM2 axis as a potential target for modulating adipocyte dysregulated inflammation.

overall_design: Bulk RNA-Seq on white Adipose tissue from obese persons

first: Michelle

last: Damen

first: Pablo

middle: C

last: Alarcon

first: Calvin

last: Chan

first: Traci

last: Stankiewicz

first: Hak

last: Chung

first: Keisuke

last: Sawada

first: Cassidy

last: Ulanowicz

first: John

last: Eom

first: Jarren

middle: R

last: Oates

first: Jennifer

middle: L

last: Wayland

first: Jessica

last: Doll

first: Rajib

last: Mukherjee

first: Miki

last: Watanabe-Chailland

first: Lindsey

last: Romick-Rosendale

first: Sara

last: Szabo

first: Michael

last: Helmrath

first: Joan

last: Sanchez-Gurmaches

middle: E

last: Moreno-Fernandez

first: Senad

last: Divanovic


title: Mechanosensitive calcium channels and integrins coordinate the reprogramming of colorectal cancer cells into a fetal-like state

city: Utrecht

first: Martijn

last: Gloerich

state: Utrecht

address: Universiteitsweg 100

department: Center for Molecular Medicine

institute: University Medical Center Utrecht

summary: Plate-based scRNA-seq data of murine CRC organoids that were embedded in either Matrigel-or Collagen I matrices and harvested after 1 day.

overall_design: Murine colorectal cancer organoids (genetic background VillinCre-ERT2; ApcFL/FL; KrasLSL-G12D/+; Tp53KO/KO; R26R-Confetti; Lgr5DTR-eGFP) were cultured for 3 days in Matrigel. The CRC organoids were isolated from the Matrigel drops using dispase treatment and re-embedded in either Matrigel or Collagen I matrices. After 1 day the organoids were subjected to fluorescence associated cell sorting and analyzed by plate-based single-cell RNA sequencing.

first: MC

last: van der Net

first: MJ

last: Vliem

first: LJS

last: Kemp

first: C

last: Perez-Conzalez

first: TS

last: Haddad

first: EA

last: Strating

first: A

last: Krotenberg-Garcia

first: RM

last: Houtekamer

first: W

last: Pannekoek

first: KB

last: van den Anker

first: S

last: Zwakenberg

first: JL

last: Monster

first: SEM

last: van der Horst

first: HJG

last: Snippert

first: AA

last: Khalil

first: J

last: van Rheenen

first: SJE

last: Suijkerbuijk

first: O

last: Kranenburg

first: F

last: Simmer

first: ID

last: Nagtegaal

first: D

last: Matic Vignjevic

first: M


title: Induction of CDX2 as a differentiation therapy in colorectal cancers [xenograft]

first: Pradipta

last: Ghosh

overall_design: CRC xenograft nude mice model representing the colorectal cancer was used in  this study. Standard cell biological, functional and phenotypic assays were used to assess the prodifferantiation and anticancer actions of the PF compound : 1) prodifferantiation induction, 2) cytotoxicity through calculating the tumor volume

first: Saptarshi

last: Sinha


title: ATAC sequencing analysis of non-irradiated salivary gland organoids

first: Davide

last: Cinat

type: Genome binding/occupancy profiling by high throughput sequencing

summary: To identify transcription factors important for salivary gland organoids and associated to salivary gland stem/progenitor cells, we performed ATAC-seq of organoids derived from non-irradiated mice of different ages.

overall_design: Salivary glands from 12-week and 3-month old mice were harvested and used to grow organoids. Organoids from passage 1 (P1) and passage 2 (P2) were used for ATAC-seq analysis.

first: Yi

last: Wu

first: Inge

last: Holtman

first: Rob

last: Coppes


title: Rare non-canonical megakaryocyte progenitors increase in number and gain enhanced function with age

city: Santa Cruz

first: Paloma

last: Medina

address: 1156 High St.

institute: University of California Santa Cruz

overall_design: CITEseq via the 10X Genomics platform was performed simultaneously with our previously published scRNAseq data of young and aged FlkSwitch mice. Briefly, cKit-enriched BM was sorted into CD150+ and CD150- fractions and incubated with CITEseq antibodies (BioLegend) per manufacturer’s instructions. All other steps as described in Poscablo et al., 2024. Chromium Next GEM Single Cell 3’ v3.1 (Dual Index) reagents and protocols utilized as specified. Sequencing depth of 5,000 read pairs per cell was performed.  Cells expressing fewer than 200 genes were excluded from the analysis. Cells were further filtered based on surface protein marker expression; specifically, double-negative cells for CD117 ADT and Kit RNA were excluded, removing 13 cells from the dataset. To normalize the CITE-seq data, we implemented a centered log-ratio (CLR) transformation for each cell. For each cell's antibody-derived tag (ADT) count vector, we first computed the natural logarithm of the counts, offset by one, for all non-zero elements. The sum of these log-transformed values was then divided by the total number of features, and the exponential of this mean was used to normalize the original counts. Finally, a log transformation was applied to the resulting normalized values to stabilize variance across features.

first: Bryce

last: Manso

first: Camilla

last: Forsberg


title: KANSL3 directs transcriptional programs essential for hepatic metabolism and differentiation [scRNA-seq]

first: Asifa

last: Akhtar

summary: Understanding the molecular mechanisms governing liver homeostasis and disease progression is crucial for developing new therapeutic strategies for chronic liver diseases and liver cancer, with emerging evidence underscoring the key role of epigenetic regulation. Here, we show that hepatic deletion of the epigenetic regulator KANSL3, a component of the NSL complex, causes early-onset chronic liver disease, distinct from metabolic dysfunction-associated steatohepatitis (MASH). Loss of KANSL3 leads to biliary hyperplasia and early hepatic fibrosis, indicating its vital role in liver structure and function. KANSL3 acts as a master regulator of hepatocyte gene expression through histone acetylation, impacting global liver transcriptional networks. scRNA-seq analysis uncovers that KANSL3 deletion disrupts hepatocyte differentiation in vivo and in hepatic organoids. Ultimately, chronic KANSL3 loss alters the liver microenvironment and promotes an immunosuppressive premalignant state linked to hepatocellular carcinoma (HCC).

overall_design: Comparison of liver cells isolated from control mice or mice with liver-specific knockout of Kansl3 of two diferent ages. Neonatal experiment: Control (n=3) and Kansl3 LKO (n=3) neonatal (P7) livers were isolated. One piece of the liver was used for BEC isolation and the other for hepatocyte isolation. For BEC isolation single cell suspensions were prepared by 0.25mg/ml collagenase (Sigma C2674) digest at 37°C for 1 hr. For the BECs population Zombie NIR (Biolegend, 423105) negative (live cells), CD45/CD31/CD11b- and EpCAM+ cells were sorted. For the hepatic stellate cell (HSC) enriched population Zombie NIR (Biolegend, 423105) negative (live cells), CD45/CD31/CD11b/EpCAM- cells were sorted. For hepatocyte isolation, single cell suspensions were prepared  by 0.8mg/ml collagenase (Sigma C2674) and 50 U/μl) DNase I (Applichem) in DMEM) digest at 37°C for 30 min. For the hepatocyte enriched population Zombie NIR negative, large cells were sorted. For the scRNA-seq experiment, BECs, hepatocytes and HSC populations were isolated from three AlbCre and three Kansl3 LKO mice. For each population, the samples from each genotype were pooled. The BECs, hepatocytes and HSC populations were mixed in an 1:1:1 ratio. This cell mix was directly subjected to 10x scRNA-seq library preparation. One 10x reaction was performed per genotype. A total of 16,000 cells per genotype were processed using the 10X Genomics protocol CG00052 RevB from the Chromium Single Cell 3’ Library & Gel Bead Kit v2 (PN-120237). The libraries were quantified using a fragment analyzer and pooled for multiplexed sequencing on a NovaSeq 6000. Old liver experiment: 90-week-old control (n=2) and Kansl3 LKO (n=2) livers were isolated and digested in 0.8mg/ml collagenase (Sigma C2674) and 50 U/μl) DNase I (Applichem) in DMEM) at 37°C for 30 min. Cell suspension was cryopreserved in FCS supplemented with 1% DMSO and stored in liquid nitrogen. Frozen sample thawed and viable cells were enriched using the LeviCell 1.0 device (Levitas Bio), selecting the option “large cells”. All samples had a viability of approximately 70%. The cells were then prepared for 10x scRNA-seq library preparation. Two 10x reactions were performed per genotype, one for each animal. A total of 16,000 cells per genotype were processed according to the 10X Genomics protocol CG000204 RevD using the Chromium Single Cell 3’ Library & Gel Bead Kit v3.1 (PN-1000121). Libraries were quantified with a fragment analyzer and pooled for multiplexed sequencing on a NovaSeq 6000.

first: Meike

last: Wiese

first: Cecilia

last: Pessoa-Rodrigues


title: KANSL3 directs transcriptional programs essential for hepatic metabolism and differentiation [ChIP-seq]

overall_design: Hepa1-6 experiment: H4K16ac level in Hepa 1-6 HA-dTAG-KANSL3 cells upon degradation of KANSL3. Hepa 1-6 HA-dTAG-KANSL3 cells were treated for 24hrs with either dTAG-NEG control compound or dTAG13 to rapidly degrade KANSL3. Wildtype liver experiment: Identification of KANSL3 binding targets and histone modifications in wildtype liver tissue.

