title: Effect of eyelid UVB irradiation on gene expression of rat meibomian gland

city: Paris

first: Min

last: ZHAO

state: France

address: 15 rue de l'Ecole de Médecine

country: France

institute: INSERM U1138, Centre de Recherche des Cordelier, University Paris Descartes

summary: We have developed a rat model of UVB-induced ocular surface and eyelid damages mimicking ocular rosacea, a common chronic inflammatory and neurovascular ocular surface disease associated with meibomian gland dysfunction. Rat eyelids were exposed to UVB for 5 minutes daily (300mJ/cm2) for 5 days. UVB-exposed rats displayed altered meibocyte activity and lipid production, ductal epithelial hyper-keratinization, apoptosis, mitochondrial dysfunction and oxidative stress. Corneal epithelial defects, barrier disruption and abnormal innervation occurred 2 weeks after UVB exposure, subsequent to meibomian gland dysfunction. The aim of this study was to investigate the transcriptomic signature associated with meibomian gland dysfunction induced by UVB in rats. We revealed pathways related to keratinization, cell cycle and proliferation, DNA damage and repair, inflammation, immune responses, oxidative responses, and fatty acid metabolism. These regulations supported the observed functional changes of meibomian gland and were consistent with the transcriptomic signature of human meibomian gland dysfunction.

overall_design: We compared gene expression profile in meibomian gland between UVB-irradiated and non-irradiated rats.

first: Linxin

last: ZHU

first: Francine

last: Behar-Cohen


title: Asprosin Transcription Underlies Obesity Relapse and Inheritance [RNA-seq]

status: Public on Dec 31 2025

city: Cleveland

first: Brian

last: Kim

state: OHIO

address: 10900 Euclid Ave

country: USA

institute: Case Western Reserve University

type: Expression profiling by high throughput sequencing

summary: Obesity is a unique disease, marked by its near-certain relapse after weight loss and its transmission to offspring of obese mothers. The biological mechanisms behind these phenomena remain elusive. We have found that the obesity-associated cytokine Tgf-β1 activates Fbn1 transcription in adipocytes, driving overproduction of the appetite-stimulating hormone asprosin. Remarkably, a single exposure to elevated Tgf-β1 reshapes chromatin at the Fbn1 locus, cementing its overexpression in a manner that is unrelenting, even after weight loss and normalization of Tgf-β1 levels. This results in an enduring plasma asprosin elevation despite weight loss, sustaining heightened appetite and a ceaseless pull toward regaining the lost weight. Strikingly, maternal Tgf-β1 passes through the placenta leading to fetal adipose reprogramming and plasma asprosin elevation that persists in childhood, transmitting obesity across generations. Our findings reveal a powerful chromatin remodeling and transcriptional event that results from a single exposure to obesity, causing a profoundly enduring elevation of an appetite-stimulating hormone, fueling both relentless recurrence and hereditary transmission.

overall_design: To investigate transcriptomic changes that occur in adipocytes, we treated differentiated 3T3-L1 cells with recombinant mouse Tgf-β1 for 4 days. We also investigated changes that occur when active  Tgf-β1 signaling is removed, so we also had a sample where cells were exposed to  Tgf-β1 fo4 4 days, then an additional  Tgf-β1 Free media for 14 days. We then performed gene expression profiling analysis comparing all the conditions

first: Atul

last: Chopra


title: Somatic loss-of-function variants in leptin alter adipose tissue physiology by promoting proliferation and impairing differentiation

city: Leipzig

first: Linnaeus

middle: Tapia

last: Bundalian

address: 15 Albert-Scwheitzer Str.

country: Germany

institute: Universitatklinikum Leipzig

summary: This study identified a missense LEP c.250C>A, p.(Gln84Lys) somatic variant in a spontaneous lipoma of a lean male, which may lead to a loss of function based on in silico modeling. This finding impliesthat somatic leptin (LEP) alterations may influence adipose tissue physiology independently of central functions and may therefore contribute to pathologies, such as obesity or lipomas Our aim was to investigate whether leptin loss of function may adversely affect adipocyte physiology.

overall_design: We used control WT and  leptin knock down in undifferentiated and differentiated adipocytes.


title: Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [scRNA-seq]

city: Plainsboro

first: Yong

last: Wei

state: NJ

address: LTL227 Wathington Road

department: Molecular Biology

institute: Princeton University

summary: Cancer affects the function of distant organs beyond metastasis, conversely, dysfunction in distant organs can also impact tumor progression. However, the mechanisms underlying these interactions remains poorly understood. Here, we uncover that metadherin (MTDH), previously identified as a cancer metastatic gene, expressed in different host tissues, manipulates systemic lipid metabolism to control CD8+ T cell-mediated antitumor immunity. Genetic ablation of MTDH in host tissues significantly suppresses tumor growth and lung metastasis. Mechanistically, MTDH loss in hepatocytes prevents tumor environment-driven dysfunction of lipid metabolism. MTDH deficiency in hepatocytes increases PPARa-mediated lipid oxidation, resulting in reduced systemic lipid levels. Moreover, reduced systemic lipid levels metabolically reprogram MTDH knockout (KO) tumor-infiltrating CD8+ T cells by increasing mitochondrial biogenesis and resistance to lipid peroxidation-induced death. This increased metabolic fitness enhances the effector function of MTDH KO tumor-infiltrating CD8+ T, triggering ASCL4-depedent ferroptosis in tumor cells, contributing to tumor suppression. Targeting host MTDH efficiently synergizes with anti-PD-1 therapy across colorectal and metastatic breast cancer models, providing a promising therapeutic strategy for immunotherapy non-responsive cancers. Thus, our study identifies MTDH as an essential bridge connecting tumor and distant liver communications through metabolic reprogramming, revealing a previously unknown mechanism by which cancer is regulated as a systemic disease.

overall_design: Mtdh KO and wild type control mice were irradiated to deplete their own immune system. Irradiated mice received donor bone marrow cells from Mtdh KO or wild type control mice, and then developed their new immune system with 4 types of combinations of Mtdh status in immune cells and other non-immune cells. After 8 weeks with bone marrow transfer, the four types of bone marrow transplanted female mice together with Mdth KO and wild type female mice, were used as recipient to engraft Py8119 cells to develop mammary tumors. Four weeks after tumor cell injection, mammary tumors were harvested and processed into single cell suspension. Live CD45+ cells were isolated through FACS sorting. Sorted cells directly processed to scRNAseq.

last: Tang

first: Jennifer

middle: M

last: Miller

first: Wei

last: Wang

first: Yibin

last: Kang


title: RNA-seq analysis further corroborated the reversal effect of asp on AOA-enhanced ISG expression in L929 cells [2]

city: Shanghai

first: YH

last: Liao

address: Dongan road 131

country: China

institute: Fudan university

summary: To assess the functional significance of asp in the cGAS-STING pathway, these two metabolites were individually added along with AOA to the culture medium, followed by HT-DNA stimulation for 6 hours. Interestingly, asp fully reversed the amplification effect of A on STING-mediated immune response

overall_design: L929 cells were treated with 0.5 mM A for 1h followed by HT-DNA stimulation for 6h in the absence or presence of 20 mM asp, and then cells were harvested for qPCR analysis of IFN response gene expression

first: Yuheng

first: Hao

last: Lin


title: Organoid Culture Induces an Activated Pro-angiogenic Phenotype in Human Pericytes: Implications for Ascending Thoracic Aortic Aneurysm Pathophysiology

city: Pittsburgh

first: Julie

middle: A

last: Phillippi

state: PA

address: 450 Technology Drive, Suite 300

department: Cardiothoracic Surgery

institute: University of Pittsburgh

summary: Pericytes serve critical roles including stabilization of neovessels during vasculogenesis and angiogenesis. In larger blood vessels such as the aorta, pericytes are associated with the vasa vasorum, a microvascular network within the outer layer of the adventitia.  Using pericytes from both normal and aneurysmal human aorta, this study sought to determine the influence of spheroid culture conditions on aortic vasa vasorum-associated pericyte phenotype and function. Here, we reveal the remarkable plasticity of pericytes as three-dimensional spheroid-based culture of human aorta-derived pericytes, which yields an organoid that promotes pro-angiogenic pathways. The marker profile of pericyte-generated organoids serves as an inducible and importantly, reversible phenotypic signature of pericyte activation. Pericytes from human aneurysm exhibit diminished pro-angiogenic activation and persist in a quiescent, hypercontractile state in organoid culture, thus pointing to a potential to uncover new pathophysiology of human aortic disease.

overall_design: To investigate the impact of three-dimensional culture on human pericyte phenotype, we utilized human pericytes isolated from the ascending aorta of heart transplantation donors. We then cultured pericytes in standard monolayer conditions or as cellular spheroids formed on an agarose substrate and compared the transcriptomic profiles of monolayer versus spheroid culture in 2 patient cell lines for a total of 4 samples.


title: Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Liver]

overall_design: Livers from age-mached normal or Py8119 mammary tumor bearing femlae mice were collected. Total RNA were extracted from livers and processed to RNA sequencing. Three biological replicates of each group were collected from different mice.


title: Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity

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

overall_design: Refer to individual Series


title: Identification of differentially expressed genes in Chronic Kidney Disease

city: Kunming

first: Chunjuan

last: Xia

address: 374 Dianmian Avenue

institute: The Second Affiliated Hospital of Kunming Medical University

summary: There are currently no effective treatments for renal fibrosis of chronic kidney disease (CKD). Therefore, this study constructed an animal model of CKD and identified differentially expressed genes in renal tissues of CKD animal models using RNA-seq. The aim is to provide potential molecular mechanisms for the treatment of CKD.

overall_design: We established a model of CKD damage in 8-week-old male Sprague–Dawley (SD) rats. We got  kidney tissue. RNA purity and quantification were evaluated using the NanoDrop 2000 spectrophotometer. RNA integrity was assessed using the Agilent 2100 Bioanalyzer. The libraries were sequenced on an llumina Novaseq 6000 platform.


title: Effect of Copper deficiency on gene expression of Lin-c-Kit  cell in the bone marrow of mice

city: Hangzhou

first: Liyun

last: Chen

address: Yuhangtang Road 866

institute: Zhejiang University

summary: Copper homeostasis has been linked to human health and hematopoiesis. However, the underlying mechanisms remain elusive. Here, we demonstrate the pivotal role of the transporter Slc31a1(Ctr1) in copper uptake, during postnatal hematopoiesis. Specifically, Slc31a1-mediated copper transport sustains the differentiation and commitment of multipotent progenitors from short-term hematopoietic stem cells (HSCs). By transcriptome analyses we reveal a disrupted differentiation program in the hematopoietic stem and progenitor cells (HSPCs) derived from diet-induced copper deficiency mice or hematopoietic-specific Slc31a1 knockout (vKO) mice. Further, we show that Slc31a1 and copper are indispensable for sustaining mitochondrial activity via Complex IV within HSPCs. Notably, the copper ionophore elesclomol significantly ameliorates severe anemia in vKO mice and partially recovers mitochondrial function in vKO HSPCs. These findings demonstrate the critical role of Slc31a1/copper in maintaining HSC homeostasis via modulation of mitochondrial energy metabolism; thus, shedding light on the molecular basis of HSC fate decisions while opening new avenues to maintaining functional HSCs.

