title: Prolonged Loss of Oxidative Phosphorylation and Mitochondrial Mass Characterize CD66b+ Leukocytes from Patients with Sepsis

status: Public on Jan 20 2026

city: Gainesville

first: Philip

last: Efron

address: 1600 SW ARCHER RD

department: MD-SURGERY-CRITICAL CARE

institute: University of Florida

summary: Introduction: Sepsis leads to expansion of myeloid-derived suppressor cells (MDSC) and their subtypes. These normally transitory MDSC suppress T cell activation and alter T cell cytokine production while simultaneously promulgating systemic low-grade inflammation. Immune metabolism has been demonstrated to shape cell responses and regulate immune suppression or enhance effector activity. While the metabolism of MDSC has been extensively studied in cancer, the metabolic phenotype of this heterogeneous population in sepsis remains unclear. Our goal was to assess metabolic flux in MDSC during and after sepsis and stratify these patients by characteristics and outcome to determine differences that may guide treatment decisions. Methods: Peripheral blood mononuclear cells (PBMC) from healthy subjects and sepsis patients at four days, 2-3 weeks, and 6 months underwent CD66b+ or CD3+ isolation, followed by assessment of metabolic flux, flow cytometry, mRNA sequencing, and epigenetic analysis. Results: Mitochondrial basal oxygen consumption rates (OCR) and maximal oxygen consumption rates (SRC) were decreased in MDSC from septic patients at four days after infection and persisted for up to six months after sepsis onset. Glycolysis was not impacted by sepsis. In contrast, oxidative metabolism in CD3+ T cells was similar between sepsis patients and healthy subjects. Reduced MDSC oxidative metabolism was linked to adverse clinical outcomes. The decline in oxygen consumption from MDSC in septic patients was also linked to significant reductions in MDSC mitochondrial content. Transcriptomic analysis of CD66b+ cells isolated from PBMC healthy participants and patients with sepsis at four days, 2-3 weeks, and 6 months revealed 19 differentially expressed genes and two long non-coding RNAs as potentially responsible for this decline in mitochondrial mass. Specifically, NR4A3, NR4A2, and TAMLIN/NR4A1 (all critical for mitochondrial biogenesis) expression were persistently decreased with reduced chromatin accessibility indicative of gene silencing. Discussion: After sepsis, PBMC CD66b+ cells present with a unique metabolic signature that is not shared with CD3+ T-cell subsets in these patients or other disease cohorts. These changes in mitochondrial function result from a reduced content of these organelles. We have identified gene silencing, reduced gene expression of key transcription factors that regulate mitochondrial biogenesis, as well as increased long non-coding RNA as potential drivers of this unique metabolic phenotype. These results highlight a need to target metabolism in sepsis to promote immune homeostasis and recovery.

overall_design: A total of 38 samples were collected from septic patients: 11 samples at day four, 7 at 2-3 weeks, and 8 samples at six months, as well as individual samples from 12 healthy participants. CD66b+ cells were isolated as described above and total RNA isolated using RNeasy Mini kit (Qiagen 74104) following manufacturers’ recommendations.  RNA was quantified using Qubit RNA Broad Range Assay Kit (Ref# Q10210; Invitrogen, MA) and RNA integrity was assessed using RNA ScreenTape kit (Ref# 5067-5576) on TapeStation 4200 (Agilent). Illumina Stranded mRNA Prep and Ligation kit (Ref# 20040534; Illumina, CA) were used to prepare sample libraries following the manufacturer’s recommendations. Very briefly, 300 ng/uL high quality RNA was captured and purified, followed by reverse transcription to convert the captured mRNA into first and second strands of cDNA. The resulting double stranded cDNA molecules were then enzymatically fragmented in preparation for unique dual indexing using IDT for Illumina RNA UD Set Ligation Indexes (Ref# 20091655; Illumina, CA). The ligated samples were subsequently enriched through PCR amplification on Bio-Rad Thermal cycler (T100; Bio-Rad, CA) and purified using AMPure XP magnetic beads (Ref# A63881; Beckman Coulter, CA). The average fragment length of the library insert was measured to be ~300–400 bp using the dsDNA 1000 kit (Ref# 5067-5582) on Agilent TapeStation. Optimized libraries were pooled to a final concentration of 150pM. The libraries were sequenced on NovaSeq X Plus Platform (Illumina, CA) at UF’s Interdisciplinary Center for Biotechnology Research (ICBR).

first: Christine

last: Rodhouse

first: Evan

last: Barrios

first: Leilani

last: Zeumer-Spataro

first: Leandro

last: Balzano-Nogueira

first: Ruoxuan

last: Wu

first: Xuanxuan

last: Yu

first: Guimei

last: Tian

first: Jason

middle: O

last: Brant

first: Marie-Pierre

last: Gauthier

first: Jing

last: Chen

first: Miguel

last: Hernandez-Rios

first: Valerie

last: Polcz

first: Whitman

last: Wiggins

first: Angel

last: Charles

first: Marvin

last: Dirain

first: Ricardo

last: Ungaro

first: Jaimar

last: Rincon

first: Tyler

last: Loftus

first: Feifei

last: Xiao

first: Guoshuai

last: Cai

first: Lyle

last: Moldawer

first: Robert

last: Maile

first: Michael

last: Kladde

first: Clayton

last: Mathews


title: Mitochondrial metabolism and signaling direct dendritic cell function in antitumor immunity

status: Public on Jan 21 2026

city: Memphis

first: Hongbo

last: Chi

state: TN

address: 262 Danny Thomas Place

department: Immunology

country: USA

institute: St Jude Children's Research Hospital

type: Genome binding/occupancy profiling by high throughput sequencing

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

overall_design: Refer to individual Series


title: Transcription factor reveals interconnected regulation of carbon source utilization and carbon catabolite repression in an oleaginous yeast

city: Ithaca

first: Josh

last: Kerkaert

state: NY

address: 236 Tower Rd

institute: Cornell University

type: Expression profiling by high throughput sequencing

summary: Cells must sense and respond to available nutrients to survive. Microbes evolved mechanisms to activate genes necessary to utilize a carbon source specifically when it is present. To efficiently grow in mixed carbohydrate environments, microbes repress genes necessary to utilize carbon sources that require substantial resources to catabolize when a simpler carbon source is present, known as carbon catabolite repression. We investigated nutrient utilization in the basidiomycete, oleaginous yeast Rhodotorula (Rhodosporidium) toruloides. R. toruloides is a saprophytic fungus that utilizes the building blocks of complex polysaccharides found in plant cell walls. A transcription factor homologous to the cellulose degradation regulator CLR-2/ClrB in Ascomycete filamentous fungi, which we named Cbr1, is required for cellobiose utilization in R. toruloides. Although the role of CLR-2/ClrB is limited to regulating expression of genes involved in cellulose and hemicellulose utilization, Cbr1 is also involved in fucose and tricarboxylic acid cycle intermediate utilization. Additionally, Cbr1 inhibits carbon catabolite repression specifically during utilization of glucose-glucose disaccharides, which may have evolved to limit the glucose-mediated repression of genes encoding proteins that cleave disaccharides into glucose. In fungi, it is thought carbon source-specific transcription factors activate genes necessary for carbon source utilization, while carbon catabolite repression is regulated by transcription factors that broadly repress all nonpreferred carbon source utilization genes when a preferred carbon source is present. Our data provide evidence for a noncanonical carbon catabolite repression mechanism and suggest transcriptional mechanisms regulating carbon catabolite repression may be less broadly conserved than previously thought.

overall_design: 3'mRNA-seq profiling of Rhodotorula (Rhodosporidium) toruloides wild type and cbr1 deletion strains exposed to fucose as the sole carbon source for 8h, wild type, cbr1 deletion, and bgl1bgl2 double deletion strains exposed to cellobiose as the sole carbon source for 4 hours, and wild type, cbr1 deletion, and tct1 deletion exposed to citrate as a sole carbon source for 24 hours. Reads were counted using a GFF3 file generated by the peaks2utr software v. 1.4.1 in order to improve annotation of 3'UTRs. Wild type BAM files from the above experiments, as well as wild type cells exposed to 1% succinate as the sole carbon source for 24 hours, and wild type cells exposed to Vogel's minimal media with NH4Cl and 2% glucose as the sole nitrogen and carbon sources, respectively, were combined and used as the input for peaks2utr. The GFF3 file generated by peaks2utr is included as a supplementary file. Each experiment was performed in biological triplicate.

first: Brandon

last: Reyes-Chavez

first: Joshua

middle: D

first: Lori

middle: B

last: Huberman


title: Clonal expansion of cytotoxic CD8+ T cells in lecanemab-associated ARIA

city: Lexington

middle: M

last: Morganti

state: KY

address: 789 S. Limestone St

department: Sanders-Brown Center on Aging

institute: University of Kentucky

summary: Amyloid-related imaging abnormalities (ARIA) remain the principal safety concern limiting adoption of anti-amyloid therapies such as lecanemab, yet their underlying biology is poorly defined. To address this, we performed deep multi-omic profiling of peripheral blood mononuclear cells from three Alzheimer's disease (AD) patients who developed ARIA and three matched controls. Single-cell RNA sequencing, CITE-seq, V(D)J clonotyping, and metabolomic/lipidomic profiling revealed a coordinated reprogramming of the CD8+ compartment in ARIA+ patients. CD8+ TEM and TEMRA subsets were numerically expanded, transcriptionally enriched for cytotoxic and migratory programs, and exhibited increased clonal expansion. Transcription factor inference and metabolomics converged on a glycolytic bias, supporting short-lived effector activity. Ligand-receptor modeling identified ARIA-associated signaling from CD14+ and CD16+ monocytes that augmented antigen presentation, adhesion, and chemokine axes directed toward effector CD8s. Finally, integration with an external cerebrovascular atlas confirmed that ARIA-associated TEM/TEMRAs are transcriptionally "addressed" for vascular engagement.

overall_design:
Six individuals receiving bi-weekly infusions (10 mg/kg) of lecanemab were recruited. Three subjects with radiographically confirmed ARIA were matched with three controls by age (± 2-5 years), sex, APOE genotype, and lecanemab infusion number (± 1). PBMCs were collected immediately prior to infusion and processed using 10x Genomics Chromium Single Cell 5' chemistry with simultaneous capture of transcriptomic and surface protein expression using TotalSeq-C antibody-derived tags (ADTs) targeting 137 surface proteins. T cell receptor sequences were captured using 10x Genomics V(D)J enrichment. Libraries were sequenced on an Illumina NovaSeq 6000.

