title: Carboxy-Methylation of the Catalytic Subunit of Protein Phosphatase 2A (PP2Ac) Integrates Methionine Availability with Methionine Addicted Cancer Cell Proliferation

status: Public on Jul 03 2025

city: Irvine

first: Fiona

last: Law

state: CA

address: 839 Health Sciences Road

institute: UCI

summary: Cancer cells exhibit a well-documented, yet poorly understood, dependence on exogenous methionine, despite retaining the capacity to convert homocysteine to methionine. In contrast, non-tumorigenic cells can proliferate when methionine is replaced by homocysteine. To investigate the mechanistic basis of this methionine dependence, we examined how methionine metabolism impacts cancer cell proliferation. We identified carboxy-methylation of the catalytic subunit of Protein Phosphatase 2A (PP2A) as a critical node linking methionine availability to proliferation. PP2A methylation was found to be highly sensitive to intracellular S-adenosylmethionine (SAM) levels, with reduced methylation correlating with impaired proliferation under methionine restriction. Overexpression of Protein Phosphatase Methylesterase-1 (PME-1), which demethylates PP2A, or expression of a Leu309-deleted PP2A mutant that mimics the demethylated form, was sufficient to reduce proliferation even in methionine-independent cells. These findings support a model in which methionine limitation lowers SAM availability, thereby decreasing PP2A methylation and impairing cell proliferation. Our study reveals a mechanistic link between methionine metabolism and cell proliferation and suggests that PP2A methylation plays a key role in the unique methionine dependence of cancer cells.

overall_design: HEK293T and R1 cells were cultured in either +Met or -Met+Hcy media for 12 hours and total RNA was extracted using kit (Qiagen, 74104). Samples were then sent to Novogene Corporation Inc. for library preparation and sequencing (Sacramento, CA, USA).

first: Anna

last: Andronicos

first: Peter

last: Kaiser


title: Phosphatidylserine clustering by membrane receptors triggers LC3-associated phagocytosis

city: Memphis

first: Douglas

middle: R

last: Green

state: TN

address: 262 Danny Thomas Place

department: Immunology

country: USA

institute: St. Jude Children's Research Hospital

type: Expression profiling by high throughput sequencing

summary: LC3-associated phagocytosis (LAP) represents a non-canonical function of autophagy proteins in which ATG8 family proteins (LC3 and GABARAP proteins) are lipidated onto single-membrane phagosomes as particles are engulfed by phagocytic cells. LAP plays roles in innate immunity, inflammation and anti-cancer responses and is initiated upon phagocytosis of particles that stimulate Toll-like receptors (TLR), Fc-receptors, and upon engulfment of dying cells. However, how this molecular process is initiated remains elusive. Here we report that receptors that engage LAP enrich phosphatidylserine (PS) in the phagosome membrane via membrane-proximal domains that are necessary and sufficient for LAP to proceed. Subsequently, PS recruits the Rubicon-containing PI3-kinase complex to initiate the enzymatic cascade leading to LAP. Manipulation of plasma membrane PS content, PS-binding by Rubicon, or the PS-clustering domains of receptors prevents LAP and phagosome maturation. Therefore, the initiation of LAP represents a novel mechanism of PS-mediated signal transduction upon ligation of surface receptors.

overall_design: RAW264.7 cells were plated on 6-well plates in complete media and harvested in cold PBS the next day. Total RNA was extracted using the RNeasy Kit (Qiagen), quantified by RiboGreen (ThermoFisher), and quality-checked on a 4200 TapeStation HS RNA ScreenTape (Agilent). Libraries were prepared from 500 ng total RNA with the TruSeq Stranded mRNA Kit (Illumina), with insert sizes verified on TapeStation D1000 and concentrations measured by PicoGreen (ThermoFisher). Paired-end 100 bp sequencing was performed on a NovaSeq 6000 (Illumina) at the St. Jude Hartwell Center.

first: Boada-Romero

last: Emilio

first: Poudel

last: Suresh


title: Global transcriptional profiles of hiPSC-derived hypothalamus-pituitary organoids predicted to fail or succeed by machine learning model

city: Kyoto

first: Takuya

last: Yamamoto

address: 53 Kawahara-cho, Shogoin, Sakyo-ku

department: CiRA

country: Japan

institute: Kyoto University

summary: We have established a machine learning-based model capable of predicting the successful hypothalamus-pituitary organoid formation from human iPS cells, based solely on phase-contrast images captured at the early timing of differentiation.

overall_design: We compared human iPSC-derived hypothalamus-pituitary organoids predicted to fail or succeed at day 9 or 15.

first: Ryusaku

last: Matsumoto


title: Early-life human CD8+ T cells exhibit rapid, short-lived effector responses and a unique transcription factor landscape

city: New Haven

first: Carrie

middle: L

last: Lucas

state: CT

address: 300 Cedar St., TAC S625D

institute: Yale School of Medicine

summary: Neonates and infants are distinct in their clinical and cellular responses to viral infections, with neonatal CD8+ T cells displaying innate-like characteristics and a lower threshold for T cell receptor (TCR) activation relative to adult counterparts. However, specific molecular programs that drive these unique responses are incompletely understood, particularly in humans, and targetable pathways to modulate viral illness in this vulnerable population remain to be elucidated. Early-life immune responses may be developmentally programmed to prioritize protection from tissue immunopathology, especially while protection is conferred by maternal immunoglobulin. We set out to define the unique response characteristics and transcription factor landscape of neonatal human CD8+ T cells. Here, we report evidence that naïve neonatal human CD8+ T cells are poised for an immediate effector switch, with elevations of KLRG1, FCER1G, CD226/DNAM1, granzymes A/K, TNF, IL-2, and glycolysis compared to naïve adult CD8+ T cells. Further, rapid proliferation and cell death occur upon activation of neonatal CD8+ T cells, with cell viability largely rescued by IL-2 or IL-7. These features are coupled with a unique transcription factor landscape, including high baseline and post-activation expression of thymocyte selection–associated high-mobility group box (TOX) and HELIOS (IKZF2). Additionally, we show that these glycolytic, effector and transcription signatures continue in postnatal life until at least two months of age. We conclude that early-life human CD8+ T cells have a unique transcription factor landscape and metabolic state associated with an immediate effector switch and short-lived effector program, revealing key nodes of regulation relevant for the unique immunobiology of neonatal humans.

overall_design: Baseline and post 2 day activation with anti-CD3 and anti-CD28 and restimulation with PMA/ionomycin for 4 hours on sorted naïve CD8 T cells of full term neonates and adults between 18-30 years old

first: Nina

last: Brodsky

first: Monisha

last: Chakder

first: Dinesh Babu

last: Uthaya Kumar

first: Anis

last: Barmada

first: Julia

last: Wang

first: Weihong

last: Gu

first: Oluwabunmi

last: Olaloye

first: Anjali

last: Ramaswamy

first: Aanchal

last: Wats

first: Liza

last: Konnikova


title: Single-cell RNA-seq profiling of treatment-naïve chemo-refractory and chemo-sensitive ovarian cancer

city: Helsinki

first: Daria

last: Afenteva

address: Haartmaninkatu 8

country: Finland

institute: University of Helsinki

summary: This dataset contains single-cell RNA-seq data from treatment-naïve biopsies of nine patients diagnosed with ovarian high-grade serous carcinoma (HGSC), including four chemo-refractory and five chemo-sensitive cancers. Four of the samples (EOC204, EOC115, EOC649, EOC1127) are newly generated, while five samples have been previously published (GSE165897). The data was generated as part of the DECIDER observational trial (NCT04846933) to investigate the molecular drivers of chemo-refractory HGSC. Key findings from the study indicate that chemo-refractory HGSC is associated with reduced interferon type I (IFN-I) activity and enhanced hypoxia pathway activity, while baseline IFN-I pathway activity in chemo-naïve cancer serves as an independent prognostic factor for chemotherapy response.

overall_design:
Expression profiles of single cells from nine treatment-naïve tissue samples from four chemo-refractory and five chemo-sensitive HGSC. Patients participating in this study are from the DECIDER cohort (NCT04846933), and treated at Turku University Hospital.

***************************************************************
Due to patient privacy and data protection regulations in Finland, raw sequencing data (FASTQ files) from this study can not be deposited in GEO.
They are available through the European Genome-phenome Archive (EGA; https://www.ebi.ac.uk/ega/) under controlled access (study accession number EGAS00001005006).
This is in accordance with the ethical guidelines of the DECIDER study and Finnish legislation.
***************************************************************

first: Matias

last: Marin Falco

first: Anna

last: Pirttikoski

first: Erdogan

last: Pekcan Erkan

first: Sampsa

last: Hautaniemi

last: Vähärautio


title: Duchenne Muscular Dystrophy (DMD) Patient iPSC - derived Skeletal Muscle Organoids scRNAseq

city: Bochum

first: Holm

last: Zaehres

state: NRW

address: Universitaetsstr. 150

department: Institute of Anatomy

country: Germany

institute: Ruhr University Bochum

summary: We have performed skeletal muscle organoid (SMO) cultures from three DMD patient-derived iPSC lines and one healthy iPSC control line. scRNA sequencing has been performed to specifically evaluate the myogenic progenitor / satellite cell populations of DMD versus healthy control SMOs.

overall_design: We dissociated organoids into single cell suspension and performed droplet-based single cell RNA-Seq analysis using 10X Genomics Chromium system.

first: Urs

last: Kindler

first: Stefanie

last: Heilmann-Heimbach


title: Gut microbe-derived metabolites drive psoriatic inflammation via modulation of skin Th17 cells

status: Public on Jul 02 2025

city: Beijing

first: Chenliang

state: Beijing

address: Medical Science Building, Room D307, Tsinghua University

country: China

institute: Tsinghua University

summary: The maintenance of tissue-specific chronic inflammation results from the interplay of genetic and unidentified environmental factors. Here, we describe an immunoregulatory role for an environmentally driven microbial metabolite in Card14E138A/+-induced spontaneous psoriasis. Through metabolite screening, we demonstrate chronic skin inflammation is accompanied by alterations microbial metabolite. Notably, depletion of gut, not skin, microbes alleviates disease symptoms. We further identify indoxyl sulfate (I3S), a bacteriogenic metabolite, as a key driver of psoriatic inflammation and confirm that gut-resident indole-producing microbiota mediate this process. Mechanistically, indole-producing microbiota promote host I3S biothsynthesis via a metabolic relay, and I3S potentiates skin inflammation by reshaping chromatin accessibility in skin Th17 cells through AHR signaling. In human psoriasis cohorts, serum I3S levels correlate with disease severit. In summary, our study uncovers a mechanistic link between gut microbial factors and type 3 skin inflammation, highlighting targeting gut microbiota as a strategy for mitigating skin inflammation.

overall_design: CD45-positive immune cells were isolated from Card14E138A/+ mice and wild type littermates using flow cytometry and analyzed by scRNA-seq.