overall_design: To gain insights into the mechanism underlying the regulatory role of copper for HSC homeostasis and functionality, we conducted RNA-sequencing (RNA-seq) on freshly isolated Lin-c-Kit+ cellsorted from Copper-adequate and Copper deficieny mice


title: Study title: B Cells Promote T Cell Immunosenescence and Mammalian Aging Parameters- 5’ single cell transcriptomics with VDJ T cell receptor analyses on splenic CD3+ cells from aged µMT and WT mice

city: Novato

first: Fei

last: Wu

state: CA

address: 8001 Redwood Blvd

institute: Buck Institute for Research on Aging

summary: The goals of this experiment were two-fold: 1) To understand changes in splenic  T cells at the transcriptomic level from aged µMT and WT mice, and 2) to understand TCR diversity and clonality in aged µMT and WT mice

overall_design: T cells isolated from spleens of aged µMT and WT mice via fluorescence-activated cell sorting (FACS) and subsequently analyzed using single cell RNA sequencing.

first: Daniel

last: A Winer

first: Saad

last: Khan

first: Mainak

last: Chakraborty


title: Study title: B Cells Promote T Cell Immunosenescence and Mammalian Aging Parameters - B and T Cell Singlet and PIC Single Cell RNA Seq

summary: The goals of this experiment were two-fold: 1) To understand changes in splenic B and T cells at the transcriptomic level, and 2) to identify unique physically interacting B-T cells and their molecular signatures in young and aged mice.

overall_design: Singlet B/T cells and B-T PICs were isolated from the spleens of WT aged mice and young controls via fluorescence-activated cell sorting (FACS) and subsequently analyzed using single cell RNA sequencing.


title: Effect of Slc31a1 deletion on gene expression of Lin-Sca1+c-Kit  cell in the bone marrow of mice

overall_design: To gain insights into the mechanism underlying the regulatory role of Slc31a1 for HSC homeostasis and functionality, we conducted RNA-sequencing (RNA-seq) on freshly isolated LSK cells sorted from vKO and Ctrl mice


title: TAF1D promotes tumorigenesis and metastasis by activating PI3K/AKT/mTOR signaling in clear cell renal cell carcinoma

city: wuhan

first: xuan

last: hu

state: hubei

address: Donghu Road 169, Wuhan, Hubei, China

institute: wuhan university

summary: Clear cell renal cell carcinoma  is a malignant tumor needs more effective treatments. TATA box‐binding protein‐associated factor RNA polymerase I subunit D is a member of the selective factor 1 complex and functions in RNA polymerase I-dependent transcription. Higher TAF1D expression was found in ccRCC tumor tissues and indicated worse survival. Our study aimed to investigate the therapeutic potential of TAF1D in ccRCC. The proliferation and migration of ccRCC cells were significantly inhibited after TAF1D knockdown, while TAF1D overexpressing had opposite effects. Moreover, TAF1D knockdown induced cells to undergo G0/G1 cell cycle arrest and blockade of the epithelial-mesenchymal transition process. Mechanistically, TAF1D affect the cell cycle and EMT through the PI3K/AKT/mTOR signaling pathway, thereby promoting the proliferation and metastasis of ccRCC cells in vivo and in vitro. The inhibitory effect of TAF1D knockdown could be reverted by the AKT activator SC79 in ccRCC cells, confirming this mechanism. Besides, TAF1D knockdown in ccRCC cells had a sensitizing effect on sunitinib and enhanced tumor cell inhibiting induced by sunitinib. In conclusion, TAF1D may be a promising target for the treatment of ccRCC and for overcoming sunitinib resistance.

overall_design: To invest the function of TAF1D in ccRCC,we established Caki-1 cell lines in which target gene has been knocked down by shRNA.

first: Zhonghua

last: Yang

first: Xinghuan


title: DNA-damaging Chemotherapy altered the Cardiac Pathogenesis by reshaping the Composition and Functionality of Cardiac Resident Macrophages (scRNA-Seq).

city: St Louis

first: Ruijun

last: He

state: Missouri

address: 660 S Euclid Ave

department: Cardiology

institute: Washington University School of Medicine

summary: Cardiovascular comorbidities including heart failure and ischemic heart injury represent the most common causes of death among cancer survivors. Despite extensive investigation, we continue to have a poor understanding of how previous chemotherapy reagents exposure impact the heart. Here, we investigated the effect of chemotherapy reagent on the composition and function of the cardiac resident macrophages and found carboplatin selectively deplete the CCR2¬¬¬¬– cardiac macrophages by activating P53 signaling pathway and inducing necroptosis and apoptosis. Using Bulk-RNA-seq and lineage-tracing mice, we found CCR2– cardiac macrophages returned after Carboplatin-exposure primarily from monocytes recruitment and demonstrated a different transcriptomic profile. These reshaped CRMs attenuated heart remodeling upon hypertensive heart injury and ischemic-reperfusion injury while selective ablation of the reshaped CRMs abolished this mitigation phenotype. Using bulk-seq, single-cell RNA seq and lineage-tracing mice, we showed that the reshaped CRMs in carboplatin-exposed mice mitigated ventricle remodeling via elevated IFN-I signaling. Together, this study characterized how DNA-damaging chemotherapy reagent change the cardiac immune landscape and demonstrated a novel protective mechanism in adverse cardiac injury response that depends on the carboplatin-reshaped CRMs. These findings highlight the importance of type-I interferon signaling in the long-term effect of chemotherapy and provide promising pathway to retard cardiac pathogenesis.

overall_design:
We collected hearts from 20 adult mice that were randomly grouped into 4 groups, PBS+Sham, CBP+ Sham, CBP +AngII/PE, and PBS+AngII/PE (each group has 5 mice of mixed gender). Mice were injected with Carboplatin (45 mg/kg, i.p., twice a week) or equal volume of PBS for two weeks. Then, all the mice underwent 4-week recovery. Next, we implanted osmotic minipump subcutaneously to each mouse. The minipump will either infuse Angiotensin II (1.5mg/kg/d) and PE (50mg/kg/d), or Saline (Sham group) for 7 days. Seven days after the minipump implantation, the CD64+ cardiac mononuclear phagocytes (CD45+CD11b+Ly6G–Ly6Clo) were sorted through FACS. Ten thousand cells from each group were pooled to make Single-cell barcoded cDNA libraries using 10X Genomics 3‘v1kit following manufacturer’s manual.
GTAC core of WUSM conducted the quality control, sequencing, and alignment through cellRanger. Further analysis was performed using R studio (Seurat, DEseq2, ggplot2). The obtained single-cell RNA sequencing data contain 21681 features across 38066 samples. After being filtered as mitochondrial gene proportion(prompt) < 10.0%, nCounts of RNA<30000, and nFeature RNA counts< 7000 & >500, 20290 features across 17438 samples remained. We utilized graph-based clustering and UMAP (Uniform Manifold Approximation and Projection) visualization of the combined four groups (Dim=1:80, resolution=0.6, normalized by SCTransform). According to the feature genes of each cluster, the contamination from cardiomyocytes, endothelial cells, fibroblasts, lymphocytes were found and removed together with two junk clusters. The proliferating cells, monocytes, and mono-phagocytes including Dendritic cells and macrophages are kept for further analysis.

first: Andrew

last: Koenig

first: Kory

middle: J

last: Lavine


title: DNA-damaging Chemotherapy altered the Cardiac Pathogenesis by reshaping the Composition and Functionality of Cardiac Resident Macrophages (bulk RNA-Seq).

overall_design:
To study the acute effect of carboplatin on the cardiac macrophages, we injected CCR2-GFP mice (Ccr2Gfp/+, JAX027619, half male half female, 8- to 12-week-old) with carboplatin (Sigma, C2538, 45 mg/kg, dissolved in PBS, i.p.) or equal volume of PBS. Three days later, the mice from Carbo group and PBS group were euthanized. The heart of these mice was dissected out and perfused with pre-cool HBSS before being digested with hyaluronidase, DNase I, and collagenase type IV on a shaker at 37 ℃. The cardiac macrophages were sorted on the BD Melody FACS platform by gating on the CD45+CD11b+ Ly6G-CD64+Ly6Clo alive singlets. CCR2+ cardiac macrophage and CCR2- cardiac macrophage were differentiated by GFP expression and were sorted into separate tubes for RNA extraction and Bulk-RNA-sequencing.
To study the long-term effects of carboplatin on the cardiac macrophages, we injected CCR2-GFP mice (Ccr2Gfp/+, JAX027619, half male half female, 8- to 12-week-old) with carboplatin (Sigma, C2538, 45 mg/kg, dissolved in PBS, i.p.) or equal volume of PBS for two weeks (twice a week). These experimental mice recovered for four weeks before being euthanized for cardiac macrophage isolation. The CCR2+ and CCR2- macrophages were differentiated by GFP expression and sorted into separate tubes for RNA extraction and Bulk-RNA-Sequencing.


title: GeoMx DSP- profiling of mouse spleen

summary: GeoMx DSP- profiling of mouse spleen

sample_organism:
Mus musculus
synthetic construct

platform_organism:
Mus musculus
synthetic construct

overall_design: Mouse spleen from young and old C57BL/6 mice were compared using spatial transcriptomics. Areas of interaction between t- and b-lymphocytes were selected explicitly for ROI selection.

first: Nicolas

last: Martin

first: Serban

last: Ciotlos


title: Host MTDH orchestrates liver lipid metabolism and CD8+ T cells to suppress antitumor immunity [Tumor CD8 T cells]

first: Yong

last: Wei

overall_design: Py8119 cells were injected into mice with vary Mtdh status, i.e wild type vs Knockout. Tumors were harvested and CD8+ T cells infiltrating these tumors were sorted and harvested for transcriptome profiling using bulk RNAseq. Four biological replicates of each group were collected.

last: Tang

first: Yibin

last: Kang


title: scRNA-seq and TCR-seq of T cells and APCs in tumor-draining lymph nodes with versus without pharmacological LXR activation.

city: Berlin

first: Benjamin

middle: N

last: Ostendorf

address: Augustenburger Platz 1

institute: Charité University Medicine

summary: Here we assessed the impact on the transcriptomes of T cells and APCs in tumor-draining lymph nodes from mice administered control chow versus chow containing the synthetic LXR agonist RGX-104. In addition, TCR-seq was performed to assess the impact on clonal expansion of T cells upon LXR activation.

overall_design: T cells and antigen-presenting cells (APCs) were isolated from tumor-draining lymph nodes from mice by flow cytometry and subjected to scRNA-seq and TCR-seq.


title: Histone H3K4me3 modification regulates innate immunity.

city: Zunyi

first: yan

last: Zhang

state: Guizhou

address: Honghuagang

department: College of Basic Medicine

institute: Zunyi Medical University

summary: Deficiencies in member of the histone H3 lysine 4 trimethylation (H3K4me3) complex-ASH-2, WDR-5, and SET-2 (the H3K4 methyltransferase) functioned in germline to increase the susceptibility to pathogen bacteria pseudomonas aeruginosa (PA14) through down-regulated the immune response genes.

overall_design: Place wild-type nematode N2 and mutant nematode RB1304, wdr5.1 (ok1417) in a culture medium coated with Pseudomonas aeruginosa for 24 hours to test their innate immune ability against C. elegans.