first: Chiara

last: Bella

first: Yidan

last: Sun


title: Discovery of tissue-specific proteomic signatures in juvenile dermatomyositis highlights pathways reflecting persistent disease activity, clinical heterogeneity, and myositis-specific autoantibody subtype

status: Public on Sep 22 2025

city: San Francisco

first: Jessica

last: Neely

state: California

address: 550 16th Street

department: Pediatrics

institute: UCSF

summary: Objectives  Juvenile dermatomyositis (JDM) is a heterogeneous autoimmune condition needing targeted treatment approaches and improved understanding of molecular mechanisms driving clinical phenotypes. We utilised exploratory proteomics from a longitudinal North American cohort of patients with new-onset JDM to identify biological pathways at disease onset and follow-up, tissue-specific disease activity, and myositis-specific autoantibody (MSA) status.  Methods  We measured 3072 plasma proteins (Olink panel) in 56 patients with JDM within 12 weeks of starting treatment (from the Childhood Arthritis and Rheumatology Research Alliance Registry and 3 additional sites) and 8 paediatric controls. Twenty-four patients with JDM who had 6-month follow-up samples were assessed. We identified differentially expressed proteins (DEPs) between groups by fitting linear mixed effects models and associated DEPs with validated disease activity measures. We assessed for cell/tissue specificity using the Human Protein Atlas and JDM muscle single nuclei and skin single-cell transcriptomic datasets. Differences within MSA subgroups were also analysed.  Results  We uncovered persistent dysregulation of innate immune activation, cell death, and redox signalling at 6 months despite multidrug immunosuppression. By leveraging tissue and cell-specific proteomes, we identified overrepresentation of circulating endothelial proteins associated with disease activity and verified endothelial cell marker expression in JDM muscle and skin. We discovered pathways associated with MSA subtypes that reflect JDM phenotypes. NXP2+ JDM-associated proteins reflected angiogenesis and extracellular matrix remodelling and were expressed in endothelial cells and fibroblasts. MDA5+ JDM was associated with circulating type III interferon and surfactant proteins.  Conclusions  These proteomic findings will inform future biomarker and treatment development considering the unique tissue- and autoantibody-associated inflammation in JDM.

first: Sara

last: Sabbagh

first: Jeffrey

last: Dvergsten

first: Chioma

last: Madubata

first: Celine

last: Berthier

first: Zilan

last: Zheng

first: Christine

last: Goudsmit

first: Sophia

last: Matossian

first: Sean

last: Ferris

first: Gabriela

middle: K

last: Fragiadakis

first: Marina

last: Sirota

first: J

middle: M

last: Kahlenberg

first: Hanna

last: Kim

last: Turnier


title: Induction of CDX2 as a differentiation therapy in colorectal cancers [cell lines]

first: Pradipta

last: Ghosh

overall_design: Two colorectal cancer cell lines  representing the colorectal cancer were used in  this study. Standard cell biological, functional and phenotypic assays were used to assess the prodifferantiation and anticancer actions of the PF compound : 1) prodifferantiation induction, 2) cytotoxicity assay  3)apoptosis, 4) invivo anticancer effect, 4) RNA sequencing

first: Saptarshi

last: Sinha


title: Single-cell mRNA analysis and surface marker expression profiling of circulating immune cells in human with alpha-gal syndrome

city: Chapel Hill

first: Austin

last: Hepperla

state: NC

address: 7018B Mary Ellen Jones Building

institute: UNC Chapel Hill

summary: Alpha-gal syndrome (AGS) is an IgE-mediated allergy to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal). Alpha-gal is found in the tissues of non-catarrhine mammals, and the characteristic delayed reactions are caused by the consumption of red meat, visceral organs, dairy, gelatin, and other products, including medications sourced from non-primate mammals. The syndrome is profoundly influenced by geographic locale, reflecting the important role of tick bites in sensitization. However, the specific immune cells, their interactions, and the downstream signaling cascades triggered by tick bites are not well understood. To address this gap, we conducted a comprehensive study utilizing CITE-seq to analyze the immune cells in the blood of AGS subjects compared to those of healthy controls.

overall_design: Peripheral blood mononuclear cell preparations were enriched for B cells from the same patient and sequentially labeled with sample tags and BD AbSeq oligo-conjugated antibodies. Sequencing libraries were prepared to targeted mRNA, antibody-oligonucleotides, and sample tags from AGS and control subjects. Multimodal analysis of both transcriptomes and surface marker expression of immune cells at the single-cell level was used to profile the immune response in AGS in comparison to control.

first: Shailesh

last: Choudhary

first: Scott

last: Commins


title: A genome-wide survey reveals a diverse array of enhancers coordinate the Drosophila innate immune response

city: Boston

first: Zeba

last: Wunderlich

state: Massachusetts

address: 610 Commonwealth Ave

department: Biology

institute: Boston University

summary: To defend against microbes, animals regulate a complex immune response. The Drosophila innate immune system deploys a large transcriptional induction of signaling proteins, anti-microbial effectors, and other critical immune factors. This transcriptional response is encoded in enhancers, cis-regulatory sequences that modulate gene expression by binding transcription factors (TFs). While enhancers and transcription factor binding sites (TFBS) have been identified for several immune responsive genes in Drosophila, most enhancers that regulate immune-induced genes are unknown. By identifying enhancers, we can understand how their composition controls expression and contributes to infection outcome. We employed STARR-seq (Self Transcribing Active Regulatory-Region sequencing) in a hemocyte-like cell line to identify immune-specific enhancers across the D. melanogaster genome and performed ATAC-seq in hemocytes extracted from adult flies to assess the chromatin state of these enhancers before and after immune stimulus. We identified thousands of enhancers responsive to IMD stimulation, one of the two primary immune signaling pathways in Drosophila. As expected, immune enhancers are enriched for motifs of Relish, an NF-κB factor, and Kay/Jra, a bZip heterodimer pair, involved in the Imd and JNK pathways respectively, compared to enhancers active in unstimulated cells. However, when grouping enhancers by their target gene’s expression timing or functional role or by the enhancers’ chromatin accessibility pre- or post-stimulus, different groups of TFBS motifs are enriched, suggesting distinct regulatory logic for different parts of the immune response. Identification and characterization of the diverse array of enhancers that regulate the innate immune response expands our understanding of how animals fight infections.

overall_design:
RNA-seq of S2* cells with three Treatments: Control, 20E and IMD stimulation. IMD stimulation includes 20E treatment and heat killed Serratia marcescens (HKSM).
STARR-seq in S2* cells transfected with a genome wide library of from iso-1 flies in the pSTARR-seq plasmid
ATAC-seq on hemocytes extracted from Oregon R adult files 24 hours after injection with heat killed Serratia marcescens (Imd stimulation) .

first: Lianne

middle: B

last: Cohen

first: Tamara

last: Hadzic

first: Caitlin

last: Sauer

first: Julia

last: Gibbs


title: The protective effect of hydrocinnamic acid on Crohn’s disease.

city: Guangzhou

first: Yijun

last: Zhu

state: Guangdong

address: Zhongshan Er Lu

country: China

institute: The First Affiliated Hospital of Sun Yat-sen University

summary: Polyphenols are promising therapeutics for Crohn’s disease (CD), yet their bioavailability is largely dependent on the gut microbiome. The bioactive metabolites, metabolic pathways, and anti-inflammatory mechanisms underlying their effects remain poorly defined. Through integrated multi-omics and dietary analysis, we identified hippuric acid as a reduced metabolite in CD patients and a biomarker of polyphenol–microbiome interactions. We further demonstrate that hydrocinnamic acid, derived from microbiome metabolism of dietary trans-cinnamic acid and subsequently converted to hippuric acid by the host, ameliorates colitis in mice via the PPAR-γ pathway. Notably, we identified Bifidobacterium breve Bbr60 and Escherichia coli FAH as novel hydrocinnamic acid producers, complementing the established pathway in Clostridium sporogenes and suggesting additional microbial contributors. Collectively, our findings establish hydrocinnamic acid as a diet-dependent, colon-produced, mild PPAR-γ agonist with the potential to minimize adverse effects associated with traditional PPAR-γ agonists. This work establishes a foundation for developing microbiota-targeted, polyphenol-based therapeutic strategies for CD patients.

overall_design: First, we administered DSS solution to induce colitis in mice. Then, intraperitoneal injections of hydrocinnamic acid were given to the experimental group of mice, while the control group received intraperitoneal injections of saline.

first: Liyuan

last: Xiang

first: Wanrong

last: Luo

first: Wenjie

last: Zhang

first: Wenhua

last: Lai

first: Xueting

last: Wu

first: Sifan

last: Chen

first: Shuguang

last: Fang

first: Shuyu

last: Zhuo

first: Boya

last: Feng

first: Minhu

first: Peng

last: Bai

first: Rui


title: Sjögren’s syndrome patients shares stereotypic B cell receptor clonotypes including homologous rheumatoid factor clonotypes present in more than a half of the patients

city: Seoul

first: Namphil

last: Kim

address: Gwanak-ro 1

department: Electrical and Computer Engineering

country: South Korea

institute: Seoul National University

summary: Autoantibodies play a key role in Sjögren's syndrome (SS) pathogenesis but its B cell receptor (BCR) repertoire has not been studied thoroughly. We analyzed peripheral blood BCR repertoire of twenty SS patients. It showed increased class switch recombination, elevated clonality, skewed usage of IGHV and IGHJ genes and its recombination pairing. Stereotypic BCR clonotypes were significantly more frequent, dominated by IgA2 isotype and showed increased somatic hypermutation. The most prevalent stereotypic clonotype specific to SS patients was shared by seven patients. And five very homologous clonotypes were present in seven other patients. All these clonotypes were proved to be rheumatoid factor.

