title: Progenitor effects and unique transcriptomic signatures linked to differentiation phenotype in clonally expanded antigen-specific CD8 T memory stem cells (TSCM)

city: Sdyney

first: Yanran

last: Zhao

address: Sydney NSW 2033

institute: UNSW

summary: Memory stem CD8 T cells (TSCM) are a long-lived T cell subset displaying stem cell-like properties, which play a significant role in anti-viral defense and exhibit a gene expression profile between naïve and central memory T cells. Yet, comprehensive transcriptional profiling of antigen-specific CD8 TSCM cells at the single cell level has not previously been undertaken. In this analysis, we utilized an in vitro single cell colony expansion protocol to study human CD8 T cell clones specific for Cytomegalovirus (CMV) epitopes - phenotypically, functionally, and in transcriptomes. We characterized clonal lineages from 3 donors by single cell sorting dextramer positive CD8 T cells of varied effector and memory surface phenotypes, all recognizing one of two HLA restricted CMV epitopes. Phenotypic and functional characterization of clonal lineages derived from antigen-specific TSCM revealed differentiated memory and effector subsets (TCM, TEM, TEFF) as well as TSCM, with the latter subset featuring multi-potentiality and multi-cytokine production. Studying TSCM-derived progeny of these varied differentiation phenotypes in single cell transcriptomic analysis revealed strong progenitor-to-progeny effects, whereby daughter cells from a shared progenitor clustered closely regardless of progeny differentiation phenotype, suggesting a dominant impact associated with heritable genes. The TSCM-derived TSCM-progeny revealed distinct transcriptomic profiles featuring expression of both recognized early differentiation memory T cell genes, such as IL7R, CCR7, SELL and CD27; as well as several novel genes which were shared across subjects and epitopes. The transcriptional features of clonal lineages are strongly dependent on the progenitor cell, but TSCM have an additional transcriptomic signature likely underpinning the unique differentiation and functional characteristics. These findings have important implications for identification of long-lived and multi-potent CD8 T cells for immunotherapy and immunization against viral infections.

overall_design: Single CMV-specific CD8 T cells were cultured in vitro with autologous PBMCs and IL-2/IL-15, as well as cognate peptide for 7-21 days and then sorted via flow cytometry single cell sorting.

first: Jerome

last: Samir

first: Hui

last: Li

first: Fabio

last: Luciani

first: Andrew

last: Lloyd


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (MM1S_SOC)

status: Public on Oct 20 2025

city: Cambridge

first: Walter

last: Lenoir

state: MA

address: 301 Binney St

country: USA

institute: Kronos Bio

type: Expression profiling by high throughput sequencing

summary: The oncogenic transcription factor (TF) IRF4 is a universal multiple myeloma (MM) dependency that remains undrugged owing to its disordered structure. Using transcriptional regulatory network (TRN) mapping, an unbiased multi-omic approach to nominate druggable TF cofactors, we identified the chromatin coactivator lysine acetyltransferase (KAT) p300 as a key IRF4 partner. We developed KB528, a highly selective p300 KAT inhibitor to explore the regulatory relationship between IRF4 and p300. Instead of broadly inhibiting transcription, partial p300 KAT inhibition selectively downregulates IRF4 and its downstream gene expression program leading to apoptosis selectively in MM cells. IRF4 dependency is a hallmark of MM that exists downstream of existing MM therapies. Consequently, p300 KAT inhibition exhibits strong antiproliferative activity ex vivo and in vivo as a single agent as well as in combination regimens in treatment refractory models. p300 KAT inhibition is well-tolerated in vivo motivating further clinical development in MM.

overall_design: RNA-seq dose response of multiple myeloma standard of care therapeutics and p300 inhibitors. Experiment was done in triplicate and sampled at 0 hour (WT), 6 hour, and 24 hour for each compound. Tested compounds include 0.5 uM KB528 (p300-KAT), 0.3 uM GNE-781 (p300-BRD), 3 uM CCS-1477 (inobrodib, p300-BRD), JQ1 (0.5 uM BET inhibitor), and Lenalidomide (1 uM, imid)

first: Marek

last: Kobylarz

first: Michelle

last: Shum

first: W

middle: F

first: Pete

last: Rahl


title: scRNA-seq and snATAC-seq reveal differentiation trajectories of several pancreatic islet induction protocols

city: Beijing

first: Cheng-ran

last: Xu

address: NO.5 YIHEYUAN ROAD HAIDIAN DISTRICT, BEIJING, P.R.CHINA

department: School of Basic Medical Sciences

country: China

institute: Peking University

type: Genome binding/occupancy profiling by high throughput sequencing

summary: With the help of scRNA-seq and snATAC-seq, we unraveled the differentiation trajectories and gene co-expression networks of current islet induction protocols. Inspired by our understanding to in vivo pancreatogenesis, we improved the current protocol by inducing human anterior lip endoderm at stage 2 and promoting ventral pancreas fate. This refined differentiation protocol simplifies the existing multistage processes and generates higher-quality sc-islets with larger beta cell proportion and enhanced function of glucose regulation, which are validated by scRNA-seq and snATAC-seq.

overall_design: Single cells were collected from the culturing system of Protocol A, B and C in different stages and sequenced following the Smartseq3 protocol. Protocol A and B are current islet induction protocols, while Protocol C is the refined protocol rised from this article. To investigate the effects of detail conditions implemented in Protocol C, we also leveraged Smartseq3 to optimize the small molecules' concentration and acting duration. Furthermore, we performed snATAC-seq to study the epigenetic differences between Protocol A and C. We examined the robustness of Protocol C's improvement by applying our induction systerm to human IPS cell line (hIPSC). Smartseq3 scRNA-seq showed the Protocol C's superiority maintained in hIPSC-induced sc-islets. Finally, we transplanted Protocol A and C generated sc-islets into diabetic mice. The 30 days post-transplanted grafts were collected and sequenced following the Smartseq3 protocol, that showed the Protocol C's grafts contained larger proportion of sc-beta cells.

first: Xin-Xin

last: Yu

first: Xin

last: Wang

first: Liu

last: Yang

first: Mao-Yang

last: He

first: Xi

first: Wen-Rui

first: Yi-Ning

first: Ya-Xin

first: Xin-Yu

last: Liu

first: Zi-Ping

first: Cheng-Ran


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (MM1S_ChIP_KB528)

first: Walter

overall_design: H3K27ac, H3K27me3, and H3K18ac in MM1.S at 0 (DMSO), 1, 3, 6, and 24 hour treated with 100 nM KB528 (p300 KAT inhibitor). Additionally p300 and IRF4 DMSO MM.1S samples are included.

first: Frank

middle: W

first: Wayne

last: Glore


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (IRF4KD)

overall_design: siRNA mediated knock down of IRF4 followed by RNA-seq analysis was performed using ON-TARGET pooled siRNA reagents (Dharmacon Horizon Discovery). One million cells were transfected using an electroporation protocol (Neon NxT) with parameters: 1600 V, 10 ms, 3 pulses. Transfected cells were plated in 6 cm petri dishes and siRNA knock down was done for 48 hours to attain sufficient suppression of protein expression. Samples were then prepared for western blot confirmation of knock down and RNA-seq analysis.

first: Marek

first: W


title: Smug1 DNA glycosylase modulates the perception of smell in mouse brain through downregulation of olfactory receptor genes

city: Oslo

first: Yohan

last: Lefol

state: Oslo

address: Sognsvannsveien 20 Rikshospitalet

department: Institute of Clinical Medicine

country: Norway

institute: University of Oslo

summary: The SMUG1-DNA glycosylase is the primary enzyme responsible for excising 5-hydroxymethyluracil (5hmU) from genomic DNA. SMUG1 activity is high in the brain and is therefore proposed to be particularly important for regulating 5hmU levels in the brain. 5hmU has been proposed as an epigenetic mark, but it is still unclear whether, and in which contexts, it may have regulatory functions. Here we show that accumulation of 5hmU in Smug1 deficient mice leads to widespread gene expression alterations across multiple brain regions, and that this is accompanied by a complex behavioural phenotype. We demonstrate that 5hmU serves as a transcriptional regulator of olfactory receptor genes in the olfactory bulb. The persistence of 5hmU in the genome leads to deficits in sensory perception of smell and influences reward-related behaviour. Mechanistically, we identify a specific function for SMUG1 in removing 5hmU from promoters of olfactory receptor genes, promoting transcription and proper olfaction function.

overall_design: Five brain regions were of interest to study from a Smug1 KO perspective. We required three replicates of both Smug1KO and WT in order to validate biological significance. This resulted in utilizing 6 mice, three WT and three Smug1KO. These mice reached 6 months of age and were then sacrificed. Each brain region of interest were immediately dissected and fresh frozen for subsequent RNA sequencing.

first: Diana

last: Bordin

first: Garry

last: Wong

first: Nurye

last: Tekin

first: Junbai


title: p300 catalytic inhibition selectively targets IRF4 oncogenic activity in multiple myeloma (DF_pt)

overall_design: RNA-seq coming from primary MM patient samples (CD138+). Each sample comes from a unique patient, samples are matched at 12 hours treated with KB528 (1 uM) vs CTRL

first: Michelle

first: Pete


title: CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination.

city: Stanford

first: Joseph

middle: C.

last: Wu

state: California

address: 240 Pasteur Dr

department: Stanford Cardiovascular Institute

institute: Stanford university

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination [human]

summary: The mRNA vaccines against COVID-19 are highly effective yet associated with rare myocarditis cases, particularly in young males post-second dose. Here we explore the mediators of this adverse effect and its potential solutions, aiming to enhance the safety of future mRNA vaccines. Analysis of post-vaccination plasma highlighted a substantial increase in CXCL10 and IFN-γ levels in patients. Correspondingly, human iPSC-derived macrophages exposed to COVID-19 mRNA vaccines exhibited increased production of these two cytokines. iPSC-derived cardiomyocytes subjected to these cytokines exhibited impaired contractility, arrhythmogenicity, and myocarditis-like gene expression patterns. Genistein, an anti-inflammatory phytoestrogen, notably mitigated these effects, reducing cytokine-induced proteasomal degradation of cardiac proteins and preserving contractile function. In vivo, genistein significantly decreased cardiac injury markers and immune cell infiltration in a mouse model of cytokine-induced myocarditis. These findings underscore CXCL10 and IFN-γ as key mediators of myocarditis post-mRNA vaccination and propose genistein as a potential therapeutic to mitigate associated cardiovascular risks.

overall_design: (1) For human macrophage samples: human induced pluripotent stem cell-derived macrophages were treated either eitehr BNT162b2 (Pfizer), or mRNA-1273 (Moderna) COVID19 mRNA vaccine. Cells treated with PBS were included as control. were collected 24 hours after treatment and sent for bulk RNA-seq. (2) For human cardiomyocyte samples: human induced pluripotent stem cell-derived cardiomyocytes were treated with a cytokine cocktail of CXCL10 and IFN-γ. Two treatment conditions were tested: a “low” concentration (1 ng/mL of CXCL10 and 0.5 ng/mL of IFN-γ) and a “high” concentration (10 ng/mL CXCL10 and 5 ng/mL IFN-γ). cells treated with PBS were included as control. Cells were collected 48 hours after treatment and sent for bulk RNA-seq.

