title: Dog aortic endothelial cells as a model for studying the effects of nanoplastics

city: Brescia

first: Martina

last: Tambassi

state: Italy

address: Via Bianchi, 9

department: Risk Analysis and Genomic Epidemiology Unit

country: Italy

institute: Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia-Romagna, VAT IT00284840170

summary: A growing concern regards plastic fragments mainly nanoplastics (NP). The present study was set up on aortic endothelial cells (CnAEOC) since dog is a model for translational medicine. Through fluorescence microscopy, we observed an interaction between NP and cells, demonstrating a localization at the cytoplasmic level. Furthermore, the data collected show a disruption of both cell proliferation and metabolic activity. The results also show the induction of oxidative stress. In detail, NP caused an increase in the levels of ROS production and an inhibition of enzymatic defense systems. On the contrary, there was no alteration of the non-enzymatic defense mechanism. The analysis conducted to evaluate a possible induction of autophagy, a survival mechanism implemented by cells, following exposure to NP reported the absence of autophagy involvement in the model analyzed. Finally, investigations were conducted regarding the involvement of NP in gene expression processes. Both RNA-seq and RT-PCR did not highlight differentially expressed genes in treated cells.

overall_design: RNA-seq profiles of dog aortic endothelial cells treated with polystyrene nanoplastics 25 µM for 48 hours and untreated

first: Giuseppina

last: Basini

first: Simona

last: Bussolati

first: Francesca

last: Grasselli

first: Anna

last: Scalori

first: Erika

last: Scaltriti

first: Stefano

last: Grolli

first: Roberto

last: Ramoni

first: Melissa

last: Berni


title: SUMO E3 ligase SIZ1 sustains nuclear condensate-mediated immune activation in plants

status: Public on Sep 08 2025

city: Berkeley

first: ENRICO

last: CALVANESE

state: CA

address: Koshland Hall 371

department: Plant & Microbial Biology

country: USA

institute: University of California, Berkeley

type: Expression profiling by high throughput sequencing

summary: SIZ1, a major plant SUMO E3 ligase, has diverse roles in development and immunity. Although loss-of-function studies have positioned SIZ1 as a negative immune regulator, the pleiotropic effects of its broad substrate repertoire may obscure its core function. Here we report that SIZ1 overaccumulation unexpectedly triggers robust pro-immune responses and cell death, dependent on its E3 ligase activity. We demonstrate that SIZ1 functionally converges on the MOS4-Associated Complex (MAC), a key immune signaling module, with both SIZ1 and the immune receptor SNC1 recruited to MAC-dependent nuclear condensates (MDNCs) upon pathogen challenge. These condensates serve as essential platforms for potentiating immune activation and cell death. Within the MDNC, SIZ1 promotes SUMOylation and stabilizes MAC components, thereby sustaining MDNC integrity during immune responses. Our findings reveal a previously unrecognized pro-immune role for SIZ1 and establish a mechanistic link between SUMOylation, MAC stability, and condensate-mediated immune signaling in plants.

overall_design:
RNA-Seq profiling of 4-week-old soil grown Col-0, siz1-2 loss-of-function mutant and SIZ1 overexpression mutant.

For RNA-Seq, four-week-old WT and siz1-2 pSIZ1:SIZ1g-GFP seedlings were collected, and total RNA was extracted using the Direct-zol RNA Miniprep kit. Library construction, quality control, and RNA sequencing were performed by Novogene (https://en.novogene.com/) on an Illumina NovaSeq X Plus Series (PE150) platform. The raw RNA-seq reads generated were filtered using trim-galore v0.6.6 with the default parameters to remove low-quality reads. Cleaned data were then mapped to the Arabidopsis thaliana genome TAIR10 using HISAT2 v2.2.051 with default parameters. BAMs were sorted by Samtools v1.9.52.

first: Yangnan

last: Gu

first: Min

last: Jia

first: Enrico

last: Calvanese


title: A stem-loop RNA RIG-I agonist induces immunogenic death and vascular remodeling to potentiate cancer immunotherapy

status: Public on Sep 09 2025

city: Nashville

first: Shristi

last: Shrestha

address: 2213 Garland Ave

institute: Vanderbilt University

summary: The immunoreceptor retinoic acid-induced gene-I (RIG-I) is a promising target molecule for stimulating antitumor innate immunity. In this study, we evaluated the possible mechanisms of RIG-I signaling to make tumors immunogenic in the Renca cancer model. RIG-I is expressed in nucleated cells, including tumor cells, and its activation induces potent CD8 and natural killer (NK) cell responses. We used bulk RNA sequencing to uncovermolecular targets and mechanisms of action behind anti-tumor activity.

overall_design: Mice were randomized into treatment and PBS (vehicle) groups when tumors reached 100 to 150 mm3. Intratumoral injection of nanoparticles containing 3pRNA RIG-I agonist or PBS was performed at 48-hour intervals for a total of 3 treatments. Tumors (5 mice in each group) were harvested after 24 hours of last treatment.

first: John

middle: T

last: Wilson

first: Vijaya

last: Bharti


title: HIF1A regulated genes in MCF10A cells after treatment with Oncostatin M or control ligands

city: Portland

first: Laura

middle: M

last: Heiser

state: OR

address: 2730 S Moody Ave

department: Biomedical Engineering

institute: Oregon Health and Science University

summary: We employed a single-cell RNA sequencing approach to study the role of Oncostatin M (OSM) in inducing collective cell migration in MCF10A cells and its upregulation of HIF1A. To identify HIF1A-dependent transcriptional programs, we stably knocked down HIF1A using shRNA and treated cells with OSM.

overall_design: MCF10A breast epithelial cells stably expressing shHIF1A or control shSCR were grown in vitro and treated with Oncostatin M (OSM), epidermal growth factor (EGF), or a combination of EGF and interferon gamma (IFNG) for 24 hours prior to single-cell RNA sequencing.

first: Ian

middle: C

last: McLean

first: Sean

last: Gross

first: Tiera

last: Liby

first: Mark

middle: A

last: Dane

first: Daniel

middle: S

last: Derrick


title: Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus [RNA-Seq neurosphere]

city: Beijing

first: Ligong

last: Chen

address: Shuangqing Road No.30

country: China

institute: tsinghua university

summary: Iron transporters are essential for maintaining cellular iron homeostasis. Among them, SLC22A17 mediates lipocalin-2 (LCN-2)-dependent iron transport, but its precise role in the brain remains unclear. Here, we show that Slc22a17 is critical for postnatal neurogenesis by regulating hippocampal iron balance. Conditional knockout of Slc22a17 in the murine brain causes early postnatal lethality, growth retardation, neural stem cell apoptosis, and cognitive deficits, largely due to oxidative stress from iron overload. Mechanistically, Slc22a17 interacts with p62 to modulate Nrf2 activity. Its loss aberrantly activates the Nrf2/HO-1 pathway, disrupting iron efflux and promoting accumulation of reactive oxygen species (ROS). These findings establish Slc22a17 as a key regulator of neuronal development and a potential therapeutic target for neurological disorders linked to iron dysregulation.

overall_design: RNAseq of neurospheres derived from wild-type (WT) and Slc22a17-conditional knockout (cKO) mice

first: Lei

last: Tao

first: Long

last: Teng


title: Mechanical unloading triggers glutamine influx and catabolism to suppress osteoclast apoptosis

first: Wenjie

last: Shu

address: Taiping Road 27

institute: Beijing Institute of Radiation Medicine

summary: External mechanical stimuli are pivotal for the maintenance of bone homeostasis via enhancing bone formation and inhibiting bone resorption. Lack of mechanical loading during prolonged bed rest or exposure to long-term microgravity environment in space leads to a rapid decline in bone mass and bone strength. Osteoblast lineage cells are capable of sensing and transmitting mechanical signals through a variety of pathways. However, the mechanisms by which osteoclasts perceive and respond to mechanical disturbances remain largely unclear. Here, through integrating the data of single-cell transcriptome, metabolome, proteome and ubiquitinome of bone tissues from hindlimb unloading (HLU) and control mice, we clarify that in the absence of mechanical force, osteoclasts are characterized by significant increase in Gln influx and catabolism, as well as suppression of intrinsic apoptosis.

overall_design: To investigate the mechanism of bone loss in weightlessnessrole, we utilized control and hindlimb unloading mice. To more fully understand the response of different cell types in bone tissue to weightlessness, we performed single-cell RNA-sequencing of control and hindlimb unloading mice at postnatal day 28.

first: Yi

last: Ding

first: Fan

last: Tong

first: Mingqiu

last: Liu

first: Pin

last: Yang


title: Polystyrene MiPolystyrene Microplastics Induce Radiotherapy Resistance in Lung Cancer by Suppressing Ferroptosis through NF-κB Activationcroplastics Induce Radiotherapy Resistance in Lung Cancer by Suppressing Ferroptosis through NF-κB Activation

city: Yangzhou City

first: jin

last: li

address: No.88, Daxue South Road

institute: Yangzhou University

summary: Aims: Polystyrene microplastics (PS-MPs) are emerging environmental pollutants, but their impact on lung cancer treatment remains unclear. This study investigates how PS-MPs affect radiotherapy efficacy in lung cancer, focusing on their role in ferroptosis regulation and NF-κB pathway activation. Results: PS-MPs were rapidly internalized by lung cancer cells and remained detectable across multiple passages. Exposure to PS-MPs promoted lung cancer cell proliferation, increased mitochondrial length, and elevated Ki67 and c-Myc expression. Following ionizing radiation, PS-MPs significantly attenuated radiation-induced ferroptosis, as evidenced by reduced mitochondrial damage, lipid peroxidation, and GSH depletion. Transcriptomic analysis revealed that PS-MPs activated the NF-κB pathway, leading to increased phosphorylation of IKKβ, IκBα degradation, and enhanced nuclear translocation of NF-κB. In vivo, PS-MPs accumulated in lung tumor-bearing mice, reducing radiotherapy efficacy by increasing tumor volume and weight while decreasing survival rates. Knockdown of NF-κB restored ferroptosis sensitivity and mitigated PS-MPs-induced radioresistance, confirming the NF-κB-dependent inhibition of ferroptosis. Innovation and Conclusion: This study provides the first evidence that PS-MPs impair radiotherapy efficacy in lung cancer by suppressing ferroptosis via NF-κB activation. Unlike previous research focusing on microplastic toxicity in normal tissues, our findings highlight their oncological impact and potential role as an environmental factor influencing cancer therapy resistance. These results emphasize the need for further investigation into microplastics as emerging disruptors of redox homeostasis in oncology and their broader implications for environmental and cancer research.

overall_design: Add PS MPs (20 mg/mL) to A549 cells and collect the cells for transcriptome analysis after 48 hours

first: Heng

last: Zhou

first: Yali

first: Yanxian

last: Ren

first: Ningzu

last: Jiang

first: Ao

last: Sun

first: Song

last: Wu

first: Tianyi

last: Zhu

first: Jin

last: Li

first: Chenghao


title: RNA-seq profiling of cervical tissue in a lipopolysaccharide-induced rat model of preterm birth

city: Shanghai

first: Yijie

last: Gao

address: 150 Jimo Road, Pudong New Area

department: Department of Obstetrics

institute: Tongji University Dongfang Hospital

summary: This study aims to investigate the alterations in cervical remodeling and the underlying molecular mechanisms in a lipopolysaccharide (LPS)-induced rat model of preterm birth through RNA sequencing. The results demonstrate that LPS triggers preterm birth by activating inflammatory and bradykinin pathways, disrupting extracellular matrix stability, and promoting cervical insufficiency.