first: Shanshan

last: Zhang

first: Mingchao

first: Xin

last: Lin


title: Rewriting nuclear epigenetic scripts in mitochondrial diseases as a strategy for heteroplasmy control

city: Mendoza

first: Sergio

middle: Roberto

last: Laurito

state: Mendoza

address: Libertador Avenue 80

department: IHEM

country: Argentina

institute: CONICET

type: Methylation profiling by genome tiling array

summary: Mitochondrial diseases, caused by mutations in either nuclear or mitochondrial DNA (mtDNA), currently have limited treatment options. For mtDNA mutations, reducing mutant-to-wild-type mtDNA ratio (heteroplasmy shift) is a promising therapeutic option, though current approaches face significant challenges. Previous research has shown that severe mitochondrial dysfunction triggers an adaptive nuclear epigenetic response, characterized by changes in DNA methylation, which does not occur or is less important when mitochondrial impairment is subtle. Building on this, we hypothesized that targeting nuclear DNA methylation could selectively compromise cells with high levels of mutant mtDNA, favor ones with lower mutant load and thereby reduce overall heteroplasmy.

overall_design:
EPIC 850k methylation data from cybrids that were obtained from the fusion of the osteosarcoma cell line143B.206 rho0 mtDNA devoid cells with enucleated patient-derived dermal fibroblasts as previously described. The methylome of cybrids harboring wild-type mtDNA and two disease causing mutations: m.13513G>A (´13´ cybrids) and m.8344A>G (´8´cybrids) with high and low heteroplasmy levels was analyzed.
Our study reveals a previously unrecognized role for nuclear DNA methylation in regulating cell survival in the context of mitochondrial heteroplasmy. This insight not only advances our understanding of mitochondrial-nuclear interactions but also introduces epigenetic modulation as a possible therapeutic avenue for mitochondrial diseases.

first: María

middle: J

last: Pérez

first: Rocío

middle: B

last: Colombo

first: Sebastián

middle: M

last: Real

middle: T

last: Branham

first: Carlos

last: Moraes

first: Lía

last: Mayorga


title: ID8 cells manifest phenotypic plasticity and molecular heterogeneity of high-grade serous ovarian cancer in response to the local tissue niche

city: Pune

first: SHARMILA

last: BAPAT

state: Maharashtra

address: Ganeshkhind Road Pune

department: Lab 04 old building

country: India

institute: National Centre for Cell Science, Pune

summary: Spontaneously transformed mouse ovarian surface epithelial cell line ID8 generates a syngeneic mouse model, frequently used in pre-clinical evaluation. Towards a precise, subtype-specific perspective of such applications, we thought it pertinent to study its stratification into a specific molecular subtype, which would provide an accurate setting for interpretation of experimental data. Stratification of ID8 model was achieved through phenotypic, histopathological, and molecular assessment of ID8 cells grown in vitro, its primary xenografts and metastases. TME investigation of primary and metastatic tumors revealed contrasting immune populations.

overall_design: Stratification was performed on ID8 cell line and ID8 generated xenografts based on immunostaining, live cell imaging, histopathology and transcriptomics and proteomics. TME investigation for each xenograft was done through flow cytometry analysis.ID8 cells present E/M phenotype. Phenotypic plasticity retention in them causes class switching of ID8 cells in response to niche alteration, from E/M (in culture) to intermediate epithelial (iE) in orthotopic tumors while intermediate mesenchymal (iM) in subcutaneous tumors. Metastasis of ID8 primary tumor resulted into differentiated mesenchymal phenotype in ascites while differentiated epithelial phenotype in secondary intestinal tumors. Immune profiling of primary and secondary xenografts revealed differences in immune repertoire of tumors, highlighting subcutaneous tumor model to be inappropriate as compared to orthotopic model.

first: S

middle: A

last: Bapat

first: Ritika

last: Gupta

last: Shravan

first: Swapna

last: Agwane

first: R

last: Bankar


title: Enhancing RNA base editing on mammalian transcripts with small nuclear RNAs

city: La Jolla

first: Brian

last: Yee

address: 9500 Gilman Dr

department: Health

institute: UCSD

summary: Endogenous Uridine-rich small nuclear RNAs (U snRNAs) form RNA-protein complexes to process eukaryotic pre-mRNA into mRNA. Previous studies have demonstrated programmable U snRNA guide-targeted exon inclusion and exclusion. We investigated whether snRNAs can also enhance RNA base editing over state-of-the-art RNA-targeting technologies in human cells. Compared to adenosine deaminase acting on RNA (ADAR)-recruiting circular RNAs, we find that guided A>I snRNAs consistently increase adenosine-to-inosine editing for higher exon count genes, perturb substantially fewer off-target genes, and localize more persistently to the nucleus where ADAR is expressed. A>I snRNAs also more efficiently edit lncRNAs and pre-mRNA 3′ splice sites to promote splicing changes. Finally, snRNA-H/ACA box snoRNA fusions (U>Ψ snRNAs) increase targeted RNA pseudouridylation without DKC1 overexpression, facilitating improved CFTR rescue from nonsense-mediated mRNA decay in a Cystic fibrosis human bronchial epithelial cell model. Our results advance the endogenous protein-mediated RNA base editing toolbox and RNA-targeting technologies to treat genetic diseases.

overall_design: RNA-seq of human HEK 293T cells following transfection with plasmids encoding pUC19 (empty vector), U7 promoter-driven U7smOPT snRNA (targeting DMD and RAB7A) in pUC19, and U6 promoter-driven cadRNA (targeting DMD and RAB7A) in pUC19

first: Aaron

last: Smargon

first: Deepak

last: Pant

first: Trent

last: Gomberg

first: Christian

last: Fagre

first: Sofia

last: Glynne

first: Johnathan

last: Nguyen

first: Jack

last: Naritomi

first: Wendy

middle: V

last: Gilbert

first: Gene

middle: W

last: Yeo


title: SUGP1 loss drives SF3B1 hotspot mutant missplicing in cancer

first: Zhaoqi

last: Liu

address: NO.1 Beichen West Road, Chaoyang District

institute: Beijing Institute of Genomic Chinese Academy of Sciences

summary: SF3B1 is the most frequently mutated splicing factor in cancer. Such mutations cause missplicing by promoting aberrant 3' splice site usage; however, how this occurs mechanistically remains controversial. To address this issue, we employed a computational screen of 600 splicing-related proteins to identify those whose reduced expression recapitulates mutant SF3B1-induced splicing dysregulation. Strikingly, our analysis reveals only two proteins whose knockdown or knockout reproduces this effect. Extending our previous findings, loss of the G-patch protein SUGP1 recapitulates almost all splicing defects induced by SF3B1 hotspot mutations. Unexpectedly, loss of the RNA helicase Aquarius (AQR) reproduces ∼40% of these defects. However, we find that AQR knockdown causes significant SUGP1 missplicing and reduced SUGP1 levels, suggesting that AQR loss reproduces mutant SF3B1 splicing defects only indirectly. This study advances our understanding of missplicing caused by oncogenic SF3B1 mutations and highlights the fundamental role of SUGP1 in this process.

overall_design: 6 human cell line samples: K562_U2AF1 S34F and wild-type knock-in controls


title: Salmonella Typhi gut invasion drives hypoxic immune subsets associated with disease outcomes

city: Rehovot

first: Noa

last: Bossel Ben-Moshe

address: Hertzl Street

country: Israel

institute: Weizmann

summary: Salmonella Typhi (S. Typhi), the causative agent of typhoid disease, remains a major public health concern. Owing to the human-restricted nature of S. Typhi, studies of typhoid pathogenesis in animal models are limited to a murine non-typhoidal pathogen. More recently, human challenge models have been conducted, providing insight into immune correlates of infection outcomes, which are still incompletely understood. Here, we performed an integrated single-cell analysis of immune responses from the human S. Typhi challenge model and mouse model of typhoid disease, to associate biological mechanism with human infection outcome. Most prominent, we revealed immune subsets with a hypoxia-related signature in the blood of individuals who developed disease in the human challenge model. This signature was also evident in the mouse model in activated macrophages infiltrating into the Peyer's patches, but not during infection with a mutant strain impaired for gut invasion. We further identified hypoxia-related signature as a general immune correlate of disease outcome in other infection-and inflammatory-related diseases. Collectively, we identified a hypoxia-associated immune signature that correlates with disease outcomes in humans. Using a mouse model, we demonstrated that this signature is driven by bacterial invasion to the Peyer's patches, implicating a causal role in the pathogenesis of typhoid fever.

overall_design: Mice were infected with Salmonella Typhimurium for 72 hours. Peyer's patches from naïve and infected mouse were extracted, enriched for immune cells, and used for single-cell RNA-seq.

first: Shelly

last: Hen-Avivi

first: Liron

last: Levy Efrati

first: Leia

last: Veinman

first: Jennifer

last: Hill

first: Daniel

last: O’Connor

first: Marije

last: Verheul

first: Lisa

last: Stockdale

first: Florence

last: McLean

first: Andrew

last: Pollard

first: Roi

last: Avraham


overall_design: PBMCs from individuals from the SalmonellaTyphi human challenge model were defrosted and used for single cell RNA-seq


overall_design: Mice were infected with wild-type and triple mutant (invA/fliC/fljB) Salmonella Typhimurium. Peyer's patches from naïve mice, wild-type infeted mice, and triple-mutant infected mice were extracted 72 hours post-infection for RNA-seq


sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


overall_design: Mice were infected with Salmonella Typhimurium at the following time points: 0, 24, and 72 hours post-infection. The ileum, cecum, Peyer's patches, and spleen were extracted for RNA-seq.


overall_design: Frozen PBMCs from healthy donor were defrosted and were either kept in normoxia (37°c  incubator with 5% CO2) for 22 hours or transferred to a hypoxia chamber (2% O2) for 15 or 22 hours, followed by RNA extraction.


title: The genomic origin of the unique chaetognath body plan

city: London

first: Ferdinand

last: Marlétaz

address: Gower Street

department: Genetics, Evolution & Environment

country: United Kingdom

institute: University College London

type: Genome binding/occupancy profiling by high throughput sequencing

summary: The emergence of animal phyla, each with their unique body plan, was a rapid event in the history of animal life, yet its genomic underpinnings are still poorly understood. Here, we investigate at the genomic, regulatory, and cellular levels the origin of one of the most enigmatic animal phyla, the chaetognaths, whose distinctive organismal characteristics have historically complicated its phylogenetic placement.  We show that some of these characteristics are reflected at the cell-type level by the expression of genes originating in the chaetognath lineage, contributing to adaptation to planktonic life at the sensory and structural levels. Chaetognaths belong to the gnathiferan lineage (also including rotifers and several other microscopic phyla), which is marked by accelerated genomic evolution with gene loss and chromosomal rearrangements. Chaetognaths further secondarily acquired thousands of newly duplicated genes, without evidence for a whole genome duplication, yielding, for instance, tandemly expanded Hox genes, as well as many phylum-specific genes. We also detected repeat-rich highly-methylated neocentromeres and a simplified DNA methylation toolkit, which is involved in mobile element repression rather than transcriptional control, a role inherited by trans-splicing. Consistent with fossil evidence, our observations suggest that chaetognaths emerged after a phase of morphological simplification through a reinvention of organ systems paralleled by massive genomic reorganisation, explaining the uniqueness of the chaetognath body plan.