first: Xu

last: Cao

first: Masataka

last: Nishiga

first: Amit

last: Manhas

first: Arianne

last: Caudal

first: Gema

last: Mondejar-Parreño

first: Shane

middle: R

last: Zhao

first: James

last: Jahng

first: Mingqiang

first: Paul

middle: J

last: Utz

first: Kari

middle: C

last: Nadeau


title: CXCL10 and IFN-γ Mediate Myocarditis Post-COVID19 mRNA Vaccination [mouse]

overall_design: For mouse samples: BALB/C mouse were divided into three groups: Control, Cytokine treatment, Cytokine + Genistein. 6 mice in each group. Mice were pretreated for 7 days with Genistein with the Cytokine+Genistein group. Then, cytokines cocktail (2.5 ug of CXCL10 and 2.5 ug IFNr) were injected into mice through tail vein. Mice heart samples were collected 4 hours after cyokines treatment and sent for bulk RNA-seq. Mice treated with vehicle (PBS) were used as control.

last: Wang


title: The budding yeast heterochromatic protein Sir3 modulates genome-wide gene expression through transient direct contacts with euchromatin (ChIP-Seq)

city: Montpellier

first: Marta

last: Radman-Livaja

address: 1919 route de Mende

department: IGMM

country: France

institute: CNRS

summary: The SIR complex (Silent Information Regulator) is the building block of heterochromatic structures that silence underlying genes. It is well established that the silenced state is epigenetically inherited but it is not known how the SIR complex is maintained through cell divisions in optimal or variable growth conditions. The biological function of heterochromatin located in subtelomeric regions is also unclear since heterochromatin coverage appears to be limited to a few kbps near chromosome ends and the expression of subtelomeric genes is only marginally affected in the absence of the SIR complex. We use a three-pronged approach to address these questions. First, Nanopore-MetID, an in vivo foot printing technique similar to DamID that uses nanopore sequencing technology, identified over a thousand new transient contacts between Sir3 and euchromatic genes that are not detectable by ChIP-seq and revealed a previously undocumented low-density mode of Sir3 binding to subtelomeric regions that extends 15kbps downstream of subtelomeric SIR nucleation sites. Second, our measurements of genome-wide Sir3 exchange rates after exit from starvation show that heterochromatin is a highly dynamic structure in optimal growth conditions. Third, “spike-in” RNA-seq time course experiments in the same conditions reveal that Sir3 modulates global mRNA levels in correlation with fluctuations in nutrient availability. We now propose that subtelomeric regions serve as Sir3 hubs from which Sir3 is brought over to distal sites down the chromosome arm where it transiently contacts euchromatic genes in its path. We hypothesize that contacts between Sir3 and actively transcribed genes facilitate the removal of stalled transcription complexes and allow for optimal genome-wide transcription, which gives wt cells a competitive advantage over sir3Δ cells when nutrients are limited.

overall_design: We have mapped Sir3 (subunit of the heterochromatic SIR complex) genome wide binding dynamics upon yeast exit from starvation using the RITE tag switch module.

first: Pritha

last: Bhattajarchee

first: Hrvoje

last: Galic

first: Ana

last: Hrgovcic

first: Alain

last: Camasses

first: Lara

last: Demont

first: Pauline

last: Vasseur


title: Differences in biliopancreatic duct development exist in Type I congenital biliary dilatation based on microarray expression analysis of mRNAs and long noncoding RNAs

city: Chengdu

first: Chengbo

last: Ai

state: Sichuan

address: 37 Guo-Xue-Xiang, Chengdu, 610041, China.

institute: West China Hospital/West China School of Medicine

type: Non-coding RNA profiling by high throughput sequencing

summary: Congenital biliary dilatation (CBD) is a malformation presenting extra- and/or intrahepatic dilatation bile ducts and often associated with pancreaticobiliary maljunction. Different types of CBD have been noted clinical differences. LncRNA and mRNA sequencing and bioinformatics analysis in CBD can help us to further study the pathogenesis of different types of CBD at the genetic level in the context of clinical data.

overall_design: Thirty-six patients with Congenital biliary dilatation (CBD) (eighteen cystic and eighteen fusiform) were consecutively recruited between October 2019 and December 2021 from the Pediatric Surgery Department of West China Hospital, Sichuan University. All children were diagnosed clinically according to medical history and imaging such as hepatobiliary ultrasonography and magnetic resonance cholangiopancreatography and underwent cyst excision and Roux-Y hepaticojejunostomy. Extrahepatic dilatations were collected, and all specimens were stored in liquid nitrogen after excision.

first: Xiaolong

last: Xie

first: Yong

last: Lv

first: Jiaying

last: Yang

first: Qianwen

last: Zheng

first: Bo

last: Xiang

first: Jing

last: Chen


title: RNA-seq profiling of breast metastases from different sites

city: Rome

first: Stefano

last: Scalera

address: Via Elio Chianesi 53

country: Italy

institute: IRCCS Regina Elena National Cancer Institute

summary: NOT PROVIDED; REQUESTED

overall_design: We performed RNA-seq profiling of metastatic sites from 42 breast cancer patients

first: Giovanni

last: Blandino


title: The budding yeast heterochromatic protein Sir3 modulates genome-wide gene expression through transient direct contacts with euchromatin (RNA-Seq)

overall_design: Transcriptome dynamics in wt Sir3, overexpression Sir3, Sir3D, Sir2D, Sir4D and Sir3 hypomorphs Sir3_3xHA and Sir3 3XT7 strains after exit from starvation phase, normalized to a S.pombe "spike-in"


title: The budding yeast heterochromatic protein Sir3 modulates genome-wide gene expression through transient direct contacts with euchromatin


title: Thyroid Stimulating Hormone (TSH) Protects Against Osteoporosis through AMPK Signaling Pathway in Osteoclasts II

city: Jinan

first: wen

last: Zhang

address: 324 Jing 5 road

institute: Shandong Provincial Hospital

summary: It has been believed that osteoporosis associated with hyperthyroidism due to elevated thyroxine level. But patients with subclinical hyperthyroidism, decline in the level of thyroid stimulating hormone (TSH) alone, are at equal risk of osteoporosis. Research has shown that there is thyroid-stimulating hormone receptor (TSHR) on the osteoclast, but whether TSH regulates osteoclast directly and its mechanisms are still not be stated clearly. In this study, in combination of in vivo and in vitro, we took the osteoclast precursor cell conditional and systemic knockout TSHR mouse models to study the effects of TSHR knockout on bone metabolism in mice and the changes of osteoclast differentiation and function in vitro. Transcriptomics was used to screen the differential genes and signal pathways, and the in vitro experiments were verified. We found that Tshr flox/ flox Lyz2-Cre (TSHR MKO) mice display decreased femoral biomechanics and bone density, damaged bone microstructure. Serum bone resorption marker CTX-I was significantly increased, accompanied by an increase in the number of osteoclasts in bone sections in TSHR MKO mice. The percentage of CD11b+ in TSHR knockout mice was decreased compared with control littermates. Osteoclasts from Tshr -/- mice had stronger osteoclast differentiation and acid secretion ability. In vitro cell experiments confirmed TSH effecting osteoclast differentiation and function by activation of AMPK signaling pathway. In conclusion, TSH inhibits osteoclast differentiation and bone resorption by activating AMPK signaling pathway, increases bone mass, and has osteoprotective effect. This will provide a reference for the diagnosis and treatment of osteoporosis, especially thyroid function related bone metabolism bnormalities. TSH structural analogues or AMPK activators are expected to provide new ideas for the development of drugs for the prevention and treatment of osteoporosis.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for TSH on osteoclast differentition

first: Wenwen

first: Yu

first: Yan

last: Wang

first: Yanman

last: Zhou

first: Honglin

last: Guo

first: Jin

last: Xu


title: Thyroid Stimulating Hormone (TSH) Protects Against Osteoporosis through AMPK Signaling Pathway in Osteoclasts I

overall_design: Comparative gene expression profiling analysis of RNA-seq data for Tshr+/+ and Tshr −/− mice


title: TGF-beta dynamically controls epithelial identity in a 3D model of human epiblast

city: Turin

first: Andrea

last: Lauria

address: Via Accademia Albertina, 13

department: Life Sciences and Systems Biology

institute: University of Turin

first: Irene

last: Zorzan

first: Elena

last: Carbognin

first: Valentina

last: Proserpio

first: Mattia

last: Arboit

last: Paolucci

last: Drusin

first: Monika

last: Sledziowska

first: Salvatore

last: Oliviero

first: Graziano

last: Martello


title: Direct Reprogramming of Fibroblasts into Functional Mammary Epithelial cells by small molecules II

city: Guangxi

first: ben

last: huang

address: NO.100. DAXUE EAST RD, Nanning

institute: School of Animal Science and Technology, Guangxi University

summary: Mammary epithelial cells (MECs), the only cell type which could be capable of secreting milk in mammary gland, can be applied for the generation of transgenic mammary cell/gland bioreactor. However, continuously achieving large amount of high-quality goat MECs by non-invasion method, especially prepuberal MECs, in vitro has been a challenge. Here, we show that a small molecules cocktail enables the in vitro generation of chemically-induced mammary epithelial cells (CiMECs) with milk-secreting properties from goat ear fibroblasts. The properties of CiMECs were highly similar to those of naturally isolated MECs. Notably, the CiMECs lineage reprogramming process may partially imitate the MECs developmental process from embryonic to milk-secreting stages. Interestingly, fibroblasts were firstly reversed back to embryonic ectoderm/surface ectoderm-like state. Our findings constitute a substantial step toward further promoting the application of transgenic mammary bioreactors, moreover, also offer a new strategy for obtaining other cell types by reprogrammed fibroblasts.

overall_design: GEF and CiMEC cells at different timepoints

first: Dandan

first: Ben

last: Huang


title: Gene expression of ISG15-treated immortalized fibroblasts

city: Miaoli County

first: Ya-Wen

last: Chen

address: 35, Keyan Rd, Zhunan Town

department: National Institute of Cancer Research

country: Taiwan

institute: National Health Research Institutes

summary: Immortalized fibroblasts (S1F and R2 cells) were tretaed with or without 300 ng/ml ISG15 for 2 days

overall_design: Total RNA was extracted using Trizol reagent and purified using RNeasy mini kit. Genome-wide gene expression analysis was performed using the Affymetrix Human Clariom S Assay. Microarray analysis were conducted as followed the standard Affymetrix procedures. Hybridized slides were scanned by Affymetrix Gene Chip scanner 3000 7G system. Raw data were generated using Partek Genomics Suite version 7 software.

first: Ssu-Han

first: Yu-Lin


title: Exploring synthetic lethality between the PP6 phosphatase and SETDB1

city: Oxford

first: Emilia

last: Dimitrova

address: South Parks Road

department: Biochemistry

country: United Kingdom

institute: University of Oxford

summary: Genome wide CRISPR/Cas9 screening identified SETDB1 and the HUSH complex as a synthetic lethal interactor of the PP6 phosphatase. Here, we sought to discover the molecular basis for this synthetic lethality. SETDB1 is a histone H3 lysine 9 methyltransferase, reported to be important in the establishment and maintenance of heterochromatin, and the silencing of repeats and incoming viral elements. We undertook RNA sequencing to explore differences in the transcriptome in HeLa and hTERT-RPE-1 cells devoid of PP6, SETDB1 or both proteins together.

