title: Generalization of negative memories drives the development of  psychological distress-related behaviors

city: Guangzhou

first: Xin

last: Cheng

address: 74 Zhongshaner Rd

institute: Sun Yat-sen University

summary: To investigate the molecular mechanism of unpredictable aversive stress induced commobidity between fear generalization and depression, mice were treated by different training paterns (1xTr, 2xTr-same and 2xTr-altered). Therefore, mPFC were dissected to perform immunoprecipitation and RNA seq.

overall_design:
Translating profiles of the BNST-projecting mPFC neurons and transcriptomic profiles of the mPFC in mice after 1xTr, 2xTr-same and 2xTr-altered CFC trainings.
Comparative gene expression profiling analysis of RNA-seq data for BNST-projecting mPFC neurons or mPFC tissues under different treatment (1xTr, 2xTr-same, 2xTr-altered).
Immunoprecipitation was performed using GFP Recombinant Rabbit Monoclonal Antibody (Invitrogen G10362, Lot2306774).

first: Yubo

last: Hu

first: Yan

last: Zhao

first: Panwu

first: Jiale

last: Chen

first: Xiaomeng

first: Yi

first: Deshan

last: Kong

first: Chuan

last: Xiao

first: Youhua

first: Shuyu

first: Yuena

first: Yumeng

first: Hu

first: Yanni

last: Zeng

first: Wei-Jye

last: Lin

first: Xiaojing

last: Ye


title: Single-Cell RNA Sequencing Reveals that Bach2 with Inactive Heme-Binding Sites Sustains the Stemness of CD8+ T Cells

status: Public on Jan 25 2026

city: Tianjin

first: Yingxi

last: Xu

address: 288 Nanjing Road

department: State Key Laboratory of Experimental Hematology

country: China

institute: Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

type: Expression profiling by high throughput sequencing

summary: Bach2 is vital for the formation of progenitor exhausted T cells and for maintaining their stem-like properties. In B cells, Bach2 undergoes conformational changes that reduce its transcriptional repression activity due to decreased DNA-binding affinity and increased degradation, subsequently triggering Blimp1 expression. Therefore, we aimed to use scRNA-seq to determine whether mutation of the heme-binding site in Bach2 (Bach2MUT) could more efficiently preserve stem-like properties in tumor-infiltrating lymphocytes (TILs) compared to wild-type Bach2 (Bach2WT).

overall_design: P14 cells were isolated from P14 mice and then overexpressed with either Bach2WT (CD45.1) or Bach2MUT (CD45.1/.2). The cells were co-transferred into Yumm1.7-gp33 tumor-bearing mice. Nine days later, CD3+CD8+CD44+CD45.1 or CD3+CD8+CD44+CD45.1/.2 cells were sorted and subjected to CMO multiplexing followed by scRNA-seq.

first: Josep

last: Garnica

first: Ping-Chih

last: Ho


title: NR3C1, LAX1 and RCAN3 as circulating epigenetic biomarkers for prognosis and chemotherapy response prediction in metastatic pancreatic cancer

city: Cordoba

first: María Victoria

last: García-Ortiz

state: Cordoba

address: Av. Menéndez Pidal

country: Spain

institute: Maimonides Institute for Biomedical Research in Cordoba

type: Methylation profiling by genome tiling array

summary: Pancreatic cancer remains highly lethal, largely due to late diagnosis and limited efficacy of treatments. Improving first-line treatment selection and patient monitoring requires novel, non-invasive biomarkers beyond CA19-9 and imaging. This study investigates epigenetic biomarkers from liquid biopsy with prognostic and predictive potential in metastatic PDAC (mPDAC). Genome-wide methylation profiling of cell-free DNA (cfDNA) from healthy individuals and stage IV mPDAC patients identified thirteen gene-associated CpG sites with significantly altered methylation patterns. ddPCR validation confirmed consistent methylation differences in LAX1, NR3C1 and RCAN3 between healthy and patient groups. Elevated LAX1 and RCAN3 methylation and reduced NR3C1 methylation at diagnosis were associated with poor prognosis and correlated with high-risk circulating biomarker profiles, including CA19-9 levels, RAS MAF, cfDNA concentration, and cfDNA fragmentation. Notably, baseline NR3C1 methylation levels predicted response to first-line FOLFIRINOX-based treatment with an acceptable 75% sensitivity and a high specificity of 92.86%. These findings highlight the clinical significance of cfDNA methylation as a minimally invasive biomarker source, emphasizing LAX1, NR3C1 and RCAN3 as prognostic biomarkers in mPDAC. Specifically, baseline NR3C1 methylation emerges as a promising predictor of treatment response, supporting personalized therapeutic strategies in mPDAC.

overall_design: Human peripheral blood DNA from 2 healthy controls (H1–H2) and 6 patients (P1–P6) was bisulfite-converted using the EZ-96 DNA Methylation Kit (Zymo Research) and  analyzed on the Illumina Infinium MethylationEPIC BeadChip (850K) to study  genome-wide DNA methylation.  Bisulfite conversion QC was performed by qPCR  targeting DNAJC15 and GNAS loci, with deaminated DNA as positive control.  Array QC included Infinium internal controls, mean detection p-value <0.01,  proportion of failed probes <10%, and bimodal methylation distributions;  all samples passed QC and no outliers were detected.

first: Pablo

last: Cano-Ramírez

first: Marta

last: Toledano-Fonseca

first: María

middle: T

last: Cano-Osuna

first: Nerea

last: Herrera-Casanova

first: Emilio

last: Carrillo-Pecero

first: Antonio

last: Rodríguez-Ariza

first: Enrique

last: Aranda

middle: V


title: Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics

city: Boston

first: Jiao

last: Shen

state: MA

address: 450 Brookline Ave, SM-552A

department: Cancer Immunology and Virology

country: USA

institute: Dana-Farber Cancer Institute (DFCI)

summary: Cytokines dimerize two receptor chains to activate Janus kinases and STAT transcription factors that regulate immune cells but have therapeutic liabilities. We engineered “Trikines” to compel cis formation of three-chain cytokine receptor complexes at the cell surface that induce bespoke STAT transcriptional signaling programs optimized for therapeutic efficacy. Designed Trikines co-activated pSTAT5 and pSTAT3 signatures distinct from any natural cytokines, by assembling trimeric combinations of Interleukin-2 (IL-2), Interleukin-10 (IL-10), and Interleukin-21 (IL-21) receptors. An IL-2-based-Trikine restrained terminal differentiation of T cells, promoted stemness, and enhanced durability of tumor control without toxicity. Unexpectedly, an IL-10-based Trikine induced immune infiltration into poorly immunogenic tumors, showing striking efficacy in small cell lung cancer and pancreatic cancer models. Trikines obviate the need for cell engineering to customize STAT signatures for immunotherapy

overall_design: Mice were inoculated s.c. with 2.5 × 10⁵ 6694c2vTRP1 cells and received i.p. injections of PBS, mono-IL-10 (26 μg/mouse, n = 5), or IL-10/2-Trikine (30.6 μg/mouse, n = 5) every other day starting on day 8, for a total of two doses. Mice were sacrificed on day 14. CD45⁺ TILs were bead-isolated, individually labeled with hashtag antibodies, pooled by treatment group, and subjected to Single Cell 5' RNA and cell surface protein sequencing.

first: Frank

last: Peprah

first: Michael

last: Dougan

first: Stephanie

middle: K


title: RNA-seq Unveils that Exogenous Hemin Treatment Accelerates CD8+ T Cell Exhaustion

summary: Regulatory heme is known to control cellular behavior by regulating the activities of hemoproteins. We hypothesized that increased levels of regulatory heme may drive T cell exhaustion. To test this, we first confirmed that treatment with hemin, a heme analog, effectively increased intracellular regulatory heme levels in T cells. To evaluate the transcriptional changes in CD8+ T cells treated with hemin, we conducted RNA sequencing on CD8+ T cells with and without exogenous hemin treatment. The RNA-seq data revealed that hemin treatment strongly modulated gene expression patterns associated with terminally exhausted T cells. Pathway enrichment analysis further revealed that hemin suppressed pathways involved in proliferation and cytokine production while altering metabolic processes, such as cholesterol efflux and fatty acid biosynthesis, which are known to regulate T cell function. These results suggest that increased levels of regulatory heme drive T cell exhaustion differentiation.

overall_design: Primary normal CD8 T cell treated with 25uM Hemin or veicle for bulk RNA-seq analysis, 5 replicates are included in each group.

first: Yu-Ming

last: Chuang


title: Wireless, battery-free vagal electrical stimulation: A novel approach to inhibit cardiac hypertrophy via H3K18 lactylation mediated mitophagy

city: Harbin

first: Sun

middle: Hong

last: Hong

state: Heilongjiang

address: Network Information Center all rights reserved 157 Nangang District, Harbin health care road

department: Department of Pharmacology

institute: Harbin Medical University

type: Genome binding/occupancy profiling by high throughput sequencing

summary:
Background: Electrical stimulation (ES) has been established as a reliable and beneficial approach in therapeutic rehabilitation, exhibiting negligible side effects. Nevertheless, research focusing on the application of ES for cardiac hypertrophy remains limited, as it fails to provide an enduring remedy for chronic diseases. Battery-free implants have been surgically placed on the surface of the vagus nerve in rats, and wireless ES has been applied for four weeks to observe potential alterations in cardiac hypertrophy.
Methods: In this investigation, vagal ES, characterized by its wireless, battery-free, and fully implantable nature, was utilized to treat cardiac hypertrophy. The vagus nerve at the stimulation site was carefully embedded within an envelope, sealed securely using multiple bioabsorbable sutures. Subsequently, a cardiac hypertrophy model was induced in rats via abdominal aortic coarctation for four weeks. A comprehensive array of experimental techniques was employed, encompassing qRT-PCR, Western blotting, transmission electron microscopy, HE staining, WGA staining, Masson’s staining, immunohistochemistry, and immunofluorescence.
Results: The findings of this investigation demonstrated that ES markedly attenuates cardiac hypertrophy. Metabolomic analysis revealed a notable reduction in lactate levels within myocardial tissue following ES. Proteomic analysis of myocardial tissues indicated a substantial decrease in the expression of autophagy and mitophagy-related proteins after ES. Additionally, ChIP-seq results identified BCL2 interacting protein 3 (Bnip3) as a binding partner for H3K18 lactylation (H3K18la), exploring its role in modulating mitophagy. Mechanistically, it was shown that ES reduced lactate accumulation through the upregulation of monocarboxylate transporter 4 (MCT4) by decreasing norepinephrine (NE) levels. Furthermore, ES reversed cardiac hypertrophy by diminishing H3K18la levels, thus inhibiting BNIP3 protein expression.
Conclusion: Continuous ES effectively reduces intracellular lactate by lowering NE levels within myocardial tissue, inhibiting mitophagy mediated by H3K18la.This pathway assists in diminishing cardiac hypertrophy, emphasizing the critical involvement of the afferent vagal pathway in regulating cardiac hypertrophy.

overall_design: Under aseptic conditions, a midline incision was made to access the abdomen. A 1 cm segment of the abdominal aorta, located above the bifurcation of the renal arteries, was isolated and positioned with a 0.7 mm thick wire on its exterior

first: Pilong

last: Shi

first: Yang

last: Liu

first: Yuetong

last: Sha

first: Jiaxin

last: Wang

first: Jiajun

last: Zhou

first: Kai

first: Hongli

last: Sun


title: Trans-acting long non-coding RNA modulates long-range chromatin interactions associated with oncogenic MYC signaling [Iso-Seq]

status: Public on Jan 26 2026

city: Chicago

first: Rendong

last: Yang

state: IL

address: 420 E Superior St

department: Urology

institute: Northwestern University

summary: To investigate the function and affected pathways of novel lncRNA IGF1R-AS1 in the prostate cancer, we established VCaP cell lines in which IGF1R-AS1 has been knocked down by siRNA.