overall_design: BCR transcripts from PBMC of Sjogren's syndrome patients and healthy controls were sequenced using NGS.

first: Young-ho

last: Jung

first: Soyeon

last: Ju

first: Sunghoon

last: Kwon

first: Junho

last: Chung


title: Comparative analysis of B-cell receptor repertoires in severe and mild myasthenia gravis

summary: The BCR repertoire characteristics of severe and mild MuSK-MG patients were compared to those of COVID19 patients and age and sex matched healthy controls

first: Eunjae

last: Lee

first: Seungwoo


title: Transcriptomic changes in response to inducible CTNNB1 activation in murine B-ALL cells

city: New Haven

first: Mark

last: Robinson

state: CT

address: 300 George St

department: Center of Molecular and Cellular Oncology

institute: Yale University

summary: As part of canonical WNT signaling, TCF7/β-catenin-complexes promote MYC-dependent proliferation. Compared to solid tumors, we found that B-cell acute lymphoblastic leukemia (B-ALL) cells, express β-catenin protein at 80- to 200-fold lower levels and critically depend on its efficient degradation: β-catenin protein was constitutively phosphorylated by GSK3B and poised for proteasomal degradation. Lesions of the β-catenin-protein degradation machinery are common oncogenic drivers, however, B-ALL cells lacked these mutations and critically depend on unencumbered β-catenin-protein degradation. Instead of TCF7/β-catenin-complexes to activate MYC, β-catenin paired with B-lymphoid Ikaros factors, resulting in MYC-repression and acute cell death. To leverage β-catenin-protein degradation as previously unrecognized vulnerability in B-ALL, we validated GSK3B-inhibition in patient-derived xenograft models in vivo. CRISPR/Cas9 chemogenomic screens confirmed β-catenin protein degradation as central mechanistic target of established GSK3B-inhibitors. Based on favorable safety profiles in clinical trials, our results provide a rationale for repurposing existing GSK3B-inhibitors for patients with refractory B-cell malignancies.

overall_design: RNAseq in BCR-ABL1+ transformed murine pre-B with or without induction of beta-catenin activation using a CTNNB1 exon3 floxed model

first: Kadriye Nehir

last: Cosgun

first: Markus

last: Muschen


title: Bcl-xL inhibition potentiates interferon-induced apoptosis in MPN stem cells

city: Brisbane

first: Jasmin

last: Straube

state: QLD

address: 300 Herston Rd

country: Australia

institute: QIMR Berghofer

summary: This RNA sequencing data set investigates the transcriptional response of wild-type and Jak2V617F haematopoietic stem cells to the chronic administration of a pegylated form of murine interferon alpha.

overall_design: RNA sequencing was performed on wild-type (CD45.1+/CD45.2-) and Jak2V617F (CD45.1-/CD45.2+) long-term haematopoietic stem cells (Lin-/Sca1+/cKIT+/CD150+/CD48-) isolated by flow cytometry from congenic recipients (CD45.1+/CD45.2+) treated with pegylated interferon alpha for 4 weeks.

first: Megan

last: Bywater


title: snRNA-seq dataset for "Morphine regulates astrocyte transcriptional dynamics by stimulation of glucocorticoid signaling"

city: Birmingham

first: Jeremy

middle: Jason

last: Day

state: AL

address: 1825 University Blvd

department: Neurobiology

institute: UAB

summary: This dataset contains single-nucleus RNA-seq results from rat ventral tegmental area brain tissue in a chronic pain model with morphine administration.

overall_design: This experiment contains 28 biological samples, which represent four experimental groups of rats. To assess neuropathic pain response, Complete Freund’s Adjuvant (CFA) or saline vehicle (100 µl) was injected into the plantar surface of one hind paw of male and female rats (n = 3-4/sex/treatment group). Mechanical sensitivity was then evaluated 48 hours and 7 days after the injection using the Von Frey assay. 7 days after CFA injection, rats received either morphine (10mg/kg) or saline injections I.P., generating a 2x2 experimental design (Veh-Sal, Veh-Mor, CFA-Sal, CFA-Mor). One hour after injections, animals were euthanized prior to rapid decapitation. Brains were blocked in 1mm sections, and VTA tissue was obtained and flash frozen, and stored at -80°C prior to nuclei isolation. Following FACS-assisted nuclei isolation and quantification, a total of 8,000 nuclei pooled from two rats (4,000 male nuclei/4,000 female nuclei from the same treatment group) and were loaded into individual wells of the Chromium NextGem Single Cell Chip (10x Genomics, catalog no. 10000121) and processed on the 10X Genomics Chromium Controller. Libraries were constructed according to manufacturer’s instructions for Chromium Next GEM single cell 3’ library and gel bead kit (10x Genomics, v3.1 single index, catalog no. 10000121, version 3 chemistry). Libraries were sequenced on an Illumina NovaSeq6000 (S2 flow cell)  to an average read depth of ~42,000 read pairs per nuclei. Forward and reverse paired-end reads are denoted as "R1" or "R2" in raw file names.

first: Jennifer

middle: J

last: Tuscher

first: Robert

middle: A

last: Phillips III

first: Catherine

last: Newman

first: Guy

last: Twa

first: Lara

last: Ianov

last: Sorge


title: Identification of a shared drug-tolerant persister program in triple-negactive breast cancer across treatments and patients [array]

city: Paris

first: Céline

last: Vallot

address: 26 Rue D'Ulm

country: France

institute: Institut Curie

summary: Acquisition of resistance to anti-cancer therapies is a multistep process, which initiates with the survival of drug tolerant persister cells. Understanding the mechanisms driving the emergence of drug tolerant persister cells remains challenging, primarily because of their limited accessibility in patients. Here, using multiple patient-derived models to isolate persister cells, we show these cells are transcriptionally plastic in vivo and return to a common treatment-naïve like state upon relapse, regardless of the treatment they have been exposed to. We reveal hallmarks of the persister state in TNBC across treatment modalities: high expression of basal keratins together with activation of a stress response and inflammation pathways. HER2+ breast and lunger cancer cells also activate these hallmarks of drug tolerance in response to targeted therapies. Leveraging gene regulatory networks, we identify AP-1, NFKB and IRF/STAT as the key drivers of this hallmark persister state. As a proof of concept, we show that FOSL1 - an AP-1 member - is sufficient to drive cells to the persister state by binding enhancers and reprogramming the transcriptome of cancer cells. On the contrary, cancer cells without FOSL1 have a decreased ability to reach the persister state. By defining hallmarks of drug persistence to multiple therapies of the standard of care in TNBC, our study provides a resource to design novel combination therapeutic strategies to limit resistance.

overall_design: Gene expression data (Affymetrix) of HBCx10 and HBCx33 Patient Derived Xenograft (PDX) of Triple Negative Breast Cancer (TNBC) in response to chemotherapies (Capecitabine, Cisplatin and Anthracyclines)   >>> Raw data not provided due to patient privacy concerns <<<

first: Léa

last: Baudre

first: Grégoire

last: Jouault

first: Elisabetta

last: Marangoni

first: Justine

last: Marsolier


title: Maternal Cholesterol Deficiency Predisposes Congenital Heart Defect Risk

city: Nanjing

first: Jimiao

last: Gao

address: 101Longmian Avenue, Jiangning District, Nanjing 211166, P.R. China

institute: Nanjing Medical University

summary: The relationship between maternal cholesterol deficiency and the risk of congenital heart defects (CHD) in offspring is not fully understood. In a birth cohort study of 5,041 family trios, we found that low maternal cholesterol levels were significantly associated with an increased risk of CHD, with relative risk (RR) of 1.52 in the second trimester and 1.73 in the third trimester. To further investigate this link, we treated pregnant mice with cholesterol-lowering agents, namely ezetimibe or atorvastatin. Both treatments led to a significant increase in the incidence of CHD in their offspring. To identify a pathogenic variant that could provide genetic evidence linking cholesterol synthesis to CHD occurrence and serve as a target for constructing genetic mouse models, we performed whole-genome sequencing (WGS) on 103 CHD cases from the birth cohort. We identified a recurrent functional variant in the CYP51A1 gene (c.1147A>G, p.Ile383Val). We then developed a CYP51A1I383V knock-in mouse model. This variant disrupted cholesterol synthesis, resulting in CHD through impaired hedgehog (Hh) signaling. Most intriguingly, maternal dietary intervention to increase cholesterol intake effectively reduced the risk of CHD in CYP51A1I383V mutant offspring. Our study suggests that low maternal cholesterol during pregnancy increases the risk of CHD in offspring by inhibiting Hh signaling, and that maternal cholesterol supplementation during pregnancy may reduce the occurrence of CHD.

overall_design: Single cell RNA sequencing of mice E10.5 hearts from wild-type and Cyp51 I383V mutant.


title: Transcriptional memory of tomato plants using ultrasound and drought stress stimuli

city: Nyíregyháza

first: Judit

last: Dobránszki

state: Szabolcs-Szatmár-Bereg

address: Westsik Vilmos út 4-6.

