title: New insights into the interaction of the symbiotic bacterium Candidatus Erwinia dacicola with the adult olive fly Bactrocera oleae combining microscopy and proteomics analyses

city: Heraklion

first: John

last: Vontas

address: Nik. Plastira 100

country: Greece

institute: IMBB-FORTH

summary: The olive fruit fly Bactrocera oleae is the major pest of olive production. The fly is dependent upon the symbiotic bacterium Candidatus Erwinia dacicola for the survival of the larvae in unripe olives, and in the adult stage they enhance fecundity. A major site of symbiont colonization is the esophageal bulb, yet the molecular interactions within this tissue remain poorly understood. To investigate host gene expression in this symbiont-bearing organ, we performed a transcriptomic analysis of B. oleae esophageal bulbs. This dataset provides a foundational resource for elucidating the functional biology of this organ and offers insights into insect–microbe symbiosis.

overall_design: RNA-seq profiling of newly generated adult Bactrocera oleae esophageal bulb data was performed and compared with previously published RNA-seq data from Malpighian tubules to elucidate organ-specific gene expression. 90 female individuals were analyzed for each biological replicate, 6-25 days old.

first: Georgia

last: Pantidi

first: Ioannis

last: Livadaras

first: Evangelia

last: Skoufa

first: Emmanuel

last: Spanoudakis

first: Sofia

last: Kaforou

first: Christos

last: Andronis

first: Inga

last: Siden-Kiamos


title: Pressure Overload-Induced Ventricular Crosstalk Activates Regenerative Mechanisms in the Contralateral Ventricle in Neonatal Mice [scRNA-Seq]

status: Public on Apr 21 2026

city: Bonn

first: Mona

last: Malek Mohammadi

address: Venusberg-Campus 1

country: Germany

institute: University Hospital Bonn

type: Expression profiling by high throughput sequencing

summary: Pulmonary artery banding (PAB) can restore left ventricular (LV) function in infants with end-stage LV dilated cardiomyopathy (LV-DCM), yet the underlying mechanisms remain unclear. Given the transient regenerative capacity of the neonatal heart, we investigated whether pressure overload in one ventricle activates adaptive and regenerative responses in the contralateral ventricle. We induced pressure overload in neonatal mice at postnatal day (P) 0-1  using pulmonary artery banding (nPAB) or transverse aortic constriction (nTAC). In both models, ventricular mass and wall thickness increased not only in the targeted ventricle but also in the contralateral ventricle. These changes were accompanied by cardiomyocyte hyperplasia, preserved systolic function, and enhanced angiogenesis without fibrosis. Bulk and single-nucleus RNA sequencing revealed coordinated activation of pro-proliferative and angiogenic gene programs in both ventricles, including expansion of a cycling cardiomyocyte subpopulation characterized by Ccnd2. In contrast, PAB at P7 resulted in maladaptive hypertrophy, fibrosis, loss of cardiomyocyte proliferation, and impaired biventricular function.  These findings reveal an early-life window in which ventricular cross-talk enables a regenerative response to localized pressure overload, supporting the mechanistic rationale for clinical PAB in infants with LV-DCM.

overall_design: 16 samples were multiplexed, pooled, and a single library was sequenced; Control, non-injured (Cntl)-LV: n=2 each pool of 3 biological replicates, Cntl-RV: n=2 each pool of 3 biological replicates, P0nTAC-LV: 14dps, n=3 individual replicates, P0nTAC-RV: 14dps, n=3 individual replicates, P1nPAB-LV: 14dps, and P1nPAB-RV: 14dps, n = 3, each pool of 2 ventricles.

first: Fabian

last: Ebach

first: Julia

last: Nicke

first: Tianyuan

last: Hu

first: Hemmen

last: Sabir

first: Andreas

last: Müller

first: Bernd K.

last: Fleischmann


title: Pressure Overload-Induced Ventricular Crosstalk Activates Regenerative Mechanisms in the Contralateral Ventricle in Neonatal Mice [RNA-Seq]

summary: Driven by clinical evidence of funcional recovery of the left ventricle (LV) in children with left ventricular dilated cardiomyopathy upon increased right ventricular (RV) pressure by pulmonary aretry banding (PAB) and considering the regenerative capacity of the neonatal mammalian heart, we have explored whether pressure overload in one ventricle could trigger regenerative mechanisms in the other ventricle. Using RNAseq, we identified 636 genes, that were upregulated following nPAB in both the LV and the RV compared to Sham controls. 1052 genes were upregulated in the RV alone, 191 in the LV alone.  GO terms assicoated with genes that were upregulated in both ventricles include positive regulation of cell proliferation and angiogenesis. The here uploaded sequancing data supports echocardiographic and immunohistological evidence of an adaptive regulation of both the LV and the RV to an increased RV pressure.

overall_design: 22 samples were sequenced; left ventricular (LV, n=11) and right ventricular (RV, n=11) myocardium of mice operated with neontatal pulmonary artery banding (nPAB, n=6) and Sham-operated mice (n=5), respectively. Samples were harvested 7 days after surgery.


title: The effect of menin-inhibition on the human AML cell line MV4-11

city: Freiburg

first: Geoffroy

last: Andrieux

address: Breisacherstr 153

institute: University clinics Freiburg

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Transcriptomic profiling of iPSC-derived microglia(iMGL) reveals FGL2-mediated Aβ uptake impairment and argatroban rescue associated with rs73375428 genotype.

city: Daegu

first: Jichang

last: Yu

address: 333, Techno jungang-daero

department: Department of Brain Sciences

country: South Korea

institute: DGIST

summary: To elucidate how the rs73375428 major allele impairs Aβ uptake and how argatroban rescues this impairment independently of thrombin inhibition, we performed RNA sequencing and bioinformatic analyses in iPSC-derived microglia(iMGL). These datasets provide insight into transcriptomic changes associated with FGL2 modulation and Alzheimer’s disease risk.

overall_design: RNA-seq was performed on iPSC-derived microglia (iMGL) generated from isogenic hiPSC lines. Each genotype was prepared in biological triplicates under standard culture conditions. We compared gene expression profiles of iMGL carrying the major allele with and without argatroban treatment. In parallel, we also compared the gene expression profiles of iMGL carrying the major allele to those carrying the minor allele in the absence of argatroban to identify the transcriptional changes associated with the major allele.

first: Jinsoo

last: Seo


title: FABP4 Mediated Fatty Acid Transport Promotes Proliferation and Survival of Platinum-Resistant Ovarian Cancer Cells

city: Chicago

first: Daniela

middle: Elena

last: Matei

state: IL

address: 303 E Superior St

department: Obstetrics and Gynecology

country: USA

institute: Northwestern University

summary: Background: Ovarian cancer (OC) depends on fat as fuel for metastasis and growth. We previously demonstrated that cisplatin resistant (Pt-R) OC cells uptake higher amounts of fatty acids (FAs) compared to sensitive (Pt-S) cells– a process which facilitates cancer cell survival under cisplatin-induced oxidative stress. Results: Here we report that Pt-R OC cells are dependent on unsaturated FAs compared to Pt-S cells and upregulate key lipid transporters to allow increased uptake of FAs. Cell viability assays showed Pt-R cells were less viable under serum depletion, with oleic acid (OA, unsaturated) promoting proliferation of OC cells. OA alone rescued the inhibition of cell proliferation under conditions of serum depletion exerting more significant effects in Pt-R vs Pt-S cells. OA also reduced apoptosis, as shown by Annexin V assays, and decreased Caspase-3 and -8 cleavage. RNA-sequencing analysis linked OA-rescued cell proliferation to upregulation of cell cycle-related pathways, including G2/M checkpoints, driven by E2F1. OA increased S- and G2/M phase cell populations (6.95% to 11.6%; p<0.05), while E2F1 inhibition reduced OA-induced cell proliferation. Pt-R cells also expressed higher levels of FA transporter proteins FABP4 and CD36. Inhibiting FABPs reduced the IC50 to Pt and blocked OC growth in vivo. FABP4 was overexpressed in metastatic and recurrent vs. primary ovarian tumors. Implication: Pt-R OC cells are dependent on unsaturated FAs compared to Pt-S cells and upregulate key transporters to increase FAs uptake. OA supports proliferation of Pt-R cells by promoting cell cycle progression from G1 to S- and G2/M phases. Inhibiting FA transport reduces OC progression in vivo.

overall_design: To study the mechanism through which OA rescued the proliferation of OC cells, we performed RNA-seq in OVCAR5 Pt-S and Pt-R cells that were first cultured under starvation (induced by reducing the level of Fetal Bovine Serum from 10% down to 1%) for 24 h, and then supplemented with 50 uM OA for further 24 h. There were two experimentel groups: control group (cells starved for total 48h) and the OA group [cells starved for 24h, then supplemented with OA for further 24h (total: 48h)]. The RNA was then extracted and the RNA-seq libraries prepared. We compared the Pt-S cells cultured under starvation vs OA supplementation (n=3), and Pt-R cells cultured under starvation vs OA supplementation (n=3).  Later, we also performed RNA-seq investigating the effects of palmitic acid (PA) in OVCAR5 Pt-S cells. The experimental conditions were identical the previous experiment: Pt-S cells were first cultured under starvation (1% FBS) for 24 h, and then supplemented with 50 uM PA for further 24 h. The RNA was then extracted and the RNA-Seq libraries prepared. We compared the Pt-S cells cultured under starvation vs PA supplementation (n=3).

first: Ana Maria

last: Isac

first: Andres

last: Valdivia

first: Ujin

last: Kim

first: Yinu

last: Wang

first: Jian-Jun

last: Wei

first: Guangyuan

last: Zhao

first: Vanessa

last: Hernandez

first: Chinamyee

middle: V

last: Prabhu Dessai

first: Sandra

last: Orsulic

first: Ji-Xin

last: Cheng


title: Single-nucleus RNA sequencing of human visceral adipose tissue biopsies from 11 Italian participants.

city: Los Angeles

first: Kyla

last: Gelev

email: kylagelev@gmail.com, kzg@g.ucla.edu

address: 695 Charles E. Young Drive South

institute: University of California, Los Angeles

summary: We performed single-nucleus RNA-sequencing on visceral adipose tissue biopsies from 11 Italian donors from the Molecular Architecture of FAtty Liver Disease in individuals with obesity undergoing bAriatric surgery (MAFALDA) cohort.

overall_design: Frozen visceral adipose tissue biopsies (300mg per sample) were manually minced. Nuclei were isolated separately per sample using the 10x Genomics nuclei isolation protocol. Nuclei were then loaded into the 10x Chromium Chip in preparation of library construction. Single Cell 3’ v3.1 chemistry was used for library construction. Two lanes of the NovaSeq 6000 S4 were used for sequencing, and we targeted 50,000 reads per nucleus.

middle: Z

first: Päivi

last: Pajukanta

first: Stefano

last: Romeo


title: Single-Cell Transcriptomics Highlights Macrophage-Driven Regulation of EndMT and Repair in Injured Muscle

city: Milan

first: Anna Sofia

last: Tascini

address: Via Olgettina, 60

department: Center for Omics Science

country: Italy

institute: IRCCS, Ospedale San Raffaele

summary: This study investigates the interactions between innate immune cells and vascular-associated cells within the regenerating muscle niche. Specifically, the transcriptomes of Cdh5-CreERT2:R26R-tdTomato mice were analysed following the partial ablation of infiltrating macrophages (MPs) to understand their influence on endothelial cell (EC) behaviour after injury. This work provides a comprehensive transcriptomic signature of the regenerative muscle niche and highlights key molecular interactions between MPs and ECs.