overall_design: Total RNA  was extracted using Promega ReliaPrep RNA Cell system(Z6011). 3' Race was done using 5'/3' RACE Kit, 2nd Generation (Roche). One microgram of total RNA was used for reverse transcription step with olig-anchor primer 5’-GACCACGCGTATCGATGTCGACTTTTTTTTTTTTTTTTV-3’ according to the manufacturer's instructions. One microliter  of the RT product was used for the subsequent PCR reaction using IGF1-AS1 exon1 specific forward primer (5'-ACTATGTTTCAGCGGCTGGT-3') and the PCR anchor reverse primer in the kit(5’-GACCACGCGTATCGATGTCGAC-3’). The PCR product was cleaned using a PCR cleaning kit(Qiagen) and submitted for PacBio sequencing.

first: Tingyou

first: Yanan

last: Ren


title: ERCC6L2 ensures repair fidelity for staggered-end DNA double-strand breaks

city: Zurich

first: Eric

middle: J

last: Aird

address: Otto-Stern-Weg 7

country: Switzerland

institute: ETH Zurich

summary: DNA double-strand breaks (DSBs) both pose threats to genome integrity and are commonly used for genome editing applications. Structural features of DSB ends play key roles in determining DNA repair pathway usage and outcomes during genome editing, but the cellular factors involved in these processes are only partially known. Through genome-wide CRISPRi screening, we identified ERCC6L2 as critical for repairing Cas12a-induced staggered DSBs but irrelevant for Cas9-induced blunt DSBs. We show that ERCC6L2 acts as a protection factor for staggered DSBs with either 5’ or 3’ polarity, preventing large deletions and translocations stemming from DNA damage induced by Cas12a, TALENs, or dual Cas9 nicks. ERCC6L2 loss furthermore hyper-sensitizes cells to multiple staggered DSBs induced by promiscuous Cas12a activity or etoposide-induced TOP2 trapping. By combining genetics and biochemical reconstitution, we find that ERCC6L2 counteracts ATM-driven resection by binding and melting staggered DNA ends, thereby promoting accurate end joining. Our data reveal a protective role of ERCC6L2 in staggered DSB repair, which suggests the molecular underpinnings of pathology in patients with ERCC6L2 mutations and cautions against using overhang-inducing genome editing tools for their treatment.

overall_design: Endogenous anti-MRE11 ChIP-sequencing of RPE1 TP53 null WT and ERCC6L2 KO cells edited with Cas12a gMulti and collected 12 h later.

first: Almu

last: Serrano-Benitez

first: Sebastian

middle: M

last: Siegner


title: Brain lipid profiles and oligodendrocyte gene expression show discordant responses to high-fat diet in Alzheimer’s disease mice.

city: Nagoya

first: Noe

last: Kawade

address: Furo-cho, Chikusa-ku

country: Japan

institute: Nagoya university

summary: The brain is a lipid-rich organ, with myelin sheaths containing exceptionally high levels of lipids. Oligodendrocyte dysfunction and myelin lipid deregulation have been implicated in Alzheimer’s disease (AD), yet their precise roles remain unclear. In this study, we examined lipid metabolic alterations, with focus on primary myelin lipids, in AppNL-G-F/NL-G-F (App) AD model mice fed either a normal control diet (NCD) or a high-fat diet (HFD). Brain lipid profiles were altered in App mice, with differential effects depending on diet. Notably, oligodendrocyte gene expression patterns, including those involved in myelin lipid metabolic pathways, were similar between NCD- and HFD-fed App mice and did not correspond with the observed changes in brain lipid composition. This discrepancy indicates that myelin lipid homeostasis in the AD brain is regulated by mechanisms beyond transcriptional control, likely involving post-translational regulation, inter-glial metabolic interactions, and brain-periphery lipid exchange. Importantly, HFD intake did not exacerbate cognitive impairment or neuroinflammation in App mice; rather, HFD-fed App mice showed improved learning during behavioral testing and reduced astrocytic activation. These findings suggest that dietary fat intake does not worsen—and may partially ameliorate—certain aspect of AD pathology, highlighting the complex and context-dependent relationship between metabolic interventions and neurodegenerative disease.

overall_design: RNA-seq profiling of oligodendrocytes isolated from the brains of wildtype C57BL/6J Jcl mice and App NL-G-F/NL-G-F mice fed normal control diet of high-fat diet for 6 months.

first: Okiru

last: Komine

first: Akira

last: Sobue

first: Chihiro

last: Kakimi

first: Miyako

last: Tanaka

first: Takayoshi

last: Suganami

first: Mayuko

last: Shimada

first: Tomoo

last: Ogi

first: Kazutaka

last: Ikeda

first: Mai

last: Horiuchi

first: Seiji

last: Watanabe

first: Takashi

last: Saito

first: Koji

last: Yamanaka


title: An SP110-SP100 axis is a critical regulator of PML body dynamics and mitotic fidelity

summary: Stimulation of the innate immune system by foreign RNA elicits a potent interferon response and can trigger cell death. The mechanisms by which cells balance a robust response with cell-intrinsic lethality are still being uncovered. Employing genome-wide CRISPR-Cas9 genetic screens with triphosphorylated RNA stimulation, we discovered that the promyelocytic leukemia (PML) nuclear body-localized speckled protein 110 (SP110) is a potent inhibitor of type 1 interferon-driven cell death. Death suppression by SP110 counteracts a toxic activity of SP100, a major constituent of PML bodies. Loss of SP110 leads to mitotic retention of SP100 and PML bodies which associate with and perturb segregating chromosomes leading to micronucleus formation, DNA damage, and genotoxic cell death. A combination of cryo-electron microscopy, AlphaFold modeling, and cellular biochemistry reveals that SP110 dissolves toxic SP100 oligomers via necessary and sufficient direct interactions between their caspase activation and recruitment domains (CARDs). These data reveal critical roles of SP100 and SP110 in governing disassembly of PML bodies during mitosis and the repercussions if this process is mis-regulated.

overall_design: Endogenous anti-SP100 ChIP-sequencing of interferon stimulated WT and SP110 KO cells treated with interferon beta for 6 h.


title: Nanostring analyses of RNA samples from tumor, spleen, lymph node of TC-1 and TRAMP-C mouse treated with SOT101

city: Prague 9

first: Lenka

last: Palova Jelinkova

address: Ceskomoravska 2532/19b

country: Czech Republic

institute: Sotio Biotech a.c.

summary: Nanrilkefusp alfa (nanril; SOT101) is an interleukin (IL)-15 receptor βγ superagonist that stimulates natural killer (NK) and CD8+ T cells, thereby promoting an innate and adaptive anti-tumor inflammatory microenvironment in mouse tumor models either in monotherapy or combined with an anti-programmed cell death protein 1 (PD-1) antibody. In cynomolgus monkeys, a clinical schedule was identified, which translated into the design of a phase 1/1b clinical trial, AURELIO-03 (NCT04234113). In 51 patients with advanced/metastatic solid tumors, nanril increased the proportions of CD8+ T cells and NK cells in peripheral blood and tumors. It had a favorable safety profile when administered subcutaneously on days 1, 2, 8 and 9 of each 21-day cycle as monotherapy (0.25-15 μg/kg) or combined (1.5-12 μg/kg) with the anti-PD-1 pembrolizumab (200 mg). The most frequent treatment-emergent adverse events were pyrexia, injection site reactions and chills. Furthermore, early clinical efficacy was observed, including in immune checkpoint blockade-resistant/refractory patients.

overall_design: The aim of the study was to profile immune-related gene expression using the nCounter Mouse PanCancer Immune Profiling Panel of NanoString technology on 66 RNA samples isolated from tumors, spleens and lymph nodes of TC-1 and TRAMP-C tumor-bearing mice treated or non-treated with SOT101. TC-1 and TRAMP-C2 mice bearing tumor were treated with SOT101 at 40 µg/mouse at Day 1-4 and collected at Day 7.

first: Lenka P

last: Jelinkova


title: snRNAseq molecular characterization of pig dorsal root ganglion neurons [snRNAseq]

city: Toronto

first: Shreejoy

last: Tripathy

state: Ontario

address: 250 College st.

country: Canada

institute: CAMH

summary: This dataset offers snRNAseq data from dorsal root ganglia (DRG) of pigs, targeting molecular markers of sleeping nociceptors. It combines high-throughput sequencing with detailed tissue processing, advancing our knowledge of nociceptor diversity and providing insights for sensory and pain research.

overall_design: Samples obtained from male Landrace pigs, DRGs were preserved post-euthanasia, processed for nuclei isolation through methods like tissue lysis and density gradient centrifugation, and enriched for neuronal nuclei analysis.The aim is to characterize sensory neuron transcriptomic profiles in DRGs, enhancing understanding of nociceptor diversity for pain study applications. This dataset aids comparative sensory neuron research, offering a detailed molecular resource for integration with other transcriptomic datasets.

first: Hans

last: Jürgen Solinski

first: Jannis

last: Körner

first: Derek

last: Howard

first: Angelika

last: Lampert

first: Martin

last: Schmelz


title: Pig dorsal root ganglion neurons

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

overall_design: Refer to individual Series


title: The effect of 3-phenylpropionic acid (PPA) on hepatic gene expressions

city: Cincinnati

first: Joo-Seop

last: Park

address: 3333 Burnet Avenue

institute: Cincinnati Children's Hospital Medical Center

summary: Our preliminary data suggest that PPA, a gut microbiota derived metabolite, reduced APAP hepatotoxicity. The goal of our study is to determine whether PPA modulates hepatic gene expressions and thus modulate APAP hepatotoxicity.

overall_design: Method: C57BL/6 mice were treated with PPA in drinking water (or normal water as a control). After 4 weeks of PPA treatment, mice were overnight fasted (16 h), injected with APAP (i.p, 300 mg/kg) and sacrificed at 0 or 6 h after APAP administration.

first: Sungjoon

last: Cho

first: Eunah

last: Chung

first: Hyunyoung

last: Jeong


title: Decoupled glucose- and glutamine-dependent orthogonal metabolic states independently sustain cancer cell survival

status: Public on Jan 24 2026

city: Tallahassee

first: Elizabeth

last: Mazzio

state: Florida

address: College of Pharmacy and Pharmaceutical Sciences, 241 Fred Humphries Science Research Facility, 1515 MLK Blvd, Tallahassee , Florida 32307

institute: FAMU College of Pharmacy

summary: Cancer metabolism is often framed as dependence on cooperative glucose-glutamine fuels; however, whether distinct nutrients enforce discrete metabolic states remains unclear. Glucose utilization is often interpreted under Warburg physiology, involving accelerated glycolysis and clockwise TCA rotation to generate reducing equivalents; yet, emerging evidence suggests that glutamine, under certain conditions, can drive anaplerotic pathways independent of glycolysis, involving a counterclockwise TCA linked to massive lipid biosynthesis. Here, we sought to define how glucose and glutamine independently govern adaptive metabolic states, rather than functioning as cooperative co-fuels, in MDA-MB-231 breast cancer cells. Briefly, cells were cultured under four defined nutrient conditions—full (+Glc,+Gln), deficient (−Glc,−Gln), glucose-only, and glutamine-only—and applied transcriptomic, metabolomic, and lipidomic analyses to resolve nutrient-enforced transcriptional and metabolic states.