overall_design:
HeLa or hTERT-RPE-1 cells, either stably knocked out for PPP6C and SETDB1, or depleted for PPP6C and SETDB1 using siRNA interference, were subjected to RNA isolation and purification. Total cellular RNA was submitted to the Oxford genomics centre for ribosomal RNA removal, library preparation and Illumina sequencing.
[contributor]  Oxford Genomics Centre

first: Luke

last: Fulcher

first: Francis

last: Barr


title: Gene expression profile of human gastroesophageal junction (GEJ) organoids TP53/CDKN2A KO

city: Baltimore

first: Hua

last: Zhao

address: 1503 E. Jefferson Street

institute: Johns Hopkins University

summary: Inactivation of the tumor suppressor genes TP53 and CDKN2A occurs early during GEJ tumorigenesis. However, due to a paucity of GEJ-specific disease models, cancer-promoting consequences of TP53 and CDKN2A inactivation at the GEJ have been incompletely characterized. Here we report the development of the first wild-type primary human GEJ organoid model, as well as a CRISPR-edited transformed GEJ organoid model. CRISPR/Cas9 engineering to inactivate TP53 and CDKN2A (TP53/CDKN2A KO) in GEJ organoids induced morphologic dysplasia as well as pro-neoplastic features in vitro and tumor formation in vivo. Notably, lipidomic profiling identified several Platelet-Activating Factors (PTAFs) among the most upregulated lipids in CRISPR-edited organoids; and importantly, PT AF/PT AFR abrogation by siRNA knockdown or a pharmacologic inhibitor (WEB2086) significantly blocked proliferation and other pro-neoplastic features of TP53/CDKN2A KO GEJ organoids in vitro and tumor formation in vivo. In addition, murine xenografts derived from Eso26, an established esophageal adenocarcinoma (EAC) cell line, were suppressed by WEB2086. Mechanistically, TP53/CDKN2A dual inactivation disrupted both the transcriptome and the DNA methylome, likely mediated by key transcription factors, particularly Forkhead Box M1 (FOXM1). Importantly, FOXM1 activated PTAFR transcription by binding to the PTAFR promoter, further amplifying the PTAF-PTAFR pathway. In summary, we established a robust model system for investigating early GEJ neoplastic events, identified crucial metabolic and epigenomic changes occurring during GEJ model tumorigenesis, and discovered a potential cancer-therapeutic strategy, while providing insights into pro-neoplastic mechanisms associated with TP53/CDKN2A inactivation in early GEJ neoplasia.

overall_design: Examination of mRNA expression in human gastroesophageal junction organoids with or without knockout of TP53/CDKN2A.

first: Yulan

last: Cheng

first: Andrew

last: Kalra

first: Stephen

last: Meltzer

first: De

last: Lin


title: Mucin-enriched microenvironment shapes bacteriophage protection efficacy against Pseudomonas aeruginosa in airway epithelial cells

status: Public on Oct 19 2025

city: Jyvaskyla

first: Daniel

middle: de Oliveira

last: Patricio

address: Survontie 9C

department: Department of Biological and Environmental Science and Nanoscience Center

country: Finland

institute: University of Jyvaskyla

summary: Mucin hypersecretion, a hallmark of chronic respiratory diseases (CRD), creates a complex microenvironment that reshapes host immunity and microbial behavior. However, its impact on bacteriophage therapy remains poorly understood. Here, we demonstrate that, despite reducing Pseudomonas aeruginosa internalization, mucin increases bacterial-induced cytotoxicity and inflammation in airway epithelial cells, while driving CRD-like transcriptional changes, including hypoxia and stress responses. Mucin selectively downregulates virulence factors without impairing bacterial growth. P. aeruginosa-infecting bacteriophage DMS3vir retained full lytic activity in mucin-rich conditions and, in synergy with mucin, enhanced epithelial cells protection against cytotoxicity. DMS3vir also reduced IL-8 gene expression without triggering antiviral responses. Furthermore, mucin shaped phage-resistant P. aeruginosa phenotypes, altering pigmentation, pigmentation, pyocyanin production, and motility. These changes influenced virulence trade-offs. These findings uncover the dual role of mucins as modulators of infection and sensitizers to phage protection, paving the way for optimized, mucosa-adapted phage therapies in chronic lung diseases.

overall_design: RNA-seq of A549 cells exposed to 0.2 % Mucin and A549 control samples

middle: O

first: Katri

last: Niitti

first: Valtteri

last: Suokko

first: Lucilene

last: Granella

first: Gabriel

middle: M

last: Almeida

first: Lotta-Riina

last: Sundberg


title: Single-cell spatiotemporal transcriptomic and chromatin accessibility profiling in developing postnatal human and macaque PFC

first: Suijuan

last: Zhong

state: Haidian

address: No.19 Xinjiekouwai Street

institute: Beijing Normal University

summary: Unraveling the cellular and molecular characteristics of human prefrontal cortex (PFC) development is crucial for understanding human cognitive abilities and vulnerability to neurological and neuropsychiatric disorders. Here, we have created a comparative repository for gene expression, chromatin accessibility, and spatial transcriptomics of human and macaque postnatal PFC development at single-cell resolution. Integrative analyses outlined species-specific dynamic trajectories of different cell types, highlighting key windows and gene regulatory networks for processes such as synaptogenesis, synaptic pruning, and gliogenesis. We identified regulatory correlates of the prolonged development of human PFC relative to macaques. Glial progenitors showed higher proliferation capability in humans compared to macaques, which was associated with distinct gene expression profiles. Furthermore, we uncovered cell types and lineages most susceptible to neurodevelopmental and neuropsychiatric disorders, focusing on transcription factors (TFs) with human-specific expression features. In summary, our discoveries shed light on human-specific regulatory programs extending postnatal cortical maturation through coordinated neuronal and glial development, with implications for cognition and neurodevelopmental disorders.

overall_design: we sampled and performed snRNA-seq on macaque prefrontal samples  with biological replicates

first: Qian

last: Wu


title: Gene expression profiling of human CD4+T cell subsets: comparison of naive T cells, T helper 1 and T helper 17 cells.

city: Braunschweig

first: Jochen

last: Huhn

address: Inhoffenstraße 7

country: Germany

institute: HZI - Helmholtz-Zentrum für Infektionsforschung GmbH

summary: Naive CD4+T cells are highly plastic cells that - upon activation - can differentiate into various T helper (Th) cell fates characterized by the expression of specific transcription factors and effector cytokines. Their expression can be stabilized by epigenetic mechanisms including DNA methylation. So far, our knowledge about the link between DNA methylation and T helper cell differentiation processes is fragmentary. After the identification of differentially methylated regions (DMRs) in human T helper cells we enlarged the characterization by analysing the transcriptome of ex vivo isolated and sorted naive T cells, Th1 and Th17 cells. This enables us to study the differential gene expression among CD4+T helper subsets, identify links between transcriptome and methylome, and search for expressed transcription factors that could bind to DMRs.

overall_design: low input RNA seq from human ex vivo isolated Th1, Th17 and naive T cells

first: Saumya

middle: D

last: Kumar

first: Anna

last: Ntalli

first: Stefan

last: Floess

last: Huehn


title: Specific targeting of transcriptional T-box riboswitches leads to effective inhibition of S. aureus

city: Patras

first: Adamantia

last: Kouvela

address: Asklipiou 1

country: Greece

institute: Department of Biochemistry, School of Medicine, University of Patras

summary: T-box riboswitches belong to a specific class of RNA regulatory elements that control gene expression in Gram-positive bacteria, including prominent human pathogens. They sense the availability of amino acids by detecting the aminoacylation status of their cognate tRNAs and regulate the expression of genes involved in aminoacylation, amino acid transport, and metabolism. Recent advances on the structures and mechanisms of several regulatory non-coding RNAs among pathogenic bacteria have garnered attention for the development of a new generation of species-specific antibacterials. The frequently acquired resistance against current antibiotics has emerged as a significant challenge for healthcare systems and a serious threat to public health. Herein, we report the characterization of an effective T-box riboswitch inhibitor, termed T-box-i, which efficiently disrupts T-box riboswitch-mediated transcription in vivo. T-box-i was selected through a virtual screening campaign of commercially available small molecules against high-resolution crystallographic structures of T-box riboswitches. It exhibited no cytotoxicity in mammalian cells nor induced antibiotic resistance in S. aureus cultures. These findings provide valuable insights into exploiting T-box riboswitches as antibiotic targets and underscore the therapeutic potential of compounds that selectively target extensively structured regulatory RNA elements and interfaces to combat drug-resistant pathogens.

overall_design: Expression profiling by the Ion Torrent Genestudio S5 platform with Ion Chef (Ion torrent).

first: Nikoleta

last: Giarimoglou

first: Athanasios

last: Papakyriakou

first: Jinwei

last: Zhang

first: Vassiliki

last: Stamatopoulou

first: Constantinos

last: Stathopoulos


title: Knockout screens reveal genes and pathways essential for neuronal differentiation and implicate PEDS1 in neurodevelopment

city: Jerusalem

first: Alana

last: Amelan

address: 9 Wolfson Boulevard

department: Genetics

country: Israel

institute: The Hebrew University of Jerusalem

summary: Neurodevelopmental disorders (NDDs) arise from disruptions in brain development, yet the underlying pathways remain incompletely understood. Here, we demonstrate that genome-wide CRISPR knockout screens in mouse embryonic stem cells differentiating into neural lineages identify hundreds of essential genes, only a minority of which are currently implicated in NDDs. Dominant NDD genes were enriched for transcriptional regulators, whereas recessive NDD genes were predominantly involved in metabolic processes. Mouse models for eight genes (Eml1, Dusp26, Dynlrb2, Mta3, Peds1, Sgms1, Slitrk4 and Vamp3) revealed marked neuroanatomical abnormalities, including microcephaly in half of the cases. Focusing on PEDS1, a key enzyme in plasmalogen biosynthesis, we identified a bi-allelic variant in individuals with microcephaly, global developmental delay and congenital cataracts. In mice, Peds1 deficiency led to accelerated cell-cycle exit and impaired neuronal differentiation and migration. These pathways required for neural differentiation provide a genetic framework for discovering additional NDD genes.

overall_design: RNA-seq profiling of the screen on days 0, 4 and 10 of neural differentiation, and RNA-seq profiling of two Peds1 mutant clones and two wildtype clones at day 4 of neural differentiation.

first: Stephan

last: Collins

first: Nadirah

middle: S

last: Damseh

first: Nanako

last: Hamada

first: Ahd

last: Salim

first: Elad

last: Dvir

first: Galya

last: Monderer-Rothkoff

first: Tamar

last: Harel

first: Koh-ichi

last: Nagata

first: Binnaz

last: Yalcin

first: Sagiv

last: Shifman


title: Catalytic-dependent and -independent functions of H3K4 methyltransferases in C. elegans development

first: Hua

last: Wang

address: 38 Xueyuan Rd

institute: Peking University

summary: The KMT2 class of histone methyltransferases regulates the methylation of Histone 3 Lysine 4 (H3K4), a conserved post-translational modification largely associated with active transcription. However, studies have highlighted catalytic-independent biological functions of KMT2 members and questioned the influence of H3K4 methylation on gene expression. Here, we address these questions by  generating catalytic-inactive mutants of SET-2 and SET-16, the only two KMT2 members in Caenorhabditis elegans (C. elegans). By chromatin analyses we determined the effect of SET-2 and SET-16 catalytic activities on H3K4me3 deposition at regulatory elements and identified common and specific target genes. Parallel gene expression analyses indicate that lack of SET-2 and SET-16 catalytic activities results in deregulation of gene expression independent of H3K4me3 status at transcription start sites. Finally, we examinated the relevance of SET-2 and SET-16 catalytic activity on phenotypes identified in null mutants and found that the catalytic activity of SET-2 is essential for proper development and fertility, while the enzymatic activity of SET-16 has cell-type specific functions. Interestingly, animals with simultaneous loss of SET-2 and SET-16 catalytic activities are viable and fertile. Overall, our results point to catalytic-dependent and -independent roles of KMT2 members and reveal that loss of the majority of H3K4me3 is compatible with development and reproduction in C. elegans.

