title: RNA-seq analysis JARID2 knockdown effect on MDA-MB-231 cells

city: beijing

first: yan

last: wang

address: 17 panjiayuan nanli, chaoyang district, Beijing, China

country: Zimbabwe

institute: National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences

summary: The JmjC domain-containing protein JARID2 is an important regulator of gene expression in embryonic stem cells. However, what role JARID2 play in tumorigenesis is poorly understood. Here, we reported that JARID2 was highly expressed in multiple types of cancer, including breast cancer. And JARID2 promoted the glycolysis, lipid metabolism, stemness, proliferation, and invasion of breast cancer cells. Furthermore, we found that JARID2 was physically interacted with the nucleosome remodeling and deacetylase (NuRD) complex transcriptionally repressing a series of tumor suppressor genes. Overall, our data propose that JARID2 promotes tumorigenesis and development, endorsing the proposal of JARID2 as a target for cancer therapy.

overall_design: RNA sequencing (RNA-seq) experiments in MDA-MB-231 cells infected with scramble or JARID2 knockdown lentivirus (n=2 per group). Total RNA was extracted using Trizol reagent (Invitrogen, USA). Agilent 2100 Bioanalyzer (Agilent Technologies, USA) was used to evaluate the RNA quality.

first: Wei

first: Yan


title: Linking Antigen Specific T cell Dynamics in a Microchip to Single Cell Transcription Patterns

status: Public on May 11 2025

city: Suita

first: Hiroki

last: Ide

state: Osaka

address: 2-1 Yamadaoka

department: Engineering

country: Japan

institute: Osaka University

type: Expression profiling by high throughput sequencing

summary:
A new screening profile has been realized that can aid in determining T-cell activation state at single-cell-level.
Then, we performed single cell RNA sequencing to reveal the activation states of the cells from the dervied profiles can be indicative of the T-cell activation state.

overall_design: Comparative gene expression profiling analysis of scRNA-Seq data for OT-1 T cells that have interacted with OVA presenting antigen presenting cell and OT-1 cells that have interacted with nothing presenting antigen presenting cell.

first: Taiki

last: Aoshi

first: Masato

last: Saito

first: Wilfred

middle: V

last: Espulgar

first: Masahito

last: Hosokawa

first: Hiroko

last: Matsunaga

first: Koji

last: Arikawa

first: Haruko

last: Takeyama

first: Shohei

last: Koyama

first: Hyota

last: Takamatsu

first: Eiichi

last: Tamiya


title: CXCR4-LASP1-G9a-SNAIL Axis Drives NEPC Transdifferentiation via Induction of EMT and Downregulation of REST [16D CRPC xenograft]

city: Vancouver

first: Yen-Yi

last: Lin

state: British Columbia

address: 2660 Oak St

country: Canada

institute: University of British Columbia

summary: Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer that can develop from prostate cancer following aggressive hormonal therapy. Unfortunately, there are few treatment options available and new therapeutic targets and more effective treatments are urgently needed to improve management of the disease. There is now little doubt that the majority of NEPC is derived from prostatic adenocarcinoma cells via “NE transdifferentiation” that is driven at least in part by AR-axis interference and lineage plasticity. We have developed a first-in-field patient-derived xenograft model of a prostatic adenocarcinoma (LTL331) that undergoes a complete transdifferentiation to NEPC (LTL331R) upon host castration. Using this unique, high-fidelity, patient-derived prostate cancer xenograft models and powerful genomic and transcriptomic analyses, we have obtained evidence that therapy induced development of NEPC may result from epigenetic alterations which drives lineage plasticity of dormancy-capable cancer cells and functional evaluation of key regulators.   These findings may lead to more suitable targets and better therapeutic strategies for prevention and treatment of NEPC.

overall_design: RNA-seq profiling of 16D CRPC xenograft

first: Christopher

middle: J

last: Ong


title: Mineralocorticoid Receptor Antagonism by Finerenone Attenuates Established Pulmonary Hypertension in Rats

city: CHATENAY MALABRY

first: Emy

last: Ponsardin

address: rue JB Clément

country: France

institute: Université Paris Saclay

summary: We studied the ability of the non-steroidal Mineralocorticoid Receptor (MR) antagonist finerenone to attenuate vascular remodeling and pulmonary hypertension (PH) using two complementary preclinical models [the monocrotaline (MCT) and Sugen

overall_design: Comparative transcriptome analyses between PA-SMCs transfected with either a MR siRNA or a scrambled sequence were performed in our study.

first: Florent

last: Dumont

first: Ly

last: Tu


title: Hepatic NcoR1 deletion exacerbates ischemia and reperfusion (IR) induced liver injury regulated by NF-kB p65 [sham-IR]

status: Public on May 10 2025

city: shanghai

first: Li

last: qigen

address: Pujian Road 160

country: China

institute: Shanghai Jiao Tong University

summary: Background & Aims: Liver ischemia-reperfusion (IR) injury is a common and serious complication in liver transplantation surgery. Disturbances of mitochondrial function, altered lipid metabolism, and insulin resistance are pathways shown to participate in acute and chronic liver diseases. NcoR1 was previously shown to integrate in all these damage pathways in liver, adipose tissue, and muscle, whereby its mechanistic role is not fully understood. Here, we delineated hepatocytic NcoR1 in liver ischemia-reperfusion injury. Methods: We established an IR model in mice, measured liver function related enzymes in serum, SOD, and combined these data with HE staining and PCR assays from liver sections and lysates, respectively to determine the extent of liver injury. We used mice with albumin-Cre/LoxP system mediated hepatocyte-specific NcoR1 depletion (NcoR1△Hep) to investigate the role of NcoR1 in the etiopathogenesis of liver IR and to delineate potential related mechanisms. We also analysed the impact of NcoR1 on oxidative stress mediated cell damage, including activation of NFB signaling activation in hepatocytes in gain and loss of function studies, using immunoblotting and immunofluorescence. Results: Upon ischemia and reperfusion injury (IR), as evidenced by increased levels of liver enzymes (ALT, AST), and inflammatory cytokines (Tnf, Mcp1 et al), NcoR1 expression levels decreased at both, mRNA and protein levels in total liver lysates. To discriminate cell type specific effects, we successfully established NcoR1△Hep mice, and found that depletion of Ncor1 in hepacotytes exhibited more severe liver injury from IR, as compared to NcoR1fl/fl control mice, as evidenced by the aforementioned parameters. Silencing NcoR1 or Ncor1 deficiency promoted both, parameters of inflammatory and oxidative stress such as Gclc, Gclm, Hmox1, and Ccl2, et, al. in AML12 cells and primary mouse hepatocytes, while NcoR1 over-expression shows the opposite results. Further, IR treated NcoR1△Hep mice displayed increased phosphorylation of p65, an essential parameter of the NFB signaling pathway, a critical mediator of stress signals in hepatocytes. Gene silencing of p65 in primary hepatocytes increased NcoR1 expression, suggesting that NFkB/p65 signaling is a negative regulator of NcoR1 expression. Conclusion: Our results indicate that damage mediated activation of NFB/p65 signaling decreases NcoR1 expression in hepatocytes, which is required for IR aggravation.

overall_design: RNA-seq profiling of wildtype or knockdown NcoR1 mouse after Ischemia and reperfusion treatment

first: Wentao

last: Yang

first: Hailang

last: Liu

first: Jingsheng

last: Ma

first: Xiaohui

last: Guo

first: Lin

last: Zhong

first: Qigen

last: Li


title: Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at the promoters of genes expressed during meiosis [scRNA-seq & scATAC-seq]

city: Stockholm

first: Masomeh

last: Askari

address: Svante Arrhenius väg 20C

country: Sweden

institute: Stockholm University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: Meiotic prophase I characterized by homologous recombination and synapsis is an intricate step for spermatogenesis. This process entails extensive changes to chromatin and transcription. Recent studies have revealed that prior to prophase I, accessible chromatin bound by paused Pol II at meiotic gene promoters is essential for their timely activation during later stages of prophase I. However, the factor responsible for promoting accessible chromatin at meiotic gene promoters before entry into prophase I is unknown. Here, we discovered that NFYA expressed in pre-meiotic germ cells promotes accessible chromatin at meiotic gene promoters. Concordantly, conditional germline deletion of Nfya in male mice blocks meiotic entry. Functionally, our spatial and single-cell ATAC-seq data revealed that loss of NFYA in pre-meiotic cells disrupts accessible chromatin at meiotic gene promoters. Our study identifies a pioneer role for NFYA in facilitating permissive chromatin at meiotic gene promoters before meiosis, thereby controlling the timely activation of meiotic genetic program during later meiosis.

overall_design: We performed single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on adult Testis tissue to simultaneously profile the whole transcriptome and assess genome-wide chromatin accessibility at single-cell resolution.

first: Martin

last: Säflund

first: Atiyeh

last: Eghbali

first: Mukhtar

last: Mohammed Abdi

first: Ann-Kristin Iréne

last: Östlund Farrants

first: Tianxiong

last: Yu

first: Deniz

middle: M

last: Özata


title: Effect of knockdown of PPIL1 on gene expression in Huh7 hepatocellular carcinoma cells

city: Tianjin

first: 佳仪

last: 吴

address: No.94 Weijin Road

institute: Nankai University

summary: Hepatocellular carcinoma is one of the leading causes of cancer death worldwide.  Our data shows the differentially expressed genes in PPIL1 knockdown HCC cells.

overall_design: RNA-seq of profiling of wildtype Huh7 cells and PPIL1 knockdown Huh7 cells.

first: Jiayi

last: Wu


title: Genome-wide maps of JARID2 chromatin state in MDA-MB-231 cells

first: yan

last: wang

summary: In order to figure out the genomic binding landscape of JARID2, we analyzed the genome-wide transcriptional targets for JARID2 using the Chromatin immunoprecipitation based-deep sequencing (ChIP-seq) in MDA-MB-231 cells with antibodies against JARID2. Using Illumina HiSeq 2500, we found lots of JARID2-specific binding peaks and strong  enrichment on the promoters of selected genes involved in classical pathways. This study gave us a new understanding of the role of JARID2 in chromatin status and gene transcription.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for JARID2 in MDA-MB-231 cells.

first: Wei

first: Yan

last: Wang


title: Glycogen stress granules cause astrocytic mitochondrial dysfunction to aggravate ischemic damage and delay recovery after stroke

city: Hefei

first: Li

address: No. 443, Mount Huangshan Road, Shushan District

institute: University of Science and Technology of China

summary: Ischemic stroke induces pathological glycogen deposition in astrocytes, but its role in post-injury neural dysfunction remains undefined. We reveal that glycogen-laden astrocytes in the ischemic penumbra undergo HDAC3-dependent mitochondrial fragmentation via a stress granule-mediated mechanism, exacerbating neuronal injury and hindering functional recovery. Mechanistic studies demonstrate that glycogen aggregates sequester cytoplasmic HDAC3, enabling its translocation to mitochondria. There, HDAC3 deacetylates outer mitochondrial membrane protein ATAD3A, promoting oligomerization-driven mitochondrial fission. Astrocyte-specific ATAD3A ablation prevents stroke-induced synaptic disorganization, neural circuit disruption, and cognitive deficits. Therapeutically, combined administration of cotadutide (a glycogen-depleting GLP-1/GCGR agonist) and HDAC3 inhibitor RGFP966 reverses glycogen accumulation, rescues mitochondrial architecture/function, and restores synaptic plasticity and circuit reorganization, thereby accelerating sensorimotor recovery. Our work identifies glycogen stress granules as pathogenic signaling hubs linking astrocytic metabolic stress to mitochondrial failure through compartmentalized HDAC3-ATAD3A crosstalk, and proposes a dual-target paradigm addressing both substrate overload and protein acetylation dynamics for stroke neurorestoration.