first: Yi

last: Xiao

first: Fang

last: Liu

first: Hanlin

last: Zhou


title: TET3-mediated DNA demethylation attenuates hepatic stellate cell activation and liver fibrosis

city: Guiyang

first: linlin

last: feng

state: 未选择

address: Dongqing Road

institute: Guizhou Medical University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: To investigate the role of TET3 and 5hmC in TGF-β-induced activation of HSCs. We used hMeDIP sequencing to detect differential hydroxymethylation regions and the signal pathway changes of related genes in LX-2 cells genome of overexpression-TET3 and overexpression-NC

overall_design: Comparative differential hydroxymethylation regions changes of  LX-2 cells genome of overexpression-TET3 and overexpression-NC

first: LinLin

last: Feng

first: YongMei

first: Kun

last: An

first: Qinshan

last: Li


title: RRM2 Promotes Liver Metastasis of Pancreatic Cancer by Stabilizing YBX1 and Activating the TGF-beta Pathway

city: Wuhan

first: Haixin

last: Yu

state: Hubei Province

address: 1277, Jiefang Avenue

institute: Wuhan union hospital

summary: Ribonucleotide reductase subunit M2 (RRM2) has been associated with various types of cancers and is related to tumor progression. However, the role of RRM2 in the liver metastasis of pancreatic cancer remains unclear. In this study, RRM2 was found to promote the malignant biological behavior of pancreatic cancer and enhance its liver metastasis. Further investigation into the downstream molecular mechanisms of RRM2 revealed that RRM2 stabilizes YBX1, upregulates TGFBR1, and activates the TGF-beta pathway to promote the progression and liver metastasis of pancreatic cancer. To further validate our hypothesis, we performed RNA sequencing under the specified conditions to determine the impact of RRM2 on downstream genes that can affect the liver metastasis of pancreatic cancer.

overall_design:
To explore the downstream genes regulated by RRM2, we established PANC-1 cell lines with targeted knockdown of the gene of interest using shRNA technology.
We subsequently conducted a gene expression profiling analysis, utilizing data derived from RNA sequencing of two distinct cell populations: the non-targeting control cells (shNC) and those with RRM2 knockdown (shRRM2).

first: Du

last: Zhouyuan

first: Yu

last: Haixin


title: Single cell RNA-sequencing reveals murine periodontium under diabetic periodontitis resolution

city: Chongqing

first: He

last: Wang

address: No. 426 Songshi North Road, Yubei District, Chongqing, China

institute: Chongqing Medical University Affiliated Stomatological Hospital

summary: Our results highlight fibrinogen derived γ377-395 peptides efficacy on diabetic periodontitis resolution, we wonder actually how 377P influence the various cells and signaling pathways in periodontium. Thus single-cell RNA sequencing analysis was performed for the maxillary periodontium samples of db/db mice during the resolution period of periodontitis treated with 377P or RP.

overall_design: two samples from murine maxillary periodontium tissue

first: H

first: J

middle: L

last: Song


title: Atlas of the aging mouse intestine

city: Jena

first: Jing

last: Lu

state: Thuringia

address: Beutenbergstraße 11

institute: Leibniz Institute on Aging – Fritz Lipmann Institute (FLI)

summary: In this study, we generated single-cell RNA sequencing (scRNA-seq) data from epithelial cells in the intestine, focusing on six distinct subsections during aging: the proximal small intestine, intermediate small intestine, distal small intestine, cecum, proximal colon and distal colon regions. Using a hashtag-labeled method, we aimed to create a comprehensive atlas of cellular changes during aging within these regions. Our objective is to uncover the underlying mechanisms of aging, leveraging the intestine as a model due to its highly proliferative nature. This dataset will provide valuable insights into the cellular dynamics of aging and contribute to the broader understanding of age-related processes.

overall_design: Single-cell RNA seq on epithelial cells from six different sections of the mouse intestine during aging

first: Dovydas

last: Sirvinskas

first: Lisa

last: Adam

first: Francesco

last: Neri


title: The effect of polystyrene nanoparticles on the healthy lifespan of Caenorhabditis elegans

first: yan

last: Zhang

summary: Plastic is widely used in daily life, but it also brings serious environmental pollution. Plastic products can degrade into microplastic particles after physical, chemical, and biological processes, and microplastic particles can further degrade into nanoplastic particles. Microplastics and nanoplastic particles exist in water, atmosphere, and food, and enter the human body through the digestive and respiratory tracts, causing harm to animal and human health. In this study, Caenorhabditis elegans was exposed to a culture medium containing polystyrene plastic particles at a concentration of 1000 μ g/L to detect the healthy lifespan of the nematodes, further revealing the impact of polystyrene nanoparticles on human health and providing a theoretical basis for further evaluating the biological toxicity effects and potential health risks of polystyrene nanoparticles.

overall_design: This study exposed Caenorhabditis elegans to a culture medium containing polystyrene plastic particles at a concentration of 1000 μ g/L to detect its healthy lifespan and other health indicators.

first: Yingwen

last: Cui

first: Yan

first: Yi


title: Host transcriptome in human lung A549 cells infected with SARS-CoV-2 expressing wild-type and mutant (H234A and N277A) Nsp15

city: Taipei

first: Hsin-Ping

last: Chiu

address: No.1 Jen Ai road section 1

department: Microbiology

country: Taiwan

institute: National Taiwan University

summary: Coronavirus (CoV) Nsp15 is a viral endoribonuclease (EndoU) with a preference for uridine residues. CoV Nsp15 is an innate immune antagonist which prevents dsRNA sensor recognition and stress granule formation by targeting viral and host RNAs. SARS-CoV-2 restricts and delays the host antiviral innate immune responses through multiple viral proteins, but the role of SARS-CoV-2 Nsp15 in innate immune evasion is not completely understood. Here, we generate an EndoU activity knockout rSARS-CoV-2Nsp15-H234A to elucidate the biological functions of Nsp15. Relative to wild-type rSARS-CoV-2, replication of rSARS-CoV-2Nsp15-H234A was significantly decreased in IFN-responsive A549-ACE2 cells but not in its STAT1 knockout counterpart. Transcriptomic analysis revealed upregulation of innate immune response genes in cells infected with rSARS-CoV-2Nsp15-H234A relative to wild-type virus, including cGAS-STING, cytosolic DNA sensors activated by both DNA and RNA viruses. Treatment with STING inhibitors H-151 and SN-011 rescued the attenuated phenotype of rSARS-CoV-2Nsp15-H234A. SARS-CoV-2 Nsp15 inhibited cGAS-STING-mediated IFN-β promoter and NF-κB reporter activity, as well as facilitated the replication of EV-D68 and NDV by diminishing the expression of cGAS and STING and downstream innate immune responses. Notably, the decline in cGAS and STING was also apparent during SARS-CoV-2 infection. The EndoU activity was essential for SARS-CoV-2 Nsp15-mediated cGAS and STING downregulation, but not all HCoV Nsp15 share the consistent substrate selectivity. In the hamster model, rSARS-CoV-2Nsp15-H234A replicated to lower titers in the nasal turbinates and lungs and induced higher innate immune responses. Collectively, our findings exhibit that SARS-CoV-2 Nsp15 serves as a host innate immune antagonist by targeting host cGAS and STING.

overall_design: A549-ACE2 cells with mock, Nsp15WT, Nsp15H234A, and Nsp15N277A rSARS-CoV-2 infection for 8 and 24 h (MOI of 5). Total RNA with poly(A) enrichment followed by RNA sequencing analysis. N=3 for each group.

first: Yao

middle: Y

last: Yeo

first: Sizun

last: Jiang

first: Benhur

last: Lee


title: Study on antifungal activity and mechanism of ALK inhibitor

city: XI an

first: Wei

last: Liu

address: Weiyang street

institute: Shaanxi University of Science & Technology

summary: Invasive fungal infections threaten the lives and health of humans, especially immunodeficient patients or hospitalized patients with serious underlying diseases, and impose a heavy economic burden on society. The emergence of drug-resistant fungi, the formation of biofilms, and the limits and side effects of existing antifungal drugs increase the difficulty of clinical treatment, and there is an urgent need for the development of novel antifungal drugs. Therefore, based on previous kinase chemical library antifungal activity screening studies, this paper further investigates the activity of the ALK inhibitor HG-14-10-04 (HG) against various fungi and elucidates its mechanism of action. The in vitro antifungal activity of HG was evaluated by micro liquid-dilution method, time-killing curve, mycelium and biofilm formation. The results showed that HG exhibited inhibitory and even fungicidal effects against sensitive and resistant Candida albicans, Candida krusei, Cryptococcus neoformans, Candida tropicalis, Candida glabrata and Candida parapsilosis (MICs=8-16 μg/mL); HG significantly inhibited the mycelium and biofilm formation, and destroyed the mature biofilm; and it exhibited synergistic antifungal effects with amphotericin B. The antifungal mechanism of HG was investigated by flow cytometry and transmission electron microscopy, etc. Sequencing analysis showed a total of 1041 differentially expressed genes, of which 666 were up-regulated and 375 were down-regulated. According to the GO functional classification results, the up-regulated genes were mainly involved in ribosome production, oxidation-reduction and other functions, while the down-regulated genes were mainly involved in the synthesis of carbohydrate, glycoproteins, glycolipids and their metabolism, GPI anchor synthesis, and cytoskeleton and other functions. In addition, HG could significantly increase the level of ROS, induce the fungal necrosis, block the cell cycle at the G0/G1 phase, and change the ultrastructure of the fungi, especially the structure of the fungal cell wall. Therefore, the enhanced inhibitory and fungicidal activity of HG may be attributed to the elevation of ROS, alteration of cellular ultrastructure (especially cell wall structure), cell cycle arrest at the G0/G1 phase, and induction of fungal necrosis, providing a basis for the discovery of novel antifungal drugs or lead compounds.

overall_design: mRNA profiles of Candida albicans treated with HG-14-10-04

first: Yanhong

first: Ping

last: Ni

first: Mengsha


title: Gene expression profile at single nucleus level of hippocampal cells from monoacylglycerol lipase conditional knockout mice

city: San Antonio

first: Chu

last: Chen

state: Texas

address: 7703 Floyd Curl Dr

department: Cellular and Integrative Physiology

institute: UT Health San Antonio

summary: In the brain, 2-Arachidonoylglycerol (2-AG) is the most abundant endogenous cannabinoid. Enhancing 2-AG signaling by inhibiting monoacylglycerol lipase (MAGL) in astrocytes, the primary enzyme that degrades 2-AG in the brain, produces anti-inflammatory and neuroprotective effects in neurodegenerative diseases. However, the effects of neuronal MAGL inhibition and the responsible molecular mechanisms are largely unclear. To address this question, behavioral tests were performed and hippocampal nuclei were isolated from cell type-specific MAGL knockout (KO) mice. Our behavioral and electrophysiological results showed that cognitive and synaptic functions were impaired in neuronal MAGL-KO mice. Using single-nucleus RNA sequencing analysis, we show here that neuronal MAGL KO mice display distinct gene expression profiles of synaptic DEGs in neurons and glial cells

overall_design: Single nucleus transcriptomics of hippocampus from WT and transgenic mice were analyzed by snRNA-seq.

first: Chen

last: Chu

first: Zhang

last: Jian

first: Hu

last: Mei

first: Zhu

last: Dexiao


title: Growth retardation under suboptimal low temperature is controlled through chromatin remodeling at the CBF cluster.

city: Austin

first: Sibum

last: Sung

state: TX

institute: University of Texas at Austin

summary: Temperature profoundly impacts plant growth and development. Response to temperature by plants is one of most crucial ecological factors determining the natural distribution of species, and the yield potential of crops. Among various temperature responses of plants, there remains a gap in understanding molecular mechanisms underlying growth retardation caused by low temperature. Here, we addressed genetic and epigenetic determinants that mediate growth retardation under low ambient temperature in plants. Transcriptome changes mediated by low ambient temperatures include upregulation of a series of regulatory genes, consequently resulting in growth retardation. Our study identified a regulatory network in which a Polycomb protein, VERNALIZATION INSENSITIVE 3-LIKE 1 (VIL1), and a transcription factor, C-REPEAT BINDING FACTOR 1 (CBF1), operate to control growth under suboptimal low temperature. Under suboptimal low ambient temperature, VIL1 controls dynamic chromatin remodeling through transient chromatin loop formation and nucleosome rearrangement at the CBF cluster. Our study provides insights into how plants reprogram growth and development in response to suboptimal low ambient temperatures.