overall_design: Cdh5-CreERT2:R26R-tdTomato mice were used to characterize the transcriptomes of regenerating muscle tissue in two experimental conditions: Clodronate liposome (CLL)-treated mice - partial ablation of circulating monocytes and compromised MP infiltration following muscle injury - or PBS liposome-treated mice as control (SHAM). Intravenous CLL or SHAM injections were performed one day before, and two days after cardiotoxin (CTX) damage on quadriceps to ensure a steady MP depletion throughout regeneration. Five days post-injury, muscles were collected, dissociated into single-cell suspensions and subjected to single-cell RNA sequencing. Each condition included three biological replicates from independent mice, generating data from a total of six independent samples.

first: Filipa

last: Timóteo-Ferreira

first: Riccardo

last: Gamberale

first: Cristiana

last: Barone

first: Mauro

last: Bergamaschi

first: Raffaella

last: Meneveri

first: Emanuele

last: Azzoni

first: Silvia

last: Brunelli


title: Small RNA production in E13.5 placenta of intra-cytoplasmic sperm injection(ICSI)-F2 offspring

city: Kyoto

first: mito

last: shinohara

state: Kyoto

address: Sakyo-ku, Yoshida Konoe

department: Medicine

country: Japan

institute: Kyoto University

type: Non-coding RNA profiling by high throughput sequencing

summary: Various behavioural abnormalities were observed in the F2 offspring of ICSI (Kanatsu-Shinohara et al., 2023, J. Clin. Invest. 133(22):e170140). The data presented here aim to clarify the cause of these abnormalities, and gene expression in the neonatal brain was investigated using RNA sequencing (RNAseq). ICSI was performed using C57BL/6 epididymal sperm and oocytes. Males from the F1 generation were naturally mated with C57BL/6 females to produce the F2 generation. Small RNA production in E13.5 placenta of ICSI-F2 offspring was examined. Each group contains 5 biological replicates.

overall_design: Neonatal brain tissue was prepared from male F2 offspring of the C57BL/6 strain, produced by natural mating from male ICSI-F1 offspring. Control brain samples were prepared from a neonate born via natural mating to wild-type C57BL/6 parents. Total RNA samples were extracted using a miRNeasy Mini Kit (Qiagen, Cat. No. 217084), followed by treatment with RNase-free DNase (Qiagen, Cat. No. 79254). cDNA libraries were generated using a TruSeq Stranded mRNA Library Preparation Kit (Illumina, San Diego, CA, USA). Sequencing was performed using a NextSeq 550 (Illumina) with a single-read sequencing length of 76 bp. A total of ten samples were analysed.

first: Mito

last: Kanatsu-Shinohara

first: Yusuke

last: Shiromoto

first: Takashi

last: Shinohara

first: Narumi

last: Ogoniki

first: Kimiko

last: Inoue

first: Atsuo

last: Ogura


title: TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency

city: Copenhagen

first: Jan

middle: Jakub

last: Żylicz

address: Blegdamsvej 3B

department: Novo Nordisk Foundation Center for Stem Cell Medicine, reNEW

country: Denmark

institute: University of Copenhagen

summary: Metabolism has emerged as a crucial regulator of development and stem cell epigenome. This coupling is particularly evident during the in vitro exit from naïve pluripotency. However, our understanding of the dynamic metabolic rewiring at this developmental stage remains rudimentary. In this study, we reconstruct intracellular metabolite routings in pre- and post-implantation mouse embryos and their dynamic stem cell models. Our findings reveal that, instead of a simple TCA cycle shutdown, there is spatio-temporally programmed TCA cycle rewiring at implantation. Focusing on the pluripotency spectrum, we identify pyruvate as a key metabolic nexus. Indeed, pyruvate carboxylase and malic enzyme activity is essential for maintaining a balanced metabolic and transcriptional state as well as timely exit from naïve pluripotency. Additionally, we discover that formative and primed pluripotent cells exhibit increased glutamine uptake, reduced oxidative TCA activity, and reciprocal reductive glutamine metabolism. This metabolic rewiring supports increased histone acetylation turnover, primarily using glutamine as a carbon source, supplemented by pyruvate cycling. Thus, we uncover diverse nutrient strategies that are functionally coupled to epigenome programming and dynamic pluripotency cell state transitions at the time of implantation.

overall_design: RNA sequencing of control (negative/scramble) and following the repression of all three Pcx, Me1 and Me2 (3xKD) in ESCs and EpiLCs day 2

first: Eleni

last: Kafkia

first: David

last: Pladevall-Morera

first: Jan Jakub

last: Zylicz


title: Syrah: a pipeline to maximize spatial transcriptomics data output

city: Kansas City

first: Alejandro

last: Sánchez Alvarado

institute: Stowers Institute for Medical Research

summary: Spatial analysis of gene expression patterns has been a key technique for revealing the functions of genes. Traditionally, these analyses were constrained to examining only a few candidate genes per sample. However, the advent of spatial transcriptomic techniques like Slide-seqV2 has transformed this field, enabling unbiased and massively parallel exploration of gene expression patterns within their tissue contexts through RNA sequencing. Despite its potential, Slide-seq datasets often suffer from low read counts, loss of data points, and poor quality. We have identified that a significant source of these errors stems from the chemical synthesis of mRNA capture oligonucleotides used in Slide-seqV2. To address this issue, we have developed "Syrah," an analysis pipeline designed to correct these errors. Syrah can dramatically enhance Slide-seqV2 datasets by recovering nearly 30% more reads. Unlike other dataset improvement methods that rely on complex mathematical imputation or single-cell RNA-seq references, Syrah operates independently, requiring no additional datasets or intricate calculations. This innovative technique promises to salvage previously unusable Slide-seq datasets by restoring valuable reads that were inadvertently discarded during analysis.

overall_design: Comparison of standard and Syrah spatial transcriptomic data processing, including previously published Slide-seqV2 and Curio Seeker data, as well as a novel planarian Slide-seqV2 dataset.

first: Carolyn

middle: E

last: Brewster

first: Frederick

middle: G

last: Mann Jr

first: Blair

last: Benham-Pyle


title: Expression data of E13.5 placenta from intra-cytoplasmic sperm injection(ICSI)-F2 offspring

summary: Various behavioural abnormalities and congenital anomalies were observed in the F2 offspring of ICSI (Kanatsu-Shinohara et al., 2023, J. Clin.). Invest. 133(22): e170140). The data presented here aim to clarify the cause of these abnormalities. Gene expression in the ICSI-F2 placenta was investigated using RNA sequencing (RNA-seq). ICSI was performed using C57BL/6 epididymal sperm and oocytes. Male ICSI-F2 offspring was mated with wild-type C57BL/6 female, and placentae recovered from pregnant females at E13.5 were examined for gene expression. Each group contains five biological replicates.

overall_design: ICSI was performed with C57BL/6 wt female mice sere mated naturally to ICSI-F1 male, and placenta was recovered from pregnant female by caesarean section at E13.5. Control placenta samples were prepared from pregnant female at the same stage after natural mating with C57BL/6 wt male. Total RNA samples were extracted using a miRNeasy Mini Kit (Qiagen, Cat. No. 217084), followed by treatment with RNase-Free DNase (Qiagen, Cat. No. 79254). cDNA libraries were generated using a TruSeq Stranded mRNA Library Preparation Kit (Illumina, San Diego, CA). Sequencing was performed using a NextSeq 550 (Illumina) with a single-read sequencing length of 76 bp. A total of ten samples were analysed.

first: Takuya

last: Yamamoto


title: Intracellular iron homeostasis-regulated epigenetic reprogramming contributes to -7/del(7q) leukemia

city: Chengdu

first: Yiman

last: Peng

state: Sichuan

address: No.1, Keyuan 4th Road, Gaopeng Avenue, Chengdu, Sichuan, China

department: State Key Laboratory of Biotherapy, West China Hospital, Sihcuan University

country: China

institute: Sichuan University

summary: Chromosome copy number variations (CNVs) are among the most critical yet poorly understood genetic drivers of human malignancies. -7/del(7q) is one of the most common CNVs in acute myeloid leukemia (AML) and is associated with poor prognosis. It has been proposed that there might be multiple tumor suppressor genes (TSGs) in these CNVs. Previously, we identified KMT2C, a histone methyltransferase, as a tumor suppressor gene in chromosome 7q. In this study, we performed a differentiation CRISPR screening of hematopoietic stem and progenitor cells (HSPCs) and discovered that ABCB8, encoding a mitochondrial iron transporter, is essential for HSPC differentiation. ABCB8 deficiency accelerated leukemogenesis in vivo and disrupted iron homeostasis, reducing cytoplasmic iron availability and impairing iron-dependent enzymes, including the histone demethylase KDM6A. Consequently, ABCB8 loss elevated H3K27me3 levels, repressing differentiation genes in an iron- and KDM6A-dependent manner. Notably, ABCB8 and KMT2C, neighboring genes on 7q, cooperatively regulated H3K27me3 to suppress leukemogenesis. Our findings reveal ABCB8 as a novel TSG in -7/del(7q) AML and uncover an unprecedented epigenetic collaboration between neighboring TSGs, driven by iron-mediated chromatin remodeling.

overall_design: Various mouse HSPC models were applied to investigate the functions of ABCB8 and other genes function in -7/del(7q) leukemia

first: Jianan

last: Zheng

first: Xintong

last: Deng

first: Lanxin

last: Zhang

first: Zhongwang

last: Wang


title: Temporal mapping of B cell diversification mechanisms in vivo

city: Melbourne

first: Oliver

middle: Philip

last: Skinner

state: VIC

address: 792 Elizabeth Street

department: Microbiology and Immunology

country: Australia

institute: Peter Doherty Institute, University of Melbourne

summary: Naive B cells amplify and diversify their responses when activated by cognate antigen, via clonal expansion, immunoglobulin isotype switching, phenotypic variation, and somatic hypermutation (SHM). Since diversity in the antigenic targets, functional classes, and production kinetics of parasite-specific antibodies influences immunity to malaria, we test here whether individual B cell clones diversify over time in vivo during Plasmodium infection and treatment. During the first week of infection, amid widespread bystander activation, isotype switching initiates soon after Myc up-regulation, and overlaps partially with clonal expansion, resulting in isotype variegation amongst clones. During the second week of infection, expanded clones that seed germinal centres (GC) bifurcate into extra-follicular plasmablasts, exhibit isotype variegation, and initiate SHM, revealing substantial intra-clonal diversification. Over the following month, GC clones exhibit SHM at a constant rate. Anti-malarial intervention does not impede SHM, but instead exerts quantitative limits on GC size, plasma cell emergence, circulating antibody levels, and protection against re-infection. Finally, contemporaneous B cell development relocates from bone marrow to spleen during infection and treatment. Thus, multiple temporally overlapping mechanisms combine in vivo to amplify, diversify, and safeguard humoral immune responses.

overall_design: scRNAseq (gene expression and VDJ) of sorted B cells from splenocytes of female mice at various timepoints post-Plasmodium infection with or without anti-malarial drug treatment. Experiment 1: scRNAseq and BCRseq B cells at timepoints, 4-, 7-, 10-, 14-days post infection. Each timepoint contains 5x hashtagged individual mouse samples. Note, timepoint 4 days post infection includes one uninfected mouse sample. Experiment 2: scRNAseq and BCRseq B cells at timepoints 10-, 14-, 21-, 28-, 35-, 42-days post infection. At each timepoint, there are 7 hashtagged individual mouse samples: 3x samples infection only, 3x samples infection with anti-malarial drug treatment and 1x uninfected sample. Experiment 3: scRNAseq of sorted GC B cells and ASCs from a single day 14 Plasmodium infected mouse spleen. Spatial transcriptomics using Stereo-seqv1.2 was also performed on day 21 Plasmodium infected mouse spleens from two independent mice.