department: Centre for Agricultural Genomics and Biotechnology

country: Hungary

institute: University of Debrecen

type: Methylation profiling by high throughput sequencing

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

overall_design: Refer to individual Series

first: Dóra

last: Farkas

first: Anita

last: Király

first: Viktor

last: Ambrus

first: Bianka

last: Tóth


title: Direct cytotoxicity to host cells by the MARTX toxin underlies the hypervirulence of foodborne Vibrio vulnificus

city: Hong Kong SAR

first: Yating

last: XU

state: Hong Kong SAR

address: Tat Chee Avenue, Kowloon, Hong Kong SAR

institute: City University of Hong Kong

summary: Vibrio vulnificus causes severe necrotizing wound infections and life-threatening foodborne infections. While clinical isolates of V. vulnificus are well-established as human pathogens, the pathogenic mechanisms underlying the virulence of food-derived isolates, particularly in the case of wound infections, remain poorly understood. This study aimed to elucidate the pathogenic mechanisms of a highly virulent, seafood-derived V. vulnificus isolate. A molecular survey of 28 V. vulnificus isolates from Shenzhen identified four MARTX toxin types, with the D-type predominating (36%). We characterized a representative shrimp-derived isolate, Vv3, which carries a chromosomal D-type MARTX with an ACD-MCF-ABH-MCF effector architecture. Using a newly established mouse wound infection model, Vv3 induced 100% mortality within 12 hours, with high bacterial loads detected systemically. Pathological analysis revealed severe tissue damage at the infection site, marked by muscle necrosis, and significant distal organ damage. Strikingly, flow cytometry analysis of splenocytes showed a significant depletion of macrophages and lymphocytes, rather than a classic cytokine storm, which was supported by transcriptomic data. To dissect the molecular drivers underlying the pathogenicity of food-derived V. vulnificus, we generated isogenic toxin mutants. In vitro assays demonstrated that the MARTX toxin was the primary mediator of rapid cell death in both macrophages and epithelial cells. Deletion of the GD-rich repeat domain in the MARTX toxin (ΔrtxA-GD) significantly reduced cytotoxicity and allowed cells to maintain their morphology, while deletion of hemolysin (ΔvvhA) had a minor effect. Critically, In vivo mice wound infections indicated that MARTX-deficient mutants with or without deletion of vvhA is unable to cause mortality in mice. These results establish that the D-type MARTX toxin is the dominant virulence determinant in this foodborne isolate, driving mortality through a direct destruction of host cells. This study highlights the severe risk posed by foodborne V. vulnificus in wound exposures and informs that the GD-rich region serves as a potential target for intervention against V. vulnificus infection.

overall_design: To further elucidate the host transcriptional responses, we conducted high-throughput RNA sequencing (RNA-seq) on total RNA extracted from the spleen and small intestine tissues from Vv3-infected mice.


title: Microarray analysis of glucose metabolism-related genes in human umbilical cord blood derived-mesenchymal stem cells treated with everolimus under high glucose conditions

city: Cheongju

first: Hyo Youn

last: Jo

address: 1, Chungdae-ro, Seowon-gu, Cheongju-si, Chungcheongbuk-do

department: Veterinary medicine

institute: Chungbuk National University

summary: Umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) have attracted attention as a potential cell therapy due to their immunomodulatory properties, paracrine trophic effects, and differentiation capacity that promote tissue repair and functional recovery. However, exposure to diabetic conditions impairs mitochondrial function in UCB-MSCs, leading to reduced stem cell activity and increased cell death, ultimately compromising their therapeutic efficacy. Hyperglycemic stress abnormally activates mTOR signaling, driving dysregulated glucose metabolism and mitochondrial dysfunction. To assess whether everolimus, an mTOR inhibitor, can mitigate these effects, we examined glucose metabolism-related enzyme expression in UCB-MSCs exposed to high glucose with or without everolimus treatment. Microarray profiling targeted 84 glucose metabolism-related genes, including eight housekeeping genes, of which 64 genes were reliably detected. Comparison of high glucose (H) versus high glucose plus everolimus (HE) conditions (two replicates each) revealed limited transcriptional changes, with only a subset of genes showing differential expression between groups. Overall, these results indicate that everolimus does not significantly alter glucose metabolism gene expression in UCB-MSCs.

overall_design: UCB-MSCs were cultured until 70% confluency, then switched to serum-free medium for 24 hours to induce starvation. Cells were assigned to two experimental groups. In the high glucose group (H), UCB-MSCs were exposed to 25 mM D-glucose for 72 h. In the everolimus plus high glucose group (HE), UCB-MSCs were pretreated with 100 nM everolimus for 30 min, followed by the addition of 25 mM D-glucose and incubation for 72 h. Each group included two biological replicates (H1, H2, HE1, HE2).

first: Hyo

middle: Y

first: Hyun

last: Lee


title: Rod-shaped microglia interact with neuronal dendrites to regulate cortical excitability in TDP-43 related neurodegeneration

city: Rochester

first: Shuwen

last: Zhang

state: MN

address: 200 1st St SW

department: Quantitative Health Sciences

institute: Mayo Clinic

summary: Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying this early dysregulation are not fully understood. Microglia, as the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. Here we investigated the role of microglia in the motor cortical circuits in a mouse model of TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording and longitudinal in vivo calcium imaging in awake mice, we observed neuronal hyperactivity at the initial stage of disease progression. Spatial and single-cell RNA sequencing revealed that microglia are the primary responders to motor cortical hyperactivity. We further identified a unique subpopulation of microglia, rod-shaped microglia, which are characterized by a distinct morphology and transcriptional profile. Notably, rod-shaped microglia predominantly interact with neuronal dendrites and excitatory synaptic inputs to attenuate motor cortical hyperactivity. The elimination of rod-shaped microglia through TREM2 deficiency increased neuronal hyperactivity, exacerbated motor deficits, and further decreased survival rates of rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in the mouse model of TDP-43 related neurodegeneration.

overall_design: At three weeks after Dox withdrawal, single cells were isolated from rNLS8 and control mice brain using the Neural Tissue Dissociation Kit P and subsequently analyzed by scRNA-seq.

first: Manling

last: Xie

last: Wang

first: Praveen

middle: N

last: Pallegar

first: Nagaswaroop

last: Kengunte Nagaraj


title: Single-Cell RNA Sequencing Analysis of Intestinal organoids expanded in either IntestiCult™ Plus or IntestiCult™ OGM (Human)

city: Vancouver

first: STEMCELL

last: Technologies

state: BC

address: 1618 Station st

department: RND

institute: STEMCELL Technologies

summary: Conventional Intestinal organoids such as those supported by IntestiCult™ Organoid Growth medium (Human) often fail to recapitulate the cellular diversity of the intestinal epithelium and are typically comprised of Lgr5+ stem cells, transit amplifying cells, but few other cell types. IntestiCult™ Plus Organoid Growth Medium is designed to support both the expansion and differentiation of primary human intestinal organoids. Here we sought to compare the cellular diversity and transcriptomic profiles of primary organoids from 3 intestinal regions of a single donor, expanded with both IntestiCult™ OGM (Human) and IntestiCult™ Plus.

overall_design: We expanded duodenal, ileal and colonic organoids derived from a single human donor in either IntestiCult™ OGM (Human) or IntestiCult™ Plus. These organoids had been previously expanded with IntestiCult™ OGM and cryostored in Cryostor10. A single vial of each intestinal region was recovered from cryostorage and split into groups expanded with either IntestiCult™ OGM or IntestiCult™ Plus. These cultures were then passaged on a 7 day schedule three times. At the end of the third passage, The organoids were removed with the Matrigel dome with Gentle cell dissociation reagent and cells were dissociated with 0.05% Trypsin-EDTA for analysis. Single cell capture and library prep was performed using a combination of Illumina Single Cell 3' RNA Prep and 10X Genomics Chromium platforms in order to compare technologies.

first: Martin

last: Stahl

first: Eloi

last: Mercier

first: Sarah

last: Tekano

first: Marianne

last: Keown

first: Moe

last: Khajehei

first: Ryan

last: Bailey


title: Genomic and Epigenomic Coordination Maintains  Subgenome Transcriptional Balance in Allotetraploid Brassica napus

city: Wuhan

first: Jie

last: Zhou

address: 1 Lion Rock Street

institute: Huazhong Agricultural University

sample_organism:
Brassica napus
Brassica rapa
Brassica oleracea


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health [H1644_and_THESC-RNAseq]

city: Research Triangle Park

first: Francesco

middle: John

last: DeMayo

state: North Carolina

address: 111 T W Alexander Dr

department: DIR

institute: NIEHS

summary: The endometrial expression and activity of the transcriptional co-regulator, Zinc Finger MIZ-Type Containing 1 (Zmiz1),  that is co-localized with a mouse uterine estrogen receptor α (ERα)-binding super-enhancer, has not yet been evaluated. In human endometrial biopsy samples ZMIZ1 transcript and protein is dynamically expressed during the menstrual cycle. ZMIZ1 mutations are associated with some uterine tumors and ZMIZ1 RNA levels are increased in endometrium from individuals with endometriosis. Disrupting ZMIZ1 in cultured human endometrial stromal cells or in mouse uterus prevented hormone-dependent proliferation of epithelial and stromal cells as well as decidual differentiation of stroma cells, triggering sterility. Additionally, aging-dependent fibrosis was accelerated in Zmiz1-targeted mouse uterus. Notably, ZMIZ1 deletion impacted expression of stromal cell progesterone receptor (PGR), which is essential for decidual transformation. ZMIZ1 and ERα were co-localized in nuclei of mouse uterine cells, and E2F, CCNA2 and FOXM1 signaling were all decreased when ZMIZ1 was targeted, which likely underlies reduced cell cycle progression. Transcriptomic analyses revealed that loss of ZMIZ1 alters the amplitude of estrogen regulated gene responses, indicating ZMIZ1 fine-tunes endometrial cell signals needed for optimal functioning. Our findings demonstrate the importance of ZMIZ1 as an ERα co-regulator in uterine biology and pathology.