overall_design: On gestational day 17, pregnant Sprague-Dawley rats were intraperitoneally administered with either 100 μg/kg LPS or an equal volume of PBS. Cervical tissues were collected 12 hours post-injection for RNA sequencing, with four biological replicates per group.

first: Ming

first: Ping

last: Ru

first: Lulu

last: Meng

first: Yun

first: Xiaotian

last: NI

first: Ling

last: Wang


title: Integrated epigenetic and genetic programming of primary human T cells [WGBS]

city: San Francisco

first: Laine

last: Goudy

address: 400 Parnassus Ave

institute: University of California, San Francisco

type: Methylation profiling by high throughput sequencing

summary: Targeted epigenetic engineering of gene expression in cell therapies would allow programming of desirable phenotypes without many of the challenges and safety risks associated with double strand break-based genetic editing approaches. Here, we develop an all-RNA platform for efficient, durable, and multiplexed epigenetic programming in primary human T cells, stably turning endogenous genes off or on using CRISPRoff and CRISPRon epigenetic editors. We achieve epigenetic programming of diverse targeted genomic elements without the need for sustained expression of CRISPR systems. CRISPRoff-mediated gene silencing is maintained through numerous cell divisions, T cell stimulations, and in vivo adoptive transfer, avoiding cytotoxicity or chromosomal abnormalities inherent to multiplexed Cas9-mediated genome editing. Finally, we successfully combined genetic and epigenetic-engineering using orthogonal CRISPR Cas12a/dCas9 systems for targeted CAR knockin and CRISPRoff silencing of therapeutically relevant genes to improve preclinical CAR T cell-mediated in vivo tumor control and survival.

overall_design: Whole genome bisulfite sequences of human primary T cells that have been treated with CRISPRoff mRNA and sgRNAs targeting genes of interest or a NTC. Cells were collected from 2 independent donors and technical replicates were performed for each donor.

first: Alvin

last: Ha

first: Ashir

last: Borah

first: Jennifer

last: Umhoefer

first: Lauren

last: Chow

first: Carinna

last: Tran

first: Aidan

last: Winters

first: Alexis

last: Talbot

first: Rosmely

last: Hernandez

first: Zhongmei

first: Sanjana

last: Subramanya

first: Abolfazl

last: Arab

first: Nupura

last: Kale

first: Jae Hyun

middle: J

last: Lee

first: Joseph

last: Muldoon

first: Chang

first: Ralf

last: Schmidt

first: Philip

last: Santangelo

first: Julia

last: Carnavale

first: Justin

last: Eyquem

first: Brian

middle: R

last: Shy

first: Alex

last: Marson

first: Luke

last: Gilbert


title: Integrated epigenetic and genetic programming of primary human T cells [RNA-seq]

first: Laine

last: Goudy

overall_design: RNA-sequencing of human primary T cells that have been treated with CRISPRoff mRNA and sgRNAs targeting genes of interest or a NTC. Samples also include primary human T cells that have been treated with nuclease active Cas9 mRNA and sgRNAs targeting genes of interest or a NTC.

first: Alvin

last: Ha

first: Ashir

last: Borah

first: Jennifer

last: Umhoefer

first: Lauren

last: Chow

first: Carinna

first: Aidan

last: Li

last: Liu


title: RNA-seq of dTAG-NUDT21 HCT116 cells treated with DMSO+JTE-607 or dTAGV1+JTE-607.

city: Pittsburgh

first: Hun-Way

last: Hwang

state: PA

address: 3550 Terrace Street

department: Department of Pathology

institute: University of Pittsburgh

summary: We performed RNA-seq on dTAG-NUDT21 HCT116 cells treated with DMSO+JTE-607 or dTAGV1+JTE-607 for 48 hours with 4 biological replicates

overall_design: We assessed differential RNA expression by treatment conditions (DMSO+JTE-607 vs. dTAGV1+JTE-607)


title: scRNAseq data of gingival CD11b+ cells from 10% Tet2+/+ BMT and 10% Tet2-/- BMT mice

city: Chengdu

first: Hui

last: WANG

state: Sichuan

address: No.14,3Rd Section Of Ren Min Nan Rd

department: periodontics

institute: Sichuan University

summary: BM cells were isolated from C57BL/6 (CD45.2) Tet2–/– mice and Tet2+/+ littermates, as well as from congenic C57BL/6.SJL (CD45.1) mice (all genotypes purchased from JAX). lethally irradiated (9.5 Gy) CD45.1 mice received 10% Tet2–/– CD45.2 BM cells and 90% WT CD45.1 BM cells (2x105 Tet2–/– CD45.2 BM cells and 18x105 WT CD45.1 BM cells; total of 2x106 BM cells/recipient mouse). This group was designated ‘10% Tet2–/– BMT’ (experimental). For the control group that was designated ‘10% Tet2+/+ BMT’, lethally irradiated (9.5 Gy) CD45.1 mice received 10% Tet2+/+ CD45.2 BM cells and 90% WT CD45.1 cells (2x105 Tet2+/+ CD45.2 BM cells & 18x105 WT CD45.1 BM cells, thus exclusively TET2-sufficient cells; total of 2x106 BM cells/recipient mouse). At 12 weeks post-BMT (when there is complete reconstitution of hematopoiesis from transplanted long-term HSCs), ‘10% Tet2–/– BMT’ and ‘10% Tet2+/+ BMT’ mice either received no further treatment (and examined for natural periodontal bone loss) or were subjected to LIP for 5 days.

overall_design: At 12 weeks post-transplantation, both groups of recipient mice (10% Tet2–/– BMT and 10% Tet2+/+ BMT) were subjected to LIP for 5 days.  CD45.2+CD11b+ (from 10% Tet2–/– BMT) and CD45+CD11b+ (from 10% Tet2+/+ BMT) cells from the gingiva of mice were sorted using a FACSAria™ sorter.

last: Wang


title: Bulk RNA-seq study 9- RNA-seq of male KOLF2.2J hiPSC-derived cortical brain organoids homozygous null for eight different transcription factors.

city: Hinxton

first: MorPhiC

last: Consortium

address: Wellcome Genome Campus

country: United Kingdom

institute: EMBL-EBI

summary: This study aims to phenotype iPSC-derived cortical brain organoids that contain homozygous null alleles for transcription factors expressed in the early neuroectoderm. Null alleles were generated using insertion of a premature termination codon with frameshift (PTC+1). RNA-seq data was generated at the indicated day post initiation of differentiation from hiPSCs. The study included the homozygous null alleles for the following transcription factors: EMX2, FOXG1, POU3F2, SOX1, HES5, SOX21, POU3F1 and SP8. This analysis provided insight into the impact of loss of function for these transcription factors in cortical brain organoid differentiation.

overall_design: The study involved the generation of RNA-seq on 39 samples. Different time points of differentiation to cortical brain organoids were chosen according to the initiation of the transcription factor in wildtype cells within this differentiation scheme. Three biological replicates were run for gene. Additionally, three biological replicates were run of wildtype KOLF2.2J cells (the parental male cell line in which the KOs were generated) under the same differentiation conditions in the different time points. This comprehensive design allowed for a robust analysis of the effects of transcription factor manipulation on brain organoid formation.

first: Juliana

last: Diniz

first: Bill

last: Skarnes

first: Paul

last: Robson


title: A portable poison exon for small molecule control of mammalian gene expression

city: New York

first: Samie

last: Jaffrey

state: New York

address: 1300 York Ave

department: Pharmacology

institute: Weill Cornell Medicine

summary: The ability to precisely control gene expression using small molecule drugs is a valuable tool in research and has significant therapeutic potential. However, existing systems are often limited by the toxicity of the drugs and the need to alter gene sequences or endogenous regulatory elements. Here, we introduce Cyclone (acyclovir-controlled poison exon), an acyclovir-controlled poison exon cassette that can be used for small molecule control of both transgene and endogenous gene expression. Cyclone is a portable “intron-poison exon-intron” element that can be inserted into nearly any gene and is completely removed upon acyclovir treatment, leaving the native transcript intact. Cyclone offers tunable, reversible gene expression with nearly undetectable background and a ~295-fold activation. We also present Pac-Cyclone, a cassette that simplifies the generation of cell lines with acyclovir-controlled endogenous gene expression. Finally, we demonstrate the programmability of Cyclone, underscoring its potential for developing diverse genetic circuits controlled by various ligands.

overall_design: HEK293T cells (ATCC CRL-3216) were maintained at 37 °C in a humidified 5 % CO₂ incubator in Dulbecco’s Modified Eagle Medium (DMEM, Thermo 11995065) supplemented with 10 % heat-inactivated fetal bovine serum, 100 U mL⁻¹ penicillin, and 100 µg mL⁻¹ streptomycin. Cells were sub-cultured at 70–80 % confluence by trypsinisation, counted with a TC20™ Automated Cell Counter, and seeded into 10 cm dishes at 2 × 10⁶ cells dish⁻¹ 24 h before drug treatment. Six conditions in biological triplicate: (1) 250uM DMSO (vehicle for 250uM acyclovir), (2) 100nM DMSO (vehicle for 100nM branaplam), (3) acyclovir 250 uM, (4) branaplam 100 nM, (5) 500uM DMSO, (6) acyclovir 500 uM. Drugs or vehicle were added directly to culture medium; cells were incubated 72 h before harvest. Total RNA was isolated with TRIzol LS (Invitrogen 10296010) according to the manufacturer’s instructions. RNA pellets were resuspended in RNase-free H₂O, treated with 1 U DNase I (NEB M0303) 10 min at 37 °C, and purified with the RNA Clean & Concentrator-25 kit (Zymo R1018). RNA integrity (RIN > 9) was verified on an Agilent 2100 Bioanalyzer. RNA-seq libraries were prepared with the Illumina TruSeq Stranded Total RNA Library Preparation Kit (with rRNA depletion) at the Weill Cornell Medicine Genomics Resources Core Facility. Sequencing was performed on an Illumina NovaSeq X Plus platform, generating ≥70million 150 bp paired-end reads per sample. The 500 µM acyclovir group generated ≥ 32 million 150 bp paired-end reads per sample.

first: Hou

last: Qian

first: Oleynikov

last: Maxim

first: Mei

last: Xiaohan

first: Dong

last: Linghao

first: Hagen

last: Timo

first: Jaffrey

last: Samie


title: The impact of Hnrnpl deficiency on transcriptional patterns of developing muscle cells

city: Minneapolis

first: Peter

middle: B

last: Kang

state: MN

address: 2101 6th Street SE

department: Neurology

institute: University of Minnesota

summary: Heterogeneous nuclear ribonucleoproteins (hnRNPs) bind to RNA, regulating gene expression and splicing. HnRNP L contributes to muscle development and the pathogenesis of myotonic dystrophy. We hypothesized that hnRNP L regulates muscle expression and splicing patterns. Using nanopore long read transcriptome sequencing and qPCR analyses, we investigated the impact of Hnrnpl knockdown on myoblasts and knockdown of the orthologous gene smooth in Drosophila. Notch signaling genes and muscle-related genes were dysregulated in both models. Several genes had altered splicing patterns, including Lamp2, Fhl1, and Dtna. Our findings indicate that hnRNP L regulates muscle gene transcription. We demonstrate the capabilities of long read transcriptome sequencing to study muscle development. Future studies could examine therapeutic implications of hnRNP L regulation for muscle diseases.