overall_design: scRNA-seq, ATAC-seq, RNA-seq and EM-seq to characterise gene regulation

first: Laura

last: Piovani

first: Daria

last: Gavriouchkina

first: Taichiro

last: Goto

first: Luke

last: Sarre

first: Alexandre

last: Mendoza


title: Metastatic immunoediting in breast cancer cells

city: Barcelona

first: Toni

last: Celià-Terrassa

address: C/ del Dr. Aiguader, 88, Ciutat Vella,

country: Spain

institute: Hospital del Mar Research Institute

summary: During the metastatic process, most of the disseminated tumor cells fail to adapt to new tissue conditions upon arrival and die, resulting in a selection of the fittest cells. Among these hurdles, the immune system’s anti-tumor activity is one of the main barriers of metastatic colonization. Among the different Metastasis-initiating cells (MICs)  properties, immune evasion stands out as one of the most necessary traits leading metastasis. The immune landscape of distant organs impose immune pressure on tumor cells engaging a process of tumor-immune coevolution and selection of immune-evasive tumor cells, in a process called cancer immunoediting. In this study, we aimed to investigate the altered gene patterns of breast cancer cells induced by the interaction with the immune system. Specifically, we were looking for phenotypes and immune-evasive behaviour of immunoedited cells leading the metastatic colonization.

overall_design: To evaluate immunoediting of tumor cells we interrogated the transcriptome of EpRas cells after metastatic spreading in immunodeficient (NSG) and immunocompenent (Balb/c) hosts. Brain, lung and liver metastatic samples were analyzed to study common and general transcriptomic changes.

first: Rozalen

last: Catalina


title: Gene expression profile at single cell level of CD45+ immune cells from 4TO7 cells (Ctrl or Tim3-KD) liver metastasis at different timepoints

summary: In this study we describe the immunosupressive role of Tim3+ tumor cells during eraly stages of metastasis.  We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of immune cells subsets altered by Tim3 expression in the tumor cells. The aim was to determine the immune status of immunosuppressive and cytotoxic populations during the dynamic process of the metastatic colonization in the liver

overall_design: Intracardiac injection of 4TO7-Ctrl and Tim3-KD cells into Balb/c was performed. At different timepoints (micrometastasis, day 3) and (macrometastasis, day 12), immune cells were isolated from a liver section (5x5mm). Also adjacent tissue of the liver free of tumor was isolated. According to CD45 signal by fluorescent-activated cell sorting, cells were analyzed using scRNA-seq.


first: Noa

last: Bossel Ben-Moshe

overall_design: Frozen PBMCs from healthy individual were defrosted and infectet ex vivo with Salmonella Typhi for 24 hours.

first: Shelly

last: Hen-Avivi

first: Liron

last: Levy Efrati


title: Effect of acute and chronic ATF6 activation on gene expression in the colonic epithelium, in specific pathogen-free and germ-free mice.

city: Braunschweig

first: Tim

last: Kacprowski

address: Rebenring 56

department: Division Data Science in Biomedicine

institute: TU Braunschweig

summary: The induction of endoplasmic reticulum unfolded protein responses (UPRER) contributes to cancer development and progression. We recently linked microbiota-related triggers to the tumor-promoting role of signal transducer activating transcription factor 6 (ATF6) in the colon. Here we substantiate the clinical relevance of ATF6 and related bacterial genera in colorectal cancer patient cohorts. Spatial and longitudinal bacterial profiling in ATF6 transgenic mice (nATF6IEC) identified tumor-initiating and tumor-progressing shifts in the mucosa-associated microbiota. Transcriptional analysis in intestinal epithelial cells (IEC) of germ-free and specific pathogen-free nATF6IEC mice defined bacteria-specific changes in cellular metabolism enriched for fatty acid biosynthesis. Untargeted metabolomics, isotope-labeling in intestinal organoids and FASN inhibition confirmed ATF6-mediated involvement of long-chain fatty acids in tumorigenesis. Multi-omics data integration identified a bacteria-lipid network characterized by fatty acid efflux, catabolism and detoxification. We postulate chronic ATF6 signaling to drive a clinically relevant pathologic response altering lipid metabolism to select for a tumor-promoting microbiota.

overall_design: To identify the transcriptional response to ATF6 activation, we performed intestinal epithelial cell isolation from colonic tissue of mice. Gene expression profiling analysis was performed on six mice per group were used for the following experimental groups: 5 week-old fl/fl SPF, 5 week-old tg/tg SPF, 5 week-old fl/fl GF, 5 week-old tg/tg GF, fl/fl after 4d of ATF6 induction, tg/tg after 4d of ATF6 induction.

first: Olivia

middle: I

last: Coleman

first: Sandra

last: Bierwirth

first: Philipp

last: Rosenstiel

first: Christina

last: Schmidt


title: Mechanical stress induces anatomical changes, tomato early flowering, and increased yield involving ethylene and auxins

status: Public on Jul 01 2025

city: Santa Fe

first: Jenifer

last: Castro Estrada

state: Santa Fe

address: Pedro Ferré 1277

institute: Littoral Agrobiotechnology Institute

summary: Plants have evolved mechanisms to perceive and face mechanical stress (MS) caused by physical forces, including compacted soils, winds, rain, pathogens, and interactions with animals and plants. Previous research indicated that applying mechanical treatment (MT) to Arabidopsis increases both xylem area and seed yield. To explore sustainable tomato production, we applied MT - combining stem bending, weighting, and particular touching - to 10-day-old seedlings, using a specific weight on the upper stem for 48 h. Two days after the treatment, we observed stem enlargement and increased the number of xylem vessels and area in MT plants. Additionally, we noticed earlier flowering, leading to increased tomato production. The transcriptome of MT-treated plants revealed significant changes in the expression of several essential genes involved in central metabolism, growth responses, and crucial phytohormone signalling. By studying different tomato mutants in the ethylene and auxin signalling pathways, we demonstrated that both hormones play essential roles in the plant responses to combined MT. Our findings suggest that combined MT generates a beneficial MS in tomato plants that induces plant morphoanatomical changes that promote early flowering and increased yield, providing a promising strategy for sustainable agriculture.

overall_design: Stems from tomato plants of the Ailsa Craig variety were used for the analysis. The samples were taken from plants subjected to a mechanical treatment, which consisted of the application of a wooden device at the apex of the stems, generating a determined weight for 48 hours. In addition, a group of control plants was included. Stem samples were collected 6 hours after the start of the treatment and 10 days after the end of the treatment.

last: Castro-Estrada

first: Salazar

last: Sergio M.

first: Jorge A

last: Mariotti-Martínez

first: Julieta V

last: Cabello

first: Raquel L

last: Chan

first: Elina

last: Welchen


title: Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting [snRNA-seq]

city: Darmstadt

first: Tamara

last: Bender

address: Planckstraße 1

institute: GSI Helmholtzzentrum für Schwerionenforschun

summary: Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing c-MYC, a common oncogene in brain tumors. GFP+/c-MYChigh cells were isolated from tumor organoids and used in two different approaches: GFP+/c-MYChigh cells co-cultured with cerebral organoid slices or fused as spheres to whole organoids. GFP+/c-MYChigh cells used in both approaches exhibited tumor-like properties, including an immature phenotype and a highly proliferative and invasive potential. We demonstrate that the latter is influenced by astrocytes supporting the GFP+/c-MYChigh cells while X-ray irradiation significantly kills and impairs tissue infiltration of GFP+/c-MYChigh cells. In summary, the model represents major features of tumorous and adjacent normal tissue and may be used to evaluate appropriate cancer treatments.

overall_design: Single nuclei (sn) RNA profiling of control human cerebral organoids and control organoid slices at d100 of the culture.

first: Esther

last: Schickel

first: Insa

middle: S

last: Schroeder


title: ApoE4 disrupts intracellular trafficking and iron homeostasis in an improved iPSC-based model of human brain endothelial cells [Bulk RNA-seq 2]

city: Basel

first: Martina

last: Pigoni

address: Grenzacherstrasse 124

department: NRD

country: Switzerland

institute: Hoffmann-La Roche

summary: Transferrin receptor in brain endothelial cells can deliver therapeutic antibodies to the brain via transcytosis across the blood-brain barrier. Whether receptor transport remains intact in Alzheimer’s disease is still a major open question. Here, we investigated whether apolipoprotein E4 (ApoE4), the major genetic risk factor for Alzheimer’s disease, altered intracellular transport in human brain endothelial cells. To achieve this, we first developed an optimized protocol for induced pluripotent stem cells based on a defined chemical cocktail and extracellular-matrix support to differentiate brain endothelial cells (iCE-BECs). Multi-omic profiling and functional transport assays showed that iCE-BECs have a brain endothelial gene signature and recapitulate receptor-mediated transcytosis of a clinically validated BrainshuttleTM antibody against transferrin receptor. Engineered iCE-BECs homozygous for ApoE4 had altered spatiotemporal organization of early endosomes, increased transferrin receptor expression and reduced cytoplasmic iron. Our data revealed that ApoE4 can impact intracellular transport and iron homeostasis at the BBB in a cell-autonomous manner. This finding could be relevant for the brain delivery of therapeutic antibodies for Alzheimer’s disease.

overall_design: iCE-BECs were differentiated using the protocol described in the paper starting from 3 parental iPS lines ( hiPS_SFC086_03_03, BIONi010-C13 and  Bioni037-A). At least 300,000 cells were collected on day 14 (“Passage 0”). To evaluate the effect of cell passages on cell identity,  hiPS_SFC086_03_03 at day 14 were frozen, thawed and subsequently passaged for 3 consecutive times (“Passage 1-3”).

first: Roberto

last: Villasenor Solorio

first: Joanna

last: Ficek Pascual

first: Lia

last: D'Abate


title: In vivo study of the Tim3-loss in breast cancer cells during metastasis

first: Toni

last: Celià-Terrassa

summary: In metastasis, the existence tumor cells overcoming the immune system during early organ seeding is crucial, yet the dynamics of tumor-immune interactions during micrometastasis remain unclear. Examining the immune selective pressure in breast cancer (BC) mouse models, we unexpectedly found TIM3 among the most upregulated genes in metastatic surviving BC cells. The selection of TIM3+ tumor cells, was specifically occurring during early seeding of micrometastasis, escaping the immune attack and acquiring stemness. Also clinical data confirmed increased TIM3+ tumor cells in BC metastasis. The aim of the study was to understand the mechanistic insgihts of Tim3 in breast cancer cells in vivo to decipher pivotal pathways of Tim3-mediated immun-evasion.

overall_design: To evaluate Tim3 during metastasis in vivo, Ctrl and Tim3-KD 4TO7 cells  were implanted via intracardiac injection in Balb/c mice. After metastatic colonization, lung and liver were extracted for transcriptomic interrogation of tumor cells.

first: Rozalen

last: Catalina


title: Opsin 5 mediates violet light-accelerated wound healing in mammalian corneas.