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

first: Lance

middle: A

last: Johnson

first: Kai

last: Saito

first: Akhil

middle: V

last: Pallerla

first: Jessica

middle: L

last: Funnell

first: Ashley

middle: R

last: Ezzo

first: Chelsea

last: Song

first: Douglas

last: Harrison

first: Noah

middle: J

last: Norton

first: Lauren

middle: C

last: Moore

first: Linda

last: Van Eldik

first: David

middle: W

last: Fardo

first: Greg

middle: E

last: Cooper


title: Cell cycle-resolved Hi-C reveals unexpected plasticity of A/B compartments across interphase

city: Kobe

first: Ichiro

last: Hiratani

state: Hyogo prefecture

address: 2-chōme−２−3, Minatojima Minamimachi, Chuo ward

country: Japan

institute: RIKEN BDR

summary: The spatial organization of chromatin into active (A) and inactive (B) nuclear compartments is fundamental to genome regulation, yet their cell-cycle dynamics remain largely unexplored. Most research on chromatin dynamics during the cell cycle has primarily focused on events surrounding mitosis, providing only limited insight into chromatin behavior during S-phase. To address this gap, we developed a simple, drug-free approach that combines the Fucci cell-cycle indicator with in situ Hi-C to comprehensively analyze A/B compartment dynamics throughout interphase in mouse embryonic stem cells (mESCs). Unexpectedly, and contrary to prevailing views, we found that A/B compartment strength increased abruptly upon S-phase entry, stabilized during S-phase, and subsequently declined in late S/G2. This abrupt strengthening, which we termed ‘compartment maturation,’ required passage through the G1/S transition but was independent of active DNA synthesis. This maturation involved substantial architectural remodeling, particularly within the A compartment, which consolidated into a more organized structure as individual A domains rearranged to form long-range interactions. Moreover, compartment maturation was not limited to mESCs but was also observed across different developmental contexts in mice. Based on these observations, we propose a revised, stepwise model of nuclear compartmentalization during cell-cycle progression, consisting of four distinct stages: chromosome unfolding (G1), chromatin maturation (G1/S), stabilization (S phase), and refolding (G2). These findings reveal the unexpected plasticity of A/B compartments and underscore the G1/S transition as a critical period for their reorganization.

overall_design:
In situ Hi-C profiling of Fucci mESCs during the cell cycle (early G1, mid G1, late G1, early S, mid S, late S, G2), at G1/S arrest and at G1/G0 arrest.

***************************************************************
Raw sequencing data are available under BioProject PRJDB37948 at DDBJ
***************************************************************

last: Choubani


title: Comparative Landscape of Small RNAs in Tissue and Liquid Biopsies for Liver Transplant Outcomes [Perfusate small RNAseq]

city: Birmingham

first: Zhangli

last: Su

state: Alabama

address: 720 20th Street South

department: Department of Genetics

institute: University of Alabama

type: Non-coding RNA profiling by high throughput sequencing

summary: Ischemia-reperfusion injury (IRI) is an inevitable consequence of liver transplantation, arising during donor organ procurement and reoxygenation. Severe IRI is a leading contributor to early allograft dysfunction (EAD), a post-transplant complication associated with reduced graft survival. Current postoperative biomarkers provide limited time for intervention, highlighting a need to identify preoperative biomarkers of IRI. Meanwhile, tRNA fragments (tRFs) have emerged as novel biomarkers in various diseases, but remain unexplored in the context of liver transplant. We performed small RNA sequencing on donor liver biopsies to investigate IRI-associated transcript changes. In parallel, donor liver perfusates were analyzed as a non-invasive surrogate for tissue profiling.

overall_design:
Liver tissue and perfusate samples were obtained from adult orthotopic liver transplant (OLT) recipients (?18 years old) at Methodist University Hospital after obtaining informed consent. All procedures were conducted under protocols approved by the University of Tennessee Health Science Center Institutional Review Board (IRB#20-07742-XM and IRB#20-07640-XP). Participants in the LUT cohort were recruited between September 2018 and March 2020, and those in the UTL cohort were recruited between December 2020 and December 2022.
Needle biopsy specimens (L1: pre-implantation; L2: post-reperfusion) were immediately immersed in RNAlater (Thermo Fisher Scientific, Cat. #AM7021) and incubated at 4 °C overnight to ensure complete permeation. RNAlater was then removed, and the samples were stored at ?80 °C until RNA extraction.
Perfusate samples were collected at the end of organ procurement concurrently with pre-implantation liver (L1) biopsies. The solutions were centrifuged at 2,400 rpm for 30 minutes at room temperature to remove debris. The resulting supernatant was aliquoted and stored at ?80 °C until RNA isolation.
Patients were grouped based on transplant outcome, measured by day 1 AST (aspartate aminotransferase) values.  EAD (early allograft dysfunction): day 1 AST more than 2000; NF (normal function): day 1 AST less or equal to 2000.

first: Monima

last: Anam

first: Christine

last: Watkins

first: Grace

last: Rucker

first: Katie

last: Marlow

first: Mattew

last: Khalil

first: Murat

last: Dogan

first: James

last: Eason

first: Jason

last: Vanatta

first: Corey

last: Eymard

first: Cem

last: Kuscu

first: Canan


title: Tumor-specific lncRNA IGF1R-AS1 trans-regulates chromatin interactions associated with oncogenic MYC signaling

city: Chicago

first: Rendong

last: Yang

state: IL

address: 420 E Superior St

department: Urology

institute: Northwestern University


title: Comparative Landscape of Small RNAs in Tissue and Liquid Biopsies for Liver Transplant Outcomes [Tissue small RNAseq]


title: Study on the Effects of Retinoids on UVR-Induced Skin Photoaging [RNA-seq]

city: Hangzhou

first: Yicheng

last: Xie

address: 3333 Binsheng Rd

country: China

institute: Children’s Hospital Zhejiang University School of Medicine

summary: Photoaging contributes to up to 80% of visible facial aging signs, making it a major dermatological concern. While retinoids such as retinol and all-trans retinoic acid (ATRA) promote extracellular matrix (ECM) regeneration, their side effects limit widespread use. We propose that hydroxypinacolone 9-cis retinoate (9-cis HPR), a derivative of 9-cis retinoic acid, activates both retinoic acid receptor (RAR) and retinoid X receptor (RXR), enhancing efficacy while minimizing irritation. However, its in vivo anti-photoaging effects remain underexplored. This study evaluates 9-cis HPR in the UVR-damaged SKH-1 mouse model, investigating its role in inflammation control, ECM regeneration, and melanogenesis suppression.

overall_design: RNA-seq profiling of Normal human dermal fibroblasts (NHDF), and the groups were divided into untreated group, treated with 0.1 μ g/mL 9-cis HPR group, and treated with 0.251 μ M retinic acid group, and repeated 3 times.

first: Fan

last: Hu

first: Qijiang

last: Zhao

first: Chengzhi

last: Zheng

first: Ye

last: Zhong

first: Jian

last: Shen

first: Ruian

last: Qiu

first: Hao

last: Zhu

first: Tongquan

last: Wu

first: Rui

last: Ye

first: Le

last: Du

first: Daqing

last: Ma


title: Serum Amyloid A (SAA) Transcriptomics Sequencing on enteroid

city: Baltimore

first: George

middle: Henry

last: Sack

state: Maryland

address: 725 N. Wolfe Street

department: Department of Physiology, Pharmacology and Therapeutics

institute: Johns Hopkins University School of Medicine

summary: The 104 aa protein Serum Amyloid A (SAA) is a prominent member of the acute phase response (APR) a remarkably conserved and stereotyped set of serum protein changes associated with inflammation and other stimuli. N-terminal fragments of SAA can form fibrils that can accumulate in organs (“amyloidosis”). No specific biologic function has been identified for SAA; it has been considered an inert “biomarker.” In contrast to this perception of passivity, we report that exposure to both N-terminal decapeptides and intact SAA monomers can induce multiple transcripts in both enteroids and HEK293 cells. The spectrum of transcripts prominently includes proteins related to inflammation and NF-κB control, specifically NFKB1A, TNFA1P3 and IER3. SAA thus can act directly through specific transcription to alter cellular physiology with direct effects on inflammation, likely helping explain its remarkable evolutionary conservation as part of primordial defense.

overall_design: RNA-seq profiling of HEK293 cells treated with full-length SAA protein, with corresponding vehicle controls (HOH + 0.05% BSA). Samples were harvested at specific time points to capture transcriptional changes.

middle: H

last: Sack Jr

first: Joseph

last: Yun

first: Conover

last: Talbot Jr


title: Smoking promotes the progression of colorectal cancer via CKAP2L/STAT3/AREG/EGFR axis

city: Chongqing

first: Shasha

address: No.1 Youyi Road, Yuzhong District

department: Gastroenterology

institute: The First Affiliated Hospital of Chongqing Medical University

summary: Smoking is a major risk factor for colorectal cancer (CRC). But the underlying molecular mechanisms by which smoking promotes CRC remain unclear. The positive association between smoking and CRC was confirmed by both cross-sectional study and mendelian randomization analyses. RNA-seq sequencing and bioinformatics analysis were conducted to identify the key genes involved in smoking-induced CRC progression. After treatment with cigarette smoke extract in CRC cells, cell proliferation and metastasis were enhanced. Subsequently, cytoskeleton associated protein 2 like (CKAP2L) was identified as a key gene involved in smoking-induced CRC and its downregulation inhibited cell proliferation and metastasis. CKAP2L is an important part of the cell centrosome and serves a critical role in spindle formation. Previous studies have demonstrated that CKAP2L mediates the cell cycle in a variety of cancer types, promoting the progression and spread of tumors.A recent study reported that regulatory factor X5-regulated CKAP2L can promote the proliferation and metastasis of CRC cells. In this study, we upregulated CKAP2L in HCT116 cells and downregulated CKAP2L in RKO cells. Then, these cells were subjected to the RNA-seq to explore the expression of relative genes.

overall_design: RNA sequencing was performed on the negative control RKO cells (RKO-NC), knockdown CKAP2L RKO cells (RKO-shCKAP2L), control HCT116 cells (HCT116-Vector), and overexpression CKAP2L HCT116 cells (HCT116-CKAP2L).


summary: Smoking is a major risk factor for colorectal cancer (CRC). But the underlying molecular mechanisms by which smoking promotes CRC remain unclear. The positive association between smoking and CRC was confirmed by both cross-sectional study and mendelian randomization analyses. RNA-seq sequencing and bioinformatics analysis were conducted to identify the key genes involved in smoking-induced CRC progression. After treatment with cigarette smoke extract (CSE) in CRC cells, cell proliferation and metastasis were enhanced. Subsequently, we isolated the total RNA of HCT116 cells treated with CSE and subjected it to the RNA-seq to explore the differentially expressed genes.

overall_design: RNA sequencing was performed on the wild type HCT116 cells and HCT116 cells treated with CSE.


title: TEAD-independent mechanisms of YAP function in cardiomyocytes

city: Cincinnati

first: Jeffrey

last: Steimle

email: jeffrey.steimle@cchmc.org, jeffrey.steimle@bcm.edu, jsteimle@uchicago.edu, jsteimle@alumni.nd.edu

state: OH

address: 240 Albert Sabin Way

department: Molecular Cardiovascular Biology

institute: Cincinnati Children's Medical Hospital Center

summary: Adult mammalian hearts exhibit limited regenerative capacity due to the restricted renewal of cardiomyocytes. Recent studies reveal that mammalian hearts exhibit transient regenerative potential within a short time frame after birth, suggesting a regulatory mechanism that prevents adult hearts from initiating a regenerative response to cardiac injury. Here, we discovered that an active form of YAP, named YAP6SA, which is not inhibited by the Hippo signaling pathway and does not interact with TEADs, induces cardiomyocyte cell cycle re-entry. In addition, YAP6SA interacts with scaffold protein MPDZ to regulate Rho GTPases and promote cell cycle progression in cardiomyocytes (CMs). Importantly, YAP6SA overexpression is well tolerated in mammalian hearts. These findings provide new insights into YAP function in cardiomyocytes.