overall_design: Freshly dissociated single-cell suspensions were loaded to 10X Genome GenCode Single-cell instrument to generate GEMs (Gel Bead-In-EMlusion). ScRNA-seq libraries were subsequently prepared following the manufacturer’s protocol of Chromium Next GEM Single Cell 3’ Regent Kits v3.1. Libraries were then sequenced using the Novaseq 6000 platform with paired-end sequencing (PE150) mode.

first: Hongrui

last: Zhu

first: Mengmeng

last: Yang

first: Sheng


title: Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at the promoters of genes expressed during meiosis [ATAC-seq]

overall_design: Chromatin accessibility was assessed by performing ATAC-seq on fluorescence-activated cell-sorted (FACS) populations derived from adult testis samples

first: Deniz M.


title: Hepatic NcoR1 deletion exacerbates ischemia and reperfusion (IR) induced liver injury regulated by NF-kB p65

last: qigen

first: Wentao

first: Hailang

last: Liu

first: Jingsheng

last: Ma

first: Xiaohui

first: Lin

first: Qigen


title: Ellagic Acid Enhances Longevity and Healthspan in Caenorhabditis elegans via Insulin/IGF-1 Signaling Pathway

city: Changchun

first: Anran

last: Li

state: Jilin

address: Qianjin Street

institute: Jilin University

summary: The role of ellagic acid (EA), a natural antioxidant, in regulating anti-aging and its underlying mechanisms remains unclear. In this study, we investigated the anti-aging effects and molecular mechanisms of EA in Caenorhabditis elegans (C. elegans). Our results demonstrate that EA extends the lifespan of C. elegans, enhances motility, reduces lipofuscin accumulation, and improves overall healthspan. Additionally, EA reduces reactive oxygen species (ROS) accumulation in C. elegans under conditions of heat and oxidative stress. The insulin/IGF-1 signaling (IIS) pathway, a key regulator of longevity and stress resistance in C. elegans, was found to mediate EA's effects. EA treatment did not extend the lifespan of mutants defective in daf-2, daf-16, hsf-1, hlh-30, and skn-1, confirming that EA’s lifespan-extending effect operates through the IIS pathway. Furthermore, EA treatment increased the expression of stress response genes downstream of the IIS pathway. Based on RNA sequencing data, we further explored the molecular mechanisms and potential regulatory roles of EA in anti-aging.

overall_design: EA C. elegans

first: Jinze


title: Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at meiotic promoters in mice

first: Masomeh

last: Askari

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

overall_design: Refer to individual Series


title: Transcription factor NFYA directs male meiotic entry by facilitating accessible chromatin at the promoters of genes expressed during meiosis [CUT&RUN]

overall_design: CUT&RUN was performed to profile [H3K4me3 and  NFYA] binding sites in FACS-sorted cells from adult testis.

first: Martin

last: Säflund

first: Atiyeh

first: Mukhtar

first: Ann-Kristin Iréne

first: Tianxiong

first: Deniz


title: Compound-Induced Neuroplasticity Without Immediate Early Gene Activation

city: Davis

first: Ethan

last: Fenton

state: CA

address: 1544 Newton Court

department: Neuroscience

country: USA

institute: UC Davis

summary: Cortical atrophy and dysfunction are hallmarks of many neuropsychiatric diseases including depression, post-traumatic stress disorder (PTSD), and addiction. Psychoplastogens are small molecules with the potential to rapidly rescue these structural and functional deficits, leading to sustained therapeutic effects after a single administration. Classic psychedelics are among the most potent and efficacious psychoplastogens known, with recent data indicating that their clinical and preclinical effects might be more robust and durable than those of ketamine. Moreover, the advent of non-hallucinogenic psychoplastogens structurally related to psychedelics, such as tabernanthalog (TBG), has opened new opportunities for developing scalable alternatives capable of promoting structural and functional neuroplasticity in the prefrontal cortex (PFC). Currently, it is unclear what roles 5-HT2A receptors (5-HT2ARs) and immediate early gene activation play in the neuroplasticity-promoting effects of non-hallucinogenic psychoplastogens like TBG—information necessary to engineer optimized neurotherapeutics related to psychedelics. Here, we use a combination of pharmacological and genetic tools to demonstrate that several non-hallucinogenic psychoplastogens promote cortical neuron growth through the same biochemical pathway as classic psychedelics. Furthermore, we demonstrate that there is a causal relationship between TBG-induced cortical spinogenesis and its sustained antidepressant-like effects. In contrast to psychedelics, TBG promotes cortical neuron growth in the absence of a glutamate burst or immediate early gene (IEG) activation, effects assumed to be necessary for psychedelic-induced neuroplasticity. Our results elucidate how the hallucinogenic effects of psychedelics can be decoupled from their beneficial effects on cortical neuron growth.

overall_design: Mice were treated with i.p. drug (5-MeO-DMT, TBG, or VEH) and Prefrontal Cortex (PFC) was dissected 1 hour later and analyzed with snRNAseq.

first: Isak

middle: K

last: Aarrestad

first: Lindsay

middle: P

last: Cameron

first: Austen

middle: B

last: Casey

first: Daniel

middle: R

last: Rijsketic

first: Seona

middle: D

last: Patel

first: Rohini

last: Sambyal

first: Shane

last: Johnson

first: Calvin

last: Ly

first: Jayashri

last: Viswanathan

first: Eden

last: Barragan

first: Stephanie

middle: A

last: Lozano

first: Nicolas

last: Seban

first: Hongru

last: Hu

first: Noel

last: Powell

first: Milan

last: Chytil

first: Retsina

last: Meyer

first: David

last: Rose

first: Chris

last: Hempel

first: Eric

last: Olson

first: Hanne

last: Garling

first: Clara

last: Madsen

first: Gitte

last: Knudsen

first: Chase

last: Redd

first: Damian

last: Wheeler

first: Jessie

last: Muir

first: Gerald

last: Quon

first: Sunil

last: Gandhi

first: Kurt

last: Rasmussen

first: Conor

last: Liston

first: John

last: Gray

first: Boris

last: Heifets

first: Alex

middle: S

last: Nord

first: Christina

last: Kim

middle: E


title: Bioluminescence-activated proximity labeling for spatial multi-omics

city: Beijing

first: Ruixiang

last: Wang

address: No.5 Yiheyuan Road Haidian District

institute: Peking University

summary: Mapping the spatial organization of proteins and cellular interactions is crucial for understanding their biological functions. Herein, we report a biocompatible, multi-functional luminescence-activated proximity labeling (LAP) strategy for profiling subcellular proteomes and cell-cell interactions in live cells and animals. Our method capitalizes on fusing the photocatalyst miniSOG to NanoLuc luciferase, whose bioluminescence activates miniSOG via a resonance energy transfer mechanism, generating reactive oxygen species in situ to mediate proximity labeling. We achieved local transcriptome profiling by combining LAP with next-generation sequencing.

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Expression profiling by high throughput sequencing

first: Yuxin

last: Fang

first: Yanjun

last: Liu

first: Peng

last: Chen

last: Zou


title: A Retinoic Acid:YAP1 signaling axis controls atrial lineage commitment

city: La Jolla

first: Jingting

last: Yu

address: 10010 N Torrey Pines Rd

institute: Salk Institute for Biological Studies


city: Philadelphia

first: Naiara

last: Akizu

state: PA

address: 3501 Civic Center Blvd

department: Pathology And Lab Medicine

institute: Children's Hospital of Philadelphia

summary: Vitamin A/Retinoic Acid (RA) signaling is essential for heart development.  In cardiac progenitor cells (CPCs), RA signaling induces the expression of atrial lineage genes while repressing ventricular genes, thereby promoting the acquisition of an atrial cardiomyocyte cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (scRNAseq, scATACseq and ChIP-seq) to untreated and RA-treated human embryonic stem cells (hESCs)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP and TEAD4 are integrated with the atrial transcription factor enhancer network, and that YAP1 is necessary for activation of RA-enhancers in CPCs. Furthermore, scRNAseq analysis of control and conditionally YAP KO mouse E7.75 embryos (Sox2cre) revealed that the expression of atrial lineage genes such as NR2F2 is compromised by YAP deletion in the CPCs of the second heart field.  Accordingly, we found that YAP is required for the formation of an atrial chamber but is dispensable for the formation of a ventricle, in hESC-derived patterned cardiac organoids. Overall, our findings revealed that YAP1 is a non-canonical effector of RA signaling essential for the acquisition of atrial lineages during cardiogenesis.

overall_design: Single-cell RNA sequencing (scRNAseq) data were obtained from E7.75 mouse embryos, including cYAP KO (Sox2cre:Yapflox/flox) and control (Sox2cre:Yapflox/+).

first: Elizabeth

last: Abraham

first: Brett

last: Volmert

first: Thomas

last: Roule

first: Ling

last: Huang

first: April

last: Williams

first: Henry

last: Cohen

first: Aidan

last: Douglas

first: Emily

last: Megill

first: Eleonora

last: Stronati

first: Raquel

last: Fueyo

first: Mikel

last: Zubillaga

last: Elrod

first: Aitor

last: Aguirre

first: Conchi

last: Estaras


title: Improves Hepatic Differentiation from Induced Pluripotent Stem Cells by the Suppression of Epithelial-mesenchymal Transition [RNA-seq]

city: Hong Kong

first: yangyang

last: yuan

address: William MW Mong Block, 21 Sassoon Road, Pokfulam, Hong Kong SAR, China

country: Hong Kong

institute: The University of Hong Kong

summary:
Background: Induced pluripotent stem cells (iPSCs) induced hepatocytes (iHeps) are widely used in modeling human liver diseases and as a potential source for cell replacement therapy. However, most iHeps are relatively immature and hard to maintain for long-term in-vitro.
Results: The hepatic differentiation improved when EMT was inhibited at late stage of iHeps differentiation, and iHeps EMTi demonstrated the ability to be maintained in- vitro for an extended period up to Day 60. In-vitro analysis showed that iHeps EMTi exhibited significantly higher expression levels of hepatic functional markers, and enhanced hepatocyte functions, including lipid accumulation, glycogen storage, albumin secretion and urea acid metabolism. Moreover, the molecular profiles of iHeps EMTi are closer to those of primary human hepatocytes (PHHs). In addition, the in-vivo engraftment efficiency of iHeps EMTi was also improved as compared to iHeps alone.
Conclusion: We established a robust protocol via EMT suppression to generate iHeps from human iPSCs with improved function, long-term in-vitro maintenance capacity, and enhanced repopulation efficiency.

overall_design: We optimized the differentiation protocol by addition of a combination of small molecules to inhibit iHeps from epithelial-mesenchymal transition (EMT, iHeps EMTi), and further characterized their function both by in-vitro and in-vivo analysis.