overall_design: RNAseq of THESC and H1644 immortalized endometrial stromal cells treated for 72h with vehicle (V) or estradiol+medroxyprogesterone acetate+dibutyral cyclic AMP (EPC)

first: Sylvia

last: Hewitt

first: Fracesco


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health [H1644_siZMIZ1-RNAseq]

overall_design: RNAseq of H1644 immortalized endometrial stromal cells treated with siNT (non-targeting siRNA) or siZMIZ1


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health [ChIP-Seq]

overall_design: ChIPseq of H3K27Ac in H1644 endometrial stromal cells

first: Myeongjin

last: Yi


title: Identification of a shared drug-tolerant persister program in triple-negactive breast cancer across treatments and patients [scRNA-Seq]

first: Céline

last: Vallot

overall_design:
scRNAseq of HBCx39, HBCx95, HBCx172, HBCx221 and HBCx218 Patient Derived Xenograft (PDX) of Triple Negative Breast Cancer (TNBC) in response to chemotherapies (Capecitabine and Anthracyclines

***************************************************************
Raw FASTQ files are not publicly available due to patient data privacy considerations.
***************************************************************

first: Léa

last: Baudre

first: Grégoire

last: Jouault

first: Elisabetta

last: Marangoni

first: Justine

last: Marsolier


title: Identification of a shared drug-tolerant persister program in triple-negactive breast cancer across treatments and patients [RNA-Seq]

overall_design:
RNAseq of HBCx14 Patient Derived Xenograft (PDX) of Triple Negative Breast Cancer (TNBC) in response to chemotherapies (Cisplatin, Carboplatin and Anthracyclines)

***************************************************************
Raw FASTQ files are not publicly available due to patient data privacy considerations.
***************************************************************


title: Genomic and Epigenomic Coordination Maintains  Subgenome Transcriptional Balance in Allotetraploid Brassica napus [WGBS]

summary: Allopolyploidization-induced "genome shock" poses severe challenges to subgenome stability. However, the mechanisms by which subgenomes achieve functional homeostasis through genomic and epigenomic regulation remain poorly understood. This study integrates multi-omics data from Brassica napus and its putative diploid progenitors to reveal that coordinated convergence of genomic and epigenomic plays a central role in maintaining subgenome functional homeostasis within allopolyploids. Here, we present the first comprehensive, high-quality epigenomic maps to date for the diploid Brassica rapa and Brassica oleracea. Comparative genomic analyses revealed that epigenomic reprogramming in A and C subgenomes of the allotetraploid drives convergent chromatin states, which substantially diminished expression divergence between homoeologous gene pairs. Notably, compared to the A subgenome, the C subgenome in the allotetraploid exhibits more pronounced sequence conservation of regulatory elements and epigenetic homeostasis. Furthermore, transcription factor binding sites (TFBSs) influenced by genomic variation in the A subgenome demonstrate convergent evolutionary patterns toward the C subgenome. This study provides novel insights into the coordinated convergence of genomic and epigenomic regulation between subgenomes in allotetraploid Brassica napus, demonstrating that allopolyploids resolve subgenomic conflicts through multi-layered regulatory networks. These findings establish a novel paradigm for elucidating the molecular basis of polyploidy advantages in crops and for enabling rational design of synthetic polyploids.

platform_organism:
Brassica napus
Brassica rapa
Brassica oleracea

overall_design: Whole-genome bisulfite sequencing (WGBS) for young leaves of B. rapa and B. oleracea.


title: Genomic and Epigenomic Coordination Maintains  Subgenome Transcriptional Balance in Allotetraploid Brassica napus [RNA-seq]

overall_design: RNA-seq for young leaves of B. rapa and B. oleracea.


title: Genomic and Epigenomic Coordination Maintains Subgenome Transcriptional Balance in Allotetraploid Brassica napus [ChIP-seq]

overall_design: Chromatin Immunoprecipitation followed by seqencing (ChIP-seq) for histone modifications (H3K4me3, H3K4me1, H3K27me3 and H3K9me2) in young leaves of B. rapa and B. oleracea.


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health [Array]

summary: The endometrial expression and activity of the transcriptional co-regulator, Zinc Finger MIZ-Type Containing 1 (Zmiz1),  that is co-localized with a mouse uterine estrogen receptor α (ERα)-binding super-enhancer, has not yet been evaluated. In human endometrial biopsy samples ZMIZ1 transcript and protein is dynamically expressed during the menstrual cycle. ZMIZ1 mutations are associated with some uterine tumors and ZMIZ1 RNA levels are increased in endometrium from individuals with endometriosis. Disrupting ZMIZ1 in cultured human endometrial stromal cells or in mouse uterus prevented hormone-dependent proliferation of epithelial and stromal cells as well as decidual differentiation of stroma cells, triggering sterility. Additionally, aging-dependent fibrosis was accelerated in Zmiz1-targeted mouse uterus. Notably, ZMIZ1 deletion impacted expression of stromal cell progesterone receptor (PGR), which is essential for decidual transformation. Transcriptomic analyses revealed that loss of ZMIZ1 alters the amplitude of estrogen regulated gene responses, indicating ZMIZ1 fine-tunes endometrial cell signals needed for optimal functioning. ZMIZ1 and ERα were co-localized in nuclei of mouse uterine cells. E2F, CCNA2 and FOXM1 signaling were all decreased when ZMIZ1 was targeted, which likely underlies reduced cell cycle progression. Our findings demonstrate the importance of ZMIZ1 as an ERα co-regulator in uterine biology and pathology.

overall_design: Samples from Zmiz1-f/f (Flox) or Zmiz1-d/d (KO) mice collected 20 hours after decidual (d) stimulus (intraluminal oil injection) or with no decidula stimulus (nd) were compared.


title: NLRP1 inflammasome activation in skin equivalents reveals mechanistic insights into the roles of keratinocytes in psoriasis

city: Geneva

first: Phil

middle: Fang

last: Cheng

address: Rue Gabrielle-Perret-Gentil 4

department: Oncology

country: Switzerland

institute: Hopitaux universitaires de Geneve

summary: Psoriasis is a common inflammatory disease that affects mainly the skin. The pro-inflammatory cytokines interleukin(IL)-1β and IL-36γ are involved in its pathogenesis. However, the molecular and cellular mechanisms underlying the regulation of these pathways in psoriasis are incompletely understood. IL-1β activity is produced downstream of a group of protein complexes termed inflammasomes, which are primarily expressed by immune cells. To address the function of the NLRP1 inflammasome in epidermal keratinocytes, we activated NLRP1 pharmacologically in human skin equivalents (SEs), an organotypic three-dimensional skin model. In the epidermis of these SEs, IL-1β secretion induced a histological phenotype that resembles psoriasis and is associated with a characteristic pro-inflammatory gene expression signature, including the induction of IL-36γ expression and secretion. Whereas expression of IL-36γ is induced by IL-1β, IL-36γ secretion occurs downstream of NLRP1 activation through gasdermin D pores. Most importantly, we detected inflammasome activation in suprabasal keratinocytes in lesional psoriasis. Release of endogenous double stranded (ds) RNA to the cytoplasm is associated with cellular perturbations in several inflammatory conditions, including psoriasis. In keratinocytes in monoculture, we identified short self-derived dsRNA as a novel activator of the NLRP1 inflammasome. These data suggest a critical role of keratinocytes in the pathogenesis of psoriasis through activation of the NLRP1 inflammasome. Furthermore, NLRP1-activated SEs represent a novel in vitro model for this condition, based on human primary skin cells. Most importantly, pharmacological targeting and inhibition of NLRP1 appears as a novel treatment option for psoriasis.

overall_design:
Triplicates of control skin equivalents and ASC knock-out skin equivalents were treated with vehicle or 0.3 uM talbostat for 3days. Epidermal and dermal RNA were isolated separately. >>Submitter states: Requests can be made to the PI for access to the raw data.<<

***************************************************************
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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middle: F

first: Michela

last: Di Filippo

first: Hans-Dietmar

last: Beer


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


city: Houston

first: Long-Jun

last: Wu

state: TX

address: 1825 Pressler Street

institute: University of Texas Health Science Center

overall_design: At three weeks after Dox withdrawal, FFPE brain slices were prepared from the brains of rNLS8 and control mice and subsequently analyzed using spatial transcriptomics.