overall_design: To investigate the molecular basis of suboptimal low ambient temperature-mediated growth retardation in WT and vil1 mutants, we performed RNA-sequencing (RNA-seq) analysis using whole rosettes at growth stages of 1.12 -1.13 (when 12 or 13 rosette leaves are greater than 1mm) of both WT and vil1 mutants grown at 12℃ or 22℃ in short day and compared the two transcriptomes.

first: Junghyun

last: Kim


title: The effect of aspartame on the innate immune ability of Caenorhabditis elegans.

first: yan

summary: Aspartame is a non carbohydrate artificial sweetener widely used in medicine and food. Some scholars believe that aspartame has neurotoxicity, mainly due to the presence of phenylalanine in its metabolites, which can pass through the blood-brain barrier, change the brain amino acid ratio, and interfere with neurotransmitter transmission. However, whether aspartame has an impact on human innate immunity is still unknown. This experiment will use Caenorhabditis elegans as a model to study its effect on innate immunity and provide reliable data support for the safety of aspartame as a sweetener.

overall_design: Expose C. elegans to 100 μM aspartame and place the nematodes in Pseudomonas aeruginosa to test their innate immune ability.

last: Xiao

first: Li

first: Yan

first: Yinwen


title: ATF3's Dual Role in Zebrafish: Early Proliferation Enhancement and Modulates Muscle Growth while Accelerated Aging in Adulthood via Overexpression and Deficiency

city: Tokyo

first: Jiancheng

last: Liang

state: Bunkyo

department: Graduate school of Agricultural and Life Sciences

country: Japan

institute: The University of Tokyo

summary: Transcriptomic data for 2-month and 4-month wildtype, ATF3 overexpression and ATF3 knockout zebrafish on major organs：B: brain, E: eyes, G: gills, H: heart, M: muscle, I: intestine, S: skin.

overall_design: We successfully constructed ATF3 deficient zebrafish lines and ATF3 overexpression lines using CRISPR and pTol2 separately. When zebrafish were cultured for 2 months and 4 months, were euthanized using Tricaine, dissected, and the corresponding organs (brain, eyes, gills, heart, intestine, muscle, and skin) kept in NucleoProtect RNA (TAKARA) solution. Tissue corresponding RNA was extracted and purified using NucleoSpin RNA Clean-up Kit (TAKARA) and verified the RNA quality and concentration using TapeStation RNA ScreenTape (Agilent). RNA library preparation followed the Illumina Stranded mRNA Prep protocol and checked the quality using High Sensitivity D1000 ScreenTape (Agilent). Finally, libraries were paired-end sequenced on NovaSeq X Plus sequencing platform.

first: Yusuke

last: Kijiama

first: Kazutoshi

last: Yoshitake

first: Shuichi

last: Asakawa

first: Shigeharu

last: Kinoshita


title: The long non-coding RNA ELDR suppresses tumorigenicity of AML cell lines with MLL rearrangements by interfering with DNA replication and chromatin accessibility [RNA-Seq]

city: Montreal

first: Tarik

last: Moroy

state: QC

address: 110, West Pine Avenue, 597

country: Canada

institute: Institut de recherches cliniques de Montréal

summary: RNA-seq analysis comparing the transcription of stable ELDR overexpressing THP-1 lines (C1 and C3) with empty vector (EV) controls.

overall_design: RNA was extracted using RNeasy Mini Kit (Qiagen) and RNA libraries were prepared from 900ng of total RNA previously checked for integrity (RIN above 9.5). Ribodepletion and library preparation were performed with Zymo-Seq RiboFree Total RNA Library Kit (Zymo Research). Library size distribution was assessed on a 2100 bioanalyzer (Agilent Technologies) and libraries were quantified by qPCR. Equimolar libraries were sequenced in paired end reads (PE50) on a Novaseq 6000 system (Illumina), with a NovaSeq S1 flow cell and a coverage of 50M fragments per library. Sequencing reads were aligned to the GRCh38 genome using STAR v2.7.9a . The raw counts were calculated with FeatureCounts v2.0.3 based on the human reference genome (release 102).DESeq2 R package was used to compute FPKM values and logFC.A genome coverage file was generated and scaled to RPM using Bedtools.

first: Kaifee

last: Arman

first: Virginie

last: Calderon

last: Möröy


title: METTL3 Promotes Histone H3K9 Acetylation through Recruitment of Histone Acetyltransferase 1 to Chromatin II

city: Riverside

first: Yinsheng

last: Wang

state: California

address: 501 Big Springs Road

institute: UC-Riverside

summary: METTL3 constitutes the catalytic subunit of the major methyltransferase complex mediating the formation of N6-methyladenosine (m6A) in mRNA. Although the resulting m6A is known to regulate numerous cellular processes, the protein interaction network of this complex remains largely unknown. Here, we employed ascorbate peroxidase-based proximity labeling followed by LC-MS/MS analysis to examine systematically the interaction proteins of METTL3 and METTL14 in HEK293T cells. Aside from many proteins involved in mRNA splicing, a subset of histone regulatory proteins are enriched in the proximity proteome of METTL3, including histone acetyltransferase 1 (HAT1). In addition, genetic ablation of METTL3 led to reduced chromatin occupancy of HAT1 isoform-a, which is expressed exclusively in the nucleus, and diminished H3K9Ac in HEK293T cells, especially in retrotransposons. Depletion of HAT1 led to diminished H3K9Ac, which could be restored by wild-type HAT but not the one fused with the nuclear export sequence (NES) of PKI to remove it from the nucleus. Our in vitro acetylation assay further confirmed the acetylation activity of HAT1 isoform-a on nucleosome histone H3K9. The reduced retrotransposons H3K9Ac in METTL3-/- cells could be restored by ectopic expression of wild-type METTL3, but not its catalytically inactive D395A mutant. Together, we assessed the protein interactome of METTL3, uncovered a new function of HAT1 in acetylating H3K9 in chromatin, and revealed a crosstalk between METTL3-mediated formation of m6A and HAT1-catalyzed formation of H3K9Ac in chromatin.

overall_design: Genome-wide profiling analysis of HAT1 in HEK293T cells, METTL3-/- cells, and two rescued cell lines

first: Xiaomei

last: He

first: Yen-Yu

last: Yang


title: Driver mutation landscape of acute myeloid leukemia provides insights for neoantigen-based immunotherapy [RNA-seq]

city: Shanghai

first: Peng

last: Jin

address: Ruijin Rd. II

department: Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics

institute: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

summary: Acute myeloid leukemia (AML) has lagged in benefiting from immunotherapies, primarily due to the scarcity of actionable AML-specific antigens. While driver mutations are considered optimal sources for immunogenic targets, a comprehensive characterization of the AML driver mutational landscape and their resultant candidate neoantigens is lacking. Herein, we extensively integrated somatic mutation data from over 2,800 AML cases, identifying the driver genes in AML, notably characterized by a significant proportion of insertions and deletions (indels). Neoantigen prediction analysis revealed that indels triggered a higher abundance of neoantigens both in quantity and quality, compared with single nucleotide variants (SNVs) and gene fusions. We further integrated peptide features pertinent to neoantigen presentation and T cell recognition to establish two robust models of epitope immunogenicity that significantly enriched immunogenic neoepitopes derived from both gene mutations and fusions. The predicted number of neoantigens correlated with decreased survival in AML, partially attributed to the immunosuppressive microenvironment and exhausted CD8+ T cells, as supported by the deconvolution of large-scale bulk transcriptomes and the integration of single-cell RNA sequencing with multiparametric flow cytometry. Altogether, this study not only offers a valuable resource for adoptive cell-based therapy or personalized vaccine development but also underscores the necessity of incorporating strategies to revitalize the immunosuppressive milieu in conjunction with neoantigen-targeted therapies.

overall_design:
Comprehensive transcriptome sequencing  was performed on a total of 147 AML patients  .

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Submitter statement concerning missing raw data: Law restrictions prohibit us from publicly sharing raw sequencing data, which however can be made available upon reasonable request and permission of the local ethics committee.
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first: Junmin

last: Li


title: RNA-seq analysis further corroborated the reversal effect of asp on AOA-enhanced ISG expression in L929 cells

first: YH

last: Liao

address: Dongan road 131

institute: Fudan university

summary: To assess the functional significance of asp in the cGAS-STING pathway, these two metabolites were individually added along with AOA to the culture medium, followed by HT-DNA stimulation for 6 hours. Interestingly, asp fully reversed the amplification effect of A on STING-mediated immune response

overall_design: L929 cells were treated with 0.5 mM A for 1h followed by HT-DNA stimulation for 6h in the absence or presence of 20 mM asp, and then cells were harvested for qPCR analysis of IFN response gene expression

first: Yuheng


title: Serial and regional assessment of the right ventricular molecular and functional response to pressure-loading

city: Toronto

first: Michael

middle: Bradley

last: Dewar

state: Ontario

address: 661 University Avenue

department: Physiology

institute: University of Toronto

summary: Background: Right ventricular(RV) function determines outcomes in RV pressure-loading. A better understanding of the time-course and regional distribution of RV remodeling may help optimize targets and timing for therapeutic intervention. We sought to characterize RV remodeling between zero and 6-weeks after initiation of RV pressure-loading. Methods and results: Thirty-six rats were randomized to either sham surgery or to pulmonary artery banding(PAB). After echocardiography and conductance catheter studies, groups of rats were euthanized at 1-week, 3-weeks, and 6-weeks after sham surgery, or induction of RV pressure-loading, for RV histological, RNA and molecular analysis. A vigorous inflammatory response characterized by increased RV inflammatory cytokines, chemokines and macrophage markers was observed at 1-week following PAB. Metabolic changes, TGF-β1 canonical signaling, collagenous fibrosis deposition and apoptosis were already significantly increased by 1-week after PAB. Genes marking fibroblast activation were upregulated at 1-week but not 6-week post-PAB surgery. Mitochondrial dysfunction as evidenced by increased PDK activity and decreased PDH phosphorylation significantly at 6-week post PAB. These processes preceded the development of overt myocardial hypertrophy and impaired echo parameters of systolic and diastolic function which occurred significantly from 3-weeks after PAB. Conclusion: RV myocardial inflammation, metabolic shift, metabolic gene transcription and pro-fibrotic signaling occur early after initiation of pressure-loading when RV pressures are only moderately elevated, before the development of overt myocardial hypertrophy and dysfunction, suggesting that adaptive hypertrophy and maladaptive remodeling occur simultaneously. These results suggest that therapeutic intervention to reduce adverse RV remodeling may be needed earlier and at lower thresholds than currently employed

overall_design: Young male Sprague-Dawley rats were subjected to either sham surgery (thoracotomy) or pulmonary artery banding to induce right ventricle (RV) pressure overload. The RVs were then dissected at either 1-week or 6-weeks post-surgery and stored at -80°C. Finally, RNA was isolated from whole-RV samples and prepared for bulk RNA-sequencing.

first: Kana

last: Yazaki

first: John

last: Duaz

first: Yohei

last: Akazawa

first: Mei

last: Sun

first: Golam

last: Kabir

first: Jean-Francois

last: Dejardin

first: Kim

last: Connelly

first: Mark

last: Friedberg

first: Scott

last: Heximer


title: RNA sequencing of lung tissue from wildtype and hypoxia-induced pulmonary hypertension/hypoxia-induced pulmonary hypertension mice under aerobic exercise conditions

city: Zhuzhou

first: Ziyu

state: Hunan

address: Tianyuan district

institute: Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University

summary: Pulmonary hypertension (PH) is a hemodynamic disorder defined as abnormally increased pulmonary artery pressure that could be caused by various etiologies. It has been evidenced that exercise training could benefit for patient with PH. However, the mechanism of exercise training induced cardiovascular protection in PH has not been clarified. This study is designed to explore the underlying mechanism of exercise training by RNA sequencing in a mouse PH model.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for lung tissue from wildtype and hypoxia-induced pulmonary hypertension/hypoxia-induced pulmonary hypertension mice under aerobic exercise conditions

first: Yuan

last: Guo

first: Zhu

last: Chen

first: Changhu

last: Xiao


title: Driver mutation landscape of acute myeloid leukemia provides insights for neoantigen-based immunotherapy [scRNA-seq]

first: Peng

overall_design:
Single cell RNA sequencing from 4 patient tumors enrolled in the study. Biopsies were taken from bone marrow at diagnosis.