last: Li

first: Rui

last: Wei

first: Yangyang

last: Yuan


title: Regulation of autophagy by Rab27B in colorectal cancer

city: Lawrence

first: Dan

last: Dixon

state: Kansas

address: 1200 Sunnyside Ave

department: Molecular Biosciences

institute: University of Kansas

summary: Autophagy is a cellular recycling process that can promote tumor growth, anti-tumor immune response, and resistance to therapy in colorectal cancer (CRC). Here, we show that small GTPase Rab27B, a known regulator of vesicle trafficking and extracellular vesicle secretion, to control the autophagy process in CRC. Depletion of Rab27B in CRC cells showed an abnormal accumulation of autophagy vesicles and increased autophagy markers, indicating a defect in autophagy flux. Imaging analysis indicated that autophagy flux is blocked at the autophagosome/lysosome fusion step when Rab27B is lost. Loss of Rab27B significantly impacted CRC cell growth in both in vitro 3D growth and in vivo tumorigenesis studies. Together, these results demonstrate a new role of Rab27B in the autophagy trafficking process in CRC and identify Rab27B as a potential therapeutic target for CRC.

overall_design:
To investigate the effects of Rab27B silencing in colorectal cancer, Rab27B was deleted by CRISPR/Cas9 in CRC cell line HCT116
Three biological replicates were analyzed for each of 2 genotypes (HCT116 wt and Rab27B KO)

first: Sahida

last: Afroz

first: Ranjan

last: Preet

first: Vikalp

last: Vishwakarma

first: Andrew

last: Evans


title: Circular RNA expression profile from murine ocular tissues

city: shantou

first: xiaoqiang

last: xiao

state: Guangdong

address: North dongxia road

institute: Joint Shantou International Eye Center,Shantou University and the Chinese University of Hong Kong

summary: Investigating the differential expression profile of circular RNA  in ocular tissues derived from  VLDLR deletion and Wild type mouse with t 75% oxygen treatment(postnatal day 7 to postnatal day 12)

overall_design: Mice with VLDLR deletion or wild type control were treated with 75% oxygen for five days (postnatal day 7 to 12) and then feed those treated mice into air taken out the ocular tissues immediately after high oxygen treatment(P12) or at the day after P12(P13), The ocular tissues were then used for total RNA extraction with TRIZol reagent .And those total RNAs samples further treated with Dnase 1 and used for high-through put circRNA sequencing

first: Xiaoqiang

last: Xiao


title: Transcriptomic analysis of the diethylnitrosamine (DEN)-induced HCC mRNA from Pck1 KO and WT mice

city: Chongqing

first: rui

last: Liu

address: No. 1 Medical College Road, Yuzhong District

institute: CHONGQING MEDICAL UNIVERSITY

summary: To investigate the role of hepatic Pck1 in the diethylnitrosamine (DEN)-induced HCC, a Pck1 knockout mouse in the liver was developed with Alb-Cre.HCC was induced in mice by combined treatment with DEN (75 mg/kg) and CCl4 (2 mL/ kg, twice per week for 12 weeks).At 32 weeks, the mice were sacrificed after fasting for 12 hours, and liver tissues with tumors were collected for examination. RNA was extracted from the livers of mice from all treatment groups and used for RNA seqencing. RNAseq data demonstrated that a lack of Pck1  can play an important role in the development of HCC.

overall_design: Use RNA-sequencing to investigate the role of Pck1 inthe diethylnitrosamine (DEN)-induced HCC on a transcriptomic level, by comparing the HCC of WT and Pck1-null mice  using Illumina technology.

first: W

last: Kai

first: T

last: Ni


title: ‘B1-like’ innate B cells present within adult human organs

status: Public on May 09 2025

city: Cambridge

first: Ondrej

last: Suchanek

address: Francis Crick Avenue

department: Department of Medicine, Molecular Immunity Unit

country: United Kingdom

institute: University of Cambridge

summary: Innate-like B cells produce natural antibodies, and include marginal-zone (MZ) B cells and B1 cells.  B1 cells have been well-studied in mice where they are pre-natally seeded into serous cavities, and are an important source of regulatory cytokines. A recent cell atlas study described putative ‘B1’ cells in human prenatal organs, but whether these cells persist in adult humans is unclear. Here, we identified ‘B1-like’ cells in the IgM+/IgA+ memory compartment in multiple human organs including kidney, lung and spleen. These cells were transcriptionally similar to murine B1 cells and human prenatal ‘B1’ cells, but distinct from MZ B cells. These adult human ‘B1-like’ cells expressed several canonical murine B1 cell markers, including AHNAK and BHLHE41. B-cell receptor (BCR) sequencing of paired human kidney and spleen samples showed IgM/IgA clones among adult kidney BCRs with a lower diversity and mutation rate than splenic cells, suggesting seeding independent of splenic B cells. Functionally, adult ‘B1-like’ cells expressed the regulatory cytokine TGF-beta, and had the highest number of inferred interactions with tissue myeloid cells, with macrophages in turn expressing B cell pro-survival cytokines. Altogether, our study provides evidence of ‘B1-like’ cells in homeostatic adult human organs.

overall_design: Flushed adult human kidneys (n=5) retrieved for transplantation but deemed unsuitable for implantation (e.g., for anatomical reasons) together with matched spleen tissue were promptly homogenized into single cell suspensions. Live single CD45+CD19+ cells were subsequently FACS-sorted from these suspensions and subjected to bulk BCR sequencing to assess BCR repertoire differences between both organs at steady state.

first: Menna

last: Clatworthy


title: Haploid genome activation exposes genes with a specific chromatin signature for pollen selection

city: wuhan

first: zhu

last: bo

state: beijing

address: shi zi shan street

department: National Key Laboratory of Crop Genetic Improvement

institute: Huazhong Agricultural University

type: Methylation profiling by high throughput sequencing

summary: Here, we obtained datasets of single cell and/or cell type transcriptomes and epigenomes of the rice male germ line isolated at the different developmental stages from hybrid and/or inbred varieties. Analysis of the data pinpoints to a premeiotic set-up of a chromatin state to instruct male germ cell-type specific gene expression during the gametogenesis, reveals that the male haploid genome activation occurs shortly after meiosis, and uncovers a specific chromatin signature for haploid gene expression which has implication in haploid and pollen selection.

sample_organism:
Oryza sativa Indica Group
Oryza sativa Japonica Group

overall_design: Germ cells were obtained by micromanipulation. DNA methylation and transcriptome libraries were constructed by scBS-seq and scRNA-seq techniques. Histone modification library was constructed using CUT&Tag technology.

first: Bo

last: Zhu

first: Feng

last: zhao


title: Mu transposon insertion sites in matched leaf and endosperm samples from Mu-active W22 maize

city: Athens

first: Brad

last: Nelms

state: GA

address: 120 E Green St

institute: University of Georgia

summary: Mu transposon insertions were sequenced in the parents and offspring from 4 maize families using MuSeq2. Male parents were Mu-active while female parents were Mu-inactive, and so all new transposon activity can be associated with the male parent. Matched endosperm and leaf from each offspring were sequenced, allowing inherited insertions to be unambiguously identified as these tissues diverge prior to fertilization (each is derived from a sister sperm cell in pollen during double fertilziation). The data were analyzed to follow the transmission of de novo Mu insertions from parent to offspring.

overall_design: Matched endosperm and leaf tissues were collected from Mu-active plants. Endosperm samples were first obtained by seed chipping; then the chipped seed was grown to collect V2 seedling leaves. Plants were Mu-active, generated by crossing a Mu-active male parent to a Mu-inactive female parent, both of the W22 maize inbred background

first: Justin

last: Scherer


title: MVD

city: New Haven

first: Fu

last: Gao

state: CT

address: 55 Prospect Street

institute: Yale University

summary: MVD for scRNAseq

overall_design: Single cell RNA sequence


title: DsbA-L deficiency attenuates LPS-induced acute kidney injury via NF-κB/AP-1 regulation of macrophage polarization

city: Nanning

first: Pengcheng

last: Cui

address: Da-Xue-Dong Road No.100

institute: Guangxi University

summary: Background: Disulfide bond A oxidoreductase-like protein (DsbA-L) drives acute kidney injury (AKI) progression in proximal tubular cells by directly upregulating voltage-dependent anion-selective channel levels; however, its role in immune cells remains unclear.  Methods: We used the mouse model of AKI induced by LPS to explore the mechanism of how DsbA-L deficiency regulating macrophages and kidney injury under the guidance of transcriptome and metabolic.  Results: DsbA-L knockout resulted in significant changes in the JNK pathway, which might affect macrophage polarization to reduced AKI injury based on the cellular and stimulus-dependent characteristics of JNK function

overall_design: The mice were divided into four groups: naïve-WT, naïve-DsbA-L-/-, LPS-WT and LPS-DsbA-L-/- (n = 3-6 mice in each group). Each mouse in the naïve and experimental groups was intraperitoneally injected with 200 µL saline and 10 mg/kg LPS (Sigma-Aldrich, USA, L2630), respectively.

first: Chao

last: Chen

first: Yan

first: Xia

last: Qiu

first: Kaiye

last: Yue

first: Tengfang

last: Li

first: Hedong

last: Zhang

first: Wenjia

last: Yuan

first: Yixin

last: Xie

first: Yong

last: Guo

first: Zhouqi

last: Tang

first: Yaguang

first: Xin

last: Jiang

first: Xuewei

last: Luo

first: Helong

last: Dai


title: Characterization of gene expression in epididymal white adipose tissue of mice fed a normal or high-fat diet.

city: Tokushima-city

first: Masashi

last: Kuroda

state: Tokushima

address: 3-18-15, Kuramoto-cho

institute: Tokushima University

summary: C57BL/6 male mice were started on a high-fat diet (60% fat) at 9 weeks of age. Seven weeks after the start of the high-fat diet (16 weeks of age), epididymal white adipose tissue was collected and total RNA was isolated by Trizol reagent. Thereby, we tried to measure Gene expression signatures affected by high fat feeding in epididymal white adipose tissue.

overall_design:
There are two feeding conditions (normal chow and high-fat diet), and one sample for each.
*** Submitter states that missing raw files are due to file loss ***

first: M


title: Brg1 defect causes aberrent nucleosome landscape and affects totipotency & pluripotency transcriptional factors binding during embryogenesis

city: Shanghai

first: Xinyu

last: Wang

address: Siping Road 1239

institute: Tongji University

summary: Mammalian embryogenesis involves intricate epigenetic reprogramming and chromatin remodeling. In this study, we investigated the role of Brg1, a catalytic ATPase subunit of the SWI/SNF complex, in early embryonic development and mouse embryonic stem cell (mESC) pluripotency. By generating Smarca4 flox/flox Gdf9-Cre female mice to knockout Brg1 in MII oocytes and using CRISPR-Cas9 to knockout Brg1 in mESCs, we found that Brg1 deficiency led to multiple defects. In mouse embryos, maternal knockout of Brg1 caused reduced blastocyst formation, delayed development, elevated nucleosome occupancy at gene promoters, and dysregulation of zygotic genome activation (ZGA) genes, potentially due to disrupted binding of totipotency-related transcription factors (TFs). In mESCs, Brg1 knockout resulted in abnormal clone morphology, decreased pluripotency marker expression, and reduced cell proliferation. Brg1 affected pluripotency mainly by influencing the binding of pluripotency-related TFs such as Oct4 through enhancer accessibility. We identified those TFs as totipotency/pluripotency Brg1-dependent TFs. Overall, this study demonstrates the crucial role of Brg1 in ZGA and mESC identity maintenance in affecting specific TF binding on proximal and distal regulatory elements.