overall_design: Nanopore long-read sequencing performed on extracted RNA of two replicates each of Hnrnpl-shRNA treated C2C12 myoblasts and scrambled control cells.

first: Hannah

last: Littel

first: Mekala

last: Gunasekaran

first: Audrey

middle: L

last: Daugherty

first: Natalya

last: Wells

first: Johnnie

last: Turner

first: Christine

last: Bruels

first: Christina

last: Pacak

first: Isabelle

last: Draper


title: SETBP1 variants outside the degron disrupt DNA-binding, transcription and neuronal differentiation capacity to cause a heterogeneous neurodevelopmental disorder [fibroblast]

city: Nijmegen

first: Maggie MK

last: Wong

address: Wundtlaan 1

department: Language and Genetics

country: Netherlands

institute: Max Planck Institute for Psycholinguistics

summary: Different types of germline de novo SETBP1 variants cause clinically distinct and heterogeneous neurodevelopmental disorders: Schinzel-Giedion syndrome (SGS, via missense variants at a critical degron region) and SETBP1-haploinsufficiency disorder. However, due to the lack of systematic investigation of genotype-phenotype associations of different types of SETBP1 variants, and limited understanding of its roles in neurodevelopment, the extent of clinical heterogeneity and how this relates to underlying pathophysiological mechanisms remain elusive. This imposes challenges for diagnosis. Here, we present a comprehensive investigation of the largest cohort to-date of individuals carrying SETBP1 missense variants outside the degron region (n=18). We performed thorough clinical and speech phenotyping with functional follow-up using cellular assays and transcriptomics. Our findings suggest that such variants cause a clinically and functionally variable developmental syndrome, showing only partial overlaps with classical SGS and SETBP1-haploinsufficiency disorder. We provide evidence of loss-of-function pathophysiological mechanisms impairing ubiquitination, DNA-binding, transcription, and neuronal differentiation capacity and morphologies. In contrast to SGS and SETBP1 haploinsufficiency, these effects are independent of protein abundance. Overall, our study provides important novel insights into diagnosis, patient care, and aetiology of SETBP1-related disorders.

overall_design:
RNA-seq profiling of human skin fibroblasts from healthy controls and patients with SETBP1-related disorders. Three technical replicates were included per cell line and are listed as CELL LINE NAME_1, CELL LINE NAME_2, CELL LINE NAME_3

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

first: Maggie

first: Simon

middle: E

last: Fisher


title: Platelet Activation and a Platelet Biosignature Associates with Enhanced Cardiovascular Risk in Patients with Controlled Psoriasis.

city: New York City

first: Florencia

last: Schlamp

address: 435 East 30th Street

institute: NYU Langone Health

summary: The underlying mechanisms of atherosclerosis and strategies identifying high cardiovascular (CV) risk in psoriasis are incompletely understood. Platelet activity is increased in psoriasis and induces vascular dysfunction. We investigated the platelet phenotype and platelet transcriptome as one potential mechanism to explain CV risk in psoriasis. Psoriasis and controls underwent platelet aggregation and activation studies and platelet RNA sequencing to generate a psoriasis platelet transcriptomic score. The relationship between the platelet transcriptomic score and CV risk was assessed by arterial stiffness, coronary calcium, and longitudinally in an independent cohort of high CV-risk individuals undergoing lower extremity arterial revascularization (LER).

overall_design: Platelet RNA-seq expression profiling of 52 patients with psoriasis and 39 controls

first: Michael

last: Garshick

first: Kamelia

last: Drenkova

first: Filipp

last: Kazatsker

last: Boothman

first: Matthew

last: Muller

first: Elliot

last: Luttrell-Williams

first: Kristen

last: Lo Sicco

first: Andrea

last: Neimann

first: Jose

middle: U

last: Scher

first: Brittany

last: Weber

first: Joel

last: Gelfand

first: James

last: Krueger

first: Jill

last: Buyon

first: Jeffrey

last: Berger


title: Clonal lineage tracing of innate immune cells in human cancer

first: Caleb

last: Lareau

address: 417 E 68th St, Zuckerman - ZRC 1132

institute: Memorial Sloan Kettering

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Innate immune cells constitute the majority of the tumor microenvironment (TME), where they mediate both natural anti-tumor immunity and immunotherapy responses. While single-cell T- and B-cell receptor sequencing has provided fundamental insights into the clonal dynamics of human adaptive immunity, the lack of appropriate tools has precluded similar analysis of innate immune cells. Here, we developed a method leveraging somatic mitochondrial DNA (mtDNA) mutations to reconstruct clonal lineage relationships between single cells across native human tissues. We jointly sequenced single-cell transposase-accessible chromatin and mtDNA to profile 124,958 cells from matched tumor, non-involved lung tissue (NILT) with peripheral blood of early-stage non-small cell lung cancer (NSCLC) patients, as well as 93,757 cells from matched tumor and peripheral blood of ovarian cancer patients. Our single-cell concomitant profiling of lineage and cell states of thousands of immune cells resolved clonality across cell types, tissue sites, and malignancies. By resolving clonal populations across innate immune subtypes, we demonstrated that TME-resident myeloid subsets, including macrophages and type 3 dendritic cells (DC3), are clonally linked to both circulating and tissue-infiltrating monocytes. Further, we identified distinct DC-biased and macrophage-biased myeloid clones, enriched in the tumor and NILT, respectively, and found that their circulating monocyte precursors exhibit distinct epigenetic profiles, suggesting that myeloid differentiation fate may be predetermined before TME infiltration. These results delineate the clonal pathways of intratumoral myeloid cell recruitment and differentiation in human cancer and suggest that remodeling of the tumor myeloid compartment may be peripherally programmed.

overall_design: Human tumors and tissue samples were resected and processed for single-cell genomics library preparation.

first: Vincent

last: Liu

first: Ansuman

last: Satpathy


title: Tissue localization of Natural Killer Cell cells dictates surveillance of lung metastasis

city: Zurich

first: Marijne

last: Vermeer

address: Winterthurerstrasse 190

country: Switzerland

institute: University of Zurich

summary: The lung is a common metastatic site for various cancer types. Successful immune surveillance of lung metastasis depends on Natural Killer (NK) cells, but the underlying mechanisms are elusive. Here, we show that the pulmonary vasculature recruits and maintains highly cytotoxic and differentiated CD11bhigh NK cells through the integrins Lymphocyte Function-associated Antigen 1 (LFA-1) and Very Late Antigen (VLA-4). These NK cells rapidly eradicate metastasizing tumor cells within the vasculature. However, after the initial clearing phase, pulmonary NK cells fail to track extravasated tumor cells and remain intravascular, outside of the emerging nodules. In contrast, metastatic nodules are preferentially infiltrated with bloodborne and less differentiated CD27high NK cells. Within the metastatic lung, CD11bhigh NK cells undergo a rapid impairment of their migratory and cytotoxic features, while the intranodular CD27high subset transitions towards a transforming growth factor β (TGF-β)-driven state with reduced capacity to persist in the tumor tissue. Our findings demonstrate that the compartmentalization of NK cells is key for effective tumor cell surveillance in lung metastasis and that the use of TGF-β-resistant CD27high NK cells might be a novel strategy to enhance local anti-tumor activity.

overall_design: Lungs were dissociated and Live NK1.1+NKp46+  cells were sorted from both lungs and blood. Lung and blood NK cells were distinguished with unique barcodes (Totalseq B0304 and B0306, Biolegend)  before scRNA-seq using 10x Genomics platform.


title: SETBP1 variants outside the degron disrupt DNA-binding, transcription and neuronal differentiation capacity to cause a heterogeneous neurodevelopmental disorder [induced neurons]

first: Maggie MK

last: Wong

overall_design:
RNA-seq profiling of induced neurons generated from human skin fibroblasts from healthy controls and patients with SETBP1-related disorders. Three biological replicates, i.e. differentiation experiments, were included.

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

first: Maggie

first: Simon

last: Fisher


title: miRNA Accumulation Correlates with Increased Phloem Cell Proliferation in Tomato hawaiian skirt Mutants

city: Tsukuba

first: Fabien

last: Lombardo

address: 1-1, Tennodai 1-Chōme

country: Japan

institute: The University of Tsukuba

type: Non-coding RNA profiling by high throughput sequencing

summary: The cambium is the meristem responsible for production of plant vascular tissues, the xylem and phloem, during plant radial growth. The tomato hws mutant exhibits miRNA accumulation and produces a markedly enlarged phloem, suggesting a role for miRNAs in regulating vascular development. This study aims to identify the accumulated miRNAs associated with the vascular phenotype in hws mutants Key miRNAs, including miR319 and miR164, were identified as highly accumulated in the mutant pedicels, with predicted targets linked to meristematic activity.

overall_design: The distal parts of pedicels, from above the abscission zone to below the calyx, of 10-DAA WT and hws-1 fruits were collected. Five pedicel segments were bulked into one sample. Total RNA was extracted  and three biological replicates for each line were sequenced using a Illumina NovaSeq X Plus platform at a depth of one million-read per sample. Raw sequence data was analyzed with the sRNAminer pipeline with default settings.

first: Tarek

last: El mestari

first: Thomas

last: Kirat

first: Muhammad

middle: I

last: Jondah

first: Julie

last: Marsaudon

first: Norbert

last: Bollier

first: Chiaki

last: Matsukura


title: Differential chromatin accessibility, gene expression and mRNA splicing between developing cochlear inner and outer hair cells [ATAC-Seq]

city: Chicago

first: Jaime

last: Garcia-Anoveros

state: IL

address: 303 E Chicago Ave, Ward 10-070, Chicago, IL 60657

department: Anesthesiology

institute: Northwestern University

summary: The mammalian cochlea has two types of low abundance and highly specialized inner (IHC) and outer (OHC) mechanosensory hair cells. Their malfunction or death are common causes of congenital and acquired deafness. We separately collected developing IHCs and OHCs to identify their mRNAs and chromatin state. We examined their transcriptomes by RNA-seq to reveal differences in gene expression and alternative mRNA splicing. We examined their chromatin conformation by ATAC-seq to reveal open vs closed promoter and enhancer elements. Combining both approaches we find that developing IHCs and OHCs have differentially accessible promoters in differentially expressed genes, differ in both levels of gene expression, extent of mRNA splicing and transcription start sites, and utilize unique promoters and mRNA isoforms absent in other cell types. We provide a resource for the identification of promoter and mRNA isoforms of every gene expressed by IHCs or OHCs.

overall_design: ATAC-seq profiling of wild type inner and outer hair cells from neonatal mouse cochlea.

first: Chuan Zhi

last: Foo

first: Anne

last: Duggan

first: Elizabeth

last: Bartom

first: Litao

last: Tao

last: García-Añoveros


title: Differential chromatin accessibility, gene expression and mRNA splicing between developing cochlear inner and outer hair cells [RNA-Seq]

overall_design: RNA-seq profiling of wild type inner and outer hair cells from neonatal mouse cochlea.