city: seattle

first: Ethan

middle: D

last: Buhr

state: WA

address: 750 Republican St

department: Ophthalmology

institute: University of Washington

summary: The goal is to test whether the expression of opsin 5 in the cornea after wounding regulates transcriptional networks of the whole cornea.

overall_design: Bulk RNA transcripts of 4 replicates of Opn5-null and 4 replicates of wt corneas were compared. Corneas were debrided 12 hours prior to harvest. Total RNA was harvested and frozen. Samples were converted into cDNA and sequenced on a DMB machine.


title: Oxidative stress-regulatory role of miR-10b-5p in the diabetic human cornea revealed through integrated multi-omics analysis

city: los angeles

first: yizhou

last: wang

address: 8700 beverly blvd

institute: cedars-sinai medical center

summary: The corneal epithelium is maintained by limbal epithelial stem cells (LESCs) and are largely responsible for corneal optical transparency and protection by continuous population of corneal epithelial cells. Diabetes mellitus (DM) has been shown to affect all structures of the eye including the cornea which can result in delayed wound healing and potential vision loss. MicroRNAs (miRNAs) are short non-coding oligonucleotides that regulate various cellular functions, including oxidative stress response, by repressing translation. miR-10b-5p was previously identified to be upregulated in diabetic vs. non-diabetic limbal cells and our purpose was to understand the role of miR-10b-5p in human limbal epithelial cells in normal and pathological conditions such as diabetes mellitus. It was hypothesized that miR-10b-5p influences corneal epithelial homeostasis by modulating antioxidant defenses and wound healing processes. Through integrated transcriptomic and proteomic analyses, we identified GCLM and LANCL1 as key miR-10b-5p targets, revealing its profound impact on glutathione metabolism, sulfur compound biosynthesis processes, and antioxidant defenses. Our finding suggests that miR-10b suppression disrupts redox balance which potentially leads to heightened oxidative stress, impaired wound healing and increased cellular vulnerability in diabetic corneas. Further research into miR-10b inhibitors or gene modulation strategies may pave the way for novel treatments aimed at mitigating oxidative stress-related corneal dysfunction, particularly in diabetes-induced ocular diseases.

overall_design: Human primary LECs were transfected with 50 nM hsa-miR-10b-5p mimic or negative control using Lipofectamine RNAiMAX in Opti-MEM and their standard culture medium for 48 hours, then allowed 24 hours of recovery.

first: Mehrnoosh

last: Ghiam

first: Daxian

last: Zha

first: Joshua

last: Gamez

first: Shaghaiegh

last: Ebrahimi

first: Yizhou

last: Wang

first: Nagendra

last: Verma

first: Adam

last: Poe

first: Seok

last: White

first: Ruchi

last: Shah

first: Andrei

last: Kramerov

first: Onkar

last: Sawant

first: Chintda

last: Santiskulvong

first: Aleksandr

last: Stotland

first: Zhiping

middle: P

first: Jennifer

middle: E

last: Van Eyk

first: Alexander

last: Ljubimov


title: Human cerebral organoids model tumor initiation and infiltration in an autologous astrocyte-supported setting [RNA-Seq]

first: Tamara

last: Bender

overall_design: RNA-seq profiling of control human cerebral organoids, control organoid slices, tumor spheres geneted using genetically engineered tumor-like cells, assembloids formed by the fusion of a cerebral organoid containing and a tumor sphere at ~d100 of the culture.

first: Esther

last: Schickel

first: Insa

last: Schroeder


title: Kif11-haploinsufficient oocytes reveal spatially differential requirements for chromosome biorientation in the spindle

city: Fukuoka

first: Tappei

last: Mishina

address: 744 Motooka Nishi-ku

institute: Kyushu University

summary: Bipolar spindle assembly and chromosome biorientation are prerequisites for chromosome segregation during cell division. The kinesin motor KIF11 (also widely known as Eg5) drives spindle bipolarization by sliding antiparallel microtubules bidirectionally, elongating a spherical spindle into a bipolar-shaped structure in acentrosomal oocytes. During meiosis I, this process stretches homologous chromosome pairs, establishing chromosome biorientation at the spindle equator. The quantitative requirement for KIF11 in acentrosomal spindle bipolarization and homologous chromosome biorientation remains unclear. Here, using a genetic strategy to modulate KIF11 expression levels, we show that Kif11 haploinsufficiency impairs spindle elongation, leading to the formation of a partially bipolarized spindle during meiosis I in mouse oocytes. While the partially bipolarized spindle allows chromosome stretching in the inner region of its equator, it fails to do so in the outer region, where merotelic kinetochore-microtubule attachments are favored to form. These findings demonstrate the necessity of biallelic functional Kif11 for bipolar spindle assembly in acentrosomal oocytes and reveal a spatially differential requirement for homologous chromosome biorientation within the spindle.

overall_design: To investigate the quantitative requirements for KIF11 in mouse oocytes, we used a strategy of heterozygous constitutive deletion and meiotic-specific conditional deletion of the Kif11 gene. For conditional deletion, we crossed a newly established floxed Kif11 allele (Kif11fl) with the meiosis-specific Spo11-Cre and the oocyte-specific Gdf9-Cre and Zp3-Cre recombinases. Offspring derived from mice carrying the conditional deletion allele were used to establish a constitutive deletion allele of Kif11 (Kif11del) for the Spo11-Cre +/- background and Kif11 flox/flox for the Gdf9-Cre or Zp3-Cre +/- background. We then estimated the expression levels of full-length Kif11 mRNA and any residual Kif11 in isolated mature oocytes using poly(A) RNA sequencing followed by counting of reads corresponding to the first and last exon of the Kif11 gene, respectively.

first: Aurélien

last: Courtois

first: Shuhei

last: Yoshida

first: Kohei

last: Asai

first: Hiroshi

last: Kiyonari

first: Tomoya

last: Kitajima


title: MZB1 knockout in human melanoma cells significantly modulates genes associated with cancer immune signaling

city: Madison

first: Nihal

last: Ahmad

state: Wisconsin

address: WIMR II, 1111 Highland Ave

department: Dermatology

institute: University of Wisconsin

summary: We performed differential gene expression analysis using high throughput multiplex analysis via NanoString nCounter Immune Profiling panel, which analyzes 785 genes (including 12 internal reference genes) related to immune pathways. nSolver software was used to analyze the data and a heat map was generated to show differential expression of 773 genes. Further, using a fold cut-off of ≥1.5 and p-value <0.05, we observed that MZB1 KO significantly modulated the expression of multiple cancer immune genes.

overall_design: CRISPR/Cas9 mediated MZB1 knockout (KO) melanoma lines were generated by the Genome editing services of the Biotechnology Center at the University of Wisconsin-Madison. RNA was extracted from control and MZB1 KO melanoma cells, followed by the determination of expression of 785 genes (including 12 internal reference genes) via the NanoString Immune Profiling Panel using the nCounter platform at the TRIP lab UW-Madison.

first: Gagan

last: Chhabra


title: Mycobacterium tuberculosis HN878 transcriptomes from replicating broth culture, THP1 macrophage-like cells, caseum surrogate, and rabbit caseum

city: Seattle

first: Richard

last: Jones Jr

department: Microbiology

summary: Among the many influences affecting patient outcomes, the heterogeneity of Mtb populations in remote lesion compartments and the nature of pathogen physiology in these stressful environments are increasingly appreciated as factors that limit the efficacy of current therapies. The transcriptional state of Mtb during infection has been difficult to study and represents a potentially game-changing area for intervention. Limited studies in humans and animals have suggested that subpopulations of Mtb persist in the caseum (soft necrotic debris) that accumulates in the center of necrotic TB granulomas. Stress factors in the caseous foci include hypoxia, iron deprivation, and nutrient limitation. To persist in this environment, it is likely that this population elicits sweeping, transcriptionally coordinated molecular changes that are reflected in their gene expression profiles. Determining the basis of Mtb’s ability to persist in this environment is a critical hurdle in addressing whether intracaseum Mtb are the rate-limiting step for successfully curing TB infection and designing interventions specific to this subpopulation. To address this population, we are adapting the developing GenomeCaptureSeq technology to isolate TB transcripts, determine the transcriptional profile of Mtb in caseum and characterize caseum-specific molecular programs that are utilized by Mtb in this environment to generate targets for intervention. This process involves fragmenting Mtb genomic DNA, linking to beads and then fishing Mtb transcripts from caseous material. Our approach has been applied to caseum samples from Mtb-infected rabbits and we have successfully sequenced TB-specific transcripts from multiple infected lesions. We aim to define a caseum-specific transcriptional signature that will help direct future studies of this subpopulation of interest.

overall_design: Replicating broth cultures of Mtb strain HN878, infected THP1 macrophages, and Mtb allowed to acclimate to surrogate caseum are compared with freshly harvested rabbit caseum samples. RNAseq was performed using hybridization capture with Transcript Capture Sequencing probes made from H37Rv gDNA.

first: David

last: Sherman


title: Transcriptomic analysis of two human pancreatic cancer cell lines treated with the HDAC inhibitor romidepsin and/or the RNA helicase eIF4A inhibitor des-methyl pateamine A

city: Angers cedex 02

first: Agnes

last: Basseville

address: 15 rue André Boquel

country: France

institute: Institut de Cancerologie de l'Ouest

summary: Our study explores a small molecule combination that induces epigenetic reprogramming as a novel therapeutic strategy for pancreatic cancer. We have identified marked sensitivity of pancreatic cancer cells to the combination of a novel inhibitor of RNA helicase eIF4A, des-methyl pateamine A (DMPatA or MZ735), and a histone deacetylase (HDAC) inhibitor, romidepsin. A short-duration, low dose exposure to romidepsin treatment, when combined with DMPatA, triggers persistent global histone acetylation, transcriptional upregulation, replication inhibition, and augmented DNA damage. This combined effect induces a synergistic anti-proliferative response in pancreatic cancer cell lines.

overall_design: Global gene expression analysis was performed by RNA-seq in triplicate on 2 human pancreatic cancer cell lines (KLM and MIA PaCa-2) after treatment with either the HDAC inhibitor romidepsin (15 nM for a 6h treatment followed by 12h incubation with romidepsin-free medium),  the  RNA helicase eIF4A inhibitor DMPatA (2 nM, 18h), or a combination of both.