overall_design: RNA-seq of MDA-MB-231 breast cancer cells cultured under four defined nutrient conditions—full (+Glc,+Gln), deficient (−Glc,−Gln), glucose-only, and glutamine-only—supported by evidence of  metabolomic, and lipidomic changes.

first: Renee

last: Reams

first: Jean-Baptiste

last: Lamango

first: Zonnelle

last: Hanley

first: Karam

last: Soliman


title: Spatial transcriptomic molecular characterization of pig dorsal root ganglion neurons [Visium]

summary: This dataset comprises 10X Visium spatial transcriptomics data from the pig dorsal root ganglia (DRG) of female pigs. It aims to map the spatial gene expression patterns within the DRG, offering insights into the molecular identity of neuronal populations, including nociceptors. This work provides a unique spatial perspective on gene expression, facilitating a deeper understanding of DRG molecular architecture and its implications in sensory processing.

overall_design: The study sourced DRGs from 7 female pigs, with tissues processed for Visium spatial transcriptomics. DRGs were fresh-frozen, sectioned, and prepared on Visium slides for spatial sequencing. The objective is to characterize spatial gene expression within pig DRGs, identifying distinct neuronal populations and their molecular markers.

first: Marisol

last: Moreno

first: Theodore

last: Price


title: Loss of the O-GlcNAcylation in Hepatic Differentiation utilizing choline-deficient ethionine supplemented diet

city: Kansas City

first: Dakota

last: Robarts

state: KS

address: 3901 Rainbow Blvd

institute: University of Kansas Medical Center

summary:
We studied the effects of loss of hepatic O-GlcNAc Transferase (OGT), the enzyme that attaches the O-GlcNAc to protein, in a choline-deficient and ethionine (CDE) supplemented model.  We placed hepatocyte-specific OGT knockout mice (OGT-KO) and controls on the CDE diet for 2 weeks. We then performed RNA sequencing. We then repeated the 2-week CDE diet with the addition of a 7-day normal diet recovery period.
We then performed RNA-Sequencing on isolated RNA from whole liver lysate to determine differentially expressed genes.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for control and OGT-KO mice (equally pooled RNA from n of 3) with no recovery and a 7 day recovery after CDE diet. cDNA was sequenced using 2 lanes targeting 25 million reads/sample.

middle: R

first: Sumedha

last: Gunewardena

first: Udayan

last: Apte


title: Placental Remodeling in Gestational Diabetes Mellitus (GDM) Disrupts Lipid Metabolism

city: Gandhinagar

first: Surya

last: Ramachandran

state: Gujarat

address: near the Gujarat International Finance Tec (GIFT)-City

country: India

institute: Gujarat Biotechnology University

summary: Gestational diabetes mellitus (GDM) is a pregnancy-specific metabolic disorder associated with adverse maternal and fetal outcomes, with epigenetic dysregulation increasingly implicated in fetal programming. As the placenta plays a central role in maternal–fetal nutrient and hormonal exchange, this study investigated structural, epigenetic, and metabolic alterations in placentas from GDM pregnancies. Pregnant women recruited from PRS Hospital Pvt. Ltd. were classified as normoglycemic and GDM based on oral glucose tolerance test results, and maternal blood, cord blood, and placental tissues were collected for histological evaluation, DNA methylation profiling, lipid analysis, and gene expression studies. GDM placentas exhibited pronounced morphological abnormalities, including increased syncytial knots, chorangiosis, villous immaturity, and fibrinoid necrosis. Epigenomic analysis identified 521 differentially methylated regions, with significant enrichment in lipid metabolism pathways; notably, the lipid-associated gene PLIN1 was hypermethylated and significantly downregulated in GDM placentas. Concordantly, lipid profiling of maternal and cord blood revealed marked dyslipidemia in GDM subjects, indicating disrupted lipid homeostasis at both molecular and systemic levels. Collectively, these findings demonstrate that GDM induces coordinated structural, epigenetic, and metabolic alterations in the placenta that may influence fetal lipid exposure and contribute to long-term metabolic risk, highlighting PLIN1 as a potential biomarker and therapeutic target.

overall_design: We aimed to characterize the placental methylome in pregnancies complicated by Gestational Diabetes Mellitus (GDM) to identify potential epigenetic markers. Placental DNA from 11 pregnant women, comprising 5 GDM and 6 normoglycemic pregnancies, was analyzed using the Infinium MethylationEPIC BeadChip array, which interrogates approximately 930,000 CpG sites.

first: Aswathy

last: Swaminathan

first: Abdul

last: Jaleel

first: Bala

last: Sreedevi


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development [nascent RNA-seq]

city: HangZhou

first: Zhengyi

last: Li

state: ZheJiang

address: 866 Yuhangtang Rd, Hangzhou

department: Institute of Genetics

institute: Zhejiang University School of Medicine

summary: Zygotic genome activation is critical for early embryogenesis, and its failure results in developmental arrest, posing a clinical challenge to women's fertility. Here we show that in vitro fertilized human embryos ceased development at 8-Cell ZGA stage are associated with a specific down-regulation of an endogenous retrovirus, MLT2A1. The depletion of MLT2A1 causes a failure in embryo development and reduction in ZGA gene expression. Mechanistically, we uncover that MLT2A1s synthesize chimeric transcripts with both coding and non-coding sequences, while predominantly fusing with downstream heterologous retrotransposons. While these diverse fusion sequences expand the genome-targeting spectrum of MLT2A1 RNAs, the shared MLT2A1 sequences partner with HNRNPU to recruit RNA Pol II to promote transcription. This enables MLT2A1 to broadly target and activate global ZGA genes, alongside amplifying its own sub-family expression. Our study uncovers an interlocking network formed by MLT2A1 chimeric RNAs, which act synergistically to boost global ZGA transcription and reinforce human early embryogenesis.

overall_design: MLT2A1 KD,  HNRNPU KD and control KD were respectively transfected into 8CLC or hESC. After 20h, 4-sU was added into the cell culture medium. After 4h, samples were colltected for RNA-seq.

first: Yangquan

last: Xiang

first: You

last: Wu

first: Shaorong

last: Gao

first: Hongqing

last: Liang


title: Single-nucleus RNA sequencing dataset of diverse tissues from wild-type monkey and Tau-P301L transgenic monkey

first: BoFeng

last: Han

state: Guangdong

address: No. 601, West Huangpu Avenue, Tianhe District, Guangzhou, Guangdong Province, China

institute: Jinan University

summary: Utilizing non-human primates to study the role of human Tau and its related pathologies is logical and important due to their closer similarity to human brain structure and function. In our earlier research, we generated a transgenic cynomolgus monkey model expressing Tau (P301L) through lentiviral infection of monkey embryos. These monkeys exhibited age-dependent neurodegeneration and motor dysfunction. Single-cell RNA sequencing (scRNA-seq) is a powerful and promising technique for elucidating the cellular complexity and pathology across different tissues. However, single-cell data from non-human primate models of Tau pathology are currently nonexistent. In this study, we performed single-nuclei RNA sequencing (snRNA-seq) on the hippocampus, striatum, and spinal cord of Tau (P301L) monkey, providing the first single-cell atlas of multiple tissue regions in a non-human primate model that simulates human tauopathies. This will offer crucial data references for cross-species single-cell level studies of tau and its related pathologies.

overall_design: We performed single-nuclei RNA sequencing (snRNA-seq) on the hippocampus, striatum, and spinal cord of Tau (P301L) monkey and wilde type control

first: Zhuchi

last: Tu

first: Bofeng

first: Weijie

last: Ouyang

first: Yan

last: Chen

first: Danyi

first: Weien


title: Single-cell RNA-seq analysis of the immune response triggered by gut microbiota during inflammatory bowel disease

first: Zichan

last: He

address: 94 Weijin Road, Nankai District

institute: Nankai university

summary: Whether gut microbiota is pro-inflammation or anti-inflammation during the development of inflammatory bowel disease (IBD) remains controversial. To clarify this issue, using a dextran sodium sulfate (DSS) induced IBD mouse model, we showed that compared to specific pathogen free (SPF) mice, pseudo germ-free (pGF) mice exhibit milder IBD symptoms, suggesting a pro-inflammatory role of gut microbiota. We then employed single-cell RNA-sequencing to profile the immune cells in the colon of SPF and pGF mice at day 0, 2, and 7 of DSS treatment. DSS induces the increment of innate immune cells, including macrophages and dendritic cells, as well as proliferative CD8+ T cells, in SPF mice, while the numbers of innate immune cells and proliferative CD8+ T cells decline in DSS-treated pGF mice. Conversely, more prominent activation of T cells, especially CD4+ regulatory T cells (Tregs), was observed in DSS-treated pGF mice. Further analyses revealed that the major histocompatibility complex-class I (MHC-I) -CD8 and MHC-class II (MHC-II) -CD4 interactions promote the expansion of proliferative CD8+ T cells and CD4+ Tregs respectively. Moreover, we demonstrated that guanine deaminase (GDA) promotes inflammation through facilitating microtubule polymerization in macrophages. 7-methylguanine, a GDA inhibitor, mitigates DSS-induced IBD. In summary, our results demonstrate the pro-inflammatory function of gut microbiota during IBD pathogenesis, shed light on the regulatory mechanism of immune responses, and identify potential therapeutic targets for IBD.

overall_design: Using single-cell RNA-sequencing to profile the immune cells in the colon of  specific pathogen free and pseudo germ-free mice at day 0, 2, and 7 of DSS treatment.

first: Xueying

first: Huabin

first: Baofa

last: Sun

first: Lingyi


title: Gene expression profiles from multimodal patch-seq neuron samples of the pig dorsal root ganglion

first: Shreejoy

last: Tripathy

summary: This dataset comprises single-cell transcriptomic profiles derived from the dorsal root ganglia (DRG) of pigs, aimed at elucidating the molecular identity of mechano-insensitive C-fibres (CMis) implicated in neuropathic pain. Using an innovative approach that combines electrophysiological characterization with Patch-seq, we have successfully captured and analyzed the transcriptomes of primary sensory neurons. These neurons were characterized based on their electrophysiological properties, mirroring those of human CMis, which play a pivotal role in the persistence of neuropathic pain. The presented dataset enriches our understanding of the cellular and molecular landscape of neuropathic pain but also opens new avenues for the development of targeted therapeutic interventions. This dataset is expected to serve as a valuable resource for researchers in the fields of sensory biology and pain neuroscience.

overall_design: DRGs from cervical, thoracic, and lumbar segments were processed through mincing, enzymatic digestion, mechanical trituration, and centrifugation for neuron isolation. Cultured neurons were assessed electrophysiologically and analyzed via Patch-seq for molecular profiling. The experimental design concentrated on assaying the diverse array of neuron types in the DRG by examining their electrophysiological characteristics and gene expression.The study aimed to identify molecular markers of mechano-insensitive C-fibres (CMis) to advance understanding of neuropathic pain mechanisms. Objectives included electrophysiological characterization of pig sensory neurons and integration with larger RNA-seq reference atlas data.

first: Jannis

last: Korner

first: Derek

last: Howard

first: Angelika

last: Lampert


title: A generative AI-designed vascular liner prevents restenosis

city: Shanghai

first: Lingsen

last: You

state: Shanghai

address: 180 Fenglin Road, Xuhui District

institute: Zhongshan Hospital Fudan University

summary: A leading cause of global mortality is coronary artery disease. Unfortunately, in-stent restenosis and thrombosis often compromise the long-term efficacy of percutaneous coronary intervention treatments. Current metallic and polymeric stents fundamentally fail to integrate with the vessel wall, instead triggering pathological inflammatory and fibrotic responses. To address these problems, we turned to a literature-informed generative AI-driven platform to design and validate a self-expanding, bio-instructive endovascular liner that effectively prevents restenosis.  Using this platform, we identified an optimal hydrogel formulation that combines native-vessel compliance and fatigue resistance with anticoagulant activity, which we report here. In both rabbit abdominal aorta and preclinical porcine coronary artery models, the hydrogel liner demonstrated superior long-term vessel patency and minimal neointimal hyperplasia compared to clinical-grade bare-metal and bioresorbable stents. Spatial transcriptomic analysis revealed that the liner material actively reprograms the post-injury vascular microenvironment by downregulating genes associated with inflammation, fibrosis, and smooth muscle cell proliferation. This work establishes a new class of AI-designed vascular implants and represents a paradigm shift from mechanically passive or cytotoxic interventions to a bio-instructive strategy for suppressing pathological vascular remodeling.

