title: Lack of cortistatin drives neuroimmune and vascular dysfunction in brain ischemia

city: Granada

first: Jose

middle: Luis

last: Ruiz Rodriguez

state: Granada

address: Avda. del Conocimiento 17. P. T. Ciencias de la Salud

institute: IPBLN-CSIC

summary:
Ischemic stroke remains a leading cause of death and disability, with limited therapies addressing its
pathophysiology. Neuroinflammation, blood–brain barrier disruption, and immune dysregulation critically contribute
to both acute neuronal injury and chronic functional decline. Elucidating the endogenous factors that govern these
processes and understanding the intricate interplay among them is essential for developing effective therapeutic
strategies. Cortistatin, a neuropeptide expressed in the nervous and immune systems, exhibits potent immunomodulatory
actions, but its role in neuroinflammatory diseases remains unclear.
In this study, we combined human and murine transcriptomic analyses with a preclinical stroke model
in cortistatin-deficient mice to investigate the endogenous and therapeutic roles of cortistatin during the acute (48 h)
and subacute (7 days) phases of ischemic stroke.
We demonstrate for the first time that cortistatin deficiency amplified ischemia-induced transcriptional programs,
heightening neuroinflammation and glial/neurovascular dysfunction, and worsening neurological outcomes.
Interestingly, cortistatin deficiency accelerated aging-associated pathological features, underscoring its essential role
in neuroimmune and cerebrovascular homeostasis. Conversely, cortistatin administration improved neuronal survival,
mitigated immune dysfunction, and preserved myelin and vascular integrity during both the acute and subacute
stages. These findings provide the first evidence identifying cortistatin as an endogenous neuroimmune regulator
in ischemic stroke and a promising multimodal therapeutic agent for improving acute and long-term outcomes.

overall_design: RNA-seq study of KO and WT mice for the neuropeptide cortistatin, both control or subjected to the MCAO model

first: J

last: Castillo-González

first: P

last: Vargas-Rodríguez

first: I

last: Serrano-Martínez

first: A

last: Cuenca-Martagón

last: Forte-Lago

first: M

last: Price

first: L

last: Buscemi

last: Hirt

last: Ruiz

first: E

last: González-Rey


title: Single-cell transcriptomics analysis of colorectal cancer (CRC)

status: Public on Jun 15 2026

city: Houston

first: Fuduan

last: Peng

state: TX

address: 1881 East Rd

country: USA

institute: MD Anderson Cancer Center

type: Expression profiling by high throughput sequencing

summary: Understanding cellular processes underlying colorectal cancer (CRC) development is needed to devise intervention strategies. Here, we performed single-cell RNA sequencing (scRNA-seq) of human treatment-naive colorectal cancer.

overall_design: Gene expression profiling by high throughput scRNA-seq analysis

first: Haoyue

last: Liu

first: Florencia

last: McAllister


title: ORCA-mediated Polycomb Repressive Complex stabilization maintains 3D-genome architecture and controls replication timing [Cut & Run]

city: Urbana

first: Supriya

last: Prasanth

state: IL

address: 601 S Goodwin Avenue

department: Cell and Developmental Biology

institute: University of Illinois Urbana Champaign

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Polycomb bodies, also called Polycomb group (PcG) protein complexes, are implicated in gene regulation, especially during development, differentiation, and during the maintenance of tissue-specific functions in multicellular organisms. Predominantly, in transformed cells, PcG bodies  form distinct nuclear foci, within which PcG-bound DNA is localized. These structures likely represent misregulated gene expression due to the loss of normal regulatory mechanisms, yet the molecular function of these bodies in cellular homeostasis remains unknown. Using TSA-Seq (Tyramide signal amplification), we provide the first-of-a-kind comprehensive view of the genomic regions, including specific centromeric and telomeric sites that are in proximity to the PcG bodies. Further, these regions are enriched for the repressive histone marks, H3K27me3, H3K9me3 and depleted for active marks, H3K4me3 consistent with a lack of accessible chromatin. We find high density of replication origins around PcG bodies, consistent with the replication factor, ORCA/LRWD1 localizing at these sites. ORCA interacts with the PRC complex, stabilizes the H3K27 methyltransferase, and facilitates the deposition of this histone mark at specific chromatin sites. Loss of ORCA impacts the chromatin organization around the PcG bodies, leading to decompaction of the repeat regions, and enhanced initiation from replication origins. Our results indicate that ORCA interacts with the PcG complex-bound chromatin and maintains a repressed heterochromatin environment to control the timing of replication origin firing.

overall_design: CUT&Run of BMI1, RNF2 and EZH2 in U2OS cells with presence or absence of ORCA.

first: Neha

last: Chetlangia

first: Bhushan

middle: L

last: Thakur

first: Christophe

middle: E

last: redon

first: Oraya

middle: J

last: Zinder

first: Lorinc

middle: S

last: Pongor

first: YouJin

last: Song

first: Darya

last: Asoudegi

first: Dazhen

first: Chris

last: Fields

first: Kannanganattu

middle: V

first: Mirit

middle: I

last: Aladjem

middle: G


title: Delayed molecular aging, preservation of energy metabolism and enhanced exercise response in exercise-trained human muscle

status: Public on Jun 16 2026

city: Amsterdam

first: Georges

last: Janssens

address: Meibergdreef 9

country: Netherlands

institute: Amsterdam UMC

summary: Exercise is fundamental to healthy aging, yet how it mitigates age-related molecular changes and how fitness level shapes exercise responses remain unclear. To address this, we performed transcriptomics, lipidomics, and metabolomics on skeletal muscle of young and older adults with differing physical function, both before and after an acute bout of sub-maximal exercise. At baseline, older adults exhibited reduced expression of genes associated with cellular respiration and energy metabolism compared to young adults with comparable activity levels. Here we show that in trained older adults, 50% of these age-related differences were absent, resulting in profiles resembling those of young adults. While all participants displayed transcriptional immune and stress responses upon acute exercise, the magnitude of these responses in older adults correlated positively with their physical fitness. Integrated multi-omic analyses further revealed links between mitochondrial respiration, lipid metabolism, stress responses and NAD⁺ biology. These findings demonstrate that sustained physical training transforms age-related molecular profiles and provides a molecular atlas for studying fitness-dependent aging mechanisms.

overall_design:
RNAseq of poly-a libraries of human muscle of various age and fitness levels before and after exercise

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due to ethical considerations for human data and participant consent forms.
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first: Janssens

last: Georges E.


title: Exploratory identification of candidate biomarkers and molecular contributors to paclitaxel-induced peripheral neuropathy in patients with breast cancer through proteomic analysis

city: Shimamoto-cho, Mishima-gun

first: Keiichi

last: Minami

state: OSAKA

address: 3-1-1 Sakurai

department: Minase Research Institute

country: Japan

institute: Ono Pharmaceutical

summary: Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant adverse effect of paclitaxel in patients with breast cancer. However, reliable biomarkers for early detection and monitoring of CIPN are lacking.Methods: We investigated neurofilament light chain (NfL) and galectin-3 as candidate biomarkers for CIPN, and performed proteomic analysis to identify novel molecular contributors in two cohorts of patients with breast cancer undergoing paclitaxel therapy. Blood samples were collected longitudinally to measure NfL and galectin-3 levels. Differentially expressed proteins associated with CIPN onset were identified by proteomics.Results: NfL levels significantly increased in patients with CIPN, from as early as 3 weeks after treatment initiation. NfL levels were markedly higher in patients with vs. without CIPN. There were no changes or between-group differences in galectin-3 levels. Proteomic analysis identified upregulation of alcohol dehydrogenase 4 (ADH4) and downregulation of vesicular overexpressed in cancer prosurvival protein 1 (VOPP1) in CIPN, implicating oxidative stress and disrupted mitochondrial dynamics in the pathogenesis of CIPN.Conclusion: NfL represents a candidate biomarker for early detection of CIPN, and we identified proteins potentially associated with the development of CIPN. Our findings provide further insights into the pathogenesis of CIPN. Integrating biomarkers and proteomics paves the way for precision medicine to manage chemotherapy-induced toxicities.

overall_design: In 12 breast cancer patients, plasma samples were collected at four time points: before the start of paclitaxel administration, and at 4 weeks, 8 weeks, and 12 weeks. Proteomics analysis was conducted using SomaScan by Somalogic. Due to the discontinuation of treatment in some patients, there are missing data points.

first: Nobuyoshi

last: Kittaka


title: ORCA-mediated Polycomb Repressive Complex stabilization maintains 3D-genome architecture and controls replication timing

summary: Polycomb bodies, also called Polycomb group (PcG) protein complexes, are implicated in gene regulation, especially during development, differentiation, and during the maintenance of tissue-specific functions in multicellular organisms. Predominantly, in transformed cells, PcG bodies  form distinct nuclear foci, within which PcG-bound DNA is localized. These structures likely represent misregulated gene expression due to the loss of normal regulatory mechanisms, yet the molecular function of these bodies in cellular homeostasis remains unknown. Using TSA-Seq (Tyramide signal amplification), we provide the first-of-a-kind comprehensive view of the genomic regions, including specific centromeric and telomeric sites that are in proximity to the PcG bodies. Further, these regions are enriched for the repressive histone marks, H3K27me3, H3K9me3 and depleted for active marks, H3K4me3 consistent with a lack of accessible chromatin. We find high density of replication origins around PcG bodies, consistent with the replication factor, ORCA/LRWD1 localizing at these sites. ORCA interacts with the PRC complex, stabilizes the H3K27 methyltransferase, and facilitates the deposition of this histone mark at specific chromatin sites. Loss of ORCA impacts the chromatin organization around the PcG bodies, leading to decompaction of the repeat regions, and enhanced initiation from replication origins. Our results indicate that ORCA interacts with the PcG complex-bound chromatin and maintains a repressed heterochromatin environment to control the timing of replication origin firing.

overall_design: We wanted to understand how ORCA knockdown impacts transcription, we performed RNA-seq in control and siORCA conditions.


title: ORCA-mediated Polycomb Repressive Complex stabilization maintains 3D-genome architecture and controls replication timing [ChIP-seq]

overall_design: ChIP-seq involves crosslinking cells with formaldehyde, extracting and sonicating chromatin, then immunoprecipitating with antibodies against validated ChIP-grade antibodies. After stringent washing, DNA eluted, purified, and sequenced.


title: Targeting Mannosylation of Nicastrin N-glycans Attenuates γ-Secretase Activity and Notch-dependent Leukemia Progression

status: Public on Jul 06 2026

city: HangZhou

first: Hua

last: Jiang

state: Zhejiang

address: Hangzhou, Zhejiang province, China

country: China

institute: Westlake University

summary: γ-Secretase is a transmembrane protease complex that cleaves multiple type I transmembrane proteins, including amyloid precursor protein and NOTCH. Although numerous γ-secretase inhibitors and modulators targeting Notch-dependent cancers have been developed in recent decades, their clinical translation has been hampered by low substrate specificity and on-target gut toxicity. Using a proteomics-based screening approach, we identified dedicator of cytokinesis protein 2 (DOCK2) as an interactor of the γ-secretase subunit Nicastrin (NCSTN). We further demonstrate that DOCK2 regulates mannosylation of NCSTN N-glycans, which in turn modulates γ-secretase activity toward NOTCH receptors. Both genetic depletion of DOCK2 and pharmacological inhibition of NCSTN mannosylation with Kifunensine attenuated Notch-dependent leukemia progression in vivo. Collectively, these findings uncover a regulatory mechanism underlying substrate-specific activation of γ-secretase and suggest a promising therapeutic strategy for Notch-related diseases.