first: Manling

last: Xie

last: Wang

first: Jiaying

last: Zheng

first: Zachary

last: Fogarty


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health [Mouse_uterus_V_E24-RNAseq]

overall_design: RNAseq of uterine RNA from Zmiz1-f/f control mice or Zmiz1-cKO mice treated for 24h with vehicle (V) or estrogen (E24)


title: The Novel Transcriptional Co-regulator, ZMIZ1, Modulates Hormone Responses that are Essential for Optimal Endometrial Health [H1644-HiC]

overall_design: HiC of  H1644 immortalized endometrial stromal cells treated for 72h with vehicle (V) or estradiol+medroxyprogesterone acetate+dibutyral cyclic AMP (EPC)


title: Genomic and Epigenomic Coordination Maintains  Subgenome Transcriptional Balance in Allotetraploid Brassica napus [ATAC-seq]

first: Jie

last: Zhou

overall_design: Assay for Transposase-Accessible Chromatin with high throughput sequencing (ATAC-seq) for young leaves of B. rapa and B. oleracea.


title: RNAseq analysis of cytokine-treated human neutrophils

city: Liverpool

first: Helen

middle: Louise

last: Wright

address: 6 West Derby Street

department: Institute of Life Course and Medical Sciences

country: United Kingdom

institute: University of Liverpool

summary: We report gene expression profiles of blood neutrophils from healthy individuals treated with cytokines G-CSF, GM-CSF, IFNalpha, IFNgamma, IL-1beta, IL-8, TNFalpha or untreated for 1h in vitro.

overall_design: Neutrophils (purity >97%) were isolated from peripheral blood by centrifugation through density-gradient reagent (Polymorphprep). RNA was isolated using Trizol:chloroform, cleaned up by Qiagen RNeasy kit including on-column DNase digest and sequenced on the Illumina HiSeq 2000 platform.

first: Huw

last: Thomas

first: Steven

middle: W

last: Edwards


title: Cdk8 kinase activity regulates transcriptional responses to pathological cardiac hypertrophy [ChIP-seq]

city: Iowa City

first: Chad

last: Grueter

state: IA

address: 169 Newton Rd, 4332 PBDB

department: Internal Medicine

institute: University of Iowa

summary: Purpose: The objective of this study was to determine the role of CDK8 kinase activity in hypertrophic transcriptional regulation using an in vitro rat neonatal cardiomyocyte hypertrophy model

overall_design: Methods: Neonatal rat cardiomyocytes were treated with phenylephrine in the presence or absence of CDK8 kinase inhibitor, Senexin A

first: Rachel

last: Minerath

first: Kayla

last: Henry


title: Adipose tissue gene expression profiling  in women with overweight or obesity following early vs. late time-restricted eating

city: Nuthetal

first: Michail

last: Lazaratos

address: Arthur-Scheunert-Allee 114-116

institute: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

summary: Time-restricted eating (TRE) is a promising strategy to prevent obesity and type 2 diabetes, but data on its effects on adipose tissue metabolism are limited. Therefore, we conducted a crossover study examined 31  women with overweight or obesity who followed both a two-week early TRE (eTRE) and a two-week late TRE (lTRE). Gene expression profiles in subcutaneous adipose tissue collected after both TRE interventions were compared using RNA sequencing. These data provide a first insight into the remodelling of the human adipose tissue transcriptome by the eating timing during TRE, warranting consideration in future dietary research and recommendations.

overall_design: Women with overweight or obese women have completed the randomized 10-weeks crossover clinical trial. After a 4-week baseline phase, two isocaloric 2-week interventions – (i) eTRE and (ii) lTRE - were conducted, separated by a 2-week washout phase. During the baseline phase, the participants consumed their usual food quality and quantity at their usual meal times. In the eTRE intervention, participants were asked to consume the same kind and amount of food as during the baseline but reduce their eating window to 8 h per day for a daytime from 8 am to 4 pm, while in the lTRE intervention, the 8-hour eating window shifted to 1 pm to 9 pm. Between the two interventions, participants returned to their usual eating times. Throughout the 10 weeks of the study, participants were asked to maintain their usual lifestyle habits in terms of physical activity and sleep. Subcutaneous adipose tissue samples were collected periumbilically at 9.30 a.m. after both interventions (visits 2 and 4) using a needle biopsy. Samples from 15 study participants were analysed using RNA-seq technology.

first: Olga

last: Pivovarova-Ramich

first: Markus

last: Jähnert


title: Liver gene expression of rats intoxicated with pure fumonisin B1

city: Godollo

first: Tibor

last: Nagy

address: Páter Károly street 1.

institute: Hungarian University of Agriculture and Life Sciences

summary: Purified fumonisin B1 (FB1) mycotoxin was intraperitoneally administered at the no observed adverse effect level (NOAEL, 0.2 mg/kg bw/day, group 1X) and 5 and 10-times above (5X and 10X) to male rats, in a controlled (group C), 5-day study (n=8/group, total n=32), to study in vivo hepatotoxic effects.

overall_design: liver and kidney samples

first: Zoltán

last: Doleschall


title: Gene expression during conidia germination in Tolypocladium ophioglossoides

city: West Haven

first: Francesc

last: Lopez

department: Department of Genetics

institute: Yale University

summary: Comparative transcriptomics to assess infectiou process of Tolypocladium ophoiglossoides, a parasite of false truffle mushrooms. Two media, PDA and mushroom powder agar were used, and four stages of conidial germination were examined.

overall_design: Conidia germination is critical for fungi to colonize various habitats. We sampled RNA expression at four stages of conidia germination, including fresh conidia (15min), polar growth (120min), doubling of long axis (240min), and first hyphal branching (360min) in Tolypocladium ophioglossoides. Cultures were made on PDA and mushroom powder medium, and two biological replicates were collected for all data points. The growth was under a labratory condition of 25C and constant light.

last: Lopez-Giraldez

first: Jeffrey

middle: P

last: Townsend

first: Zheng


title: Tumor suppresson protein p53 governs human trophoblast lineage development [scRNA-seq]

city: Pokfulam

first: Yunying

last: Huang

state: Hong Kong

address: Rm503, JCBIR, 5 Sassoon Road

department: School of Biomedical Sciences

country: Hong Kong

institute: The University of Hong Kong

summary: In addition to being a potent tumor suppressor, the p53 protein (encoded by Trp53 in mouse and TP53 in human) has important functions in embryo development and stem cells. The Trp53-null mice exhibit developmental defects whereas p53 activation causes implantation failure. However, it remains unclear how p53 affects early embryonic cell lineage development. We report here that p53 is highly expressed in the trophectoderm (TE) of the blastocyst and that blocking p53 activities arrests preimplantation embryo development. We have subsequently investigated p53 using human pluripotent stem cells (hPSCs) in the generation of human trophoblast stem cells (hTSCs). Genetic ablation of TP53 or chemical inhibition of p53 activities hinders the generation of hTSCs while enhancing the generation of amniotic cells. Furthermore, p53 deficiency in hTSCs results in epigenetic dysregulation of the trophoblast regulatory network involving the generation of mature syncytiotrophoblasts (STBs). In contrast, the generation and invasiveness of extravillous trophoblasts (EVTs) is enhanced. Single-cell transcriptomics analysis and experimental investigation further revealed the importance of p53 functions at multiple stages of human trophoblast development and identify that p53-mediated cell-cycle state determines trophoblast cell fate propensity. These findings for the first time demonstrate the important functions of p53 in human early embryonic cell lineage development and implicate possible links between the role of p53 in early development and tumor suppression.

overall_design: Single-cell RNA sequencing of hEPSCs, cells on differentiation day 2 and day 7 in the hTSC generation from hEPSCs, and established hTSCs with or without TP53 knockout.

first: Ling

last: Xu

first: Pentao

last: Liu


title: Single-cell gene expression profiling of myxoid liposarcoma cell line 402-91

city: Göteborg

first: Emma

last: Jonasson

address: Medicinaregatan 1F, floor 5

department: Sahlgrenska Center for Cancer Research

country: Sweden

institute: University of Gothenburg

summary: Myxoid liposarcoma (MLS) is a rare tumor type generally occuring in deep soft tissues. Genetically, it is characterized by the FUS-DDIT3 fusion oncogene with few additional mutations. MLS 402-91 is one of few existing MLS cell lines. The purpose of this dataset is to study the variation in gene expression in MLS at the single-cell level.

overall_design: Single-cell RNA sequencing using PIPseq T2 (Fluent Biosciences) of cells from myxoid liposarcoma cell line 402-91

first: Anders

last: Ståhlberg


title: Differences in gene expression between myxoid liposarcoma and Ewing sarcoma cell lines

summary: FET fusion oncoproteins, containing the N-terminal of a FET protein (FUS, EWSR1 and TAF15) together with a DNA-binding transcription factor partner, are characteristic for around 20 different sarcomas and leukemias, including myxoid liposarcoma (MLS) and Ewing sarcoma (EWS). Many of these tumors have few other genetic abberrations. Using RNA-sequencing on MLS and EWS cell lines, we showed that gene expression patterns varied between FET sarcoma subtypes. Together with other data, the information from this experiment can help to determine the oncogenic mechanism in FET sarcomas and how a common oncogenic mechanism can give rise to different tumor types, explaining the tumor-type specificity of FET oncoproteins.

overall_design: RNA sequencing of two Ewing sarcoma cell lines (EWS 6647 and TC-71) and three myxoid liposarcoma cell lines (MLS 1765-92, 402-91 and 2645-94), each in four replicates.