overall_design: To investigate the enzymatic activity of SET-2 and SET-16, we generated catalytic inactive mutants of SET-2 and SET-16, set-2(zr1504) and set-16(zr1804)


title: Role of the mineralocorticoi receptor in parietal epithelial cells activation

city: Paris

first: Sheerazed

last: BOULKROUN

address: 56 rue Leblanc

institute: Inserm

summary: Focal segmental glomerulosclerosis (FSGS) is a common histological lesion in adults worldwide. It is caused by initial podocyte injury followed by a maladaptive activation of the glomerular parietal epithelial cells (PECs) and conduct to progressive scarring of glomeruli. Current knowledge of the pathophysiological mechanisms leading to PECs actvation is limited. Recent evidence indicates an active, destructive role for PECs in extracapillary glomerular diseases. This suggests that targeting such maladaptive responses could represent a novel therapeutic option to prevent kidney failure in patients. Yet, druggable pathways to prevent or stop PEC pathogenic behavior are still elusive. Here, we examined the role of the mineralocorticoid receptor (MR) signaling in PECs. We demonstrate that MR gene targeting specifically in PECs prevents PEC migration and proliferation after DOCA-salt administration and uninephrectomy in mice, a robust model of maladaptive FSGS. Remarkably, both MR deficiency in PECs ad MR pharmacological blockade using eplerenone were also efficient in preventing extracapillary lesions and glomerular failure in nephrotoxic serum-induced crescentic glomerulonephritis. Finally, we revealed a noteworthy overlap between pathways triggered by HB-EGF/EGFR signaling and aldosterone/MR signaling in PECs. Together, our results highlight the role of MR signaling in the pathophysiology of extracepillary glomerulopathies, FSGS, and crescentic glomerulonephritis, supporting MR antagonists as potential complementary therapeutic agents with original mode of action for such diseases.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PEC cells in response to different treatments (HB-EGF, eplerenone and HB-EGF+eplerenone)

first: Helene

last: Lazareth

first: Olivia

last: Lenoir

last: Boulkroun

first: Maria-Christina

last: Zennaro

first: Pierre-Louis

last: Tharaux


title: Effect of silencing of DEPDC1 on gene expression in MDA-MB 231 TNBC cell line

status: Public on Oct 18 2025

city: Trieste

first: Silvano

last: Piazza

address: localita' Padriciano 99

institute: ICGEB

summary: DEPDC1 supports tumor growth, migration and metastases formation. To investigate what is the gene expression network regulated by DEPDC1, we silenced its expression in MDA-MB-231 Triple Negative Breast Cancer (TNBC) cell line. We then performed gene expression profiling analysis using data obtained from RNA-seq of MDA-MB 231.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for MDA-MB 231 cells transfected with Control or DEPDC1 siRNAs, with 3 and 4 replicates respectably.

first: Giannino

last: Del Sal

first: Manuel

last: Caputo

first: Alessandra

last: Rustighi


title: 4-Vinylcyclohexene diepoxide induces ovarian toxicity and oocyte damage in mice: mechanisms involving m6A/IGF2BP3-mediated meiotic mRNA stability regulation

city: Guangzhou

first: yang

middle: li

last: Li

state: guangdong

address: No. 111, Dade Road, Guangzhou City, Guangdong Province

institute: The Second Clinical College, Guangzhou University of Chinese Medicine

summary: This study investigates the role of m6A RNA methylation and IGF2BP3 in VCD-induced ovarian toxicity in mice. VCD exposure caused follicular depletion, oxidative stress, DNA damage, and meiotic defects in oocytes. Mechanistically, VCD altered m6A modifiers (METTL3, FTO, ALKBH5) and destabilized key meiotic mRNAs (e.g., Cenpa, Bub1, Polq) via IGF2BP3 downregulation, leading to spindle defects and chromosomal missegregation. Our findings reveal an m6A/IGF2BP3 axis as a critical mediator of environmental ovotoxicity.

first: Yang

first: Yu

middle: L

last: Zhou

first: Jian

last: Liu

first: Hong

middle: Y

last: Yang

first: Guang

middle: N

last: Nie

first: Fang

middle: P

last: Cheng


title: T-cell Repertoire Characteristics of Asymptomatic and Re-detectable Positive COVID-19 Patients

city: Fushan

first: Jianhua

last: Xu

state: Guangdong

address: No. 12, Jinsha Avenue, Shunde District, Foshan, Guangdong, P.R. China

institute: Department of Laboratory Medicine Shunde Hospital of Guangzhou University of Chinese Medicine

summary: The prevention of COVID-19 pandemic is highly complicated by the prevalence of asymptomatic and recurrent infection. Many previous immunological studies have focused on symptomatic and convalescent patients, while the immune responses in asymptomatic patients and re-detectable positive cases remain unclear. Here we comprehensively analyzed the peripheral T-cell receptor (TCR) repertoire of 54 COVID-19 patients in different courses, including asymptomatic, symptomatic, convalescent and re-detectable positive cases. We identified a set of V-J gene combinations characterizing the upward immune responses through asymptomatic and symptomatic courses. Furthermore, some of these V-J combinations could be awakened in the re-detectable positive cases, which may help predict the risk of recurrent infection. Therefore, TCR repertoire examination has the potential to strengthen the clinical surveillance and the immunotherapy development for COVID-19.

first: Dongdong

first: Yongsi

last: Wang

first: Yaling

last: Shi

first: Jiaqi

last: Zhang

last: Hu

first: Yuntao

first: Dongzi

last: Lin

first: Jing

first: Wei

first: Haolan

last: He

first: Wentao

last: Fan

first: Linlin

first: Kejian

first: Dawei


title: RNA-Seq profiling of nup50c mutants

city: Weifang

first: Yu

last: Tang

state: Shandong

address: No. 699, Binhu Road, Xiashan Ecological Economic Development Zone

institute: Peking University Institute of Advanced Agricultural Sciences

summary: Purpose: To understand the molecular mechanism and severe phenotype caused by the mutation of Nup50c, we performed the whole genome transcriptome analysis on 9-day-old seedlings of WT and nup50c. Conclusions: Nup50c regulates stress-related gene expression

overall_design: mRNA profiles of 9-day-old seedlings of wild type (Col-0), nup50c mutants were generated by deep sequencing, in triplicate, using Illumina HiSeq PE-150.

first: Xiangyun


title: Cathepsin D-Mediated MHC-I Degradation Contributes to Immune Evasion in Microsatellite Stable Colorectal Cancer

first: Weixiang

last: Zhan

address: 广东省广州市天河区员村二横路东璟花园

institute: Sun Yat-sen university

summary: Microsatellite stable (MSS) colorectal cancer (CRC) is often characterized as a "cold" tumor, exhibiting minimal responsiveness to monotherapy with PD-1 antibodies. The underlying mechanisms of this intrinsic unresponsiveness to immunotherapy have been elusive. Here, we report that cathepsin D (CTSD) is highly expressed in MSS CRC, significantly contributing to its resistance to immunotherapy. Specifically, CTSD facilitates immune evasion by shielding cancer cells from cytotoxic T-cell-mediated killing. Mechanistically, as a protease, CTSD interacts with the α2 domain of the major histocompatibility complex class I (MHC-I) molecule via its catalytic domain's light chain, promoting the degradation of MHC-I through lysosomal pathways and disrupting the recycling of MHC-I to the cell surface. Notably, deletion or pharmacological inhibition of CTSD with pepstatin A prevents this immune evasion and enhances the efficacy of anti-PD-1 antibodies. Collectively, these findings highlight the role of CTSD in immune evasion and provide a compelling rationale for the development of a novel combination therapy involving CTSD inhibition and anti-PD-1 immunotherapy in CRC.

overall_design: To investigate the functional role of CTSD in CRC, NC and CTSD knockdown CT26 tumors. To elucidate the impact of CTSD depletion on the immune microenvironment of MSS CRC, we conducted single-cell RNA sequencing (scRNA-seq) to profile transcriptomic alterations in shCTSD versus shNC CT26 syngeneic tumors. After stringent quality control, we obtained 68,159 high-quality single-cell transcriptomes from both tumor groups

first: Yang

last: Fu

first: Yina

first: Runkai

last: Cai

first: Fan

last: Bai

first: Chenxu

last: Guo

first: Yi

first: Zehua

last: Wu

first: Ge

last: Qin

first: Yuqian

last: Xie

first: Jianwei

first: Yanhong

last: Deng


title: A noncanonical cytoplasmic role for BUB1 in restraining DNA damage-induced dsRNA  accumulation and viral mimicry within stress granules [cytoplasmic RNA-seq]

city: Durham

first: Mengjie

state: North Carolina

address: 1228 Northcreek Dr

institute: Duke University

summary: BUB1 is a nuclear serine/threonine protein kinase and a vital spindle assembly checkpoint (SAC) complex member responsible for proper chromosome segregation before mitosis. Here we report that BUB1 plays an unexpected cytoplasmic role in restraining DNA damage-induced accumulation of cytoplasmic dsRNA and ensuing immune response. We showed that tumors deficient in BUB1 were sensitive to radiotherapy in a CD8+T-cell-dependent manner. Furthermore, we discovered increased immune cell infiltration accompanied by elevated type I interferon production from irradiated BUB1-deficient cells, caused by enhanced cytoplasmic dsRNA accumulation and activation of the MDA5/MAVS/IRF7 dsRNA-sensing pathway. Mechanistically, we discovered that after exposure to ionizing radiation, BUB1 underwent a robust nucleus-to-cytoplasm migration, where it bound and phosphorylated the polyA-binding protein PABPC1, which was degraded together with its associated mRNAs stored in the stress granules, thereby preventing dsRNA accumulation and activation of the innate immune response. Our study, therefore, reveals a novel biological role for BUB1 in suppressing DNA-damage-induced cytoplasmic dsRNA accumulation/viral mimicry and provides a rationale for inhibiting BUB1 to enhance cytotoxic cancer therapy immunologically.

overall_design: To investigate the cytoplasmic RNA involved in Bub1 deficiency-mediated enhancement of radiotherapy, we established Bub1-deficient HCT116 cells by using the CRISPR-Cas9 technology and fractionated vector control and Bub1KO HCT116 cells after radiaiton treatment

first: Dong

last: Pan

first: Meng

last: Jiao

first: Xuhui

last: Bao

first: Xinjian

last: Liu

first: Fang

last: Li

first: Chuan-Yuan


title: Irinotecan activates anti-tumor immunity in HCT116 tumor cells

city: Nanjing

first: Xinghua

last: Gao

state: Jiangsu

address: #639 Longmian Dadao

institute: China Pharmaceutical University

summary: Topoisomerase I (Top1) is a classical drug target for anticancer therapy, but its role in immune signaling in cancer cells remain unclear. Here, we aimed to explore the possible role and mechanism of Irinotecan (CPT-11) in anti-tumor immunity.

overall_design: mRNA expression profiles of CPT-11-treated HCT116 tumor cells were generated by deep sequencing, in duplicate.

first: Yong

last: Yang

first: Yanting

last: Lin


title: A noncanonical cytoplasmic role for BUB1 in restraining DNA damage-induced dsRNA  accumulation and viral mimicry within stress granules [RNA-seq]

last: Hu

overall_design: To investigate the molecular mechanism involved in Bub1 deficiency-mediated enhancement of radiotherapy, we established Bub1-deficient B16F10 cells by using the CRISPR-Cas9 technology.