overall_design: RNA-seq profiing of DND41 WT cells and DOCK2 KO cells, as well as treated with γ-Secretase inhibitor DBZ and Kifunensine

first: Weixiang

last: Bian

first: Yanjun

last: Cao

first: Zhuo

last: Zhang

first: Yijia

last: Chen

first: Yue

last: Sui

first: Hongqiang

last: Qin

first: Xu

last: Li


title: Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma [mouse RNA-Seq]

status: Public on Jun 13 2026

city: Bronx

first: Deyou

last: Zheng

state: NY

address: 1301 Morris Park Avenue

department: Department of Genetics

institute: Albert Einstein College of Medicine

summary: Squamous cell carcinomas (SCCs) are common epithelial malignancies frequently associated with EZH2 upregulation, which correlates with aggressive growth and poor prognosis. EZH2 functions as the catalytic subunit of Polycomb repressive complex 2 (PRC2), which deposits the repressive H3K27me3 histone mark, yet PRC2 function in SCC pathogenesis remains unresolved. Here, we uncover a paradox: although EZH2 is elevated, the PRC2-catalyzed H3K27me3 is profoundly reduced in human SCC and complementary murine models. Mechanistically, we identify that oncogenic Ras signaling causes degradation of the PRC2 subunit EED, destabilizing PRC2 and depleting H3K27me3. Loss of EED reprograms keratinocytes into an aggressive tumor-specific cell state and induces paracrine factors that remodel the tumor microenvironment, driving metastasis. Remarkably, reintroducing EED suppresses tumor growth via restoring PRC2 integrity and H3K27me3 levels, revealing the reversibility of this epigenetic collapse. These findings link oncogenic signaling to epigenetic reprogramming and uncover PRC2 reconstitution as a potential therapeutic option in epithelial cancers.

overall_design: FACS isolate epidermal basal cells from the back skin of control and K14-Eed iKO mice. RNA from the sorted cells was analyzed by RNA-seq.

first: Meng-Yen

first: Xiang Yu

first: Elena

last: Ezhkova


title: Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma [human CUT & RUN]

overall_design: The H3K27me3 and PRC2 complex CUT&RUN in normal human skin and A431 transplant tumors, 400,000 FACS-enriched epidermal  cells were isolated from the human skin . 400,000 FACS-enriched A431 cells were isolated from tumors of A431transplant. CUT&RUN used the CUTANA™ ChIC/CUT&RUN Kit for FACS-isolated epidermal cells or A431 cells. Sequencing libraries were generated using NEBNext Ultra II DNA Library Prep Kit for Illumina


title: Oncogenic Ras drives EED degradation and PRC2 dysfunction to promote aggressive squamous cell carcinoma [mouse CUT & RUN]

overall_design: The H3K27me3 CUT&RUN in normal mouse skin and SCC, 100,000 FACS-enriched epidermal basal cells were isolated from the back skin of P70 C57BL/6 wildtype mice. 100,000 FACS-enriched SCC cells were isolated from tumors of control-DMBA, Eed iKO-DMBA, SCC-GFP, and SCC-Eed-expressing  using the CUTANA™ ChIC/CUT&RUN Kit for FACS-isolated epidermal keratinocytes or SCC cells. Sequencing libraries were generated using NEBNext Ultra II DNA Library Prep Kit for Illumina


title: C1QBP expression and function in acute myeloid leukaemia.

status: Public on Jun 14 2026

city: Dalian

first: Xuehong

state: Liaoning

address: No. 9 West Section Lvshun South Road, Dalian 116044, Liaoning, China

department: Institute of Cancer Stem Cell

institute: Dalian Medical University

summary: Acute myeloid leukemia (AML) is a lethal hematological malignancy that originates from unlimited proliferation of immature progenitors characterized by medullary and extramedullary invasion, with a 5-year overall survival (OS) rate of <30% with chemotherapy. Infiltration of bone marrow (BM) malignant leukemia cells into tissues other than the BM to form an extramedullary mass, referred to as extramedullary infiltration (EMI), is a common concomitant symptom of AML, with an incidence at initial diagnosis ranging from 2.5% to 30.5%,4-10 to even 65% if diagnosed by positron emission tomography/ computed tomography. Our privios study have identified the most featured macrophage-like C1Q+ population associated with EMI and adverse outcome and confirmed its unique function in migration. Here, we want to know the expression and function of C1QBP as the surface globular C1Q receptor in patients with AML who experience EMI.

overall_design:
Comparative gene expression profiling analysis of RNA-seq data for bone marrow samples from patients with AML and healthy donors.

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

last: Lu

first: Jinsong

last: Yan


title: Macrophage Niche Reconstitution Reveals Dynamic Transcriptional and Communication Networks Renal Macrophage-Epithelial Communication

status: Public on Jun 12 2026

city: New Orleans

first: Xuebin

state: LA

address: 1430 Tulane Avenue

department: Pathology

institute: Tulane University

summary: Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To the end, we employed an inducible hCD59 intermedilysin (ILY) ablation system to achieve rapid and specific depletion, and subsequent replenishment of RMs, followed by longitudinal scRNA-seq analysis of kidneys at baseline and days 1, 3, and 7 post-ablations. RM ablation triggered a rapid and sustained upregulation of Cx3cl1, predominantly in proximal tubular epithelial cells (PTC1/PTC2), establishing a persistent chemotactic niche signal that coincided with macrophage repopulation. Regenerating RMs transitioned from inflammatory/stress-associated states toward metabolically active and proliferative phenotypes enriched in glycolysis, oxidative phosphorylation, MYC, and cell-cycle programs, with attenuation of canonical inflammatory pathways. Cell–cell communication analysis revealed an early burst of intercellular signaling at day 1, followed by progressive normalization, with fibronectin (Fn1), osteopontin (Spp1), chemokine (Ccl), and amyloid precursor protein (App) axes emerging as key mediators of niche restoration. Transcriptional network analysis identified a conserved regulatory module (Tfe3, Mitf, Hif1a, Myc, Gabpa, Rcor1) coordinating macrophage differentiation and regenerative programming, linking metabolic adaptation to lineage reconstitution. Sub-clustering revealed five dynamically shifting RM subsets with distinct inflammatory, remodeling, proliferative, and surveillance states, reflecting a hierarchical regeneration process. Functional validation using clodronate-mediated depletion in Spp1 (Opn)-deficient mice demonstrated impaired macrophage repopulation, establishing osteopontin as a critical regulator of RM regeneration. Together, these data define a coordinated epithelial–immune circuit in which CX3CL1-driven chemotaxis, Spp1-dependent signaling, and a core transcriptional network orchestrate macrophage niche reconstitution and kidney repair following acute immune cell ablation.

overall_design: Single-cell RNA sequencing was performed on mouse kidney single-cell suspensions to characterize renal macrophage ablation and regeneration after inducible hCD59/intermedilysin-mediated depletion. Cx3cr1CreER+/−/ihCD59+/− mice were treated with tamoxifen to induce hCD59 expression in Cx3cr1-expressing cells. Fifteen days after tamoxifen induction, mice received a single intravenous dose of intermedilysin (ILY, 120 ng/g body weight) to deplete renal-resident macrophages. Kidneys were collected at baseline/control and at days 1, 3, and 7 after ILY administration. Single-cell suspensions were prepared from perfused kidneys and processed using the 10x Genomics Chromium Single Cell 3′ RNA-seq platform. One single-cell RNA-seq library/sample was generated for each condition/time point.

first: Mohammad

last: Islamuddin

first: Lixuan

last: Ji

first: Yilin

first: Kejing

last: Song

first: Calder

middle: R

last: Ellsworth

first: Jack

last: Rappaport

first: Chenxiao

last: Wang

first: Shumei

last: Liu

first: Jay

last: Kolls

first: Xiaojiang

last: Xu


title: Regenerative macrophages enhance stem cell-derived beta-cell function and engraftment

city: Vancouver

first: Bruno

middle: Felipe de Abreu

last: Freitas

state: British Columbia

address: 938 W 28th Ave

department: Surgery

country: Canada

institute: University of British Columbia - BC Children's Hospital Research Institute

summary: The generation of insulin-producing beta cells from human embryonic stem cells (SC-β cells) holds promise for treating type 1 diabetes. Transplantation of SC-β cells is already in clinical testing, but generating mature cells with insulin-secreting properties similar to endogenous cells has been challenging. Since macrophages are essential for islet development, we hypothesized they could enhance SC-β-cell differentiation and function. We co-aggregated SC-macrophages which were either unpolarized (SC-MUnp), or polarized to inflammatory (SC-MInf) or regenerative (SC-MReg) states during stage 7 of SC-β-cell differentiation. SC-MRegs improved maturity marker expression, glucose-stimulated insulin secretion, and metabolic activity in SC-β cells. Transplantation of SC-β cells co-aggregated with SC-MRegs into diabetic mice normalized glycemia significantly faster than transplantation of SC-β cells alone. The finding that addition of macrophages during SC-β differentiation accelerates functional maturation represents a significant advance in the production of SC-β cells as a regenerative cell therapy for type 1 diabetes.

overall_design: scRNA-seq of 1) INS-GFP Stem cell derived-beta cells cultured in vitro alone, 2) INS-GFP stem cell derived-beta cells with stem cell-derived CD68-mScarlet macrophages polarized to the regenerative phenotype with IL-4 and IL-13, and 3) stem cell-derived CD68-mScarlet macrophages polarized to the regenerative phenotype with IL-4 and IL-13 alone.

middle: F

first: Sean

middle: A

last: Fox

first: Paul

middle: C

last: Orban

first: Jane

last: Velghe

first: Majid

last: Mojibian

first: Derek

last: Dai

first: Galina

last: Soukhacheva

first: Francis

last: Lynn

first: Megan

middle: K

last: Levings

first: Bruce

last: Verchere


title: From iPSC to manufactured iNK cells using CombiCult® screening platform

status: Public on Jun 11 2026

city: Stevenage

first: Marina

last: Tarunina

state: Hertfordshire

address: Plasticell Ltd., Stevenage Bioscience Catalyst, Gunnels Wood Road

country: United Kingdom

institute: Plasticell Ltd.

summary: We used Parse Biosciences scRNAseq to characterize human induced pluripotent stem cell (iPSC)-derived NK cells (iNKs) at transcriptional level. Gene expression profiles of iNKs were compared with reference samples.

overall_design: iNKs were differentiated from iPSCs using static culture or manufactured using Stirred Tank Bioreactor (STR). iPSCs, peripheral blood (PB)-CD34+ cells, umbilical cord blood (UCB)-CD34+ cells, peripheral blood mononuclear cells (PBMCs) and PBMC-derived NK cells (PBMC-NK) were included in the scRNAseq as reference samples.

first: Giuseppe

last: D'Agostino

first: Lam

last: Lam

first: Tatyana

last: Ponomaryov


title: Highly efficient and low-mosaicism piggyBac transgenesis platform for rapid founder phenotyping [Amplicon-seq]

city: Otsu

first: Shoma

last: Matsumoto

state: Shiga

address: Setatsukinowa-cho

department: Research Center for Animal Life Science

institute: Shiga University of Medical Science

summary: Pronuclear microinjection is the most widely used method for producing transgenic (Tg) animals. Because its efficiency is typically <20%, phenotypic characterization of Tg animals is usually performed from the next generation (F1) onwards. Conventional Cre-loxP-based conditional knockout (cKO) mouse production requires generating two genetically modified strains and multiple rounds of breeding before cKO mice are available for analysis. Here, we optimized a piggyBac transposon-based method of Tg mouse production and established conditions under which nearly all founder (F0) embryos are transgenic. Using a single-cell RNA sequencing-based strategy, we characterized mosaicism in F0 embryos and demonstrated that piggyBac-mediated transgene integration occurs early in embryonic development. We also achieved ~70% efficiency in generating bacterial-artificial-chromosome-Tg mice. By combining this method with genome editing, we developed a strategy for tissue-specific-knockout phenotyping in the F0 generation. Our findings establish a highly efficient piggyBac-based platform that expands experimental options for Tg animal production by supporting rapid F0-based phenotypic assessment while also facilitating efficient generation of F0 animals for subsequent breeding.

overall_design: Amplicon-seq for E11.5 transgenic mouse embryos and embryonic stem cells with DNA barcode-linked GFP. The libraries were constructed from genomic DNA from mES BC lines, their mixtures and mouse embryos and sequenced to detect bona fide DNA barcodes integrated into thier genome.

first: Eiichi

last: Okamura

first: Masatsugu

last: Ema


title: Highly efficient and low-mosaicism piggyBac transgenesis platform for rapid founder phenotyping [Transgene-specific scRNA-seq]

overall_design:
Single-cell RNA-seq for E11.5 transgenic mouse embryos with DNA barcode-linked GFP.  Two founder generation Tg mice (F0_8 and F0_9), F1 generation mouse (F1_1), and pseudobulk sample (F1_mix) were multiplexed using CellPlex Kit from 10x Genomics. From the scRNA-seq cDNA library, only transgene loci were amplified using transgene-specific primers.