overall_design: Wildtype ICR mice were subcutaneously injected with 1*10^11 viral genomes of AAV9 virus containing cTnT-GFP, cTnT-YAP5SA, or cTnT-YAP6SA expression constructs at P6. Two hearts from each virus were collected at P9 and cardiomyocyte nuclei were enriched using anti-PCM1 pulldown. RNA was isolated using the RNeasy Plus Micro kit and poly-A enriched, non-directional libraries were generated by Novogene America and sequenced on the Illumina NovaSeq6000. Reads were mapped to the mouse genome (mm10, Ensembl GRCm38.94) using STAR. Lowly expressed genes were removed within each condition using median log2-transformed counts per gene per million mapped reads of 1, and a union set of genes was generated from each condition. Differential expression analysis was performed using edgeR using a general linear model framework with an additional covariate to mitigrate an apparent batch effect.

first: Bing

first: James

middle: F

last: Martin


title: Study on the Effects of Retinoids on UVR-Induced Skin Photoaging [Spatial Transcriptomics]

first: Yicheng

last: Xie

overall_design: Spatial Transcriptomics profiling of the skin of SKH-1 mice, and the Model-Blank sample contains UVR group (upper), Control group (lower), the Administration sample contains UVR and treated with 0.1% Retinol group (upper), UVR and treated with 0.03% 9-cis HPR group (lower).

first: Fan

last: Hu

first: Qijiang


title: T cell-intrinsic VISTA deficiency dampens the efficacy of CTLA4 blockade by limiting TCR repertoire diversity and effector function of tumor specific CD8+ cytotoxic T cells

city: Cleveland

first: Lily

last: Wang

address: 9500 Euclid Ave

institute: Cleveland Clinic

summary: This study examines the effects of T cell-intrinsic VISTA deficency on the responses and repertoire of tumor-infiltrating CD8+ T cells in preclinical melanoma models.

overall_design: WildType (WT) and VISTA knockout (KO) Tcells from tumor tissue were analyzed using 10X genomics 5' kit including single cell gene expression with paired VDJ analysis.


title: ECD co-operates with ERBB2 to promote tumorigenesis through upregulation of unfolded protein response and glycolysis

city: Omaha

first: Vimla

last: Band

state: Nebraska

address: 601 Saddle Creek road

department: Department of Genetics, Cell Biology & Anatomy,

institute: University of Nebraska Medical Center

summary: The mammalian orthologue of the Drosophila ecdysoneless (ECD) mRNA and protein are overexpressed in breast cancer, and its overexpression correlates with poor prognosis and short patient survival, particularly in ERBB2/HER2-positive breast cancer (BC). This work investigates the co-operative oncogenic mechanism of ECD and ERBB2 by deriving transgenic mice overexpressing ECD and/or ERBB2 (huHER2) in mammary epithelium under MMTV promoter (ECD+HER2Tg), as well as human mammary immortal epithelial cell lines (hMECs) overexpressing ECD and/or ERBB2. While huHER2Tg mice developed more homogenous solid nodular carcinomas, double transgenic mice (ECD; huHER2Tg) developed heterogenous and histologically aggressive mammary tumors with basal-like phenotype and epithelial mesenchymal transition (EMT) features, similar to ECDTg tumors.  Importantly, transcriptomic profile of ECD; huHER2Tg tumors revealed upregulation of two major oncogenic pathways, unfolded protein response (UPR) and glycolysis. Consistently, ECD; huHER2Tg tumors exhibited increased mRNA levels of cancer stem cell markers and EMT related genes.  Further, hMECs expressing both ECD and ERBB2 as compared to ECD or ERBB2 expressing cells showed significant increase in oncogenic traits, such as enhanced migration, anchorage independence, mammosphere, and organoid formation. RNA sequencing analysis of single and double transfectants showed significant upregulation of glycolysis and UPR pathways in ECD+ERBB2 expressing cells as compared to ECD or ERBB2 overexpressing hMECs.  Given our recent finding that ECD directly binds to RNA, we demonstrate mRNAs of three key glycolytic enzymes (LDHA, PKM2 and HK2) and mRNA of a major UPR regulated gene GRP78 directly associated with ECD protein using RNA immunoprecipitation assay. Higher expression of glycolytic mRNAs and GRP78 in ECD+ERBB2-expressing cells was due to increased mRNA stability. Lastly, we show an increase in glucose uptake and enhanced glycolytic rate in ECD+ERBB2-overexpressing cells as compared to ECD- or ERBB2-overexpressing hMECs.  Taken together, our findings support a co-operative role of ECD and ERBB2 in oncogenesis by enhancing two major oncogenic pathways, UPR and glycolysis. These results provide experimental proof and mechanistic insights to our previous findings that ECD is overexpressed in ERBB2-positive BC patients, and its’ overexpression correlates with poor prognosis and short survival in patients.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: RNA-seq profiling of Vector expressing, ECD overexpressing, ERBB2 overexpressing and ECD+ERBB2 overexpressing 76NTERT human mammary epithelial cells. In adition, RNAseq profiling of ECDTg mouse mammary tumors, huHER2Tg mouse mammary tumors and ECD; huHER2Tg mouse mammary tumors

first: Band

last: Vimla

last: Hamid

first: Mohapatra

last: Bhopal


title: Biomarkers that prospectively predict HIV-1 infection in high risk adults

city: Kilifi

first: Abdirahman

last: Abdi

state: Not US or Canada

address: Mombasa-Malindi Road

department: Bioscience

country: Kenya

institute: KEMRI-Wellcome Trust Research Programme

summary: We sequenced the RNA content of plasma-derived extracellular vesicles from a historical high risk HIV cohort at the Coast of Kenya. We found that an immunosuppresive transcriptional profile and the presence of Pegivirus C associate with HIV acquisition in this particular cohort.

overall_design: To determine circulating biomarkers that prospectively predict HIV-1 infection in high risk adults.

first: Kioko

last: Mwikali

first: Shaban

last: Mwangi

first: Eunice

last: Nduati


title: Study on the Effects of Retinoids on UVR-Induced Skin Photoaging [scRNA-seq]

overall_design: scRNA-seq profiling of the skin of SKH-1 mice, and the groups were divided into control group (repeated 1), model group (repeated 1), low dose group  (repeated 2), middle dose group  (repeated 2), positive control 1 group  (repeated 2), positive control 2 group  (repeated 2).

last: Zhao

first: Chengzhi

last: Zheng

first: Ye

last: Zhong

first: Jian

last: Shen

first: Ruian

last: Qiu

first: Hao

last: Zhu

first: Tongquan

last: Wu

first: Rui

last: Ye

first: Le

last: Du

first: Daqing

last: Ma


title: CD9 regulates macrophage-mediated remodeling of adipose tissue in obesity

city: Philadelphia

first: David

last: Hill

state: PA

address: Abramson Research Building, 1208B, 3615 Civic Center Blvd.

department: Division of Allergy and Immunology

institute: Children's Hospital of Philadelphia

summary: Dysfunctional white adipose tissue contributes to the development of obesity-related morbidities, including insulin resistance, dyslipidemia, and other metabolic disorders. Adipose tissue macrophages (ATMs) accumulate in obesity and play both beneficial and harmful roles in the maintenance of adipose tissue homeostasis and function. Despite their importance, the molecules and mechanisms that regulate these diverse functions are not well understood. Lipid-associated macrophages (LAMs), the dominant subset of obesity-associated ATMs, accumulate in crown-like structures and are characterized by a metabolically activated and proinflammatory phenotype. We previously identified CD9 as a surface marker of LAMs. However, the contribution of CD9 to the activation and function of LAMs during obesity is unknown. Using a myeloid-specific CD9 knockout model, we show that CD9 supports ATM-adipocyte adhesion and crown-like structure formation. Furthermore, CD9 promotes the expression of pro-fibrotic and extracellular matrix remodeling genes. Loss of myeloid CD9 reduces adipose tissue fibrosis, increases visceral adipose tissue accumulation, and improves global metabolic outcomes during diet-induced obesity. These results identify CD9 as a causal regulator of pathogenic LAM functions, highlighting CD9 as a potential therapeutic target for treating obesity-associated metabolic disease.

overall_design:
Bulk RNA-seq of CD9+ and CD9- Adipose tissue macrophages isolated from male mice fed a high fat diet for 12 weeks. Samples from CD9+ adipose tissue macrophage samples from GSE113594 were reanalyzed for this study. Bulk RNA-seq of whole epididymal white adipose tissue isolated from male Control and CD9 myeloid-specific (LysMCre+/-) knockout mice fed a high fat diet for 12 weeks.

***************************************************************
The table below lists GEO accessions reused/reanalyzed for this study.
***************************************************************

first: Julia

last: Chini

first: Nicole

last: DeMarco

first: Dana

last: Mitchell

first: Sam

last: McCright

first: Divyansi

last: Pandey

first: Kaitlyn

first: Rachel

last: Clement

first: Jessica

last: Miller

first: Rajan

last: Jain

first: Deanne

last: Taylor

first: Mitchell

last: Lazar


title: Chromatin accessibility landscapes define stromal cell identities across tissues

city: Toronto

first: Amin

last: Nooranikhojasteh

state: ON

address: 101 College Street

country: Canada

institute: Princess Margaret Cancer Centre

summary: Chromatin accessibility landscapes are pivotal in regulating gene expression and maintaining cellular identity across diverse tissues. Using single-cell ATAC sequencing (scATAC-seq), we profiled chromatin accessibility across nine murine organs, encompassing 51,248 cells, to decipher the cis-regulatory mechanisms underlying tissue-specific and cell type-specific functions. Our analysis uncovered 28 major cell types with distinct chromatin accessibility signatures, revealing conserved and unique regulatory patterns. We identified transcription factor (TF) motifs associated with these regions, highlighting TF dynamics in cell differentiation and organ-specific functions. Additionally, we demonstrated that chromatin accessibility can trace stromal cells, including endothelial cells and fibroblasts, back to their tissue of origin, offering new insights into tissue-specific epigenomic landscapes. This innovative approach of leveraging epigenomic features to trace cells of origin represents a significant advancement, providing valuable insights into both normal and pathological states where identifying the tissue of origin is critically important.

overall_design: Single cell chromatin accessibility (scATAC-Seq) profiles from nine mouse organs. Experiments were performed according to the Chromium Single Cell ATAC reagent kit v1.1 user guide (10x Genomics, CG000209 Rev F)

first: Elias

last: Orouji


title: Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development [CUT&RUN]

city: New Haven

first: Mandar

middle: Deepak

last: Muzumdar

state: CT

address: 333 Cedar Street

department: Genetics

institute: Yale University

summary: Pancreatic endocrine-exocrine crosstalk plays a key role in normal physiology and disease and can be altered by host metabolic states, such as obesity. Classically, endocrine islet beta (β) cell secretion of insulin is thought to promote the development of obesity-associated pancreatic adenocarcinoma (PDAC), an exocrine cell-derived tumor. Here, we show that β cell expression of the peptide hormone cholecystokinin (CCK) is necessary and sufficient for obesity-associated PDAC progression in mice and that CCK expression – rather than insulin – correlates strongly with enhanced tumorigenesis. Single-cell RNA-sequencing, in silico latent-space archetypal and trajectory analysis, and experimental lineage tracing in vivo reveal that obesity induces the expansion of postnatal immature β cells, which adapt to express CCK via stress-responsive JNK/cJun signaling. Finally, obesity perturbs CCK-dependent peri-islet exocrine cell transcriptional states and enhances islet-proximal tumor formation. These results define endocrine-exocrine CCK signaling as a bona fide driver of obesity-associated PDAC development and uncover new avenues to target the endocrine pancreas to subvert exocrine tumorigenesis.