overall_design: Stereo-seq of rabbit arterial segments after the stent having been deployed.

first: Yicheng

last: Lv

first: Shanyuan

last: Hong

first: Xiaoling

last: Fu

first: Li

last: Shen

first: Yingjun

last: Wang

first: Junbo

last: Ge


title: β-Elemene Enhances the Efficacy of PD-L1 Inhibitor in Lung Cancer by Reprogramming Tumor-Associated Macrophages to M1 Phenotype via Suppressing FLT1/PI3K/AKT Signaling

city: Chongqing

first: Jianmin

address: No.6, Panxi Seventh Branch Road, Jiangbei District

institute: Chongqing Traditional Chinese Medicine Hospital

summary: Immune checkpoint inhibitors (ICI), epitomized by PD-1/PD-L1 antibodies, have ushered in a new era in lung cancer treatment. However, ICI monotherapy is only applicable to a small subset of patients with high PD-L1 expression, while most patients with low expression require combination therapies. In this study, we found that β-elemene promotes M1 polarization of tumor-associated macrophages (TAM) and enhances the efficacy of PD-L1 antibody (aPD-L1) in C57BL/6 mice. RNA sequencing and surface plasmon resonance revealed that β-elemene directly binds to FLT1 and inhibits the PI3K/AKT/FOXO1 signaling pathway, thereby mediating TAM M1 polarization. Using FLT1 knockout mice, we further validated the critical role of FLT1 in TAM polarization and confirmed that M1 polarization synergizes with aPD-L1 treatment. Furthermore, co-immunoprecipitation demonstrated that the intracellular domain of FLT1 interacts with and phosphorylates the p85α subunit, initiating downstream signaling cascades. These findings elucidate the synergistic mechanism between β-elemene and aPD-L1. Importantly, as both agents are already clinically approved, we plan to conduct a clinical trial to evaluate the efficacy and safety of this combination therapy.

overall_design: We performed RNA-seq on bone marrow-derived macrophages (BMDM) after their co-culture with LLC cells and subsequent treatment with either 100 µg/mL β-elemene or PBS for 24 hours.

first: Yongxin

last: Yu


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (8CLC-LINE1-KD)

first: Zhengyi

last: Li

overall_design: LINE-1 ASO and control ASO were respectively transfected into 8CLC. After 24h, samples were colltected for RNA-seq.

first: Yangquan

last: Xiang

first: Hongqing

last: Liang


title: Systemic immune correlates of long-term survival after Delta-24-RGD based on the therapeutic adenovirus for recurrent glioblastoma effect trial (TARGET)

city: Houston

first: Sanjay

last: Singh

state: TX

address: 6767 Bertner St

department: Neurosurgery

institute: MD Anderson Cancer Center

summary: Purpose: Treatment of high grade gliomas, particularly glioblastoma (GBM), with the oncolytic adenovirus Delta-24-RGD has previously produced anti-tumor effects in phase 1 clinical trials. These effects are mediated through direct oncolysis and activation of an anti-tumor immune response. In this study, we combined  Delta-24-RGD with interferon gamma (IFN-𝛾), a potent activator of T-helper 1 CD8+ cell immune response. Patients and Methods: In the Phase 1b, multicenter, randomized, study (NCT02197169), we evaluated the combination of intratumoral injected Delta-24-RGD with subcutaneous administered IFN-𝛾 in 37 patients with recurrent high grade glioma and investigated potential systemic immune correlates of long-term survival. Twenty-seven patients were randomized 2:1 into two cohorts; Delta-24-RGD with IFN-𝛾 or Delta-24-RGD alone via a standard nashold biopsy needle. In an expansion cohort, 10 patients received intra-tumoral injected Delta-24-RGD via the MEMS Cannula (Neela Therapeutics). Results: Although the addition of IFN-𝛾 to Delta-24-RGD did not significantly increase the percentage of long term survivors compared to Delta-24RGF alone, the IFN-𝛾 cohort has the longest surviving patients after treatment (OS 44.2, 23.7, 20.6 and 20.1 months). Post-hoc analysis of plasma and peripheral blood mononuclear cells using viral phage immunoprecipitation sequencing antibody reactome profiling of viral epitopes (VirScan) and single cell RNA sequencing (scRNA seq) revealed that levels of circulating anti-adenovirus specific IgG and CD8+ NKT-like cells 2 months after treatment with Delta-24-RGD distinguished long term survivors from short term survivors. Conclusions:  Immunological fitness assessed by an anti-adenoviral specific antibody response and higher levels of activated CD8+ NKT-like cells after Delta-24-RGD treatment could be used as early surrogates of a robust systemic immune response that correlates with rate of tumor growth and long-term survival.

overall_design:
Cryopreserved peripheral blood mononuclear cells obtained from patients (n=7) enrolled in the study before and after treatment were sequenced. Viable CD3+ T-cells within peripheral blood mononuclear cells were stimulated overnight using anti-CD3/anti-CD28 co-stimulation. Single cell RNA-sequencing of stimulated CD3+ T-cells was performed using the 10x Genomics platform.

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

first: Chibawanye

middle: I

last: Ene

first: Thiagarajan

last: Venkataraman

first: Lynette

last: Phillips

first: James

middle: P

last: Long

first: Deep

first: Nam

middle: D

last: Tran

first: Frank

last: Tufaro

first: P

last: Anand

first: Nicholas

last: Navin

first: Sujit

last: Prabhu

first: Jeffrey

middle: S

last: Weinberg

first: Benjamin

last: Larman

first: Candelaria

last: Gomez-Manzano

first: Juan

last: Fueyo

first: Frederick

middle: F

last: Lang


title: ScRNA-seq datasets of Blood transcriptomics reveals the value of Hub genes in patients with NTM - PD

first: Guoling

last: Yang

address: No. 507 Zhengmin Road

department: Department of Tuberculosis

institute: Shanghai Pulmonary Hospital

summary: To identify and validate peripheral blood mRNA signatures as non-invasive diagnostic biomarkers for nontuberculous mycobacterial pulmonary disease (NTM-PD), we performed an integrated transcriptomic analysis combining scRNA-seq and bulk RNA sequencing (RNA-seq), followed by experimental validation.Peripheral blood samples were collected from a total of 8 participants, including 3 patients with Mycobacterium avium complex pulmonary disease (MAC-PD), 3 patients with Mycobacterium abscessus pulmonary disease (MAB-PD), and 2 healthy controls (HC). All samples were subjected to scRNA-seq to dissect the single-cell transcriptomic landscape of peripheral blood, and paired bulk RNA-seq was conducted simultaneously to achieve comprehensive transcriptomic profiling.Integrated analysis of scRNA-seq and bulk RNA-seq datasets revealed that eight core genes were significantly upregulated in NTM-PD patients compared with HCs. Notably, this gene signature exhibited superior specificity relative to other candidate gene combinations, highlighting its potential as a diagnostic biomarker for NTM-PD.

overall_design:
For both NTM-PD patients and healthy controls, 5 ml of fresh peripheral blood was collected from each participant and stored in EDTA-anticoagulated blood collection tubes. Subsequently, cells were isolated from the whole-blood samples using BD Pharm Lyse™ lysing solution (BD, USA). The prepared cell suspensions were processed for 10× Chromium Single Cell 3′ library construction with the Chromium Single Cell 30 v3 reagent (10× Genomics) in strict accordance with the manufacturer’s instructions, followed by high-throughput sequencing performed on an Illumina Nova 6000 platform following the corresponding standard operating procedures.

***************************************************************
Raw sequencing data (FASTQ files) are not included due to patient privacy protection requirements.
***************************************************************

first: Li

last: Wang

first: Xubin

last: Zheng

first: Lan

last: Yao

first: Jianxia

last: Chen

first: Peng

first: Wei

last: Sha


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development [8CLC-MLT2A1-rescue]

first: Zhengyi

last: Li

overall_design: To rescue MLT2A1 expression in 8CLC, the non-targetable chimeric RNAs were co-transfected with dup_161/2477 ASOs into 8CLC. After 24h, cells were collected for transcriptome profiling.

first: Yangquan

last: Xiang

first: Hongqing

last: Liang


title: Radiotherapy plus neoadjuvant and concomitant IL-13Rα2-directed immunotoxin therapy for diffuse intrinsic pontine glioma

city: Rochester

first: Alexandra

last: Krivonos

state: MN

address: 200 1st St SW

department: Quantitative Health Sciences

institute: Mayo Clinic

summary: Radiotherapy (RT) is the standard-of-care for diffuse intrinsic pontine glioma (DIPG); however, it functions as a palliative treatment. Interleukin 13 receptor subunit alpha 2 (IL-13Rα2) is upregulated in most DIPG tumors, posing a promising therapeutic target. Immunotherapies harnessing IL-13Rα2 to selectively deliver cytotoxic payloads such as pseudomonas exotoxin A (PE) are safe in DIPG patients and efficacious in preclinical disease models. Here, we used DIPG cell lines and mouse models to compare RT alone with RT plus the IL-13Rα2-targeted PE immunotoxin GB13 (IL13.E13K-PE4E). DNA strand breaks were evaluated by γH2AX and apoptosis, as well as other on-target effects, by Western blot and immunofluorescence. CellTiter-Glo® and colony formation delineated cell viability and proliferation. In vivo efficacy was based on survival of mice with orthotopic tumors. Animals received fractionated focal irradiation and neoadjuvant and concomitant GB13 by convection-enhanced delivery. GB13 improved the efficacy of RT in vitro through inhibition of DNA damage repair and convergent modulation of apoptotic signaling. Combined RT and intratumoral administration of GB13 decreased tumor burden and prolonged survival in orthotopic xenograft and genetically engineered mouse models. These findings indicate that RT plus GB13 is well tolerated and effective, informing future investigation of a novel therapeutic approach for DIPG.

overall_design: Baseline gene expression of patient-derived diffuse midline glioma H3 K27 altered.

first: Julian

last: Rechberger

first: Wouter

last: Vanbilloen

first: Leo

last: Nonnenbroich

first: Jizhi

last: Ge

first: Randy

last: Schrecengost

first: Rachael

middle: A

last: Vaubel

first: Liang

last: Zhang

first: David

last: Daniels


title: Single-cell transcriptomic comparison of the developing human fetal stomach and pluripotent stem cell-derived gastric organoids

first: Daniel

middle: O.