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The table below lists GEO accessions reused/reanalyzed for this study.
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first: Hideto

last: Mori

first: Nozomu

last: Yachie


title: Highly efficient and low-mosaicism piggyBac transgenesis platform for rapid founder phenotyping [single-cell RNA-seq]

overall_design: Single-cell RNA-seq for E11.5 transgenic mouse embryos with DNA barcode-linked GFP. Two founder generation Tg mice (F0_8 and F0_9), F1 generation mouse (F1_1), and pseudo-mosaic sample (F1_mix) were multiplexed using CellPlex Kit from 10x Genomics.


title: HDL-mimetic peptide treatment reverses APOE4-induced transcriptomic and lipidomic alterations in the brain of humanized APOE mice

city: Minneapolis

first: Ling

last: Li

email: lil@umn.edu, linglilab@umn.edu

state: MN

address: 2001 6th Street SE Rm 4-208

department: Department of Experimental and Clinical Pharmacology

institute: University of Minnesota

summary: INTRODUCTION: The apolipoprotein E4 (APOE4) allele is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). APOE4 has reduced lipidation capacity and impaired lipid transport, disrupting neuronal maintenance. The high-density lipoprotein (HDL)-mimetic peptide 4F offers a potential therapeutic strategy. METHODS: To investigate how APOE4 alters brain gene expression and lipid metabolism and to evaluate the therapeutic potential of 4F, we performed dual-omics analysis in APOE4/4 (E4/4) and APOE3/3 (E3/3) mice treated intraperitoneally with D-enantiomer of 4F (D4F) or vehicle for 12 weeks to 13 months of age. RESULTS: APOE4/4 mice showed widespread transcriptomic and lipidomic alterations, including downregulation of lipid metabolism and synaptic pathways, increased ceramides, sphingomyelins, and cholesteryl esters, and decreased triglycerides and diglycerides. D4F treatment restored gene expression and lipid profiles toward APOE3/3 levels. DISCUSSION: These findings reveal molecular mechanisms underlying APOE4-driven dysregulation and support the therapeutic potential of HDL-mimetic peptides to mitigate APOE4-associated alterations in AD.

overall_design: We performed bulk RNA-seq to investigate transcriptomic alterations associated with APOE genotype and the impact of 4F treatment in E4/4 and E3/3 mice (10.5 ± 0.1 months old at baseline). Brain tissue from 32 mice (16 males and 16 females) was collected after 12 weeks of daily 4F or vehicle administration, to 13.2 ± 0.1 months of age. Libraries were sequenced on the Illumina NovaSeq 6000 platform, yielding an average of ~20 million 150-bp paired-end reads per sample.

first: Allison

last: Chang

first: Minwoo

last: Kim

first: Wenhui

last: Qu

first: Matthew

last: Glittenberg

first: Danni


title: An Exploratory Integrative Analysis of Plasma Transcriptomic and Proteomic Predictors of Response to Total Neoadjuvant Therapy in Locally Advanced Rectal Cancer

status: Public on Jun 10 2026

city: fuzhou

first: 豪博

last: 黄

address: 本人（申请人）

institute: 福建医科大学附属协和医院

summary: Aims to screen and identify plasma biomarkers associated with treatment response to TNT in patients with locally advanced rectal cancer (LARC) to predict pathological complete response (pCR). Pre-treatment plasma RNA sequencing and functional annotation were performed in six patients with LARC (three pCR and three non-pCR) to identify differentially expressed genes (DEGs) associated with TNT response. Compared to the non-pCR group, 365 DEGs were upregulated, and 198 were downregulated in the pCR group. These genes are involved in pathways related to cell growth and death, signal transduction, metabolism, the immune system, insulin secretion, mitophagy, and neutrophil extracellular trap formation.

overall_design: RNA-seq profiling of plasma extracted from 6 LARC patients (3 pCR vs. 3 non-pCR).

first: Zonglin

last: Zhu

first: Bin

first: Liping

last: Fan

first: Haobo

last: Huang


title: Comparative transcriptomics (RNA-Seq) of Trifolium pratense roots infected with the fungal pathogens Fusarium oxysporum or Phoma medicaginis

city: Scarborough

first: Mehran

last: Dastmalchi

state: Ontario

address: 1265 Military Trail

department: Cell & Systems Biology

institute: University of Toronto

summary: The study examines transcriptomes of Trifolium pratense (red clover) roots challenged with the fungal pathogens Fusarium oxysporum and Phoma medicaginis. Fungal infection broadly activated both core metabolic processes and specialized metabolic pathways, including transcripts encoding phenylpropanoid and (iso)flavonoid biosynthetic enzymes. Among 33 predicted isoflavonoid-pathway genes, many were differentially expressed in at least one fungal treatment, with the late steps of pterocarpan biosynthesis particularly induced by P. medicaginis. These comparative transcriptomes provide insight into the activation and regulation of biotic stress responses as well as the engagement of legume-specific isoflavonoid biosynthesis, a pathway closely linked to antimicrobial defense.

first: Lee Marie

last: Raytek


title: Decoupling oxidative resilience from reprogramming to rejuvenate the RPE and restore vision [GSTA4_RNA-seq_1]

city: Cambridge

first: Yuancheng Ryan

last: Lu

state: MA

address: 455 Main St

institute: Whitehead Institute for Biomedical Research

summary: OCT4, SOX2, and KLF4 (OSK) Yamanaka factors can reverse age-related epigenetic changes, yet alternate mechanisms by which they promote tissue resilience remain poorly understood. Oxidative stress contributes to retinal pigmented epithelium (RPE) degeneration in age-related macular degeneration. Here, we show that OSK expression in RPE promotes Tet2-independent oxidative resilience through acute, memory-free transcriptomic changes, and restores visual function in aged mice. Integrative functional genomics helped identify GSTA4, a detoxifying enzyme that clears the lipid peroxidation byproduct 4-HNE, as a key OSK downstream effector. OSK directly and dynamically activates GSTA4, recapitulating a stem cell-derived stress resilience program. GSTA4 overexpression alone enhances oxidative resilience, rejuvenates the aged RPE transcriptome, and reverses visual decline while avoiding OSK’s pleiotropic effects. GSTA4 is upregulated across diverse lifespan-extending interventions suggesting a broader pro-longevity role. These findings uncover a previously unrecognized protective axis directly regulated by OSK, that can be decoupled from reprogramming, providing a framework for developing more precise rejuvenation therapies.

overall_design: RPE cells from young or aged mice, as well as aged mouse RPE cells collected after AAV2‑tTA or AAV2‑tTA;TRE‑OSK treatment, were first preserved in RNAprotect Cell Reagent and subsequently processed with TRIzol for RNA extraction.


title: Single-cell RNA-seq of human non-lesional whole skin adjacent to an invasive melanoma excision scar, 5cm from the scar biopsy, and at a distant photoprotected site

status: Public on Jun 09 2026

city: Woolloongabba

first: Katie

middle: June

last: Lee

state: QLD

address: 37 Kent St

department: Frazer Institute

country: Australia

institute: The University of Queensland

summary: Potentially carcinogenic mutations are widespread throughout the skin, and it is unknown why only some sites develop into a malignancy while most others continue to function normally. Using 10x Genomics Chomium Flex scRNA-seq, we explored differences in skin with similar levels of photodamage adjacent to and proximal to (5cm away from) a melanoma excision scar, and distant photoprotected skin.

overall_design: Whole skin biopsies were collected from the back at three sites per participant: 1) adjacent to a melanoma excision scar ("scar-adjacent"), 2) 5cm from the scar-adjacent biopsy in skin with clinically similar photodamage (“proximal”), and 3) photoprotected skin on the hip or buttock (“distant photoprotected”). Each sample was cryogenically preserved and dissociated into a fixed single cell suspension, then pooled based on biopsy site to produce a scar-adjacent pool, proximal pool, and distant photoprotected pool. The scar biopsy pool contained cells from 12 participants (2 female, 10 male), with a mean age 55.8 years, mean total naevus >5mm count 45.9, and Fitzpatrick skin types I-III. Tthe proximal pool contained cells from 13 participants (3 female, 10 male), with a mean age 58.4 years, mean total naevus >5mm count 50.7, and Fitzpatrick skin types I-III. The distant photoprotected pool cells from 14 particpants (4 female, 10 male), with a mean age 59.3 years, mean total naevus count >5mm 43.9, and Fitzpatrick skin types I-III.

first: Yung-Ching

last: Kao

first: Mitchell

last: Stark


title: Spatial transcriptomic profiling of seborrhoeic keratoses

city: WOOLLOONGABBA

summary: Seborrhoeic keratoses (SKs) are common benign skin tumors arising from epidermal keratinocytes and frequently observed in older adults. We used spatial transcriptomics to profile a range of SKs, investigating their cellular composition and gene expression landscapes.

overall_design: The dataset is comprised of different subtypes of seborrhoeic keratoses with and without immune cell infiltration.

first: Harald

last: Oey


title: Proteome-wide identification of the druggable CRBN interactome

status: Public on Jun 08 2026

city: Lausanne

first: Nicolas

last: Thomä

address: Rte Cantonale

country: Switzerland

institute: EPFL

summary: Molecular glue degraders (MGDs), such as pomalidomide, induce degradation of non-native substrates by the E3 ligase CRL4CRBN through its substrate receptor CRBN. To explore CRBN programmability, we tested whether reported CRBN-MGD substrates are part of a network of latent CRBN interactors, proteins capable of MGD-induced CRBN binding without detectable degradation. Leveraging highly parallel interaction measurement (GluePCA) between CRBN and zinc-fingers (ZFs), we identified ~210 ZFs bound to CRBN-pomalidomide, where top binders are already reported as degraded by dedicated MGDs. To map latent CRBN-MGD interactions proteome-wide and define the accessible CRBN interaction space, we combined AI-derived protein surface queries (MaSIF-mimicry) with GluePCA. This pipeline identified 6 known and 43 novel CRBN-pomalidomide binders, including orthogonally validated hits. We find that these binders provide privileged starting points for MGD development. We expect this binding-focused workflow to be applicable to other MGD/E3 ligase systems, potentially extending the scope of this emerging drug class.