first: Maryam

last: Safari

first: Susan

last: Bates

first: Thomas

last: Litman


title: Riboseq and RNAseq in embryophyte mutants with assembly defects in photosynthetic complexes

city: Jena

first: Rabea

last: Ghandour

address: Winzerlaer Straße 2

department: Institute of Microbiology

institute: Friedrich Schiller University

summary: In the model green alga Chlamydomonas (Chlamydomonas reinhardtii), the synthesis of several chloroplast-encoded photosynthetic subunits is feedback-regulated by the assembly state of the respective protein complex. This regulation is known as control by epistasy of synthesis (CES) and matches protein synthesis with the requirements of protein complex assembly in photosystem II (PSII), the cytochrome b6f complex (Cyt b6f), photosystem I (PSI), ATP synthase and Rubisco . In embryophytes, however, CES was only described to coordinate synthesis of the large and small subunits of Rubisco, raising the question if additional CES mechanisms exist in land plants or if stoichiometric photosynthetic protein accumulation is only achieved by the wasteful degradation of excess subunits. We systematically examined suitable tobacco and Arabidopsis mutants with assembly defects in PSII, PSI, Cyt b6f complex, ATP synthase, NDH (NAD(P)H dehydrogenase-like) complex and Rubisco for feedback regulation. Thereby, we validated the CES in Rubisco and uncovered translational feedback regulation in PSII, involving psbA, psbB, psbD and psbH and in Cyt b6f, connecting PetA and PetB protein synthesis. Remarkably, some of these feedback regulation mechanisms are not conserved between the green alga and embryophytes. Our data do not provide any evidence for CES in PSI, ATP synthase or NDH complex assembly in embryophytes. In addition, our data disclose translational feedback regulation adjusting PSI levels with PSII accumulation. Overall, we discovered commonalities and differences in assembly-dependent feedback regulation of photosynthetic complexes between embryophytes and green algae.

overall_design: To get a comprehensive picture of potential CES in embryophytes, we used ribosome profiling to survey assembly-dependent feedback regulation in selected tobacco and Arabidopsis mutants of each of the photosynthetic complexes.

first: Reimo

last: Zoschke


title: The c-MYC-WDR43 signalling axis promotes chemoresistance and growth in colorectal cancer by inhibiting p53 activity

city: Guangzhou

first: Ziyang

last: Wang

state: Guangdong

address: 58 Zhongshan Second Road

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

summary: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Oxaliplatin chemoresistance is a major challenge in the clinical treatment of CRC. Through bioinformatics analysis, we identified WDR43 as a critical potential oncogenic factor in CRC pathogenesis. Clinically, WDR43 is highly expressed in CRC, and WDR43 overexpression is associated with poor prognosis in CRC patients. WDR43 knockdown significantly inhibits cell growth by arresting the cell cycle and enhances the effect of oxaliplatin chemotherapy capacities in vitro and in vivo. Mechanistically, upon oxaliplatin stimulation, c-MYC promotes the transcriptional regulation and expression of WDR43. WDR43 enhances the ubiquitination of p53 by MDM2 by binding RPL11, thereby reducing the stability of the p53 protein, which further induces the proliferation and chemoresistance of CRC cells. Thus, WDR43 may not only mark CRC progression but also be a potential therapeutic target of chemoresistance in CRC.

overall_design: WDR43 were knocked down in HCT116 cells, and the differences in gene expression were compared with shNC, respectively, using RNAseq.

first: Yuqin

last: Di

first: Weiling

last: He


title: Cancer cell-derived arginine fuels polyamine biosynthesis in tumor-associated macrophages to promote immune evasion

status: Public on Jun 30 2025

city: Hangzhou

first: Xin

last: Du

state: Zhejiang

address: No. 1, Banshandong Road

department: Breast Cancer Center

institute: The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

summary: Cancer cell metabolic reprogramming reshapes the tumor microenvironment (TME) into a pro-tumor niche. Arginine metabolism plays complex roles in regulating tumor progression through metabolic cross-feeding among various cell types within the TME, but the primary intercellular communication dominating the collective impact of arginine on tumor progression remains unclear. Here, we investigated the role of arginine metabolism in breast cancer progression using clinical analysis, single-cell RNA sequencing data analysis, and in vivo animal models. We found that the metabolic interplay between cancer cells and macrophages exerts a predominant influence on breast cancer progression mediated by arginine metabolism. Breast cancer cells act as the major source of arginine within the TME, where this tumor-derived arginine fosters a pro-tumor shift in tumor-associated macrophages (TAMs), leading them to suppress the anti-tumor activity of CD8+ T cells. Notably, this cancer cell-macrophage interaction overrides the stimulatory effect of arginine on the anti-tumor capability of CD8+ T cells. Mechanistically, polyamines derived from arginine metabolism mediate TAM polarization via TDG-mediated DNA demethylation, driven by p53 signaling. Importantly, inhibiting the arginine-polyamine-TDG axis across cancer cells to macrophages effectively suppresses breast cancer growth by modulating the immune microenvironment, suggesting therapeutic potential in targeting this axis for breast cancer therapy.

overall_design: The study involved the utilization of six-week-old BALB/c mice, C57BL/6 mice. For the allograft experiments,Wild-type(WT) or Ass1 knockdown (shAss1) 4T1 cells or EO771 cells were injected into the mammary fat pads of mice with the genetic background of the BALB/c and C57BL/6 (1 × 106 cells in 100 μL PBS), respectively. Single-cell RNA seqencing (Chromium, 10X Genomics) was performed to compare the difference of the tumor microenvironment between WT group and shAss1 group.

first: Yinghua

last: Zhu

first: Ziwei

last: Zhou

first: Yue

first: Si

last: Chen

first: Zhenkun

first: Zhiyong

last: Wu

first: Xiaorong

last: Lin

first: Jiaxin

last: Zhong

first: Beinan

last: Han

first: Wenkui

last: Fu

first: Hongde

last: Li

first: Man-Li

last: Luo

first: Hai

last: Hu


title: Lestaurtinib inhibits therapy resistant ovarian cancer

city: Rochester

first: Esther

last: Rodman

state: Minnesota

address: 200 1st St SW

institute: Mayo Clinic

summary: Ovarian cancer is the deadliest gynecological malignancy, owing to its late-stage diagnosis and high rates of recurrence and resistance following standard-of-care treatment, highlighting the need for novel treatment approaches. Through an unbiased drug screen, we identified the kinase inhibitor, lestaurtinib, as a potent antineoplastic agent for chemotherapy- and PARP-inhibitor (PARPi)-sensitive and -resistant ovarian cancer cells and patient derived xenografts (PDXs). RNA-sequencing revealed that lestaurtinib potently suppressed JAK/STAT signaling and lestaurtinib efficacy was shown to be directly related to JAK/STAT pathway activity in cell lines and PDX models. Most ovarian cancer cells exhibited constitutive JAK/STAT pathway activation and genetic loss of STAT1 and STAT3 resulted in growth inhibition. Lestaurtinib also displayed synergy when combined with cisplatin and olaparib, including in a model of PARPi resistance. In contrast, the most well-known JAK/STAT inhibitor, ruxolitinib, lacked antineoplastic activity against all ovarian cancer cell lines and PDX models tested. This divergent behavior was reflected in the ability of lestaurtinib to block both Y701/705 and S727 phosphorylation of STAT1 and STAT3, whereas ruxolitinib failed to block S727. Consistent with these findings, lestaurtinib additionally inhibited the serine/threonine kinases, JNK and ERK, leading to more complete suppression of STAT phosphorylation. Concordantly, combinatorial treatment with ruxolitinib and a JNK or ERK inhibitor resulted in synergistic antineoplastic effects at dose levels where the single agents were ineffective. Taken together, these findings indicate that lestaurtinib, and other treatments that converge on JAK/STAT signaling, are worthy of further pre-clinical and clinical exploration for the treatment of highly aggressive and advanced forms of ovarian cancer.

overall_design: MDAH and OVSAHO (OVS) cells treated with DMSO vehicle (Veh) or 500nM lestaurtinib (Lest) in triplicate for 24 hours and conducted gene expression profiling via RNAseq to understand what genes are regulated by lestaurtinib treatment.

first: John

last: Hawse


title: Senataxin promotes recombination fidelity during antigen receptor gene diversification

status: Public on Jun 23 2025

city: Stanford

first: Richard

last: Frock

state: California

address: 269 Campus Drive

department: Radiation Oncology

institute: Stanford University

summary: Immunoglobulin (Ig) and T cell receptor (TCR) V(D)J gene recombination relies on non-homologous end-joining (NHEJ), which repairs DNA double-strand breaks (DSBs) introduced by the RAG1/2 nuclease complex. Functional redundancies exist between NHEJ and the ATM kinase-dependent chromatin DSB response, likely masking the activity of additional factors. Here, we performed parallel targeted CRISPR-Cas9 screens in pro-B cells and found that  Senataxin (SETX) participates in V(D)J recombination.  We find that SETX supports V(D)J recombination, particularly in condition of ATM kinase inhibition or XLF deficiency. Furthermore, we show that SETX suppresses the formation of aberrant coding end-to-signal end hybrid joints during V(D)J recombination and prevents the aberrant joining of AID-induced DNA ends during Ig heavy chain class switching, revealing an essential role for SETX in promoting recombination fidelity during antigen receptor gene diversification.

overall_design: Bone marrow cells  proficient or deficient in SETX and v-Abl pro-B cells deficient in p53 alone or in combination with XLF, XRCC4, SETX, or XLF/SETX deficiency were isolated for genomic DNA and subjected to LAM-HTGTS JoinT-seq DNA junction mapping using Jkappa1 coding end bait primers as described  PMID: 38412274.

first: Alice

last: Libri

first: Jinglong

last: Wang

first: Ludovic

last: Deriano


title: Systemic viral dissemination and inflammation associate with fatal outcome in a new African green monkey mucosal exposure model of Lassa fever

status: Public on Jun 27 2025

city: Galveston

first: Jacquelyn

last: Turcinovic

state: TX

address: Galveston National Laboratory, 301 University Blvd.

department: Microbiology and Immunology

institute: University of Texas Medical Branch

summary: Lassa virus (LASV) is the causative agent of Lassa fever (LF) and causes significant human morbidity and mortality in endemic areas of West Africa. LF is listed by the World Health Organization as one of the diseases posing the greatest threat to public health due to its pandemic potential and lack of medical countermeasures suitable for human use. Animal models are needed to test the efficacy of candidate vaccines and treatments and therapies to combat LF. Previous studies have shown that cynomolgus monkeys of Asian origin best reproduce clinical features of human LF. However, because of the worldwide shortage of macaques caused by the COVID-19 pandemic, research on high consequence pathogens including LASV has been severely hindered. To address this problem, we assessed the pathogenic potential of a contemporary LASV isolate in both Mauritius origin cynomolgus monkeys and African green monkeys (AGM) to find a more available alternative nonhuman primate species to model LF. Here, we show similarity in transcriptomic host responses related to interferon signaling, cytokinemia, and immune cell deregulation; however, AGMs more consistently reproduced hallmark features of lethal human LF better than Maurits origin cynomolgus macaques with AGMs developing more overt hemorrhagic manifestations closer to that seen in humans. We further show that the LD50 of LASV of AGMs exposed by a natural mucosal route is approximately 27 PFU. This low LD50 further highlights the concern about the public health threat posed by LASV. Our data support the further development and use of AGMs to test promising vaccines and treatments for LF.