middle: P


title: Gelsenicine disrupted the intestinal barrier of Caenorhabditis elegans

city: Fuzhou

first: Peichun

last: Ye

address: No.1 Xuefu North Road, Fuzhou, Fujian, China

institute: Fujian Medical University

summary: The treatment of gelsenicine resulted in the increase of nematode intestinal permeability. The toxicological mechanisms underlying this effect involved the disruption of intestinal barrier integrity, an imbalance between oxidative and antioxidant processes mediated by the SKN-1/DAF-16 pathway, and abnormal unfolded protein reaction.

overall_design: The objective of this study was to assess enterotoxicity induced by gelsenicine in the nematodes Caenorhabditis elegans.

first: Zekai

last: Wu

first: Jian

first: Yajiao

first: Mengting

last: Chen


title: Single-nucleus RNA sequencing of human visceral adipose tissue biopsies from 63 Italian participants.

first: Kyla

last: Gelev

summary: We performed single-nucleus RNA-sequencing on visceral adipose tissue (VAT) biopsies from 63 Italian donors from the Molecular Architecture of FAtty Liver Disease in individuals with obesity undergoing bAriatric surgery (MAFALDA) cohort.

overall_design:
Frozen VAT biopsies (n=63) were pooled and batched into 8 batches. There were 7-8 VAT samples per batch. We randomly assigned samples to batches to minimize associations with phenotypes of interest. We isolated nuclei in groups of two samples (50 mg per sample) prior to pooling all samples into their respective batch using the 10x Genomics nuclei isolation protocol. Batches of nuclei were then loaded into the 10x Chromium Chip, and library construction was performed using the Single Cell 3’ v3.1 chemistry. Sequencing was performed across two lanes of the Novaseq X Plus 25B. We targeted 70,000 reads per nucleus.

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There are patient privacy concerns regarding public access to the raw data
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first: Päivi

last: Pajukanta

first: Stefano

last: Romeo


title: HNF1B integrates signals in a feed-forward loop driving kidney disease progression [RNAseq_P60d2]

city: Paris

first: Pierre

last: Isnard

address: 156-160, rue de Vaugirard

country: France

institute: INEM

summary: Chronic kidney disease (CKD) is a complex disorder with substantial unexplained heritability. While GWAS have identified common variants, rare variants and gene-environment interactions likely play a major role. HNF1B, a transcription factor essential for kidney development, is also a  cause of monogenic CKD but its function in adult kidneys remains unclear. Here, we show that HNF1B loss in adult mouse kidneys induces rapid CKD with epithelial dedifferentiation, aberrant cell cycle re-entry, and replicative stress. Strikingly, suppression of the HNF1B transcriptional program is observed across multiple human and experimental CKD models, independent of cause. These findings position HNF1B as a central regulator of renal epithelial integrity and reveal a feed-forward mechanism in which HNF1B dysfunction contributes to and is reinforced by CKD progression. Our results provide insight into shared pathways underlying diverse forms of CKD and suggest new targets for therapeutic intervention.

overall_design: In order to understand the early molecular events that lead to a progressive phenotype (tubular lesions, fibrosis and kidney failure) in mice lacking HNF1B in kidney tubular cells, we performed RNAseq on kidneys from p60 wildtype and HNF1Bflox/KSPcre ERT2 mice, 2 days after deletion of HNF1B.

first: Munevver

last: Makinistoglu

first: Michel

last: Leibovici

first: Serge

last: Garbay

first: Fabiola

last: Terzi

first: Marco

last: Pontoglio


title: Expression data of E19.5 placenta from intra-cytoplasmic sperm injection(ICSI)-F1/F2 offspring

first: mito

last: shinohara

summary: Various behavioural abnormalities and congenital anomalies were observed in the F2 offspring of ICSI (Kanatsu-Shinohara et al., 2023, J. Clin.). Invest. 133(22): e170140). The data presented here aim to clarify the cause of these abnormalities. Gene expression in the ICSI-F1/F2 placenta was investigated using RNA sequencing (RNA-seq). ICSI was performed using C57BL/6 epididymal sperm and oocytes. The ICSI-F2 generation was produced using the sperm of the ICSI-F1 generation via in vitro fertilisation. Placentae recovered by caesarean section at E19.5 were examined for gene expression. Each group contains four biological replicates.

overall_design: ICSI was performed with C57BL/6 wt female mice sere mated naturally to ICSI-F1 male, and placenta was recovered from pregnant female by caesarean section at E19.5. Control placenta samples were prepared from pregnant female at the same stage after  natural mating. Total RNA samples were extracted using a miRNeasy Mini Kit (Qiagen, Cat. No. 217084), followed by treatment with RNase-Free DNase (Qiagen, Cat. No. 79254). cDNA libraries were generated using a TruSeq Stranded mRNA Library Preparation Kit (Illumina, San Diego, CA). Sequencing was performed using a NextSeq 550 (Illumina) with a single-read sequencing length of 76 bp. A total of eight samples were analysed.

first: Mito

last: Kanatsu-Shinohara

first: Takashi

last: Shinohara

first: Takuya

last: Yamamoto

first: Narumi

last: Ogoniki

first: Kimiko

last: Inoue

first: Atsuo

last: Ogura

first: Keiji

last: Mochida


title: Accelerated Reprogramming of hiPSCs into Functional Brain Endothelial Cells with Multiplexed CRISPR Activation

city: Ottawa

first: Ziying

last: Liu

state: ON

address: 1200 Montreal Road

country: Canada

institute: National Research Council, Canada

summary: The blood-brain barrier (BBB) is comprised of brain endothelial cells, which are utilized in vitro to model the BBB under normal and disease conditions. Despite physiological shortcomings, in vitro BBB models derived from human induced pluripotent stem cells (hiPSC) are favored due to their species specificity and superior barrier qualities. Here, we demonstrate the generation of hiPSCs-derived brain endothelial cells (iBEC) using transcriptional reprogramming with a multiplex CRISPR/dCas9 activation (CRISPRa) strategy that selectively activates essential BEC genes. Transcriptional reprogramming simplified the differentiation of iPSCs into mature iBECs and accelerated differentiation from 13 to only five days. Furthermore, CRISPRa reprogrammed iBECs exhibit robust barrier formation with TEER values > 230 Ω x cm2 and correspondingly low transcellular permeability values (< 0.015 x10-3 cm/min). The iBECs expressed a panel of key BBB markers (Claudin-5, ZO-1, CDH5, PECAM1, Occludin, GLUT-1) and transporters involved in receptor-mediated transcytosis (TFR1, IGF1R, TMEM30A). Importantly, the CRISPRa iBECs exhibited a robust angiogenesis phenotype that was absent in the non-engineered iPSCs. This novel CRISPRa-directed differentiation strategy not only accelerates differentiation to the BEC phenotype but also demonstrates the utility of CRISPR gene regulation in modifying the phenotype of iPSC-derived cells.

overall_design: CRISPRa-mediated Reprogramming of iPSCs into Brain Endothelial Cells

first: Roy

middle: W

last: Hwang

first: Will

middle: J

last: Costain

first: Tyler

last: Renner


title: Arabidopsis transcriptomic response to Flavobacterium sp. 98 inoculation

city: Leiden

first: Salma

last: Balazadeh

address: Sylviusweg 72

department: Plant Cluster

country: Netherlands

institute: Leiden University

summary: Drought is one of the most detrimental environmental factors that adversely affect crop production, thus jeopardizing food supplies for a growing world population. Over the past years, it has become evident that microorganisms associated with plants can enhance drought tolerance. However, the specific genetic and molecular mechanisms underpinning bacterial induction of drought tolerance in plants are still largely unknown. In our work, we have shown that a root endophytic Flavobacterium sp. 98 confers significant drought tolerance to Arabidopsis thaliana without compromising growth and yield. Here, we compared the transcriptome of Arabidopsis seedlings inoculated with Flavobacterium or mock (time series) to identify transcription reprograming induced by Flavo in plants.

overall_design: To investigate the molecular mechanisms underlying Flavobacterium SP. 98'S function in enhancing of root hair formation and elongation and confering drought tolerance, Arabidopsis seedlings were inoculatied with with mock (100mM MgSO4) or Flavobacterium and roots were collected at different time points (12, 48, and 72 hours and 6 days) and subjected to transcriptome analysis using RNA-seq.

first: Arezoo

last: Rahimi

first: Guillermo

last: Edigo

first: Victor

last: Carion Bravo


title: RNA Folding Energy Regulates Discontinuous Transcription in Coronaviruses

city: Boston

first: Stephen

middle: Joseph

last: Ross

state: Massachusetts

address: 72 E Concord St

institute: Boston University School of Medicine

summary: Coronaviruses use discontinuous transcription to generate subgenomic RNAs (sgRNAs) that encode structural and accessory proteins. However, the factors regulating sgRNA abundance remain unclear. Here, we combined strand-specific RNA sequencing, RNA:RNA interaction mapping, thermodynamic modeling, and targeted mutagenesis to define the regulation of (-) sgRNA synthesis in SARS-CoV-2 infection. We demonstrate that the relative (-) sgRNA abundance across viral genes is stable throughout infection and strongly correlates with corresponding (+) sgmRNA levels. Through meta-analysis of published SPLASH data, we found that the frequency of long-range interactions between the 5′ genomic transcription regulatory sequence (TRS)-Leader and downstream TRS-Body sequences correlates with sgRNA abundance. Notably, the thermodynamic stability (ΔG) of these duplexes quantitatively predicts (-) sgRNA transcript levels. Mutations in non-coding regulatory regions that altered the ΔG resulted in corresponding changes in (-) sgRNA expression, establishing a causal role for TRS duplex stability in transcriptional regulation. Analysis of naturally occurring mutations near regulatory sites further suggests that modulation of duplex stability may also serve as an evolutionary mechanism to fine-tune viral gene expression. Together, our findings identify TRS-Leader:TRS-Body thermodynamics as a key determinant of discontinuous transcription and reveal how RNA structure encodes gene expression levels in the coronavirus genome.

sample_organism:
Chlorocebus aethiops
Mus musculus

platform_organism:
Chlorocebus aethiops
Mus musculus

overall_design: SARS-CoV-2 and rMHV NGS RNA-Sequencing by bulk and poly(A) Sequencing

first: Chengjin

last: Ye

first: Simon

last: Moxon

first: Elke

last: Mühlberger

first: Luis

last: Martinez-Sobrino

first: Daniel

last: Cifuentes


title: Excitatory neurons and astrocytes-specific dysregulation and aberrant interactions are vulnerable to FCDI as suggested by single-cell spatial transcriptomics [Spatial transcriptomic]

city: Shenzhen

first: Yaqian

last: Zhang

state: Guangdong Province

address: Guangming

department: Department of Neurology

institute: The Seventh Affiliated Hospital, Sun Yat-sen University

summary: Focal cortical dysplasia (FCD) is a common neurodevelopmental disorder characterized by malformations of cortical development and is a leading cause of drug-resistant epilepsy. In this study, we employed single-nucleus RNA sequencing (snRNA-seq) and spatial transcriptomics sequencing (ST-seq) to investigate the molecular pathological features of FCD type I (FCDI) brain tissue from both cell type-specific and spatial heterogeneity perspectives. This integrated analysis provides novel theoretical insights into the pathogenesis of FCDI associated epilepsy.

overall_design: Epileptogenic cortical tissues from three FCDI patients and three relatively normal neocortical tissues as controls were analyzed using single-nucleus RNA-seq and spatial transcriptomic for multi-omics integration.