overall_design: Scanning of the molecular glue induced interaction of single and dual zinc-finger with CRBN and deep mutational scanning of dual zinc-finger with CRBN-molecular glue

first: Pius

last: Galli

first: Shuhao

last: Xiao

first: Yanxiang

last: Meng

first: Alexander

last: Hanzl

first: Alexandra

middle: M

last: Bendel

first: Regina

last: Baur

first: Jacob

last: Aguirre

first: Anna

last: Diaz-Rovira

first: Georg

last: Kempf

first: Lukas

last: Kater

first: Kenji

last: Shimada

first: Ye

last: Wie

first: Andreas

last: Scheck

first: Dominique

last: Klein

first: Siomne

last: Cavadini

first: Ben

last: Lehner

first: Guillaume

last: Diss

first: Bruno

last: Correia

middle: H


title: Human lungs maintain tissue-resident memory T cells against a broad spectrum of pathogens.

status: Public on Jun 07 2026

city: La Jolla

first: Pandurangan

last: Vijayanand

state: CA

address: 9420 Athena Cir

institute: La Jolla Institute for Immunology

summary: Immune responses in the lungs are essential for the prevention and control of a wide range of infections. Tissue-resident memory T (TRM) cells are critical for frontline immunity, yet in murine lungs they undergo rapid attrition, raising questions about their durability in the human lung. Here, using a T-cell receptor (TCR)-guided approach integrating single-cell transcriptomics with paired TCR repertoire profiling, we mapped over 87,000 pathogen-specific T cells from human lung tissue across 40 donors, many of whom harbored substantial TRM populations specific to multiple respiratory viruses. These findings suggest, contrary to observations in murine infection models, that the human lung is likely to serve as a reservoir of clonally expanded TRM cells specific to a broad spectrum of pathogens. Although the lung-associated lymph nodes (LLN) contained a small population of TRM cells, most TCRs from highly expanded TRM clones in the lungs were absent in the LLN, suggesting that LLNs are unlikely to serve as a major reservoir for lung TRM cells. While acquisition of the TRM phenotype in the lung was not biased towards specific pathogens, pathogen specificity influenced the transcriptional profiles of CD8+ TRM cells. Notably, influenza A virus (IAV)-specific CD8+ TRM cells expressed significantly higher levels of transcripts linked to tissue residence and effector properties compared to TRM cells specific to other pathogens. Overall, our findings reveal that the human lung retains a stable, yet diverse compartment of pathogen-specific TRM cells, with implications for understanding tissue-resident memory responses that persist after infections and vaccinations.

overall_design: Single-cell RNA-seq and T-cell receptor (TCR) repertoire profiling of CD3+ T cells from lung samples (n=40; study cohort) and lung-associated lymph node (LLN) samples (n=8; study cohort). Separately, single-cell TCR repertoire profiling of CD4+ T cells specific to a broad sprectrum of pathogen and vaccine antigens as captured by applying the antigen-reactive T cell enrichment (ARTE) assay to PBMC samples from 61 donors (resource cohort).

first: Vicente

last: Fajardo-Rosas

first: Aquib

last: Ehtram

first: Isabel

last: Marchand-Casas

first: Serena

last: Chee

first: Monalisa

last: Mondal

first: Celia

last: Ferrández-Alaminos

first: Francisco

last: Castaneda-Castro

first: Zubin

last: Roy

first: Lindsey

last: Chudley

first: Michael

last: Shackcloth

first: Judith

last: Cave

first: Aiman

last: Alzetani

first: Edwin

last: Woo

first: Elizabeth

last: Phillips

first: Simon

last: Mallal

first: Alba

last: Grifoni

first: Benjamin

last: Schmiedel

first: Alessandro

last: Sette

first: Bjoern

last: Peters

first: Christian

last: Ottensmeier


title: Systematic investigation reveals extensive Epstein-Barr virus transcriptional regulation of the human genome

city: Cincinnati

first: Matthew

last: Weirauch

state: Ohio

address: 3333 Burnet Avenue

department: Center for Autoimmune Genomics and Etiology (CAGE)

institute: Cincinnati Children's Hospital Medical Center

summary: We systematically investigate interactions between Epstein-Barr virus (EBV) transcriptional regulators (vTRs) and the human genome. Starting with 16 known and candidate vTRs, we identify nine whose introduction into human cells results in substantial alterations to host gene expression. Genome-scale determination of vTR genomic binding events and alterations to chromatin accessibility reveals a detailed map of EBV's functional interactions with the human genome, including >100,000 vTR binding events impacting almost a quarter of all human genes. BMRF1 emerges as a potent regulator, impacting >7,000 genes and altering >37,000 chromatin regions. Our results provide new evidence that EBV RTA interacts with and stabilizes the binding of human RBPJ. Network analysis reveals that many human genes are targeted by multiple EBV vTRs, highlighting the vast coordinated impact of EBV on human gene expression. This study provides a valuable, extensive resource for examining EBV-induced alterations to human gene regulation, with data available on multiple platforms.

overall_design:
We performed RNA-seq on Flp-In-293 cell lines that had been transiently transfected with one of 16 potential Epstein-Barr virus transcriptional regulators or a control. Experiments were performed in triplicate.

We performed RNA-seq, ATAC-seq and anti-GFP ChIP-seq on Flp-In-293 cell lines that had been transfected with one of nine Epstein-Barr virus transcriptional regulators or a control. Experiments were performed in triplicate.

For 3 cell lines, we also performed anti-RBPJ ChIP. Experiments were performed in triplicate.

We performed anti-GFP ChIP-seq on a Flp-In-293 cell line that had been transfected with a GFP-tagged YY1 construct. The experiment was performed twice.

We performed anti-EBNA2 ChIP-seq in 2 biological replicates from EBNA2+ EBV (B95.8) infected Ramos B cells.

We performed anti-GFP ChIP-seq on Akata cell lines that had been transfected either with the Epstein-Barr virus transcriptional regulator ZTA or a control. The experiments were performed in triplicate.

first: Leah

last: Kottyan


title: The lateral septum orchestrates state-dependent modulation of associative threat memory dynamics across the ovarian hormone cycle

city: Birmingham

middle: Kathleen

last: Lucas

state: AL

department: Psychiatry and Behavioral Neurobiology

institute: University of Alabama at Birmingham

summary: Single-nucleus ATAC- and RNA-sequencing data from adult female proestrus C57Bl/6J mouse brain lateral septum, threat conditioned and naive control animals. This GEO submission contains the processed RNA-seq/single-nucleus RNA-seq data associated with existing SRA records.

overall_design: This GEO processed-data package contains only the RNA-seq/single-nucleus RNA-seq processed data. The processed objects and tables are pooled/integrated from four existing SRA experiments: SRX32234682, SRX32234683, SRX32234684, and SRX32234685 from BioProject PRJNA1426424/SRP678460. Adult C57BL/6J female mice in proestrus were randomly assigned to threat-conditioned or threat-naive groups (n = 4 per group).


title: The Transcription Factor IRF8 drives tumor-specific exhaustion in CD8 T cells

status: Public on Jun 05 2026

first: Jesus

last: Corria-Osorio

state: Vaud

address: Chemin des Boveresses 155

department: Department of Fundamental Oncology

institute: Ludwig Institute for Cancer Research. Lausanne Branch. UNIL

summary: T-cell exhaustion is a hallmark of chronic infection and cancer and constitutes a major barrier for successful immunotherapies. In this study, we establish the central role of IRF8 as a transcription factor regulating tumor-induced T cell exhaustion. IRF8 is highly expressed in CD8 T cells in tumors but not during chronic infection, where the Irf8 locus is less accessible. Its expression depends on TCR stimulation but is altered in the presence of type I IFN. Overexpression of IRF8 strongly enforced T cell dysfunction while IRF8 knock-out in tumor specific CD8 T cells reduced TOX expression and ameliorated effector function by increasing IFNγ, GrzB and TNF production, resulting in a better tumor control. By comparing IRF8 to IRF2 and IRF4, we showed that the IRF family display some redundancy in the regulation of T cell exhaustion converging on TOX-dependent programs. Altogether, we established a new role for IRF8 as a tumor specific regulator of T cell function.

overall_design: scRNA-seq experiment was performed on ex vivo FACS sorted CD8 TILs issued from a cotransfer experiment. B6-Cas9 Mice were engrafted with B16-gp33 tumors, followed by a cotransfer of retrovirally transduced P14-Cas9 Control together with P14-Cas9 IRF(2, 4 or 8) KO CD8 T cells at day 7. 7 days after adoptive CD8 T cell transfer, mice were sacrificed, and tumors were passed through a 70 μm cell strainer. CD8 T cells were enriched using a positive CD8 TILs selection (Miltenyi), following manufacturer’s instructions. After CD8 TILs enrichment, cells were stained for FACS sorting as described above (viability marker, CD8-biotin, CD45.1, CD45.2, CD90.1). In a second step, cells were incubated with TotalSeq hashtagging streptavidin-APC antibodies (BioLegend) for multiplexing. Control and IRF KO cells issued from the same tumor were thus labeled with the same hashtagging sequence, allowing for a paired analysis of cells exposed to the same TME. The samples were pooled and FACS sorted based on viability and the expression of CD8a, CD90.1 and CD45.1/CD45.1.2, to separate P14 Control from P14 IRF KO cells.  CUT&RUN: CD8+ T cells from WT B6 mice were enriched by negative selection following the manufacturer’s protocol (Stemcell) and cultured following an in vitro chronic TCR stimulation protocol to induce exhaustion. Briefly, cells have been activated during 3 days with antiCD3 and aCD28 antibodies. Cells were then put on freshly aCD3-coated plates for 3 further rounds of stimulation every second day. CD8+ T cells were then FACS sorted and processed for CUT&RUN-seq following the manufacturer’s instructions (EpiCypher) with the modification of increasing the bead concentration to ensure smaller fragments were not lost during the purification process. Libraries were pooled and subjected to three further rounds of bead purification to exclude the adapter dimers present in the libraries.

first: Marco

last: Ongaro

first: Grégory

last: Verdeil

first: Yi-Chuan

last: Wang


title: Characterization of a Human Cutaneous Squamous Cell Carcinoma Xenograft Mouse Model

city: Salzburg

first: Giorgia

last: Nasi

address: Hellbrunner strasse 34

country: Austria

institute: University of Salzburg

summary: To study the biology of immune cell biology (e.g. human cutaneous gamma delta T cell) in human skin tumours, an in vivo SCC xenograft mouse model was established. To closely resemble the human skin microenvironment, human tumour cells were introduced into an engineered human skin on the back of NSG mice. Transcriptome analysis of bulk-RNAseq data generated from biopsies of the xenograft model as well as human skin and tumour was conducted to test which features of the model resemble the situation in humans.

overall_design: Engineered skin (ES) was generated from E6E7 immortalized human fibroblasts and keratinocytes, which were in vitro expanded and added to a silicone chamber implanted on the backs of NSG mice. Xenograft SCC (xSCC) was generated using SCC-13 cells, which were intradermally injected into ES. Total RNA was extracted from biopsies of human healthy donor (HD) skin (n=5), human SCC (huSCC, n=5), ES (n=5) and xSCC (n=5). Libraries were prepared for mRNA sequencing on Illumina NovaSeq6000 instrument. Reads were mapped to GRCh38 using STAR (v2.7.11b) aligner with GENCODE v46 annotations.