title: Xcr1+ type 1 conventional dendritic cells are essential mediators for atherosclerosis progression

city: Xinxiang

first: Tianhan

last: Li

state: Henan

address: No.601, Hualan Road

institute: Xinxiang Medical University

summary: Atherosclerosis is characterized by lipid accumulation within plaques, leading to foam cell formation and inflammatory response within the aortic lesions. Lipid disorders have been extensively investigated, however the cellular and molecular mechanisms that trigger the inflammatory response in atherosclerotic plaques remain far from being fully understood. Xcr1+ cDC1 cells are newly identified antigen-presenting cells in activating immune cells. However, the role of cDC1 cells in atherosclerosis development remains highly controversial. We first confirmed the presence of cDC1 within human atherosclerotic plaques and discovered a significant association between the increasing cDC1 numbers and atherosclerosis progression in mice. Subsequently, we established Xcr1Cre-Gfp Rosa26LSL-DTA Apoe–/– mice, a novel and complex genetic model, in which cDC1 was constitutively depleted in vivo during atherosclerosis development. Intriguingly, we observed a notable reduction in atherosclerotic lesions in hyperlipidemic mice, alongside suppressed T cell activation of both CD4+ and CD8+ subsets in the aortic plaques. Notably, aortic macrophages and serum lipid levels were not significantly changed in the cDC1-depleted mice. Single-cell RNA sequencing revealed heterogeneity of Xcr1+ cDC1 cells across the aorta and lymphoid organs under hyperlipidemic conditions. As Xcr1 is the sole receptor for Xcl1, we next explored to target Xcr1+ cDC1 cells via Xcl1 by establishing Xcl1–/–Apoe–/– mice. Xcl1–/–Apoe–/– mice exhibited decreased atherosclerotic plaque formation and reduced aortic cDC1 accumulation, indicating that Xcl1 contributes to cDC1-mediated atherosclerotic lesion development. Our results reveal crucial roles of cDC1 in atherosclerosis progression and provide insights into the development of immunotherapies by targeting cDC1 through Xcl1.

overall_design: Eight-week-old male Apoe–/– mice were fed with 20-week ND or HFD. The single cell suspension of spleen, lymph node and aorta were obtained according to the flow cytometry analysis section. Single cell suspension from spleens and lymph nodes were firstly removed the CD5+, CD19+ and CD11b+ cells via SAV conjugated beads. Then two million live cells from spleen and lymph node were stained with mix1 (CD45.2-PE-Cy7, CD11c-PE-Cy5.5, CD172α-FITC, MHCII- APC-eFluor780 and Xcr1-APC), and all cells from aorta were stained with mix2 (CD45.2-PE-Cy7, CD11b-super bright 600, CD11c-PE-Cy5.5, MHCII- FITC, CD3- Alexa Fluor 700, CD19- Alexa Fluor 700, Ly6G- Alexa Fluor 700 and Xcr1-APC) for 30 minutes at 4 °C. After washing with 1 mL FACS buffer two times, cells from different organs were stained with different anti-CD45 antibodies conjugated with barcode oligos from BD™ Ms Single Cell Sample Multiplexing Kit (BD Bioscience, Cat: 633793). Finally, cells were resuspended with Sytox blue and CD11c+ MHCII+ Xcr1+ cells were sorted and subjected to the BD Rhapsody Express system. Then cDNA and sample tag libraries were built with BD Rhapsody whole transcriptome amplification (WTA) reagent kit (BD Bioscience, Cat: 633733, 633773, 633801, 664887) following manufacturer’s instructions, and sequenced on an illumine Novaseq 600 sequencer. Pair-end Fastq files of sample tag and WTA data were processed via BD RhapsodyTM analysis pipeline v2.0, and the resultant dataset was mainly analysis using SeqGeqTM software, which contain Lex-BDSMK and Seurat v4.04 plugin components. This experiment was performed once, and both raw data and processed data were uploaded into GEO (Accession number: GSE279370).

first: Juanjuan

last: Qiu

first: Xin

last: Dong

first: Liaoxun

last: Lu

first: Yinming

last: Liang

first: Lichen

last: Zhang


title: Unraveling the molting associated genes in the subterranean termites, Coptotermes formosanus, Coptotermes gestroi, and their hybrids using RNA-seq analysis

city: College Station

first: Kyung

middle: Seok

last: Kim

state: TX

address: 2556 F&B ROAD

department: Dept of Entomology

institute: Texas A&M University

summary: The Formosan subterranean termite (Coptotermes formosanus) and the Asian subterranean termite (Coptotermes gestroi) are the most destructive termite pests in the world. Both species have spread to various regions worldwide with overlapping distributions in a few areas in which pre- and post-zygotic barriers against hybridization between the two species have been lifted. Although initial colony growth rates of hybrid colonies are similar to those of the parental species, colony growth appears to slow down in the hybrids after several years. Observations suggest that workers in hybrid colonies are slower to molt than those of the parental species, suggesting a disruption in this process. To understand the comprehensive gene expression profiles during the molting cycle of workers, differential gene expression profiles based on RNA-seq analysis were recorded for four mating combinations (2 conspecific workers and 2 heterospecific workers) at three different molting periods (pre-, post- and inter-molt). Many differentially expressed genes were identified between heterospecific and conspecific matings at each molting stage as well as within termite species among molting periods. We successfully  identified molting-related genes by characterizing gene expression profiles of the parental species during the molting cycle conducting a time course analysis of transcriptome data. We then compared expression levels of these molting-related genes in the hybrids to identify genes that were over or under expressed compared to the parental species. Genes related to the molting cycle, muscle contraction, response to stress, and ecdysone metabolism were found to be under-expressed in hybrids relative to their parents. These differences will help elucidate the stability and fitness of hybrids between these two Coptotermes species. Moreover, identification of molting related genes in subterranean termites highlights the molecular pathways involved in the molting process in termites.

sample_organism: Coptotermes formosanus x Coptotermes gestroi

overall_design: RNA-seq profiling during the molting cycle of workers, differential gene expression profiles based on RNA-seq analysis were recorded for four mating combinations (2 conspecific workers and 2 heterospecific workers) at three different molting periods (pre-, post- and inter-molt)

first: Kyung Seok

first: Darshan

last: Chetty

last: Chouvenc

first: Joseph

middle: F

last: Velenovsky IV

first: Sang-Bin

last: Lee

first: Edward

last: Vargo


title: Fine-tuning mechanical constraints reveals uncoupled patterning and gene expression programs in murine gastruloids [RNAseq_time]

city: Lausanne

first: Lucille

last: Lopez-Delisle

address: Station 19

institute: EPFL

summary: Understanding the interplay between cell fate specification and morphogenetic changes remains a central challenge in developmental biology. Gastruloids, self-organizing pseudo-embryos that mimic post-implantation mammalian development, provide a powerful platform to address this question. Here, we show that physical parameters, particularly system size, critically influence the timing and outcomes of morphogenetic processes. Larger gastruloids exhibit delayed symmetry breaking, increased multipolarity, and prolonged axial elongation, with morphogenesis driven by system size. Despite these variations, transcriptional programs and cell fate composition remain remarkably stable across a broad size range. Notably, extreme sizes show distinct transcriptional modules and clear shifts in gene expression patterns. Intriguingly, size perturbation experiments rescued the morphogenetic and pattern phenotypes observed in extreme sizes, demonstrating the remarkable adaptability of gastruloids to their effective system size. These findings establish gastruloids as versatile models for studying spatiotemporal dynamics in mammalian embryogenesis and reveal how physical constraints decouple transcriptional from morphogenetic programs.

overall_design: RNA-seq on hydrogel embedded gastruloids (1mM and 1.5mM, at 72h vs 96h)

first: Alexandre

last: Mayran

first: Jérôme

last: Ng Wong

first: Judith

last: Pineau

first: Thomas

last: Gregor

first: Denis

last: Duboule


title: Overlapping peri-implantation phenotypes of ZNHIT1 and ZNHIT2 despite distinct functions during early mouse development.

city: Amherst

first: Jesse

last: Mager

state: Massachusetts

address: 661 N Pleasant St

department: Veterinary and Animal Sciences

institute: University of Massachusetts Amherst

summary: Mammalian preimplantation development culminates in the formation of a blastocyst which undergoes extensive gene expression regulation to successfully implant into the maternal endometrium. Zinc-finger HIT domain-containing (ZNHIT) 1 and 2 are members of a highly conserved family, yet they have been identified as subunits of distinct complexes. Here we report that knockout of either Znhit1 or Znhit2 results in embryonic lethality during peri-implantation stages. Znhit1 and Znhit2 mutant embryos have overlapping phenotypes, including reduced proportion of SOX2-positive ICM cells, a lack of Fgf4 expression and aberrant expression of NANOG and SOX17. Furthermore, we find that the similar phenotypes are caused by distinct mechanisms. Specifically, embryos lacking ZNHIT1 likely fail to incorporate sufficient H2A.Z at the promoter region of Fgf4 and other genes involved in cell projection organization resulting in impaired invasion of trophoblast cells during implantation. In contrast, Znhit2 mutant embryos display a complete lack of nuclear EFTUD2, a key component of U5 spliceosome, indicating a global splicing deficiency. Our findings unveil the indispensable yet distinct roles of ZNHIT1 and ZNHIT2 in early mammalian embryonic development.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for mouse embryos with genotypes of Znhit1 wt, het, mutant or Znhit2 wt, het, mutant.

first: Xinjian D

last: He

first: Louis

last: Taylor


title: Fine-tuning mechanical constraints reveals uncoupled patterning and gene expression programs in murine gastruloids [RNAseq_concentration]

overall_design: RNA-seq on hydrogel embedded gastruloids (0.7mM, 0.8mM, 1mM)

first: Pierre

last: Osteil


title: Slc22a17 governs postnatal neurogenesis by maintaining the iron homeostasis in hippocampus [ATAC-Seq]

city: Beijing

first: Ligong

last: Chen

address: Shuangqing Road No.30

institute: tsinghua university

summary: Iron transporters are essential for maintaining cellular iron homeostasis. Among them, SLC22A17 mediates lipocalin-2 (LCN-2)-dependent iron transport, but its precise role in the brain remains unclear. Here, we show that Slc22a17 is critical for postnatal neurogenesis by regulating hippocampal iron balance. Conditional knockout of Slc22a17 in the murine brain causes early postnatal lethality, growth retardation, neural stem cell apoptosis, and cognitive deficits, largely due to oxidative stress from iron overload. Mechanistically, Slc22a17 interacts with p62 to modulate Nrf2 activity. Its loss aberrantly activates the Nrf2/HO-1 pathway, disrupting iron efflux and promoting accumulation of reactive oxygen species (ROS). These findings establish Slc22a17 as a key regulator of neuronal development and a potential therapeutic target for neurological disorders linked to iron dysregulation.

overall_design: ATAC sequencing (ATAC-seq) on neurospheres derived from wild-type (WT) and Slc22a17-conditional knockout (cKO) mice.

first: Lei

last: Tao

first: Long

last: Teng


title: SKP1A-mediated degradation of PRC2 triggers activation of Polycomb-silenced genes : CUT&Tag 2

city: Yokohama

first: Takaho

middle: A.