first: Qihang

last: Zou

first: Yingying

first: Liemin

last: Zhou


title: HNF1B integrates signals in a feed-forward loop driving kidney disease progression [ChIPseq_Hnf1b]

first: Pierre

last: Isnard

summary: Chronic kidney disease (CKD) is a complex disorder with substantial unexplained heritability. While GWAS have identified common variants, rare variants and gene-environment interactions likely play a major role. HNF1B, a transcription factor essential for kidney development, is also a cause of monogenic CKD but its function in adult kidneys remains unclear. Here, we show that HNF1B loss in adult mouse kidneys induces rapid CKD with epithelial dedifferentiation, aberrant cell cycle re-entry, and replicative stress. Strikingly, suppression of the HNF1B transcriptional program is observed across multiple human and experimental CKD models, independent of cause. These findings position HNF1B as a central regulator of renal epithelial integrity and reveal a feed-forward mechanism in which HNF1B dysfunction contributes to and is reinforced by CKD progression. Our results provide insight into shared pathways underlying diverse forms of CKD and suggest new targets for therapeutic intervention.

overall_design: In order to determine the HNF1B transcriptional program, we performed Chromatin immunoprecipitation-sequencing (ChIP-seq) for HNF1B on adult mice kidneys.

first: Munevver

last: Makinistoglu

first: Michel

last: Leibovici

first: Serge

last: Garbay

first: Fabiola

last: Terzi

first: Marco

last: Pontoglio


title: Excitatory neurons and astrocytes-specific dysregulation and aberrant interactions are vulnerable to FCDI as suggested by single-cell spatial transcriptomics [snRNA-seq]

last: Liu


title: Expression data from MDA-MB-231 and MCF10 cells

city: cairo

first: Monica

last: Rostom

state: Cairo

address: first settlement, Banafseg 4

country: Egypt

institute: German University in Cairo

summary:
MDA-MB-231 cells are treated with Maraviroc and DZH_2 and MCF10 are treated by DZH_2 for evaluation of cytotoxic effect on normal breast cells
We used microarrays to compare the differential gene expression after treatment with Maraviroc and DZH_2 and investigate the possible pathway of DZH_2.

overall_design: MDA-MB-231 cells were treated with DZH_2 and Maraviroc and MCF10 were treated with DZH_2 for RNA extraction and hybridization on Affymetrix microarrays.

middle: M


title: HNF1B integrates signals in a feed-forward loop driving kidney disease progression [RNAseq_UUOd1]

overall_design: In order to investigate the expression patterns of HNF1B target genes in an early mouse model of chronic kidney disease (CKD), we performed RNA-sequencing analysis on kidney tissue collected 24 hours after unilateral ureteral obstruction (UUO) in mice.

first: Frank

last: Bienaime


title: Conservation and divergence of UVR8 photoreceptor-mediated UV-B signaling in Marchantia polymorpha

city: Geneva

first: Roman

last: Ulm

address: 30 Quai E. Ansermet

country: Switzerland

institute: University of Geneva

summary: Ultraviolet-B radiation (UV-B) poses a major challenge to all forms of plant life. The liverwort Marchantia (Marchantia polymorpha) serves as a key model organism for studying signaling pathways and inferring their evolution throughout the green lineage. Marchantia expresses key components of UV-B signaling, including the photoreceptor UV RESISTANCE LOCUS 8 (MpUVR8), the WD40-repeat protein REPRESSOR OF UV-B PHOTOMORPHOGENESIS (MpRUP), the E3 ubiquitin ligase complex CONSTITUTIVELY PHOTOMORPHOGENIC 1 / SUPPRESSOR OF phyA-105 (MpCOP1/MpSPA), and the transcriptional regulator ELONGATED HYPOCOTYL 5 (MpHY5). Here, we show that whereas the core UVR8 photocycle is well conserved, regulatory roles of SPA and HY5 diverged during plant evolution. Unlike the case in Arabidopsis (Arabidopsis thaliana) and in contrast to the strong Mpcop1 mutant phenotype, Mpspa mutants developed only a very weak constitutive photomorphogenesis phenotype, indicating that COP1 function is much more independent of SPA in Marchantia than in Arabidopsis. Moreover, in contrast to Arabidopsis SPAs, Mpspa showed enhanced UV-B acclimation and UV stress tolerance, indicating that MpSPA is a negative regulator of MpUVR8 signaling. Similar to Arabidopsis HY5/HYH, MpHY5 functioned antagonistically to MpCOP1, but its role in UV-B-mediated gene expression changes was more limited. Our findings demonstrate that although core components of UV-B signaling existed in the last common ancestor of extant land plants, regulatory interactions have diversified in different lineages since their divergence more than 400 million years ago.

overall_design: Wild type Tak-1, Mpuvr8, Mprup, Mpcop1, Mpspa and Mphy5 mutants gemmalings were grown for 7 days in 50 μmol m-2 s-1 white light and exposed or not to supplemental UV-B (1.5 μmol m-2 s-1) for 3h.

first: Yuanke

last: Liang

last: Podolec


title: A Novel Strain of Bacillus velezensis Exhibits Biocontrol Activity Against Maize Pathogens and Promotes Plant Growth

status: Public on Apr 20 2026

city: Hangzhou

first: yuanlin

last: qi

address: No. 666, Wusu Street, Lin'an District

department: Donghu Campus

institute: Zhejiang A&F University

summary: Southern corn leaf blight (SCLB), caused by Bipolaris maydis, poses a serious threat to maize production worldwide. In our previous study, Bacillus velezensis BV3 was isolated and demonstrated strong antagonistic activity against maize leaf spot pathogens and effective disease control in greenhouse experiments.

overall_design: In this study, inoculation with BV3 significantly promoted maize growth. Moreover, BV3 treatment induced extensive transcriptional and metabolic reprogramming in maize. Transcriptomic analysis identified numerous differentially expressed genes (DEGs) mainly enriched in plant–pathogen interaction, plant hormone signal transduction, MAPK signaling pathway, and phenylpropanoid biosynthesis pathways. Metabolomic analysis revealed substantial changes in metabolite accumulation, particularly in lipids, amino acids, sugars, organic acids, and polyphenols, with enriched pathways including secondary metabolite biosynthesis, phenylpropanoid biosynthesis, and flavonoid biosynthesis. LC/MS and GC/MS analyses further revealed that BV-3 produced diverse bioactive compounds. 2,4-DTBP and surfactin exhibited strong antifungal activities, particularly against B. maydis and E. turcicum. Overall, Bacillus sp. BV3 exhibits strong biocontrol efficacy against maize leaf spot pathogens and significant plant growth-promoting activity, highlighting its potential as an eco-friendly biocontrol agent for the management of southern corn leaf blight.

first: Yuanlin

last: Qi

first: Jinai

last: Yao


title: Effect of Fibrosis in FMO3 Knockout Mice in a bleomycin-induced fibrosis Model

city: Ann Arbor

first: Bioinformatics

last: Core

state: MI

address: BRCF Bioinformatics Core, 2800 Plymouth Rd

institute: University of Michigan

summary: FMO3 knockout attenuates bleomycin-induced lung fibrosis

overall_design: Female C57BL/6J mice (8–12 weeks old) and FMO3 knockout mice (C57BL/6J-Fmo3^em1Bdgr/J; strain #037364) were obtained from The Jackson Laboratory.  Mice received daily subcutaneous (s.c.) injections of bleomycin (10 mg/kg/day) or phosphate-buffered saline (PBS) for 10 days (5 days per week). Animals were euthanized on day 22, and lung were used for RNA isolation.

first: Priyanka

last: Verma

first: John

last: Varga


title: LASER couples damage sensing to ESCRT assembly for lysosome repair

city: Berkeley

first: Roberto

last: Zoncu

state: CA

address: Li Ka Shing Center

institute: University of California, Berkeley

summary: Lysosomal membrane integrity is essential for cell survival, but how damage sensing is spatiotemporally coupled to repair remains poorly understood. Recruitment and assembly of Endosomal Sorting Complex Required for Transport (ESCRT) I-III rapidly counteracts membrane damage, but how ESCRT-I recognizes defective lysosomal membranes is unclear. Leveraging genome-wide CRISPRi screens in a damage-sensitized genetic background, we discovered LC3/GABARAP Assisted Stimulator for ESCRT Recruitment (LASER), a multicomponent protein assembly that forms rapidly upon calcium release from damaged lysosomes, and which couples sensing of lysosomal membrane damage to ESCRT-dependent repair. At the core of LASER is Trk-fused gene (TFG), an ER exit sites (ERES) resident protein that translocates to damaged lysosomes by binding to ATG8 family proteins (LC3/GABARAP) conjugated to lysosomal phospholipids. ATG8-bound TFG forms oligomeric assemblies that directly recruit the essential ESCRT-I subunit, Tumor Suppressor Gene 101 (TSG101), via conserved motif recognition enhanced by avidity-driven interactions. TFG binding to TSG101 stimulates sequential ESCRT I-II-III polymerization and promotes membrane repair. TFG mutations that drive hereditary spastic paraplegia disrupt its oligomerization and impair lysosomal ESCRT recruitment and membrane resealing, implicating defective repair as a driver of TFG-associated neurodegeneration. Thus, LASER promotes ESCRT polymerization at damaged lysosomes and couples damage sensing to membrane repair.

overall_design: Genome-wide growth-based CRISPRi screen performed in sgNT or sgNPC1 K562 cells treated with DMSO or LLOME.

first: Claire

last: Goul

first: Aakriti

last: Jain

first: Samira

last: Yitiz

first: Elly

last: Soltani

first: Serim

last: Yang

first: Simon

last: Rapp

first: Martina

last: Spacci

first: Scot

last: Federman

first: James

last: Sacco

first: Huinan

last: Li

first: Lauren

middle: D

last: Enriquez

first: Nalan

last: Liv

first: Laralynne

last: Przybyla


title: The effect of menin-inhibition on the human AML cell line MV4-11 [ATAC-seq]

city: Freiburg

first: Geoffroy

last: Andrieux

address: Breisacherstr 153

institute: University clinics Freiburg

summary: Allogeneic hematopoietic stem cell transplantation remains the most efficacious treatment for many hematological malignancies. However, its therapeutic potential is affected by the most prominent side effect graft versus host disease. Despite advances in the treatment of graft versus host disease in recent years, morbidity and mortality remains high, which requires the development of new treatment approaches. In vitro, we have observed an upregulation of MHC / HLA molecules in several AML cell lines after treatment with the menin-inhibitor MI-463. We hypothesize that menin-inhibition increases the graft-versus-leukemia effect via targeting and sensitizing MLL-mutant AML cells, thus enhancing HLA-dependent killing.

overall_design: MV4-11 cells were cultured for one week in cell culture flasks in Iscove's Modified Dulbecco's Media with 10% FCS and 100 I.U./mL penicillin and 100 μg/mL streptomycin. After the cell number was increased, the cells were seeded in cell culture 12-well-plates with a concentration of 0.5 x 10e6 cell/mL in 2 mL of respective media. 6 wells were either treated with DMSO or 1 µM MI-463 in 2 µL/mL. The cells were incubated for 48h. After 48h, the cells were collected and analyzed.