first: Iris

last: Gratz


title: Deep phenotyping of an ATDC5 in-vitro cartilage model system

city: Freiburg

first: Anna

last: Klawonn

address: Hugstetter Str. 55

country: Germany

institute: University Hospital Freiburg

summary: Cartilage is characterized by a highly specialized extracellular matrix (ECM) secreted by chondrocytes and limited self-regenerative capacity. In vivo investigations of chondrogenesis are limited by difficult and traumatic access, especially in humans. While it is known for decades that disturbances of chondrocyte differentiation and changed cartilage ECM composition cause severe phenotypes skeletal phenotypes in vertebrates, a detailed molecular understanding of chondrogenesis and cartilage ECM formation is still missing, especially in the context of human genetic skeletal diseases.

overall_design: ATDC5 cells, derived from AT805 mouse teratocarcinoma cells, have been used in the past to model chondrogenic differentiation, however, most studies have investigated few major cellular differentiation markers only so that the composition of the secreted ECM as well as effects on the ATDC5 transcriptome upon differentiation are still unclear. Here, we performed time-resolved transcriptomic and ECM proteomic analyses of differentiating ATDC5 cells. Both datasets confirmed the formation of a cartilage-like matrix with increasing expression of key chondrocyte genes over the course of differentiation. ECM proteomics further revealed a number of ECM components not previously reported in ATDC5 cells or the secreted ECM, encompassing collagens, proteoglycans, glycoproteins and other secreted factors. Overall, our findings provide a more detailed molecular characterization of ATDC5 chondrogenesis and highlight the potential of this model system for ECM-focused studies.

first: Stefan

last: Tholen

first: Ilona

last: Skatulla

first: Chiara

last: Schröder

first: Sebastian

last: Arnold

first: Oliver

last: Schilling

first: Miriam

last: Schmidts


title: Anti-osteoporosis mechanism of resistance exercise in ovariectomized rats based on transcriptome analysis: a pilot study

status: Public on Jun 06 2026

city: Nanjing

first: Qing

address: No.138 Xianlin Street

institute: Nanjing University of Chinese Medicine

summary: Postmenopausal osteoporosis is the main cause of fractures in women. Resistance exercise has a positive effect on bone mineral density in postmenopausal osteoporosis patients, but its mechanism is unclear. The purpose of this study was to explore the mechanism of resistance exercise in improving ovariectomized osteoporotic rats based on the transcriptome sequencing technique. Eighteen female Sprague-Dawley rats were randomly divided into the sham-operated group, the non-exercise group, and the resistance exercise group. The rat model of postmenopausal osteoporosis was established by bilateral ovariectomy. Ten weeks after the operation, the resistance exercise group received 2 weeks of adaptive training, and 12 weeks of resistance exercise began in the 13th week. The rats were trained 5 days per week, in 4 sets of 3 repetitions per day. After the intervention, all rats were sacrificed, and the body weight, bone mineral density, trabecular bone microarchitecture, and bone biomechanics were examined. At the same time, RNA-seq and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes were performed on the left tibias, followed by Elisa and RT-qPCR verification. It had been found that resistance exercise can effectively counteract the weight gain of ovariectomized osteoporotic rats, and has a good effect on bone mineral density and trabecular bone microarchitecture. Enrichment analysis showed that regulation of gene expression and osteoclast differentiation is the most closely related biological process and signaling pathway shared by RE/Ovx and NE/Ovx groups. Our results revealed that resistance exercise can play a role in inhibiting osteoclast activation and preventing the enhancement of osteoclast bone resorption function in ovariectomized osteoporotic rats by inhibiting Fos/Fosb-regulated TRAP activation and relieving Calcr inhibition, which has important application value in preventing bone loss caused by estrogen deficiency.

overall_design: The left tibias of three rats in each group (the Sham group, the NE/Ovx group, and the RE/Ovx group) were selected for transcriptome sequencing.


title: Arabidopsis aneuploidy mutant C30-81-as6, possesses enormous variations in multiple phenotypic characteristics

city: Wako

first: Asanga

middle: Deshappriya

last: Nagalla

address: 2-1 Hirosawa

department: RIKEN Nishina Center for Accelerator-Based Science

institute: RIKEN

summary: The mutant line of C30-81-as6 is an ion beam-generated, Arabidopsis Col-0 based, aneuploid mutant line confirmed by elevated DNA quantity by flow cytometry analysis and microscopic observations of additional chromosome. The mutant shows abnormal leaf shapes, petioless rosette leaves, elevated trichome bases and later flowering phenotypes. A set of candidate causal genes were identified using up and downregulated differentially expressed genes (DEGs) in transcriptome analysis. Gene ontology analysis further supports mutant phenotypic characteristics and provides insights into its functional priorities including promotion of cellular structure and energy production. Meanwhile, the downregulation of senescence-related GO terms validates its extended vegetative phase. The gene density mapping of upregulated DEGs, densely positioned on the long arm of chromosome 2 and phenotype of C30-81-as6 largely resembles Arabidopsis additional chromosome 2 containing aneuploidy mutant.

overall_design: Three samples from C30-81-as6 and Col-0 from the same age plant leafs were used for RNA extraction

first: Asanga Deshappriya

first: Kotaro

last: Ishii

first: Tomonari

last: Hirano

first: Sumie

last: Ohbu

first: Yuki

last: Shirakawa

first: Yusuke

last: Kazama

first: Tomoko

last: Abe


title: RNAseq data for Nitrogenase regulation in Vibrio natriegens differs from other γ-proteobacteria

status: Public on Jun 04 2026

city: Bloomington

first: James

last: McKinlay

address: 1001 E 3rd Street

institute: Indiana University

summary: Regulation of nitrogenase, which converts nitrogen gas (N2) into ammonium (NH4+), typically involves a conserved set of regulatory proteins across diverse N2-fixing (diazotrophic) bacteria. However, the interactions and relative influence of these regulators can vary between species. Thus, one cannot make assumptions about nitrogenase regulation when working with uncharacterized diazotrophs like Vibrio natriegens, a γ-proteobacterium of growing interest for synthetic biology. Here, we characterized the roles of several annotated V. natriegens nitrogenase regulatory proteins in response to NH4+ versus N2. This data set describes global transcript levels for a parent strain ntrBC and nifA deletion mutants in non-growing cell suspensions where nitrogenase is expressed.

sample_organism: Vibrio natriegens NBRC 15636 = ATCC 14048 = DSM 759

overall_design: RNAseq was performed with non-growing Vibrio natrigens strains in minimal MDC175 medium without any nitrogen source.

first: Nicholas

middle: W

last: Haas

first: Emma

middle: E

last: Wiesler

first: Ankur

middle: B

last: Dalia

first: Xindan

last: Wang


title: Targeting YAP1 Attenuates Persistent Oxidative Stress-Driven Tubular Cell Senescence

status: Public on Jun 03 2026

city: Taiyuan

first: Zhibo

last: Zhao

address: Shuangtasi. 29

institute: Shanxi Provincial People's Hospital

summary: Persistent oxidative stress induced by hydrogen peroxide (H2O2) upregulates the expression of YAP1 and triggers cellular senescence in HK-2 (human kidney-2) cells. Conversely, knockdown of YAP1 not only downregulates the Hippo signaling pathway but also suppresses genes involved in extracellular matrix (ECM) reorganization. Furthermore, this YAP1 depletion effectively reduces tubular cell senescence, suggesting that YAP1 acts as a key mediator linking oxidative stress to fibrotic and aging phenotypes in renal tubular cells.

overall_design: Bulik RNA-seq profiling of samples from H2O2-treated HK-2 cells with or without YAP1 knockdown


title: Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis - retina snRNA-seq data

city: Mannheim

first: Lucas

last: Schirmer

address: Theodor-Kutzer-Ufer 1-3

institute: University of Heidelberg

summary: Triggered by the relevance of Piezo mechanosensitive ion channels in different organs with functions beyond touch and pain sensation, we aimed to investigate Piezo2 in the central nervous system with a focus on the anterior visual system, especially because its role in the CNS lacks understanding. We found a bimodal expression pattern with Piezo1 in progenitors and Piezo2 in mature oligodendrocytes, which was conserved between mice and humans. Using two different OL-specific loss-of-function approaches, we found Piezo2 to be relevant for myelin compactness and white matter integrity in aged mice. Ultrastructural imaging was paired with snRNA-seq analysis and motor function testing that confirmed regulatory roles of Piezo2 in motor function and white matter integrity. We complemented our work with a validation study in human control and multiple sclerosis optic nerve tissue, and found Piezo2 to be downregulated in OLs towards the lesion rim.

overall_design: RNA-seq profiling of retina samples from female Piezo2f/f control mice and from female oligodendrocyte-specific Piezo2-depleted (Olig2-cre;Piezo2f/f) mice at 120 days of age.

first: Amelie

last: Rabitsch

first: Julia

last: Dyckow-Schubart

first: Christina

last: Mayer

first: Manuel

last: Friese


title: Oligodendrocyte Piezo2 is a regulator of age-dependent myelin integrity and dysregulated in multiple sclerosis - ON snRNA-seq data

overall_design: RNA-seq profiling of optic nerve samples from female Piezo2f/f control mice and from female oligodendrocyte-specific Piezo2-depleted (Olig2-cre;Piezo2f/f) mice at 120 days of age.

first: Celia

last: Lerma-Martin


title: Effect of HSD and HFD on cardiac function in Drosophila

city: MARSEILLE

first: Nathalie

last: Arquier

address: 163 avenue de Luminy

department: Inserm, Aix-Marseille Université

country: France

institute: TAGC U1090

summary: Type 2 diabetes is a multifactorial disease that has a pandemic development worldwide. Associated cardiac dysfunctions are affecting one-third of the patients. Drosophila has proven to be a valuable model to study cardiac function in physiological and physio-pathological contexts. Indeed, adult flies challenged on rich diets (high sugar or high fat) developed cardiac dysfunctions similar to diabetic cardiomyopathies. In order to better characterize the molecular events leading to these cardiac diseases, we performed an RNA-sequencing on poly(A) extracted from 10 days old female flies reared on ND (Normal Diet), HSD (High Sugar Diet) or HFD (High Fat Diet). The differential expression of genes was evaluated for each rich diet versus normal diet. Genes exhibiting a fold change ≥ 1.5 were considered as good candidates. Gene Ontology analysis for cellular localization showed a significant enrichment in extracellular component. This was supported by the presence of a signal peptide in 27% in HSD and 44% in HFD of the candidate genes. These results suggest that putative new secreted proteins have been identified, putting forward the role of the heart as a secretory organ in hyperglycemia and hyperlipidemia. We functionally validated some interesting candidates by specific cardiac-KO and evaluated the different cardiac phenotypes by high-speed live imaging on undissected flies. We focused on the fit gene, encoding a previously identified satiety hormone and characterized its paracrine as well as its systemic cardiac function in the adult. Our results illustrate a yet unknown cardiac function for the Fit hormone and suggest it as a new fly cardiokine.

overall_design: Female flies were reared on normal (ND), high sugar (HSD) or high fat (HFD) diet for 10 days after eclosion and whole heart were dissected before mRNA sequencing. 9 samples were sequenced (3 samples for each diet).