last: Kechele

state: OH

address: 3333 Burnet Ave Location R3.034

department: Developmental Biology

summary: The goal of engineering increasingly complex in vitro human organoid models is to more accurately model human organogenesis and disease. Recently, human antral gastric organoids (hAGOs) were engineered to contain splanchnic mesenchyme (SM) and enteric neural crest cells (NCCs), resulting in the formation of functional three germ layer gastric organoids. It is unclear how three-germ layer hAGOs compare with the human fetal stomach and how the added germ layers alter gastric differentiation in vitro. To determine the robustness of hAGOs and how additional germ layers impact development, we benchmarked hAGO with and without added SM and NCC to a single cell atlas of the developing human stomach. A comparison of hAGOs in vitro to fetal organs confirmed that they were gastric and most similar to 7 week stomach with the epithelium comprised primarily of gastric precursors and surface mucous cells. The SM added to hAGOs formed fetal gastrointestinal-like mesenchyme whereas the NCCs in hAGOs differentiated into neuronal precursors and glial cells similar to those found in developing endodermal organs. The addition of SM and NCCs did not drastically alter the cellular diversity of the epithelium in vitro but maintained more uncommitted precursors similar to 7 week stomach. Following transplantation and growth for 10 weeks, hAGOs with SM grew and matured into tissue more similar to the 14 week fetal stomach. Bioinformatic inference of cell-cell communication confirmed known signaling crosstalk between germ layers but also identified new signaling candidates that may regulate tissue assembly. Together, these data show that three-germ layer hAGOs faithfully modeled the multilayer complexity of the fetal stomach at a single cell transcriptomics level and provided insight into human stomach development.

overall_design: Day 37 in vitro human antral gastric organoids with added splanchnic mesenchyme and/or neural crest cells (one to two biological replicates), day 35 HIO (one replicate), or HAGO with mesenchyme following 10 wk in vivo grown under mouse kidney capsule were dissociated to single cells were subjected to 10X single cell RNA sequencing.

middle: O

first: Jacob

last: Enriquez

first: Konrad

last: Throner

first: Praneet

last: Chaturvedi

first: Guillermo

last: Sanchez

first: James

last: Wells


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development [4C_KD161_2477]

first: Zhengyi

last: Li

overall_design: 161 ASO, 2477 ASO and control ASO were respectively micro-injected into human 3PN zygotes, and embryos were collected for RNA-seq when reaching 4C stage.

first: Yangquan

last: Xiang

first: Yuli

last: Qian


title: IFN-γ induces hematopoietic stem cell myelopoiesis through Meis1 in tumor

city: guangzhou

first: Songqi

last: Zhu

state: guangdong

address: No. 74, Zhongshan 2nd Road, Yuexiu District

institute: Sun Yat-sen University

summary:
Background
Tumors associated overproduction of tissue-damaging myeloid cells and loss of lymphoid cell production were caused by chronic inflammation. Hematopoietic stem cells (HSCs) were the origin of all innate and adaptive immune cells and differentiate through a series of lineage-biased multipotent progenitors (MPPs) dependent on situations.
Methods
MC38 tumor and Lewis lung cancer models were performed to evaluate HSCs differentiation biased. Through elisa assay and bioinformatic analysis, the key pro-inflammatory cytokine was selected, which promoted myeloid-biased differentiation of HSCs. Next, the main transcription factor was found in tumor induced myeloid-biased differentiation. Finally, HSC-derived myeloid-derived suppressor cells (MDSCs) and impaired T cell functions were measured to evaluate the reason of tumor progression. By targeting myeloid-biased HSCs, Emapalumab was used to suppress tumor progression.
Results
Here we found HSCs preserved myeloid-biased differentiation in MC38 tumor and Lewis lung cancer models, which reflected extensive properties in tumor models, and was induced by one of pro-inflammatory cytokines, IFN-γ. Transcriptional profiling indicated Meis homeobox 1 (Meis1) was enriched in tumor primed HSCs, and ablation of Meis1 in HSCs prevented HSCs-associated myeloid cell differentiation. HSC-derived MDSCs, which were primary factors, promoted tumor progression. Targeting myeloid differentiated HSCs, combination of anti-PD-1 and Emapalumab, an anti-IFN-γ antibody, inhibited HSC-derived MDSCs and enhanced T cells associated adoptive immune response to suppress tumor progression. Myelodysplastic syndrome (MDS), which was displayed abnormal myeloid cell differentiation induced by hematopoietic failure, was improved by treated with Emapalumab or Meis1 inhibitor.
Conclusions
These results suggested that targeting HSCs was a new approach to treat tumor, and combination of PD-1 and Emapalumab might serve as a novel therapeutic strategy to improve the response and efficacy of anticancer therapy.

overall_design: RNA-seq profiling of HSCs from both normal and MC38 colon cancer C57BL/6J mice to investigate the mechanism underlying the myeloid-bias of HSCs induced by tumorigenesis.

first: Xue

last: Han

first: Minyi

last: Zhao

first: Kexin

last: Wang

first: Weiwei

last: Ma

first: Ruiqing

last: Zhou

first: Uet

last: Yu

first: Bangxue

last: Jiang

first: Xiaoqing

last: Bai

first: Peng

last: Lei

first: Shunqing


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (8CLC-LINE1-ChIRP)

overall_design: LINE-1 ChIRP was performed in 8CLC to profile the genomic binding sites of LINE-1 RNA.

first: Hongqing

last: Liang


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development [hESC-MLT2A1-RNA-OE]

overall_design: RNA-seq was performed to find DEGs by comparing GFP OE, 5' MLT2A1 OE, 3' fusion OE and FL OE samples.


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (4C-MLT2A1-RNA-OE)

overall_design: To over-express MLT2A1 chimeric RNAs in human embryos, the in vitro transcribed dup_161, dup_2477 chimeric RNAs and control GFP mRNA were injected into embryos at the zygotic stage on day 1. Control RNA and MLT2A1 RNA-injected embryos were collected on day 2 at the 4C stage for transcriptome profiling.


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (8C-HNRNPU-KD)

overall_design: HNRNPU siRNA and control siRNA were respectively micro-injected into human 3PN zygotes, and embryos were collected for RNA-seq when reaching 8C stage.


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development [4C-MLT2A1-rescue]

overall_design: MLT2A1 rescue experiments were performed in human 4C embryo to validate the function of MLT2A1 in regulating ZGA gene expression with more strigency.


title: Wild-Type vs BTP2 Treated Th1 and Pathogenic Th17 cells_ 96h

city: Los Angeles

first: Yousang

last: Gwack

state: CA

address: 10833 Le Conte Ave, 53-159 CHS

department: Physiology

institute: Uuniversity of California Los Angeles

summary: Transicriptome comparison between murine WT and BTP2 Treated Th1 and pTH17cells at 96 hours following differentiation

overall_design: Naive CD4+ T-cells were isolated and purified from wild-type mice. Naïve CD4+ T cells were enriched by magnetic sorting from single-cell suspensions generated by mechanical disruption of spleens and lymph nodes of adult mice using MagniSort naïve CD4+ T cell enrichment kit (catalog # 8804-6824-74,ThermoFisher Scientific). For effector T cell differentiation, cells were stimulated with anti-CD3 antibody (1452C11, Bio X Cell) and anti-CD28 antibody (Clone 37.51, Bio X Cell) for 48 hours on a plate coated with rabbit anti-hamster antibody (MP Biomedicals). CD4 + CD25 - T cells were cultured with anti-IL-4 antibody (Peprotech) and 10 μg/ml anti-IFN-γ antibody, 30 ng/ml IL-6 (Peprotech), 10 ng/ml IL-23 (R&D Systems) and 10 ng/ml IL-1β (R&D Systems) for pathogenic Th17 differentiation and cultured in T cell medium. For Th1 cell differentiation, CD4 + CD25 - T cells were cultured with anti-IL-4 antibody (Peprotech) and IL-12 for Th1 differentiation. In the BTP2 treatment groups, BTP2 was applied transiently between 24-48 hrs during differentiation. Cells were collected at 96h and prepared for bulk RNA sequencing analysis.

first: Beibei

last: Wu

first: Spyridon

last: Hasiakos

first: Shawn

last: Cokus

first: Matteo

last: Pellegrini

first: Sonal

last: Srikanth


title: Integrated Clinical Trial and Molecular Profiling Reveals Immune Drivers of Chronic Hand Eczema

city: Toulouse

first: Rüçhan

last: Ekren

address: CHU Purpan – BP 3028 –  Toulouse Cedex, 3

department: INFINITY

country: France

institute: Inserm UMR 1291

summary: Chronic hand eczema (CHE) is a painful, itchy and inflammatory skin disease of multifactorial origin. CHE can be categorized based on etiology and/or clinical presentation, including intertwined atopic-contact eczema-psoriasis traits, making it challenging to diagnose and treat. While being the most frequent work-related dermatosis, the underlying immune mechanisms remain unclear. Here we performed a randomized controlled study comparing dupilumab and placebo and demonstrated that CHE is a type 2 immunity driven disease, regardless of etiological factors or clinical presentation. We conducted a comprehensive molecular profiling of CHE patients of all etiologies and morphologies to identify potential common features and evaluated the consequences of blocking IL-4Rα during 16 weeks. This phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. We found that CHE patients share complex transcriptomic signatures with those of atopic dermatitis and psoriasis patients, with dysregulated genes involved in skin barrier, leukocyte migration, cytotoxicity, type 1, 2 and 3 immunity. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of CHE patients, while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis. These findings demonstrate that IL-4Rα signaling is a critical regulator of CHE pathological features, independent of atopic dermatitis background or environmental triggers, and propose reclassifying CHE as a type 2 immune disorder, with dupilumab or IL-4/13 targeted therapy as the mainstay treatment for moderate to severe disease.

overall_design: Hand skin biopsy samples from back or palm were collected from patients with moderate to severe chronic hand eczema (CHE) at baseline and at week 16. Arm or abdomen control skin samples were obtained from healthy donors matched for age and sex. The dataset includes patient samples for longitudinal analysis, along with healthy control samples serving as reference for non-lesional skin comparisons.

first: Perrine

last: Gery

first: Aurélie

last: Du-Thanh

first: Emilie

last: Bérard

first: Fatma

last: Jendoubi

first: Vanina

last: Lenief

first: Hugo

last: Rimet

first: Nadia

last: Raison-Peyron

first: Amel

last: Bouznad

first: Maria

last: Konstantinou

first: Jonathan

last: Rioual

first: Lilian

last: Basso

first: Juliette

last: Mouiren

first: Manon

last: Boussier

first: Brigitte

last: Milpied

first: Cristina

last: Bulai Livideanu

first: Louise

last: Jaulent

first: Florence

last: Hacard

first: Marine

last: Lefevre

first: Audrey

last: Nosbaum

first: Julien

last: Seneschal

first: Marc

last: Vocanson

first: Carle

last: Paul

first: Nicolas

last: Gaudenzio

first: Marie

last: Tauber


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (MLT2A1 subfamily KD in 4C and 8C embryos)

first: Zhengyi

last: Li

summary: MLT2A1 was highly and specifically expressed in human totipotent embryos. To unveil the function and biological significance of MLT2A1 in regulating human totipotent embryo development and human zygotic genome activation, RNA-seq was performed for MLT2A1 KD and Ctrl KD 4-Cell and 8-Cell embryos.

overall_design: RNA-seq was performed to find DEGs and DETEs by comparing MLT2A1 KD and Ctrl KD samples

first: Hongqing

last: Liang

first: Yangquan

last: Xiang


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (4C-LINE1-KD)

overall_design: LINE-1 ASO and control ASO were respectively micro-injected into human 3PN zygotes, and embryos were collected for RNA-seq when reaching 4C stage.

first: Yuli

last: Qian


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (Nanopore-seq in 8CLC and 8C embryo)

summary: Previous studies revealed that endogenous retroviruses can fuse with downstream sequences to generate chimeric transcripts. To identify the chimeric transcripts produced by MLT2A1 in 8C-like cells and 8C embryos and to unveil their potential biological function, Nanopore sequencing was utilized.

overall_design: Nanopore long-reads sequencing was used to identify the full-length of MLT2A1-generated chimeric transcripts

first: Jiaxu

last: Wang


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (Control and arrested 8C embryos)

overall_design:
RNA-seq was performed to find the transcriptome of arrested 8C embryos.
To find DEGs and DETEs, we compared arrested 8C embryos with normal 8C embryos. For the comparisons of normal 2PN 8C embryos and arrested 8C embryos, we downloaded normal 2PN 8C embryo samples from short reads achieve (SRA) database (accession: SRP163205), we reprocessed this data and merged our data together for further analysis.
To collect embryos arrested at 8-Cell stage, 0PN and 3PN embryos that reached 8-Cell at day 3 were monitored for another 24h and those ceased development were collected for transcriptome profiling.