title: Tumor suppresson protein p53 governs human trophoblast lineage development

overall_design: To investigate the role of TP53 knockout or inhibition in the development of mouse or human trophoblast development, we established TP53KO-hEPSCs, TP53KO-cells at three time points during trophoblast differentiation and TP53KO-hTSCs and their derived hEVTs. In addition, inhibition of p53 was performed during mouse pre-implantation embryos for 20 hours. We then performed gene expression profiling analysis using data obatined from RNA-seq of these samples. Biological duplicates were performed for statistical analysis.


title: Tumor suppresson protein p53 governs human trophoblast lineage development II

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for p53 and histone modification H3K27ac, H3K4me3 and H3K27me3 and assay for transposase-accessible chromatin using sequencing (ATAC-seq) in WT- and TP53KO-hTSCs.


title: Identification of a shared drug-tolerant persister program in triple-negative breast cancer across treatments and patients [CUT&Tag]

city: Paris

first: Céline

last: Vallot

address: 26 Rue D'Ulm

institute: Institut Curie

summary: Acquisition of resistance to anti-cancer therapies is a multistep process, which initiates with the survival of drug tolerant persister cells. Understanding the mechanisms driving the emergence of drug tolerant persister cells remains challenging, primarily because of their limited accessibility in patients. Here, using multiple patient-derived models to isolate persister cells, we show these cells are transcriptionally plastic in vivo and return to a common treatment-naïve like state upon relapse, regardless of the treatment they have been exposed to. We reveal hallmarks of the persister state in TNBC across treatment modalities: high expression of basal keratins together with activation of a stress response and inflammation pathways. HER2+ breast and lunger cancer cells also activate these hallmarks of drug tolerance in response to targeted therapies. Leveraging gene regulatory networks, we identify AP-1, NFKB and IRF/STAT as the key drivers of this hallmark persister state. As a proof of concept, we show that FOSL1 - an AP-1 member - is sufficient to drive cells to the persister state by binding enhancers and reprogramming the transcriptome of cancer cells. On the contrary, cancer cells without FOSL1 have a decreased ability to reach the persister state. By defining hallmarks of drug persistence to multiple therapies of the standard of care in TNBC, our study provides a resource to design novel combination therapeutic strategies to limit resistance.

overall_design: CUT&Tag was performed on a pool of samples of MDA-MB-468, WT or GOF (HA and VPR), treated with DMSO or 5-FU, for H3K27ac and FOSL1.

first: Léa

last: Baudre

first: Grégoire

last: Jouault

first: Justine

last: Marsolier


title: Identification of a shared drug-tolerant persister program in triple-negative breast cancer across treatments and patients [CITE-seq]

overall_design: CITE-seq was performed on a pool of 5 samples MDA-MB-468 (GOF VPR control, VPR FOSL1 gRNA2, VPR FOSL1 gRNA3, HA control and HA FOSL1)


title: N6-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis via disrupting NRF1 binding capacity [ALKBH1-6mA-seq]

city: Beijing

first: Xiaohong

last: Wang

address: Haidian district

institute: Peking university cancer hospital

summary: DNA N6-methyladenine (6mA) is an emerging epigenetic modification that regulates various biological processes. Here, we demonstrated the role of DNA 6mA modification in gastric cancer (GC). GC cells and tumors displayed a marked reduction in 6mA levels compared with normal gastric tissues and GES1 cells. 6mA-IP-seq revealed that 6mA was abundant in the surrounding transcription start sites and occurred at consensus motifs. Among the 6mA regulators, ALKBH1, a demethylase, was significantly overexpressed in GC tissues compared to adjacent normal tissues (n=32, P<0.05). Moreover, high ALKBH1 expression was associated with poor survival of patients with GC in three independent GC cohorts (cohort I: n=276, P=0.0093; cohort II: n=136, P=0.001; TCGA dataset: n=381, P=0.0061). Functionally, ALKBH1 knockout increased DNA 6mA and suppressed GC cell growth and cell migration in vitro, and inhibited tumorigenicity and metastasis in vivo. ALKBH1 knockout in mice impairs chemically induced gastric carcinogenesis. Mechanistically, ALKBH1 mediates DNA 6mA demethylation to repress gene expression. In particular, the 6mA sites were enriched in NRF1 binding sequences and targeted for demethylation by ALKBH1. ALKBH1-induced 6mA demethylation inhibited NRF1-driven transcription of downstream targets, including multiple genes involved in the AMPK signaling pathway. Accordingly, ALKBH1 suppressed AMPK signaling, causing a metabolic shift towards the Warburg effect that facilitates tumorigenesis. In conclusion, we revealed, for the first time, that ALKBH1 plays an oncogenic role in GC. ALKBH1 demethylates 6mA within the NRF1-binding regions of tumor suppressor genes to attenuate the binding of NRF1, which subsequently inactivates AMPK signaling and promotes the “Warburg” phenotype.

overall_design: Analysis 6mA-seq data for GC and GES1 cells.

first: Chi

middle: C

last: Wong

first: Huarong

last: Chen

first: Kaili

last: Fu

first: Lingxue

last: Shi

first: Hao

last: Su

first: Shang

last: Guo

first: Hongyan

last: Gou

first: Xiaoxu

last: Hu

first: Lianhai

last: Zhang

first: Jiafu

last: Ji

first: Jun

last: Yu


title: The role of histone acetyltransferases Gcn5 and Esa1 in recruiting RSC and maintaining nucleosome depleted regions genome-wide in Saccharomyces cerevisiae

first: Chhabi

last: Govind

state: mi

address: 333 Science and Engineering Building

department: Biological Sciences

institute: Oakland University

summary: Chromatin remodelers are essential for the maintenance of chromatin structure and gene regulation. In this study, we examined the role of histone acetyltransferases Gcn5 and Esa1 in regulating RSC and histone occupancies and transcription genome-wide. We identify the contrasting roles of HATs in modulating RSC occupancies in promoters and ORFs. In HAT mutants, we found RSC occupancies unexpectedly accumulate in the NDRs harboring the “fragile nucleosomes (FNs)” than those with the stable -1 nucleosomes. Moreover, the accumulation was more significant in the H4 HAT Esa1 mutant than in the Gcn5 mutant. However, NDR accumulation was not observed in the cells lacking the H3 or H4 tails, suggesting that unacetylated/hypoacetylated tails are critical for the increased RSC observed in the mutants. Furthermore, we observe marked increases in histone occupancies in NDRs in the mutants genome-wide. An increase in both RSC and histones at NDRs in the HAT mutants suggests that FNs use hypoacetylated tails to recruit RSC to NDRs, and acetylation is needed for efficient histone eviction. Thus, our data implicate HATs, in addition to RSC, in maintaining NDRs. Increased histone and RSC occupancies in promoters and reduced RSC occupancies in ORFs in the HAT mutants reduce TBP and Pol II binding at promoters.

overall_design: Formaldehyde crosslinked yeast cells were subjected either to MNase digestion or sonication to obtain chromatin. The input MNase, and ChIPed sonicated and MNase chroamtin was subjected to paired-end Illumina 4K sequencing.

first: Emily

last: Biernat


title: Dietary supplement vanadyl sulfate selectively eliminates senescent cells

city: Chicago

first: Ruitu

last: Lyu

state: IL

address: 929 E 57th Street

department: Chemistry

institute: The University of Chicago

summary: During human evolution, lifestyles including dietary choices have had a major impact on shaping of human physiology and health, including aging. However, the underlying mechanisms remain largely unknown. Here, we use a blood nutrient compound library-based screening approach to demonstrate that dietary supplement vanadyl sulfate (VS) selectively induces cell death in senescent cells and ameliorates phenotypes of aging and age-related disorders in vivo. Integrated chemical biology and multi-omics studies reveal that senescent cells are specifically sensitive to VS due to reduced cysteine reactivity with accumulated glutathione disulfide. VS selectively inactivates reactive cysteines on proteins to induce formation of incorrect disulfide bonds in senescent cells with imbalanced cellular redox status, causing aberrant protein misfolding and aggregation and eventual cell death. Our findings uncover a new senolytic mechanism to mitigate age-related disorders and reshape human physiology.

overall_design: KAS-seq of induced senescent BJ cells to detect transcriptional responses of VS treatment.

first: Rong

last: Wu

first: Tong


title: N6-methyladenine DNA demethylase ALKBH1 promotes gastric carcinogenesis via disrupting NRF1 binding capacity

first: Xiaohong

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

overall_design: Refer to individual Series


title: BMAL2 controls adipose tissue inflammation and metabolic adaptation during obesity

status: Public on Sep 21 2025

city: Odense M

first: Morgane

middle: Anita

last: Philippe

address: Campusvej 55

department: BMB

country: Denmark

institute: University of Southern Denmark

summary: We profile the transcripts of adipose progenitors defined as CD45-CD31-PDGFRb+ isolated from eWAT of wild-type and Bmal2-/- C57BL/6J mice fed with normal diet or high-fat diet for 12 weeks. We show that Bmal2 invalidation strongly impacts the transcriptome profile in adipose progenitors and, when associated with obesogenic diet, enhances its deleterious effects. Loss of Bmal2 alters metabolic and maintenance pathways in adipose progenitors and strongly enhances their inflammatory function during diet-induced obesity.

overall_design: Bulk RNA-seq profiling of CD45-CD31-PDGFRb+ FACS sorted cells from eWAT of WT and Bmal2-/- (KO) C57BL/6J male mice fed with normal diet (ND) or 12 weeks high-fat diet (HFD).