first: Eyleen

last: Corrales

first: Viktor

last: Fetsch

first: Schwobel

last: Lennard

first: Robert

last: Zeiser

first: Melanie

last: Boerries


title: Using iCLIP-seq to analyze the distribution of XRCC5/6 on HBV RNA

city: 武汉市

first: jiangpeng

last: FENG

state: 湖北省

address: 武昌区小洪山中区

institute: Wuhan institute of virus

summary: In this study, we found that XRCC5/6, as pseudourindine reader proteins, can bind Ψ on HBV RNA and regulate HBV expresion. To directly analyze the binding sites of XRCC5/6 on HBV RNA, iCLIP-seq was performed in HepG2.2.15 cells using antibodies against XRCC5 and XRCC6, PUS1. The results revealed that XRCC5/6, PUS1, specifically bind 3'UTR of HBV RNA, with significant enrichment around the Ψ sites.

overall_design: iCLIP-seq of XRCC5 and XRCC6 on HBV genome RNA in HepG2.1.15 cell line.

first: Jiangpeng

last: Feng

first: Wuxiang

last: Guan


title: Tectochrysin alleviates Ang II-induced pathological cardiac hypertrophy by binding to STING and inhibiting STING/NFκB-mediated inflammation

city: Chongqing

first: Yanghao

last: Chen

address: No. 288, Tianwen Avenue, Nan'an District, Chongqing

institute: Chongqing Medical University

summary: Angiotensin II (Ang II)-induced cardiac inflammation plays a pivotal role in the pathogenesis of pathological cardiac hypertrophy and hypertension-related heart failure. Tectochrysin (Tec) is a flavonoid natural compound exhibiting significant anti-inflammatory activity. However, the role of Tec in hypertensive heart failure and its molecular targets remain unclear. The therapeutic efficacy of Tec was assessed in the Ang II-induced mouse model using echocardiography, histopathological staining, and serological tests. Its anti-hypertrophic effect was further examined in vitro by phalloidin staining. Investigate the mechanism of action of Tec through transcriptome sequencing. The interaction of Tec with STING was detected by DARTS, CETSA, and SPR assays. Western blotting assay detected the effect of Tec on Ang II-induced activation of the STING/NFκB pathway. The functional dependency of Tec on STING was demonstrated using the STING inhibitor H151. In vivo experiments confirmed that Tec alleviates Ang II-induced myocardial inflammation, pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction. Further in vitro studies revealed the efficacy of Tec in inhibiting cardiomyocyte hypertrophy. Mechanistically, Tec significantly suppressed Ang II-induced activation of the STING/NFκB signalling pathway by targeting STING. Crucially, administration of the STING inhibitor H151 alleviates pathological myocardial hypertrophy, however its use diminishes the therapeutic effect of Tec. Our findings confirmed STING as a critical therapeutic target in pathological ventricular remodeling, with Tec exerting its anti-hypertrophic effects through STING inhibition.

overall_design: we performed RNA sequencing analysis on the heart tissues of three Ang II mices and three Ang II mices treated by Tectochrysin

first: Zhiyu

last: Ling


title: Functional evolution, modification, and derivatization of mammalian developmental enhancers

city: Seattle

first: Tony

state: WA

address: 3720 15th Ave NE

department: Genome Sciences

institute: University of Washington

summary: This dataset encompasses two complementary massively parallel reporter assay (MPRA) studies that together dissect the functional architecture and evolutionary dynamics of mammalian cis-regulatory elements (CREs) at nucleotide resolution, using five parietal endoderm enhancers as a model system. The first study maps the functional evolution of these enhancers by testing orthologous sequences from 480 extant and ancestrally reconstructed mammalian genomes (Zoonomia/Cactus). Using a model-driven reconstitution strategy guided by deep learning predictions of chromatin accessibility, we traced causal transcription factor binding site (TFBS) changes across lineages, revealing pervasive context-dependent epistasis and diverse modes of evolutionary divergence. Targeted enhancer editing further demonstrated a striking asymmetry: ablation of enhancer activity required as few as one to seven mutations, whereas activity enhancement was constrained by element-specific ceilings. The second study subjects the same five enhancers to intensive sequence perturbation, assaying over 35,000 variants organized into four classes: dense multi-size tiling, multi-hit saturation mutagenesis, model-guided compaction, and TFBS-anchored sequence derivatization including synthetic thripsis. This dissection revealed sharp non-additivity between fragment size and activity, a spectrum of mutational robustness, rare but consequential inter-TFBS epistasis, and a strong influence of background sequence on enhancer output independent of TFBS arrangement. Together, these datasets provide a comprehensive resource for understanding how enhancer sequences encode function, robustness, and evolvability across the mammalian phylogeny.

overall_design: To link molecular barcodes (mBCs) to their corresponding CRE sequences, we performed CRE-BC association mapping. Using paired-end Illumina sequencing, each mBC and its associated CRE were captured within a single amplicon, generating a lookup dictionary for each library prior to massively parallel reporter assay (MPRA) experiments.

first: Jean--Benoit

last: Lalanne

first: Jay

last: Shendure


title: CytoSignal Detects Locations and Dynamics of Ligand-Receptor Signaling at Cellular Resolution from Spatial Transcriptomic Data

first: Joshua

last: Welch

address: Palmer Commons, 100 Washtenaw Ave

department: Department of Computational Medicine & Bioinformatics

summary: Nearby cells within tissues communicate through ligand-receptor signaling interactions. Emerging spatial transcriptomic technologies provide a tremendous opportunity to systematically detect ligand-receptor signaling, but no method operates at cellular resolution in the spatial context. We developed CytoSignal to infer the locations and dynamics of cell-cell communication at cellular resolution from spatial transcriptomic data. CytoSignal is based on the simple insight that signaling is a protein-protein interaction that occurs at a specific tissue location when ligand and receptor are expressed in close spatial proximity. Our cellular- resolution, spatially-resolved signaling scores allow several novel types of analyses: we identify spatial gradients in signaling strength; separately quantify the locations of contact-dependent and diffusible interactions; and detect signaling-associated differentially expressed genes. Additionally, we can predict the temporal dynamics of a signaling interaction at each spatial location. CytoSignal is compatible with nearly every kind of spatial transcriptomic technology including FISH-based protocols and spot-based protocols without deconvolution. We experimentally validate our results in situ by proximity ligation assay, confirming that CytoSignal scores closely match the tissue locations of ligand-receptor protein-protein interactions. Our work addresses the field's current need for a robust and scalable tool to detect cell-cell signaling interactions and their dynamics at cellular resolution from spatial transcriptomic data.

overall_design: Two E12.5 whole mouse embryos from separate biological samples were used for this study. For each sample, we performed serial sectioning, took the middle slice for Visium HD spatial transcriptomics, and saved the other two or three spatially adjacent slices for proximity analysis (PLA).

first: Jialin

last: Liu

first: Hiroaki

last: Manabe

first: Noriaki

last: Ono


title: Multisensory integration at the dawn of land plant evolution

city: Valencia

first: Javier

last: Forment

address: Ingeniero Fausto Elio, s/n

country: Spain

institute: Instituto de Biología Molecular y Celular de Plantas, IBMCP (Universitat Politècnica de València-CSIC)

summary: Land plant colonization was a pivotal event in the evolution of photosynthetic eukaryotes. The transition from aquatic to terrestrial environments required complex multisensory systems that enabled plants to perceive and integrate a broader range of environmental cues, such as light intensity and temperature. However, it remains unclear whether this ability was a pre-adaptation or an innovation during early plant terrestrialization. Here, we show that the aquatic streptophyte ancestor of land plants could integrate light and temperature through a complex regulatory network. A conserved regulatory nexus, comprising phytochromes and transcription factors, was active in the last common ancestor of land plants, allowing the first terrestrial colonizers to adapt and flourish on the harsh terrestrial surface of our planet. Thus, we propose that the multisensory integration that enables extant plants to achieve perceptual disambiguation and fine-tune growth in various ecological niches was a pre-adaptation encoded in the genomes of ancestral land plants.

sample_organism:
Marchantia polymorpha
Arabidopsis thaliana
Ostreococcus tauri
Mesotaenium endlicherianum

overall_design: To assess the integration of light and temperature at a transcriptomic level in different plant species, we grew Arabidopsis thaliana, Marchantia polymorpha, Mesotaenium endlicherianum and Ostreococcus tauri in different combinations of light and temperature conditions.

first: Bruno

last: Catarino

first: Fernando

last: Rodríguez-Marín

first: Cristina

last: Úrbez

first: Christina

last: Arvanitidou

first: Eva

last: Álvarez

first: Federico

last: Valverde

first: José

last: Franco-Zorrilla

first: Francisco

last: Romero-Campero

first: Miguel

middle: A

last: Blázquez


title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity [ATAC-seq1]

city: Memphis

first: Hongbo

last: Chi

state: TN

address: 262 Danny Thomas Place

department: Immunology

institute: St Jude Children's Research Hospital

summary: ATAC-seq profiling of WT and OPA1-deficient cDC1s

overall_design: Splenic cDC1s were purified from WT or CD11c-Cre; OPA1 flox mice, followed by ATAC-seq analysis

first: Hao

last: Shi

first: Zhiyuan

last: You


title: Cellular Signatures of Melanocortin Pathway Genes Across the Locus Coeruleus [snRNA-seq]

city: New York

first: Fahrunisa Meryem Betul

last: Erol Gulsen

state: NY

address: 1150 St Nicholas Ave

department: Pediatrics

institute: Columbia University

summary: Obesity and Alzheimer’s disease (AD) are epidemiologically associated. The locus coeruleus (LC) – the brain’s primary and most significant source of norepinephrine – is one of the earliest sites of neurodegeneration in AD. The LC participates in feeding behavior through connections with the hypothalamus. The cellular composition of the LC has been characterized at single-cell resolution. However, the constituent cellular signatures of genes related to energy homeostasis – such as the melanocortin pathway genes – in the LC are unclear. We performed single-nucleus RNA sequencing and spatial transcriptomics (Visium) in the human LC, and HiPlex RNAscope in the LC of mice. The melanocortin pathway gene MRAP2 was expressed in the majority of DBH neurons across the LC. Mrap2 was also co-expressed with AD-associated genes such as App, Psen1, Psen2, and Sorl1. More than 20% of Dbh neurons in the LC were positive for Mrap2, App, Psen1, and Psen2. Mrap2 is expressed in the central nervous system and modulates the trafficking and signaling of all five G-protein coupled receptors (GPCRs) of the melanocortin receptor family: Mc1r, Mc2r, Mc3r, Mc4r, and Mc5r. In mice, among the melanocortin receptors, Mc5r showed the highest co-expression with Mrap2, accounting for 17.9% of Mrap2-positive cells, followed by Mc2r with 10.9% of Mrap2-positive cells. Mc1r, Mc3r, and Mc4r showed very limited co-expression with Mrap2. Our study reveals that many Mrap2-positive cells do not express any melanocortin receptor genes, warranting future studies into metabolically relevant GPCRs downstream of MRAP2 in the LC. In summary, our study characterizes melanocortin molecular substrates in the human and mouse LC and highlights MRAP2 as a potential link between pathways of energy homeostasis and neurodegeneration.

overall_design:
Postmortem human locus coeruleus (LC) tissue from one neurotypical adult female donor (74 years old) was profiled by single-nucleus RNA sequencing (snRNA-seq) to characterize cell-type-specific expression of melanocortin pathway genes and co-expression with Alzheimer's disease-associated genes at single-nucleus resolution.