title: STAMBP is required for long-term maintenance of neural progenitor cells derived from hESCs

city: HONG KONG

first: JITIAN

last: ZHANG

address: Tat Chee Avenue

institute: CITY UNIVERSITY OF HONG KONG

summary: Mutations in STAMBP have been well-established to cause congenital human microcephaly-capillary malformation (MIC-CAP) syndrome, a rare genetic disorder characterized by global developmental delay, severe microcephaly, capillary malformations, etc.We report here that STAMBP is dispensable for the pluripotency maintenance or neural differentiation of hESCs. However, neural progenitor cells (NPCs) derived from STAMBP-deficient hESCs fail to be long-term maintained/expanded in vitro. We identified the anti-apoptotic protein CFLAR is down-regulated in those affected NPCs and ectopic expression of CFLAR rescues NPC defects induced by STMABP-deficiency.

overall_design: RNA-seq analysis revealed that apoptosis related genes are enriched in up-regulated genes in mutants neural progenitor cells when comparing with WT nerual progenitor cells and  both up-regulated and down-regulated genes in KO NPCs are partially restored in KO+CFLAR NPC.

first: Jitian

first: Yanqi

first: Yancai

last: LIU

first: Xiao

last: SHU


title: Gene expression in whole seedlings (wild-type, dof1.7-KO)

city: Bunkyo-ku

first: Yasuhito

last: Sakuraba

state: Tokyo

address: Yayoi 1-1-1

department: Agro-Biotechnology Research Center

country: Japan

institute: The University of Tokyo

summary: To examine differential effect of the mutation of Arabidopsis dof1.7 on the gene expressions, we performed microarray analysis using whole seedlings of wild-type and dof1.7-KO mutant.

overall_design: whole seedlings from 10 day-old wild-type and dof1.7-KO seedlings grown under nitrogen-sufficient and nitrogen-defficient conditions

first: Shuichi

last: Yanagisawa


title: RNAseq analysis of skeletal muscle transcriptomes from wild type and MLL4SETf/fHSA-Cre mice

first: Zhenji

last: Gan

address: 12 Xuefu Road

department: Model Animal Research Center of Nanjing University

institute: Nanjing University

summary: Enhancers play central role in controlling gene expression in time and space. Primed enhancers are marked by histone H3 lysine 4 (H3K4) mono/di-methylation (H3K4me1/2). Mixed-lineage leukemia 4 (MLL4/KMT2D) is an evolutionarily conserved H3K4me1/2 methyltransferase that is required for enhancer activation. To investigate the physiological importance of MLL4 in skeletal muscle nutrient handling, skeletal muscle-specific Mll4-knockout (MLL4SETf/fHSA-Cre) and wild-type (WT) littermates were placed on HFD (60% kcal from fat). Remarkably, muscle-specific deletion of MLL4 protects against high-fat diet-induced obesity and improves systemic glucose homeostasis. To dissect the underline mechanism, we conducted a comprehensive study of the muscle transcriptome induced by MLL4 deletion, HFD feeding, or the combination. Comparison of gene expression profiles in MLL4SETf/f muscle revealed 638 genes in total whose expression was significantly regulated by HFD, and comparison between WT and MLL4SETf/fHSA-Cre muscle showed 1430 and 1490 genes that were influenced by MLL4 abrogation on CD and HFD, respectively. Categorized into four subgroups, gene ontology (GO) pathway analysis not only showed HFD-induced immune and inflammatory pathways that were suppressed by MLL4 deficiency, but also revealed muscle metabolic and contractile gene networks that were substantially altered by MLL4 abrogation.

overall_design: Gastrocnemius muscle mRNA profiles of 20-week-old WT and MLL4SETf/fHSA-Cre mice were generated by deep sequencing, in triplicate, using Illumina NovaSeq 6000.

first: Chenyun

last: Ding


title: Tissue Engineered Elastic Cartilage-Mimetic Auricular Grafts for Microtia Reconstruction

status: Public on Oct 17 2025

city: Basel

first: Filippo

middle: M.

last: RIJLI

address: Maulbeerstrasse 66

country: Switzerland

institute: Friedrich Miescher Institute for Biomedical Research

summary: Microtia, the congenital malformation of the external ear, imposes a significant psychosocial burden on affected children1-4. The current gold standard treatment, autologous costal cartilage reconstruction, requires multiple complex surgeries, including the harvest of rib cartilage5-7. Tissue engineering offers a promising alternative, enabling the generation of patient-specific auricular grafts from a small biopsy (~5 mg). However, despite multiple decades of research, clinically viable, tissue engineered auricular grafts remain unavailable8. Key challenges include fibrocartilage formation in vitro, heterogeneous extracellular matrix development, and mechanical inferiority, all resulting in graft deformation and degradation in vivo9-15. Here, we report the successful fabrication of bioprinted auricular grafts that closely resemble native human auricular cartilage. Our grafts demonstrated a uniform distribution of elastin, glycosaminoglycans, and collagen II, lacked collagen I, and achieved a compressive modulus of 803 ± 134 kPa after 9 weeks of maturation in vitro (human auricular cartilage: 1023 ± 101 kPa). In vivo, grafts maintained their structural integrity for 6 weeks in a subcutaneous rat model and showed a transition towards mature elastic fiber. These grafts represent the closest approximation to native elastic cartilage reported to date and lay the foundation for a clinically viable, long-term treatment for children affected by microtia.

overall_design: RNA-seq profiling of tissue engineered auricular cartilage grafts made of primary human auricular chondrocytes of patients undergoing otoplasty procedure in either hyaluronan transglutaminase (HATG) or HATG-Alginate (HATG-Alg) grafts evaluated after 3 and 9 weeks of in vitro culture/maturation

first: Philipp

last: Fisch

first: Sandra

last: Kessler

first: Simone

last: Ponta

first: Anna

last: Puiggali-Jou

first: Guoliang

last: Lyu

first: Killian

last: Flégeau

first: Anastasiya

last: Martyts

first: Florian

last: Roth

first: David

last: Fercher

last: Rijli

first: Daniel

last: Simmen

first: Eva

last: Novoa Olivares

first: Thomas

last: Linder

first: Marcy

last: Zenobi-Wong


title: The Candida albicans transcription factor Efg1 regulates in vitro filamentation through a cAMP-Protein Kinase A independent mechanism

city: Iowa City

first: Damian

last: Krysan

state: IA

address: 25 South Grand, 2040 ML

department: Division of Pediatrics & Infectious Disease

institute: University of Iowa Hospitals and Clinics

summary: Candida albicans is one of the most common causes of human fungal disease. One of the most studied C. albicans virulence traits is its ability to adopt both yeast and filamentous morphologies. Accordingly, the regulation of the yeast-to-filament transition has been area of intense study in medical mycology. A longstanding mechanistic paradigm in this field is that the cAMP-protein kinase A pathway phosphorylates a master transcriptional regulator of C. albicans filamentation, Efg1, to drive filamentation. This model has been generalized over the years despite the fact that the initial work showed that it applied to only specific in vitro filamentation conditions. Here, we reinvestigated the protein kinase A-Efg1 paradigm by generating new strains containing alleles of EFG1 with the putative protein kinase A phosphorylation site (T208) mutated to either Ala or Glu which blocks or mimics phosphorylation, respectively. We integrated these alleles into efg1∆∆ mutants so that they are expressed from the endogenous promoter. We assayed the effect of these Efg1 mutations on: 1) in vitro filamentation under a wide range of inducing condition; 2) biofilm formation; 3) in vivo filamentation; 4) virulence in a model of disseminated candidiasis; and 5) gene expression during in vitro filamentation. We found no evidence that blocking or mimicking protein kinase phosphorylation of Efg1 affected its function during filamentation, biofilm formation, of infection. These observations indicate that the protein kinase A-Efg1 model for the regulation of C. albicans filamentation should be reconsidered.

overall_design: RNA-seq profiling of wild-type C. albicans and strains containing an EFG1 (T208A) mutation or deletion.

first: Juraj

last: Kramara

first: Rohan

last: Wakade

first: Corey

last: Frazer

first: Mark

middle: A

last: Stamnes

first: Richard

last: Bennett


title: Sequential verification of transcription by Integrator and Restrictor [U170K_POINT-seq]

city: Exeter

first: Steven

last: West

state: Devon

address: Stocker Rd

department: Living Systems Insitute

institute: University of Exeter

summary: The decision between productive elongation and premature termination of promoter-proximal RNA polymerase II (RNAPII) is fundamental to metazoan gene regulation. Integrator and Restrictor complexes are implicated in promoter-proximal termination, but why metazoans utilise two complexes and how they are coordinated is unknown. Here, we show that Integrator and Restrictor sequentially and non-redundantly monitor distinct early steps of transcription. Integrator predominantly engages paused RNAPII to trigger premature termination, which can be prevented by cyclin-dependent kinase 7/9 activity. Crucially, we reveal a previously unrecognised and universal checkpoint imposed by Restrictor after promoter-proximal pausing. This restriction zone presents an additional opportunity to verify RNAPII. Progression through this second checkpoint requires U1 small nuclear ribonucleoprotein (snRNP), which antagonises Integrator and Restrictor in a U1-70K dependent manner. These findings reveal the principles of a sequential validation mechanism governing the balance between productive and attenuated transcription, rationalising the necessity of Integrator and Restrictor complexes in metazoans.

overall_design: Expression profiling by POlymerase Intact Nascent Transcript sequencing (POINT-seq) for dTAG-U170K degron cell line (with or without dTAG)

first: Chris

last: Estell

first: Krystian

last: Łazowski

first: Joshua

last: Eaton


title: Mitochondrial dysfunction in PRRSV-2 infected macrophages

city: Saint-Paul-lez-Durance

first: Thien-Phong

last: Vu Manh

address: CEA Cadarache, Zone Cité des Énergies BIAM

department: BIAM

institute: CNRS

summary: Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is one of the most economically devastating viruses for the global swine industry. PRRSV has a known tropism for lung macrophages, where it causes impaired immune responses. This study evaluated the metabolic and immune profiles of primary porcine alveolar macrophages (PAM) and pulmonary intravascular macrophages (PIM) infected with different strains of PRRSV-2 isolated from North Carolina (NC) pig herds (NC134, NC18-9-7 referred to as NC174, NC20-1 referred to as NC144), and VR2232, a PRRSV-2 prototype strain. Primary enriched mononuclear phagocytes were infected ex vivo with NC134 and NC174, sorted, and the total RNA was used for a transcriptomic approach; additionally, gene expression was further validated by RT-qPCR and NanoString technology. Complementary functional assays with additional NC strains were used to further investigate the oxidative stress, mitochondrial and metabolic dysfunction induced by PRRSV-2 infection. PAM infected with both NC PRRSV-2 strains NC174 and NC134 showed similar transcriptomic profiles during the early stage of infection, with downregulation of genes involved in the oxidative phosphorylation and electron transport chain pathways. PIM infected with both NC174 and NC134 strains showed limited alteration in the transcriptomic profiles compared to uninfected cells. The genetic reprogramming matched the PRRSV-2 induced mitochondrial impairment observed in functional assays performed with Seahorse technology. Mitochondrial respiration displayed slightly different profiles between PIM and PAM infected with the different PRRSV-2 strains, with PAM showing a more substantial decrease in mitochondrial fitness compared to control cells. When reactive oxygen species (ROS) and nitric oxide (NO) production were evaluated, no differences were observed between PRRSV-2 infected PAM and PIM and control cells. These results provide valuable insights into the pathogenetic mechanism of different North Carolina PRRSV-2 strains, focusing on the alteration of mitochondrial function in lung macrophages during early infection and highlighting differences in lung macrophages responses to distinct PRRSV-2 strains

overall_design: Lung bronchoalveolar lavage (BAL) and parenchyma (PAR) samples were isolated from two male and two female animals between 8-12 weeks of age were used. For each pig, thirty million enriched mononuclear pahgocytes (MNP) from both BAL and PAR were infected with NC134 and NC174 at MOI=1 or left uninfected in 50 ml falcon tubes for 12h. Infections were synchronized and after 12h cells were washed and stained with a five-color flow cytometry staining to sort AM, PIM, monocyte derived dendritic cells (moDC) and classical DC (cDC),  PAM were sorted from BAL samples and PIM, cDC and moDC were sorted from PAR samples. After sorting, approximately 300,000 PAM and 100,000 PIM were collected for each condition.A range between 63,000 and 100,000 were collected for moDC and cDC. Total RNA was obtained from 63,000-100,000 sorted PAM, PIM, moDC, cDC of four pigs (two females and two males) using the PicoPure RNA Isolation Kit (Thermo Fisher, KIT0204) following manufacturer’s instructions. RNA quantity was determined using a Nanodrop 1000 (Thermo Fisher) and an Agilent Bioanalyzer (Agilent), with RIN values ranging from 7.1-9.6 and concentrations ranging from 0.11-21.61 ng/uL. RNA-seq libraries were generated from 1ng of total RNA per sample, using a NEBNext Single Cell/Low Input RNA Library Prep Kit for Illumina (New England Biolabs) and NEBNext Multiplex Oligos for Illumina (New England Biolabs) following the manufacturer’s instructions. Amplified cDNA quality and quantity were assessed using an Agilent Technologies 2200 TapeStation with high sensitivity D5000 tape. For library preparation, 2ng of amplified cDNA per sample were used. Library quality was assessed using an Agilent Technologies 2200 TapeStation with D1000 tape. Libraries were quantified by RT-qPCR using a NGS Library Quantification kit (Takara Bio) following the manufacturer’s instructions. A total of 47 cDNA libraries were diluted to 10 nM, pooled, and submitted to Novogene for 150-bp paired-end sequencing on a NovaSeq 6000 S4 lane (Illumina).