first: Lucie

last: Khamvongsa-Charbonnier

first: Laurent

last: Kremmer

first: Laurence

last: Röder

last: Perrin

first: Magali

last: Torres


title: Emergence of Disease-relevant Aberrant Epithelial Cell States in Human Alveolar Organoids

status: Public on Jun 01 2026

city: Nashville

first: Abraham

middle: Scott

last: McCall

state: TN

department: Medicine

institute: Vanderbilt University medical Center

summary: Single-cell RNA-sequencing of human lung epithelial cell organoids cultured with permutations of SFFFM and ADM media as well as pharmacologic activation and manipulation of hypoxia-inducible factors.

overall_design: Single cell suspensions were generated from human epithelial organoids, fixed, and sequenced using 10X Flex Chromium Human Transcriptome Probe Set v1.1.0 after treatment with permutations of SFFFM (serum free feeder free media) or ADM (alveolar differentiation media) and treatment +/- Roxadustat, PT-2385, and M-1002

first: McCall

last: A. Scott

first: Kropski

last: Jonathan A.


title: ChIP-seq data for Nitrogenase regulation in Vibrio natriegens differs from other γ-proteobacteria

first: James

last: McKinlay

summary: Regulation of nitrogenase, which converts nitrogen gas (N2) into ammonium (NH4+), typically involves a conserved set of regulatory proteins across diverse N2-fixing (diazotrophic) bacteria. However, the interactions and relative influence of these regulators can vary between species. Thus, one cannot make assumptions about nitrogenase regulation when working with uncharacterized diazotrophs like Vibrio natriegens, a γ-proteobacterium of growing interest for synthetic biology. Here, we characterized the roles of several annotated V. natriegens nitrogenase regulatory proteins in response to NH4+ versus N2. This data set describes the NtrC binding sites in Vibrio natrigens grown with NH4+ versus N2 using chromatin immunopreiciptation combined with combined with massively parallel sequencing (ChIP-seq).

platform_organism: Vibrio natriegens NBRC 15636 = ATCC 14048 = DSM 759

overall_design: ChIP-seq and whole genome sequencing experiments were performed with Vibrio natrigens strains, with or without His-tagged NtrC (C-terminal tag), grown under fermentative anoxic conditions in minimal MDC175 medium with either ammonium or nitrogen gas as the sole nitrogen source.

first: Nicholas

last: Haas

first: Emma

last: Wiesler

first: Ankur

last: Dalia

last: Wang


title: Bulk ATAC-seq of young HSCs and Selp high vs Selp low HSCs in pre-aged mice

city: Tianjin

first: Chong

last: Yang

state: Tianjin

address: 288 Nanjing Rd, Tianjin 300020, China.

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

summary: Aging of hematopoietic stem cells (HSCs) is accompanied by changes in chromatin organization that precede and shape functional decline. P-selectin (Selp/CD62P) expression has been associated with inflammatory and stress-related hematopoietic states, yet how Selp expression relates to chromatin accessibility during the early stages of HSC aging remains largely unexplored. To address this, we performed bulk ATAC-seq on phenotypically defined HSCs isolated from young mice and from pre-aged mice, with the latter further subdivided according to surface Selp expression (Selp_high and Selp_low). Genome-wide accessibility profiling was used to identify regulatory elements and transcription factor–associated regions that distinguish early aging and Selp-associated heterogeneity within the HSC compartment. These data provide a resource for investigating epigenetic remodeling and regulatory priming associated with early hematopoietic stem cell aging.

overall_design: HSCs were isolated from mouse bone marrow by fluorescence-activated cell sorting using established immunophenotypic markers defining the SLAM HSC compartment. Three biological groups were examined: HSCs from young mice, and HSCs from pre-aged mice further subdivided into Selp_high and Selp_low populations based on surface Selp expression levels. For chromatin accessibility profiling, ATAC-seq libraries were prepared using the Hyperactive ATAC-Seq Library Prep Kit for Illumina and TruePrep Index Kit V2 for Illumina (Vazyme), following the manufacturer’s instructions.

first: Toshio

last: Suda


title: Clonal expansion and phenotypic alterations of TCR Vβ3⁺ T cells in juvenile-onset recurrent respiratory papillomatosis: Implications for tumor-associated immunity and chemokine-mediated T-cell trafficking

city: Beijing

first: shilan

last: li

address: No. 56 Nanlishi Road, Xicheng District

department: Department of Otolaryngology – Head and Neck Surgery

institute: Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health

summary: Juvenile-onset recurrent respiratory papillomatosis (JORRP) is a rare, human papillomavirus (HPV)-driven pediatric disease characterized by recurring papillomas in the respiratory tract. The contribution of dysregulated T-cell immunity to disease severity remains poorly understood. This study included 97 JORRP patients and 124 controls

overall_design:
Due to sample limitations, downstream analyses including flow cytometry, TCR, and RNA sequencing were performed on distinct patient subsets (detailed in Methods). We identified a selective expansion of TCR Vβ3⁺ T cells, including expanded TRBV28 clonotypes, in patients with aggressive disease. These T cells exhibited heightened cytotoxicity and activation markers and were enriched in papilloma tissues. Within the tumor microenvironment, gene expression profiling revealed upregulated chemokine signaling pathways (CCR2/CCL7, CXCR6/CXCL16) and key immunosuppressive markers, including PD-L1 and TGFB1. Our findings demonstrate a tumor-specific clonal expansion and functional alteration of TCR Vβ3⁺ T cells in JORRP, suggesting these pathways as preliminary targets for further investigation.
"OSA" samples serve as our control group for the squamous epithelium, though they are not from strictly "healthy" volunteers. These samples were collected from pediatric patients diagnosed with simple adenoid hypertrophy and obstructive sleep apnea syndrome (OSA). To ensure their suitability as controls for our study, we strictly excluded patients with any history of recurrent tonsillitis or recurrent respiratory tract infections. The specific tissues obtained are palatoglossal arch mucosa, which were collected during the patients' routine tonsillectomies. We selected this mucosal tissue because it shares the exact same pathological structure  squamous cell epithelium  as the papilloma tissues investigated in our study, making it an ideal structural and regional control.

first: Shilan

last: Li


title: A cuffed CRISPR guide RNA for microRNA activity-dependent genome editing

city: Vancouver

first: Arman

middle: Foyez

last: Adel

address: 6088 University Boulevard

department: The School of Biomedical Engineering

institute: the University of British Columbia

summary: miRNA target sequencing of EGFP+ and unsorted mouse ES cells and in-vitro differentiating mouse smooth muscle cells transduced with a library of circular guide RNAs (cgRNA)

overall_design: Clonal mouse embryonic stem cells (129(+Ter)/SvJcl (female mouse) × C57BL/6NJcl (male mouse)) (mESCs) engineered with an EGFP base-editing reporter and enhanced Target-AID C-to-T base-editor were transduced in either the ES state or at day 3 or day 6 of smooth muscle cell (SMC) differentiation with a cgRNA library containing targets covering the mouse miRNAome as annotated by miRbase v22. After transductions, cells were sorted either 6 days or 8 days after transduction and puromycin selection for EGFP+ cells and portion of cells were kept as an unsorted control.

first: Nozomu

last: Yachie


title: DNA methylation mediates MBSR induced cardioprotection in patients after PCI

city: Kunming

first: Min

last: Zhang

address: No. 295, Xichang Road

institute: The First Affiliated Hospital of Kunming Medical University

type: Methylation profiling by high throughput sequencing

summary: Background: Mindfulness-Based Stress Reduction (MBSR) improves well-being in patients with acute myocardial infarction (AMI), but its molecular cardioprotective mechanisms remain unclear.

overall_design: Methods: In this prospective pilot study, 51 post-PCI AMI patients (17 receiving MBSR plus standard therapy, 34 controls) were assessed for inflammatory markers (CRP, IL-6, PCT), echocardiographic parameters, and functional capacity at baseline and 6 months. Genome-wide DNA methylation profiling was performed in a subgroup (n=5/group).

first: Mengyuan

last: Xiong

first: Xingkui

last: Dou

first: Jifa

last: Tao

first: Fei

last: Hu

first: Pan

last: Jing

first: Zhao

last: Zhao

first: Hongyan

last: Cai


title: Effects of Phthalate Metabolite Mixture Exposure on Mouse Oocyte Development

city: Urbana

first: Huanyu

last: Qiao

state: Illinois

address: 2001 South Lincoln Avenue

department: Comparative Biosciences

institute: University of Illinois Urbana-Champaign

summary: Phthalates are pervasive endocrine-disrupting chemicals widely used in consumer products, resulting in chronic human exposure to complex mixtures rather than single compounds. Despite extensive studies on individual compounds, the combined effects of their phthalate metabolites on oogenesis remain poorly understood. Here, we  developed a precise microinjection-based single-oocyte toxicological assay to examine the impact of a defined phthalate metabolite mixture on meiotic progression. Phthalate mixture exposure markedly impaired oocyte maturation, as most oocytes failed to extrude the first polar body. Mechanistic analyses revealed severe meiotic defects, including disrupted spindle morphology, chromosome misalignment, disorganized actin cytoskeleton, and impaired mitochondrial function, accompanied by excessive reactive oxygen species (ROS) accumulation and DNA damage. Single-cell transcriptomic profiling further identified differentially expressed genes enriched in biological processes related to exocytosis, secretory pathway regulation, and cytoskeletal organization, as well as in MAPK, JAK-STAT, cGMP-PKG, and GnRH signaling pathways that are essential for follicular development and oocyte maturation. Together, these findings demonstrated that combined phthalate exposure directly compromises female gamete quality and underscore the importance of evaluating mixture effects when assessing risks to women’s reproductive health.

overall_design: Single-cell RNA sequencing was conducted using the Smart-seq3 workflow to profile the transcriptomes of germinal vesicle (GV) stage oocytes from phthalate-injected and water-injected (control) groups.

first: Juan

last: Dong

first: Shuangqi


title: Evaluating exon skipping in the central nervous system in Duchenne muscular dystrophy using spatial transcriptomics

city: Leiden

first: Qirong

last: Mao

state: South Holland

address: Albinusdreef 2

department: Human Genetics

institute: Leiden University Medical Center

summary: Duchenne muscular dystrophy (DMD) causes progressive muscle degeneration due to dystrophin deficiency. Dystrophin is also expressed in the brain during development and postnatally, yet a characterization of dystrophin isoform expression across brain cells and regions is lacking, limiting our understanding of the cognitive impairment affecting one-third of the patients and hampering development of dystrophin-restoring drugs in the central nervous system (CNS). Here, we applied spatial transcriptomics to map Dmd isoforms across mouse brain regions and cell types. Mdx52 mice received exon 51-skipping therapies restoring the Dp427-sized isoform at transcript and protein level. We observed distinct spatial patterns: full-length isoforms localized to deeper cortical layers and CA1, while shorter isoforms were enriched in cortical layer 1 and dentate gyrus. We present evidence of isoform restoration, immune activation following treatment, and a framework to evaluate exon skipping therapies in the CNS using spatial transcriptomics.

overall_design: We performed Xenium in situ analysis (10X Genomics) on hemi-coronal brain sections from 12 individual mice across 4 groups: wildtype (N=3), mdx52 mice treated with PBS  (N=3), mdx52 mice treated with either ASO (tcDNA) (N=3) or AAV-U7snRNA targeting Dmd exon 51 skipping (U7ex51) (N=3) (Material and Method). All samples, including those from WT, were collected at 14 weeks of age

first: Alireza

last: Ahmadi

first: Sharon

last: de Vries

first: Laura

middle: G

last: Heezen

first: Ophélie

last: Vacca

first: Mathilde

last: Doisy

first: Annemieke

last: Aartsma-Rus

first: Maaike

last: van Putten

first: Aurélie

last: Goyenvalle

first: Ahmed

last: Mahfouz

first: Pietro

last: Spitali


title: Lenvatinib enhances the response of biliary tract cancer to anti-HER2 therapy

first: Huishan

last: Sun

state: Beijing

address: No.1 Shuaifuyuan Wangfujing Dongcheng District, Beijing,China

institute: Peking union medical college hospital

summary: HER2 is a frequently overexpressed gene in biliary tract cancer (BTC). Although several targeted agents, including trastuzumab, have been approved for the treatment of BTC, their clinical efficacy remains limited. To explore this issue, we treated two BTC cell lines—SNU1196 and GBC-SD—with different anti-HER2 agents. We then performed gene expression profiling analysis using data from RNA-seq of 2 different cells treated with different drugs.