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

first: Alisha

last: Basak

first: Fahrünisa Meryem Betül

last: Erol

first: Maria Caterina

last: De Rosa

first: Zhangji

last: Dong

first: Victor

last: Ogbolu

first: Hannah

last: Glover

first: Rick

last: Rausch

first: Gunnar

last: Hargus

first: Jordi

last: Creus-Muncunill

first: Heather

last: Buchanan

first: Yu

last: Bai

first: Qi

last: Su

first: Betty

last: Chang

last: Adler

first: Delaney

last: Flaherty

first: Benjamin

last: Ciener

first: Harrison

last: Xiao

first: Hasini

last: Reddy

first: Pascaline

last: Aime-Wilson

first: Christiane

last: Reitz

first: Mark

last: Sleeman

first: Judith

middle: Y

last: Altarejos

first: Rudolph

middle: L

last: Leibel

first: Liang Oscar

last: Qiang

first: Andrew

middle: F

last: Teich

first: Claudia

last: Doege


title: Single cell variant to enhancer to gene map for coronary artery disease [ChIP-seq]

city: Singapore

first: Roger

last: Foo

address: 14 Medical Drive, MD6

country: Singapore

institute: National University of Singapore

summary: Although genome wide association studies (GWAS) in large populations have identified hundreds of variants associated with common diseases such as coronary artery disease (CAD), most variants lie within non-coding regions of the genome, rendering it difficult to determine the downstream causal gene and cell type. Here, we performed paired single nucleus gene expression and chromatin accessibility profiling from 44 human coronary arteries. To link disease variants to molecular traits, we developed a meta-map of 88 samples and discovered 11,182 single-cell chromatin accessibility quantitative trait loci (caQTLs). Heritability enrichment analysis and disease variant mapping demonstrated that smooth muscle cells (SMCs) harbor the greatest genetic risk for CAD. To capture the continuum of SMC cell states in disease we used single cell caQTL modeling for the first time in tissue to uncover QTLs which are cell state aware and expand our insight into gene regulation in heterogenous cell populations. We identified a variant in the COL4A1/COL4A2 CAD GWAS locus which becomes a caQTL as SMCs de-differentiate through a transcription factor binding site change for EGR1/2. To unbiasedly prioritize functional candidate genes, we built a genome-wide single cell variant to enhancer to gene (scV2E2G) map in human CAD to link disease variants to causal genes in cell types. Using this approach, we found several hundred genes predicted to be linked to disease variants in different cell types. We validated these predictions using enhancer targeted perturb sequencing (TAP-seq). Next, we performed genome-wide HiC in 16 human coronary arteries to build tissue specific gene regulatory networks and map disease variants to integrated chromatin hubs and distal target genes not previously implicated. Using this approach, we show that rs4887091 within the ADAMTS7 GWAS locus modulates function of a super chromatin interactome through a change in a CTCF binding site. Finally, by integrating human genetics with single cell multi-omics we show that CAD genetic risk is enriched in de-differentiated fibromyocytes. Collectively we provide a disease agnostic framework to translate human genetic findings to identify pathologic cell states and genes driving disease, producing a comprehensive scV2E2G map with genetic and tissue level conviction for future mechanistic and therapeutic studies.

overall_design:
One million human coronary artery smooth muscle cells (HCASMC) and human coronary endothelial cells (HCAEC) from the same lot used for HiChIP experiments were crosslinked with 1% Formaldehyde for 10 min at room temperature and quenched with glycine (125mM) for 5 min.
The cells were rinsed twice with cold 1XPBS and sonicated in nuclei lysis buffer (50mM HEPES-KOH, pH 7.5, 150mM NaCl, 1mM EDTA, 1% Triton X, 0.1% Sodium deoxycholate, 1% SDS, Takara, 1x protease inhibitor) using the Bioruptor sonicator to obtain chromatin fragments between 200 to 500 bp.
The fragmented chromatin was immunoprecipitated overnight at 4ºC, with 5 μg of H3K27ac antibody (Abcam, ab4729) and 50 μl of protein G beads (Invitrogen, 10004D). Subsequently, the beads were washed and immunoprecipitated DNA was de-crosslinked and eluted in elution buffer (50 mM Tris-HCI, pH7.5, and 10 mM EDTA). Eluted ChIP fragments were isolated using Phenol-Chloroform extraction method, and DNA was purified by ethanol precipitation.

first: Chang Jie Mick

last: Lee

first: Anene-Nzelu

last: Chukwuemeka

first: Amrute

last: Junedh

first: Stitziel

last: Nathan


title: Gene expression alteration in mouse articular chondrocytes by 25-hydroxycholesterol, 25-hydroxycholesterol-3-sulfate and GW3965 treatment

city: Xi'an

first: Huanbo

last: Wang

address: No. 127, Changle West Road

institute: Xijing Hospital, Fourth Military Medical University

summary: Previous studies have demonstrated that 25-hydroxycholesterol (25HC), which is involved in the initiation and progression of osteoarthritis (OA), can be sulfated by SULT2B1 to produce 25-hydroxycholesterol-3-sulfate (25HC3S). Given this background, this study aims to investigate whether 25HC3S and 25HC have different functional effects on articular chondrocytes. Additionally, since 25HC has been proven to be an endogenous ligand of liver X receptor (LXR), this study also compares the effects elicited by the LXR agonist GW3965 on articular chondrocytes to provide insights into whether 25HC and its sulfated derivative, 25HC3S, exert distinct influences on the LXR signaling pathway.

overall_design: mRNA was extracted from articular chondrocytes of 6-week-old mice following 48-hour treatments with DMSO (Vehicle), 20μM 25-hydroxycholesterol, 20μM 25-hydroxycholesterol-3-sulfate, or 2μM GW3965.

first: Chao

last: Zheng

first: Liu

last: Yang

first: Bowei

last: Ni


title: Inosine suppresses liver A-to-I RNA editing to promote cancer-associated cachexia in a riboswitch-like manner.

city: WuHan

first: XiaoTing

last: Wu

address: Luojiashan Street

institute: Wuhan University

summary: Cancer-associated cachexia (CAC) is a devastating syndrome and a major cause of morbidity and mortality in advanced cancer patients while liver is emerging as a key organ during CAC progression1. However, how tumor dysregulates liver function to promote CAC remains largely unknown. Here, we employ NMR spectrometry to detect that the elevation of 13C-inosine availability, attributed to the tumor-induced cytosolic 5'-nucleotidase II (NT5C2) protein accumulation, decreases the abundance of adenosine deaminase act on RNA 1 p150 isoform in a riboswitch-like manner. Intriguingly, reduced liver A-I mRNA editome enhances the stability of Cathepsin L mRNA to aggravate liver autophagy, triggering the secretion of serum amyloid A1, while CTSL-/- mice fail to develop cachectic phenotype upon inosine treatment. Strikingly, NT5C2 inhibitor CRCD2, a frontline leukemia treatment drug, greatly attenuates CAC progression. Conclusively, our finding reveals that inosine-mediated liver A-to-I mRNA editome alteration promotes CAC progression in a riboswitch-like manner, shedding light on the clinical applications for early CAC diagnosis and intervention.

overall_design: Genomic data for mice recived inosine intraperitoneal injection and control.

first: Wei

last: Yan

first: Xiao-Ting


title: Inosine suppresses liver A-to-I RNA editing to promote cancer-associated cachexia in a riboswitch-like manner

overall_design: mice recived inosine intraperitoneal injection and control.

last: WU


title: YAP rejuvenates cardiomyocytes by changing mitochondrial substrate utilization

city: Houston

first: Yi

last: Zhao

state: Texas

address: 6770 Bertner Avenue

institute: The Texas Heart Institute at Baylor College of Medicine

summary: Postnatal cardiomyocyte (CM) maturation, marked by a metabolic transition from glycolysis to fatty acid oxidation, impedes adult CM proliferation and heart regeneration. Our research reveals that Hippo-YAP signaling facilitates CM cell cycle re-entry by reducing lipid utilization in CMs, thereby preserving mitochondrial homeostasis, and promoting CM rejuvenation. On the other hand, overloaded fat by a maternal high-fat diet significantly enhances fatty acid oxidation and maturation in neonatal CMs, counteracting YAP-mediated rejuvenation effects. Through metabolomic and transcriptomic analyses, we discovered that YAP-induced mitochondrial substrate utilization change predominantly depends on reducing Cpt1b activity. Additionally, we identified Mef2 as a crucial activator for CM maturation, which is inhibited upon YAP overexpression, leading to decreased Cpt1b levels in CMs. Our results highlight the heterogeneity and adaptability of neonatal CM energy metabolism and establish YAP as a key regulator of CM substrate utilization. Furthermore, we elucidate a mechanistic framework by which YAP reverses metabolic maturation in cardiomyocytes, thereby facilitating heart regeneration. This insight advances our understanding of metabolic remodeling in heart regeneration and the therapeutic potential of YAP.

overall_design: Single nuclei RNA sequencing  were performed to examine control versus AAV-cTNT-YAP5SA induction in neonate murine hearts, with or without maternal HFD treatment.

first: Lin

last: Liu

first: Xiao

last: Li

first: James

last: Martin


title: Glutathione triggers trap movement for carnivory in carnivorous plants

city: Beijing

first: daoxin

last: Xie

address: Tsinghua University Haidian District

institute: Tsinghua University

summary: Charles Darwin was infinitely fascinated with Drosera (sundew plants), which have behaved as the most sagacious animals and evolved as flesh-eaters with modified leaves, called traps, to catch and digest insects. However, the molecular basis underlying movement of carnivorous plants remains very limited. Here, we uncover glutathione (GSH) as an endogenous signaling molecule in sundew plants that triggers trap movement for carnivory. To better understanding the molecular basis of sundew carnivory, we further performed transcriptomic profiling of closed sundew traps stimulated by living fruit flies and GSH.

overall_design: Trap closure of Cape sundew was indued either by feeding living fruit fly on leaf or applying 100 mM GSH on to the leaf petiole. Such closed sundew traps as well as the mock control sundew traps were collected and further subjected to transcriptome profiling.

first: Rui

first: Yongfang

first: Jianbin

first: Qinggang

last: Liao

first: Haidong

last: Chen

first: Xiaoyi

last: Shan

first: Daoxin


title: CD5L promotes phagocytic removal of Amyloid β oligomers and improves cognitive function in a mouse model of Alzheimer's disease [RNA-Seq]

city: Shinjuku

first: Natsumi

last: Maehara

state: Tokyo

address: 8-1, Kawata-cho

department: Department of Molecular Biomedicine for Pathogenesis

institute: The Institute for AIM Medicine

summary: Alzheimer's disease (AD), a neurodegenerative disorder, is the leading cause of dementia. Amyloid-beta (Aβ) and tau are major contributors to AD onset and progression. Here, we investigate the therapeutic potential of CD5L, a macrophage-specific secretory protein, in reducing Aβ accumulation and improving AD pathology. CD5L directly binds to Aβ, particularly the neurotoxic Aβ42, and blocks their aggregation. Moreover, CD5L enhances microglial phagocytosis against several forms of Aβ40 and Aβ42. In 5xFAD mice, a well-established AD murine model, forced expression of CD5L reduced Aβ plaque size and number. RNA sequencing revealed that CD5L promotes phagocytic activity in microglia within the 5xFAD mouse brain. Furthermore, adeno-associated virus (AAV)-mediated delivery of CD5L improved cognitive function, as demonstrated by enhanced performance in the T-maze test. These findings highlight the role of CD5L in inhibiting Aβ aggregation and facilitating Aβ clearance via enhanced phagocytosis, offering a promising therapeutic strategy for AD.

overall_design: Bulk RNA sequencing was performed to compare gene expression profiles between 5xFAD  mice, 5xFAD mice with forced expression of mouse CD5L via a transgene regulated by the human PDGF-B promoter (5xFAD/Cd5l tg/wt) and wild-type mice. Total RNA was extracted from brain tissues (cerebellum removed) and used for library preparation and sequencing.