last: Endo

state: Kanagawa

address: 1-7-22 Suehiro, Tsurumi

department: IMS

institute: RIKEN

summary: Polycomb group (PcG) proteins are evolutionarily conserved repressors of developmental genes. Paradoxically, the same PcG proteins also play roles in gene activation via mechanisms that are not yet fully understood. Here, we found that S-phase kinase-associated protein 1A (SKP1A), an essential factor of SCF (SKP1A/CULLIN1/F-box) ubiquitin ligases and a subunit of the PCGF1 (Polycomb group RING finger protein 1) component of Polycomb repressive complex 1 (PCGF1-PRC1), mediates the link between PcG-dependent gene regulation and ubiquitin-dependent proteasomal degradation. By using differentiating mouse embryonic stem cells, we found that SKP1A removes EED, a core component of Polycomb repressive complex 2 (PRC2) that is bound to PcG target gene promoters, via proteasomal degradation, and it thereby sensitises these genes for subsequent activation. Furthermore, we show that SKP1A removes EED from the Meis2 promoter in the midbrain of developing mouse embryos, leading to Meis2 gene expression. In summary, we reveal here a previously unknown role of SKP1A in activating PcG-target genes via the proteasomal degradation of PRC2. This implies that SKP1A-containing PCGF1-PRC1 may confer reversibility on PcG-mediated gene silencing for robust spatiotemporal regulation of target genes.

overall_design: Skp1 WT and KO of embryonic stem cell or embryoid body

first: Shunsuke

last: Ito

first: Takashi

last: Kondo

first: Hakurihi

last: Koseki


title: SKP1A-mediated degradation of PRC2 triggers activation of Polycomb-silenced genes : Gene expression 1

overall_design: Comparative gene expression between Skp1 WT and KO of embryonic stem cell or embryoid body.


title: SKP1A-mediated degradation of PRC2 triggers activation of Polycomb-silenced genes : Gene expression 2


title: Fine-tuning mechanical constraints reveals uncoupled patterning and gene expression programs in murine gastruloids

first: Lucille

last: Lopez-Delisle

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

overall_design: Refer to individual Series


title: Genomic stress mediated STING signaling in oligodendroytes drives Alzheimer's Disease

city: Charlottesville

first: Anwaruddin

last: Mohammad

state: VA

address: Pinn Hall

department: Bioinformatics Core

institute: University of Virginia

summary: Oligodendrocytes are a vital yet understudied cell type, especially in the case of neurodegeneration. This is despite their potential to mitigate neuronal degeneration through axonal structural support and metabolic supplementation, which may be pivotal in reinforcing neurons in times of cellular stress. Neuronal degeneration runs rampant in Alzheimer’s Disease (AD), which is the most common form of dementia. Exhaustive research into AD pathogenesis has yet to yield safe and effective treatment. Even the most recent amyloid monoclonals do little to slow progression of disease and indeed any improvement seems to be clinically indiscernible. Additionally, these drugs carry a significant risk of vascular events. While amyloid-beta and tau accumulation and neuronal pathology are main hallmarks of AD, a wide cascade of cellular events are also present. Demyelination is a prominent pathological hallmark of AD and has even been shown to occur in the preclinical phase of disease. Studies have suggested that oligodendrocyte and myelin deficits precede tau and Aβ accumulation, perhaps playing their own role in precipitating neurodegeneration and neuronal/axonal decline. The mechanisms of oligodendrocyte dysfunction in AD remain unknown. DNA damage has been increasingly linked to AD progression, and markers of DNA damage have been shown to be upregulated in oligodendrocytes in particular within both AD patients and animal models. This DNA damage can activate the nucleic-acid sensing pathway mediated by stimulator of interferon related genes (STING) as well as the Type I interferon response, further impacting oligodendrocyte homeostasis. DNA damage in oligodendrocytes and its ramifications could deprive neurons of crucial support, thereby accelerating degeneration. Indeed, DNA damage in oligodendrocytes as well as the role its resulting cascade of pathways have in the AD brain have not yet been explored.

overall_design: GeoMx spatial profiling of OLIG2+ cells, 3 biological replicates each (females) from WT/Black6 and 5XFAD brain, all 6 months of age

first: Tula

last: Raghavan

first: Shreyas

last: Gujar

first: Stefan

last: Prokop

first: Alban

last: Gaultier


title: C5a-C5AR1 axis as a potential trigger of the rupture of intracranial aneurysms

city: Nishi-Shinbashi, Minato-ku

first: Tomohiro

last: Aoki

state: Tokyo

institute: Jikei University School of Medicine

summary: Subarachnoid hemorrhage due to rupture of intracranial aneurysm (IA) still has poor prognosis once after the onset in spite of modern technical advancement in medical care. The development of the novel therapeutic strategy based on molecular machineries regulating the rupture is thus mandatory for social health. Here, recent studies have clarified the potential role of neutrophil-mediated inflammatory responses in the process leading to rupture. Thereby, factors mediating the recruitment of neutrophils in situ could be the therapeutic targets to prevent rupture of IAs. In the present study, complement C5a receptor 1 (C5AR1) was picked up as the candidates from comprehensive gene expression profile data. The induction of C5AR1 in IA lesions exclusively in rupture-prone or ruptured lesions was then confirmed in immunohistochemistry. The ligand of C5AR1, C5a, was induced through the enzymatic digestion by tissue-type Plasminogen Activator and, intriguingly, forms the auto-amplification in C5a-C5AR1 axis to exacerbate neutrophil infiltration and resultant neutrophil-mediated inflammation in situ, which triggers rupture of IAs. In conclusion, we have, in the present study, examined potential factors mediating the infiltration of neutrophils into IA lesions and then identified C5a-C5AR1 axis. This cascade could become the therapeutic target to prevent rupture of IAs.

overall_design: To investigate the difference of gene expression patterns between intracranial aneurysms and normal intracranial arteries in rats

first: Kampei

last: Shimizu


title: SKP1A-mediated degradation of PRC2 triggers activation of Polycomb-silenced genes : CUT&Tag 1


title: A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease [P60 Tfr1KO;KspCre]

city: Hannover

first: Christian

last: Hinze

address: Carl-Neuberg-Str. 1

department: Department of Nephrology and Hypertension

country: Germany

institute: Hannover Medical School

summary: Periconceptual maternal iron deficiency (FeD) is a worldwide problem resulting in prematurity and low birth weights. Yet, it is not known whether FeD affects all developing tissues, or rather targets specific lineages. To address these questions, we investigated the targeting of the kidney by FeD. We found that FeD reduced both serum transferrin-iron and non-transferrin-bound-iron (NTBI), and these deficiencies targeted the renal proximal nephron rather than renal collecting ducts or stroma. In contrast, proximal tubular deletions of TfR1 (TfD) caused only modest defects in kidney development implying compensation by NTBI in the embryo. Yet, after the first two postnatal weeks, proximal TfD resulted in striking segmentally specific hypoplasia, as well as well as pervasive cystic transformation with Bardet-Biedel or Nephronothesis protein deficiencies. Treatment with NTBI as well as systemic activators of HIF which induce iron trafficking bypassed TfD and rescued the cystic disease and suppressed kidney damage. In sum, iron depletion resulted in new forms of chronic kidney disease. Its phenotype resulted from the alternative use of two different forms of iron, NTBI and Tf-iron at different stages and in different cells of the developing kidney.

overall_design: Examining the transcriptional profile of conditional Tfr1 knockout (KspCre) in the mouse kidney compared to control at post-natal day 60.  n=3 biological replicates, respectively.

first: Jonathan

last: Barasch


title: A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease [P15 FeD]

overall_design: Examining the transcriptional profile of iron deficient mouse kidney compared to control at post-natal day 15. n=3 biological replicates, respectively.


title: Integrated profiling of proteins, glycoforms and mRNA in single cells reveals dynamic glycan remodeling during T cell differentiation

status: Public on Sep 07 2025

first: Junjie

last: Xia

address: 10th floor of KCBD, 900 E. 57th Street

department: Chemistry

institute: University of Chicago

summary: Protein glycosylation is a critical post-translational modification that plays vital roles in cellular function and disease, including infection, autoimmunity and cancer. Techniques that measure specific glycosylated proteins face challenges in sensitivity and throughput, preventing applications in single cells. We introduce Glycan Proximity Sequencing (GPS) for the integrated profiling of proteins, glycosylation and protein-specific glycoforms, as well as mRNA in single cells. GPS achieves affinity-based detection of proteins and their modifications via proximity-based single-cell RNA sequencing. Experiments using mixtures of T and B cells, together with a GnTI-knockout mutant, demonstrated sensitive detection of both global and protein-specific glycosylation differences. Applied to human peripheral blood mononuclear cells, GPS revealed dynamic glycan remodeling patterns during T cell differentiation and potential galectin-binding glycoproteins for modulating immune responses. Notably, we identified a new CD45:LELhigh subcluster of terminally differentiated effector memory  CD8+ T cells that are enriched for poly-LacNAc and 𝛼2,3-sialylation modifications and associated with exhaustion and susceptibility to galectin-1–induced apoptosis. GPS also captured glycosylation changes in response to perturbations like sialidase treatment and T cell activation. GPS is a scalable and sensitive platform for single-cell glycoproteomics and protein-specific biomarker discovery, and it can reveal mechanistic insights on the role of glycosylation in T cell differentiation.

overall_design: Single-cell GPS assays were performed on three human peripheral blood mononuclear cell (PBMC) samples using the 10x Genomics Chromium pipeline. Two samples, both derived from the same donor (donor 1), were processed together in a single run; one of these was stimulated with Concanavalin A (ConA) for 24 hours prior to the GPS workflow. The third sample, obtained from a different donor (donor 2), was processed in a separate run. All human PBMCs were purchased from STEMCELL Technologies. Both mRNA expression and proximity ligation assay (PLA) features were captured in all assays.

first: Bijentimala

last: Keisham

first: Jia

last: Pang

first: Abinash

last: Padhi

first: Huili

last: Wang

first: Gabriel

last: Mercado-Vasquez

first: Mia

last: Huang

first: Savas

last: Tay


title: sRNA-Seq of Arabidopsis thaliana tho2-8 mutant

city: Nan Jing

first: La

middle: yu

last: mei

state: Jiang Su

address: XuanWu

institute: Nanjing Agricultural University

summary: The mechanistic connection between the THO/TREX complex and RdDM remains poorly understood. To address this, we performed EMS mutagenesis in a transgenic Col-0 background harboring pro2×35S::LUC and pro2×35S::NPTII reporters and homozygous for rdr6, and identified a low-fluorescence mutant, tho2-8. Unlike null alleles, tho2-8 is a viable homozygous allele, offering a unique opportunity to explore THO2 function in DNA methylation. Here, we report that THO2 is required for proper siRNA accumulation and RdDM activity, revealing a previously uncharacterized role for the THO/TREX complex in epigenetic gene silencing. This study expands our understanding of the molecular coordination between RNA metabolism and epigenetic regulation in plants.

overall_design: sRNA-Seq of tho2-8;Col-LUC

first: Yumei

last: La

first: Honggui


title: A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease [P13 Tfr1KO;Six2Cre]

overall_design: Examining the transcriptional profile of conditional Tfr1 knockout (Six2Cre) in the mouse kidney compared to control at post-natal day 13.  n=3 biological replicates, respectively.