first: Amine

last: Toubal


title: Preliminary Mechanistic Study on the Preventive Effect of Soybean PA Extract on Obesity Induced by High-Fat Diet

city: Nanjing

last: Xie

state: Jiangsu

address: 2#, Sipailou street

institute: Southeast University

summary: We systematically observed the effects of PA by constructing an obesity model in mice. Preliminary results indicate that a high-fat diet (HFD) containing PA can reverse the obesity process in mice. In mice fed with HFD, the addition of PA can prevent the elevation of lipoprotein a [LP(a)] levels, which is a risk factor for atherosclerosis. These results suggest that PA may have the potential to prevent obesity as well as cardiovascular and heart-related diseases.To further explore the mechanism of action of PA, we continued RNA-seq experiments on mice fed with a normal diet (ND), HFD, and HFD supplemented with different concentrations of PA (HFD + PA). The results indicate that hundreds of HFD-regulated genes are functionally enriched in fat metabolism and defense systems. The high-fat diet containing PA reverses a significant portion of the upregulated and downregulated genes induced by HFD, with the reversed genes significantly enriched in metabolism and defense Gene Ontology (GO) terms. This suggests that PA may prevent obesity and inflammatory infections in mice by interfering with lipid synthesis and improving defense systems.

overall_design: Each cage was allocated 4-5 male C57BL/6J mice at 3 weeks of age. The mice were acclimated to standard conditions for one week before being randomly divided into two groups. One group was fed with standard rodent chow, while the other group was fed with high-fat chow (containing 15% lard, 10% sugar, and 3% egg yolk powder). After 11 weeks, the group fed with high-fat chow formed the obesity model mice. In the 12th week, the obesity model mice were re-divided into three groups: the first group continued to be fed with high-fat chow (HFD, n=7), the second group was fed with high-fat chow containing 0.25% PA (HFD + 0.25% PA, n=8), and the third group was fed with high-fat chow containing 1% PA (HFD + 1% PA, n=8). Normal mice continued to be fed with standard rodent chow. The body weight of the mice was measured weekly throughout the study.


title: A dynamic gene regulatory code drives synaptic development of hippocampal granule cells [snMO]

city: leuven

first: Danie

last: Daaboul

address: Herestraat 49

department: Department of Neuroscience

country: Belgium

institute: KU Leuven

summary: Connecting neurons into functional circuits requires the formation, maturation, and plasticity of synapses. While advances have been made in identifying individual genes regulating synapse development, the molecular programs orchestrating their action during circuit integration of neurons remain poorly understood. Here, we have employed a combination of single nuclei transcriptome and epigenome sequencing (single nuclei multiome)  to study the development of the hippocampus. The hippocampus contains several excitatory and inhibitory cell types, as well as astrocytes, glia and other immune cells of the brain. The hipocampal trisynaptic circuit (DG-CA3-CA1)  is essential for learning and memory. This study provides single-cell multiome data of hippocampal postnatal (P) development (P5, P10, P15, and P28), offering an in-depth analysis of gene regulatory networks during granule cell synapse formation. Together, these findings highlight the networks of key TFs and target genes orchestrating GC synapse development.

overall_design: Hippocampi from C57Bl6 mice were homogenized, nuclei were isolated and processed for both RNA sequencing and ATAC sequencing. This process was repeated using hippocampi from mice at postnatal day (P)5, P10, P15 and P28.

first: Blanca

last: Lorente-Echeverría

first: Jeroen

last: Vandensteen

first: Gabriele

last: Marcassa

first: Willem

last: Naert

first: Joris

last: Vandenbempt

first: Elke

last: Leysen

first: Malou

last: Reverendo

first: Ine

last: Vlaeminck

first: Lise

last: Vervloessem

first: Jochen

last: Lamote

first: Suresh

last: Poovathingal

first: Kristofer

last: Davie

first: Keimpe

last: Wierda

first: Dan

last: Dascenco

first: Stein

last: Aerts

last: De Wit


title: RNA Sequencing (RNA-Seq) analysis of sex-matched neural stem cells derived from early-onset Alzheimer’s disease (EOAD), late-onset Alzheimer’s disease (LOAD), and wild-type controls

city: Richardson

first: Adedamola

middle: Saidi

last: Soladogun

state: Texas

address: 800 W Campbell Rd

institute: University of Texas at Dallas

summary: Neural stem cells derived from early-onset Alzheimer’s disease (EOAD) patients with PSEN1 mutations, late-onset Alzheimer’s disease (LOAD) patients with APOE4 genotypes, and sex-matched wild-type (WT) controls were cultured and differentiated to neurons. Undifferentiated cells (UD, cultured for 1 day) and differentiated cells (DIF, cultured for 35 days) were compared to study gene expression changes. Oligomeric amyloid beta (Aβ, 0.5 µM) was applied to differentiated WT neurons for 24 hours prior to RNA sequencing. Differential gene expression analysis revealed that genetic background differences between healthy controls, as well as between EOAD and LOAD, contribute as many expression changes as AD-specific mutations. Comparing differentiation-induced gene expression changes between AD neurons and corresponding healthy controls circumvents background variability and highlights disease-specific alterations.Analysis of over 100 AD-associated genes showed altered expression in differentiated EOAD and LOAD neurons, consistent with roles in neuronal functions and AD etiopathogenesis. Notably, LOAD neurons, but not EOAD neurons, exhibited significant deficiencies in heme and redox homeostasis, with reduced expression of genes associated with heme metabolism, oxidative phosphorylation, and NAD/NADH homeostasis. These deficiencies may underlie neuronal dysfunction and contribute to LOAD pathogenesis. Gene Ontology enrichment analysis identified pathways uniquely dysregulated in EOAD and LOAD, offering insights into the molecular mechanisms distinguishing these forms of Alzheimer’s disease. This study emphasizes the critical role of redox and heme homeostasis in LOAD and identifies gene expression patterns altered specifically by AD mutations.

overall_design: RNA sequencing was performed on neural stem cells derived from EOAD patients (PSEN1), LOAD patients (APOE), and male and female wild-type (WT) controls. Conditions included: EOAD (PSEN1): Undifferentiated (UD, 1 day), Differentiated (DIF, 35 days); LOAD (APOE): Undifferentiated (UD, 1 day), Differentiated (DIF, 35 days); WT: Undifferentiated (UD, 1 day), Differentiated (DIF, 35 days), and Differentiated + Aβ (DIF + Aβ, 35 days + 24 hours). Triplicate biological replicates were included for each condition, totaling 30 samples.

middle: S

first: Chantal

last: Vidal

first: Maria Del Carmen

last: Chacon Castro

first: Heng

last: Du

first: Li

last: Zhang


title: 3D Tumor Tissue Analogs: Tumor Microenvironment and Therapeutic Implications in DIPG

city: Los Angeles

first: Brendan

middle: H

last: Grubbs

state: CA

address: 4661 W. Sunset Blvd.

department: Obstetrics and Gynecology

institute: University of Southern California

summary: To investigate how interactions between the neoplastic and the non-neoplastic cell types in the developing tumor influence the microenvironment and alter properties of DIPG growth and therapeutic response.

overall_design: Comparative gene expression profiling analysis of whole transcriptome sequencing data for two patient derived DIPG cell lines (SU-DIPG-VI and SU-DIPG-XIII) C3H10T1/2 cells was performed when cultured alone and when grown with non-neoplastic stromal cell types that included endothelial cells (HBEC-5i) and Microglia (HMC-3).

first: Meenakshi

last: Upreti

first: Peter

last: Chiarelli

first: Matthew

last: Thornton


title: Transcriptomical characterization of T-Large Granular Lymphocyte Leukemia (T-LGLL) patients having different STAT3/STAT5B genetic status and clinical manifastations

city: Padova

first: Stefania

last: Bortoluzzi

address: via G. Colombo 3

department: Department of Molecular Medicine

country: Italy

institute: University of Padova

summary:
T-Large Granular Lymphocyte Leukemia is a rare lymphoproliferative disorder characterized by the abnormal clonal expansion of cytotoxic T-LGL.
The immunophenotype, clinical presentation, and prognosis are associated with activating mutations in STAT3 and STAT5B genes, which define four distinct subsets of the disease: CD8+ with STAT3 mutation, CD8+ wild-type, CD4+ with STAT5B mutation, and CD4+ wild-type.
RNA-seq data analysis of these patients reveals aberrant genes and non-coding RNA expression, pathways dysregulation, and the peculiarities of STAT3 mutated cases, which are associated with severe symptoms.
This study offers new insights into the pathogenesis and clinical characteristics of T-LGLL patients, highlighting potential new targetable oncogenic axes for this disease.

overall_design: T-Large Granular Lymphocytes were purified from the peripheral blood of 20 T-LGLL patients by magnetic microbeads coated with anti-human CD57 or CD56 monoclonal Abs, and CD8 for 5 healthy donors. Subsequently, total RNA was extracted and used for RNA-seq.

first: Andrea

last: Binatti

first: Giulia

last: Calabretto

first: Antonella

last: Teramo

first: Alessia

last: Buratin

first: Vanessa

middle: R

last: Gasparini

first: Cristina

last: Vicenzetto

first: Enrico

last: Gaffo

first: Gregorio

last: Barilà

first: Livio

last: Trentin

first: Monica

last: Facco

first: Gianpietro

last: Semenzato

first: Renato

last: Zambello