overall_design: RNA-seq, ULI-MNase-seq and ATAC-seq of mouse embryo and ESC.To get MII oocytes for ICSI, B6D2F1 or Smarca4flox/flox Gdf9 Cre C57BL/6 female mice (8–12-weeks old) were superovulated by injection with 7 IU each of pregnant mare serum gonadotropin (PMSG), followed by injection of 5 IU of human chorionic gonadotropin (hCG) (San-Sheng Pharmaceutical) 48 h later. Brg1 knockout R1 ES cell lines are generated by CRISPR-Cas9 technology targeting the exon 4 & 5 of Smarca4.

first: Qi

last: Shi

first: Chong

first: Shaorong

first: Xiaoyu

last: Liu


title: miRNA-1229-5p promotes the migration and invasion of endometrial cells by regulating STMN1/EMT in ovarian endometriosis

city: shijiazhuang

first: LuSha

address: 12 Jiankang Road

department: Deportment of Gynecology

institute: The Fourth hospital of hebei medical research

summary: Emerging evidence suggests that aberrantly expressed microRNAs (miRNAs) participate in endometriosis pathogenesis. Our previous miRNA microarray analysis revealed dysregulated expression of miR-1229-5p in eutopic endometrial stromal cells (ESCs) from ovarian endometriosis patients compared with healthy controls. However, the role and mechanism of miR-1229-5p in EMs remain unclear.

overall_design: miR-1229-5p mimics and its negrative control mimics-NC were transfected into the Ishikawa cells to detect the change of downstream target genes.

first: Lusha

first: Lixian

last: Hao

first: Naiyi

last: Du


title: Spatial and Single-cell Transcriptomic Characterization of WIF1-induced Normal-tension Glaucoma [Visium]

city: Shatin, NT

first: CHUHAN

last: LI

state: shatin

address: The Chinese University of Hong Kong, Central Ave

institute: CUHK

summary: To explore the potential roles of WIF1 upregulation in glaucoma pathogenesis, we performed WIF1 overexpression in mouse retina via AAV delivery and then assessed its impact on IOP, retinal visual function, and RGC survival. We found it causes visual function defects and RGC loss, especially the RGCs from periphery retina. Our integrative analyses from single cell RNA-seq, ATAC-seq, and spatial transcriptomics have further uncovered the dynamic signaling changes from various retinal cells to RGCs. And our spatial transcriptomics results have also revealed the various changes of central and peripheral RGCs after WIF1 overexpression.

overall_design: Two different AAV2/2 were generated for Wif1 overexpressing, CMV-Wif1-HA-IRES-GFP, and CMV-Wif1-HA, whereas the AAV carrying CMV-IRES-GFP was used as a control in this study. To further investigate the mechanism underlying the WIF1-mediated glaucoma, we established the single-cell (sc) omics blueprint of the WIF1-overexpressing retina. We harvested fresh retinas from six mouse eyes, two from the wild-type control group (Ctrl), two at 2 weeks AVI (WIF1-2w), and two at 4 weeks AVI (WIF1-4w), to isolate single nuclei for simultaneous scRNA-seq and scATAC-seq using the 10x Genomics Chromium. And we also performed 10x Visium spatial transcriptomics (ST) on the Ctrl, WIF1-2w, and WIF1-4w retinas on order to gain new insights into the spatial communication between RGCs and other cell populations in the WIF1-overexpressing retina. Then integrated analysis was performed to visualize the temporal spatial cell composition changes, TCF4, WNT signaling pathway regulator, mediated target gene activity changes, cell-cell interaction changes and center vs periphery RGC changes after WIF1 overexpression.

first: Ting

first: Qinqin

last: Deng

first: Chuhan


title: Effects of hyperbaric oxygen on tissue-specific aging and senescence in mice and human stromal cells

first: Qiaoyu

last: Fu

address: 639 Zhizaoju Road

department: Depart of Plastic & Reconstructive Surgery

institute: Shanghai 9th People’s Hospital  School of Medicine  Shanghai Jiao Tong University

summary: This study investigates the effects of hyperbaric oxygen (HBO) on cellular senescence and aging-related phenotypes. In naturally aged mice, HBO treatment reduced systemic senescence burden and reversed aging-related transcriptomic signatures in skin, liver, and kidney tissues. Additionally, single-session HBO exposure was shown to preferentially suppress SASP propagation in human stromal cells. This dataset includes transcriptomic profiles of skin, liver, and kidney tissues from young, aged, and HBO-treated aged mice, as well as human primary prostate stromal cells (PSC27).

overall_design: Total RNA was extracted from frozen tissues or cultured cells. Transcriptomic profiles were generated using the Illumina platform. For mouse tissues, RNA was extracted from skin, kidney, and liver tissues of young (2 months), aged (21 months), and HBO-treated aged mice (21 months). For HBO treatment, aged male mice were exposed to 2.0 ATA HBO for one month. Sham-treated aged mice and 2-month-old young mice served as controls. For cultured cells, RNA was extracted from bleomycin-induced senescent human primary prostate stromal cells with or without single-session 2.0 ATA HBO, with proliferative cells serving as controls.


title: Nano-immunomodulation of the Aβ-STING feedback machinery in microglia for Alzheimer’s disease treatment

city: NanJing

first: Limin

last: Tian

address: Longmian Avenue, Jiangning District

institute: China Pharmaceutical University

summary: Imbalanced production and clearance of amyloid-β (Aβ) is a hallmark pathological feature of Alzheimer’s disease (AD). While several monoclonal antibodies targeting Aβ have shown reductions in amyloid burden, their impact on cognitive function remains controversial, with the added risk of inflammatory side effects. Dysregulated stimulator of interferon genes (STING) signaling is implicated in neurodegenerative disorders, yet the biological interaction between this pathway and Aβ, as well as their combined influence on AD progression, is poorly understood. Here we show that while microglia play a protective role in clearing extracellular Aβ, excessive Aβ engulfment triggers the cytosolic leakage of mitochondrial DNA for cGAS-STING cascade. This creates a negative feedback loop that not only exacerbates neuroinflammation but also impairs further Aβ clearance. To address this, we present a nanomedicine approach termed “Aβ-STING Synergistic ImmunoSilencing Therapy (ASSIST)”. ASSIST comprises STING inhibitors encapsulated within a blood-brain barrier (BBB)-permeable polymeric micelle that also serves as an Aβ scavenger. Through a multivalent mechanism, ASSIST efficiently destabilizes Aβ plaques and prevents monomer aggregation, subsequently promoting the engulfment of the dissociated Aβ by microglia rather than neurocytes. Furthermore, the STING signaling induced by excessive Aβ uptake is blocked, reducing inflammation and restoring microglial homeostatic functions involved in Aβ clearance. Intravenous administration of ASSIST significantly reduces Aβ burden and improves cognition in AD mice, with minimal cerebral amyloid angiopathy or microhemorrhages. We provide a proof-of-concept nanoengineering strategy to target the maladaptive immune feedback loop arising from conventional immunotherapy for AD treatment.

overall_design: A is the control, the administration is Saline, Z is the administration group, the administration of ASSIST, H is the administration group, the administration of H151-NP, and the mice in the above three groups are all 5xFAD mice

first: Guangyu

last: Long

first: Siqi

last: Zhu

first: Yuelong

first: Pengcheng

last: Xu

first: Lifeng

first: Hong

last: Yao

first: Shentong

last: Fang

first: Shuqing

last: Chen

first: Suxin

last: Li


title: Model-to-crop conserved NUE Regulons enhance machine learning predictions of nitrogen use efficiency

city: New York

first: Ji

last: Huang

state: NY

address: 12 Waverly Place

department: Center for Genomics & Systems Biology

institute: New York University

summary: In this data-rich era, the promise of systems biology is to learn gene regulatory networks controlling key agricultural traits. However, validating these networks in crops remains challenging. By integrating gene regulatory network and machine learning, we functionally validated network regulons predicting nitrogen use efficiency (NUE) in Arabidopsis and maize. Our time-course nitrogen response transcriptome analysis uncovered a conserved N-response cascade between maize and Arabidopsis. Using Dynamic Factor Graph, we inferred N-regulated gene regulatory networks (N-GRNs) in maize and validated TF-target interactions for 23 maize TFs with the TARGET, a cell-based TF-perturbation assay. We pruned the N-GRNs by Precision-Recall analysis. Combining these data, we uncovered a previously unknown role for KNOTTED1 in the dynamic N-signaling network. We learned gene-to-NUE trait models across 16 maize varieties using XGBoost trained on N-response genes conserved model-to-crop. Integrating NUE importance scores within our GRN, we ranked maize TFs by their NUENet scores. In a model-to-crop approach, we validated orthologous N-regulated TF-targets for the top-ranked maize NUENet TFs (MYB34/R424 targets) and the orthologous Arabidopsis TF (AtDIV123 targets) using the cell-based TARGET assay. The genes in this orthologous model-to-crop NUENet regulons were superior at predicting NUE traits in XGBoost models learned in both maize and Arabidopsis. Thus, our model-to-crop approach combining GRNs, machine learning, and orthologous network modules offers a strategic framework for crop trait improvement.

overall_design: We conducted ChIP-Seq on KN1 tagged with a small biotin ligase recognition peptide (BLRP) overexpressed in maize protoplasts.

first: Chia-Yi

last: Cheng

first: Gloria

last: Coruzzi


overall_design: We performed TARGET (Transient Assay Reporting Genome-wide Effects of Transcription factors) assay for 23 TFs in maize seedling leaf protoplasts.


overall_design: We conducted the fine time-course nitrogen treatement experiment in maize B73 seedlings.On the day of the sampling (day ten), two hours after the start of the light period (10 am), seedlings were transferred to the fresh hydroponic medium containing either the Nitrogen in MS medium (20 mM KNO3 + 20 mM NH4NO3) or 20 mM KCl and harvested at time intervals 0, 5, 10, 15, 20, 30, 45, 60, 90, and 120 minutes.


title: Comparative characterization of AHC associated mutations in ATP1A3 reveals diverse neurological alterations in mice.

first: Scott

middle: Ian

last: Adamson

state: New York

address: 101 6th Ave

institute: New York Genome Center

summary: Pathogenic variants the neuronal Na+/K+ ATPase transmembrane ion transporter (ATP1A3) cause a spectrum of neurological disorders including alternating hemiplegia of childhood (AHC). The most common pathogenic variants in AHC are the p.D801N (~40%) and p.E815K (~25%) variant, which lead to spontaneous death with early mortality in mice. Nevertheless, the characterization and knowledge on the development of clinically relevant neurological phenotypes without the induction of premature death, is critical for the identification of pathophysiological mechanisms and ultimately, testing of therapeutic strategies in disease models. Here, we used hybrid vigor attempting to mitigate the fragility of AHC mice and then, combined behavioral, electrophysiological, biochemical, and molecular testing to comparatively analyze mice that carry the most common patient observed p.D801N and p.E815K variant in the Atp1a3 gene. Collectively, our data reveal the presence but also the differential impact of the p.D801N and p.E815K variant on disease relevant alterations such as spontaneous and stress-induced paroxysmal episodes, motor function, behavioral and neurophysiological activity, and neuroinflammation. Our alternate AHC mouse models and their phenotypic deficits open novel avenues for the investigation of disease biology and therapeutic testing for ATP1A3 research.

overall_design: This study contains 48 RNA-seq samples. These samples were made from RNA harvested from brainstem (BS), cerebella (CM), cortex (CX), or hippocampus (HP) of mice with one of the following genotypes: B6C3.Atp1a3 D801N/+, B6C3.Atp1a3 E815K/+, and B6C3.Atp1a3 +/+ referred to as D801N, E815K, and WT respectively. Samples are derived from 2 male and 2 female mice per condition (tissue-genotype pair).