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (MLT2A1 subfamily KD in 8CLC)

summary: MLT2A1 was highly and specifically expressed in human totipotent embryos. To unveil the biological significance of MLT2A1, RNA-seq was performed for MLT2A1 KD and Ctrl KD samples in 8C-like cells

overall_design: Differentially expressed genes and TEs were calculated by comparing the MLT2A1 KD with Ctrl KD samples


title: Ribo-seq analysis of alternative splicing under PEG treatment in osfkbp20-1b mutant compared to wild-type (ZH11) rice.

city: Daejeon

first: Haemyeong

last: Jung

address: 125 Gwahak-ro, Yuseong-gu

department: Plant Systems Engineering Research Center

country: South Korea

institute: KRIBB

summary: To investigate whether intron containing transripts from alternative splicing are abundant in monosome of osfkbp20-1b upon drought stress, we analyzed Ribo-seq to identify the quantitative profiling and alternative splicing.

overall_design: Total RNA was precipitated from monosome and polysome of osfkbp20-1b or WT shoot and extracted in condition of 20% PEG-6000 for 6 h treatment using 1-week-old rices.

first: Hye Sun

last: Cho

first: Hyun Ji

last: Park


title: Dysregulation of miRNA-mRNA expression in fetal growth restriction in a caloric restricted mouse model

status: Public on Jan 23 2026

city: Aurora

first: JAMES

last: BARDILL

state: CO

department: Surgery

institute: UNIVERSITY OF COLORADO-ANSCHUTZ MED

type: Non-coding RNA profiling by high throughput sequencing

summary: Fetal growth restriction (FGR) is associated with aberrant placentation and accounts for a significant proportion of perinatal deaths. microRNAs have been shown to be dysregulated in FGR. The purpose of this study was to determine microRNA-regulated molecular pathways altered using a caloric restricted mouse model of FGR. Pregnant mice were subjected to a 50% caloric restricted diet beginning at E9. At E18.5, RNA sequencing of placental tissue was performed to identify differences in gene expression between caloric restricted and control placentas. Significant differences in gene expression between caloric restricted and control placentas were observed in 228 of the 1546 (14.7%) microRNAs. Functional analysis of microRNA-mRNA interactions demonstrated enrichment of several biological pathways with oxidative stress, apoptosis, and autophagy pathways upregulated and angiogenesis and signal transduction pathways downregulated. Ingenuity pathway analysis also suggested that ID1 signaling, a pathway integral for trophoblast differentiation, is also dysregulated in caloric restricted placentas. Thus, a maternal caloric restriction mouse model of FGR results in aberrant microRNA-regulated molecular pathways associated with angiogenesis, oxidative stress, signal transduction, apoptosis, and cell differentiation. As several of these pathways are dysregulated in human FGR, our findings suggest that this model may provide an excellent means to study placental microRNA derangements seen in FGR.

overall_design: miRNA sequencing of control (n=10) and IUGR (FGR) (n=10) mouse placenta samples

first: Gallagher

last: Lauren

first: Bardill

last: James

first: Derderian

last: Chris (Sarkis)


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (MLT2A1 single copy KD in 8CLC)

summary: MLT2A1 formed chimeric transcripts with downstream seqeunces, including annotated and unannotated regions. To study the function of chimeric transcripts as well as the biological significance of MLT2A1 single copies, dup_161 and dup_2477 chimeric transcripts were depleted in 8C-like cells

overall_design: RNA-seq was performed to find DEGs and DETEs by comparing single copy KD and Ctrl KD samples


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development

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

overall_design: Refer to individual Series


title: Type 2 lymphocytes restrict type 3 lymphocytes during liver fibrosis and co-localize in fibroblast niches

city: Tübingen

first: Jun-Hoe

last: Lee

address: Otfried-Müller-Str. 37

department: Quantitative Biology Centre (QBiC)

country: Germany

institute: University of Tuebingen

summary: Fibroblasts are dynamic structural cells that direct both beneficial tissue repair and pathologic organ fibrosis through interactions with tissue-resident type 2 and type 3/17 lymphocytes (T2L and T3L). We performed spatial transcriptomics to profile heterogenous fibroblast populations within fibrotic, adventitial, and parenchymal regions of resting and fibrotic murine livers as well as to determine their crosstalk with T2L and T3L. Our analysis suggests a spatially associated crosstalk between liver lymphocytes and fibroblast niches.

overall_design: Four mouse models with genetic depletion of IL-5+ lymphocytes and IL-17A+ lymphocytes were used for the analysis: 4-week CCl4- and placebo-treated IL5-Cre mice, 4-week CCl4-treated IL-5 deleter mice, and 4-week CCl4-treated IL-5;IL-17A double deleter mice.

first: Julia

last: Sbierski-Kind

first: Kelly M

last: Cautivo

last: Nilsson

first: Taeeun

last: Gu

first: Hyeewon

last: Seo

first: Hyun Je

last: Kim

first: Ari

last: Molofsky


title: A fully defined protocol and PEG-based platform for probing transcriptional responses to matrix cues in human iPSC-derived intestinal organoids

city: Lausanne

first: Eileen

last: Gentleman

address: Quartier Centre

institute: University of Lausanne

summary: Human intestinal organoids (hIOs) are powerful models of development and disease, yet reliance on ill-defined murine basement membrane extracts limits reproducibility, mechanistic interrogation of extracellular matrix (ECM) cues, and translational relevance. Here, we establish a fully defined, animal product-free workflow for generating human induced pluripotent stem cell (iPSC)-derived hIOs, combining recombinantly produced human protein substrates for early 2D differentiation with synthetic polyethylene glycol (PEG) hydrogels for 3D culture. This platform decouples biochemical and mechanical matrix cues, enabling independent control of ligand presentation and stiffness while robustly supporting hIO growth and intestinal epithelial patterning. Transcriptomic analyses showed that epithelial cells from PEG-cultured hIOs align closely with human duodenal epithelium and are comparable to Matrigel-grown controls, while exhibiting subtle shifts in markers associated with epithelial maturation. Systemic modulation of PEG stiffness revealed that epithelial cells retain sensitivity to mechanical cues in 3D culture, whereas mesenchymal transcriptional programs were more strongly influenced by matrix composition and integrin-mediated adhesion than by stiffness alone. PEG-cultured hIOs also remained responsive to inflammatory stimulation. Together, this work establishes a defined and mechanically tunable organoid culture platform that decouples biochemical and mechanical matrix cues, providing a versatile framework for organoid mechanobiology across tissue engineering and disease modeling applications.

overall_design: RNA-seq profiling of sorted epithelial (EpCAM+) and mesenchymal (CD90+) populations from human iPSC-derived small intestine organoids. Organoids were cultured in three matrix conditions: Matrigel (control), PEG hydrogels with a storage modulus (G') of ~0.5 kPa, or PEG hydrogels with increased stiffness (PEG Stiff), to investigate matrix-dependent gene expression changes.

first: Alicja

last: Kuziola

first: Tamara

last: Fawzi

first: Emma

middle: H

last: Kromann

first: Marion

last: Leleu

first: Joanna

last: Magon

first: Cecile

last: Dreiss

first: Joana

last: Neves


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (MLT2A1 ChIRP in 8CLC)

first: Zhengyi

last: Li

summary: Previous data showed that MLT2A1 RNAs participated in the regulation of totipotent embryo development and totipotent gene expression. Thus, to further study the mechanisms of how MLT2A1 RNAs regulated gene expression, we performed ChIRP-seq to identify the genomic binding sites of MLT2A1 RNAs

overall_design: MLT2A1 ChIRP probes were used to precipitate MLT2A1 RNAs and genomic DNA was extracted and sequenced to identify the binding sites of MLT2A1 RNAs by peak calling comparing with input

first: Hongqing

last: Liang

first: Yangquan

last: Xiang


title: Transcriptome analysis of alternative splicing under PEG treatment in osfkbp20-1b mutant compared to wild-type (ZH11) rice

first: Haemyeong

last: Jung

summary: To investigate whether observed changes in pre-mRNA splicing led to OsFKBP20-1b depletion upon drought stress, we analyzed RNA-seq to identify the quantitative profiling and alternative splicing.

overall_design: Oryza sativa. L (ssp. japonica) total RNA was extracted from osfkbp20-1b and WT shoot after mock or 20% PEG-6000 for 6 h treatment using 1-week-old rices.

first: Hye Sun

last: Cho

first: Hyun Ji

last: Park


title: A novel pyrrolidine-chalcone derivative exhibits synergistic anti-cervical cancer activity by dual-targeting MDM2-p53 axis and ferroptosis pathway

city: Urumqi

first: xinyi

last: deng

address: No. 393 Xinyi Road

department: College of Pharmacy

institute: Xinjiang Medical University

summary: Cervical cancer remains a serious threat to women’s health, driving the need for effective and low-toxicity therapeutics.

overall_design: In this study, we designed and synthesized a novel series of pyrrolidine-chalcone derivatives targeting the MDM2-p53 interaction. The lead compound, B1, exhibited potent, nanomolar- level cytotoxicity against cervical cancer cells (HeLa/SiHa; IC50 = 0.22/0.24 µM) with minimal toxicity to normal cervical epithelial cells (H8). Mechanistic studies revealed that B1 acts through a novel dual mechanism: it activates the p53 pathway by downregulating MDM2, inducing cell cycle arrest and apoptosis, while simultaneously triggering ferroptosis via reactive oxygen species accumulation, glutathione depletion, and suppression of SLC7A11/ GPX4. These findings identify B1 as a promising dual-mechanism lead compound worthy of further investigation in cervical cancer.

first: Xinyi

last: Deng


title: Endogenous retroviruses synthesize heterologous chimeric RNAs to reinforce human early embryo development (HNRNPU KD in 8CLC)

summary: RNA pulldown-MS showed that HNRNPU was the most enriched RNA binding protein to complex with MLT2A1 RNA. Thus, to study the function of HNRNPU, RNA-seq was performed for siNC and siHNRNPU samples in 8C-like cells

overall_design: Differentially expressed genes and TEs were calculated by comparing the siHNRNPU with siNC samples


title: Single-cell RNA-seq of eWAT stromal vascular fraction cells from WT and Camk2d myeloid conditional knockout mice after high-fat diet

first: Qiancheng

last: Xiao

address: Building 25, No. 1188, LIANHANG Road, Pujiang Town, Minhang District, Shanghai

institute: Shanghai OE Biotech Co., Ltd

summary: Epididymal white adipose tissue (eWAT) stromal vascular fraction (SVF) cells were profiled by 10x Genomics Chromium Single Cell 3′ v1 scRNA-seq to characterize immune-cell states in diet-induced obesity. SVF cells were isolated by collagenase digestion, filtered, and processed when viability exceeded 85%. Libraries were sequenced on an Illumina NovaSeq 6000 (PE150). Reads were aligned to mm10 and gene–cell count matrices were generated with Cell Ranger count v5.0.0 and aggregated across samples with Cell Ranger aggr. Downstream analyses were performed in Seurat v4.1.1 with QC filtering, ambient RNA correction (SoupX v1.3.0), doublet detection (DoubletFinder v2.0.2), batch correction (fastMNN), clustering/UMAP, and differential expression testing (MAST). Cell types were annotated using SingleR v1.4.1 and canonical markers; non-immune cells were excluded for immune-focused analyses. Additional analyses included pseudotime inference (Monocle2 v2.14.0) and cell–cell communication analysis (CellChat v0.0.2).