***************************************************************
Submitter statement concerning missing raw data: Law restrictions prohibit us from publicly sharing raw sequencing data, which however can be made available upon reasonable request and permission of the local ethics committee.
***************************************************************

first: Junmin


title: STAT5A knockout endows fibroblasts with features of young mesenchymal stem cells

city: Kunming

first: Lihua

last: Qiu

state: Yunnan

address: Puxin Road

institute: Kunming University

summary: Fibroblasts and mesenchymal stem cells are very similar in cell morphology and expression of specific antigens on the cell surface. There are studies indicating that fibroblasts can be derived from mesenchymal stem cells, while there has also been a report suggesting that fibroblasts can be dedifferentiated into mesenchymal stem cells. However, the key factor/ gene that regulates the mutual transition between fibroblasts and mesenchymal stem cells has not been fully elucidated. Here we report that knocking out STAT5A in fibroblasts can make fibroblasts gain multipotent differentiation capability similar to that of mesenchymal stem cells and that STAT5A knockout fibroblasts are closer to mesenchymal stem cells in terms of molecular characteristics. STAT5A knockout fibroblasts also acquired immunomodulatory capabilities similar to the capabilities of mesenchymal stem cells and showed multiple characteristics of cellular rejuvenation. After transplantation of human STAT5A knockout fibroblasts into old immunodeficient mice, they can differentiate into osteoblasts in vivo and significantly improve the number and density of lumbar trabecular bone, besides, they do not form tumors. Transplantation of human STAT5A knockout fibroblasts into old NOD/SCID mice significantly reduced senescent cells in multiple tissues. These data indicate that STAT5A is a pivotal factor regulating cellular identity between mesenchymal stem cells and fibroblasts, and STAT5A knockout simultaneously confers multipotent differentiation capacity and youthful characteristics on fibroblasts.

overall_design: To elucidate the key factors/genes that regulate the intertransformation between fibroblasts and mesenchymal stem cells

first: Yanjiao

first: An

last: Yu


title: WDFY3 loss-of-function leads to increased proliferation and altered differentiation of neuronal cells underlying the haploinsufficient human phenotype

city: Leipzig

first: Linnaeus

last: Bundalian

address: 15 Albert-Scwheitzer Str.

institute: Universitatklinikum Leipzig

summary: Neurodevelopmental disorders (NDD) are poorly understood, and late diagnosis and interventions result in a high burden for the society and health system. WD Repeat and FYVE Domain Containing 3 (WDFY3) encodes for the autophagy adaptor protein ALFY. Loss-of-function (lof) variants in WDFY3 result in a monogenic condition characterized by mild to moderate developmental delay, neuropsychiatric disorders, and altered brain size. We present a comprehensive description of lof WDFY3-associated phenotypes in  the largest cohort of patients to date (n = 26).

overall_design: To dissect effects of WDFY3 lof, we knocked down (KD) WDFY3 in the human neuroblastoma cell line, SH-SY5Y.  WDFY3 KD resulted in impaired clearance of aggregated Huntingtin protein and decreased protein levels of the ubiquitin-binding protein p62/SQSTM1. Through transcriptomic analyses, we delineated dysregulated gene networks primarily involved in nervous system development, neuron projection development, and signaling pathways such as MAPK/ERK1/2 and WNT/β-catenin. The dysregulation of signaling pathways was further confirmed at protein level, as shown by increased levels of ERK1/2 and decreased levels of endogenous β-catenin. We found an increase in neuronal cell proliferation as evidenced by elevated cell counts, and of the proliferation marker Ki-67 and PCNA gene expression. Conversely, neuronal cell differentiation was impaired, as indicated by reduced neurite outgrowth. Notably, differentiated neuronal cells show a significantly increased WDFY3 expression compared to undifferentiated cells, suggesting involvement of ALFY in neuronal differentiation. Lastly, we found that treatment with lithium chloride was associated with an increased expression of WDFY3, which may point to a potential therapeutic option for patients with impaired ALFY function.


title: Single-nuclear RNA sequencing of human left atrial appendage

first: Xi

last: Fan

state: --- Select One ---

address: No.12, Urumqi Middle Road, Shanghai, China

institute: Huashan Hospital of Fudan university

summary: We herein utilized SnRNA-Seq to analyze left atrial appendage (LAA) tissues to construct a comprehensive human transcriptional profile of AF. We identified a cardiomyocyte subpopulation with high energy metabolic activity (CM_1) and an adipocyte subpopulation with a specific metabolic regulating ability (Adip_0). We also demonstrated a specific myocardial energy metabolic remodeling in AF that promoted glycolytic metabolism and inhibited mitochondrial respiratory capacity. Our results showed that epicardial adipose tissues (EAT) played a unique role in regulating this process and that cell death-inducing DFFA-like effector A (CIDEA) in EAT triggered myocardial metabolic remodeling by promoting the paracrine effects.

overall_design: SnRNA-Seq was performed on LAA samples from three patients with no history of AF (No-AF), three patients with paroxysmal AF (Paro-AF, duration ≤ 7 days), and three patients with persistent AF (Pe-AF, duration＞7 days).

first: Yiqing

last: Wang

first: Xiaotian


title: Transcriptome Atlas of the Developing Honeybee Brain

city: Beijing

first: Xiasang

address: 2 Yuanmingyuan West Road. Institute of Apicultural Research, Chinese Academy of Agricultural Sciences

institute: State Key Laboratory of Resource Insects, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences

summary: Neural cells regulate brain functions, yet our understanding of how brain functions are influenced by different developmental stages in a cell type-specific manner is still incomplete. Here, we present a developmental cell atlas of the honeybees, including single-cell transcriptomes from entire brains of three different developmental stages: pupae, nurse bees, and foragers. We have identified 13 distinct neural cell types and have conducted detailed analysis of their cell type-specific features at various developmental stages of honeybees. The results demonstrated that these cell types varied in their proportions across developmental stages, with Kenyon cells having the highest proportion in the honeybee brain, followed by cell types related to the optic and antennal lobes. Functional differentiation of different cell types is closely associated with honeybee behaviors and physiological demands, which suggests enhanced and complex regulation of neural networks during honeybee brain development. This transcriptomic atlas provides a valuable resource for exploring the structural and functional changes in the honeybee brain during labor division differentiation.

overall_design: The brains of pupae, nurses, and foragers were dissociated for single-cell RNA-seq (10x Genomics Chromium)

first: Ying

last: Liu

first: Li

last: Ke

first: Tong

last: An

first: Bin

last: Gou

first: Pinli

last: Dai

first: Yongjun


title: Single cell atlas of enthesitis reveals a mechanical strain responsing and SOX5 programmed SDC1+ sheath fibroblast in ankylosing spondylitis [bulk RNA-seq]

city: Shenzhen

first: Jiajie

last: Lin

address: 3025# Shennan Road

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

summary: Ankylosing spondylitis (AS) is an osteoimmunology related disease characterized by enthesitis. Previous researches demonstrated that mechanical strain played the evoked role in AS enthesitis, but the detailed cell interaction and molecular mechanism in microenvironment were unclear. Herein, we constructed the hind paw loading/unloading model in SKG mice and revealed the single cell atlas of mechanical strain related enthesitis. Through single cell RNA sequencing, fibroblast was determined as the major mechanotransductive signal converter in AS enthesitis, and a SDC1+ subpopulation was identified to positively relate to both mechanical strain and disease progression. Located at the sheath side of enthesis, SDC1+ fibroblasts converted the physical strain signal into various cytokines signal, forming the interaction network with downstream inflammatory cells in the enthesitis. Furthermore, computational trajectory analysis uncovered a distinct fate branch of mechanical strain responsing SDC1+ sheath fibroblasts under the control of transcriptional factor SOX5 mediated enhancer and super-enhancer. Specifically inhibiting SOX5 expression in enthesis fibroblast using rAAV9.HAP-1 carrying siRNA sequence for Sox5 intercepted mechanical strain responsing SDC1+ sheath fibroblasts generation, and markedly remit AS enthesitis development. This study may not only contribute to the elucidation of AS pathogenesis but also provide insight into clinical therapy for AS.

overall_design: The fibroblasts of the enthesis were isolated from un-diseased or diseased SKG mice for RNA sequencing.

first: Zhongyu

last: Xie

first: Zepeng

last: Su

first: Wenhui

first: Chenying

last: Zeng

first: Guiwen

last: Ye

first: Yunshu

last: Che

first: Yipeng

first: Zhikun

last: Li

first: Weihao

last: Zhang

first: Yi

last: Zhou

first: Zipeng

first: Jinteng

first: Yanfeng

last: Wu

first: Huiyong

last: Shen


title: An ultraconserved pseudo 5' splice site fine-tunes development by regulating alternative splicing within TOR-related pathways

first: Zhan

last: Ding

address: 300 Feng Lin Road

institute: CAS Center for Excellence in Molecular Plant Sciences

summary: Introns have expanded dramatically during evolution, in which ultraconserved RNA motifs may play essential regulatory roles. Sharing the sequence with the actual 5' splice sites (5'SSs), pseudo-5'SSs are widespread in introns but never spliced. We searched homologous introns and identified eight ultraconserved pseudo-5'SSs (UCP-5'SSs). The most conserved one resides in the animal ENOX1/Enox genes that are involved in plasma electron transport and cell enlargement. In vivo deletion of this 9-nt UCP-5'SS in Drosophila results in a significantly enlarged ovary and increased fecundity. We demonstrate that this UCP-5'SS is a silencer for alternative splicing (AS) regulation of an upstream ultraconserved essential exon through interaction with the U1 snRNP-core proteins. The AS changes are observed in all the tested Drosophila mutants from the dTOR and Insulin-like pathways. Remarkably, loss of this UCP-5'SS significantly mitigates the changes. Conservatively, multiple-source human cells treated with the mTOR/Insulin pathway inhibitors also change the AS and specifically increase the translation of U1-70K. This study reveals an ultraconserved regulatory network in which a short intronic RNA motif functions as a sensor of TOR-related pathways during ovarian development.

overall_design: To investigate the function of conserved motifs in the enox gene of fruit flies, we established strains with deletions in the enox motif and the enox gene, followed by RNA-seq analysis.

first: Zhuo-Ya

last: Fang

first: Hao

first: Yong-Zhen

last: Xu


title: MicroRNA miR-20a-5p targets CYCS to inhibit apoptosis in hepatocellular carcinoma.