first: Aika

last: Hirota

first: Kai

last: Kudo

first: Yuri

last: Yoshikawa

first: Satoko

last: Arai

first: Toru

last: Miyazaki


title: CD5L promotes phagocytic removal of Amyloid β oligomers and improves cognitive function in a mouse model of Alzheimer's disease


title: An ERF-CEP5 Induced Root Hair Formation module: A Drought Adaptation Mechanism Unveiled by Flavobacterium

city: Leiden

first: Salma

last: Balazadeh

address: Sylviusweg 72

institute: Leiden University

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

overall_design: Refer to individual Series


title: Acquired genetic and cell state changes in IDH-mutant glioma progression

city: New Haven

first: Kevin

middle: C

last: Johnson

state: CT

address: 333 Cedar Street

department: Neurosurgery

institute: Yale University

summary: Isocitrate dehydrogenase (IDH)-mutant gliomas are malignant brain tumors that typically arise in early- to mid-adulthood and nearly always recur following treatment. However, the genetic and cellular state changes that drive IDH-mutant glioma progression under treatment remain incompletely understood. Here, we integrated single-nucleus transcriptomic profiles, chromatin accessibility profiles and bulk DNA/RNA sequencing from 75 temporally separated gliomas across 35 patients comprising both the oligodendroglioma and astrocytoma IDH-mutant glioma tumor types. We show that malignant cell states transcriptionally resemble stages of normal glial-neuronal lineage development or a reactive mesenchymal-like state, mirroring states previously described in IDH-wildtype glioblastoma. Malignant cell states displayed distinct chromatin accessibility profiles that were comparable between both IDH-mutant glioma types. The abundance of less differentiated malignant cells increased with grade and with genetic alterations such as PDGFRA amplification. Longitudinal analysis highlighted two major malignant cell state transition patterns. First, reduced lineage differentiation and increased proliferative malignant cells at recurrence were pronounced in gliomas that acquired recurrence-associated genetic events, including treatment-associated hypermutation, increased copy number changes, and cell cycle alterations. Second, increased mesenchymal-like state abundance occurred independently of acquired genetic alterations and instead coincided with heightened macrophage expression. Overall, our findings provide an integrative model that traces the cell-intrinsic and extrinsic factors that shape cellular states during IDH-mutant glioma disease progression.

overall_design:
MGG152, an IDH-mutant patient-derived glioma cell line, was profiled by single-cell RNA sequencing (10x Genomics, 3' v3 (polyA)) across different experimental conditions. The conditions included a parental MGG152 cell line, MGG152 CDKN2A-/- single guide RNAs 1 & 3 (MGG152 CDKN2A-/- sgRNA1 and sgRNA3), and a non-targeting control (MGG152 NTC).

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

first: Roel

last: Verhaak

first: Ester

last: Calvo Fernández

first: Julie

last: Miller

first: Hiroaki

last: Wakimoto

first: Daniel

last: Cahill

first: Mario

last: Suvà


title: Identification of ERF115 and ERF114 downstream genes

summary: Drought is one of the most detrimental environmental factors that adversely affect crop production, thus jeopardizing food supplies for a growing world population. Over the past years, it has become evident that microorganisms associated with plants can enhance drought tolerance. However, the specific genetic and molecular mechanisms underpinning bacterial induction of drought tolerance in plants are still largely unknown.In our work, we have shown that a root endophytic Flavobacterium confers significant drought tolerance to Arabidopsis thaliana. We showed that the bacterium enhances drought tolerance by maintaining (and inducing) root hair formation and elongation under drought. By combining molecular, genetics, and omics technologies we identified an essential role of ethylene and two ethylene-induced transcription factors belonging to the ERF family (ERF115 and ERF114) through which flavobacterium exerts its effect on plant root hair formation and drought tolerance. Here we performed transcriptome analysis using RNA-seq to identify genes downstream of the two ERF transcription factors.

overall_design: To investigate downstream target genes of ERF115 and ERF114 in roots, we perform RNAseq analysis and compared the transcriptome of 4 day old roots of wild-type (Col-0), ERF115OX, ERF114OX and ERF115-SRDX transgenic lines.

first: Arezoo

last: Rahimi

first: Guillermo

last: Edigo

first: Victor

last: Carion Bravo


title: The effect of menin-inhibition on the human AML cell line MV4-11 [gene expression]

first: Geoffroy

last: Andrieux

summary: Allogeneic hematopoietic stem cell transplantation remains the most efficacious treatment for many hematological malignancies. However, its therapeutic potential is affected by the most prominent side effect graft versus host disease. Despite advances in the treatment of graft versus host disease in recent years, morbidity and mortality remains high, which requires the development of new treatment approaches. In vitro, we have observed an upregulation of MHC / HLA molecules in several AML cell lines after treatment with the menin-inhibitor MI-463. We hypothesize that menin-inhibition increases the graft-versus-leukemia effect via targeting and sensitizing MLL-mutant AML cells, thus enhancing HLA-dependent killing.

overall_design: MV4-11 cells were cultured for one week in cell culture flasks in Iscove's Modified Dulbecco's Media with 10% FCS and 100 I.U./mL penicillin and 100 μg/mL streptomycin. After the cell number was increased, the cells were seeded in cell culture 12-well-plates with a concentration of 0.5 x 10e6 cell/mL in 2 mL of respective media. 6 wells were either treated with DMSO or 1 µM MI-463 in 2 µL/mL. The cells were incubated for 48h. After 48h, the cells were collected and analyzed.

first: Andrieux

last: Geoffroy

first: Viktor

last: Fetsch

first: Lennard

last: Schwobel

first: Zeiser

last: Robert

first: Boerries

last: Melanie


title: SFPQ rescues F508del-CFTR expression and function in cystic fibrosis bronchial epithelial cells

city: Baltimore

first: Supriyo

last: De

state: Maryland

address: 251 Bayview Blvd

department: Laboratory of Genetics and Genomics

institute: NIA-IRP, NIH

summary: Here, we investigated the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung epithelial cells. We find that the expression of SFPQ is reduced in F508del-CFTR CF epithelial cells compared to WT-CFTR control cells. Interestingly, the overexpression of SFPQ in CF cells increases the expression as well as rescues the function of F508delCFTR. Further, comprehensive transcriptome analyses indicate that SFPQ plays a key role in activating the mutant F508del-CFTR by modulating several cellular signaling pathways. This is the first report on the role of SFPQ in the regulation of expression and function of F508del-CFTR in CF lung disease.

overall_design: The role of SFPQ in CF lung disease using CF lung epithelial cell culture systems.

first: Roopa

last: Biswas

first: Myriam

last: Gorospe


title: Anti-epileptic drugs are endocrine disruptors for the human fetal testis ex vivo.

city: Rennes

first: Frédéric

last: Chalmel

state: France

address: 9 avenue du Pr. Léon Bernard

department: Physiology and physiopathology of the urogenital tract

institute: Inserm U1085-Irset

summary: Identifying and characterizing the effects of valproic acid (VPA) on the differentiation and function of the different testicular cell types, and at understanding the mechanisms underlying these effects.

overall_design:
Short term exposure of human fetal testes to VPA at 10-5M
------------------------
Authors state:
For privacy concerns related to the use of human samples, we have only submitted processed data here. Raw data will be submitted to a dedicated databases (such as dbGaP).

first: Laurianne

last: Lesné

first: Indusha

last: Kugathas

first: Séverine

last: Mazaud-Guittot


title: The imbalance of Th17/Treg cells induced by prenatal chronic stress exposure is associated with activation of the PI3K/Akt/NF-κB signaling pathway in offspring

city: Yinchuan

first: Ye

last: Li

address: School of Public Health and Management, Ningxia Medical University, Yinchuan 750004, China

institute: Ningxia Medical University

summary: Maternal immune dysregulation, caused by gestational psychological stress, infection, and other perturbations, results in altered offspring immune development and increases risk for immune related disorders. However, the number of studies reporting the effects of prenatal stress on immune system of offspring is very limited. In this study, we examined whether prenatal stress stimuli, based on the CUMS model, may activate the PI3K/Akt/NF-κB signaling pathway and cause an imbalance of Treg/Th17 in the offspring's spleen. Through the establishment of CUMS model, we discovered that prenatal stress increased the plasma levels of corticosterone, IL-1β and IL-6 in the rats that were exposed to it, as well as the serum levels of IL-6, TNF-α and TGF-β in the offspring. We also discovered a correlation between the levels of cytokines in the female rats and the offspring. Additionally, the outcomes of the transcriptome sequencing and PCR experiment demonstrated that the differentially expressed mRNAs in offspring exposed to prenatal stress may cause an imbalance of Th17/Treg via activating the Gng3-related PI3K/Akt/NF-B pathway.

overall_design:
Achronic mild stress stimulation model (CUMS) was established and high-throughput RNA sequencing (RNA-seq) was performed to examine the spleen tissue transcriptome of offspring to investigate the pathogenetic effect of PI3K/AKT/NF-κB pathway in the pathogenesis of chronic stress induced MIA damaging the balance of offspring Th17/Treg imbalance.
The rats in the PM group were exposed to the procedure of chronic unpredictable mild stress (CUMS) to establish a prenatal maternal stress model(21). The following nine stressors, which lasted 21 days, were a part of the CUMS protocol: ①crowding environment (7-8 rats in each cage, 24 h), ②humid sawdust (60%–70% humidity, 24 h), ③shaking stress (one time per second, 30 min), ④tilting cage (tilt 45°, 24h), ⑤restraint stress (2h), ⑥fasting and water deprivation (24h), ⑦swimming in ice water (5min).
The day of birth was designated postnatal day 0 (PND 0). At PND 21, male and female offspring were weaned and placed in separate cages. 8 offspring from the PC group were randomly chosen as group C, while 8 offspring from the PM group were randomly chosen as group M. The sample tissue was spleen tissue from these M and C groups.

first: Guixiang

last: Yao


title: 3D Chromatin organization of signal-induced specific enhancers safeguards early ESC differentiation by promoting cluster gene expression [Hi-ChIP]

city: Guangzhou

first: Weipeng

last: Mo

state: Guangdong

address: 58 Zhongshaner Rd

department: The First Affiliated Hospital

institute: Sun Yat-sen University

summary: Cells undergo fate transformation in response to external signaling stimuli, a process that depends on the precise expression of specific genes, but the intrinsic regulatory mechanisms remain largely unclear. Here, by integrating bulk RNA sequencing, single-cell RNA sequencing, 4D-SmartDIA quantitative proteomics data, and a CRISPR/Cas9-mediated RA receptor deletion model, we find that RA signaling-induced early ESC differentiation is multilineage. During early ESC differentiation, in the context of attenuated and enhanced RA signaling, we identified Cyp26 and HoxB cluster genes as its direct downstream targets. Upon activation of RA signaling, RA receptors induce new specific enhancers in the proximal/distal regions of cluster gene loci, whereas inhibition of RA signaling significantly reduces proximal/distal enhancer activity, chromatin accessibility and cluster gene expression. Mechanistically, we found that proximal/distal enhancers form specific chromatin loops with cluster gene loci under RA induction, and RA receptor deletion significantly reduces these  chromatin interactions. Knockout of the proximal/distal enhancers inhibits cluster gene expression, thereby further disrupting RA-induced early ESC differentiation. In summary, our findings reveal an insightful mechanism underlying the signal-induced specific 3D genomic structure and cluster gene expression critical for early ESC fate transitions.

overall_design: To detect specific transcriptomes induced by RA signalling, we induced differentiation for 12h and 24h in WT cells that were depleted of LIF/2i or added 2 μM RA (Sigma).