overall_design: Min6 cells were plated (2.5 million) and grown for 3 days prior to treatment with the JNK inhibitor SP600125 (20 uM, Med Chem Express) or DMSO (control) for 48 hours. 550,000 cells were harvested per reaction and condition. Cells were processed using the CUTANA ChIC/CUT&RUN Kit (14-1048), JUN/cJun CUTANA CUT&RUN antibody (SKU:13-2019), and positive (anti-H3K4Me3) and negative (IgG) control antibodies from the kit following the manufacturer’s protocol. Library preparation was performed by the Yale Center for Genome Analysis followed by sequencing to a depth of 30 million paired-end 150 bp reads (2x150) per sample on NovaSeq (Illumina).

first: Cathy

last: Garcia

first: Aarthi

last: Venkat

first: Daniel

last: McQuaid

first: Sherry

middle: S

last: Agabiti

first: Alexander

last: Tong

first: Boby

last: Mathew

first: Rebecca

last: Cardone

last: Starble

first: Christian

last: Ruiz

first: Christy

last: Zheng

first: Akin

last: Sogunro

first: Jeremy

last: Jacox

first: Ken

last: Loh

first: Richard

middle: G

last: Kibbey

first: Smita

last: Krishnaswamy


title: Commensal myeloid crosstalk in neonatal skin regulates cutaneous type 17 inflammation

city: San Francisco

first: Henry

last: Rodriguez

address: 1322 3rd avenue

institute: University of California San Francisco

summary: Early life microbe-immune interactions at barrier surfaces have lasting impacts on the trajectory towards health versus disease. Monocytes, macrophages and dendritic cells are primary sentinels in barrier tissues, yet the salient contributions of commensal-myeloid crosstalk during tissue development remain poorly understood. Here, we identify that commensal microbes facilitate accumulation of a population of monocytes in neonatal skin. Transient postnatal depletion of these monocytes resulted in heightened IL-17A production by skin T cells, which was particularly sustained among CD4+ T cells into adulthood and sufficient to exacerbate inflammatory skin pathologies. Neonatal skin monocytes were enriched in expression of negative regulators of the IL-1 pathway. Functional in vivo experiments confirmed a key role for excessive IL-1R1 signaling in T cells as contributing to the dysregulated type 17 response in neonatal monocyte-depleted mice. Thus, a commensal-driven wave of monocytes into neonatal skin critically facilitates immune homeostasis in this prominent barrier tissue.

overall_design:
CD45+ cells were isolated from four healthy human donor (one fetal, one pediatric, two adults donors) by FACS and analyzed using scRNA-seq
Please note that this is human data associated to already deposited mouse data under GSE244177.

first: Miqdad

last: Dhariwala

first: Ricardo

last: Carale

first: Andrea

last: DeRogatis

last: Rodriguez-Valbuena

first: Joy

last: Okoro

first: Christina

last: Ekstrand

first: Antonin

last: Weckel

first: Victoria

last: Tran

first: Irek

last: Habrylo

first: Rio

last: Barrere-Cain

first: Oluwasunmisola

last: Ojewumi

first: Allison

last: Tammen

first: Jessica

last: Tsui

first: Saba

last: Shaikh

first: Shivaram

last: Yellamilli

first: Ahmed

last: Aladhami

first: Robin

last: Schwartz

first: John

last: Leech

first: Geil

last: Merana

first: Kamir

last: Hiam-Galvez

first: Matthias

last: Mack

first: Joanna

last: Halkias

first: James

last: Gardner

first: Rachel

last: Rutishauser

first: Gabriela

last: Fragiadakis

first: Matthew

last: Spitzer

first: Alexis

last: Combes

first: Tiffany

last: Scharschmidt


title: Beta cell-derived cholecystokinin drives obesity-associated pancreatic adenocarcinoma development

first: Mandar

last: Muzumdar

overall_design: Male 16 week-old wild-type (WT) C57/B6 mice (Stock #000664) and male C57/B6 mice fed a 60% kcal fat diet (Research Diets 12492) for 10 weeks (Stock #380050) starting at 6 weeks of age were obtained from JAX. Islets were isolated, pooled for each group (n=4 mice per group), and dispersed into single cells for single-cell RNA sequencing.

first: Cathy

last: Garcia

first: Aarthi

last: Venkat

first: Daniel

last: McQuaid

first: Sherry

last: Agabiti

first: Alexander

last: Tong

first: Boby

last: Mathew

first: Rebecca

last: Cardone

last: Starble

first: Christian

last: Ruiz

first: Christy

last: Zheng

first: Akin

last: Sogunro

first: Jeremy

last: Jacox

first: Ken

last: Loh

first: Richard

last: Kibbey

first: Smita

last: Krishnaswamy

middle: D


title: Oligodendrocyte precursor cell regulates microglial transition to neuroprotective phenotype by BMP4 driven acquisition of disease associated state in Alzheimer’s disease

city: Daegu

first: Jaemyung

last: Jang

address: 61, Cheomdan-ro, Dong-gu

country: South Korea

institute: Korea Brain Research Institute

summary: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by cognitive decline and memory loss. Oligodendrocyte precursor cells (OPCs) reciprocally communicate with microglia in a context-dependent manner probably for immune surveillance, extending beyond their initial function as progenitor cells. In this study, we showed that late-OPC, also known as committed oligodendrocyte precursors (COPs), markedly upregulated expression of Bmp4 in response to Amyloid-β (Aβ). Selective Bone morphogenetic protein 4 (Bmp4) knock-out in OPCs of AD mouse model led to impairment of microglial clustering around Aβ plaque and Aβ phagocytosis, resulting in a substantial increase of Aβ deposition alongside dystrophic neurites. Mechanistically, Mothers against decapentaplegic homolog (Smad) signaling pathway, activated by Bmp4 derived from late-OPC, directly induced Triggering receptor expressed on myeloid cells 2 (Trem2) expression in microglia. This molecular cascade was required for robust acquisition of the disease-associated microglia (DAM) transcriptome, ultimately contributing to the development of neuroprotective DAM at early stage of amyloid deposition, prior to severe neuronal loss. Late-OPC sourced Bmp4 dependent appearance of DAM facilitated microglial barrier for Aβ plaque compaction, thereby insulating toxic Aβ species from adjacent neurites. Notably, intracerebroventricular administration of adeno-associated virus (AAV) carrying Bmp4 to AD mouse enhanced Trem2 expression of microglia around Aβ plaque, resulting in acceleration of plaque compaction. Consequently, this intervention alleviated synaptic damage and memory loss. Taken together, our findings strongly suggest that OPC-specific Bmp4 drives a molecular cascade to turn microglia into protective phenotype, providing a theoretical basis for a novel therapeutic strategy to target AD onset.

overall_design: To uncover how oligoednrocyte precurosor cells sourced Bmp4 is involved amyloid pathology, we performed Single-cell RNA sequencing (scRNA-seq) of cortex  from 5xFAD;PdgfraCreERT2;Bmp4+/+  and 5xFAD;PdgfraCreERT2;Bmp4-/-  mice.

first: Soonbong

last: Baek

first: Jong-Pil

last: Kim

first: Seungeun

last: Yeo

first: Hyun

last: Jung

first: Youngshik

last: Choe


title: Gene expression profile  of WT and mdig/mina53 KO MDA-MB 231 breast cancer cells [RNA-Seq]

city: Stony Brook

first: Fei

last: Chen

state: New York

address: Lauterbur Drive Stony Brook, NY 11794

institute: Stony Brook Cancer Center

summary: The mineral dust-induced gene (mdig, also called as MINA or RIOX2) is upregulated in breast cancer and predicts poor overall survival of breast cancer patients. Our studies suggested the anti-metastasis feature of mdig in regulating the cell motility of breast cancer cells. Here we studied the transcriptomic profile of human triple negative breast cancer cells MDA-MB-231 that were knocked out for mdig via CRISPR-Cas 9 gene editing. Our analysis identified distinct transcriptomic profiles in mdig knockout cells, where genes  associated with epithelial-mesenchymal transition (EMT) and TGF-β pathways were upregulated

overall_design: Wildtype type (WT) and mdig knockout (KO) MDA-MB-231 cells were subjected to RNA-Sequencing

first: Chitra

last: Thakur


title: The PIDDosome controls cardiomyocyte polyploidization during postnatal heart development

city: Freiburg

first: Katharina

last: Moos

address: Breisacherstr. 153

department: Medical Faculty

country: Germany

institute: University of Freiburg

summary: The mammalian adult heart is a post-mitotic organ characterized by mainly polyploid cardiomyocytes (CMs). The post-mitotic status of polyploid adult CMs poses a clear limit to heart regeneration. Thus, understanding how polyploid CMs acquire this status is relevant to heart regeneration therapies. Here, we aim to unveil whether the PIDDosome, a multi-protein complex known to limit scheduled and accidental polyploidization events by activating p53, implements a CM-specific genetic program that controls CM polyploidization during heart development. Flow cytometric DNA content analysis coupled with image-based 3D volumetric measurements of CM nuclei showed that PIDDosome knockout animals harbor significantly more polyploid CMs compared to WT animals. This increased CM ploidy levels do not interfere with both cardiac structure and functional output in steady-state and is a cell-autonomous phenotype. During heart development, ploidy analyses revealed that the PIDDosome starts to shape CM ploidy status at postnatal day 7 (P7), reaching a plateau of its action at P14. Moreover, PIDDosome activation in CM is dependent on PIDD1 localization to the extra mother centrioles via the distal appendage protein ANKRD26. Interestingly, in opposite to prior observations the PIDDosome limits CM polyploidization in a p53-independent manner that still involves p21, as confirmed in genetic and nuclear RNAseq analysis. Together these results identify a new molecular machinery that controls proliferation of polyploid CMs postnatally, adding a set of new players that control the tightly regulated program of the terminal CM differentiation occurring in the postnatal heart.

overall_design: We performed bulk RNA-seq of both Casp2 deficient (XMLC2(+)Casp2(fl/fl)) and control (XMLC2(-)Casp2(fl/fl)) postnatal cardiomyocyte nuclei in mice. Cardiomyocytes were collected at postnatal days 1, 7 and 14. Four replicates were collected per postnatal day and genotype. To obtain sufficient RNA material, several hearts were pooled per replicate (P1: 15 hearts, P7: 6 hearts, P14: 2 hearts).

first: Marina

last: Leone

first: Nadine

last: Kinz

first: Felix

last: Eichin

first: David

last: Obwegs

first: Valentina

last: Sladky

first: Dario

last: Rizzotto

first: Claudia

last: Manzl

first: Etienne

last: Jacotot

first: Clarissa

last: Savko

first: Mark

last: Sussmann

first: Melanie

last: Boerries

first: Andreas

last: Villunger


title: Modeling Spastic Paraplegia 4 using Human Corticospinal Motor Neuron enriched Cortical Organoids Uncovers Genotype–Phenotype Distinctions and HDAC6-Targetable Pathology

status: Public on Jan 19 2026

first: Liang

last: Qiang

address: 2900 Queen Lane room183

institute: Drexel University

summary: Spastic Paraplegia 4 (SPG4), the most common form of Hereditary Spastic Paraplegia, causes progressive gait deficiency due to corticospinal tract degeneration. SPG4 results from mutations in the SPAST gene, which encodes spastin, a microtubule-severing AAA-ATPase. To dissect genotype–phenotype relationships, we generated isogenic human induced pluripotent stem cell lines carrying either a SPAST missense (SPASTWT/C448Y) or truncation (SPASTWT/S245X) mutation and differentiated them into motor cortical organoids. These models revealed mutation-specific patterns of aberrant neuronal activity, microtubule hypoacetylation and axonal degeneration. We identified mutant M1-spastin-induced hyperactivation of histone deacetylase 6 (HDAC6), a major tubulin deacetylase as the key pathogenic culprit. Pharmacological inhibition of HDAC6 with Tubastatin A restored microtubule acetylation and rescued axonal degeneration in organoids, with corresponding improvements in corticospinal tract integrity and gait defects in SPG4 transgenic mice. Our study uncovers HDAC6 hyperactivation as a targetable mechanism for SPG4 and verifies human organoids as a platform for therapeutic discovery.