title: mRNA-Seq of Arabidopsis thaliana tho2-8 mutant

overall_design: mRNA-Seq of tho2-8;Col-LUC


title: WGBS of Arabidopsis thaliana tho2-8 mutant

overall_design: BS-seq of tho2-8;Col-LUC;ros1-7.


title: Gene expression profile of B55a/PPP2R2A knocked-down Parkin-expressing HeLa cells

city: Rome

first: Valentina

last: Cianfanelli

address: Viale Marconi 446

institute: University Roma TRE

summary: Or study identified the PP2A-B55a/PPP2R2A Ser-Thr phosphatase as a regulator of Parkin-dependent mitophagy and mitochondrial biogenesis. HeLa cells expressing Parkin and knocked-down for B55a/PPP2R2A induce a lysosome- and mitochondria-related transcriptional programmes down-stream TFEB and PGC-1a transcription factor activation.

overall_design: Total RNA was extracted from B55a/PPP2R2A kncked-down cells, induced for Parkin expression with Doxycycline. Cells transiently transfected with a control oligo were used a control sample.

first: Cianfanelli

last: Valentina

first: Nanni

last: Monica

first: De Cegli

last: Rossella


title: Characterization of translational dynamics during macrophage activation

city: Hangzhou

first: Yuanhui

last: Mao

state: Zhejiang

address: WenYi west street

institute: Zhejiang University School of Medicine

summary: Macrophages require rapid and tightly controlled regulatory mechanisms to respond rapidly to environmental disruptions while preventing excessive inflammatory responses. While transcriptional regulation has been well-characterized in macrophage activation, whether and how translational control contributes to macrophage activation remains less understood. Here, we investigate the dynamic landscape of translational regulation in macrophages across acute, intermediate, and prolonged LPS exposure.

overall_design: Ribosome profiling (ribo-seq) and RNA sequencing (RNA-seq) were conducted on RAW264.7 macrophages after LPS stimulation at various time points.

first: Shiqi

last: Luo


title: Riboseq of Tissues of Mice

summary: Codon usage bias is a fundamental aspect of molecular biology, influencing the efficiency and accuracy of protein synthesis. In a recent study, we investigated codon usage patterns across various tissues in mice, revealing a consistent and significant trend.

overall_design: Ribosome profiling (ribo-seq)  was performed on tissues from 4-week-old mice


title: Epigenetic, ribosomal, and immune dysregulation in Paediatric Acute Neuropsychiatric Syndrome

city: Westmead

first: Brian

last: Gloss

state: NSW

address: 176 Hawkesbury Rd

department: Scientific Platforms

country: Australia

institute: Westmead Institute of Medical Research


title: Verification of gene expression profiles in the liver tissues of mice after schistosomiasis infection

city: Hefei City

first: gong

last: li

state: Anhui Province

address: South First Ring Road

institute: Anhui Medical University

summary: In order to further improve our method for measuring gene expression after different days of schistosomiasis infection, we adopted whole-genome microarray expression analysis as the sequencing platform to identify those genes with potential for distinguishing different infection times (applicable for the corresponding exposure range of medical decisions in cases of schistosomiasis infection after different days). We infected 15-day, 24-day and 45-day healthy mice with schistosomiasis and determined a consensus characteristic of successful schistosomiasis infection, which could distinguish infection days and control samples. Through real-time PCR, the expression of genes with significant differential expression (such as DDAH1) in the same RNA samples was quantified, confirming the low-level expression after infection and the expected schistosomiasis infection response pattern.

overall_design: In the liver tissues of mice, the gene expression changes caused by schistosome infection were measured at 0, 15, 24 and 45 days after infection. Three independent experiments were conducted at each time point, and different donor samples were used in each experiment.

first: liu

last: miao


title: Effect of Simvastatin on endothelial cells (heart ATAC-seq)

city: Stanford

first: Lek Wen

last: Tan

state: CA

address: 450 Serra Mall,

institute: Stanford University

summary: Statins, a class of hydroxy-methylglutaryl-coenzyme A reductase inhibitors that repress the mevalonate pathway, have been increasingly recognized to reduce cardiovascular risks in a pleiotropic manner independent of their lipid-lowering effects. Yet, the precise molecular mechanisms underlying their cardiovascular protection effects remain elusive. As an unlimited alternate source of human primary cells, we sought to use human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) to tackle this question. We treated iPSC-ECs with or without statins in both baseline and diabetic conditions, and evaluated their biological functions specifically at the transcriptional and epigenetic levels using an array of state-of-the-art technologies, such as transcriptome profiling, chromatin immunoprecipitation sequencing (ChIP-seq), assay for transposase-accessible chromatin using sequencing (ATAC-seq), CRISPR knockout and CRISPR interference (CRISPRi). Furthermore, we validated our in vitro findings of the endothelial protective role of statin using a diabetic mouse model. We observed that, compared to vehicles, statins significantly improved endothelial functions in both baseline and diabetic conditions in iPSC-ECs. Mechanistically, statins could reduce chromatin accessibility at TEAD elements and ultimately at endothelial-to-mesenchymal transition (EndMT)-regulating genes in a yes-associated protein (YAP)-dependent manner. Interestingly, inhibition of geranylgeranyltransferase I (GGTase I), a mevalonate pathway intermediate, was able to block YAP nuclear translocation and thereby YAP activity by suppressing RhoA signaling. We also identified a direct target of statin-YAP signaling, a novel enhancer of SOX9 gene, which plays a critical role in EndMT process. Based on these observations, we further confirmed that inhibition of any component of the GGTase-RhoA-YAP-SOX9 signaling axis using either genetic or pharmacological approaches was effective to rescue EndMT-associated endothelial dysfunction both in vitro and in vivo, especially under diabetic conditions.

overall_design: Mouse hearts and iPSC_derived Endothelial Cells were analyzed using ATAC-seq and RNA-seq.

first: Chun

last: Liu

first: Liu

last: Yu

first: Joseph

last: Wu


title: Effect of Simvastatin on endothelial cells (iEC ATAC-seq)


title: Effect of Simvastatin on endothelial cells

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus


title: mRNA expression data of benzene exposed mice and IGF2BP1 overexpressed mice

first: Ai

last: Gao

address: Capital Medical University, 10 Xitoutiao, You An Men, Beijing 100069, P. R. China

institute: Capital Medical University

summary:
Benzene induced bone marrow damage, and IGF2BP1 was reduced in mice.  IGF2BP1 is a RNA binding protein, and can regulate the RNA expression. Therefore, we constructed IGF2BP1 overexpression mice to explore the role of IGF2BP1
We used microarrays to detail the global programme of gene expression after benzene exposure and identified distinct classes of IGF2BP1-regulated genes during this process.

overall_design: Mice were randomly divided into 4 groups (10 mice per group): (1) control group (AAV‐null), (2) control-AAV‐IGF2BP1 group, (3) benzene group (benzene + AAV‐null), and (4) benzene-AAV‐IGF2BP1 group. AAV‐null (2.5×1011viruses in 200 μL normal saline), or AAV‐ IGF2BP1 (2.5 ×1011 viruses in 200 μL normal saline) were injected through the tail vein using sterile disposable syringes. Two-week post injection, mice were exposed to 0 and 50 ppm benzene for 6 h/ day, 6 days/week and 9 weeks. The femur and tibia of mice were collected. The bone was cut off at both ends and bone marrow was flushed out with sterile phosphate buffered saline (PBS) using a syringe. Bone marrow cells were obtained by filtrating through a 70 μm cell strainer (SORFA, Beijing, China). After centrifugation at 1500 rpm for 5 min, cells were resuspended for counting. The total RNA was isolated from 1 × 106 bone marrow cells using TRIzol reagent (Invitrogen, CA, USA) for Affymetrix microarray profiling.

first: Jingyu

last: Wang


title: BamA self-insertion drives inner to outer membrane remodelling in diderm Firmicutes

status: Public on Sep 06 2025

city: Vancouver

first: Elitza

last: Tocheva

state: BC

address: 2350 Health Sciences Mall

department: Microbiology and Immunology

country: Canada

institute: University of British Columbia

summary: Endospore formation in Firmicutes is a complex morphological process triggered by environmental stress. At the end of this process, a mature spore containing the condensed genome is released through lysis of the mother cell. The mature spore is encased by several protective layers, including an inner and an outer spore membrane (IsM and OsM, respectively), both derived from the inner membrane (IM) of the mother cell. While this process is well understood in monoderm bacteria like Bacillus subtilis, less is known about diderm spore-formers such as Acetonema longum, which retain and remodel their OsM into a true outer membrane (OM) during germination. Our results show that outer membrane proteins (OMPs), including the essential β-barrel Assembly Machinery (BAM) component BamA, are present in vegetative and germinating cells but absent from mature spores. These observations highlight an unprecedented mechanism of inner to outer membrane remodelling in the absence of BamA. Expression profiles of cells at different growth stages and phylogenomic analyses identified two novel proteins, co-expressed and in an operon with BamA, that were highly conserved among diderm Firmicutes: a β-barrel OMP containing three polypeptide transport-associated (POTRA) domains (SonA) and a putative OM lipoprotein (SonB). In vitro experiments further demonstrated that both BamA and SonA can self-insert into liposomes under physiological conditions. Together, we propose a model in which BamA and its functional partners, SonA and SonB, drive membrane remodelling during germination. The process is initiated by self-insertion of BamA, which then assists the folding and insertion of other OMPs, including LptD, progressively shifting the protein and lipid composition of the OsM to produce a true OM. Collectively, our findings provide new insights into the functional role of BamA in membrane remodelling during OM biogenesis.

overall_design: RNAseq profiling of Acetonema longum APO-1 (DSM 6540) across discrete stages of the sporulation cycle: vegetative growth (3 day subcultures in exponential phase), sporulation (5 day subcultures in stationary phase) and germination (pure germinating spores at 16 hours post-inoculation).

first: Polina

last: Beskrovnaya

first: Ameena

last: Hashimi

first: Danielle L.

last: Sexton

first: Gregory E.

last: Nikas

first: Elitza I.


title: Gene expression following myocardial infarction in mice with Stimulated by retinoic acid gene 6 (Stra6) germline deletion, Vitamin A deficiency, and the combination of both

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

institute: HCI - Helmholtz Centre for Infection Research

summary: mRNA expression of hearts obtained from mice with Stimulated by retinoic acid gene 6 (Stra6) germline deletion, Vitamin A deficiency (VAD) induced by lecithin-retinol acyltransferase (Lrat) germline deletion and feeding with vitamin A-deficient diet, and the combination of both. Mice were subjected to myocardial infarction (MI) or Sham surgery.

overall_design: C57/Bl6J mice were subjected to myocardial infarction or Sham surgery and sacrificed 3-days post-surgery. mRNA was extracted from the infarct border zone, and libraries were prepared for high throughput sequencing.