sample_organism:
Macaca fascicularis
Chlorocebus sabaeus

overall_design: Time series NanoString data from cynomolgus macaques and African green monkeys challenged Lassa virus

first: Joseline

last: Velasquez-Reyes

first: Robert

last: Cross

middle: H

last: Connor

first: Thomas

last: Geisbert


title: Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration

city: Beijing

first: Jing

address: qinghuayuan

institute: Tsinghua university

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

overall_design: Refer to individual Series


title: The alteration of gene expression in fulvestrant resistant breast cancer cell by cold atmospheric plasma (CAP)

status: Public on Jun 24 2025

city: Goyang

first: Sooseong

last: Choi

country: South Korea

institute: Dongguk university

summary: Cold atmospheric plasma (CAP) contributes to recovery of fulvestrant sensitivity in fulvestarnt resistant breast cancer cell.

overall_design: RNA-seq profiling of fulvestrant resistant breast cancer cells treated cold atmospheric plasma

first: Sanghyun

last: Jung

first: Sun Jung

last: Kim


title: Spatial transcriptomics data of RM9-hSTEAP1 tumor tissues treated with CAR-T cells

status: Public on Jun 25 2025

city: London

first: Jun

last: Ishihara

address: 86 Wood Lane

department: Bioengineering

institute: Imperial College London

summary: Immunosuppressive microenvironments, the lack of immune infiltration, and antigen heterogeneity pose challenges for chimeric antigen receptor (CAR)-T cell therapies applied to solid tumors. Previously, CAR-T cells were armored with immunostimulatory molecules, such as interleukin-12 (IL-12), to overcome this issue, but faced high toxicity. Here, we show that collagen-binding domain-fused IL-12 (CBD-IL-12) secreted from CAR-T cells to target human six transmembrane epithelial antigen of the prostate 1 (STEAP1) is retained within murine prostate tumors. This leads to high intratumoral interferon-γ levels, without hepatotoxicity and infiltration of T cells into non-target organs compared with unmodified IL-12. Both innate and adaptive immune compartments are activated and recognize diverse tumor antigens after CBD-IL-12-armored CAR-T cell treatment. Combination of CBD-IL-12-armored CAR-T cells and immune checkpoint inhibitors eradicated large tumors in an established prostate cancer mouse model. Additionally, human CBD-IL-12-armored CAR-T cells showed potent anti-tumor efficacy in an 22Rv1 xenograft while reducing circulating IL-12 levels compared with unmodified IL-12-armored CAR-T cells. CBD-fusion to potent payloads of CAR-T therapy may remove obstacles to their clinical translation towards elimination of solid tumors.

overall_design: NanoString GeoMx Digital Spatial Profiler (DSP) whole transcriptome analysis (WTA) was performed on RM9-hSTEAP1 tumor samples collected at 10 days after CAR-T cell treatment. PFA-fixed, paraffin embedded tumor blocks were sectioned, and Twelve regions of interest (ROI) were chosen across four different tumor sections in each treated group followed by library preparation and sequencing. A tumor sample in unarmored CAR-T treatment group was not used because the tissue section was damaged.

first: Koichi

last: Sasaki

first: Vipul

last: Bhatia

first: Yuta

last: Asano

first: Jakob

last: Bakhtiari

first: Pooja

last: Kaur

first: Chuyi

first: Takumi

last: Matsuo

first: Olivier

last: Dubois

first: Po-Chuan

last: Chiu

first: Donny

last: Gun

first: Charanjit

last: Singh

first: Ioanna

last: Panagi

first: Laurine

last: Noblecourt

first: Maria

last: Nikolaidi

first: Truman

last: Chong

first: Gerardo

last: Javier

first: Saul

last: Priceman

first: Aude

middle: G

last: Chapuis

middle: K

last: Lee


title: Modularity of OCT4 underlies its functional diversity in reprogramming and embryonic development [RNA-seq]

status: Public on Jun 20 2025

city: Edinburgh

first: Abdenour

last: Soufi

address: 5 Little France Drive

department: School of Biological Sciences

institute: University of Edinburgh

summary: Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation.  Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.

overall_design: RNA-seq profiling of human fibroblasts (hFibs), hunan ES cells (hESCs) and human iPS cells derived from  hFibs using OCT4 wildtype (hiPSCs-O-WT), OCT4-lin95-117 mutant (hiPSCs-O-lin95-117), and OC4-lin-mini nutabt (hiPSCs-O-lin-mini).


title: Modularity of OCT4 underlies its functional diversity in reprogramming and embryonic development [ATAC-seq]

summary: Amongst the multiple cell fates orchestrated by OCT4, its ability to maintain pluripotency is thought to underpin reprogramming. How OCT4 drives pluripotency from diverse cellular contexts is unclear. By systematically dissecting OCT4, we find that reprogramming requires OCT4 domains dispensable for pluripotency maintenance and development throughout gastrulation but important for the embryo competence to develop through late gestation. Removing OCT4 essential domains in reprogramming leads to more non-specific OCT4 enrichment at accessible somatic sites, unlike removing the non-essential domains, which expands genomic targeting of closed pluripotency sites. Delineating the interaction of OCT4 with chromatin-associated proteins in reprogramming and pluripotency maintenance reveals that OCT4 essential domains engage a unique set of proteins during reprogramming. Remarkably, OCT4 can induce pluripotent and trophoblast stem cells using many similar domains and yet it can be truncated to only induce pluripotency. Our findings demonstrate that the ability of transcription factors to control diverse cell types is encoded within their modular nature.

overall_design: ATAC-seq profiling of human fibroblasts (hFibs) during early reprogramming (OSKM48h), after TNIP2, STAT3 were knocked down by siRNA using non-targeting siRNA (CTRL_siRNA) as a control.


title: SOX2 Binds to CD133 in Glioblastoma Stem Cells to Regulate Cellular Stress Pathways Underlying Treatment Resistance

city: AURORA

first: Etienne

last: Danis

state: CO

department: Cancer Center

institute: University of Colorado, Denver - Anschutz Medical Campus

summary: Glioblastoma (GBM) remains a formidable challenge in clinical settings due to limited treatments available for patients. The surface protein CD133 identifies glioblastoma stem cells (GSCs), cells capable of overcoming therapeutic pressures and correlate with more aggressive tumor phenotypes. In our study, we utilized a CRISPR-based genetic screen and Cleavage Under Targets and Release Using Nuclease (CUT&RUN) workflows to distinguish molecular differences between healthy neural stem cells (NSCs) and GSCs. This revealed heightened SOX2 expression directly binds to the PROM1 gene in GSCs, and upregulates genes associated with stress responses including those contributing to chemoradiation resistance. Our findings demonstrate the power of complementary genomic tools, CRISPR screens with CUT&RUN, to unravel complex gene regulatory networks. This integrated approach offers insights into overlapping fields of cancer biology and stem cell research.

overall_design: Cleavage Under Targets and Release Using Nuclease (CUT&RUN) was used to profile the glioblastoma cell lines and neural stem cells.

first: Neil

last: Savage

first: Chitra

last: Venugopal

first: Sheila


title: Surgical and blood-based minimal residual disease in patients with ovarian cancer after frontline therapy: Clinical outcomes and translational opportunities [Spatial Transcriptomics]

city: Houston

first: Sanghoon

address: 1881 East Road

institute: The University of Texas MD Anderson Cancer Center

summary: Minimal residual disease (MRD) after frontline treatment of advanced stage ovarian cancer remains a longstanding barrier to cure. We investigated the prognostic and translational value of MRD detection by second look laparoscopy (SLL) and circulating tumor DNA (ctDNA) at the completion of frontline therapy. Patients with high-grade epithelial ovarian cancer with complete clinical response to frontline therapy who underwent SLL and plasma collection for ctDNA were included.  Progression-free survival (PFS) and overall survival (OS) were estimated based on MRD and clinicopathologic status. Spatial transcriptomics (GeoMx and Visium) and proteomics (CODEX) profiling were performed on serial samples from select patients. Forty of 95 (42.1%) patients had surgically detected MRD, and this was associated with worse PFS (median PFS 7.4 vs 23.8 months; p<0.001) and OS (median OS 33.9 vs not reached; p<0.001). SLL positivity was found to be an independent negative prognostic factor for OS (HR 4.40, 95% CI 1.37-14.21, p=0.013) in multivariable analysis. Among 44 patients who underwent SLL and had ctDNA testing, 34% (15/44) were ctDNA-positive, which was associated with worse PFS (6.4 vs 28.1 months; p<0.001) and OS (32.4 months vs not reached; p=0.008). We demonstrated the feasibility of spatial multi-omics in studying MRD, and their ability to provide hypothesis-generating observations, implicating the upregulation of the hypoxia signaling pathway, expression of multiple druggable targets (CDK6, GLS, MSLN, and ERBB2), and immune exclusion, in the development of MRD lesions. In summary, approximately half of patients in clinical remission after frontline therapy have assessable MRD which can inform prognosis, therapeutic target discovery, and clinical trials.

overall_design: Tumor samples from 4 MRD-positive cases were collected and profiled with Visium.

first: Dai

last: Yibo

first: Lee

last: Sanghoon

first: Wang

last: Linghua

first: Jazaeri

last: Amir A.


title: Modularity of OCT4 underlies its functional diversity in reprogramming and embryonic development (mES ATAC-seq)

status: Public on Jun 19 2025

overall_design: ATAC-seq profiling of mouse emrbyonic stem cells (mESCs) containing the knockin mutation Pou5F1lin-del in three independent clonal lines (CL1, CL3, and CL7) compared to wildtype (WT).


title: Modularity of OCT4 underlies its functional diversity in reprogramming and embryonic development.


title: Modularity of OCT4 underlies its functional diversity in reprogramming and embryonic development (mES RNA-seq)

overall_design: RNA-seq profiling of mouse embryonic stem cells (mESCs), containing the knockin mutation Pou5F1lin-del in three independent clonal lines (CL1, CL3, and CL7) compared to wildtype (WT). The mESCs were grown under LIF and LIF-2i conditions.


title: X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels [RNA-seq]

city: Rotterdam

first: Beatrice

last: Tan

address: Dr. Molewaterplein 40

department: Developmental Biology

country: Netherlands

institute: Erasmus MC

summary: Gene dosage compensation mechanisms are crucial for mammalian development. In mice, recent findings show that cells can sense the number of X chromosomes. Loss or inactivation of one of the two X chromosomes is compensated by upregulating the remaining active X chromosome, a process termed X-chromosome upregulation (XCU). However, how cells sense X-chromosome dosage and induce XCU remains unclear. Here, we show that heterozygous X chromosome fragment deletions in mouse pluripotent stem cells induces XCU in trans, and that compensation takes place at the mRNA and protein level. Furthermore, we found that inducing gene silencing in cis on autosomes induces gene dosage compensation in trans. This work provides significant insights into the molecular foundations of mammalian gene dosage compensation.

overall_design: We performed scRNA-seq, bulk RNA-seq and ChIP-seq on XX, XY, and XO cells, as well as on cell lines with large deletions on the X-chromosome, to investigate X-chromosome upregulation.