first: Alba

last: Frias-De-Diego

first: Abigail

last: Williams

first: John

last: J. Byrne

first: Chaitawat

last: Sirisereewan

first: Julie

last: Hicks

first: Liu

last: Hsiao-Ching

first: Elisa

last: Crisci


title: TRIM15 forms a regulatory loop with the AKT/FOXO1 axis and LASP1 to modulate the sensitivity of HCC cells to TKIs

city: Changsha

first: Huaiyuan

last: Liang

address: 183 Renmin Middle Road

institute: Institute of Urological Cancer, Central South University

summary: For patients with advanced or metastatic Hepatocellular carcinoma (HCC) who are not suitable for surgical resection, systemic therapy has been considered to be the standard treatment. In recent years, a small subset of patients with unresectable HCC have been benefit from tyrosine kinase inhibitors (TKIs), and the overall survival time of these patients is significantly increased. However, all responders ultimately develop resistance to TKI treatment. The tripartite motif (TRIM) family member TRIM15 acts as an E3 ligase to mediate the polyubiquitination of substrates in cells. However, the biological role of TRIM15 in HCC is still an enigma. In our study, our results demonstrated that TRIM15 was abnormally upregulated in liver cancer cells after treated with TKIs and that this upregulation of TRIM15 contributed to TKI resistance in liver cancer cells. Then, we demonstrated that the upregulation of TRIM15 after TKI treatment was mediated by the AKT/FOXO1 axis. Moreover, we demonstrated that TRIM15 induced the nuclear translocation of LASP1 by mediating its K63-linked polyubiquitination, which modulated sensitivity to TKIs by increasing the phosphorylation of AKT and the expression of Snail in liver cancer cells. Collectively, we identified a novel AKT/FOXO1/TRIM15/LASP1 loop in cells, which provided potential candidates for overcoming TKI resistance in HCC.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for the HCC cells after kncokdown of TRIM15.

first: Xin

last: Jin


title: Sequential verification of transcription by Integrator and Restrictor [ZC3H4_INTS4_chrRNA-seq]

overall_design: Expression profiling by chromatin-associated RNA sequencing (chrRNA-seq) for dTAG-INTS4/ZC3H4-DHFR degron cell line (with or without dTAG, TMP)


title: Sequential verification of transcription by Integrator and Restrictor [ZC3H4_EXOSC3_nucRNA-seq]

overall_design: Expression profiling by nuclear RNA sequencing (nucRNA-seq) for dTAG-EXOSC3/ZC3H4-DHFR degron cell line (with or without dTAG, TMP)


title: Intercellular crosstalk within human preimplantation lineages regulates Trophectoderm specification

city: Shanghai

first: Tu

middle: zhi

last: fen

address: Tongji University Siping Road Campus

department: life science and technology

institute: Tongji University

summary: our study reconstructs a comprehensive communication network for human preimplantation lineages and integrates it with downstream gene regulatory networks, thus offering vital insights into lineage specification and cell fate regulation during human embryonic development.

overall_design: Transcription profiling of TFAP2C knockout in nTE cells

first: Yan

last: Bi

first: Zhifen

last: Tu

first: Yixuan

last: Wang


title: RNAseq analysis of liver transcriptomes from wild-type and MLL4SETf/fHSA-Cre mice

first: Zhenji

last: Gan

summary: Evidence is emerging that skeletal muscle metabolic reprogramming could be a modifier of hepatic steatosis. Skeletal muscle-specific Mll4-knockout (MLL4SETf/fHSA-Cre) and wild-type (WT) littermates were placed on HFD (60% kcal from fat). Interestingly, muscle MLL4 deficiency prevents HFD-induced hepatic steatosis. To gain insight into the liver metabolic reprogramming in MLL4SETf/fHSA-Cre mice, we performed RNA-Seq analysis on mRNA isolated from liver of the MLL4SETf/fHSA-Cre mice and littermate controls. Gene ontology (GO) analysis of down-regulated genes revealed significant enrichment in lipid metabolic process, inflammatory response as well as collagen fibril organization. Conversely, pathways of oxidation-reduction and epoxygenase P450 were significantly enriched in the upregulated gene set. Gene expression validation studies demonstrated that the expression of the gene encoding lipid uptake and de novo lipogenesis was reduced in HFD-fed MLL4SETf/fHSA-Cre liver, concomitant with an increased in the expression of the oxidation-reduction genes. These findings suggest that MLL4 deletion in skeletal muscle decreases lipid uptake and denovo lipogenesis in the liver, leading to protection from HFD-induced hepatic steatosis.

overall_design: Liver mRNA profiles of 20-week-old WT and MLL4SETf/fHSA-Cre mice were generated by deep sequencing, in triplicate, using Illumina NovaSeq 6000.

first: Chenyun

last: Ding


title: L-Chiral Hydrogel Accelerates Wound Healing via Lactate-Mediated RNF123 K57 Lactylation

first: Ruizhe

last: He

address: No. 639, Zhizaoju Road

institute: Shanghai Jiao Tong University

summary: Chronic wounds, characterized by delayed healing and persistent inflammation, represent a major clinical burden with limited effective therapies. Inspired by the stereoselective interactions in biological systems, we developed an L-chiral hydrogel composed of self-assembled helical nanofibers from L-histidine derivatives, which preferentially enriches lactate to promote wound repair. Compared to D-chiral and racemic hydrogels, the L-chiral hydrogel significantly accelerated wound closure in rat models, achieving nearly 90% healing by day 14 and reducing healing time to 16-17 days. Transcriptomic and metabolomic analyses revealed enhanced wound response pathways and elevated lactate levels in the L-chiral group. Mechanistically, enriched lactate induced K57 lactylation of RNF123, mediated by AARS1, altering RNF123 conformation and weakening its binding to UBAC1. This modification enhanced ubiquitination and processing of NF-κB p105 into p50, inhibiting the NF-κB pathway and promoting angiogenesis via enhanced endothelial cell migration, tube formation, and sprouting. Rescue experiments with lactate inhibitor Oxamate and exogenous lactate confirmed the lactate-dependent mechanism. This study not only demonstrates a drug-free chiral biomaterial for efficient wound healing but also unveils the molecular role of lactate-mediated lactylation in mechanoregulating inflammation and vascularization, offering new insights for regenerative medicine.

sample_organism:
Homo sapiens
Rattus norvegicus

platform_organism:
Homo sapiens
Rattus norvegicus

overall_design: This dataset contains two parts: the first part is RNA-seq from animal experiments, collecting wound margin tissues from rats treated with L-chirality hydrogel and negative control group on day 14 for RNA-seq analysis; the second part is RNA-seq of Human Umbilical Vein Endothelial Cells (HUVEC), constructing stable transfected cell lines of RNF123 wild-type and K57R HUVEC for RNA-seq analysis.


title: PAGE4, upregulated in a novel iPSC-derived hepatoblastoma model, promotes hepatoblastoma progression

city: Sapporo

first: Issei

last: Kawakita

state: Hokkaido

address: N14 W5, Kita-ku

department: Graduated school of Medicine

institute: Hokkaido University

summary: Hepatoblastoma is a primary malignant liver tumor in children, thought to arise from abnormal liver development during the fetal period. Approximately 90% of cases harbor activating mutations in CTNNB1, which encodes β-catenin, while other genetic mutations are rare. Recent studies have shown that CTNNB1 mutations are frequently accompanied by increased expression of the transcriptional coactivator YAP, which promotes cell proliferation and suppresses apoptosis. Based on these findings, we established a hepatoblastoma model by introducing active forms of CTNNB1 and YAP into human iPSC-derived hepatoblasts. Cells transduced with both genes showed distinct morphological changes and upregulation of CTNNB1, YAP, and their downstream target genes. RNA-seq followed by Gene Set Enrichment Analysis (GSEA) revealed that the gene expression profile of these cells closely matches that of hepatoblastoma patients. Utilizing this model, we identified Prostate-Associated Gene 4 (PAGE4)  as a novel candidate gene involved in hepatoblastoma progression. Functional analysis in hepatoblastoma cell lines (Huh6, HepG2) demonstrated that PAGE4 plays a role in promoting cell proliferation and resistance to apoptosis. Since PAGE4 is a known cancer/testis antigen with tumor-specific expression, it has been recognized as a potential target in cancer therapy. Our findings indicate that PAGE4 represents a novel and promising therapeutic target for hepatoblastoma.

overall_design: RNA-seq profiling of iPSC-derived human hepatoblasts and their Day 14 derivatives overexpressing CTNNB1, YAP, or both CTNNB1 and YAP.

first: Shohei

last: Honda

first: Yuta

last: Yamada

first: Shugo

last: Tanaka

first: Yuko

last: Katayama

first: Takeshi

last: Shionoiri

first: Asuka

last: Ishii

first: Hiroyuki

last: Kurosu

first: Kazuya

last: Hamada

first: Kentaro

last: Kumagai

first: Kensuke

last: Nakazono

first: Rino

last: Saito

first: Chihiro

last: Terasaka

first: Ryo

last: Takahashi

first: Insu

last: Kawahara

first: Momoko

last: Ara

first: Sari

last: Iwasaki

first: Satoshi

first: Atsushi

last: Niida

first: Eiso

last: Hiyama

first: Akinobu

last: Taketomi

first: Koji

last: Taniguchi


title: Long-term remissions and marked decreases in resident memory T cells following high induction dosing with risankizumab in randomized patients with moderate-to-severe plaque psoriasis

city: Ann Arbor

first: Poulami

last: Dey

address: 1301 Catherine St

institute: Michigan Medicine

summary: The phase 2 KNOCKOUT (NCT05283135) study evaluated higher-than-approved doses of risankizumab, an interleukin-23 inhibitor, for treatment of moderate-to-severe plaque psoriasis. Patients received either 300 or 600 mg of risankizumab at Weeks 0, 4, and 16 and were monitored through Week 100 without further dosing. Efficacy and safety were tracked throughout the study and RNASeq was performed on lesional/non-lesional tissue. Nine patients per treatment group completed dosing. At Weeks 28 and 52, Psoriasis Areas and Severity Index 75/90/100 responses were achieved by 94.4%/94.4%/83.3% and 77.8%/61.1%/44.4% of all patients, respectively, with no new safety signals. At Week 52, TRM cell numbers in lesional skin were markedly reduced, with numbers similar to non-lesional resident memory T cell numbers at Week 0. High skin clearance rates with higher-than-approved initial dosing of risankizumab with prolonged maintenance of skin clearance, despite the lack of continuous dosing, represent a potential novel treatment strategy for patients with psoriasis.

overall_design:
To investigate changes in cell type composition and transcriptional profiles in psoriatic skin from patients with psoriasis after high-dose risankizumab treatment (at week 52), compared with paired baseline lesional samples collected at week 0.