first: Christian

last: Riehle


title: Gastrointestinal digestion enhances the in vitro antitumor activity of red grape anthocyanins against colorectal cancer cells

city: Cluj-Napoca

first: Simona

last: Visan

state: Cluj

address: 34-36 Republicii

department: Functional Genomics, Proteomics and Experimental Pathology

country: Romania

institute: The Oncology Institute “Prof Dr. Ion Chiricuta”,

summary: To investigate the key mechanisms regulated by digested red grape anthocyanins in colorectal cancer cells, we employed whole-genome microarray expression profiling as a discovery tool to identify the signaling networks affected by this treatment, in vitro. Treatment of DLD1 cells with the digested red grape anthocyanin extract at IC50 concentration, significantly altered the expression of 873 genes (p adj.<0.05), showing a fold regulation greater than |±1.5|. Treatment with the extract impacted key cancer-related functional signaling networks, including apoptosis and cellular movement.

overall_design: The whole transcriptome analysis  was implemented on four biological replicates in DLD1 cells vs. DLD1 cells treateted with the IC50 concentration of the digested red grape anthocyanin extract at 24h after treatment.

first: Daniel

last: Cruceriu

first: Denisa

last: Dobos

first: Stefan

last: Miron

first: Oana

last: Sava

first: Loredana

last: Balacescu

first: Ovidiu

first: Zorita

last: Diaconeasa


title: The transcriptome of platelet from antiphospholipid syndrome (APS)

city: Shanghai

first: Tingting

last: Liu

state: Shanghai

address: No. 197 Ruijin Second Road

institute: Shanghai Jiao Tong University

summary: Platelet mRNA sequencing from APS patients and healthy controls performed in this study presented the distinct mRNA profile of the two groups.

overall_design: Platelet mRNA sequencing from APS patients(n=3) and healthy controls(n=3) performed in this study.

first: Chengde

last: Yang

first: Zihan

last: Tang


title: Brown remodeling of white adipose tissue protects against abdominal aortic aneurysm via a novel batokine FSTL1 [CL316,243]

city: Guangzhou

first: Yao

last: Lei

address: 107 Yan Jiang West Road

department: Department of Cardiology

institute: Sun Yat-sen Memorial Hospital, Sun Yat-sen University

summary: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease without effective medical therapies. Emerging evidences have suggested a crosstalk between adipose tissue and vascular cells and brown adipose tissue is beneficial for cardiovascular health. Nevertheless, whether brown remodeling of white adipose tissue would protect against AAA remains unclear. Here we showed that patients with AAA had a decreased browning level of adipose tissue and induction of adipose tissue browning significantly reduced AAA incidence and attenuated AAA development in mice. Using LC-MS/MS and proteomic analysis, we further identified Follistatin-like 1 (FSTL1) as a novel vessel-protective adipokine secreted by browning adipocytes. Mechanistically, FSTL1 inhibited VSMC apoptosis through DIP2A/AKT signaling. Furthermore, we demonstrated that adipocyte-specific deficiency of FSTL1 abrogated the protective effect of browning induction. Moreover, supplementation of FSTL1 either systemically or patched into hydrogel placing around abdominal aorta markedly limited aortic dilation and AAA progression. Our data suggest a protective role of adipose tissue browning and a novel batokine FSTL1 in the development of AAA, which may represent a novel intervention strategy for AAA.

overall_design: RNA sequencing of aortic tissues from Ang II-infused mice treated with or PBS.

first: Chunling

last: Huang

first: Yuna

first: Boshui

first: Lei

last: Yao


title: pH modulation restores proteostasis and extend lifespan in a yeast model of Huntington’s Disease [pH]

city: London,

first: Khaleda Afrin

last: Bari

state: ON

address: 1151 Richmond St

department: Anatomy and Cell Biology

institute: Western University

summary: Loss of proteostasis is a hallmark of the aging process and is associated with the onset of several neurodegenerative diseases, including Huntington’s Disease (HD) where aberrant polyglutamine (polyQ) expanded Huntingtin aggregates into insoluble inclusions bodies (IBs)  associated with toxicity in neuronal cells. In yeast, chronological lifespan (CLS) assays  are used to model aging of non-dividing cells such as neurons. During CLS, acidification of the culture media due accumulation of acetic acid is one of the major cell extrinsic factors responsible for cell death. Thus, buffering media pH to prevent acidification significantly extends longevity. Here, we found that cells expressing pathogenic polyQ expansions display increased sensitivity to acetic acid and shortened CLS. Buffering media pH promotes both polyQ aggregation into IBs and longevity. We found that growth at higher pH induces the activation of heat shock response (HSR) in young cells. Such hormetic HSR activation  subsequently allowed aged cells to mount a proper HSR in response to stresses such as heat shock or polyQ misfolding, leading to lifespan extension. Thus, our study provides new insight into how pH can promote proteotoxic stress resistance and longevity.

overall_design: mRNA of W303 cells grown in 2% synthetic media compared to W303 cells grown in buffered media (NAOH) pH 6.5

first: Gabriela

last: Librais

first: Martin

last: Duennwald

first: Patrick

last: Lajoie


title: Brown remodeling of white adipose tissue protects against abdominal aortic aneurysm via a novel batokine FSTL1

overall_design: RNA sequencing of  VSMCs treated with or without recombinant FSTL1.


title: pH modulation restores proteostasis and extend lifespan in a yeast model of Huntington’s Disease [polyQ]

overall_design: mRNA of strains expressing 25 polyglutamine compared to strains expressing 46 polyglutamine


title: The effection of celastrol treatment on SKM-1 cell

city: Shenzhen

first: Fuxiang

last: Zheng

address: Fuhua 1 Road

department: Department of Clinical Laboratory

institute: The fourth Clinical Medical College of Guangzhou University of Chinese Medicine

summary: Myelodysplastic syndromes (MDS) are myeloid hematopoietic stem cell tumors displaying complex pathogenesis with a high risk of transformation to acute myeloid leukemia (AML). The efficacy of current clinical drugs is limited. Thus, identifying high-efficiency drugs of MDS remain urgent. Celastrol, a natural small molecule compound derived from the traditional Chinese medicinal herb Tripterygium wilfordii, has shown powerful antitumor effects. However, the effects of celastrol on MDS are unknown. In this study, we found that celastrol significantly inhibited the viability of MDS cell lines and bone marrow mononuclear cells (BMMCs) from MDS patients, and induced apoptosis. Through transcriptome sequencing, we found that celastrol induced the pro-apoptotic ER stress response in MDS cell. Mechanistically, celastrol activated the pro-apoptotic ER-stress branch involving the pancreatic eIF2α kinase (PERK) pathway.

overall_design: We treat SKM-1 cell with celastrol and DMSO.

first: Wenjun

last: Shao

first: Li

first: Ji

last: Zhang


title: Blood transcriptional signatures of asymptomatic FDG-PET/CT-defined Subclinical TB lesions and their prediction of future TB progression II

city: Melbourne

first: Dylan

last: Sheerin

state: VIC

address: 1G Royal Parade

institute: WEHI

summary: Diagnostic tests for tuberculosis (TB) infection poorly predict future incident disease risk. We investigated a cohort of asymptomatic HIV-uninfected household contacts of TB in South Africa in which baseline lung lesions indicative of Subclinical TB identified by [18F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission/computed tomography (PET/CT) had high predictive value for future TB over 5 years. RNA-sequencing analysis of whole blood samples at baseline PET/CT, 5-15m PET/CT2, and the TB diagnosis of incident TB revealed persistent enrichment of neutrophil and monocyte transcriptional modules in those with Subclinical TB and worsening and discrete lung abnormalities, while expression of a core set of type I IFN genes related to FDG-avid lymph nodes. Leveraging multiple machine learning algorithms, we derived gene signatures of various PET/CT lesion Subclinical phenotypesTB, future lesion worsening and TB diagnosis. prevalent and incident TB. Validating signatures in two independent cohorts against TB progression within 6,12,18 and fup to 24-29-months, confirmed gave AUC of 0.75-0.95 and 0.77-0.87 with performance above optimal sensitivity and wminimum specificity for the WHO target product profile for TB progression.

overall_design:
Asymptomatic, HIV uninfected, adult, household contacts of drug-resistant (at least Rifampin resistant) TB were recruited. Their sputa (induced/spontaneous) underwent Xpert MTB/RIF and culture and blood was drawn for QuantiFERON in-tube-Gold (QFT-Gold), QFT-Plus, and Tempus tubes for RNA. A baseline PET/CT was performed in 250 individuals who were Xpert negative at baseline, and a second PET/CT was performed in 112 participants after 5 to 15 months and some participants had a third PET/CT at endpoint TB diagnosis. Participants were followed for up to five years, with repeat symptom and induced sputum screening between years 2-3 at any time when they presented to the clinical with TB signs or symptoms and at completion of follow-up via interrogation of their health service encounters via the Western Province Provincial Health Data Centre and clinic medical records. PET/CT features at baseline consistent with TB were assessed by readers blinded to clinical details and classified by prespecified radiographic and microbiologic criteria.
This repository consists of the final 98 RNA-seq samples, categorized primarily by PET/CT features identified at the visit, changes between visit 1 and visit 2 or visit 2 and visit 3, and TB diagnosis at baseline (prevalent TB) or during folllow-up (incident TB).

first: Hanif

last: Esmail

first: Jerry

last: Ellner

first: Padmini

last: Salgame

first: Robert

last: Wilkinson

first: Anna

middle: K

last: Coussens


title: SARS-CoV-2 NSP14 Inhibitor Confers Potent Antiviral Efficacy and Reverses NSP14-triggered Host Cell Modulation

first: Wei

last: Xie

address: No. 866 Yuhangtang Road, West Lake District

institute: Zhejiang University

summary: The emergence of SARS-CoV-2 variants and drug-resistant mutants necessitates additional antivirals. SARS-CoV-2 NSP14 N7-guanosine methyltransferase is responsible for viral RNA capping, facilitating replication and evading immune detection. NSP14 has emerged as a promising drug target, but the role of NSP14 in host-virus crosstalk and the cellular effects of NSP14 inhibition are poorly understood. Here, we performed structure-based virtual screen to identify non-nucleoside inhibitors targeting NSP14 SAM-binding pocket. Hit to Lead optimization resulted in the development of C10 that potently inhibited SARS-CoV-2 and variants with the EC50 values from 64.03 to 301.9 nM, comparable to FDA-approved drug remdesivir in our cell-based model. C10 is a selective inhibitor of β-coronavirus NSP14 and directly suppresses SARS-CoV-2 replication, as demonstrated by a SARS-CoV-2 replicon system. C10 specifically reversed NSP14-mediated host transcriptome alterations and, phenotypically, restored host cell cycle progression disrupted by NSP14. The antiviral efficacy of C10 was further validated in a transgenic mouse model of SARS-CoV-2 infection. Our findings indicate C10 holds promise for developing effective treatments against SARS-CoV-2 and emerging variants, as well as uncover a novel pathogenic role of NSP14 beyond its function in viral RNA capping, which may be also adaptable to other viral capping methyltransferase.

overall_design: RNA-sequencing (RNA-seq) of cells expressing nsp14 treated by C7 or C10 to reveal its molecular effects on host cells.

first: Mengxin

last: Luo


title: A novel lymphoma-associated macrophage interaction signature (LAMIS) provides robust risk prognostication in diffuse large B-cell lymphoma clinical trial cohorts of the DSHNHL

first: Robin

last: Kosch

address: Carl-Neuberg-Straße 1

institute: Hannover Medical School

summary: Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2–2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2–2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3–2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy.