middle: F

first: Ryan

middle: N

last: Allsop

first: Jeffrey

last: Boeren

first: Joost

last: Gribnau

first: Vincent

last: Pasque


title: A SOX2-VSX2 axis modulates a core cis-regulatory circuitry to safeguard retinal neural competence

city: Pittsburgh

first: Shuchang

last: Liu

state: PA

address: 203 Lothrop Street

institute: University of Pittsburgh


title: X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels [scRNA-seq]

overall_design: We performed scRNA-seq, bulk RNA-seq, and ChIP-seq on XX, XY, and XO cells, as well as on cell lines with large deletions on the X-chromosome, to investigate X-chromosome upregulation.


title: Modularity of OCT4 underlies its functional diversity in reprogramming and embryonic development [ChIP-seq]

overall_design: ChIP-seq of OCT4 wildtype, compared to OCT4 lin29-42, lin95-117, and lin-mini mutants during early reprogramming (OSKM48h).  ChIP-seq of OCT4 in human ES cells (hESCs) was used as a control. ChIP-seq enrichment was normalised against input DNA.


title: X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels


title: Anthracyclines induce global changes in chromatin accessibility in cardiomyocytes that overlap with cardiovascular disease loci [CUT&Tag]

status: Public on Jun 17 2025

first: Michelle

middle: C.

last: Ward

email: miward@UTMB.edu, ermatthe@UTMB.edu

address: 301 University Blvd., MRB 7.150

department: Biochemistry and Molecular Biology

institute: UTMB-Galveston

summary: Breast cancer drugs including anthracyclines (ACs) and Trastuzumab increase the risk for cardiovascular diseases (CVDs) such as atrial fibrillation (AF) and heart failure (HF) that ultimately affect the heart muscle. These CVDs are associated with hundreds of genetic variants in non-coding regions of the genome. However, how these drugs affect the regulatory potential of the non-coding genome of the heart and CVD risk loci is unknown. We therefore measured global chromatin accessibility across iPSC-derived cardiomyocytes derived from four healthy individuals that we treated with topoisomerase II (TOP2) inhibiting ACs, Doxorubicin, Epirubicin, and Daunorubicin, and the anthracenedione, Mitoxantrone as well as the TOP2-independent monoclonal antibody Trastuzumab, for three and 24 hours. We identified tens of thousands of open chromatin regions that are differentially accessible in response to TOP2 inhibitor treatments over time, and no changes in response to Trastuzumab. Early AC-responsive regions are promoter-proximal and are enriched for regions bound by TOP2 beta. Late AC-responsive regions are enriched for AC response genes particularly those associated with mismatch repair. AC-response regions near AC response genes are enriched for FOS:JUNB transcription factor motifs. Three AC-induced cardiotoxicity-, 28 AF- and 14 HF-associated SNPs directly overlap late AC-responsive regions. Early AC-responsive regions are enriched for AF SNPs including rs3176326, which is also associated with HF, and is an eQTL for CDKN1A in heart tissue. This SNP associates with increased chromatin accessibility at a TOP2 beta-bound region, increased histone acetylation, and increased CDKN1A expression in response to all ACs. Our results demonstrate large-scale changes in chromatin accessibility in cardiomyocytes treated with ACs, which correspond to several regions harboring AF and HF risk loci. The identified drug-responsive chromatin regions can be used to annotate variants in cancer patient populations to contribute to risk estimation for CVD.

overall_design: We collected CUT&Tag data from iPSC-derived cardiomyocytes derived from four healthy female individuals (A-D). Each individual was treated with 0.5 uM of one of the following breast cancer drugs: Doxorubicin (DOX), Epirubicin (EPI), Daunorubicin (DNR), Mitoxantrone (MTX), or a vehicle control (VEH) for three or 24 hours.

first: Elizabeth

middle: R

last: Matthews

first: Raodatullah

last: Abodunrin

first: John

last: Hurley

middle: C


title: Anthracyclines induce global changes in chromatin accessibility in cardiomyocytes that overlap with cardiovascular disease loci [ATAC-seq]

overall_design: We collected ATAC-seq data from iPSC-derived cardiomyocytes derived from four healthy female individuals (A-D). Each individual was treated with 0.5 uM of one of the following breast cancer drugs: Doxorubicin (DOX), Epirubicin (EPI), Daunorubicin (DNR), Mitoxantrone (MTX), Trastuzumab (TRZ), or a vehicle control (VEH) for three or 24 hours.


title: X-chromosome upregulation operates on a gene-by-gene basis at RNA and protein levels [ChIP-seq]


title: Multiregional single-cell profiling reveals extensive field cancerization and an immunosuppressive microenvironment in oral squamous cell carcinoma

city: Seoul

first: Nam Sukl

last: Sim

address: Sinchon

institute: Yonsei University, College of Medicine

summary: Oral squamous cell carcinoma (OSCC) is highly heterogeneous and metastatic, and the mechanisms driving OSCC development, progression, and metastasis are poorly understood. We performed multiregional single-cell RNA sequencing on 268,131 cells obtained from tumor core, tumor periphery, adjacent non-tumor tissue, and metastatic lymph node samples from 10 patients with human papillomavirus (HPV)–negative metastatic OSCC.

overall_design: Single-cell RNA-seq: 10X data of 36 samples from 10 OSCC patients

first: Yoon-Woo

last: Koh


title: Dissecting Non-Coding GWAS Loci with High-Resolution 3D Chromatin Interactions Reveals Causal Genes with Relevance to Heart Failure [Perturb-seq]

status: Public on Jun 16 2025

city: South San Francisco

first: Ittai

middle: Ethan

last: Eres

state: CA

address: 750 Gateway Boulevard

department: CRADI

institute: Amgen

summary: Heart failure is caused in part by cardiac remodeling processes that include the death of cardiac myocytes and their replacement by cardiac fibroblasts. We hypothesized that these two cell types may harbor epigenetic contexts in which heart disease-associated non-coding SNPs perturb gene expression relevant to disease. Accordingly, we generated high-resolution Hi-C data layered with functional genomic information to annotate and link putative distal regulatory elements in heart disease-associated loci to gene promoters. Our analysis identified several target genes with established roles in cardiac fibrosis and/or heart disease (GJA1, TBC1D32, CXCL12, IL6R, and FURIN). Perturb-seq in cardiac fibroblasts after knocking out putative regulatory elements confirmed regulatory relationships involving GJA1, CXCL12, and FURIN, in addition to changes in transcriptomic signatures associated with fibroblasts in heart failure. Our results demonstrate how integrative multi-omic approaches can delineate pathophysiologically relevant regulatory circuits that connect protein-coding genes to non-coding genetic variants associated with disease.

overall_design: Hi-C, ATAC-seq, and RNA-seq data were generated from primary cells--human cardiac myocytes (HCM) and normal human cardiac fibroblasts--ventricular (NHCFV). ATAC-seq and RNA-seq were also generated for immortalized human cardiac fibroblasts (iHCF), which were additionally used for gene editing experiments to validate SNP-gene predictions.

first: Richard

last: Gill

first: Daniel R.

last: Lu

first: Jiamiao

last: Yu

first: Tracy

last: Yamawaki

first: Hong

last: Zhou

first: Baikang

last: Pei

first: Junedh M.

last: Amrute

first: Yen-Sin

last: Ang

first: Songli

last: Wang

first: Kory J.

last: Lavine

first: Brandon

last: Ason

first: Chi-Ming

last: Li

first: Yi-Hsiang

last: Hsu


title: Cellular and genetic mechanisms that shape the development and evolution of tail vertebral proportion in mice and jerboas

status: Public on Jun 15 2025

city: La Jolla

first: Ceri

middle: J

last: Weber

address: 9500 Gilman Dr

institute: University of California San Diego

summary: Limbs and vertebrae elongate by endochondral ossification, but local growth control is highly modular such that not all bones are the same length. Compared to limbs, which have a different evolutionary and developmental origin, far less is known about how individual vertebrae establish proportion. Using the jerboa and mouse tail skeleton, we find that cell number is a common driver of limb and vertebral proportion in both species. However, chondrocyte hypertrophy, which is a major driver proportion in all mammal limbs, is limited to the extreme disproportionate growth of jerboa mid-tail vertebrae. The genes associated with differential growth in the vertebral skeleton overlap significantly but not substantially with genes associated with limb proportion. Among shared candidates, loss of Natriuretic Peptide Receptor 3 in mice causes disproportionate elongation of the proximal and mid-tail vertebrae, in addition to the proximal limb. Our findings therefore reveal cellular and molecular processes tuning growth of individual vertebrae while also identifying natriuretic peptide signaling among genetic control mechanisms that shape the entire skeleton.

sample_organism:
Mus musculus
Jaculus jaculus

platform_organism:
Mus musculus
Jaculus jaculus

overall_design: RNA-seq comparison of pooled mouse and jerboa cranial growth cartilages from tail vertebrae 1 and 6 during rapid bone elongation at postnatal day 7 and postnatal day 16 respectively

first: Alexander

last: Weitzel

middle: Y

last: Liu

first: Erica

last: Gacasan

first: Susan

last: Chapman

first: Robert

middle: L

last: Sah

first: Kimberly

last: Cooper


title: Dissecting Non-Coding GWAS Loci with High-Resolution 3D Chromatin Interactions Reveals Causal Genes with Relevance to Heart Failure [Hi-C]

first: Ittai

last: Eres

first: Richard

last: Gill

first: Daniel R.

last: Lu

first: Jiamiao

first: John

last: Yu

last: Yamawaki


title: Dissecting Non-Coding GWAS Loci with High-Resolution 3D Chromatin Interactions Reveals Causal Genes with Relevance to Heart Failure [RNA-seq]

first: Tracy

first: Hong

last: Zhou

first: Baikang

last: Pei

first: Junedh M.

last: Amrute

first: Yen-Sin

last: Ang

last: Wang


title: Loss of YTHDF2 enhances Th9 programming and CAR-Th9 cell antitumor efficacy

city: Los Angeles

first: Sai

last: Xiao

address: 1500 E. Duarte Road

institute: City of Hope

type: Methylation profiling by high throughput sequencing

summary: CD4+ T cells differentiate into various subsets, including T helper 1 (Th1), Th2, Th9, Th17, and regulatory T cells, which are essential in immune responses and cancer immunotherapy. However, the role of RNA N6-methyladenosine (m6A) modification in this differentiation remains unclear. Here, we demonstrate that YTHDF2, a key m6A reader protein known to destabilize m6A-modified mRNA, negatively regulates Th9 cell differentiation. Ablation of Ythdf2 in both mouse and human naïve CD4+ T cells significantly promotes Th9 differentiation by stabilizing Gata3 and Smad3 mRNA under IL-4 and TGF-β signaling. Ythdf2-deficient Th9 cells produce higher levels of IL-9 and IL-21, leading to increased tumor infiltration and cytotoxicity by CD8+ T and NK cells, thereby improving antitumor activity versus wild-type Th9 cells. Moreover, YTHDF2 depletion in CAR-Th9 cells enhances immune activation, reduces terminal differentiation, and augments antitumor efficacy. Targeting YTHDF2 thus represents a promising strategy for enhancing Th9 and CAR-Th9 cell-based cancer immunotherapies.