overall_design: Two experimental groups (WT vs Camk2d myeloid conditional knockout) were compared after 10 weeks of high-fat diet. For each biological replicate, eWAT SVF was dissociated and ~10,000–13,000 cells were loaded per Chromium channel to generate one scRNA-seq library per sample.

first: Yifan

last: Tu

first: Ke

last: Sui

first: Zheng

last: Wang

first: Jiawei

last: Zhang

first: Ying

last: Gu


title: HIV impairs and exploits pulmonary Th17 and Th22 cell-mediated immune responses to Mycobacterium tuberculosis

city: Galveston

first: Haiping

last: Hao

state: Texas

address: 301 University Blvd

institute: UTMB NGS Core

summary: Tuberculosis (TB), caused by the bacteria Mycobacterium tuberculosis (Mtb), is the world’s leading cause of death by infectious disease, as well as the leading cause of death in people with HIV.  The cytokines interleukin (IL)-17 and IL-22 are chemical messengers that are essential for a protective immune response to Mtb infections and tissue repair following bacterial clearance, respectively. The CD4+ T cell subsets that are primary sources of these cytokines, Th17 and Th22 cells, are also primary targets for HIV infection at mucosal surfaces like the gut and lung. Our work reveals Th17 as important HIV viral reservoirs in organs of Mtb/HIV co-infection, with defective immune signals compared to Mtb single infection in the humanized mouse model. Th22 responses were also decreased by HIV in both mono- and Mtb/HIV co-infection as early as nine days after infection. These results have potential applications for future TB therapeutic vaccine design and may implicate possible targets to augment TB therapy.

overall_design: RNA-seq profiling lung tissues of mouse with human immune stem cells either mock infected, infected with TB, infected with HIV, or co-infected with TB and HIV.

first: Yazmin

middle: B

last: Martinez-Martinez

first: Matthew

last: Huante

first: Kubra

last: Naqvi

first: Mithil

middle: N

last: Shah

first: Joshua

middle: G

last: Lisinicchia

first: Megan

last: Files

first: Jaid

last: Perez

first: Benjamin

last: Gelman

first: Mark

last: Endsley

first: Janice


title: Genome-wide identification of transcriptional targets of H4K12 lactylation and GR in 786-O cells with or without dexamethasone treatment.

city: Beijing

first: Lin

last: He

address: Xueyuan Road 38

institute: Peking University

summary: To investigate the genome-wide transcriptional targets associated with H4K12 lactylation in renal cell carcinoma, cleavage under targets and tagmentation (CUT&Tag) was performed in 786-O cells with or without dexamethasone treatment using  specific antibodies against H4K12 lactylation or GR. Following CUT&Tag, genomic DNA fragments were amplified under non-biased conditions and sequenced on the Illumina NovaSeq 150PE platform to generate high-resolution maps of H4K12 lactylation or GR–associated chromatin regions.

overall_design: CUT&Tag was performed to profile genome-wide H4K12 lactylation in 786-O renal cell carcinoma cells treated with or without dexamethasone, enabling the identification of H4K12 lactylation or GR–associated transcriptional regulatory regions.

first: Kenan


title: Genome-wide identification of transcriptional targets for H4K12 lactylation in ccRCC cells

summary: To investigate the genome-wide transcription targets of H4K12 lactylation in ccRCC cells, cleavage under targets and tagmentation (CUT&Tag) was performed in 786-O and Caki-1 cells using antibody against H4K12 lactylation. Following CUT&Tag,  DNAs were amplified using non-biased conditions, labeled, and sequenced with Illumina NovaSeq 150PE.

overall_design: CUT&Tag of H4K12 lactylation in  786-O and Caki-1 cells


title: Cyanidin-3-rutinoside(C3R) Attenuates Free Fatty Acid-Induced Hepatic Lipid Accumulation in HepG2 Cells

city: Tianjin

first: Jingxu

last: Duan

institute: Tianjin university

summary: Non-alcoholic fatty liver disease (NAFLD) is characteristic by pathological lipid accumulation in hepatocytes. This study investigates how Cyanidin-3-rutinoside(C3R), a natural anthocyanin with antioxidant and metabolic regulatory properties, counteracts this process. In a free fatty acid (FFA)-induced HepG2 steatosis model, C3R significantly reduced intracellular triglycerides, total cholesterol, and LDL-C levels, suppressed lipid droplet formation, and alleviated oxidative stress by enhancing SOD/CAT activities and GSH content while lowering MDA and ROS. RNA-seq analysis revealed that C3R reversed FFA-induced transcriptomic alterations. Mechanistically, C3R inhibited SREBP2-mediated cholesterol synthesis, activated the PCSK9/LDLR pathway to promote cholesterol clearance, and upregulated PPARγ-dependent CYP7A1 expression to stimulate bile acid synthesis from cholesterol. C3R also enhanced autophagic flux, facilitating lipid droplet degradation. Molecular docking confirmed high-affinity binding of C3R to INSIG1, PCSK9, and PPARγ, with hydroxyl groups forming specific hydrogen bonds at active sites, supporting direct target engagement. These findings establish a multi-targeted mechanism for C3R in ameliorating hepatic steatosis and provide a molecular basis for anthocyanin-mediated regulation of lipid metabolism.

overall_design: To elucidate the lipid-lowering mechanism of C3R in the high-fat HepG2 cell model, transcriptome sequencing was performed to analyze differentially expressed genes. The experimental design comprised five groups: a blank control (NC), a high-fat model induced with 500 μM FFA (FFA), and three C3R intervention groups at 25 μM (FCL), 50 μM (FCM), and 100 μM (FCH), each with three biological replicates. Following the treatment protocol in section 2.5, cells were trypsinized, washed with PBS, and total RNA was extracted using TRIzol reagent (1 mL per 5×10⁶ cells). RNA concentration and purity were measured with a Nanodrop2000, integrity was verified by agarose gel electrophoresis, and RQN values were determined using an Agilent 5300 system. Qualified RNA samples were submitted to Shanghai Majorbio Bio-pharm Technology Co., Ltd. for library preparation (Illumina NovaSeq Reagent Kit) and sequencing. Sequencing reads were aligned to the human reference genome (Ensembl: Homo_sapiens) using HiSat2, followed by gene expression quantification with RSEM.

first: Wancong

last: Yu

first: Yujia

last: Niu

first: Jiao

last: Li

first: Zhaohui

last: Xue


title: Decoding and Rewiring Promoter Architecture Using Large Language Models and Diffusion Frameworks

first: wang

last: xing

address: No. 382, Outer Ring East Road, Guangzhou University Town, Panyu District

institute: South China University of Technology

summary: High-performance promoters are essential tools for precisely regulating gene expres-sion, yet their rational design within the vast combinatorial sequence space remains a major challenge. Here, we present a hybrid framework that integrates a large lan-guage model (LLM) with a diffusion model to enable data-driven and interpretable promoter design. The fine-tuned LLM predicts promoter strength with high accuracy and, through pseudo-sequence mutations, identifies biologically essential core motifs. A diffusion model is then conditioned on these motifs to reconstruct non-core regions and generate complete promoter sequences. We experimentally validated this approach in E. coli by high-throughput barcoded promoter activity sequencing: over 90% of the generated promoters showed measurable activity, and the best variants achieved ap-proximately ∼20-fold higher expression than the benchmark promoter (BBa_J23119). By explicitly coupling interpretability with generative design, this strategy provides a generalizable path to accelerate synthetic biology efforts and advance large-scale regu-latory sequence engineering.

overall_design: This study employs a high-throughput barcoded sequencing assay to quantify the transcriptional activities of a synthetic promoter library in Escherichia coli DH5[alpha]. Each promoter was cloned into a plasmid reporter construct and uniquely associated with a barcode. The pooled plasmid library was introduced into E. coli DH5α and cultured in LB medium supplemented with 50 µg/mL kanamycin at 37 °C with shaking. At a defined time point, cells from the same pooled cultures were harvested for parallel extraction of total RNA and plasmid DNA. Barcode abundances in RNA (after reverse transcription) and DNA were determined by high-throughput sequencing. Promoter activity was quantified based on normalized RNA/DNA barcode ratios across biological replicates.

first: Xin

last: Lei

first: Xing

last: Wang

first: Yuzhong

last: Liu

first: Yangyu

last: Zhang

first: Jiesheng

last: Huang

first: Tianjiao

last: Peng

first: Ce

last: Liang

first: Quhuan

first: Huaiguang

last: Jiang

first: Wei

last: Xiong


title: The miRNA expression profiles in exosomes derived from M0 macrophages (M0-Exo) and M2 macrophages (M2-Exo).

city: Lanzhou

first: Zhenchang

state: Gansu

address: No. 222, Tianshui South Road

department: The Second Hospital & Clinical Medical School

institute: Lanzhou University

summary: Macrophage-derived exosomes hold significant promise for clinical disease therapy. Macrophages can be categorized into several subtypes. The resting state is known as the M0 subtype, and the exosomes they secrete are termed M0-Exo. Macrophages can be polarized to the M2 subtype by combined induction with IL-4 and IL-13, and the exosomes derived from M2 macrophages are referred to as M2-Exo. miRNAs are important cargo within exosomes. Since both M0-Exo and M2-Exo exhibit therapeutic effects in inflammatory responses, we performed miRNA sequencing on the contents of M0-Exo and M2-Exo to investigate the underlying mechanisms of their therapeutic actions.

overall_design: To ensure sufficient exosome yield, Raw264.7 cells were utilized for exosome isolation. The cells were divided into two groups. M0-Exo group: Raw264.7 cells were cultured under normal conditions for 24 hours, followed by a switch to serum-free medium. The supernatant was then collected for M0-Exo extraction.M2-Exo group: Raw264.7 cells were co-induced with 20 ng/ml IL-4 and 20 ng/ml IL-13 for 24 hours. Subsequently, the medium was replaced with serum-free medium, and the supernatant was collected for M2-Exo extraction.High-throughput sequencing was performed to analyze the miRNA expression profiles in both M0-Exo and M2-Exo.

first: Jinyang

last: Song

first: Gang

last: Su

last: Cheng

first: Xiaodong

last: Xie


title: Immune landscape of the affected brain in Rasmussen encephalitis

first: Geoffrey

last: Owens

address: 300 Stein Plaza Ste 562

institute: UCLA

summary: Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive brain atrophy. We used single cell RNA sequencing to define the types of immune cells in affected brain tissue removed to control seizures. Our analysis highlights the complexity of the immune landscape in brain areas affected by RE and supports the involvement of clonally expanded antigen experienced resident memory CD8 T cells in the etiology of the disease.

overall_design: Blocks of fresh resected brain tissue were obtained from three RE surgery cases and immune cells were isolated. Single cell RNA-sequencing was used to analyze the types of immune cells present in the affected brain tissue and the potential crosstalk between them.