overall_design: The generated corticospinal motor neuron enriched cortical organoids were dissociated and processed using 10X genomics, 3' NEXT-GEM kit. The wild-type organoids sc-RNAseq data was used to identify the different cell-populations.

first: Neha

last: Mohan

first: Skandha

last: Ramakrishnan

first: Xiaohuan

last: Sun

first: Ying

first: Theresa

last: Connors

first: Victor

last: Chai

first: Emanuela

last: Piermarini

first: Peter

last: Baas

first: James

last: Cai

first: Mei

last: Liu


title: LSD1 inhibitor, TAS1440, disrupts INSM1-LSD1 complex activating tumor-suppressive pathways via transcriptional reprogramming in neuroendocrine SCLC

city: chiba

first: YINGBO

last: GONG

department: Medicine

institute: CHIBA University

summary: Small cell lung cancer (SCLC) is aggressive with limited treatment options, requiring new therapies. Lysine-specific histone demethylase 1 A (LSD1) maintains neuroendocrine state by repressing NOTCH/TGF-β signaling; their reactivation suppresses proliferation and induces differentiation. However, mechanisms of LSD1 inhibition and chemoresistance remain unclear. Here we developed TAS1440, a histone H3-competitive LSD1 inhibitor, using structure-based engineering to improve specificity and reduce off-target effects. Unlike irreversible inhibitors targeting the flavin adenine dinucleotide site, TAS1440 non-covalently targets the H3-binding pocket to enhance safety and efficacy. TAS1440 suppressed proliferation in INSM1/ASCL1-high SCLC-A cells and induced tumor regression in xenografts. TAS1440 acts through dual mechanisms: inhibiting LSD1 activity and disrupting LSD1-repressive complexes, remodeling histone marks and activating transcription factors INSM1 and SMAD2. These actions reprogram tumor-suppressive TGF-β/NOTCH signaling, supporting TAS1440 as epigenetic therapy for SCLC. Loss of LSD1 enzymatic activity or INSM1 knockout abrogated TAS1440 effects, defining its mode of action and chemoresistance. These findings support TAS1440 as a next-generation epigenetic therapy candidate for INSM1-high SCLC-A.

overall_design:
To study the transcriptional signatures and the effects of the LSD1 inhibitors in SCLC cell lines, we sequenced the bulk RNA of the 22 SCLC cell lines under DMSO/LSD1 inhibitors treatment.
To elucidate whether the TAS1440-dependent dissociation of INSM1 from the LSD1 complex is crucial for inhibition of cell growth, we established NCI-H1417 and NCI-H146 cells lacking INSM1 using the CRISPR/Cas9 system. We then sequenced NCI-H1417 and NCI-H146 cells lacking INSM1 under DMSO/TAS1440 treatment.

first: Takumitsu

last: Machida

first: Yingbo

last: Gong

first: Sayaka

last: Tsukioka

first: Atsushi

last: Onodera

first: Akitoshi

last: Nakayama

first: Naoko

last: Hashimoto

first: Takahiro

last: Fuchigami

first: Satoshi

last: Yamashita

first: Tatsuya

last: Suzuki

first: Ryo

last: Hatanaka

first: Yasuo

last: Kodama

first: Shuichi

last: Ohkubo

first: Tomoaki

last: Tanaka


overall_design: To identify the transcription factors involved in LSD1 inhibitor-dependent changes in histone modifications, we performed ChIP-seq (H3K4me1, H3K4me2, H3K4me3 and H3K27ac) using the NCI-H1417 cell line.


title: RECQL dysfunction contributes to social and depressive-like behavior and aldolase activity changes in mice [Neuroinflammation]

first: Supriyo

last: De

address: 251 Bayview Blvd

department: Laboratory of Genetics and Genomics

institute: NIA-IRP, NIH

summary:
The RecQ helicase family plays a vital role in maintaining genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five RecQ helicases: RECQL1, Bloom syndrome (BLM), Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ proteins is associated with genetic disorders, tumorigenesis, premature aging, and neurodegeneration. The biological importance of RecQ helicases is well established; However, it is still unknown the potential outcomes after DNA damage, and there is no systematic study yet to compare the behavioral changes amongst various RecQ-deficient mice. In this study, we investigated the effects of IR treatment on three RecQ-deficient mouse models (Recql1, Wrn and Recql4). Here we provided evidence that RecQ dysfunction impaired social ability and induced depressive-like behavior in mice, with or without irradiation stress, while abnormal cognitive behaviors only existed in RecQ-deficient mice without IR treatment, suggesting RecQ proteins contribute to mood and cognition. Furthermore, transcripts and metabolomics analysis revealed significant alterations in the RecQ-deficient mice, especially after IR treatment. Particularly, pathways related to neuronal and microglia functions, DNA damage repair, cell cycle, and reactive oxygen response were downregulated in the RecQ4 and Wrn mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes, Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our finding suggested that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that aldolase activity may be associated with these changes, representing it as a potential therapeutic intervention.
To understand what Neuroinflammation-related gene expression changes are induced by γ-irradiation in the WT,  RecQ1, WRN, RecQ4 deficient mice. They were exposed the whole body with γ-irradiation (IR, 6 Gy), thereafter prefrontal cortex tissues were collected from each mouse and subjected to RNA isolation.

overall_design: We analyzed a total of 33 samples of mouse prefrontal cortex either exposed with γ-irradiation (IR) or not as follows: WT_vehicle (n=4), RecQ4_vehicle (n=4),  WRN_vehicle (n=3), RecQ1_vehicle (n=4), WT_IR (n=5), RecQ4_IR (n=5), WRN_IR (n=3), and RecQ1_IR (n=5). Analysis employed nCounter Advanced Analysis suite of tools.

first: Vilhelm

last: Bohr


title: CGRP signaling Links Tumor-Associated Pain to Immune Evasion in Oral Squamous Cell Carcinoma

city: Kingston

first: Sebastien

last: Talbot

address: 18 Stuart st

department: DBMS

institute: Queen's University

summary: Peripheral sensory nerves are thought to contribute to solid tumor growth, particularly in oral squamous cell carcinoma (OSCC); however, the link between pain and immunosuppression remains unresolved. Here, using a prospective observational study, we demonstrate an inverse relationship between OSCC-induced pain mediated by calcitonin gene-related peptide (CGRP)-expressing nerves and tumor-associated immunity. Bulk RNA sequencing of tumor-innervating sensory neurons from mice revealed differential regulation of genes associated with excitability, neurotransmission, and axonal sprouting. Using a gain-of-function approach with persistent stimulation of peptidergic afferents, we show that sensory neurons promote oral tongue tumor growth and limit the activation of effective anti-tumor immune responses via efferent CGRP release. Conversely, loss-of-function approaches—including local ablation of nociceptive nerves and systemic CGRP receptor antagonism—slowed tumor growth and improved anti-tumor immunity. Targeting CGRP may therefore represent a therapeutic strategy in OSCC to reduce pain and improve treatment response.

overall_design: Retrogradely labeled trigeminal ganglion (TG) neurons were isolated from sham and tumor-bearing mice by fluorescence-activated cell sorting. Briefly, bilateral TGs were harvested, dissociated, and cell viability was assessed by microscopy. DiI⁺ neurons were sorted directly into 500 µL TRIzol reagent and stored at −80 °C until RNA extraction. Gating was established using TG neurons from naïve mice and DiI-injected sham controls.  Bulk RNA sequencing was performed to compare gene expression between MOC1 tumor-bearing and sham control mice (n = 11 total; 6 MOC1 and 5 sham). RNA extraction, library preparation, and sequencing were carried out at the IRIC Genomics Platform (Université de Montréal). RNA integrity was verified using an Agilent Bioanalyzer. Poly(A)⁺ RNA was enriched from total RNA, and libraries were prepared using the KAPA RNA HyperPrep Kit with poly(A) selection according to the manufacturer’s instructions. Libraries were sequenced on an Illumina NextSeq 500 to generate single-end reads over 75 sequencing cycles (maximum read length 1 × 85 nt).  Reads were trimmed with Trimmomatic v0.35 and aligned to the mouse reference genome GRCm38 (mm10) using STAR v2.7.1a with strand-specific parameters. Gene-level quantification was performed using STAR and RSEM.  Differential expression analysis was conducted in R using DESeq2, with significance determined using Benjamini–Hochberg adjusted p-values (padj < 0.05). Significant genes were annotated with gene symbols and exported for downstream analyses. Data visualization included volcano plots (ggplot2, ggrepel) and heatmaps of z-score–normalized expression for significant genes, with rows annotated by −log10(padj) and columns labeled by condition. Expression of selected genes (e.g., Trpv1, Calca, and Ngfr) was compared between groups using box plots; statistical testing used Wilcoxon rank-sum tests with Benjamini–Hochberg correction. Principal component analysis (PCA) was performed on rlog-transformed counts to assess sample clustering and overall variance, and visualized using ggplot2 and plotly. All analyses were performed in R to support reproducibility.

first: Amin Reza

last: Nikpoor

first: Maryam

last: Ahmadi

first: Nicole

last: Scheff


title: Outer membrane vesicles of carbapenem-resistant Acinetobacter baumannii derive enhanced inflammatory response

city: Suzhou

first: Yang

last: Yang

address: NO. 899, Pinghai Road

institute: the First Affiliated Hospital of Soochow University

summary: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a critical nosocomial pathogen with limited treatment options. Although antibiotic resistance in CRAB is well-characterized, its interactions with host immunity and the contribution of outer membrane vesicles (OMVs) to pathogenesis remain poorly understood. We examined a clinical CRAB isolate and compared it with the reference strain A19606. Antimicrobial susceptibility testing revealed complete resistance of CRAB to commonly used antibiotics in clinical practice, while A19606 remained susceptible to most agents. In murine intranasal infection models and bone marrow-derived macrophages, CRAB induced significantly stronger activation of inflammatory signaling pathways and elevated levels of pro-inflammatory cytokines relative to A19606. Transcriptomic analysis of infected lung tissue identified differentially expressed genes, enriched for inflammatory response pathways. proteomics showed upregulated proteins in CRAB related to secretion systems. OMVs characterization revealed that CRAB-derived OMVs highly enriched in proteins associated with periplasmic and outer membrane spaces, and more potent in triggering macrophage inflammatory signaling. CRAB displays expansive antibiotic resistance and enhanced pro-inflammatory potential mediated in part by unique OMVs properties. Targeting OMVs formation or host immune modulation may represent effective strategies for combating CRAB infections.

overall_design: Mice were uninfected with 1 × 107 CFU of CRAB or A19606 for 6 h (n = 3), lungs were harvested and prepared for RNA-sequencing.

first: Nana

last: Tang

first: Yuanyuan

last: Zeng

first: Jianjie

last: Zhu

first: Jiajia

last: Wang

first: Zeyi

last: Liu

first: Jian-an

last: Huang


title: MYC modulates TOP2A diffusion to promote substrate detection and activity.