overall_design: RNA-seq profiling of SNU1196 BTC cells treated with either Vehicle, pyrotinib, afatinib, CP724-714, or trastuzumab. RNA-seq profiling of GBC-SD cells  treated with either Vehicle, pyrotinib, afatinib, CP724-714, or trastuzumab.

first: Haitao


title: Integration of zebrafish pineal transcriptomes reveals cell type-specific timing

city: Tel Aviv

first: Yoav

last: Gothilf

address: Sherman Building, room 405

department: Neurobiology

country: Israel

institute: Tel Aviv University

summary: This study aimed at expanding our knowledge of the cellular composition of the zebrafish pineal gland and identify cellt ype-specific circadian rhythmicity and light response. This was accomplished by combining single-cell RNA-seq datasets and by integrating them with bulk RNA-seq datasets which examined gene rhythmicity and light response in the pineal gland. The analysis identified 10 cell types, including novel photoreceptor and projecting neurons subtypes. The integrated analysis with the bulk datasets provided evidence for cell-type specific rhythmicity: neuronal circadian clocks are driven by rod-like photoreceptors, whereas the clock of accessory cells, which support photoreception function, are partially autonomous.

overall_design: The submitted data includes single-cell mRNA sequencing of 12 adults zebrafish pineal glands of the aanat2:eGFP transgenic line, kept under 14h-10h light/dark cycles. Tissue were collected at ZT15 (1 hour into the dark phase). This dataset was integrated with a similar published dataset, in which tissues were collected during daytime (GEO: GSE123778).

first: Yair

last: Wexler

first: Dengfeng

last: Huang

first: Jun

last: Yan


title: Decoding Immune Dysregulation in Newly Diagnosed Cancer through integrated Single-Cell RNA-Seq, Spectral Immune Phenotyping and Machine Learning

city: Rostock

first: Brigitte

last: Müller-Hilke

address: Schillingallee 70

department: Core Facility for Cell Sorting and Cell Analysis

institute: Rostock University Medical Center

summary: Early cancer detection remains a major clinical challenge. Circulating immune biomarkers provide a promising, non-invasive diagnostic opportunity, yet their potential remains insufficiently defined. Here, we present an integrated multi-omics analysis of peripheral blood mononuclear cells (PBMCs) from treatment-naïve cancer patients, combining immune phenotyping (flow cytometry, FC), multiplex cytokine profiling, and single-cell RNA sequencing (sc-RNA-seq). Compared with healthy controls, patients exhibited widespread immune dysregulation, including expansion of FOXP3+ regulatory T cells, depletion of CD16+CD11b+ monocytes and CD56dim NK cells, and elevated plasma IL-6/IL-4 levels. Sc-RNA-seq identified novel cancer-specific immune signatures, notably consistent upregulation of THBS1 and CH25H, indicative of systemic imprinting by tumor-derived cues. Deep learning models integrating single cell multi-omics data (sc-FC + sc-RNA-Seq) achieved performance comparable to clinical models, enabling cancer-type stratification and mechanistic insight. These findings establish a framework for immune-based, multi-omics diagnostics in early cancer detection and disease monitoring.

overall_design: Immmune profiling of XX cancer patients via scRNA-seq using BD-Rhapsody platform

first: Peggy

last: Berlin

first: Amin

last: Mirzaei

first: Felix

last: Steinbeck

first: Martin

last: Becker

first: Wendy

last: Bergmann-Ewert

first: Daniel

last: Dubinski

first: Thomas

last: Freiman

last: Strüder

first: Theresa

last: Momper

first: Annabell

last: Wolff

first: Philipp

last: Kaps

first: Julia

last: Henne

first: Clemens

last: Schafmayer

first: Michael

last: Linnebacher

first: Charlotte

last: Wagner

first: Karen

last: Rischmüller

last: Philipp

first: Georg

last: Lamprecht

first: Paul

last: Meissner

first: Marcus

last: Frank

first: Christian

last: Junghanss

first: Sonja

last: Oehmcke-Hecht

first: Claudia

last: Maletzki


title: Platelet-Immune-Neuron Crosstalk Modulates Cutaneous Inflammation and Pruritus

city: Guangzhou

first: Ximin

last: Hu

address: Department of Burn and Plastic Surgery, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong

summary: Background: Recent studies have shown that platelets actively contribute to most inflammatory reactions and neural signaling, yet the involvement of platelets in the cutaneous inflammation and pruritus in skin is largely unknown. Methods: Optogenetic platelet activation, platelet depletion, serotonin depletion and TRPV1+ neuron specific deletion of HTR2B were used to determine the functional relevance of platelets in cutaneous inflammation and itch. Results: Upon optogenetic stimulation, activated platelets were attracted to the inflamed lesion, which elicits erythema, edema and pruritus in mice. Then a characteristic transcriptomics of photostimulated lesion showed a pathogenetic resemblance to skin disorders, especially atopic dermatitis (AD). Platelet depletion alleviated scratching behaviors and skin pathology in AD, whereas platelet activation exacerbated both. Subsequently, depletion of serotonin (5-HT) released from platelets reduced the spontaneous scratching and cutaneous inflammation by C-fiber excitability and suppressing macrophage infiltration. For itch transmission, genetic approaches reveal that platelet-derived serotonin activates TRPV1⁺ pruriceptors through HTR2B receptors in AD. Conclusions: These data showed the sufficiency of platelet activation for cutaneous inflammation and itch, which uncovered a novel platelet-immune-neuron axis as a promising therapeutic target for AD and potentially other skin disorders.

overall_design: RNA-seg profiling of photostimulated PF4Cre; Ai32 and Ai32 control mice at Day11. RNA-seg profiling of MC903-treated PF4Cre; iDTR and iDTR control mice at Day11.

first: Fujun

last: Wan

first: Ting

last: Wang

first: Yifei

last: Liu

first: Lei

last: Zhang

first: Libei

first: Ronghua

last: Yang

first: Jing

last: Feng


title: Downregulated transcription in chromosomal domains of midbrain dopamine neurons linked to schizophrenia. [RNA-Seq]

city: New York

first: Swadha

last: Singh

state: NY

address: 1470 Madison Ave

department: Psychiatry

institute: Icahn School of medicine, Mount sinai

summary: Ventral midbrain dopaminergic neurons are a key cell type for schizophrenia pathophysiology but information about cell type-specific genomic dysregulation in diseased brains is missing. We generated a unique midbrain functional genomics resource with 98 RNA-seq and 34 Hi-C chromosomal contact libraries for Nurr1+/NeuN+ dopaminergic and their surrounding Nurr1-/NeuN- nuclei, collected from donors diagnosed with schizophrenia (SCZ), bipolar disorder (BD) and compared to neurotypical controls. Among the 954 dopamine neuron genes specifically dysregulated in SCZ, 331 were downregulated, with selective enrichment for risk-associated synaptic plasticity and neuronal connectivity pathways and embedded within dopamine neuron-specific topologically associated chromosomal domains (TAD). Transcript-resolved analysis revealed 2,350 transcripts with altered expression in SCZ dopamine neurons, affecting key susceptibility genes such as the FOXP1, MAPK10, PCM1 and NRNX1. Therefore, genomic dysregulation in the ventral midbrain of subjects diagnosed with SCZ selectively affects dopaminergic neurons, and includes a unilateral association of genetic risk with down-, but not upregulated transcription at the sites of highly organized chromosomal domains harboring neuron-specific genes with complex transcriptional architectures.

overall_design: Postmortem human ventral midbrain tissue was used to isolate nuclei from dopaminergic neurons (Nurr1+/NeuN+) and surrounding non-neuronal cells using FANS. RNA-seq libraries (~60M reads/sample) were generated from these sorted nuclei to profile cell-type–specific transcriptomes and 3D genome architecture. Donors included schizophrenia, bipolar disorder, and neurotypical controls. Differential expression and chromatin structure analyses were performed to identify disease-associated molecular alterations in dopaminergic neurons.

first: Marina

last: Iskhakova

first: Tova Y

last: Lambert

first: Aditi

last: Valada

first: Neda

last: Shokrian

first: Viviana

last: Evans

first: Jaroslav

last: Bendl

first: Pavan K

last: Auluck

first: Stefano

last: Marenco

first: Minghui

first: Bin

first: Gabriel E

last: Hoffman

first: Kiran

last: Girdhar

first: Panos

last: Roussos

first: Schahram

last: Akbarian


title: Downregulated transcription in chromosomal domains of midbrain dopamine neurons linked to schizophrenia. [Hi-C]

last: Wang


title: Aberrant immunomodulatory signature in β-propeller protein-associated neurodegeneration patient iPSC-derived microglia

city: Munich

first: Lena

last: Burbulla

address: Feodor-Lynen-Straße 17

institute: LMU

summary:
Targeted gene expression profiling was performed on iPSC-derived microglia generated from BPAN patients and healthy controls using the NanoString nCounter Human Neuroinflammation Panel. This study aimed to identify disease-associated immune and inflammatory transcriptional signatures relevant to BPAN pathogenesis.
Microglia are the brain’s resident immune cells, essential for homeostasis and implicated in common neurodegenerative diseases like Alzheimer’s and Parkinson’s disease (PD), where their early activation and sustained inflammatory mediator release precede neuronal loss. By contrast, their contribution to rare disorders is unclear. β-propeller protein-associated neurodegeneration (BPAN), caused by WDR45 mutations, shares key features with PD, including iron accumulation and dopaminergic neuron loss, but the impact of microglia and mutant WDR45 in BPAN remains unexplored.  To address this, we established the first iPSC-derived microglia model from BPAN patients. Integrated transcriptomic and proteomic profiling revealed a shift from a homeostatic to a reactive, pro-inflammatory state with dysregulation of autophagy, and stress response, and chronic immune activation. Complementary secretomic analysis identified impaired lysosomal function and increased antigen presentation, supporting persistent microglial activation. These findings implicate dysfunctional microglia in BPAN pathogenesis and suggest new directions for immunomodulatory therapies.

overall_design: iPSC-derived microglia from BPAN patients (n=3) and healthy control individuals (n=3) were analyzed under basal  conditions using NanoString nCounter gene expression profiling with Neuroinflammation gene panel.

first: Gamze

last: Özata

first: Rachel

last: Wise


title: Clip2 as a novel regulator of osteocyte maturation and morphology

city: Boston

first: Courtney

last: Mazur

address: 50 Blossom Street

department: Endocrine Unit

institute: Massachusetts General Hospital

summary: The genes driving osteocyte maturation and function are not fully understood. We identified CD61 (integrin beta-3) as a marker of osteocyte maturation and developed a flow cytometry-based assay to quantify surface CD61 protein levels. Surface CD61 expression increases during osteocyte maturation, and CD61-high cells express higher levels of osteocyte marker genes. In a genome-wide screen, we identified Clip2, which encodes a microtubule binding protein, as one of dozens of genes necessary for CD61 expression.