first: Markus

last: Terrey

first: Georgii

last: Krivoshein

middle: I

first: Elena

last: Aristarkhova

first: Laura

last: Anderson

first: Sara

last: Perkins

first: John

last: Szwec

first: Shelby

last: McKee

first: Holly

last: Jones

first: Pierre-Alexandre

last: Piec

first: Vijay

last: Selvam

first: Dweet

last: Chhaya

first: Ari

last: Dehn

last: Savage

first: Natalie

last: Morsci

first: Kathleen

last: Sweadner

first: David

last: Knowles

first: Arn

last: van den Maagdenberg

first: Stephen

last: Murray

first: Cathleen

last: Lutz


title: Spatial and Single-cell Transcriptomic Characterization of WIF1-induced Normal-tension Glaucoma [Single Cell Multiome ATAC + Gene Expression]

first: CHUHAN

last: LI

first: Ting

last: Xie

first: Qinqin

last: Deng

first: Chuhan

last: Li


title: A novel role of CDK2 inhibition in restraining microglial overactivation

city: Beijing

first: Lu

last: Shi

address: Shuangqing road

department: School of Pharmaceutical Sciences

institute: Tsinghua University

summary: Intrinsic immune checkpoints in microglia are vital for maintaining homeostatic immune response and preventing overactivation. Neuroinflammation, frequently driven by microglial overactivation, significantly influences a wide range of neurological disorders. While MEF2C has been associated with a syndromic form of autism spectrum disorder (ASD) and various other neurological disorders in humans, its specific role as an immune checkpoint remains poorly defined. By harnessing MEF2C-knockout (KO) induced microglia-like cells (iMGLs) through differentiation from human pluripotent stem cells (hPSCs), here we observed that these cells, following LPS stimulation, exhibited overactivation similar to patterns seen in various neurological disorders. High-throughput screening identified BMS265246, a CDK2 inhibitor, as effective in specifically suppressing the overactivated phenotypes of MEF2C-KO iMGLs, and in restoring inflammatory response closer to normal levels. Mechanistically, we uncovered that MEF2C regulates p21 transcription, a critical step in preventing CDK2 activation in microglia. Loss of MEF2C results in CDK2-induced RB phosphorylation and degradation, leading to enhanced NF-κB p65 subunit nuclear translocation and exacerbated inflammatory responses. Remarkably, BMS265246 treatment rectified microglial overactivation and ASD-like behaviors in both global and microglia-specific Mef2C heterozygous knockout mice. Overall, our findings elucidated a previously unknown immune checkpoint mechanism governed by MEF2C, and highlighted CDK2 as a potential key factor driving neuroinflammation through microglial overactivation. These insights positions CDK2 as a promising therapeutic target for treating various neurological diseases influenced by overactivated microglia.

overall_design: mRNA profiles of WT and MEF2C-/- (KO) iMGLs, treated with or without 5 μM BMS, in the presence or absence of 100 ng/mL LPS for 12 hours, were generated through the Illumina Novaseq 6000 platform with 150 bp paired-ends.

first: Xiaodan

last: Hu

first: Tianhua

last: Ma

first: Sheng

last: Ding


title: SM22α-lineage stromal cells in perivascular adipose tissue contribute to abdominal aortic aneurysm

first: Xiaoxi

last: Pan

address: 197 Ruijin 2nd Road, Shanghai, China

institute: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine

summary: Background: Perivascular adipose tissue (PVAT) is a key regulator of vascular dysfunction. Impairment of PVAT phenotypic plasticity with aging may play a role in vascular pathology including abdominal aortic aneurysms (AAA). Yet, the mechanisms underlying PVAT plasticity in aneurysm pathogenesis remain elusive. Methods: Single-cell RNA sequencing (scRNA-seq) was performed on perivascular stromal cells (PVSCs) from young (2-3-month-old) and aged (18-20-month-old) mice. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) was measured in PVAT of aged mice and human aneurysm samples. Loss- and gain-of-function approaches were employed to investigate the role of SM22α-lineage PVSCs-derived PGC-1α in aneurysm development. Molecular mechanisms were explored through transcriptome and functional studies in young and aged mice, SM22αCre; Rosa26RFP/+; PGC1αf/f and SM22αCre; Rosa26RFP/+ mice with angiotensin II (AngII)- and DOCA/salt- induced AAA models. Results: SM22α+ cells accumulated in PVAT of angiotensin II-treated aged mice and patients with aortic aneurysms. scRNA-seq analysis revealed that aging disrupted the differentiation potential of SM22α-lineage PVSCs and led to reduced PGC-1α level. PGC1α downregulation in PVAT was observed in both mice AAA models and human aneurysm lesions. In mice with SM22α-driven PGC-1α-deletion AngII induced AAA formation was accompanied by PVSC-to-myofibroblast differentiation. in vitro PGC1α-knockdown suppressed nuclear YAP signaling, reducing adipocyte differentiation, while increasing MMP2-secreting myofibroblasts. Furthermore, PGC-1α overexpression in aged mice or administration of the YAP signaling inhibitor Verteporfin in SM22αCre; Rosa26RFP/+; PGC1αf/f mice restored PVAT function and conferred protection against aneurysm formation. Lastly, we employed the radiomics analysis to non-invasively evaluate PVAT in the context of AAA severity in humans. Conclusions: PGC-1α deficiency in SM22α-lineage stromal cells disrupts the balance between adipogenic and myofibrogenic differentiation through regulating the YAP signaling, ultimately promoting aneurysm development. Radiomics assessment may present a promising noninvasive approach for PVAT evaluation in aneurysms, offering valuable potential for clinical research.

overall_design: Perivascular stromal cells were isolated from pervascular adipose tissue of young and old mice and analyzed using scRNA-seq.

first: Run

last: Zhang

first: Bingling

last: Lu

first: Siyuan

last: Chen

first: Hongjin

first: Mengyao

first: Le

last: Qin

first: Zhiyun

last: Song

first: Yi

last: Yang

first: Zhe

last: Wang

first: Fuhua

last: Yan

first: Aijun

last: Sun

first: Fang

last: Wu

first: Lichi

first: Jiguang

first: Tomasz

last: Guzik

first: Pingjin

last: Gao


first: Ji

last: Huang

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

sample_organism:
Arabidopsis thaliana
Zea mays

platform_organism:
Arabidopsis thaliana
Zea mays

overall_design: Refer to individual Series


title: Selpercatinib mitigates cancer cachexia independent of anti-tumor activity

city: Oklahoma City

first: Jie

state: OK

address: 975 NE 10th Street

department: Stephenson Cancer Center

institute: University of Oklahoma Health Sciences Center

summary: We determine whether the RET protein tyrosine kinase inhibitor selpercatinib alleviates skeletal muscle atrophy in the HT1080 tumor model in mice.

overall_design: RNA-seq was performed (4 biological replicates/each) on gastrocnemius from 3 groups of mice. Group NTV is tumor-free mice treated with vehicle, group TV is HT1080 tumor-bearing mice treated with vehicle, group TL is HT1080 tumor-bearing mice treated with selpercatinib (30 mg/kg/day for for 19 days).


overall_design: We performed TARGET (Transient AssayReporting Genome-wide Effects of Transcription factors) assay for DIV1 in Arabidopsis leaf.

first: Nathan

last: Doner

first: Gloria

last: Coruzzi


title: Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [scRNA-Seq]

first: Rachel

last: Duffié

address: Jerome L Greene Sciene Building

department: Biochemistry and Molecular Biophysics

institute: Columbia University

summary: Singular olfactory receptor (OR) expression is critical for vertebrate olfaction because the sequence of the chosen OR protein determines both the receptive field and axon guidance properties of each olfactory sensory neuron (OSN). However, numerous single cell RNA-seq studies reveal that OSN progenitors co-transcribe seemingly random combinations of OR genes before a gradual transition to transcriptional singularity. Here, we show that MEX3A, a RING and KH domain protein expressed during polygenic OR transcription, prevents efficient OR protein expression before the emergence of a prevalent, transcriptionally dominant OR allele. Consequently, MEX3A deletion enhances OR mRNA and OR protein abundance in OSN progenitors, resulting in premature induction of Perk signaling, biased OR gene choice, and OSN axon mistargeting. Our experiments uncover a novel, post-transcriptional mechanism of OR gene regulation that assures that the identity of the expressed OR can influence the identity of the OSN only at the onset of singular OR choice.

overall_design: scRNA-Seq from whole or zonally microdissected olfactory epithelium from Mex3a cKO mice and WT littermate controls

first: Stavros

last: Lomvardas


title: Cellular senescence in skeletal muscle aging: new mechanisms and therapeutic potential for sarcopenia [cut&run_seq_MuSC]

first: CHUHAN

last: LI

summary: Skeletal muscle allows voluntary movement and plays a key role in regulating metabolism and homeostasis in the organism. Adult muscle stem cells, MuSCs, are responsible for muscle growth and regeneration. Skeletal muscle suffers from sarcopenia (muscle mass and function loss) during the aging process. Burgeoning evidence suggests that cellular senescence drives MuSC dysfunction in muscle aging. Activation of senescence-associated secretory phenotype (SASP) factors, which is one of the hallmarks of senescence, may be a driving mechanism of sarcopenia but no study so far has clearly defined cellular senescence atlas and SASP components in aging human muscles. Here in this study we propose to profile aging and senescence atlases in aging muscles using the state-of-art multiomics approaches.  Our pilot results demonstrate the prevalence of cellular senescence and the dynamics/heterogeneity of SASPs in aging human muscle. Furthermore, regulators governing senescence state and SASP induction were defined. Moreover, we demonstrated the potential of senotherapeutic targeting for sarcopenia treatment. In the project we propose (1) To complete single cell multiomics mapping of aging muscle atlas.  (2) To further elucidate cellular senescence in aging muscle. (3) To investigate JUNB regulation of MuSC SASP induction in aging muscle. (4) To test the potential use of senotherapeutics on aging muscle. Once completed, findings from this study will uncover novel knowledge of how MuSC senescence is involved in niche alteration and muscle aging through SASPs and demonstrate the possibility of developing senotherapeutics for treating sarcopenia.