city: Solna

first: Vladislav

last: Kuzin

state: Stockholm

address: Solnavägen 9

department: Cell and Molecular Biology

country: Sweden

institute: Karolinska Institute

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

overall_design: Refer to individual Series


title: Rapid production of precisely edited cattle and mice via a single AAV delivered miniature IscB#/ωRNA# [dataset 2]

city: Hohhot

first: Lei

state: Inner Mongolia Autonomous Region

address: 24 Zhaojun Rd.

department: State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock

institute: Inner Mongolia University

summary: Utilising adeno-associated virus (AAV) to deliver CRISPR/Cas has enhanced the generation of knock-out mice, but single-AAV delivery of Cas and homology-directed-repair (HDR) templates in livestock remains a challenge. Here, we introduce all-in-one AAV vectors containing shortened IscB#, the progenitor of Cas9, along with either miniature ωRNA#, or ωRNA# with a large HDR-template. Encouragingly, we efficiently generated knock-out and knock-in cattle and mice by infecting zygotes with AAV::IscB#/ωRNA#-HDR without costly micromanipulators.

overall_design:
The novel strategy to generate genetically modified mice and ruminant cattle by transduction of engineered IscB and its ωRNA (termed IscB#-ωRNA#) components into pre-implantation embryos via co-culture with adeno-associated viruses (AAVs).
To evaluate the specificity of IscB-ωRNA, the Cas-OFFinder was used to predict the potential off-target sites. Off-target sites of each group were selected from the lower number of mismatches to the higher number of mismatches. Sites with TAM were retained for IscB. Off-target sites of each guide sequence were selected in order from the lowest number of mismatches to the highest number of mismatches.


title: Proteostasis failure and mitochondrial dysfunction contribute to chromosomal instability-induced microcephaly

city: Barcelona

first: Camille

last: Stephan Otto Attolini

state: Select a State or Province

address: Baldiri Reixac 10

department: Biostatistics and bioinformatics Unit

country: Spain

institute: IRB Barcelona

summary: Mosaic variegated aneuploidy (MVA), a rare human congenital disorder that causes microcephaly, is characterized by extensive abnormalities in chromosome number and caused by mutations in genes involved in accurate mitotic chromosome segregation. Here we generated a Drosophila model of microcephaly caused by depletion of a single spindle assembly checkpoint (SAC) gene in the neural stem cell (NSC) compartment to characterize the cellular mechanisms underlying this disease. We present evidence that loss of stemness of NSCs – compromised identity and proliferative capacity - is the underlying cause of the disease and results in a reduced number of neurons and glial cells. We show that loss of stemness is a consequence of the accumulation overtime of an unbalanced number of gains and losses of more than one chromosome, rather than a direct consequence of chromosomal instability-induced DNA damage or the production of simple aneuploidies. We unravel a contribution of proteostasis failure, most probably as a consequence of the imbalance in the whole protoeome, and mitochondria dysfunction to the negative impact of complex aneuploidies on stem cell identity. We identify autophagy activation -either directly or through TOR depletion –, overexpression of Radical Oxygen Species scavengers, or restoration of mitochondria proteostasis as genetic interventions capable of dampening the deleterious effects of aneuploidy on NSC identify and brain development

overall_design: The samples used for this study are late L3 larvae from Drosophila melanogaster (96 hours after egg laying at 29 ºC). For the control, we have used w; worniu-gal4, UAS-gfp-i larvae. For the experimental condition, we have used w; worniu-gal4, UAS-bub3-i larvae. 3 replicates from different days were performed and 3 brains were dissected per each genotype and per replicate. All the larvae used were females.

last: Stephan-Otto Attolini

first: Marco

last: Milan

first: Amanda

last: González


title: A PLETHORA3/7 transcription factor shapes cucumber shoot architecture [DAP-seq]

city: Wageningen

first: Merijn

last: Kerstens

address: Droevendaalsesteeg 1

department: Plant Developmental Biology

country: Netherlands

institute: Wageningen University & Research

summary: PLETHORA transcription factors (PLTs) are master regulators of plant development. In Arabidopsis, loss of shoot meristematic PLTs leads to destabilised phyllotaxis, but whether these factors have similar functions in more distantly related species, is not known. Here, we investigated the role of PLTs in shaping cucumber shoot architecture. Through transcriptional analysis, we determined that two of the four homologs - CsPLT3/7 and CsPLT5 - are expressed in complementary domains in the shoot apex. In situ hybridisation showed that whereas CsPLT3/7 was expressed in the shoot apical meristem summit and leaf axils, CsPLT5 transcripts localised beneath the CsPLT3/7 domain and to the adaxial side of leaf primordia. Both transcription factors recognised an ANT-like consensus motif and bound to SAM organising genes in vitro. Using a panel of TILLING mutants of each of the four CsPLT homologs, we only identified strong phenotypic defects for Csplt3/7 mutants. The combination of Csplt1/2 and Csplt3/7 proved embryonic lethal. In young seedlings, loss of CsPLT3/7 caused absence of a shoot apical meristem, which regenerated de novo shoot from a flat shoot apex during subsequent seedling development. Mature Csplt3/7 shoots exhibited defects in internode length stabilisation, revealing both extremely short and long internodes, stem architecture, flower morphology, and axillary organ initiation. Moreover, phyllotactic patterns were slightly shifted from a spiral towards a distichous orientation. We thus provide the first evidence of a role for PLTs in shoot development outside of Arabidopsis.

overall_design: CsPLT3/7 and CsPLT5 DAP-seq on gDNA derived from 6 dpg cucumber (Rijk Zwaan proprietary parental line) shoot apical meristems grown in germination pouches

first: Kelvin

last: Adema

first: Olga

last: Kulikova

first: Florian

last: Müller

first: Magdalena

last: Lastdrager

first: Ben

last: Scheres

first: Viola

last: Willemsen


title: Impaired removal of dying brain cells by microglia in GPR34 deficient mice

status: Public on Jan 22 2026

city: Cambridge

first: Joshua

last: Levin

state: MA

address: 75 Ames St

department: Stanley Center

institute: Broad Institute

summary: GPR34, a G protein coupled receptor present selectively in microglia and other myeloid cells, is highly expressed in homeostatic microglia but is downregulated in disease associated microglia such as are found in Alzheimer’s disease brain. However, little is known about GPR34’s role in microglia function or brain development. Here, we studied Gpr34 knockout (KO) mice at postnatal 18-day (18 d) and 3 months (3 mo) age. In the brains of 18 d GPR34 KO mice, there were elevated numbers of neurons, oligodendrocytes and microglia, many of which were IHC-positive for cell death markers cleaved-caspase 3, phospho-RIP3, or annexin V. There was no increase in cell death markers or in steady state numbers of neurons, oligos and microglia at 3 months, indicating that GPR34-independent mechanisms are able to compensate during brain maturation. Based on RNA sequencing analysis and phagocytosis functional assays, as well as computational modeling, we provide evidence  that Gpr34 KO microglia have deficiencies in chemotaxis, but not phagocytic efficiency, which leads to a slower clearance of dead cells from the developing brain. Collectively, these results indicate that Gpr34 is required for microglia to clear dead or dying cells.

overall_design: GPR34 KO and WT mice were generated, and for each numerous brain regions were sequenced with RNA-seq. For more details see our publication.

first: Diana

last: Bohannon

first: Ana

last: Geller

first: Sean

middle: K

last: Simmons

first: John

last: Cintron

first: William

last: Martenis

first: Katherine

last: Stalnacker

first: Autumn

last: Masse

first: Min Jee

last: Kwon

first: Yan-Ling

last: Zhang

middle: Z

first: Prabhat

last: Kunwar

first: Morgan

last: Sheng


title: Targeted citrullination enables p53 binding to non-canonical sites [ChIP-seq]

first: Priyankara

last: Wickramasinghe

address: 3601 Spruce Street

department: Bioinformatics

institute: The Wistar Institute

summary: TP53 encodes for the transcription factor p53, which binds to a diverse set of target genes in response to stress.  Activation of p53 results in highly specific transcriptional responses, but the regulation of promoter selectivity by p53 is poorly understood.  Here we report that sequence-specific binding of p53 is regulated by its target gene and binding partner PADI4.  PADI4 enzymatically converts peptidyl-arginine to peptidyl-citrulline in a process known as citrullination.  We show p53 is citrullinated in vitro at the C-terminus by PADI4, and we confirm two citrullination events in vivo (R306, R363).  ChIP-seq reveals that PADI4 expression causes a redirection of p53 away from canonical binding sites to target genes associated with the ETS transcription factor and the interferon response.  Chromatin profiling using citrullination-specific p53 antibodies supports this conclusion.  These findings link citrullination to p53 function and illustrate how chromatin modifiers like PADI4 can redirect the p53 transcriptional response.

overall_design: Chromatin immunoprecipitation followed by DNA-sequencing (ChIP-seq) of H3K27ac and p53 in HCT116 cells transfected with a tetracycline-inducible system to induce PADI4 or it's catalytically dead mutant (D350A) expression. Cells were either treated with vehicle (untreated), nutlin, or the combination of nutlin and doxycyline for 24 hours.

first: Alexandra

last: Indeglia

first: Andrea

last: Valdespino

first: Giulia

last: Pantella

first: Sarah

last: Offley

first: Connor

last: Hill

first: Alessandro

last: Gardini

first: Maureen E.

last: Murphy


title: The ribosome synchronizes folding and assembly to promote oligomeric protein biogenesis

city: Heidelberg

first: Günter

last: Kramer

address: Im Neuenheimer Feld 329

institute: Center for Molecular Biology of Heidelberg University (ZMBH)

summary: Natural proteins are structurally diverse and often form intricate multidomain, oligomeric architectures. This presents a prima facie challenge to cellular homeostasis, as topologically complex proteins seldom refold efficiently in vitro. How cells overcome sequence-intrinsic folding limitations to optimize protein biogenesis is incompletely understood. Here, we show that efficient folding and assembly of a model 5-domain homotetramer is obligatorily coupled to its synthesis on the ribosome, and define the underlying mechanisms. During refolding of full-length protein from denaturant, maturation of the catalytic TIM barrel domain is frustrated. Assembly outpaces monomer folding, and non-native oligomers accumulate. The ribosome directs the order of folding events and specifies the pathway of oligomer assembly. Efficient de novo folding is characterised by segmental folding of the TIM barrel, shaped by binding of a nascent amphipathic helix to a cryptic pocket on the ribosome surface. Homomer assembly initiates cotranslationally via recruitment of a full-length subunit to the nascent polypeptide, and the failure to do so results in misassembly. Our results reveal how the ribosome can dictate the timing of folding and assembly to enable efficient biogenesis of a topologically complex protein.

overall_design: Probing cotranslational assembly of beta-galactosidase by selective ribosome profiling (https://doi.org/10.1038/s41586-018-0462-y) and disome selective profiling (DOI: 10.1126/science.abc7151).

first: Alžběta

last: Roeselová

first: Santosh

last: Shivakumaraswamy

first: Gabija

last: Jurkeviciute

first: Josef

last: Auburger

first: Jaro

last: Schmitt

first: Bernd

last: Bukau

first: Jessica

last: Zhiyun He

first: Radoslav

last: Enchev

first: David

last: Balchin


title: Cut&Tag-seq for HER1 location using α-HER1  antibody, and Cut&Tag-seq for WT and her1 using α-H3K9me2 antibody

city: Chengdu

first: Daiming

last: Guo

state: Sichuan

address: 211 Huimin Road, Wenjiang

department: Rice Research Institute

institute: Sichuan Agricultural University

summary: To investigate the effect of the HER1 and identity its downstream targets, we analysed HER1 binding regions and genome-wide H3K9me2 levels in WT and the mutant her1 using Cut&Tag-seq.