overall_design: 1) Compare transcriptomes of Ocy454 cells at differentiation days 1, 7, 10, 14.  2) Compare transcriptomes of live FACS-sorted Ocy454 cells with the 10% highest expression of CD61 and 10% lowest expression of CD61.

first: Tadatoshi

last: Sato

first: Marc

last: Wein


title: Mechanistic insights into PFAS-induced effects on B lymphocyte activation and antibody secretion [PBMCs]

city: Wageningen

first: Benthe

last: van der Lugt

address: Akkermaalsbos 2

institute: Wageningen University & Research

summary: Per- and polyfluoroalkyl substances (PFASs) are man-made organofluoride chemicals widely present in the environment, with exposure associated to various adverse health effects, including immunotoxicity. Recently, we showed that PFASs can directly impair antibody production, leading to decreased immunoglobulin (Ig) M and IgG release in human peripheral blood mononuclear cells (PBMCs) obtained from both male and female healthy donors. However, the underlying molecular mechanisms remain largely unknown. In this study, we aimed to address this gap by performing RNA sequencing to identify pathways and genes potentially involved in the observed immunotoxic effects. PBMCs were exposed to selected PFASs for 24 hours, and to assess effects on antibody production, a subset was subsequently stimulated with CpG oligodeoxynucleotide ODN2006 and rhIL-2 for an additional  six days. Transcriptomic analysis indicated activation of the glucocorticoid receptor (GR) and associated signaling pathways, supported by the upregulation of several GR-target genes and the prediction of glucocorticoids or the GR agonist dexamethasone as upstream regulators in Ingenuity Pathway Analysis. Moreover, the inhibitory effects of PFASs on antibody secretion were shown to be reversable by the GR antagonist Mifepristone, supporting the involvement of the GR in PFAS-mediated suppression of antibody secretion. Overall, this research advances our understanding of PFAS-induced immunotoxicity and identifies potential biomarkers for evaluating PFAS exposure and its associated health effects.

overall_design: PBMCs were isolated from 5 male and 5 female donors and seeded in 48-wells plates containing 1.26 x 10^6 PBMCs in 1 mL of complete medium. PBMCs were exposed either to PFOA or PFOS (at the concentration of 12.6 µg/mL), DEX (150 µg/mL) or DMSO as vehicle control (final concentration 0.1% (v/v)) and incubated for 24 hours without subsequent stimulation. Following exposure, RNA was extracted and used for RNA sequencing.

first: Martina

last: Iulini

first: Karsten

last: Beekmann

first: Ron

last: Hoogenboom

first: Valentina

last: Galbiati

first: Giulia

last: Russo

first: Francesco

last: Pappalardo

first: Stella

last: Fragki

first: Alicia

last: Paini

first: Emanuela

last: Corsini

first: Aafke

last: Janssen


title: Distal 4q Duplication and Extended 10q Deletion in a Preterm Infant with Severe Growth Restriction and Obesity: Disruption of Epithelial-Mesenchymal Cross-Talk and Metabolic Regulation Revealed by Gene Expression Profiling

city: Augsburg

first: Victoria

middle: Elisabeth

last: Fincke

address: Stenglinstraße 2

institute: Childens Cancer Center - University hospital Augsburg

summary: We describe a male preterm infant (28+6 weeks gestation) with a paternally inherited unbalanced translocation t(4;10)(q31.1;q26.1), resulting in a 48.46 Mb duplication of 4q31.22q35.5 and a 10.77 Mb deletion of 10q26.13q26.3. The patient exhibited characteristic features associated with distal 4q duplication and distal 10q deletion, including severe growth restriction, early-onset obesity, delayed neurodevelopment, and a giant umbilical hernia - but notably lacked renal or thumb anomalies.

overall_design: Presentation of RNA data from the blood of a pateint with a 48.46 Mb duplication of 4q31.22q35.5 and a 10.77 Mb deletion of 10q26.13q26.3

first: Eva

middle: T

last: Toepfer

first: Marion

last: Zaehringer

first: Michael

last: Baumgartner

first: Anne

last: Garbe

first: Desiree

last: Dunstheimer

first: Moneef

last: Shoukier

first: Ulrike

last: Walden

first: Pascal

middle: D

last: Johann

first: Cornelia

last: Daumer-Haas

last: Fruehwald

first: Melanie

middle: L

last: Conrad

first: Fabian

last: Fahlbusch


title: Mechanistic insights into PFAS-induced effects on B lymphocyte activation and antibody secretion

first: Benthe

last: van der Lugt

overall_design: PBMCs were isolated from 5 male and 5 female donors and seeded in 48-wells plates containing 1.26 x 10^6 PBMCs in 1 mL of complete medium. PBMCs were exposed to PFOA or PFOS (at the concentration of 12.6 µg/mL), rapamycin (2 µg/mL) and DMSO as vehicle control (final concentration 0.1% (v/v)) for 24 hours and subsequently stimulated with 100 IU/mL of rhIL-2 and 1 μg/mL ODN2006 for 6 days to induce B cell differentiation and activation. Following exposure, RNA was extracted and used for RNA sequencing.

first: Martina

last: Iulini

first: Karsten

last: Beekmann

first: Ron

last: Hoogenboom

first: Valentina

last: Galbiati

first: Giulia

last: Russo

first: Francesco

last: Pappalardo

last: Fragki


title: The Oxidative Cost of Losing Low Temperature Viability Protein 1 [Ltv1]: Insights into Cellular Damage and Homeostasis

city: Highland Heights

first: Erin

last: Strome

state: KY

address: Nunn Drive, Northern Kentucky University

department: Department of Biological Sciences

institute: Northern Kentucky University

summary: The Ltv1 protein has been characterized with roles in ribosome biogenesis, maintenance of rRNA stability, ATP export, osmotic stress response, and signaling activation of the Target of Rapamycin pathway. We have conducted an in-depth characterization of ltv1Δ/ltv1Δ mutants for additional phenotypic manifestations due to loss of Ltv1. We observed growth differences corresponding with Ltv1’s well characterized roles but additionally discovered increased sensitivity to reactive oxygen species (ROS)-inducing conditions sodium selenite and diamide. In further characterization of cells lacking Ltv1 we documented higher levels of endogenous ROS and a greater accumulation response of ROS to exogenous stress. Utilizing RNA-sequencing we then determined the gene expression differences underlying the ltv1-deficiency induced oxidative stress sensitivity. This work elucidates a new significant role of Ltv1 in cellular homeostasis and protection against damage.

overall_design: To explore unknown functions of Low Temperature Viability Protein 1, we deleted the ltv1 gene and explored gene expression and phenotype differences.

first: McKayla

last: Remines

first: Samuel

middle: A

last: Ammerman

first: Jill

last: Keeney


title: The transcription factor MtCLR-2 regulates cellulase production by directly modulating the expression of Mtegl2 and Mtbgl1 in Myceliophthora thermophila

city: Auckland

first: Yapeng

last: Lai

address: 55 Wellesley Street East,  Auckland Central

department: School of Science

country: New Zealand

institute: Auckland University of Technology

summary: The thermophilic fungus Myceliophthora thermophila is capable of secreting large amounts of lignocellulolytic enzymes, such as cellulases and xylanases, which are regulated by multiple transcription factors. However, the understanding of the regulatory mechanism of cellulase gene expression in M. thermophila is limited. Here, we characterized the function of MtCLR-2, a M. thermophila ortholog of CLR-2, a key cellulolytic transcriptional regulator initially identified in Neurospora crassa. Deletion of Mtclr-2 significantly reduced cellulase activities, particularly affecting endoglucanase production, whereas overexpression of Mtclr-2 led to marked elevation in cellulase secretion when M. thermophila was grown on Avicel. Subcellular localization assay of MtCLR-2 fused to green fluorescent protein (GFP) indicated that MtCLR-2 is localized to the nucleus. Real-time quantitative reverse transcription PCR (RT-qPCR) analysis revealed that disruption of Mtclr-2 caused a decrease in transcript levels of the β-glucosidase gene bgl1 (MYCTH_66804) and the endoglucanase gene egl2 (MYCTH_86753) throughout the stages of growth in cellulose medium. Furthermore, electrophoretic mobility shift assays (EMSAs) demonstrated that MtCLR-2 directly binds to the promoter regions of bgl1 and egl2 in a zinc-dependent manner. The comparative transcriptomic analysis also showed that MtCLR-2 positively regulates the expression of ribosomal protein genes under cellulosic conditions. These findings contribute to a better understanding of the regulatory network governing cellulase gene expression and provide a potential target for boosting cellulase biosynthesis in M. thermophila.

sample_organism: Thermothelomyces thermophilus ATCC 42464

overall_design: The transcription factor MtClr-2 regulates cellulase production in M. thermophila. To comprehensively clarify the regulation of MtClr-2, we conducted transcriptional profiling analysis of the WT and ΔMtclr-2 strains cultured on Avicel for 48 h after a shift from glucose.

first: Juan

last: Wang

first: Gang

last: Liu

first: Donnabella C

last: Lacap-Bugler


title: Age-independent immune subtypes in Type 1 diabetes exhibit distinct post-onset progression rates and immunotherapeutic responses

city: Milwaukee

first: Martin

last: Hessner

state: WI

address: 8701 Watertown Plank Road

department: Pediatrics

institute: Medical College of Wisconsin

summary: Through analysis of >600 participants, we defined two immunologically distinct Type 1 diabetes subgroups that uniquely respond to immune intervention. Personalized prevention and treatment strategies for Type 1 diabetes (T1D), an autoimmune disease that targets the insulin-producing pancreatic β-cell, will require a deeper understanding of disease heterogeneity.  We analyzed pre-intervention plasma samples, collected within 100 days of diagnosis, from 560 participants across six immunotherapy trials, using a bioassay in which plasma-induced transcription was measured in a well-controlled peripheral blood mononuclear cell population.  Microarray profiling identified 2,854 transcripts exhibiting high variation in at least five of the six trials.  Unsupervised analyses concordantly divided the participants into two age-independent subgroups.  The observed signatures were not due to relapsing and remitting immune activity as subgroup assignments were conserved in longitudinal analysis of post-baseline samples.  Phenotypic analyses and follow-up studies of an independent new-onset T1D cohort determined that subgroup 1 was enriched with participants possessing neutral or low-risk HLA haplotypes and included the youngest participants possessing the most rapid rate of C-peptide decline.  This subgroup exhibited elevated plasma cytokine and chemokine levels, increased circulating CD4+ CD45RO+ memory T-cells, and a better therapeutic response to anti-CD20.  Subgroup 2 was enriched with participants of Hispanic ancestry, individuals with insulin auto-antibody titers, elevated levels of plasma miR-155-5p and miR-409-3p, and a better therapeutic response to CTLA4-Ig.  These analyses support the existence of immunologically distinct endotypes and the potential for biomarker-driven stratification for more targeted therapeutic interventions in T1D.

overall_design: UPN827 cells were stimulated with TrailNet plasma samples at baseline (n=560) or the 3-6 months post-baseline (n=183)  from six TrailNet new-onset T1D intervention trails. Plus stimulated with our local  Recent onset T1DM plasma (n=61). Gene expression analysis was perfromed in order to evaluate the transcriptional signature associated with T1D.

first: Amina

last: Bedrat

first: Nathan

last: Truchan

first: Tarun

last: Pant

first: Shuang

last: Jia

first: Mark

last: Roethle

first: Yi-Guang

last: Chen

first: Chien-Wei

last: Lin

first: Martin J