first: To detect the specific transcriptome regulated by Cyp26a1

last: we added 2 μM RA (Sigma) after removing LIF/2i in WT cells and Cyp26a1-KO cells and induced differentiation for 24 hours.

first: Guangsong

last: Su

first: Wange

last: Lu


title: Using Chip-seq to analyze the distribution of XRCC5/6 on HBV DNA

city: 武汉市

first: jiangpeng

last: FENG

address: 武昌区小洪山中区

institute: Wuhan institute of virus

summary: In this study, we found that XRCC5/6, as DNA-binding proteins, can bind to HBV DNA and regulate HBV transcription. To directly analyze the binding regions of XRCC5/6 on HBV DNA, ChIP-seq was performed in HepG2.2.15 cells using antibodies against XRCC5 and XRCC6. The results revealed that XRCC5/6 were abundantly distributed across the HBV genomic DNA, with significant enrichment around the HBV promoters.

overall_design: Chip-seq of XRCC5 and XRCC6 on HBV genome DNA in HepG2.1.15 cell line.

first: Jiangpeng

last: Feng

first: Wuxiang

last: Guan


title: Thrombospondin-1, CD47, and SIRPa display cell-speciﬁc molecular signaturesin human islets and pancreata

city: Farmington

first: Yuqi

last: Zhao

address: 273 Main Street A4

institute: City Of Hope

summary: Thrombospondin-1 (TSP1) is a secreted protein minimally expressed in health but increased in disease and age. TSP1 binds tothe cell membrane receptor CD47, which itself engages signal regulatory protein a (SIRPa), and the latter creates a checkpointfor immune activation. Individuals with cancer administered checkpoint-blocking molecules developed insulin-dependent diabe-tes. Relevant to this, CD47 blocking antibodies and SIRPa fusion proteins are in clinical trials. We characterized the molecularsignature of TSP1, CD47, and SIRPa in human islets and pancreata. Fresh islets and pancreatic tissue from nondiabetic individu-als were obtained. The expression of THBS1, CD47, and SIRPA was determined using single-cell mRNA sequencing, immunoﬂuo-rescence microscopy, Western blot, and ﬂow cytometry. Islets were exposed to diabetes-afﬁliated inﬂammatory cytokines andchanges in protein expression were determined. CD47 mRNA was expressed in all islet cell types. THBS1 mRNA was restrictedprimarily to endothelial and mesenchymal cells, whereas SIRPA mRNA was found mostly in macrophages. Immunoﬂuorescencestaining showed CD47 protein expressed by b cells and present in the exocrine pancreas. TSP1 and SIRPa proteins were notseen in islets or the exocrine pancreas. Western blot and ﬂow cytometry conﬁrmed immunoﬂuorescent expression patterns.Importantly, human islets produced substantial quantities of secreted TSP1. Human pancreatic exocrine and endocrine tissueexpressed CD47, whereas fresh islets displayed cell surface CD47 and secreted TSP1 at baseline and in inﬂammation. Theseﬁndings suggest unexpected effects on islets from agents that intersect TSP1-CD47-SIRPa

first: Neslihan

last: Erdem

first: Kuan-Tsen

last: Chen

first: Meirigeng

last: Qi

first: Xiwei

last: Wu

first: Isaac

last: Garcia

first: Teresa

last: Ku

first: Enrique

last: Montero

first: Ismail

middle: H

last: Al-Abdullah

first: Fouad

last: Kandeel

first: Bart

middle: O

last: Roep

first: Jeffrey

middle: S

last: Isenberg


title: scRNA-seq of cardiac neural crest cells following left atrial ligation

city: La Jolla

first: Stephanie

middle: E

last: Lindsey

address: 9500 Gilman Dr.

institute: UC San Diego

summary: We have employed a single cell sequencing approach using 10x Genomics scRNAseq to study the affect of altered hemodynamic patterning on cardac neural crest cells (CNCCs). CNCCs play an important role in tunica media formation of the great vessels, cardiac septation,  and contribute to cardiomyocytes of he ventricle.

overall_design: Following left atrial ligation in the chick embryo, retrovirally labeled cardiac neural crest cells were isolated by Fluorescence activated cell sorting (FACS) and analyzed via scRNA-seq

first: Robert

last: Porter

first: Aining

last: Fan


title: Spatially Resolved Obesity-Driven Molecular Changes in Early Breast Cancer

city: Oklahoma city

first: Bethany

last: Hannafon

state: OK

address: 975 NE 10th Street

department: Obstetrics and Gynecology

institute: University of Oklahoma Health Sciences Center

summary: Obesity is an established risk factor for invasive breast cancer; however, the specific molecular heterogeneity distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) within the obese tumor microenvironment is not well defined. In the current study, spatially resolved transcriptomics was utilized to profile the epithelial, stromal, and immune compartments of DCIS and IDC lesions stratified by host body mass index, categorized as non-obese (≤29.9 kg/m2) or obese (≥30 kg/m2). These analyses reveal that the transcriptional signatures defining the invasive state differ significantly across BMI categories. In non-obese patients, IDC lesions exhibited canonical profiles driven by proliferation and epithelial-to-mesenchymal transition, compared with DCIS. Conversely, the obese setting was characterized by a distinct "stress-adaptive" phenotype, enriched for metabolic adjustment, oxidative stress response, and inflammatory signaling. The epithelial component was accompanied by a fibro-inflammatory stromal signature and an immunosuppressive niche characterized by B cell depletion and M2 macrophage enrichment. Furthermore, SULF2, an extracellular endosulfatase involved in extracellular matrix organization and signaling, was consistently upregulated within the obese epithelium, providing a plausible link between metabolic stress and structural remodeling. Collectively, these data indicate obesity-associated differences consistent with an alternative invasive transcriptional program that is less dominated by classical proliferative drivers in this cohort. Consequently, standard prognostic markers may be context-dependent, highlighting the need to integrate metabolic health into precision risk stratification.

sample_organism:
Homo sapiens
synthetic construct

platform_organism:
Homo sapiens
synthetic construct

overall_design: Each sequenced library corresponds to a single GeoMx Digital Spatial Profiler region-of-interest segment or technical control collected into an individual well of a 96-well plate. The submitted dataset contains libraries from formalin-fixed, paraffin-embedded human breast tissue sections from ductal carcinoma in situ and invasive ductal carcinoma cases stratified by body mass index, including epithelial (cytokeratin-positive), stromal/myoepithelial (alpha-smooth muscle actin-positive), and immune (CD45-positive) segments, together with a no-template control. ROI-level metadata include slide number, ROI identifier, segment identity, area, nuclei count when available, scan coordinates, and panel annotation.

first: Cole

last: Hladik

first: Malika

last: Sekhri

first: Haoning-Howard

last: Cen

first: Suganthapriya

last: Elayapillai

first: Schuyler

last: Lee

first: Bifeng

last: Gao

first: William

last: Dooley

first: Ty

last: Milligan

first: Haddon

last: Hill

first: Alexander

last: Filatenkov

first: Elizabeth

last: Wellberg

middle: N


title: An SPFH Protein Couples Membrane Stress to Differentiation in Bacillus subtilis

city: Bielefeld

first: Christian

last: Ruckert-Reed

address: Sequenz 1

department: Medical School OWL

institute: Bielefeld University

summary: Bacillus subtilis adapts to fluctuating environmental stress, such as membrane perturbation or alkaline conditions, using membrane-associated regulatory complexes. Here, we rename the previously termed pspA-ydjGHI operon to pspA-samGHI (for starvation and motility) to reflect its functional roles in membrane envelope stress signalling. The SamG–SamH membrane proteins recruit SamI, a cytosolic SPFH protein, which stabilizes focal membrane localization and recruitment of PspA, an ESCRT-III homolog. Under normal conditions, this system transiently assembles at the membrane, stabilizing it and allowing proper motility, secretion, and biofilm formation. Loss of SamI (ΔsamI/ΔydjI) leads to unbalanced SamG–SamH activity leading to a constitutive stress signalling, and global transcriptional changes reminiscent of starvation situations. This, in turn, blocks secretion of the matrix protein BslA, preventing biofilm formation, and reducing motility. Deletion of samH in combination with ΔsamI restores biofilm formation, while ΔpspA mutants form biofilms normally, indicating that PspA is dispensable for the developmental phenotype. Our findings reveal that beside membrane integrity SamGHI coordinates transcriptional homeostasis and multicellular development through formation of a membrane integral stress sensor complex.

overall_design: Whole transcriptomes of the Bacillus subtilis subsp. subtilis str. 168 wildtype and a ΔsamI (ΔydjI) deletion mutant grown as biofilms on agar plates, using 3 biological replicates each.

first: Sarah

last: Baur

first: Urška

last: Repnik

first: Tobias

last: Busche

first: Louisa

last: Rau

first: Alisa

last: Mondry

first: Marc

last: Bramkamp


title: Targeting CCR1-Mediated Macrophage Phenotypic Switching to Alleviate Bladder Pain and Urinary Dysfunction in Interstitial Cystitis

first: Jialiang

last: Chen

address: Tianhe Road 600

department: Urology

institute: Third Affiliated Hospital of Sun Yat-Sen University

summary: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammatory condition with limited treatments. Although macrophages are implicated in its pathogenesis, the mechanisms driving their phenotypic switching remain unclear. This study identifies CCR1's role in IC/BPS and evaluates CCR1 inhibition as a therapeutic strategy. Integrated bulk and single-cell RNA sequencing reveal enrichment of pro-inflammatory CCR1⁺ macrophages in bladder tissue from patients with IC/BPS. In a lipopolysaccharide-induced rat model, pharmacological inhibition of CCR1 suppresses M1 polarization, promotes M2 polarization, and improves pain thresholds, urinary symptoms as well as bladder inflammation. Mechanistically, CCR1 knockdown enhances FOXO1 phosphorylation and degradation, reduces its nuclear translocation, and activates PPARγ signaling to promote M2 polarization. Analysis of clinical samples shows increased CCL7 levels in bladder tissue and urine, with urinary levels correlating with symptom severity. These findings identify CCR1 as a candidate target for further therapeutic evaluation in IC/BPS.

overall_design: RNA-seq profiling of normal and siCCR1 THP-1-derived M0 macrophages after exposure to inflammatory conditioned medium (derived from SV-HUC-1 cells stimulated with 10 ng/mL TNF-α for 24 hours), performed in duplicate.

first: Ruixiang

last: Luo

first: Wenshuang

last: Li

first: Bolong

last: Liu

first: Junlong

last: Huang

first: Honglu

last: Ding

first: Chi

last: Zhang

first: Xiaoyang

first: Ziqiao

last: Wang

first: Zheng

first: Xiangfu

last: Zhou


title: Diminished and Altered Cellular Senescence Response in Delayed Wound Healing of Aging

city: Boston

first: Danny

last: Roh

state: MA

address: 609 Albany Street

institute: Boston University School of Medicine

summary: The transient upregulation of cellular senescence within wound tissues has been demonstrated to be an important biological process facilitating efficient tissue repair. Dysregulation of this transient wound‐induced senescence response can result in impaired healing outcomes. We performed single‐cell RNA sequencing analysis of all cells isolated from day 6 wounds in young (2 month) and aged (24 month) male mice.

overall_design: Single-cell RNA sequencing of all cells isolated from day 6 full-thickness dorsal skin wounds of young (2-month) and aged (24-month) C57BL/6 mice to characterize age-dependent differences in the wound senescence response.

first: Maria

last: Shvedova

first: Qiaoling

first: Jannat

last: Dhillon

first: Rex

last: Jeya Rajkumar Samdavid Thanapaul

first: Grace

last: Shin

first: Daniel