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

first: Johann

middle: E

last: Gudjonsson

first: Lam

last: Tsoi


title: Sequential verification of transcription by Integrator and Restrictor [INTS4_U1AMO_chrRNA-seq]

first: Steven

last: West

overall_design: Expression profiling by chromatin-associated RNA sequencing (chrRNA-seq) for dTAG-INTS4/ZC3H4-DHFR degron cell line (with or without dTAG, treated with control or U1 antisense morpholino)

first: Chris

last: Estell

first: Krystian

last: Łazowski

first: Joshua

last: Eaton


title: Sequential verification of transcription by Integrator and Restrictor [ZC3H4_mNET-seq]

overall_design: Expression profiling by mammalian Native Elongating Transcript sequencing (mNET-seq) for ZC3H4-DHFR degron cell line (with or without TMP)


title: Gc inhibition preserves insulin sensitivity and reduces body weight without loss of muscle mass

city: Davis

first: Taiyi

middle: Diana

last: Kuo

address: One Shields Ave

department: Neurobio, Physio & Behavior

institute: University of California Davis

summary: Obesity and type 2 diabetes (T2D) are metabolic diseases that have been increasing in prevalence worldwide. Obesity often leads to T2D, which is caused by an imbalanced supply and demand of insulin. Insulin resistance and impaired beta-cell function contribute to the onset of hyperglycemia. Previously, we reported that ablation of Gc, encoding a secreted protein with a primary role in vitamin D transport, improves pancreatic beta-cell function in models of diet-induced insulin resistance. Here, we show that Gc ablation has systemic insulin-sensitizing effects to prevent weight gain, hyperglycemia, glucose intolerance, and lower NEFA and triglyceride in mice fed a high-fat diet. Interestingly, weight loss in Gc-ablated mice resulted from selective fat mass loss with preserved lean mass. Hyperinsulinemic-euglycemic clamps show that Gc ablation protects insulin’s ability to reduce hepatic glucose production and increases glucose uptake in skeletal muscle and adipose tissue. Moreover, acute Gc inhibition, by way of adeno-associated virus encoding a short hairpin RNA to promote Gc mRNA degradation, prevents glucose intolerance caused by high fat feeding. The data suggest that Gc inhibition can provide an approach to increase insulin production in beta-cells and insulin action in peripheral tissues, while shedding fat mass.

overall_design: We performed RNAseq in liver extracts from male mice. Mice were fasted overnight and refed a high-fat diet. There were a total of 4 conditions: fasted WT, fasted GcKO, refed WT, refed GcKO.

first: Richard

last: Gill

first: Taiyi Diana


title: Dual PAX3 and PAX7 transcriptional activities spatially encode spinal cell fates through distinct gene networks

city: Paris

first: Robin

last: Rondon

address: 15 rue Hélène Brion

institute: Institut Jacques Monod / CNRS UMR7592 / Universite Paris Cite

summary: Understanding how transcription factors regulate organized cellular diversity in developing tissues remains a major challenge due to their pleiotropic functions. We addressed this by monitoring and genetically modulating the activity of PAX3 and PAX7 during the specification of neural progenitor pools in the embryonic spinal cord. Using mouse models, we show that the balance between the transcriptional activating and repressing functions of these factors is modulated along the dorsoventral axis and is instructive to the patterning of spinal progenitor pools. By combining loss-of-function experiments with functional genomics in spinal organoids, we demonstrate that PAX-mediated repression and activation rely on distinct cis-regulatory genomic modules. This enables both the coexistence of their dual activity in dorsal cell progenitors and the specific control of two major differentiation programs. PAX promotes H3K27me3 deposition at silencers to repress ventral identities, while at enhancers, they act as pioneer factors, opening and activating cis-regulatory modules to specify dorsal-most identities. Finally, we show that this pioneer activity is restricted to cells exposed to BMP morphogens, ensuring spatial specificity. These findings reveal how PAX proteins, modulated by morphogen gradients, orchestrate neuronal diversity in the spinal cord, providing a robust framework for neural subtype specification.

overall_design: Profiling of PAX3 and PAX7 recruitment by CUT&Tag in spinal neuronal progenitors differenciated from HM1 ES cells in presence or absence of BMP4. RNA-Seq, ATAC-Seq, and CUT&Tag profiling (H3K4me2 and H3K27me3 marks) in spinal neuronal progenitors differenciated in presence or absence of BMP4 from wildtype HM1 ES cells, as well as the knock-out cell lines (Pax3-/-, Pax7-/-, or Pax3-/-; Pax7-/- (DKO)).

first: Théaud

last: Hezez

first: Julien

last: Richard Albert

first: Shinichiro

last: Hayashi

first: Bernadette

last: Drayton-Libotte

first: Gloria

last: Gonzalez Curto

first: Frédéric

last: Auradé

first: Elie

last: Balloul

first: Claire

last: Dugast-Darzacq

last: Relaix

first: Pascale

last: Gilardi-Hebenstreit

first: Vanessa

last: Ribes


title: Transriptional effects of blocking mitochondrial fission-fusion in aging Drosophila clock neurons

city: Waltham

first: Shlesha

last: Richhariya

address: 415 South St

institute: Brandeis University/HHMI

summary: Mitochondria are dynamic organelles and undergo fission-fusion in response to various environemtal cues. But the roles of these two very different mitochondrial forms – predominantly spherical and tubular - are not well-characterized in neurons of animals and especially in aging neurons. This is important because neurons are long-lived and mitochondrial dynamics is associated with neurodegenerative diseases. We used here an efficient cell type-specific CRISPR approach to knockout key fission-fusion genes and disrupt mitochondrial dynamics within the inessential clock neurons of Drosophila. In order to understand the cellular effects of these perturbations, transcriptomic profiling was performed from young and old clock neurons with and without disrupted mitochondrial dynamics.

overall_design:
To perturb mitochondrial dynamics in Drosophila clock neurons we used a cell type-sepcific CRISPR approach. We used CLK856-Gal4 driver to label clock neurons and under UAS-control, expressed Cas9 and 3X-gRNA against gene of interest along with eGFP to label the neurons for sorting. Following genes were targeted: Drp1 (involved in fission), Marf (involved in fusion of the outer mitochondrial membrane) and Opa1 (involved in fusion of inner mitochondrial membrane). Cas9 alone was used as a control.
Bulk RNAseq was performed from FACS-purified clock neurons of the 4 genotypes (Cas9-control, Drp1-mut, Marf-mut and Opa1-mut) at two ages - Young (~15days old) and Old (~35 days old).
Differential expression analysis was performed for each of the mutants from the Cas9 control at both ages independently

first: Michael

last: Rosbash


title: The enedioic acid analogue 326E alleviates MASH in preclinical studies and its signatures in patients via dual targeting at ACLY and PPARα [RNA-Seq]

first: Jingya

last: Li

address: 189 Guo Shou Jing Road

institute: Shanghai Institute of Materia Medica

summary: The alarming rise in the prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is attributed significantly to dysregulated lipid metabolism. The present study discovered that a novel enedioic acid ACLY inhibitor 326E, an investigational new drug in Phase 2a study for hypercholesterolemia, markedly reduces hepatic lipid accumulation and alleviates MASH in two different mouse models of MASH. Mechanistic studies demonstrated that 326E exerts these effects not only by inhibiting ATP-citrate lyase (ACLY) to reduce de novo lipogenesis but also as a PPARα agonist to increase hepatic fatty acid oxidation with promoted mitochondrial biogenesis. Subsequent studies in cynomolgus monkeys (Macaca fascicularis) confirmed the effectiveness of 326E for MASH in primate species. In a randomized Phase 1b/2a clinical trial in MASH patients 326E was well tolerated and demonstrated a therapeutic potential for MASH signatures. Our results reveal a promising therapeutic potential of 326E for MASH via distinctive dual mechanisms of inhibiting ACLY while activating PPARα.

overall_design: To elucidate possible mechanisms responsible for 326E’s effect in ameliorating MASH, we conducted RNA-seq in the liver samples of CDAA-HFD fed mice after 6 weeks of treatment with 30 mg/kg 326E.

first: Long

last: Cheng


title: The enedioic acid analogue 326E alleviates MASH in preclinical studies and its signatures in patients via dual targeting at ACLY and PPARα [ATAC-seq]


title: Heritable changes in chromatin contacts linked to transgenerational obesity [ChIP-seq]

city: Charlestown

first: Toshihiro

last: Shioda

address: Building 149 - 7th Floor, 13th Street

department: Center for Cancer Research

institute: MGH Cancer Center

summary: Burgeoning evidence demonstrates that responses to environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations. This is controversial because underlying mechanisms remain to be identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology. Here, we used an established murine model of transgenerational obesity to show that direct or ancestral exposure to the obesogen tributyltin (TBT) elicited persistent changes in topologically associating domains (TADs) in primordial germ cells (PGCs) isolated from embryos of exposed and subsequent unexposed generations. New TAD boundaries were formed within the Ide gene encoding insulin degrading enzyme in the exposed PGCs, then stably maintained in PGCs of the subsequent (unexposed) two generations. Concomitantly, Ide mRNA expression was decreased in livers of male descendants from the exposed dams. These animals were hyperinsulinemic and hyperglycemic, phenocopying Ide-deficient mice that are predisposed to adult-onset obesity. Creation of new TAD boundaries in PGCs, suppression of hepatic Ide mRNA, increased fat mass, hyperinsulinemia and hyperglycemia were male-specific. Our results provide a plausible molecular mechanism underlying transmission of the transgenerational predisposition to obesity caused by gestational exposure to an environmental obesogen. They also provide an entry point for future studies aimed at understanding how environmental exposures alter chromatin structure to influence physiology across multiple generations in mammals.

overall_design: Chromatin immunoprecipitation DNA-sequencing (ChIP-seq) for CTCF in adult male mouse liver.

first: Shioda

last: Toshihiro

first: Chang

last: Richard

first: Blumberg

last: Bruce


title: NLN Depletion Enhances WNT3A Secretion and Therapy Resistance in mCRPC via KIF11-Mediated Cellular Trafficking

city: Dallas

first: Ping

last: Mu

state: Texas

address: 5323 Harry Hines Blvd.