overall_design: JunB CUT&RUN-seq was performed with freshly isolated muscle stem cells from DMSO and MVC treated mice; H3K27ac CUT&RUN-seq was performed with freshly isolated muscle stem cells

first: Huating

first: Yang

last: Li

first: Chuhan


title: Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [RNA-Seq]

overall_design: RNA-Seq from FAC sorted cell populations in the Main Olfactory Epithelium (MOE), including 1) WT cells along the neuronal differentiation trajectory, 2) from mice expressing transgenes of Mex3a and 3) with a conditional deletion of Mex3a (Foxg1iresCre driver)


title: Cellular senescence in skeletal muscle aging: new mechanisms and therapeutic potential for sarcopenia [cut&run_seq_IMR90]

overall_design: JUNB CUT&RUN-seq was performed with untreated (Ctrl) and Etoposide-treated (ETO) IMR-90 cell line


title: Cellular senescence in skeletal muscle aging: new mechanisms and therapeutic potential for sarcopenia [RNA-seq]

overall_design: Bulk RNA-seq was performed with freshly isolated muscle stem cells from DMSO and MVC treated mice


title: Mex3a-dependent post-transcriptional silencing assures olfactory receptor diversity and axon guidance specificity [Ribo-Seq]

overall_design: Ribosome-profiling Sequencing from FAC sorted cell populations in the Main Olfactory Epithelium (MOE) that carry the Ngn1 GFP transgene or the OMP-ires-GFP knock-in allele with a conditional deletion of Mex3a (Foxg1iresCre driver) or without the Cre driver for controls


title: Cellular senescence in skeletal muscle aging: new mechanisms and therapeutic potential for sarcopenia

overall_design: scRNA-seq was performed with muscle mononuclear cells isolated form DMSO and MVC treated mice


title: Cellular senescence in skeletal muscle aging: new mechanisms and therapeutic potential for sarcopenia [snMultiome_ATAC+GEX]

overall_design: snRNA and snATAC were performed with young/aged human muscle monoclear cells, base on the 10x snMultiome platform


title: TimeLapse-seq after amino acid starvation in Mettl3 knockout MEF

first: Samie

last: Jaffrey

address: 1300 York Ave

department: Pharmacology

institute: Weill Cornell Medicine

summary: Degradation of mRNA containing N6-methyladenosine (m6A) is essential for cell growth, differentiation, and stress responses. Here, we show that m6A markedly alters ribosome dynamics and that these alterations mediate the degradation effect of m6A on mRNA. We find that m6A is a potent inducer of ribosome stalling, and these stalls lead to ribosome collisions that form a unique conformation unlike those seen in other contexts. We find that the degree of ribosome stalling correlates with m6A-mediated mRNA degradation, and increasing the persistence of collided ribosomes correlates with enhanced m6A-mediated mRNA degradation. Ribosome stalling and collision at m6A is followed by recruitment of YTHDF m6A reader proteins to promote mRNA degradation. We show that mechanisms that reduce ribosome stalling and collisions, such as translation suppression during stress, stabilize m6A-mRNAs and increase their abundance, enabling stress responses. Overall, our study reveals the ribosome as the initial m6A sensor for beginning m6A-mRNA degradation.

overall_design: TimeLap-seq was performed as previously described.  Briefly, cells were grown to 80% confluency.  Cells were washed with PBS for three times, and then incubated in amino acid replete or amino acid-depleted media for 3 h with 500 µM 4-thiouridine (4sU, SigmaAldrich, T4509).  After 3 h, total RNA was collected using Qiagen RNeasy Mini kit RLT buffer (Qiagen, 74104) supplemented with 1% 𝛽-mercaptoethanol (BME).  Cells were lysed by passing through a 22-gauge needle, and RNA was isolated following the manufacturer’s instruction with RPE buffer supplemented with 1% BME.  10 µg total RNA was treated with 2,2,2-trifluoroethylamine (TFEE) and sodium periodate (NaIO4) at 45 °C for 1 h to convert 4sU to N4-trifluoroethylcytosine.  RNA was then purified twice using RNAClean beads (Beckman Coulter, A63987). 1 µg of treated RNA was used for RNA-seq library preparation using NEBNext®rRNA Depletion Kit(NEB, E6310X) and NEBNext®Ultra™II Directional RNA Library Prep Kit (NEB, E7760L).  Library quality was assessed on Agilent TapeStation4200 using High Sensitivity DNA ScreenTape (Agilent, 5067-5584).  Library was quantified on Qubit4 Fluorometer using Qubit 1X dsDNA HS Assay Kit (ThermoFisher, Q33231).  Libraries were sequenced with pair-end 2x100 cycles on Illumina NovaSeq 6000.

first: Shino

last: Murakami


title: m6A alters ribosome dynamics to initiate mRNA degradation


title: m6A is decoded by modified tRNAs to coordinate mRNA decay [RNA-Seq]

city: Heidelberg

first: Bastian

last: Linder

address: Meyerhofstraße 1

department: Genome Biology Unit

country: Germany

institute: European Molecular Biology Laboratory (EMBL)

summary: Chemically modified mRNA nucleotides are emerging as key regulators of gene expression. Their effects are typically thought to be mediated through reader proteins that selectively bind to RNA molecules containing these modifications. Here, we present a new mechanism by which N6 methyladenosine (m6A) couples the translation of messenger RNA (mRNA) to its decay. m6A-modified codons are decoded inefficiently by the ribosome, rendering them “non-optimal”. At these codons, m6A slows down elongating ribosomes and thereby triggers translation-dependent decay of the mRNA. Inefficient decoding of m6A-modified codons is counteracted by the transfer RNA (tRNA) anticodon modification 5-methoxycarbonylmethyl-2-thiouridine (mcm5s2U). mcm5s2U increases the decoding efficiency of a subset of m6A codons and thereby alleviates m6A-mediated mRNA decay. This unanticipated link between the mRNA and tRNA epitranscriptomes controls the decay of mRNAs of important oncogenic signaling pathways. The biogenesis of m6A and mcm5s2U is coordinated in normal tissues but dysregulated in cancer, where a shift towards more mcm5s2U stabilizes these RNAs and is associated with higher tumor aggressiveness and poor prognosis. Thus, the balance between m6A and mcm5s2U acts as a pan-epitranscriptomic mechanism that regulates gene expression and curtails tumorigenesis.

overall_design: WT and METTL14-KO cells were either left untreated or treated with 200 µM of the translation inhibitor emetine. To determine mRNA decay rates, RNA-Seq was performed at 0h, 1 and 3h after transcription was inhibited with actinomycin D.

first: Puneet

last: Sharma

first: Kai

last: Fenzl

first: Hannah

last: Vorgerd

first: Florian

last: Erhard

first: Sebastian

last: Leidel

first: Lars

last: Steinmetz


title: Deciphering Epigenetic Regulation of Enhancers in High-Risk Prostate Cancer

city: Dublin

first: Alexandra

last: Tuzova

address: Belfield

country: Ireland

institute: University College Dublin

summary: Prostate cancer (PCa) is associated with widespread promoter hypermethylation. We hypothesized that aberrant DNA methylation also targets gene enhancers, modulating their activity and contributing to disease etiology. DNA methylation was assessed in a discovery set (n = 37) of primary PCa via the Infinium methylation EPIC array, using high-risk (HR; n=13), low-risk (LR; n=11), and histologically benign (n=13) tissues. A higher proportion of enhancers was hypomethylated in HR (n=385, 15%) than LR (n=105, 10%) PCa, primarily targeting genes involved in development and enriched for oncoprotein binding motifs, including FOXA1. Clinical significance was evaluated by identifying a 17 enhancer differentially methylated probe (DMP) signature using a Least Absolute Shrinkage and Selection Operator model in the discovery set. A logistic regression model was trained using the HR PCa-specific signature in a training set (n=490) and validated in a testing set (n=256). The signature had a 0.81 (95% bootstrapped CI 0.78-0.9) area under the curve, for selective detection of HR PCa, achieving a 0.71 sensitivity and 0.76 specificity (testing set). Array-wide aberrant DNA methylation at enhancers highlighted their epigenetic perturbance in HR disease. A clinically significant enhancer signature from this study could be used for detecting HR PCa.

overall_design: FFPE tissue samples were collected from 37 PCa patients. DNA was isolated and methylation was measured using the Illumina Infinium Human MethylationEPIC BeadChip. Normalized beta-values were used to compare methylation patterns between different risk groups.

first: A

last: Perry


title: Harmonized single-cell landscape, intercellular crosstalk and tumor architecture of glioblastoma

city: Utrecht

first: Cristian

last: Ruiz-Moreno

state: Utrecht

address: 25 Heidelberglaan

country: Netherlands

institute: Prinses Máxima Centrum

summary: Glioblastoma, IDH wt (GB) is an aggressive brain malignancy associated with a dismal prognosis and poor quality of life. Large-scale data integration can help to uncover unexplored tumor pathobiology. To resolve the composition of the tumor milieu and recreate the cellular map of GB, we created the ‘GBmap’, a curated resource that at its core harmonizes 16 datasets gathering 110 patients and spanning over 330 thousand cells. By transfer learning, we ‘upgraded’ our atlas reference (extended GBmap) with another ten datasets, including our own profiled GB tissues resulting in a collection of 26 studies, 240 patients, and more than 1,1 million cells. We showcase the applications of our resource in several scenarios, from reference mapping to biological discoveries. The GBmap represents a framework that allows the streamlined characterization, integration, and interpretation of new data and provides a platform for exploratory analysis, hypothesis generation, and testing.

overall_design:
Single-nuclei transcriptome (snRNA-seq) of the primary GB was generated using the 10X genomics paltform.
***Due to patient confidentiality, raw sequencing data will be submitted to EGA**

first: Hendrik

middle: G

last: Stunnenberg


title: Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality [PooledCRISPR].

city: Saskatoon

first: Franco

last: Vizeacoumar

state: Saskatchewan

address: 4D40 Health Sciences Building, 107 Wiggins Road

department: Oncology

institute: University of Saskatchewan

summary: Chromosomal instability (CIN) drives tumor heterogeneity, complicating cancer therapy. Although Polo-like kinase 1 (PLK1) overexpression induces CIN, direct inhibition of PLK1 has shown limited clinical benefits. We therefore performed a genome-wide synthetic dosage lethality (SDL) screen to identify effective alternative targets and validated over 100 candidates using in vivo and in vitro secondary CRISPR screens. We employed direct-capture Perturb-seq to assess the transcriptional consequences and viability of each SDL perturbation at a single-cell resolution. This revealed IGF2BP2 as a critical genetic dependency that, when targeted, downregulated PLK1 and significantly restricted tumor growth. Mechanistic analyses showed that IGF2BP2 loss disrupted cellular energy metabolism and mitochondrial ATP production by downregulating PLK1 levels as well as genes associated with oxidative phosphorylation. Consistent with this, pharmacological inhibition of IGF2BP2 severely impacts the viability of PLK1-overexpressing cancer cells addicted to higher metabolic rates. Our work offers a novel therapeutic strategy against PLK1-driven heterogeneous malignancies.

overall_design: Pooled in vivo CRISPR knock-out screen for synthetic dosage lethal hits of PLK1.

first: Chelsea

last: Cunningham

first: Frederick

first: Yue

last: Zhang

first: Andrew

last: Freywald


title: m6A is decoded by modified tRNAs to coordinate mRNA decay.


title: Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality [Microarray]

summary:
Chromosomal instability (CIN) drives tumor heterogeneity, complicating cancer therapy. Although Polo-like kinase 1 (PLK1) overexpression induces CIN, direct inhibition of PLK1 has shown limited clinical benefits. We therefore performed a genome-wide synthetic dosage lethality (SDL) screen to identify effective alternative targets and validated over 100 candidates using in vivo and in vitro secondary CRISPR screens. We employed direct-capture Perturb-seq to assess the transcriptional consequences and viability of each SDL perturbation at a single-cell resolution. This revealed IGF2BP2 as a critical genetic dependency that, when targeted, downregulated PLK1 and significantly restricted tumor growth. Mechanistic analyses showed that IGF2BP2 loss disrupted cellular energy metabolism and mitochondrial ATP production by downregulating PLK1 levels as well as genes associated with oxidative phosphorylation. Consistent with this, pharmacological inhibition of IGF2BP2 severely impacts the viability of PLK1-overexpressing cancer cells addicted to higher metabolic rates. Our work offers a novel therapeutic strategy against PLK1-driven heterogeneous malignancies.