city: Braunschweig

first: Robert

last: Geffers

address: Inhoffenstr. 7

department: Dep. Molecular Bacteriology

institute: HCI - Helmholtz Centre for Infection Research

summary: Hepatocellular carcinoma (HCC) is a cancer with global impact and largely refractory to current treatments. Novel treatment options are therefore urgently needed. MicroRNAs play important regulatory roles in HCCs and are emerging as promising therapeutic options against HCC. We identified tumor suppressor miRNAs that may attenuate tumor development and contribute to HCC regression. We identified and validated miR-20a-5p as a promising oncogenic miRNA in HCC. To understand how miR-20a-5p affects the global landscape of gene expression, we transfected Huh7 human hepatoma cells with either the scramble control, or an inhibitor against miR-20a-5p and performed mRNA expression profiling.

overall_design: Huh7 human hepatoma cells were transfected with a scramble control or with an inhibitor against the oncogenic miRNA, miR-20a-5p and following validation of miRNA expression, were subjected to gene expression profiling.

first: Balakrishnan

last: Asha

first: R


title: Single cell atlas of enthesitis reveals a mechanical strain responsing and SOX5 programmed SDC1+ sheath fibroblast in ankylosing spondylitis [CUT&TAG]

first: Jiajie

overall_design: Fibroblasts were isolated and cultured from human spinal enthesis, then these cells were transfected with si-SOX5 or si-NC. CUT&Tag sequencing was performed to detect the signal intensity of H3K27ac and H3K4me1 modification.

first: Zhongyu

first: Zepeng

first: Wenhui

last: Yu

first: Chenying

first: Guiwen

last: Xiao


title: Bovine Formative Embryonic Stem Cell Plasticity in Embryonic and Extraembryonic Differentiation [scRNA-seq]

city: Storrs

first: Yue

address: 1390 Storrs Road

institute: University of Connecticut

summary: Bovine embryonic stem cells (bESCs) can greatly enhance understanding of bovine embryonic development and application for disease-resistance, biomedical and zoonotic pre-clinical models. However, formative bESCs with distinct morphology and complete differentiation capacity are still missing. We report here the generation of bESCs which are pluripotent both in vitro and in vivo, and efficiently converted into neural progenitor cells (NPCs) and primordial germ cell-like cells (PGCLCs) by direct differentiation. These cells exhibited distinct metabolic features from human and mouse ESCs and early embryos. Formative bESCs contributed to a wide range of cell types within embryonic and extraembryonic tissues after aggregating with mouse and bovine embryos. The establishment of bovine formative ESCs with dual developmental plasticity represents a milestone for agricultural biotechnology and decoding the underlying mechanism of bona fide bovine pluripotency.

overall_design: scRNA seq data of D25 bESC-incorperated bovine chimeric embryos.

first: Ruifeng

last: Zhao

first: Yifei

first: Guangsheng

first: Liangliang

last: Jin

first: Jiaxi

last: Liu

first: Jiaqi

last: Zhu

first: Neha

last: Mishra

first: Deborah

last: Kaback

first: Siu

last: Pok Yee

first: Chuzhao

last: Lei

first: Jingyue

middle: E

last: Duan

first: Xiuchun

middle: C

last: Tian

first: Young

last: Tang


title: Single cell atlas of enthesitis reveals a mechanical strain responsing and SOX5 programmed SDC1+ sheath fibroblast in ankylosing spondylitis [scRNA-seq]

first: Jiajie

last: Lin

overall_design: Hind limb loading/unloading models were constructed using SKG mice, and then their enthesis tissue of the Achilles tendon were disaggregated for scRNA-seq

first: Zhongyu

last: Xie

first: Zepeng

last: Su

first: Wenhui

last: Zeng

last: Ye

first: Yunshu

last: Che

first: Yipeng

first: Zhikun

last: Li

first: Weihao

last: Zhang

first: Yi

last: Zhou

first: Zipeng

first: Jinteng

first: Yanfeng

last: Wu

first: Huiyong

last: Shen


title: Differential DNA methylation reveals metabolic adaptation in recent modern human evolution

city: Jerusalem

first: Daniel

last: Batyrev

address: Edmond J, Safra Campus (Givat Ram)

department: Department of Genetics, The Institute of Life Sciences, Silberman Building

country: Israel

institute: The Hebrew University of Jerusalem

summary: The advent of agriculture approximately 12,000 years ago heralded significant shifts in human diets, lifestyles, and population densities, presenting new selective pressures on human populations. Recent studies have focused on genetic adaptations to these changes, but the role of epigenetic mechanisms, particularly DNA methylation, in human evolution remains underexplored. Here, we reconstructed whole-genome DNA methylation maps for 39 ancient human bone samples spanning the past 11,000 years, and identified genomic regions displaying methylation changes across time. To reveal potential regulatory sequences within these differentially methylated regions (DMRs), we further mapped enhancers in human bone using Chromatin Immunoprecipitation Sequencing (ChIP-Seq) for H3K27 acetylation (H3K27ac). Globally, our analysis revealed increased DNA methylation, particularly around promoters and transcription start sites (TSS), in the more recent samples, suggesting recent evolutionary epigenetic adaptation. Among the DMRs, we identified 49 enhancers showing significant negative correlation with sample age. Enrichment analysis of the annotated genes point to metabolic-related phenotypes. Our findings suggest that DNA methylation changes in regulatory regions may have played a significant role in human adaptation. This study highlights the importance of considering epigenetic mechanisms in the study of recent human evolution and suggests that environmental changes, such as diet, can induce epigenetic adaptations.

overall_design: Chromatin immunoprecepitation DANN-seqencing (ChIP-seq) for histone variants H3K27ac in human bone tissue

first: Thabat

last: Khatib

first: Malka

last: Nissim-Rafinia

first: Eran

last: Meshorer


title: Molecular Profile of Interleukin-17RA Blockade by Brodalumab in Japanese Patients with Psoriasis: Results from the ESPRTI study

city: New York

first: James

last: Krueger

state: NY

address: 1230 York Avenue

department: Center for Clinical and Translational Science

institute: The Rockefeller University

summary: Brodalumab, an anti-interleukin-17 receptor antibody, is presumed to be effective in psoriasis due to its action on the IL-17 pathway. This study is an analysis of an exploratory intervention study (ESPRIT) conducted in Japanese patients with moderate to severe plaque psoriasis. The efficacy of brodalumab was analyzed by clinical changes and modulation of skin inflammation by changes in gene expression in the skin and protein expression in blood samples.

overall_design: The study was conducted at five sites in Japan from March 2020 to March 2022. Eligible patients were at least 18 years of age at the time of consent and had moderate to severe plaque psoriasis, psoriasis skin severity (PASI) score >10 or body surface area (BSA) >10%. Healthy volunteers are selected whose age and sex were similar to those of psoriasis patients. Brodalumab dosing was consistent with the label: 210 mg subcutaneously at Week 0, 1, and 2, and every 2 weeks thereafter until 12 weeks. The primary efficacy endpoints were: (i) clinical changes in terms of PASI score and PASI score 0 achievement rate at Week 12, (ii) molecular profile changes from Week 0 (baseline) to Week 12, and (iii) changes in inflammation-related and cardiovascular risk factors at Week12.

middle: G

first: Akimichi

last: Morita

first: Mona

last: Uchida-Yamada

first: Yasumasa

last: Kanai

first: Sandra

last: Garcet


title: Defining the vascular niche of human adipose tissue across metabolic conditions

city: Aarhus

first: Joanna

middle: Maria

last: Kalucka

address: Høegh-Guldbergs Gade, 10

department: Biomedicine

country: Denmark

institute: Aarhus University

summary: White adipose tissue requires a well-maintained vascular network to function properly. Although advances in single-cell transcriptomics have allowed the development of comprehensive human white adipose tissue atlases, there has been a little focus on deciphering the heterogeneity and the functional states of adipose vascular cells, including blood adipose endothelial cells (AdECs), adipose lymphatic endothelial cells (AdLECs), and mural cells (pericytes and vascular smooth muscle cells). Using single nucleus RNA sequencing (snRNA-seq), we mapped human subcutaneous adipose tissue cellular clusters, and focused on cells comprising the vascular niche. We further integrated our in-house generated cohort with seven publicly available datasets of human SAT single cell RNA-seq (scRNA-seq) and snRNA-seq. The generated atlas comprised nearly 70,000 vascular cells from 65 donors, which allowed us to explore the adipose vascular niche. By mining this rich resource, we identify eight endothelial populations, comprising seven canonical subtypes and one additional heterogeneous population of sub-endothelial AdECs. We also provide detailed analyses comparing the transcriptomes of vascular cells from individuals living with or without obesity and type 2 diabetes. These data provide an extensive atlas for the exploration of the adipose vascular niche and its modulation of adipose tissue biology in health and disease.

overall_design: Human deep subcutaneous adipose tissue samples were obtained from lean donors undergoing hemicolectomy, laparoscopic transabdominal preperitoneal approach, fundoplication with mesh hiatoplasty, or band-reinforced gastric bypass and obese donors undergoing elective cosmetic abdominoplasty, gastric sleeve resection, or gastric bypass surgeries at the Clinic for General, Visceral, and Pediatric Surgery of the University Medical Center Göttingen in Göttingen, Germany. Given the wide range of obesity and type 2 diabetes phenotypes, we used all the available clinical parameters to classify the donors. Obesity was defined based on body mass index (BMI) (kg/m2): Lean donors (BMI < 30) and donors with obesity (BMI > 30). Donors were classified as having diabetes based on the presence of a previous history of type 2 diabetes and antidiabetic medication. This yielded three groups in total matched for age and BMI; lean (2 females/ 2 males, age: 45.75±13.27, BMI: 23.27±0.72), obese (3 females/ 4 males, age: 38±5.78, BMI: 53.22±8.94), and obese diabetic (2 females/ 1 male, age: 42±6.16, BMI: 51.3±6.16). The human samples used in the present study were obtained based on the presence of a signed consent according to the University Medical Center Göttingen institutional review board ethical approval (38/4/21).

first: AlZaim

last: Ibrahim

first: Hassan

last: Mohamed N.

first: Kalucka

last: Joanna


title: SARS-CoV-2 Nsp2 recruits GIGYF2 near viral replication sites and supports viral protein production [shgigyf2_rna_seq]

city: Seoul

first: Sunghan

last: Lee

state: South Korea

address: Building 203 Room 526, 1, Gwanak-ro, Gwanak-gu

department: School of Biological Sciences

country: South Korea

institute: Seoul National University

summary: The SARS-CoV-2 genome encodes 16 non-structural proteins (Nsps), with Nsp2 being the least conserved and least understood. In this study, we found a crucial role of Nsp2 in the SARS-CoV-2 life cycle and demonstrated its interaction with GIGYF2, which causes the relocation of GIGYF2 to near double membrane vesicles (DMVs) and the enhancement of viral protein production. Deletion of the Nsp2-coding region from the viral genome led to a drastic reduction in viral RNA synthesis early in infection (3–4 hours post infection). Through interactome analysis of Nsp2 in virus-infected cells, we identified GIGYF2—a protein involved in translational regulation—as a key partner of Nsp2. We confirm the interaction between GIGYF2 and Nsp2 from both SARS-CoV-1 and SARS-CoV-2. Depleting GIGYF2 or its cofactor ZNF598 phenocopied the replication defects observed with Nsp2 deletion, suggesting their critical roles in viral reproduction. Moreover, GIGYF2 and ZNF598 relocate to areas near DMVs, viral replication sites, upon infection. This relocation does not happen with the Nsp2-deleted virus, indicating Nsp2’s role in directing GIGYF2 to DMVs. Using formaldehyde crosslinking and immunoprecipitation-sequencing experiments (fCLIP-seq), we found that GIGYF2 interacts with viral RNAs, particularly in regions encoding Nsp3, M, and Orf6. Depletion of GIGYF2 resulted in decreased expression of these proteins. Our findings reveal the function of Nsp2 in supporting viral protein production by exploiting GIGYF2 as a host factor.