institute: University of Texas Southwestern Medical Cente

summary: WNT signalling, an integral orchestrator in an assortment of developmental and pathological pathways, exhibits aberrant regulation in a variety of human malignancies, encompassing prostate cancer (PCa). Particularly, in metastatic castration-resistant prostate cancer (mCRPC), WNT signalling demonstrates dysregulated activity, albeit the precise molecular underpinnings of this ectopic signalling remain predominantly undefined. Within this investigation, we illuminate the role of the previously unidentified tumor suppressor, NLN, which serves as a molecular scaffold to facilitate KIF11 aggregation. A notable depletion of NLN was observed in approximately 30% of mCRPC cases, a deficiency that catalyzes the unleashing of KIF11-dependent cellular translocation of WNT3A, culminating in amplified WNT3A secretion into the tumor microenvironment (TME). This excessive extracellular WNT3A release augments the adaptive resilience of proximal mCRPC cells, fostering resistance against the prevailing standard-of-care AR-targeted therapies. The findings from this study delineate a hitherto uncharacterized, cancer cell-autonomous mechanism that modifies the TME via modulated WNT secretion, thereby inciting resistance to AR-targeted therapies. Moreover, these results underscore the potential clinical utility of NLN level assessments as a prognostic biomarker for mCRPC, and propose the potential efficacy of WNT3A inhibitors as a therapeutic approach to counteract resistance.

overall_design: Examination of transcriptomic changes in LNCaP/AR prostate cancer cell lines with KO of NLN genes


title: Effect of continued exposure to drugs on gene expression in human pancreatic cells

city: Leuven

first: Rekin's

last: Janky

address: Herestraat 49 Box 816

department: Nucleomics Core

country: Belgium

institute: VIB

summary:
Pancreatic ductal adenocarcinoma (PDAC) has a bad prognosis, a fast progression and is difficult to treat, highlighting the need for new therapeutic targets. Aggressive tumors mostly show Epithelial-to-Mesenchymal Transition (EMT). In a previous study we could show that Protein phosphatase type 2A (PP2A) plays a central role in processes of cell survival and proliferation and a link with EMT and tumor progression. In a separate study, we have investigated the effect of short and continuous inhibition of PP2A with Okadaic Acid on gene and protein expression in the human pancreatic cell line PANC-1. In this study, we investigated the cell line models of Panc-1 cells made resistant to the PP2A-small activator proteins ATUX and SMAP2.
We performed gene expression profiling analysis using data obtained from RNA-seq of 3 different cells and compared it to control 4 different Panc-1 controls.

overall_design: Comparative gene expression profiling analysis of RNA-seq data for PP2A-activators SMAP, ATUX and Sorafenib derived cell lines

first: Jos

last: van Pelt

first: Veerle

last: Janssens

first: Chris

last: Verslype


title: Heritable changes in chromatin contacts linked to transgenerational obesity

summary: Burgeoning evidence demonstrates that responses to environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations1,2. This is controversial because underlying mechanisms remain to be identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology. Here, we used an established murine model of transgenerational obesity to show that direct or ancestral exposure to the obesogen tributyltin (TBT) elicited persistent changes in topologically associating domains (TADs) in primordial germ cells (PGCs) isolated from embryos of exposed and subsequent unexposed generations. New TAD boundaries were formed within the Ide gene encoding insulin degrading enzyme in the exposed PGCs, then stably maintained in PGCs of the subsequent (unexposed) two generations. Concomitantly, Ide mRNA expression was decreased in livers of male descendants from the exposed dams. These animals were hyperinsulinemic and hyperglycemic, phenocopying Ide-deficient mice that are predisposed to adult-onset obesity. Creation of new TAD boundaries in PGCs, suppression of hepatic Ide mRNA, increased fat mass, hyperinsulinemia and hyperglycemia were male-specific. Our results provide a plausible molecular mechanism underlying transmission of the transgenerational predisposition to obesity caused by gestational exposure to an environmental obesogen. They also provide an entry point for future studies aimed at understanding how environmental exposures alter chromatin structure to influence physiology across multiple generations in mammals.

overall_design: C57BL/6 F0 mother mice were exposed to tributyltin (TBT) or control (DMSO) via drinking water. Primordial germ cells were isolated from F1-F3 offspring embryos and subjected to Hi-C sequencing.

first: Richard

last: Chang

first: Riann

middle: J

last: Egusquiza

first: Zhuorui

first: Angélica

last: Amato

first: Erika

last: Joloya

first: Hailey

middle: B

last: Wheeler

first: Angela

last: Nguyen

first: Keiko

first: Junko

last: Odajima

first: Toshi

first: Bruce

last: Blumberg

last: Lawrence


title: Single-cell RNA sequencing of peripheral blood mononuclear cell of human osteosarcoma

city: Nanning

first: Wenyu

last: Feng

state: Guangxi

address: Shuangyong road 22

department: Center for Genomic and Personalized Medicine

institute: Guangxi Medical University

summary: We performed the scRNA-seq anakysis of 3 osteosarcoma peripheral blood mononuclear cell based on the 10X Genomics platform.

overall_design: PBMC were obtained from the peripheral circulating blood of osteosarcoma patients for scRNA seq.

first: Mingwei

last: He


title: Capicua regulates the survival of Cajal-Retzius cells in the postnatal hippocampus

status: Public on Oct 16 2025

city: Edmotnotn

first: Qiumin

last: Tan

state: Alberta

address: 114 St and 87 Ave

department: Cell Biology

country: Canada

institute: University of Alberta

summary: Programmed cell death is crucial for organ morphogenesis and tissue homeostasis. Understanding programmed cell death in the developing brain is essential for comprehending both normal brain development and neurological disorders. In this study, we utilize Cajal-Retzius (CR) cells, transient neurons that populate the embryonic cortex and are predominantly eliminated in early postnatal stages, as a model to investigate the regulation of programmed cell death. While many CR cells typically undergo postnatal cell death, some persist into adulthood in the hippocampus, influencing local circuits and behaviors. Here, we show that the loss of capicua (CIC), a transcriptional repressor implicated in a rare neurodevelopmental syndrome and multiple cancers, results in aberrant survival of CR cells in the adult hippocampus. Altered cell survival is mediated by the cell-autonomous function of CIC in hippocampal CR cells. Surprisingly, the atypical persistence of CR cells following CIC loss does not impact hippocampal-dependent behaviors or susceptibility to kainic acid-induced seizures. Single-cell transcriptomic analysis unveils previously unrecognized heterogeneity among hippocampal CR cells and suggests a role of CIC in repressing Fgf1 expression. Additionally, we reveal that FGF1 and BCL2 serve as pivotal regulators enhancing CR cell survival in the postnatal hippocampus. Our findings shed light on a previously unacknowledged role of CIC upstream of FGF signaling and elucidate the apoptosis mechanism governing developmental programmed CR cell death.

overall_design: Four ΔNp73-Cre; Cicflox/+; tdT and four ΔNp73-Cre; Cicflox/flox; tdT mice (littermates) at P14 were perfused with artificial cerebrospinal fluid (aCSF; 87 mM NaCl; 2.5 mM KCl; 1.25 mM NaH2PO4; 26 mM NaHCO3; 75 mM sucrose; 20 mM glucose; 2 mM CaCl2; 2 mM MgSO4) equilibrated in carbogen (95% O2, 5% CO2) via a gas stone. The brain was promptly removed and kept in aCSF as the hippocampus was dissected. Dissected tissue was kept submerged in aCSF saturated with carbogen on ice.


title: Lung adenocarcinoma cells respond differently to mechanical stress in 3D versus 2D environments [3D]

city: Toyama

first: Naoya

last: Kitamura

state: Toyama

address: 2630, Sugitani

department: Thoracic Surgery

institute: University of Toyama

summary: Two-dimensional (2D) culture models are commonly used in cancer research, but fail to recapitulate complex mechanical cues of native tissues. In this study, we developed an ex vivo three-dimensional (3D) lung cancer model by seeding human lung adenocarcinoma cells into decellularised rat lungs and culturing them in a pressure chamber and perfusion system mimicking respiratory motion (RM) and blood flow. In 3D culture, RM promoted cell adhesion and proliferation, enhanced the nuclear translocation of β-catenin and YAP, and increased the expression of integrin β1 and E-cadherin. In addition, upregulation of extracellular matrix- and cell adhesion-related genes was particularly notable. In contrast, in 2D culture, RM suppressed cell proliferation and induced apoptosis, with prominent upregulation of tumour suppressor genes. Our findings demonstrate that dimensionality and mechanical stress synergistically influence lung cancer cell dynamics and underscore the need for 3D models in cancer research that closely replicate the native lung tissue microenvironment.

overall_design: A549 human lung adenocarcinoma cells were divided into two groups: one subjected to respiratory motion and the other not. After four days of culture, samples were collected and subjected to RNA sequencing.

first: Mayumi

last: Iwatake

first: Satoshi

last: Mizoguchi

first: Shadil

last: Wani

first: Komei

last: Kobayashi

first: Muhammad

last: Hasnain

first: Dung

middle: V

first: Ryo

last: Yokoyama

first: Naru

last: Kitade

first: Toshihiro

last: Ojima

first: Koichiro

last: Shimoyama

last: Koba

first: Hideki

last: Hatta

first: Micha Sam

last: Raredon

first: Kenichi

last: Hirabayashi

first: Yoshitomo

last: Morinaga

first: Tomoshi

last: Tsuchiya


title: Multi-omics reveal gut microbiota–metabolite–adipose axis as the driver of hesperidin-mediated metabolic improvement in obese mice

city: Hangzhou

first: Jiaxiong

last: Wu

state: ZHEJIANG

address: Yuhangtang Road 866#

institute: Zhejiang University

summary: Hesperidin, a citrus flavonoid glycoside, was investigated for its protective effects against high-fat diet (HFD)-induced metabolic syndrome in mice. Twelve weeks of supplementation markedly attenuated body weight gain, hepatic steatosis, adipocyte hypertrophy, dyslipidemia, and systemic inflammation, while enhancing glucose tolerance and insulin sensitivity. 16S rRNA sequencing demonstrated that hesperidin partially restored microbial diversity and selectively enriched beneficial taxa, including Lactobacillus, Bifidobacterium, and Akkermansia. Serum metabolomics revealed increased levels of microbial-derived metabolites such as cinnamic acid, hippuric acid, and sulfated phenolic acids, compounds associated with anti-obesity, antioxidant and anti-inflammatory activities. Transcriptomic profiling of inguinal white adipose tissue identified broad remodeling of metabolic pathways, with notable activation of calcium signaling, implicating both UCP1-dependent browning and UCP1-independent calcium futile cycling in thermogenesis. Importantly, antibiotic treatment abolished the metabolic benefits and suppressed the generation of bioactive metabolites, underscoring the indispensable role of gut microbiota in hesperidin bioactivity. Together, these findings delineate a microbiota–metabolite–adipose tissue axis through which hesperidin confers systemic metabolic protection, highlighting its potential as a microbiota-targeted dietary strategy for managing obesity-related disorders.

overall_design: Male mice were fed a control diet (CD) or high-fat diet (HFD) with or without hesperidin supplementation (HEP) for 12 weeks. Multi-omics approaches, including 16S rRNA sequencing, untargeted serum metabolomics, and adipose transcriptomics, were employed.

first: Laiming

last: Zhang

first: Chengxiao

last: Yu

first: Haibo

last: Pan

first: Xingqian

last: Ye

first: Jianle

last: Chen

first: Shiguo


title: Investigating the role of Cmtr1 in splicing: control Cmtr1 fl/fl fibroblasts expressing empty vector

city: Glasgow

first: Alison

last: Galloway

address: Garscube Estate, Switchback Road

institute: Beatson CRUK

summary: We investigated role of CMTR1 in RNA splicing in MEFs to compare to our findngs in T cells. These samples are from Cmtr1 fl/fl fibroblasts transfected with empty vector and are from the same experiment as samples in GSE200103 where Cmtr1 cKO MEF transcriptomics can be found.

overall_design: RNA sequencing of total RNA from mouse embryonic fibroblasts transduced with different variants of HA-tagged CMTR1 and treated with Cre recombinase to remove CMTR1 exon 3 flanked by loxP sites

first: Lukoszek

last: Radoslaw

first: Victoria

last: Cowling