We used microarray to identify synthetic dosage lethal partner genes PLK1

overall_design: Samples were collected at different time points after infection with the 90k shRNA libraries and probes were prepared to hybridize to microarray chips to identify SDL partners of PLK1 gene.


title: Single-cell RNA sequence analysis of splenic slices transplant recipient mouse liver.

first: Yuan

last: Li

address: 38 Science Park Road, National Center for Protein Sciences (Beijing), Changping District, Beijing

department: Post-translational modification

institute: Beijing Proteome Research Center

summary: In this study, we investigated the composition of lymphocytes in the livers of splenic slices transplant recipient mice by single-cell RNA sequence analysis.

overall_design: To induce liver fibrosis, all mice were injected intraperitoneally every two days for 12 weeks with CCl4. For splenic slices transplantation, the donor spleen was carefully removed and cut into 4 small pieces. An abdominal midline incision was made and placed 3 pieces of spleen into the gastric omental. Then sorted CD45+ cells were analysed by sc-RNA-seq.

first: Ping

last: Xu

first: Tao

last: Zuo


title: Paired Metabolomic and Transcriptomic Time Series of Streptomyces coelicolor M145 Secondary Metabolism

city: Minneapolis

first: Erin

last: Carlson

state: MN

address: 207 Pleasant St. SE

department: Chemsitry

institute: University of Minnesota

summary: We utilized weighted correlation networking analysis to integrate metabolite and transcription data. We demonstrate the effectiveness of this strategy and identify potential regulatory effects on biosynthetic gene clusters.

overall_design: Examination of mRNA and Secondary metabolite levels of Streptomyces coelicolor M145 over an eight day time course in ISP2 media. Collected in biological triplicate

last: Marshall

last: Johnson


title: Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality.

overall_design: Refer to individual Series


title: Monocyte Single-Cell Multimodal Profiling in Cardiovascular Disease Risk States

status: Public on May 08 2025

first: Chenyi

last: Xue

summary: Monocytes are a critical innate immune system cell type that serves homeostatic and immunoregulatory functions. They have been identified historically by the cell surface expression of CD14 and CD16. However, recent single-cell studies have revealed that they are much more heterogeneous than previously realized.  We utilized cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and single-cell RNA sequencing (scRNA-seq) to describe the comprehensive transcriptional and phenotypic landscape of 437,126 monocytes. This high-dimensional multimodal approach identified vast phenotypic diversity and functionally distinct subsets, including IFN-responsive, MHCIIhi, monocyte-platelet aggregates, as well as non-classical, sand several subpopulations of classical monocytes. Using flow cytometry, we validated the existence of MHCII+CD275+ MHCIIhi, CD42b+ monocyte-platelet aggregates, CD16+CD99- non-classical monocytes, and CD99+ classical monocytes. Each subpopulation exhibited unique characteristics, developmental trajectories, transcriptional regulation, and tissue distribution. In addition, alterations associated with cardiovascular disease (CVD) risk factors, including race, smoking, and hyperlipidemia were identified. Moreover, the effect of hyperlipidemia was recapitulated in mouse models of elevated cholesterol. This integrative and cross-species comparative analysis provides a new perspective on comparison of alterations in monocytes in pathological conditions and offers insights into monocyte-driven mechanisms in CVD and the potential for monocyte subpopulation targeted therapies.

overall_design: Single-cell RNA sequencing (scRNA-seq) was performed on blood monocytes from wild-type mice on chow diet and LDLr-/- mice on 0, 8, or 16 weeks of chow diet or western diet

first: Alexander

last: Bashore


title: RIT1 drives lung oncogenic transformation and is an actionable target in lung adenocarcinoma [PDX]

first: Alessandro Mauro

last: Mozzarelli

address: 450 East 29th Street, ACLS - East Tower, New York, NY 10016

department: Biochemistry and Molecular Pharmacology

institute: NYU Grossman School of Medicine

summary: RIT1 is a small GTPase of the RAS family and RIT1 mutations have been identified in lung cancer, leukemias, and the developmental disorder Noonan syndrome. Mutations in RIT1 lead to increased levels of this oncoprotein due to impaired proteolysis, resulting in dysregulation of RAS/MAPK and other pathways. Here we document the diversity of RIT1 mutations in human lung cancer and show that physiologic expression of RIT1 M90I is sufficient to drive autochthonous lung tumor development in vivo in mouse models. Due to the current lack of targeted therapies for this oncoprotein, we undertake different and complementary methods to either inhibit RIT1 directly or the downstream RAS/MAPK pathway. Through a proof-of-concept chemical biology approach, we discover that RAS tri-complex inhibitors bind directly to GTP-bound RIT1 and lead to tumor shrinkage. These molecules provide a feasible therapeutic approach for RIT1-driven lung tumors.

overall_design: Lung adenocarcinoma MSK-LX1033 was injected, and tumors were allowed to grow to approximately 300 mm³. The tumors were then treated orally for three days with RMC-7977 (10 mg/kg), RMC-4550 (30 mg/kg) and Vehicle. After treatment, the tumors were collected, and RNA was extracted for RNA sequencing.

first: Alessandro

first: Yuzhe

last: Niu

first: Pau

last: Castel


title: Induced neural progenitor specification from human pluripotent stem cells by a refined synthetic Notch platform

city: Nashville

first: Jonathan

last: Brunger

state: Tennessee

address: 2400 Highland Ave

institute: Vanderbilt University

summary: Historically, studying the development of brain and central nervous system (CNS) tissues has been challenging. Human  pluripotent stem cell (hPSC) technology has allowed for in vitro reconstitution of relevant, early cell trajectories by using small molecules and recombinant proteins to guide differentiation of cells towards relevant brain and CNS phenotypes. However, many of these protocols fail to recapitulate the cell-guided differentiation programs intrinsic to embryonic development, particularly the signaling centers that emerge within the neural tube during brain formation. Located on the ventral end of the neural tube, the floor plate acts as one such signaling center to pattern the dorsal/ventral axis by secreting the morphogen Sonic Hedgehog (SHH). Here, we present a method for cell-guided differentiation using the synthetic Notch (synNotch) receptor platform to regulate SHH production and subsequent cell fate specification. We show that the widely used configuration of the orthogonal synNotch ligand green fluorescent protein (GFP) mounted on a platelet derived growth factor receptor-b transmembrane chassis does not allow for robust artificial signaling in synNotch-hPSCs (“receivers”) co-cultured with ligand-presenting hPSCs (“senders”). We discovered that refined designs of membrane-bound GFP-ligand allows for efficient receptor activation in hPSC receivers. A variant of this enhanced synNotch system drives production of SHH in hPSC sender:hPSC receiver co-cultures and gives rise to floor plate-like cell types seen during neural tube development. This revised synNotch platform has the potential to pattern hPSC differentiation programs in synthetic morphogenesis studies designed to uncover key paradigms of human CNS development.

overall_design: Day 11 bulk RNA sequencing of wild-type H9 hESCs given recombinant sonic hedgehog (C25II) compared to synNotch-driven sonic hedgehog for floor plate differentiation.

first: Catherine

last: Hamann

last: Kjar

first: Hyosung

last: Kim

first: Alan

last: Simmons

first: Hannah

last: Brien

first: Cheryl

last: Quartey

first: Bonnie

middle: L

last: Walton

first: Ken

last: Lau

first: Ethan

last: Lippmann


title: Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer [CUT&Tag]

city: Seattle

first: David

last: MacPherson

state: WA

address: 1100 Fairview Ave N

institute: Fred Hutchinson Cancer Research Center

summary: Small cell lung cancer (SCLC) responds exceptionally well to cytotoxic chemotherapy. However, relapse with the emergence of chemoresistant disease is rapid and accompanied by poor treatment outcomes. To understand the genetic basis of chemoresistance in SCLC, we applied in vivo CRISPR deletion screening to patient-derived xenograft (PDX) models. Top screen hits included genes encoding components of the transcriptional co-activator SAGA (Spt-Ada-Gcn5 acetyltransferase) complex. We demonstrate that deletion of the SAGA deubiquitylase USP22 conferred cisplatin/etoposide resistance in two chemosensitive PDX models, and that restoring expression in a PDX model harboring homozygous truncating mutation of USP22 re-sensitized tumors to chemotherapy. USP22 loss increased gene body histone H2A-K119 monoubiquitylation in genes encoding key regulators of neuronal differentiation, and suppressed neural and neuroendocrine gene expression including targets of ASCL1. Chemoresistance following USP22 loss reflected attenuated DNA damage-driven phosphorylation events and apoptosis, in conjunction with  increased expression of glycolysis and hypoxia-related genes. Glycolysis program upregulation may reflect a targetable vulnerability, as inhibition of GLUT1 re-sensitized USP22-null tumors to chemotherapy.

overall_design: We generated isogenic USP22 and control knockout models in SCLC PDX model FHSC14. Isogenic PDX tumors were collected 48 hours after in-vivo treatment with cisplatin+etoposide or saline. CUT&Tag sequencing of FHSC14 sgCtrl vs sgUSP22 tumors treated with cisplatin+etoposide or saline was performed.

first: Scott

last: Best


title: Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer [RNA-seq]

overall_design: We generated isogenic USP22-expressing and control SCLC PDX model JHU-LX33. Isogenic PDX tumors were collected 10 days after in-vivo treatment with cisplatin+etoposide or saline. Gene expression profiling of isogenic JHU-LX33 tumors containing Empty vector control vs USP22-expression vector that were treated with cisplatin+etoposide or saline was performed by RNAseq.


title: Comparative Study on the Effects of Silicon Nanoparticles and Cellulose Nanocrystals on Drought Tolerance in Tall Fescue (Festuca arundinacea Schreb.)

city: Xianyang

first: Meng

last: Li

address: No. 3 Taicheng Road, Yangling District

institute: Northwest A&F University

summary: Tall fescue (Festuca arundinacea Schreb.) is a commonly used herbaceous species for slope ecological restoration in China. However, water scarcity often constrains its growth due to the unique site conditions of steep slopes and climate-induced drought stress. This study aims to compare the ameliorative effects of silicon nanoparticles (Si NPs) and cellulose nanocrystals (CNCs) on drought stress in tall fescue, and to elucidate their underlying mechanisms of action. The results indicated that drought stress impaired photosynthesis, restricted nutrient absorption, and increased oxidative stress, ultimately reducing biomass. However, Si NPs and CNCs enhanced drought tolerance and promoted biomass accumulation by improving photosynthesis, osmotic regulation, and antioxidant defense mechanisms. Specifically, Si NP treatment increased biomass by 48.71% compared to drought-stressed control plants, while CNCs resulted in a 33.41% increase. Transcriptome sequencing further revealed that both nanomaterials enhanced drought tolerance by upregulating genes associated with photosynthesis and antioxidant defense. Additionally, Si NPs improved drought tolerance by stimulating root growth, enhancing nutrient uptake, and improving leaf structure. In contrast, CNCs play a distinct role by regulating the expression of genes related to cell wall synthesis and metabolism. These findings highlight the crucial roles of these two nanomaterials in plant stress protection and offer a sustainable strategy for the maintenance and management of slope vegetation.