overall_design:
Transcriptomics dataset of 330 formalin-fixed paraffin-embedded (FFPE) tissue samples from patients with Diffuse large B-cell lymphoma (DLBCL). Gene Expression profiles of 145 target genes were created using the NanoString nCounter technology (NanoString Technologies, Seattle, WA). The name of the study cohort was included to help distinguish the samples.
***Submitters state that the corresponding clinical data is not provided due to privacy protections, refering to the following data sharing agreement and the Leipzig Health Atlas:
Pseudonymised data will be available upon request up to 5 years after publication of this Article to researchers who provide a data sharing agreement that describes a methodically sound proposal and the data necessary for the purpose of the approved proposal. Proposals should be directed to dshnhl@uks.eu. Data will be shared once all relevant parties approve and sign the data sharing agreement. Selected data will be also available on the Leipzig Health Atlas website. For the Leipzig Health Atlas website see www.health-atlas.de<http://www.health-atlas.de/>.

first: Annette

last: Staiger

first: Michael

last: Altenbuchinger

first: German

last: Ott


title: DAXX interacts with histone acylation in gene regulation

city: Cambridge

first: Felix

last: Krueger

address: Granta Park

department: Bioinformatics

institute: Altos Labs

summary: Using proteome arrays and mass spectrometry, we find that the histone chaperone DAXX interacts with crotonylated histones. We show that histone crotonylation and gene expression changes promoted by the short-chain fatty acid crotonate depend on DAXX.

overall_design: RNA-Seq  and pan-lysine crotonylation (Kcr, PTM-501) ChIP-Seq experiments from the colon epithelium-derived HCT116 cells, where DAXX or non-targeting control small interfering RNA were used to knock down DAXX or be used as control. Then cells were either treated or not with 10 mM crotonate for 18 h. All RNA-seq experiments were performed in quadruplicate.

first: Elena

last: Stoyanova

first: Alessando

last: Cuomo

first: Oda

last: Stoevesandt

first: Claudia

last: Fonseca

first: Mike

last: Taussig

first: Tiziana

last: Bonaldi

first: Mia

last: Mosavie

first: Patrick

last: Varga-Weisz


title: A Switch in Iron Transport Mechanisms Defines Novel Forms of Congenital Chronic Kidney Disease

first: Christian

last: Hinze

address: Carl-Neuberg-Str. 1

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

overall_design: Refer to individual Series


title: Mechanistic Study on the Restoration of Intestinal Barrier Integrity and Alleviation of Inflammatory Bowel Disease by Rhynchophylline via the AhR-NR4A1 Pathway

status: Public on Sep 05 2025

city: Urumqi

first: Xuwen

last: Mao

address: CollNo.567, Shangde North Road, Shuimogou District

institute: Xinjiang medical university

summary: Restoring intestinal barrier function is considered an effective strategy for the treatment of Inflammatory Bowel Disease (IBD). Rhynchophylline (Rhy), a bioactive alkaloid sourced from the traditional herbs Uncariarhynchophylla used in Chinese medicine, is known for its antihypertensive, anti-asthmatic, and antitumor properties. This study explores the pharmacological effects and molecular mechanisms of Rhy in treating IBD.

overall_design: In vitro cell inflammation injury model was established, and the inflammatory factors, cell permeability, cell proliferation, and intercellular tight junction protein expression were measured after Rhy intervention, which verified the anti-inflammatory activity and enhancement of intestinal barrier function of Rhy. In vivo animal model of acute and chronic colitis was established, and Rhy was administered orally at three dose levels to evaluate the protective effects of Rhy on acute and chronic colitis in animals. The signaling pathways that enhance the intestinal barrier function of Rhy were identified through transcriptomics, gene knockout techniques, and molecular dynamics simulations.

first: Lufeng

last: Cheng

first: Yu

last: Liu

first: Yuche

last: Wu


title: Targeting STK17B kinase activates ferroptosis and suppresses drug resistance in multiple myeloma

city: Durham

first: Mikhail

last: Nikiforov

state: NC

address: 210 Research Drive, GSRB II Rm. 4020

institute: Duke University

summary: The progression of multiple myeloma (MM), an incurable malignancy of plasma cells, is oftenassociated with the suppression of ferroptosis, a type of cell death driven by iron-dependent lipid peroxidation. The mechanisms underlying this suppression remain largely unknown. Here, we identified STK17B kinase as a critical suppressor of ferroptosis in MM. Elevated levels of STK17B are associated with poor overall survival in MM patients and STK17B expression is significantly higher in relapsed vs newly diagnosed MM cases. We found that inhibiting STK17B in MM cells increased the labile iron pool, enhanced lipid peroxidation, and sensitized cells to conventional anti-MM therapies. Notably, an orally available, in-house-generated STK17B inhibitor induced ferroptosis and significantly reduced tumor growth in MM xenograft mouse models. Mechanistically, proximity labeling assay combined with the phospho-proteomic analysis identified two major regulators of iron uptake and transport as direct targets of STK17B: iron-responsive element binding protein 2 (IREB2) and heat shock protein family B member 1 (HSPB1). We demonstrated that STK17B phosphorylates critical regulatory sites on IREB2 (S157) and HSPB1 (S15), thereby modulating the balance between IREB2 and HSPB1 downstream effectors, pro-ferroptotic transferrin receptor and anti-ferroptotic ferritin heavy chain proteins. Furthermore, we demonstrated that STK17B indirectly maintains activating phosphorylation of STAT3, a ferroptosis suppressor and a major driver of MM pathobiology. Our findings uncovered a clinically relevant and targetable STK17B-pIREB2S157/pHSPB1S15 signaling axis that suppresses ferroptosis and contributes to drug resistance in MM.

overall_design: RNAseq of total RNA from cells from human multiple myeloma cell lines transduced with control shRNA, STK shRNAs, control vector, vector overexpressing STK17B cDNA, and cells transduces with  control shRNA treated with STK17B inhibitor or with vehicle.

first: Liang


title: RNA-seq of lungs from SCID mice pre-treated with EVs from Tsc1-null or wild-type E15.5 neural progenitors prior to ELT3 cell injection

city: Abilene

first: Magdalena

last: Karbowniczek

address: 1718 Pine Street

department: Immunotherapeutics and Biotechnology

institute: Texas Tech University Health Sciences Center

summary: Pulmonary lymphangioleiomyomatosis (LAM) is a rare metastatic sarcoma characterized by the abnormal proliferation and dissemination of TSC1/TSC2-null smooth muscle-like cells. While extracellular vesicles (EVs) are known to regulate cancer metastasis, their roles in LAM have not been fully elucidated. Here, we identify distinct LAM-EV subtypes derived from primary tumor or metastasizing LAM cells that promote metastasis via ITGα6/β1–c-Src–FAK signaling. These EVs enhance LAM cell migration, invasion, and stemness by either shuttling ATP synthesis to cell pseudopodia or activating integrin adhesion complexes. In vivo, CD9⁺CD63⁺CD81⁺ EVs isolated from Tsc1-null or wild-type E15.5 mouse embryonic neural progenitors were labeled and injected intravenously into SCID mice, followed 48 hours later by intravenous injection of 0.5×10⁶ ELT3 cells, a well-characterized LAM model. Lungs were harvested 72 hours post-injection for RNA-seq analyses. Lungs from Tsc1-null EV-treated mice showed increased metastatic burden (rat DNA content) and differential expression of 815 genes (522 upregulated, 293 downregulated) compared to wild-type EV-injected mice. Reactome analysis revealed enrichment in extracellular matrix remodeling, collagen biosynthesis, and the assembly of multimeric structures. These findings establish EVs as key mediators of LAM metastasis and identify them as potential therapeutic targets.

overall_design: To investigate the role of extracellular vesicles (EVs) in pulmonary lymphangioleiomyomatosis (LAM) metastasis, we performed RNA sequencing of lung tissues from SCID mice treated with EVs derived from Tsc1-null or wild-type neural progenitor cells. CD9⁺CD63⁺CD81⁺ EVs were isolated from E15.5 mouse embryonic neural progenitors lacking Tsc1 or from wild-type controls. EVs were fluorescently labeled and injected into the tail vein of female SCID mice. After 48 hours, mice were intravenously injected with 0.5 × 10⁶ rat ELT3 cells, a well-characterized LAM model. Lung tissues were collected 72 hours after ELT3 cell injection for RNA isolation and sequencing. The experiment was designed to assess EV subtype-dependent modulation of the lung microenvironment and its contribution to the formation of a metastatic niche. RNA-seq was performed on lung tissues from Tsc1-null EV- and wild-type EV-treated mice (n = 3 per group). Differential gene expression and pathway analyses were conducted to identify molecular pathways influenced by Tsc1-null EV.

first: Anil Kumar

last: Kalvala

first: Ashok

last: Silwal

first: Bhaumik

last: Patel

first: Apoorva

last: Kasetti

first: Kirti

last: Shetty

first: Jan

last: Markiewski

first: Jun-Hung

last: Cho

first: Gerard

last: Lara

first: Elizabeth

last: Daugherity

first: Remi

last: Diesler

first: Venkatesh

last: Pooladanda

first: Bo R

last: Rueda

first: Elizabeth Petri

last: Henske

first: Jane

last: Yu

first: Maciej


title: Coronavirus NSP14 Drives Internal m7G Modification to Rewire Host Splicing and Promote Viral Replication

city: Newark

first: Chun-Chieh (Jack)

last: Hsu

state: New Jersey

address: 205 S. Orange Avenue

department: Department of Medicine

institute: Rutgers University, New Jersey Medical School

summary: SARS-CoV-2, the causative agent of COVID-19, manipulates host gene expression through multiple mechanisms, including disruption of RNA processing. Here, we identify a novel function of the viral nonstructural protein 14 (NSP14) in inducing N7-methylguanosine (m7G) modification in the internal sequences of host mRNA. We demonstrate that NSP14 catalyzes the conversion of guanosine triphosphate (GTP) to m7GTP, which is subsequently incorporated into mRNA by RNA polymerase II, resulting in widespread internal m7G modification. This activity is dependent on NSP14's N7-methyltransferase (N7-MTase) domain and is enhanced by interaction with NSP10. Internal m7G modification by NSP14 predominantly occurs in the nucleus and is conserved across alpha-, beta- and gamma-coronaviruses. Mechanistically, we show that this RNA modification disrupts normal splicing by promoting intron retention and generating novel splice junctions. Importantly, inhibition of m7G modification, through pharmacological targeting of NSP14 or RNA polymerase II, impairs SARS-CoV-2 replication, indicating that the virus hijacks host transcriptomic machinery to support infection. Our findings reveal a previously unrecognized epitranscriptomic mechanism by which coronaviruses reprogram host gene expression and suggest that NSP14-induced m7G modification is a potential therapeutic target.

overall_design: RNA-seq profiling was performed on HEK293T cells transfected with either empty vector (EV-pCAGGS) or with plasmids encoding either SARS-CoV-2 NSP14 (NSP14-HA-pCAGGS) or its mutant (M4-HA-pCAGGS). RNA-Seq libraries were prepared from poly(A)-enriched or m⁷G-immunoprecipitated RNA.

first: Ensueno

last: Saenz-Altamirano

first: Jack Chun-Chieh