overall_design: We employed formaldehyde immunoprecipitation and sequencing (fCLIP-seq) using anti-GIGYF2 antibody after SARS-CoV-2 infection. To investigate the function of GIGYF2 and NSP2 in SARS-CoV-2 replication, we performed RNA-sequencing after infection with WT and nsp2-deleted virus. We also performed RNA-sequencing in parental and GIGYF2 shRNA cells after SARS-CoV-2 virus infection.


title: Reprogramming in the adult honeybee mushroom body induces neonicotinoid-associated glia remodeling

first: Xiasang

last: Chen

summary: Mushroom bodies play important roles in honeybee learning and memory, We performed the high-throughput single-cell sequencing analysis of honeybee mushroom body cells to investigate the effects of thiacloprid on mushroom body cell allocation in the honeybee brain.

overall_design: Honeybee mushroom bodies were digested into single-cell suspension, next, we performed 10x Genomics drop-seq and analyzed using scRNAseq.

first: Li

last: Ke

first: Airui

last: Li

first: Yong-Jun

last: Liu


title: Disseminated tumor cell of colorectal cancer adopt the wound healing program of epidermal keratinocyte [scRNA-seq]

city: Ariake

first: Ryoji

last: Yao

state: Tokyo

institute: Cancer Institute, JFCR

summary: Disseminated tumor cells (DTCs) are a critical cell population in the metastasis process, and understanding their features is essential for the development of cancer treatment. We show that DTCs of colorectal cancer (CRC) transiently adopted the cellular state resembling to the activated epidermal keratinocyte during wound healing. Using the orthotropic transplantation of patient derived organoids (PDOs), we demonstrated that collective migrating cell clusters in primary site did not contain cancer stem cells but contained cells expressing wound-inducible keratins. Mechanistically, inhibition of EZH2 methyltransferase and activation of YAP signaling synergistically promoted DTC phenotype and potentiated dissemination to the distant organs. Collectively, these observations demonstrated that CRC cells alter the cellular hierarchy and adopt re-epithelization program resembling to the tissue repair process to generate DTCs.

overall_design:
DTC organoid esatblished from mouse model of colorectal cancer was subjected to scRNA-seq analysis.

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Submitter states that missing raw files are due to patient privacy concerns.
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title: A novel ATG4B-SESN3 axis promotes the growth of T-cell acute lymphoblastic leukemia cells

city: suzhou

first: Wenjuan

last: Ma

state: Jiang su

address: 199 Ren'ai Rd

department: Hematology Center Cyrus Tang medical institute

institute: Soochow University

summary: ATG4B, a cysteine protease, plays crucial roles in the autophagy process and is implicated in various human diseases including cancers. However, little is known about ATG4B in T- cell acute lymphoblastic leukemia (T-ALL), a fatal hematological malignancy. Although ATB4B ablation hampers cancer cell growth, the molecular insight is not elucidated yet. Herein, we showed that ATG4B had significantly higher expression in T-ALL cells than control cells. ATG4B ablation through RNA interference or CRISPR/Cas9-mediated gene knockout inhibited T-ALL cell growth in vitro and in vivo. In contrast, Atg4b depletion had mild effects on normal hematopoiesis and T-cell development. Mechanistically, RNA-seq analysis revealed that ATG4B silencing significantly enhanced the expression of sestrin 3 (SESN3). Subsequent studies indicated that SESN3 plays a tumor suppressor role in T-ALLcells via a strong inhibition of protein translation caused by S6K inactivation. Rescue experiment showed SESN3 silencing partially restored the growth inhibitory effect of ATG4B ablation. Importantly, ATG4B inhibitor exhibited anti-leukemia activity in a patient-derived xenograft (PDX) model. Taken together, this study demonstrates that a novel ATG4B-SESN3 pathway plays a crucial role in T-cell leukemogenesis and targeting ATG4B provides an optional strategy for T-ALL treatment.

overall_design: To investigate the molecular mechanisms by which ATG4B silencing hampers T-ALL cell growth, RNA-Seq data were generated with ATG4B-silenced and control (scrambled) Jurkat cells from 3 independent RNA extracts. The differentially expressed transcripts comparing ATG4B-silenced cells with scrambled cells are displayed.

first: Lei

last: Zhang

first: Yan

last: Wan

first: Haixia

last: Zhou

first: Xiaoyan

last: Jiang

first: Yun

last: Zhao


title: The influence of dextran sulphate treatment on chicken macrophages

city: Yangzhou

first: Xuming

last: Hu

state: Jiangsu

address: No.48 East Wenhui Road

department: College of Animal Science and Technology

institute: Yangzhou University

summary: Dextran sulphate is a polyanionic derivative of dextran and has versatile physicochemical and biological properties. In particular, it can induce the host inflammatory response. The recent study found that Dextran sulphate can profoundly inhibited ALV-J proliferation in chicken macrophages. To further investigate the antiviral mechanisms of dextran sulphate, we performed RNA sequencing on dextran sulphate-treated chicken macrophages.

overall_design: To investigate the antiviral mechanisms of dextran sulphate, we performed RNA sequencing on dextran sulphate-treated chicken macrophages.

first: Wang

last: Guo

first: Huixian

last: Wu

first: Qi

last: Xu


title: Cell of origin alters myeloid-mediated immunosuppression in lung adenocarcinom

city: Duarte

first: Crystal

last: Marconett

email: cmarcone@usc.edu, cmarconett@coh.org

state: CA

address: 1500 E Duarte Rd

department: Integrative Translational Sciences

institute: City of Hope

summary: Lung adenocarcinoma (LUAD) is the most prevalent subtype of lung cancer with extensive biological heterogeneity, such as varying cells of origin from alveolar epithelial cells (AECs) in the distal lung. The predominant types of AECs include surfactant-producing alveolar epithelial type II (AT2) cells and large, delicate alveolar epithelial type I (AT1) cells, which are responsible for facilitating gas exchange. Although AT1 cells have been thought to be terminally differentiated and consequently unable to proliferate, we, and others, have previously reported that Gramd2+ AT1 cells can give rise to a histologically-defined LUAD1,2 on transgenic mouse model. Immunotherapy has shown a major impact on treatment of solid tumors over the past 10 years, particularly on LUAD, where it significantly improves patients’ survival rates3. However, because of the largely unknown immunosuppressive states of LUAD, there is considerable variability in patient response to therapy across LUAD patients, making immunotherapeutic treatment challenging. To determine whether cells of origin for LUAD reprogram differently tumor immune microenvironment (TIME) landscape, we employed single nucleus RNA sequencing (snRNA-Seq) on mouse KRASG12D-overexpressing Gramd2+ AT1 cell and Sftpc+ AT2 cell-derived LUADs to comprehensively characterize transcriptomic, molecular, and cellular aberrations within the TIME. We demonstrate that myeloid cells within the AT1-LUAD TIME manifest a disordered cell composition and disrupted transcriptome: increased cell number of inflammatory monocytes and macrophages but decreased cell number of myeloid-derived suppressor cells (MDSCs) were observed in AT1-LUAD TIME compared with its AT2 counterpart. In addition, a series of bioinformatic analyses, gene set enrichment analysis (GSEA), ingenuity pathway analysis (IPA) and cell-cell communication (CCC) analysis, along with immunostaining confirmed LUAD TIME derived from different cells of origin exhibits altered suppressive gene expression patterns and disparate pro-inflammatory signaling activities. Taken together, AT1-LUAD presents a proinflammatory, immunoreactive TIME, while the TIME of AT2-LUAD is relatively immunosuppressive. This study suggests that LUAD cell of origin is associated with transcriptomic aberrations and immune landscape changes that may inform ongoing translational work to improve patient responses.

overall_design: Whole lungs of each sample B6 mouse were perfused and dissociated into a single cell suspension for nuclei isolation

first: Minxiao

last: Yang

first: Edgar

last: Gonzalez

first: Jonathan

last: Castillo

first: Chunli

last: Yan

first: Keqiang

first: Leonidas

last: Arvanidis

first: Zea

last: Borok

first: W.

middle: D

last: Wallace

first: Dan

last: Raz

first: Evanthia

last: Roussos Torres


title: Disruption of the Cyp7b1 Gene in Rats Increases Secretion of Very Low Density Lipoproteins by Decreasing Low Density Lipoprotein Receptor on Plasma Membrane

city: Zaragoza

first: Luis

middle: Vicente

last: Herrera-Marcos

state: Zaragoza

address: C/Miguel servet nº177

department: Bioquimica y biologia molecular y celular

country: Spain

institute: Universidad de Zaragoza. Facultad de Veterinaria

summary:
Cytochrome P450, family 7, subfamily b, polypeptide 1(CYP7B1) is a widely expressed hydroxylase enzyme that may be involved in inactivation of sterols. Using transposon in zygotes, we have generated rats lacking Cyp7b1 expression. Homozygous mutant animals show absence of Cyp7b1 mRNA expression in liver, small intestine, adipose tissue and muscle. Elevated levels of 25-hidroxycholesterol were found in liver of mutant rats. A fat gavage test showed that postprandial hypertriglyceridemia was decreased in homozygotes lacking Cyp7b1 without changes in cholesterol, APOA1 and APOA4 contents of postprandial lipoproteins. In this experimental setting, gene expression analyses of those coding for proteins involved in HDL structure and metabolism revealed that only hepatic Abca1 mRNA expression was significantly decreased. A four-hour fasting had no impact on plasma lipids. However, after prolonged fasting, plasma triglyceride levels in the homozygous mutants were increased about 164 % of wild types.  In agreement with this, an increased hepatic secretion of VLDL in fasting rats treated with tyloxapol and absence of low-density receptor protein on the surface of hepatocytes were observed. The decrease in LDLr was not due to decreased mRNA expression but to increased expression of its protease Psck9. These data indicate that CYP7B1 and its metabolite 25-hydroxycholesterol modulates the metabolism of VLDL in liver by decreasing its capture by LDL receptor.
In agreement with this, an increased hepatic secretion of VLDL in fasting rats treated with tyloxapol and absence of low-density receptor protein on the surface of hepatocytes were observed. The decrease in LDLr was not due to decreased mRNA expression but to increased expression of its protease Psck9. These data indicate that CYP7B1 and its metabolite 25-hydroxycholesterol modulates the metabolism of VLDL in liver by decreasing its capture by LDL receptor.  These observations were partially recovered by exogenous plasmid hydrodinamic injection

overall_design: WT vs Cyp7b1 KO vs Cyp7b1 rescued Rats

first: Roberto

last: Martinez-Beamonte

first: Natalia

last: Guillén

middle: V

first: Joaquín

last: Surra

first: María

last: Navarro

first: Cristina

last: Barranquero

first: Carmen

last: Arnal

first: Juan

last: Puente

first: M

last: Jesús Rodríguez-Yoldi

first: Isabel

last: Mendiara

first: Celia

last: Domeño

last: Nerín

first: Aron

last: Geurts

first: Jesús

last: Osada

first: Martín

last: Laclaustra


title: Beta2 adrenergic receptor-mediated abnormal myelopoiesis drives neuroinflammation in aged patients post traumatic brain injury

city: Nantong

first: Zhichao

last: Lu

address: 20 Xisi Rd,

institute: Affiliated Hospital of Nantong University

summary: Short title: Aged bone marrow drives neuroinflammation post TBI

overall_design: In this study, bone marrow transcriptional information was investigated in four groups of C57BL/6 mice. The four groups of mice were, young-control (Young-CON) group, aged-control (Aged-CON) group, young-Traumatic Brain Injury (Young-TBI) group and aged-Traumatic Brain Injury (Aged-TBI) group. Three days after modeling of the TBI group (peak hematopoietic response), bone marrow of mice in each group was collected and RNA sequenced. Quality control and analysis of the sequencing data followed routine steps.