overall_design: The experiment was conducted in a greenhouse at the College of Soil and Water Conservation Science and Engineering, Northwest A&F University, Yangling, China (34°27' N, 108°07' E), from July to September 2024. The temperature was maintained at 25 ± 5℃ and humidity at 70 ± 5%, with a light cycle of 16 hours of light and 8 hours of darkness. Uniform and plump tall fescue seeds were selected, with 50 seeds sown per pot (substrate: a mixture of peat, vermiculite, and perlite in a 1:1:1 ratio). After germination, 30 healthy seedlings per pot were kept for further cultivation. When the seedlings reached 15-20 cm, a 10-day concentration screening experiment was performed. The plants were divided into six treatments with the following experimental conditions: (i) Normal control (CK): Plants were sprayed with double-distilled water (DDW) and maintained at normal soil moisture (65-75% field capacity); (ii) Si NP treatments: Plants were sprayed with Si NPs solutions at concentrations of 50, 100, 200, 300, and 500 mg/L under normal soil moisture conditions; (iii) CNC treatments: Plants were sprayed with CNCs solutions at concentrations of 25, 50, 100, 200, and 300 mg/L under normal soil moisture conditions; (iv) Drought stress control (DS): Plants were grown under drought conditions (35-45% field capacity); (v) DS_Si NP treatments: Plants were sprayed with Si NPs solutions at the same concentrations as treatment (ii) and grown under drought conditions; (vi) DS_CNC treatments: Plants were sprayed with CNCs solutions at the same concentrations as treatment (iii) and grown under drought conditions. Each treatment was repeated three times. Before spraying, the nanomaterials were diluted with DDW and sonicated for 30 minutes. After adding 0.05% Tween-20, the solution was evenly sprayed on the leaves, with applications every three days. Soil moisture was replenished daily using the gravimetric method, and plastic film was used to cover the soil surface to prevent solution leakage. After 10 days, plant growth and physiological parameters were measured. The concentration screening results indicated that 300 mg/L Si NPs and 100 mg/L CNCs effectively promoted tall fescue growth and improved its physiological performance under drought conditions . These concentrations were selected for the final experiment. After an additional 10-day treatment (for a total of 20 days), samples were collected.

first: Li

last: Meng

first: Hu

last: Sile

first: Bai

last: Xulong

first: Ren

last: Jie

first: Tian

last: Kanliang

first: Zhang

last: Huili

last: Zhilong

first: Nguyen

last: Vanquy


title: Transcriptome data of the interdigital webbing in Chinese Soft-shell Turtle (Pelodiscus sinensis)

city: Shenyang

last: Shibin

address: 120 Dongling Road

institute: Shenyang Agriculture University

summary: interdigital cell death (ICD) is an essential role in amniotes to promote the regression of interdigital tissue  for digits separation. Antagonizing this process can lead to the formation of webbed limbs. However, the mechanism of forming webbed limbs is not the same among independently evolved species, and the reason is still unclear. The Chinese softshell turtle (Pelotiscus sinensis) is a good research model, exhibiting a transitional feature from no webbed to fully webbed. In this study, we collected 8 samples of interdigital webbing from the forelimbs and hindlimbs of turtles at embryonic stage 19 (TK19) for RNA sequencing. We identified 608 potential regulatory genes through differential expression analysis. These findings not only provide new perspectives and data support for comparative studies of adaptive convergent evolution in aquatic animals, but also enhance our understanding of the mechanisms underlying quadrupedal limb morphology. In addition, these results provide potential molecular targets for studying the plasticity of programmed cell death or aging.

overall_design: At the TK19 (Tokita-Kuratani stage 19), 20 morphologically consistent fresh individuals were selected, and the four interdigital regions of the paired fore- and hindlimbs were dissected under the microscope (Leica, M165FC). A total of eight sample groups were collected for pool-sequencing, with each group containing 40 tissues from left and right sides of the 20 individuals.

first: Shibin

last: Bai

first: Shanshan

first: Zhe

last: Wang


title: LSD1 induces H3K9 demethylation to promote adipogenesis in Thyroid associated ophthalmopathy

city: HangZhou

first: Yuyan

last: Xu

address: Yuhang Tang Road

institute: Zhejiang university

summary: Thyroid-associated ophthalmopathy (TAO) is an autoimmune orbital disease, multiple factors including genetic and immune factors, contribute to TAO progression, thus there is no available drugs targeting TAO. Here, we investigated the underlying mechanism of adipogenesis in TAO from an epigenetic point, we found lysine specific demethylase (LSD1) was highly expressed in TAO compared with non-TAO, and knocking down LSD1 led to decreased expression of adipocyte markers and inflammatory genes. Mechanically, LSD1 removed the H3K9me2 mark on the promoter of adipocyte genes, activating their expression. Finally, pargyline, an inhibitor of LSD1, inhibited adpogenesis in a dose-dependent manner. Taken together, our study revealed a novel mechanism of adipocyte differentiation during TAO progression, and demonstrated LSD1 is a potential anti-adipogenesis target in TAO.

overall_design: To compare the different genes expression between TAO  orbital adipose cell and TAO orbital orbital adipose cell knocking down LSD1; to compare the distribution of H3K9me2 modification  between normal human orbital adipose cell and in orbital adipose cell of TAO patients,  TAO orbital adipose cell and TAO orbital orbital adipose cell knocking down LSD1.

first: Ling

last: Zhang


title: Differential Expression Spectrum of tRNA fragments in Alzheimer's Disease

city: Boston

first: Ami

last: Kobayashi

state: MA

address: 60 Fenwood Rd

department: Neurology

institute: Brigham & Women's Hospital

summary: We report the profiling of tRNA fragments from the temporal cortex of controls and late-stage Alzheimer's disease subjects. We show tRNA fragments expression changes between the two groups. Four upregulatedtRNA fragments in the results of Real Time-qPCR were consistent with the small RNA microarray:5'tRF_GluCTC, 5'tRF_GluTTC, 5'tRF_GlyGCC, 5'tRF_GlyCCC

overall_design: Small RNA microarray on five pairs of temporal cortex of Alzheimer's Disease patients and healthy controls


title: Loss of the USP22 deubiquitylase confers resistance to chemotherapy in small cell lung cancer

last: MacPherson

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


title: Targeting cancer through simultaneous inhibition of key metabolic enzymes

city: Giessen

first: Marek

last: Bartkuhn

state: Hessen

address: Aulweg 132

department: Biomedical Informatics and Systems Medicine

institute: Justus-Liebig-University Giessen

summary: This study explored the potential metabolic vulnerabilities of ovarian cancer cells in comparison to their non-oncogenically transformed precursor cells. A synthetic lethal screen with inhibitors of metabolic pathways showed that simultaneous administration of (R)-GNE-140 and BMS-986205 (Linrodostat) preferentially halted proliferation of tumor cells. While (R)-GNE-140 inhibits lactate dehydrogenase (LDH)A/B and thus effective glycolysis, the BMS-986205 compound, in addition to its known inhibitory activity on Indoleamine 2,3-dioxygenase (IDO1), can also restrict oxidative phosphorylation, as revealed in this study. BMS-986205, which is already in multiple phase III clinical trials, inhibits the Q site of complex I and thus ATP production through mitochondrial respiration. The energetic catastrophe caused by simultaneous interference with glycolysis and oxidative phosphorylation led to cell death or the induction of senescence in tumor cells, with the latter being completely eliminated by senolytics. The occurrence of high synergy upon inhibitor cotreatment was also tested on human colorectal cancer organoids and 119 different tumor cell lines. These experiments revealed highly synergistic activity of the compounds in one third of the tested tumor cell lines, which show statistically significant correlations with alterations in genes with known roles in metabolic regulation.

overall_design: Experiment 1: Transcriptome analysis of KRASG12V/MYC cancer cells comparing 4 hours of (R)-GNE-140 + BMS-986205 combination treatment to 4 hours of DMSO-vehicle control treatment. Experiment 2: Longitudinal transcriptome analysis of KRASG12V/MYC cancer cells over the course of 120 hours GNE+BMS combination treatment.

first: Jan

last: Dreute

first: Lienhard

last: Schmitz


title: ACBP in brown adipose tissue acts as a negative regulator of adaptive thermogenesis

city: Barcelona

first: Francesc

last: Villarroya

state: Barcelona

address: Diagonal 643

department: Biochemistry and Molecular Biomedicine

country: Spain

institute: University of Barcelona

summary: The defective activity of brown adipose tissue (BAT) is linked to obesity and cardiometabolic diseases. While there is extensive knowledge about the biological signals that trigger BAT thermogenesis, information regarding active repressors that may contribute to the pathological impairment of BAT function is quite limited. Acyl CoA-Binding Protein (ACBP), also known as Diazepam Binding Inhibitor (DBI), is a protein with intracellular functions related to lipid metabolism. It can also be secreted and act as a circulating regulatory factor that affects multiple tissues and organs. We discovered that ACBP expression and release in BAT are suppressed by noradrenergic, cAMP-dependent signals that stimulate thermogenesis. This regulation occurs through mechanisms involving gene expression and autophagy-related processes. Mice with targeted ablation of the Acbp gene in brown adipocytes exhibit enhanced BAT thermogenic activity and protection against obesity and glucose intolerance induced by a high-fat diet. This is associated with a remodeling of the BAT transcriptome, characterized by the induction of genes related to BAT thermogenesis. Treatment of brown adipocytes with exogenous ACBP suppressed oxidative activity, lipolysis, and the expression of genes associated with thermogenesis. ACBP inhibits the noradrenergic-induced phosphorylation of p38 MAP kinase and CREB, major intracellular mediators of brown adipocyte thermogenesis. Our findings identify the ACBP system as a crucial auto-regulatory repressor of BAT thermogenesis, which responds reciprocally to the noradrenergic induction of BAT activity.

overall_design: RNA-seq profiling of BAT from wild-type and conditional Brown adipocyte-ACBP knockout (Acbp BAd-KO) C57BL/6J mice in chow diet or under HFD

first: Albert

last: Blasco-Roset

first: Tania

last: Quesada-López

last: Mestres-Arenas

first: Joan

first: Rubén

last: Cerijo

first: Celia

last: Rupérez

first: Marta

last: Giralt

first: Anna

last: Planavila


title: RIT1 drives lung oncogenic transformation and is an actionable target in lung adenocarcinoma [H2110]

first: Alessandro Mauro

last: Mozzarelli

overall_design: Lung adenocarcinoma H2110 cells were injected, and tumors were allowed to grow to approximately 300 mm³. The tumors were then treated orally for three days with RMC-7977 (10 mg/kg), RMC-4550 (30 mg/kg), Trametinib (0.3 mg/kg), Cobimetinib (3 mg/kg), and Vehicle. After treatment, the tumors were collected, and RNA was extracted for RNA sequencing.

first: Alessandro

first: Yuzhe

last: Niu

first: Pau

last: Castel


title: Role of POLR2A in kidney response to DNA damage

city: Stony Brook

first: Sandeep

last: Mallipattu

address: 101 Nicolls Road

department: Department of Medicine

institute: Stony Brook University

summary: The role of POLR2A/RPB1 in kidney proximal tubule responses to DNA damage-induced acute kidney injury is unknown. We undertook treatment of HK2 cells with the DNA damaging agent aristolochic acid, with or without knockdown of POLR2A to determine the role of RPB1 in kidney cells.

overall_design: HK-2 cells were transfected with 10nM Trilencer-27 siRNA duplexes specific to POLR2A or Trilencer-27 universal scrambled control siRNA duplex (Origene), using SiTran2.0 transfection reagent (Origene), according to manufacturer’s instructions.  At the same time, cells were also treated with DMSO (control) or 25µM AAI for 24 hours.

first: Sian

last: Piret

first: Maanasa

last: Hanubal

first: Samaneh

last: DiMartino

first: Merin

last: Davis

first: Jiakang

last: Wang

first: Nehaben

last: Gujarati

first: Bismark

last: Frimpong

first: Tej

last: Bahadur

first: Asha

last: Rath

first: Robert

last: Bronstein

first: Yiqing

last: Guo