title: Omics-aided design genome editing strategy for challenging immortalized cell models

city: Mölndal

first: Benjamin

last: Keith

address: Pepparedsleden 1

country: Sweden

institute: AstraZeneca

summary: CRISPR-Cas9 has become a popular genome editing tool for biomedical research and drug development due to its capability to enable precise correction or integration of genetic mutations in the genome. However, precise genome editing competency varies dramatically between cell types depending on their capabilities for DNA damage.  In this proof-of-concept study, we took the example of HepG2 and MCF7 to show that omics profiling identifies bottlenecks that are associated with poor precise knock-in (KI) efficiency in hard-to-engineer cells. These bottlenecks include previously described factors such as the predominance of non-homologous end joining (NHEJ) repair and impaired homologous recombination (HR) capability, but also reveals apoptotic priming status of the cells as a limiting factor. Upon further comparative analysis between HepG2 and MCF7 cells, we pinpointed and validated the proliferating cell nuclear antigen (PCNA) as a target to overexpress to enhance precise KI efficiency in MCF7. Overall, we describe how employing a multi-omics approach to characterize cell models of interest can facilitate an in-depth understanding of their editability molecular signature, empowering us to manipulate the activity of key pathways for precise editing, and therefore increase efficiency of desired editing outcomes.

overall_design: In this study we applied an omics profiling approach to investigate CRISPR-induced DDR in HepG2 (HRD score = 9) and MCF7 (HRD score = 61). Both cell types were electroporated with the same CRISPR ribonucleoprotein (RNP) complex (see “Transfections” section in the methods section of the manuscript) and cultured in separate plates to avoid cross-contamination. RNA  samples were collected 24 and 48 hours after electroporation. As a result, there are two hard-to-change factors in this study. To be able to compare between different cell lines and time points, we applied the split plot design, in which each plate is considered as a whole plot.

first: Patricia

last: Mendoza-Garcia

first: Xiang


title: Comprehensive transcriptome analysis of  the Mettl18-deficient embryos

city: Toyama

first: Jun-Dal

last: Kim

state: Toyama

address: 2630 Sugitani

department: Department of Complex Biosystem Research (CBR), Institute of National Medicine (INM)

institute: University of Toyama

summary: Histidine methylation is an evolutionarily conserved but poorly understood post-translational modification. METTL18 is known to catalyze histidine Nτ-methylation in vitro, yet its physiological functions in mammals remain unclear. In this study, we performed a comprehensive analysis of gene expression changes in embryos of wild-type and Mettl18-deficient mice using RNA sequencing (RNA-seq).

overall_design: mRNA profiles of the whole worm were generated by RNA sequencing using the NextSeq 500 (Illumina).

first: Akiyoshi

last: Fukamizu


title: GID/CTLH E3 ligase complex control cell fate programs for sexual development of Plasmodium falciparum

city: Melbourne

first: Danushka

middle: Sujeeva

last: Marapana

state: VIC

address: 1G Royal Parade

country: Australia

institute: The Walter and Eliza Hall Institute of Medical Research

summary: Transmission of the malaria parasite Plasmodium falciparum requires the formation of specialised sexual cells called gametocytes. A hallmark of P. falciparum gametocyte development is its long duration, during which the parasite undergoes dramatic cellular remodelling including morphological, physiological and metabolic changes which result in the formation of a transmission ready, stage V gametocyte. Here we show that the PfGID E3 ubiquitin ligase complex regulates critical gametocyte cell fate programs through the targeted ubiquitination of key proteins. Deletion of PfGID complex components leads to an arrest in gametocyte development and a loss of transmission to mosquitoes. PfGID governs gametocyte development by fine-tuning the protein levels of two substrates: the ZFP36 family RNAbinding protein GD1, and PfDPL, a cryptochrome-like protein. Our findings reveal that PfDPL regulates the expression of male-specific proteins early in gametocyte development that are essential for gametogenesis. In parallel to the PfDPL controlled cell fate program the RNA binding protein GD1 regulates transcripts crucial for gametocyte development by holding them in a state of translational repression. These findings illuminate the intricate molecular choreography underlying Plasmodium sexual development and provide insights into how single-celled eukaryotes execute cell-fate programs to navigate complex life cycles and adapt to diverse host environments.

overall_design: RNA-seq profiling of wild type IGP2 and ∆GID1/2/7/8/9 gametocytes at day 3,6,9 and 12 of development.

first: Peter

last: Hickey

first: Matthew

middle: W

last: Dixon

first: Alan

last: Cowman


title: Targeting Ubiquitin Signaling vulnerabilities in KEAP1-Inactivated Lung Cancer

first: Igor

last: Mačinković

department: 7Department for Immunity of Inflammation

institute: Medical Faculty Mannheim Heidelberg University

summary: Lung cancer cells rely on protein homeostasis regulators, particularly the ubiquitin-proteasome system (UPS), to sustain malignancy. Genetic alterations in UPS components, such as E3 ubiquitin ligases (E3s) and deubiquitinating enzymes (DUBs), are common and create context-dependent therapeutic dependencies. To investigate how these changes drive tumor formation, we conducted CRISPR screens on metabolically stressed murine lung cancer models and identified specific cancer vulnerabilities, including KEAP1. Although KEAP1 is frequently mutated in aggressive non-small cell lung cancers (NSCLC, ~15%), our findings reveal an unexpected proto-oncogenic role for KEAP1 in a genetically defined subset of NSCLC. Mechanistically, Keap1 deletion activated NRF2 and upregulated Aldh3a1. This led to elevated NADH/NAD⁺ ratios, triggered reductive stress, and suppressed tumor growth. Given the poor prognosis of KEAP1-mutated patients, combinatorial CRISPR dropout screens revealed druggable E3s and DUBs as Keap1-dependent co-vulnerabilities. Notably, depleting these co-dependencies such as the E3 ligases Herc2, Ubr4 and Huwe1 ablated the in vivo development of Keap1-inactivated tumors. We demonstrate that targeting the UPS represents an underexplored, promising therapeutic approach for patients with KEAP1-inactivated tumors, especially under metabolic stress.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for KPL, KP, and KPP primary murine lung tumor cell lines: KI696 (1µM) treatment vs. vehicle control (DMSO)

first: Varun

middle: J

last: Shah

first: Oliver

last: Hartmann

first: Martin

last: Wegner

first: Cristian

last: Prieto-Garcia

first: Rubina

last: Kazi

first: Viktoria

last: von Heyl zu Herrnsheim

first: Amin

last: Wanli

first: Bianka

last: Bohnacker

first: Koraljka

last: Husnjak

first: Dmitry

last: Namgaladze

first: Mathias

last: Rosenfeldt

first: Manuel

last: Kaulich

first: Markus

middle: E

last: Diefenbacher

first: Ivan

last: Dikic


title: Total RNA transcriptomic profiling of mouse thoracic and abdominal perivascular adipose tissue of mice with an adipocyte-specific deletion of PRDM16 and flox control mice [snRNA-seq]

city: New York

first: Wei

last: Wang

state: New York

address: 1230 York Ave.

department: Bioinformatics Resource Center

institute: The Rockefeller University

summary: Thoracic and abdominal perivascular adipose tissue (tPVAt and aPVAT) is in direct contact with the outer layer of the aorta. While tPVAT exhibits a thermogenic phenotype, aPVAT is mostly comprised of white adipocytes with a few scattered thermogenic adipocytes. To investigate the relevance of this change in adipocyte identity along the aorta, we used mice with an adipocyte-specific deletion of Prdm16 resulting in loss of thermogenic and gain of white adipocyte-like features and compare gene expression signature in these mice.

overall_design: Total mRNA RNAseq was performed on total RNA extracted  from PRDM16flox (controls) and PRDM16flox, AdipoQCre+ mice.

first: Mascha

last: Koenen

first: Thomas

last: Carroll

first: Paul

last: Cohen


title: CARM1-mediated hypoxanthine-enriched exosome biogenesis rewires inosine metabolism of CD8+ T cells and impairs their antitumor ability

city: Jinan

first: Fabao

last: Liu

state: Shandong

address: #44 wenhua xi road

institute: Shandong university

summary: Cancer cells engage in complex interactions with tumor infiltrating immune cells to overcome barriers to tumor progression. Targeting biogenesis of tumor-derived exosomes is a promising strategy for disrupting intracellular communication. Herein, we identify co-activator-associated arginine methyltransferase 1 (CARM1) as a key regulator of tumor-derived exosome biogenesis and metabolite sorting, thereby inhibiting CD8+ T cell-mediated antitumor immunity. Genetic ablation of CARM1 in breast cancer cells impairs the secretion of immunosuppressive exosomes, leading to enhanced CD8+ T cell infiltration, proliferation, and effector function in tumors. Mechanistically, CARM1 methylates apoptosis-linked gene-2 interacting protein X (ALIX) at Arg757, facilitating its interaction with endosomal sorting complex required transport (ESCRT) components, and promoting the biogenesis of tetraspanin-enriched exosomes. CARM1-dependent ALIX methylation enables selective packaging hypoxanthine into exosomes through direct binding to ALIX at the F676 pocket. Excess hypoxanthine disrupts inosine metabolism in the activated CD8+ T cells, inhibiting glycolysis, nucleotide synthesis, and effector cytokine production. Co-administration of CARM1 inhibitor with inosine significantly increases tumor infiltrating CD8+ T cell cytotoxicity, reduces exhaustion markers programmed cell death 1 and T cell immunoglobulin mucin 3 (PD-1+TIM-3+) expression and suppresses tumor growth. Collectively, the CARM1-ALIX-hypoxanthine axis functions as immunosuppressive mechanism in tumor growth, and targeting CARM1 combined with inosine supplement may represent a novel therapeutic regimen for breast cancer therapy.

overall_design: RNA-seg profling of wildtype CD8+ T cells treated with Glucose, Inosine and Inosine combined with hypoxanthine

first: Jilong

last: Yin

first: Xi

last: Hu


title: Early-stage Col8a2Q455K mutant mouse corneal endothelium Late-stage Col8a2Q455K mutant mouse corneal endothelium Early-stage wild-type mouse corneal endothelium Late-stage wild-type mouse corneal endothelium

city: Qingdao

first: Xintian

last: Zhao

address: shangma road,Qingdao,Shangdong,China

institute: Qingdao Eye Research Institute

summary: Col8a2 mutation is one of the genetic causes of Fuchs endothelial corneal dystrophy (FECD). The Col8a2Q455K homozygous mutant mouse serves as a disease model for FECD. Corneal endothelial cells were isolated from early-stage (≤ 2 months old) and late-stage (≥ 8 months old) Col8a2Q455K homozygous mutant mice and their age-matched wild-type controls. This study investigates transcriptomic alterations associated with FECD progression caused by the Col8a2 mutation.

overall_design: This study includes corneal endothelium samples from Col8a2Q455K homozygous mutant and wild-type mice at early (≤ 2 months) and late (≥ 8 months) disease stages. Each group contains three biological replicates. RNA was extracted from the corneal endothelium and subjected to paired-end RNA sequencing on the Illumina Nova6000 platform. The goal is to elucidate transcriptomic changes underlying the early and late phases of FECD caused by the Col8a2 mutation.

first: Haoyun

last: Duan

first: ZongYi

last: Li


title: H3K27ac and p300 cut&run experiment in G549 (Injury-response/Mesenchymal GSC) cell line

city: Toronto

first: Fatemeh

last: Molaei

state: Ontario

address: 160 College St. Room 830, Terrence Donnelly Centre for Cellular & Biomolecular Research

institute: University of Toronto

summary: EP300 was identified as potential regulator of Injury-response/Mesenchymal state in Glioblastoma stem cells. Our objective was to evaluate the effect of EP300_KO on H3K27Ac within the genome in Injury-response GSC. Moreover, we aimed to identify the p300 binding sites in Injury-response GSC  to further assess how it regulates the Injury-response state.

overall_design:
CUT&RUN experiment for histone modification H3K27ac in AAVS1 and EP300 KO G549 Cells
CUT&RUN experiment for p300 binding sites in WT G549 cells

first: Graham

last: MacLeod

first: Stephane

last: Angers