first: Rui

last: Jiang

first: Chenxing

last: Wang

first: Jun

last: Xiao


title: Human Astrovirus VA1 Infection on Small Bowel Enteroids

city: Ann Arbor

first: Andres

last: Rivera Ruiz

state: MI

address: 5737A Med Sci II 1137 Catherine St

department: Microbiology & Immunology

institute: University of Michigan

summary: Understanding transcriptional effect after VA1 infection in different cell types using ileum-derived organoids single-cell RNA sequencing

overall_design: Mock or VA1-infected undifferentiated ileum-derived organoids collected at 1 and 3 days post-infection


title: S1PR3 modulates the hyper-proliferation of keratinocytes in psoriasis by activating STAT3 in PKA/Src dependent manner

city: Nanjing

first: Hongwei

address: No. 22, Hankou Road

department: School of Medicine

institute: Nnanjing University

summary: Background: Abnormal lipid metabolism influences the occurrence and development of psoriasis. Moreover, persistent activation of STAT3 signaling pathway in epidemies contributes to psoriasis. However, the molecular mechanism of lipid metabolism and STAT3 activation is unclear. Methods: Imiquimod (IMQ)-induced mouse psoriasis-like model was established to access the potential treatment of FTY720. The function of SIP receptors 3 (S1PR3) was determined by S1PR3 siRNA in HaCaTs and S1pr3 knock out in mice. RNA-seq in HaCaTs was undertaken to explore the downstream target of S1PR3. ChIP assay was applied to explore the transcription factor on S1PR3 promoter.  Findings: The upregulation of S1PR3 in the lesion from psoriasis patients and IMQ-induced mice was observed. Moreover, the pan-S1PR modulator FTY720 ameliorated the lesion in IMQ-induced mice, which was mediated by internalizing S1PR3. S1PR3 knocking downing both in vivo and in vitro significantly suppressed the hyper-proliferation of keratinocytes in a P-STAT3-dependent manner. We found that upregulated-S1PR3 expression maintained STAT3 activation in psoriasis through both short and long term. Namely, S1PR3 enhanced early STAT3 activation via promoting the binding of P-Src to gp130, and long STAT3 activation by reducing Src. Ultimately, Upregulated-S1PR3 was due to STAT3 binding to S1PR3 promoter in psoriatic skin.

overall_design: Utilize RNA-seq to investigate the transcriptome profile of HaCaT treated with IL-6 or IL-6 plus TY52156 for 24 hours.

first: Panpan

last: Lian

first: Zhiqiang

last: Huang


title: Transcriptome changes in lung after the intervention of Wendan Decoction on COPD rats

city: Qiqihar

first: Song

last: Lin

address: Bukui

institute: Qiqihar Medical University

summary: The RNA-seq of lung tissues from Wistar rats was performed. Through the analysis of differentially expressed genes, we found the genes related to the therapeutic effects of Wendan Decoction.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for COPD, Wendan Decoction and control rats.

first: Ruinan

last: Ren

first: Fang

first: Jinling

last: Zhang

first: Wenbao

first: Qi

last: Yu

first: Guoan

last: Zhao

first: Tianyang


title: Impact of lysine, methionine, and histidine deficiencies on gene expression and upstream transcriptional regulators in bovine mammary epithelial cells: an RNA-sequencing analysis

city: GUELPH

first: Boning

last: Li

state: ON

address: 50 Stone Road East

department: Animal Biosciences

institute: University of Guelph

summary: Essential amino acids (EAA) may alter bovine mammary epithelial cell functions by impacting mRNA expression of genes through their upstream transcription factors. This study investigates the transcriptional responses in bovine mammary epithelial cells under EAA deprivation (lysine, methionine, and histidine) using RNA-sequencing and pathway analysis. Differential expression genes with absolute log2 fold change ≥ 1 and a false discovery rate of < 0.05 were considered differentially expressed. QIAGEN Ingenuity Pathway Analysis identified kinetochore metaphase signaling pathway as the most significant across all treatments, suggesting a strong link to cell proliferation and apoptosis during EAA deficiency. Activation of activating transcription factor 4 (ATF4) regulates genes involved in amino acid transport, stress response, and apoptosis. Interferon signaling emerged as a novel pathway activated by EAA deficiency, contributing to reduced cell proliferation and protein synthesis. In contrast, the RAS/RAF/MEK/ERK signaling pathway was unaffected. Hypoxia-inducible factor 1α (HIF1A) increased expression, suggesting an anti-proliferative role. Downregulation of Forkhead box protein M1 (FOXM1), a key cell cycle progression factor, likely contributed to slower cell proliferation. Additionally, tumor suppressor p53 (TP53) and ER stress-related transcription factor DNA damage inducible transcript 3 (DDIT3) were identified as mediators of apoptosis. These findings reveal a complex network of transcriptional regulators and signaling pathways influenced by EAA availability, providing new insights into the regulation of milk protein synthesis and potential strategies for optimizing milk production in dairy cows.

overall_design: To identify potentially novel transcription factors that mediate the effects of essential amino acid deficiency on mammary cell activity, we used a genome-wide approach based on RNA-sequencing of gene expression in bovine mammary epithelial cell exposed to lysine, methionine, or histidine deprivation for 60 h.

first: David

last: Innes

first: Eduardo

middle: S

last: Ribeiro

first: Sergio

last: Burgos

first: John

last: Doelman

middle: P

last: Cant


title: Transcriptomic landscape of human stromal cells upon therapy-induced senescence and/or senotherapeutic intervention with melatonin

city: Shanghai

first: Yu

last: Sun

address: 320 Yueyang Rd, Life Sciences Building A #1508

department: Shanghai Institute of Nutrition and Health

institute: Chinese Academy of Sciences

summary: In eukaryotes, cellular senescence is a highly conserved stress response elicited by acute or chronic damage signals. In humans, senescent cells accumulate in multiple tissues at different rates, from 2- to 20-fold when comparing young (<35 years) to old (>65 years) healthy donors. The pathogenic role of cellular senescence in the vast majority of age-related diseases can be explained by the senescence-associated secretory phenotype (SASP). Melatonin is a methoxyindole synthesized and secreted mainly by the pineal gland during night under normal light/dark conditions. The endogenous rhythm of melatonin secretion is governed by the suprachiasmatic nuclei and entrained to the light/dark cycle. Light is able to either suppress or synchronize melatonin production in accordance with the light schedule. The nycthohemeral rhythm of this hormone can be evaluated by repeated measurement of plasma or saliva melatonin or urine sulfatoxymelatonin, the main hepatic metabolite. The primary physiological function of melatonin, whose secretion adjusts to night length, is to convey information concerning the daily cycle of light and darkness to body structures. However, there is a lack of insights into the biological capacity of melatonin in modulation of chronological aging and regulation of organismal healthspan. In this study, we aimed to evaluate the anti-aging potential of melatonin, by profiling the influence of melatonin on the transcriptome-wide expression of human stromal cells made senescent by genotoxicity in vitro. Together, this is the first report to determine the possibility of employing melatonin as a source of endogenous rhythm-related molecules in anti-aging pipelines, particularly pharmacological development for future geriatric medicine.

overall_design:
High-throughput RNA-seq examination of genome-wide transcriptional alterations of human stromal cells that underwent treatment by the chemotherapeutic agent bleomycin and/or exposure to melatonin (recombinant product).

Please note that, for melatonin-related investigations, the following samples in GSE264076/PRJNA1100940 samples were re-used/re-analyzed together with the melatonin treatment-related data:

SRR28705054 SRX24272271 GSM8209760: CTRL-01 SAMN40982160
SRR28705053 SRX24272272 GSM8209761: CTRL-02 SAMN40982159
SRR28705052 SRX24272273 GSM8209762: CTRL-03 SAMN40982158
SRR28705051 SRX24272274 GSM8209763: BLEO-01 SAMN40982157
SRR28705050 SRX24272275 GSM8209764: BLEO-02 SAMN40982156
SRR28705049 SRX24272276 GSM8209765: BLEO-03 SAMN40982155

first: Peipei


title: Study of differential gene expression in variegated and unvariegated Yucca flaccida ‘Golden Sword’

city: Beaucouzé

first: Laurence

middle: Hibrand

last: Saint oyant

state: Please choose a country or region

address: 42 rue G. Morel, INRA-IRHS-GDO

department: BAP

institute: INRAe

summary: Using in vitro plant of variegated Yucca flaccida ‘Golden Sword’, we obtained an unvariegated plant. While the centre of the variegated leaf is yellow with a green border, the non-variegated leaf is completely green. The mRNA of tissues corresponding to the edge and the centre of variegated and non-variegated leaves were compared and particularly the yellow tissue was compared with the three green tissues.

overall_design: the samples are called VE and VC for the edge and the center of the variegated plant and UE and UC for the edge and the center of the unvariegated plant. Total RNA was extracted using the NucleoSpin RNA Plus kit according to the manufacturer’s instructions (Macherey-Nagel, Duren, Germany), with minus modifications (2% PVP40 in lysis buffer). The mRNA enrichment, libriaries obtention and sequencing were performed by Novogene company. Total RNA were

first: Alexandre

last: Rouinsard

first: Latifa

last: Hamama

first: Julien

last: Jeauffre

first: Jean-Pierre

last: Renou

first: Agnès

last: Grapin

middle: H

last: Oyant


title: Critical Role of MALAT1 in Gram-negative Bacteria-induced Coagulation via regulating GSDMD-dependent TF activity

city: Changsha

first: Chuang

last: Yuan

address: Xiangya Road #87

institute: Central South University

summary: The study determines the transcriptosome of leukocytes from septic patients upon admission who were infected with gram-negative bacteria and not diagnosed with overt disseminated intravascular coagulation (DIC).Higher levels of MALAT1 are associated with the onset of DIC 48 hours after the admission.

overall_design: Leukocytes of septic patients were harvested upon admission. DIC scores were assessed 48 hours after the admission and patients with score >5 were diagnosed with overt DIC. Six samples, including three samples from patients without overt DIC versus three samples of patients newly diagnosed with overt DIC 48 hours after admission, were subjected to RNA sequencing.The transcriptosome of leukocytes from septic patients with or without newly diagnosed DIC were compared.

first: Xinyu

last: Yang


title: Hypertension Promotes Neuroinflammation, Brain Injury and Cognitive Impairment

city: Bundoora

first: Quynh Nhu

last: Dinh

state: VIC

address: Kingsbury Drive & Plenty Rd

country: Australia

institute: La Trobe University

summary: We tested the effect of hydralazine on hypertension-induced transciptomic changes in hippocampus and a whole brain hemisphere.

overall_design: N=6 per group. 4 treatment groups. 2 brain regions.

first: Quynh

first: T

middle: M

last: De Silva