overall_design: Cut&Tag-seq for HER1 location used the α-HER1  antibody, and Cut&Tag-seq for WT and her1 used the α-H3K9me2 antibody.

first: Kangxi

last: Du

first: Xianjun

last: Wu

first: Yongxiang

last: Liao


title: Midgut cell atlas of four important mosquito species and the key factors associated with DENV infection

city: Wuhan

first: Han

last: Xia

state: Hubei

department: Key Laboratory of pathogenic Viruses and Biosafety

institute: Wuhan Institute of Virology, CAS

summary: Mosquitoes serve as medically significant vectors for transmitting various arboviruses. The mosquito midgut is both the digestive organ and primary infection site via viral bloodmeals, and the midgut cells show heterogeneity on virus-vector interactions. Rapidly developed single-cell RNA sequencing (scRNA-seq) technologies allow to characterize midgut physiology and viral infection dynamics at cellular solution. At present, scRNA-seq studies about mosquito midgut cell atlas are still limited and lack established protocols for cellular isolation. Therefore, we developed and employed a compatible microwell-based scRNA-seq protocol on four important mosquito species including Aedes aegypti, Aedes albopictus, Culex pipiens pallens and Culex tritaeniorhynchus and successfully established their midgut cell atlases pre- and post-bloodmeal. Further, we performed scRNA-seq experiments on DENV-infected Ae. aegypti to characterize the viral infection dynamics at single-cell solution.

sample_organism:
Aedes aegypti
Aedes albopictus
Culex tritaeniorhynchus
Culex pipiens pallens

overall_design: To establish midgut cell atlas of four medically important mosquitoes including Aedes aegypti, Aedes albopictus, Culex pipiens pallens and Culex tritaeniorhynchus, we applied a compatible microwell-based scRNA-seq protocol to the female mosquitoes. We performed scRNA-seq experiments on the midgut samples of the four mosquito species at 7 days with only glucose solution to establish their midgut cell atlas. To decipher the transcriptional changes following the uninfectious bloodmeal, we utilized scRNA-seq experiments on both Aedes aegypti and Culex tritaeniorhynchus, respectively. Further, to characterize the dynamics of mosquito midgut post-infection, we performed scRNA-seq experiments on the DENV-infected Aedes aegypti.


title: A PLETHORA3/7 transcription factor shapes cucumber shoot architecture [RNA-Seq]

first: Merijn

last: Kerstens

overall_design: RNA profiling of 6 dpg shoot apices of cucumber '9930' seedlings grown on soil plates and in germination pouches

first: Kelvin

last: Adema

first: Olga

last: Kulikova

first: Florian

last: Müller

first: Magdalena

last: Lastdrager

first: Ben

last: Scheres

first: Viola

last: Willemsen


title: RecQ dysfunction contributes to social and depressive-like behavior and aldolase activity changes in mice [Metabolic]

city: Baltimore

first: Supriyo

last: De

summary:
The RecQ helicase family plays a vital role in maintaining genome stability, including DNA replication, recombination, and DNA repair. In human cells, there are five RecQ helicases: RECQL1, Bloom syndrome (BLM), Werner syndrome (WRN), RECQL4, and RECQL5. Dysfunction or absence of RecQ proteins is associated with genetic disorders, tumorigenesis, premature aging, and neurodegeneration. The biological importance of RecQ helicases is well established; However, it is still unknown the potential outcomes after DNA damage, and there is no systematic study yet to compare the behavioral changes amongst various RecQ-deficient mice. In this study, we investigated the effects of IR treatment on three RecQ-deficient mouse models (Recql1, Wrn and Recql4). Here we provided evidence that RecQ dysfunction impaired social ability and induced depressive-like behavior in mice, with or without irradiation stress, while abnormal cognitive behaviors only existed in RecQ-deficient mice without IR treatment, suggesting RecQ proteins contribute to mood and cognition. Furthermore, transcripts and metabolomics analysis revealed significant alterations in the RecQ-deficient mice, especially after IR treatment. Particularly, pathways related to neuronal and microglia functions, DNA damage repair, cell cycle, and reactive oxygen response were downregulated in the RecQ4 and Wrn mice. In addition, increased DNA damage responses were found in RecQ-deficient mice. Notably, two genes, Aldolase Fructose-Bisphosphate B (Aldob) and NADPH Oxidase 4 (Nox4), were differentially expressed in RecQ-deficient mice. Our finding suggested that RecQ dysfunction contributes to social and depressive-like behaviors in mice, and that aldolase activity may be associated with these changes, representing it as a potential therapeutic intervention.
To understand what metabolism-related gene expression changes are induced by γ-irradiation in the WT,  RecQ1, WRN, RecQ4 deficient mice. They were exposed the whole body with γ-irradiation (IR, 6 Gy), thereafter prefrontal cortex tissues were collected from each mouse and subjected to RNA isolation.

first: Vilhelm

middle: A

last: Bohr


title: RNAseq for WT and her1 rice

summary: To investigate the effect of the HER1, we performed RNA-seq and differential expression  analyses on stigmas from WT and the her1 mutant.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for WT and her1.


title: Bulk RNA-seq detects cMPC HO signature in hip arthroplasty patients

status: Public on Jan 18 2026

city: Boston

first: Nezihi Murat

last: Karabacak

state: Massachusetts

address: 51 Blossom St

institute: Massachusetts General Hospital

summary: Heterotopic ossification (HO), the aberrant bone in soft tissues, is one of the most debilitating complications associated with severe burn and traumatic injuries as well as joint replacement surgeries due to its insidious development. Currently, no technologies exist to either support early HO detection or to guide early prophylactic strategies. Furthermore, no technologies exist to assess treatment efficacy. In this study, we used microfluidic iChip, designed to isolate circulating rare non-hematopoietic cells from whole blood, to isolate and analyze circulating mesenchymal progenitor cells (cMPCs) released in patients that underwent hip artroplasty. RNA sequencing of cMPCs revealed the unique expression of HO-associated MPC genes observed post operation day 1, weeks earlier than gold standard radiographic diagnostic strategies.

overall_design: iChip enriched cells were lysed with RLT buffer (Qiagen Micro kit) and stored at -80C. Before proceeding to library preparation, RNA was purified with Qiagen micro kit. Total RNA libraries were prepared using Seqwell Rapid kit using manufacturer instructions.

first: Matilda

last: Holtz

first: Sneha

last: Korlakunta

first: Johanna

last: Nunez

first: Hanil

last: Kang

first: Benjamin

last: Levi

first: Murat

first: Florence

last: Lin


title: Bulk RNA Sequencing of MCMV-Specific M45 Tetramer-Positive CD8⁺ T Cells from Wild-Type and  B cell-deficient JHT mice

city: Mainz

first: Xinyuan

last: Liu

address: Langenbeckstraße 1

department: Institute for Molecular Medicine

institute: University Medical Center, Johannes Gutenberg University Mainz

summary: To assess the impact of B cell deficiency on MCMV-specific CD8⁺ T cells, equal numbers of M45 tetramer-positive CD8⁺ T cells were sorted from wild-type and B cell–deficient JHT mice. The isolated antigen-specific CD8⁺ T cells were subjected to bulk RNA sequencing to compare transcriptional profiles between the two groups.

overall_design: Wild-type and B cell–deficient JHT mice were infected with murine cytomegalovirus (MCMV). At 7 days post infection, MCMV-specific M45 tetramer-positive CD8⁺ T cells were isolated by flow cytometric sorting. Equal numbers of tetramer-positive CD8⁺ T cells from each group were collected to control for differences in cell frequency. Total RNA was extracted from the sorted cells and subjected to bulk RNA sequencing to compare transcriptional profiles between wild-type and JHT mice.

first: Ari

last: Waisman


title: FBXO3-mediated DUSP9 ubiquitination reprograms MAPK signaling to eradicate tyrosine kinase inhibitor-resistant CML stem cells

city: zhengzhou

first: Li

last: Xudong

state: Henan

address: No. 1, Jianshe East Road, Erqi District

institute: The First Affiliated Hospital of Zhengzhou University

summary: Discovering new therapeutic targets to overcome tyrosine kinase inhibitors (TKIs) resistance and clear leukemic stem cells (LSCs) is an urgent clinical need for chronic myeloid leukemia (CML) treatment. In the present study, we report that the F-box protein 3 (FBXO3) is upregulated in CD34+ CML stem cells from patients with TKI treatment failure and is regulated by BCR-ABL. Single-cell RNA sequencing (scRNA-seq) analysis indicated that FBXO3+ HSCs from CML patients have significant LSC signatures. Genetic depletion of FBXO3 significantly increased apoptosis and decreased proliferation of both imatinib-sensitive/resistant CML cell lines and CML stem cells in vitro and in vivo, with minimal effects on normal CD34+ HSCs. Mechanistically, FBXO3 interacts with DUSP9 and mediates its ubiquitination. DUSP9 knockdown partially counteracts the elimination of CML stem cells mediated by FBXO3 depleting in vitro and in vivo. RNA-seq results indicates that FBXO3-mediated ubiquitination of DUSP9 activates MAPK signaling pathway in CML cells.  Moreover, FBXO3 inhibitor alone or in combination with imatinib significantly clear CML stem cells and overcome TKI resistance in murine and human CML, with minimal effects on normal hematopoiesis.  Overall, our findings uncover novel roles of FBXO3 in CML progression and provide a rationale for combining FBXO3 inhibitors with TKIs to induce durable elimination of CML-LSCs.

overall_design: RNA-seg profiling of wildtype K562 cells and their knockdown derivatives(shDUSP9)

first: Xudong

last: Li

first: Shiyu

last: Zuo

first: Yongping

last: Song

first: Zhilei

last: Bian

first: Wei


title: Rapid production of precisely edited cattle and mice via a single AAV delivered miniature IscB#/ωRNA# [dataset 1]

first: Lei

last: Yang

overall_design: The novel strategy to generate genetically modified mice and ruminant cattle by transduction of engineered IscB and its ωRNA (termed IscB#-ωRNA#) components into pre-implantation embryos via co-culture with adeno-associated viruses (AAVs).


title: Fibrosis-memory is mediated by IL-3-producing T cells and drives progression of fibrosis

city: Regensburg

first: Michael

last: Rehli

address: F.-J.-Strauss-Allee 11

department: Internal Med III

institute: University Hospital Regensburg

summary: Repetitive injuries are an important trigger of progressive fibrosis. To study if repetitive injuries induce an accelerated pro-fibrotic process, also called “fibrosis-memory”, we established an experimental system with two consecutive, clearly separated insults in a model of renal fibrosis with reversible ureteral obstruction of the right kidney (from day 0-6) and irreversible unilateral ureteral obstruction of the left kidney (from day 17-22).

overall_design: 5' end sequencing of Tcrb mRNAs in T cells from spleen and left UUO-kidney on day 22

first: Matthias

last: Mack

first: Simone

last: Buchtler

first: Sophia

last: Neumayer

first: Claudia

last: Gebhard


title: Decoding plant defense signaling using the defenseless mutant

city: Helsinki

first: Bikash

last: Baral

address: Pallaksentie 4C, 33

country: Finland

institute: University of Helsinki

summary: Despite extensive disruption of immune signaling in the defenseless mutant, residual resistance to A. alternata and Pst DC3000 persisted at levels exceeding those of known defense-compromised controls. Our RNA-seq analysis revealed a largely preserved transcriptional response, with comparable differential gene expression profiles in both Col-0 and defenseless backgrounds. These results further emphasize that full immune suppression necessitates the concurrent disruption of multiple, potentially redundant pathways (beyond our current understanding). The persistence of some resistance further implies the presence of unidentified immune mechanisms, highlighting the complexity and resilience of the plant immune system, which we are still highly unfamiliar with.

overall_design: RNAseq-profiling of Col-0 (WT) and defenseless mutant (mutation in 6 different defense genes) in control and ozone conditions, with three replicates of each.

first: Mikael

last: Brosché


title: Drug Repurposing Identifies Proteasome Inhibitors as Antiproliferative Agents Counteracting Inflammation-Driven Chemoresistance in Triple-Negative Breast Cancer Organoids

city: Bangkok

first: Jakkrit

last: Khamjerm

address: 270 Rama VI Rd, Thung Phaya Thai, Ratchathewi

country: Thailand

institute: Faculty of Medicine Ramathibodi Hospital

summary: Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with limited treatment options, characterized by high relapse rates and poor survival outcomes due to chemoresistance. This study aimed to repurpose FDA-approved drugs for TNBC and investigate their mechanisms of action in inhibiting cancer cells and counteracting  chemoresistance. Methods: Patient-derived TNBC organoids were generated from residual tumors of patients  with disease progression despite receiving standard-of-care chemotherapy. A high throughput screen of 133 FDA-approved anticancer drugs was performed on the organoids to identify potent cytotoxic agents using image-based analysis and drug-sensitivity assays. Drug response dynamics were analyzed to evaluate the efficacy of these agents in counteracting clinical drug resistance. The molecular and functional effects of the identified agents were investigated through proteomic and transcriptomic analyses, as well as translation and cell cycle assays. Results: Proteasome inhibitors bortezomib (BTZ) and carfilzomib (CFZ) were identified as potent candidates for inhibiting TNBC organoids. These drugs significantly downregulated ribosomal protein expression, suppressing translation and disrupting cell cycle progression. While TNBC organoids exhibited resistance to conventional chemotherapeutics, they were susceptible to proteasome inhibitors. Transcriptomic profiling revealed that proteasome inhibitors counteracted inflammation-driven resistance to doxorubicin (DXR) by exerting dual anti-inflammatory and anti-proliferative effects. Conclusions: This study identifies proteasome inhibition as a promising therapeutic strategy for TNBC, offering a novel approach to address unmet clinical needs. Using patient-derived organoids, this work highlights inflammation as a driver of DXR resistance and establishes it as a therapeutic target effectively counteracted by proteasome inhibitors.

overall_design: RNA-seq profile of FDA-approved anticancer drugs was performed on TNBC organoids reveals drug resistance mechanisms.

first: Rossukon

last: Kaewkhaw


title: Single cell RNA-seq detects cMPCs expressing HO gene expression signature in B/T mouse blood samples

first: Nezihi Murat

last: Karabacak

summary: Heterotopic ossification (HO), the aberrant bone in soft tissues, is one of the most debilitating complications associated with severe burn and traumatic injuries as well as joint replacement surgeries due to its insidious development. Currently, no technologies exist to either support early HO detection or to guide early prophylactic strategies. Furthermore, no technologies exist to assess treatment efficacy. In this study, we used microfluidic iChip, designed to isolate circulating rare non-hematopoietic cells from whole blood, to isolate and analyze circulating mesenchymal progenitor cells (cMPCs) released in a clinically relevant mouse model of traumatic HO. RNA sequencing of cMPCs revealed the unique expression of HO-associated MPC genes observed as soon as 6 hours post HO-inducing injury, 41 days earlier than gold standard radiographic diagnostic strategies. Using multiple lineage tracing systems, we determined that the cMPCs derived from the periosteum rather than the bone marrow. We then formulated a cMPC HO score and evaluated the diagnostic ability of the liquid biopsy approach for the early detection of HO. By using Youden’s J Statistic for optimizing sensitivity and specificity, our score yielded a sensitivity of 82% and specificity of 100% for detecting HO in mice.

overall_design: iChip enriched cells were captured and barcoded via 10X Chromium at MGH Nextgen Core Facility.

first: Sneha

last: Korlakunta

first: Johanna

last: Nunez

first: Hanil

last: Kang

first: Chase

last: Pagani

first: Benjamin

last: Levi

first: Murat


title: Evidence that chaperone 4-PBA treatment alleviates the renal phenotype in Alport syndrome mouse models

city: Nicosia

first: Constantinos

last: Deltas

state: Aglantzia

address: Palaios dromos Lefkosias Lemesou No.215/6

department: Biology

country: Cyprus

institute: University of Cyprus

summary: Total RNA was extracted from glomeruli as described above. RNA quality and quantity were determined by the 2100 Bioanalyzer. RT2 Profiler PCR Array (QIAGEN) is the method used for qPCR assay. This technique takes advantage of real-time PCR performance and combines it with the ability of microarrays to detect the expression of many genes related to UPR pathway simultaneously. Total RNA that was purified from glomeruli which were extracted from mutant and wild type kidneys was measured and then converted into first strand cDNA. qPCR was followed by using the instrument-specific and ready-to-use RT2 qPCR Master Mixes and gene specific primer sets. Determination of the relative expression was done by ddCt

overall_design: We have performed the RNA arrays in whole mRNA that was isolated from glomerular lysates harvested from knockin (KI) and compound heterozygous (n=3) (EKO) mice (n=3) , that both bear the misssense mutation Col4a3:G1332E, in order to test whether the unfolded protein response (UPR) pathway is activated in the glomerular podocytes. mRNA from Wild type glomeruli was used as control (n=3). The analysis showed no upregulation of UPR in mutant mice.

first: Pavlos

last: Ioannou

first: Christoforos

last: Odiatis

first: Rania

last: Hadjisavva

first: Kyriaki

last: Antoniadou

first: Myrtani

last: Pieri

first: Apostolos

last: Malatras

first: Gregory

last: Papagregoriou

first: Antrea

last: Aristotelous

first: Paris

last: Skourides

first: Martina

last: Samiotaki

first: Matija

last: Horaček

first: Danica

last: Galešić Ljubanović

first: Kostas

last: Stylianou


title: Characterization of a gut-restricted LXR agonist and its utility in ameliorating liver injury in experimental short gut syndrome

city: Saint Louis

first: Gwendalyn

last: Randolph

state: Missouri

address: 425 S. Euclid

institute: Washington University in St.Louis

summary: Short bowel syndrome (SBS) results from the surgical removal of extensive portions of the small intestine and is associated with high morbidity, including intestinal failure-associated liver disease (IFALD). We aim to identify effective, targeted therapies to combat IFALD while promoting small intestinal remodeling that optimizes intestinal health and nutrient absorption. Following previous findings that an LXR agonist administered orally suppresses liver injury in a mouse model of SBS, we sought application of a gut-restricted LXR agonist to avoid potential for systemic activation of LXR. We synthesized and characterized WUSTL0717 as a potential gut-restricted hydrophobic derivative of the well-known LXR agonist GW3965and tested its ability to improve outcomes in a mouse model of SBS. Pharmacokinetic analysis in mice revealed overwhelming intestinal retention of WUSTL0717.  The  compound activated a panoply of LXR target genes, including Abca1, in the small intestine but not the liver. It also increased ileal transcript levels of Apoa1 that encodes the core protein of high-density lipoprotein (HDL) and raised HDL levels in plasma. WUSTL0717 was efficacious in protecting against IFALD. Additionally, WUSTL0717 improved nutrient absorption after small intestinal resection and promoted restoration of body weight. These data identify the LXR agonist WUSTL0717 as a gut-restricted drug that may provide therapeutic benefits for treating SBS-associated IFALD while avoiding unwanted effects of systemic LXR agonists.

overall_design: The 8-week-old C57BL/6 male mice underwent either 50-60% small bowel resection or sham surgeries. Three weeks after the operation, the mice received daily treatments of WUSTL0717 (30 mg/kg) or vehicle for 7 weeks. They were then sacrificed, and the duodenum, ileum, and liver were collected and processed for RNA sequencing.

first: Ayoung

last: Kim

first: Lingaiah

last: Maram

first: Hannah

middle: M

last: Phelps

first: Jichang

last: Han

first: Rachel

last: Mintz

first: Brad

last: Warner

first: Bahaa

last: Elgendy


title: Bulk RNA-seq detects cMPCs HO signature in B/T mouse blood samples - dataset #2

first: Nezihi Murat

last: Karabacak

first: Sneha

last: Korlakunta

first: Johanna

last: Nunez

first: Hanil

last: Kang

first: Chase

last: Pagani

first: Benjamin

last: Levi

first: Murat


title: Bulk RNA-seq detects cMPCs HO signature in B/T mouse blood samples - dataset #1


title: Claudins interact with LILRB immune inhibitory receptors to promote myeloid immunosuppression in cancer

status: Public on Jan 16 2026

city: Dallas

first: kenian

last: chen

state: TX

address: 5323 Harry Hines Boulevard

department: Population and Data Science

institute: UTsouthwestern

summary: The mechanisms underlying tumor cell-myeloid cell interactions within the tumor microenvironment (TME) remain unclear, and predictive biomarkers for patient response to myeloid checkpoint blockade are lacking. This study identified specific binding between tight-junction claudins (CLDNs) and leukocyte immunoglobulin-like receptor subfamily B members LILRB2 and LILRB5. In multiple human cancer cohorts, the spatial proximity of LILRB2⁺ macrophages to CLDN-expressing cancer cells correlated with clinical outcomes, nominating this spatial relationship as a potential biomarker. In syngeneic LILRB2-transgenic and humanized mouse models, CLDN18.2–LILRB2 interaction triggered bidirectional signaling, enhanced the immunosuppressive activity of myeloid cells, and accelerated tumor progression. These effects were reversed by LILRB2 blockade. Mechanistically, the CLDN-LILRB2 axis sustained immunosuppression by regulating NF-κB and STAT signaling pathways. Our findings reveal a novel tight junction protein-mediated mechanism of myeloid cell regulation in the TME, offering a rationale for targeting this pathway in cancer therapy.

overall_design: NSG-SGM3 mice that had received total body irradiation (250 cGy) were transplanted with 3 x 104 human cord blood CD34+ cells (STEMCELL, # 70008). After 6 weeks, when human immune cell engraftment in mouse peripheral blood was detected, 1 × 106 SK-MEL-5 or 2 × 106 MIA PaCa-2 cells were injected subcutaneously into the right flanks of each mouse. After tumor volumes reached 50 to 60 mm3, mice were randomized into groups and intraperitoneally injected with antibodies (LALAPG-mutated anti-LILRB2 antibody or isotype control) at a dose of 10 milligram per kilogram of bodyweight twice weekly. Liver and spleen metastases were observed 6 to 8 weeks post-tumor implantation. Live, single, tumor-infiltrating human CD45+ cells and  peripheral blood engrafted human CD45+ cells were FACS-enriched at 8 weeks post-implantation and subsequently used for single-cell RNA-sequencing analysis.

first: Xiaoye

last: Liu

first: Alec

last: Zhang

first: Kenian

last: Chen