overall_design: Total RNA was isolated by TRIzol reagent from fifty million  WT and Ythdf2-KO Th9 cells. m6A MeRIP sequencing was performed to detect the m6A modification alterations in two groups. YTHDF2 RNA immunoprecipitation sequencing was performed to map the target transcripts bound by YTHDF2 in Th9 cells.

first: Jianhua


title: RNA-seq of Bone Marrow Mesenchymal Stem Cells:adult female bone marrow

first: Liyuan

last: Chen

address: 22th Zhongguancun South Ave

institute: Department of Orthodontics,  Peking University School and Hospital of Stomatology, Beijing

summary: Total RNAs from aged BMMSCs (P10–12) with/without em-eNMs treatment were extracted by Trizol. Libraries were prepared using NEBNext® kit and sequenced on Illumina HiSeq 3000. QC used FastQC and FASTX toolkit. Data were mapped to human genome (NCBI build 37, mm9) by HISAT2. Three samples per group. DEGs were identified by Ballgown (≥1.5-fold, P<0.05).

overall_design: The study design involved extracting total RNA from aged BMMSCs (P10–12) with or without em-eNMs treatment using Trizol, constructing sequencing libraries via NEBNext® Ultra™ kit, and sequencing on Illumina HiSeq 3000. FastQC and FASTX toolkit were used for data QC, followed by mapping to the human genome (NCBI build 37, mm9) with HISAT2. Three biological replicates per group were analyzed for DEGs using Ballgown, with significance set at ≥1.5-fold change and P<0.05.


title: Dissecting Non-Coding GWAS Loci with High-Resolution 3D Chromatin Interactions Reveals Causal Genes with Relevance to Heart Failure [ATAC-seq]

first: Songli

first: Kory J.

last: Lavine

first: Brandon

last: Ason

first: Chi-Ming

last: Li

first: Yi-Hsiang

last: Hsu


title: CXCL10-induced chemotaxis of ex vivo-expanded natural killer cells combined with NKTR-255 enhances anti-tumor efficacy in osteosarcoma

status: Public on Jun 10 2025

city: Valhalla

first: Shiori

last: Eguchi

state: New York

address: 40 Sunshine Cottage Road

department: Pediatrics

institute: New York Medical College

summary: Osteosarcoma (OSA) has a dismal prognosis despite surgical resection and multiagent chemotherapy. While adoptive natural killer (NK) cell therapies have been successful in hematological malignancies, the application in solid tumors is challenging due to a tumor microenvironment (TME) that impairs NK cell tumor infiltration. Here, we found that ex vivo expansion of NK cells significantly increases the expression of C-X-C motif chemokine receptor 3 (CXCR3), one of the major proteins in the regulation of NK cell chemotaxis. Engineered over-secretion of CXCR3 ligands, C-X-C motif chemokine ligand (CXCL)9, -10, or -11, from OSA cells significantly enhanced expanded NK cell migration toward OSA cells in vitro and infiltration into the TME in vivo, with the highest NK infiltration rate in CXCL10-secreting tumors. Infusions of expanded NK cells significantly reduced (p = 0.02), and concomitant treatment with an interleukin (IL)-15 agonist NKTR-255 further reduced tumor burden and significantly increased survival in mice bearing CXCL10-secreting tumors compared with those with wild-type tumors (p = 0.02). Single-cell RNA sequencing and mass cytometry revealed upregulated apoptosis and transforming growth factor-β (TGF-β) signaling as the potential mechanisms of response/resistance to NK cell therapy in vivo. Our findings highlight potential application of chemokine-enhanced NK tumor infiltration in combination with an IL-15 agonist as a novel approach to effective treatment of OSA.

overall_design: To identify response/resistance mechanisms of the combination therapy of NK cells and NKTR-255, mice were inoculated subcutaneously with both WT and CXCL10-secreting osteosarcoma 143B cells on separate flanks and treated with the combination of NK cells and NKTR-255. Tumors were collected 21 days following tumor injection and dissociated into single cells for scRNA-seq.


title: Lithium Deficiency and the Onset of Alzheimer’s Disease

status: Public on Jun 12 2025

city: Boston

first: Jae Joon

last: Choi

state: MA

address: 77 Avenue Louis Pasteur

department: Genetics

institute: Harvard Medical School

summary: The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood.  Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during aging.  We demonstrate that cortical uptake of Li is the most significantly impaired of all metals analyzed in mild cognitive impairment (MCI) and AD, and that Li bioavailability is further reduced by amyloid sequestration.  Li deficiency was recapitulated by feeding AD model and wild-type mice a lithium-deficient diet.  Reducing endogenous cortical Li by ~50% markedly elevated Aβ deposition and phospho-tau accumulation, and led to proinflammatory microglial activation, synapse loss, and accelerated cognitive decline. These effects were mediated, at least in part, through activation of the kinase GSK3β in neurons, microglia, and oligodendrocytes.  Single nucleus RNA-seq showed that Li deficiency gives rise to significant transcriptome changes in all major brain cell types that overlap with transcriptome changes in AD. Replacement therapy with lithium orotate (LiO), a Li salt with reduced amyloid sequestration, prevents pathological changes and memory loss in AD mouse models and aging wild-type mice at a physiological concentration. Thus, Li deficiency may be among the earliest molecular events that link amyloid deposition to protean multisystem effects on the brain. Li replacement with amyloid-evading salts is a potentially novel therapeutic approach to AD and brain aging.

overall_design: To investigate the transcriptomic changes in microglia caused by lithium deciciency, microglia are isolated from WT and 3xTG mice undergoing control or lithium deficient diet. Comparitive gene expression profiling analysis was performed between control and deficient diet.

first: Zhen

last: Ngian

first: Jaejoon

first: Liviu

last: Aron

first: Bruce

middle: A

last: Yankner


title: Carcinoma exhibiting epithelial-mesenchymal transition manifests an M2 macrophage-enriched tumor immune microenvironment

status: Public on May 31 2025

city: Taipei

first: Huang-chun

last: Lien

address: Chung-San S. Rd.

country: Taiwan

institute: National Taiwan University

summary: We profiled genes relevant to the tumor-immune interface,in six metaplastic breast carcinomas (MpBCs).

overall_design: We profiled genes relevant to the tumor-immune interface, in invasive carcinoma of no special type (NST) [also called IDC] and its paired spindle carcinomatous (SPS) component, which is considered the EMT counterpart of the former, across six metaplastic breast carcinomas (MpBCs).

first: H


title: Genome-wide methylation analysis showng allele-specific DNA methylation

status: Public on May 28 2025

city: New Haven

first: Sung Eun

state: CT

address: 300 Cedar st

institute: Yalde University

summary: Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain. We previously discovered that euchromatic histone lysine N-methyltransferase-2 (EHMT2/G9a) inhibitors are capable of un-silencing PWS-associated genes by restoring their expression from the maternal chromosome. Here, in mice lacking the Ehmt2 gene, we document un-silencing of the imprinted Snrpn/Snhg14 gene on the maternal chromosome in the late embryonic and postnatal brain. Using PWS and Angelman syndrome patient derived cells with either paternal or maternal deletion of 15q11.2-q13, we have found that chromatin of maternal PWS-IC is closed and has compact 3D folding confirmation. We further show that a distinct noncoding RNA (TSS4-280118) preferentially transcribed from the upstream of the PWS-IC of maternal chromosome interacts with EHMT2 and forms a heterochromatin complex in CIS on the maternal chromosome. Inactivation of TSS4-280118 by CRISPR/Cas9 editing results in unsilencing of the expression of SNRPN and SNORD116 from the maternal chromosome. Taken together, these findings demonstrate that allele-specific recruitment of EHMT2 is required to maintain the maternal imprints. Our findings provide mechanistic insights and support a model for imprinting maintenance of the PWS imprinted domain.

overall_design: we aimed to report Allele‐specific methylation in CpG islands in chr15q11-q13

first: Yong-hui

last: Jiang


title: Partial restoration of the mitochondrial dysfunction by AAV-Ant1 (Slc25a4) transduction protects against dilated cardiomyopathy in Slc25a4-/- plus mtDNA mutant mice

status: Public on Jun 01 2025

city: Philadelphia

first: Joseph

middle: W

last: Guarnieri

address: 3501 Civic Center Blvd

department: Center for Mitochondrial and Epigenomic Medicine

institute: Children's Hosptial of Philadelphia

summary: Primary mitochondrial disease (PMD) patients manifesting cardiomyopathy are twice as likely to die as other PMD patients. One PMD with cardiomyopathy is caused by null mutations in the heart-muscle isoform of the adenine nucleotide translocator (SLC25A4, ANT1) gene, the severity of the cardiomyopathy being mediated by the mitochondrial DNA (mtDNA). To optimize strategies for addressing mitochondrial cardiomyopathy, we generated an Ant1 null mouse and combined it with the ND6P25L mtDNA mutation to mimic the hypertrophic versus dilated cardiomyopathies observed in patients. Here, we transduce the neonatal Ant1-/- and Ant1-/-+ND6P25L mouse hearts with an AAV2/9-pDes-Gfp-mAnt1 cDNA vector. We show that restoration of just 10% of Ant1 gene expression was sufficient to ameliorate the cardiomyopathies in these mice. Proteomics and single-nucleus RNA sequencing reveal the reversal of dysregulated mitochondrial metabolic genes, including PGC1α, as well as cardiac contractile and extracellular matrix proteins. Hence, a modest increase in cardiac mitochondrial energetics can have profound benefits on cardiac function and is effective in treating mitochondrial cardiomyopathy.

overall_design: Bulk RNA sequencing and single nucleus RNA Sequencing (snRNA-seq) analysis on C57BL/6JEiJ, C57BL/6JEiJ Ant1-/-, and C57BL/6JEiJ Ant1-/- ND6P25L mice (WT, ANT1, ANT1 ND6), pericardially injected with 2.5x10^11 vg AAV2/9Des-Gfp-mAnt1 or 2.5x10^11 vg AAV2/9Des-Gfp . 1, 3, 6, 9, and 12 months post-infection RNA was collected using TRIzol™ Reagent (Invitrogen, 15596026) from heart samples. The RNA was assessed by NanoDrop spectrophotometer (ThermoFisher Scientific) and quantified by Qubit Flex (Thermofisher Scientific) using the Qubit RNA HS Assay Kit (Thermofisher Scientific, Q32855). The RNA was diluted to 1.43 ng/ul and reverse transcribed into cDNA using the Ion Torrent™ NGS Reverse Transcription Kit (Cat. No. A45003). The RNA library was prepared using the Ion Torrent S5 Chef and Ion AmpliSeq Kit for Chef DL8 (Thermofisher Scientific, A29024) and sequenced using the Ion Torrent S5 Sequencer and Ion 540 Kit (Thermofisher Scientific, A30011). For snRNA-seq, isolated nuclei were processed using the Chromium Single Cell 3ʹ Reagent V3.1 kit from 10X Genomics. A total of 8,000 nuclei per sample were loaded into a Chip G. Barcoding, cDNA amplification, and library construction were performed according to the Chromium 3ʹ V3.1 protocol. Sequencing was performed on a DNBSEQ-T7 platform targeting 20,000 reads per nucleus.

first: Alessia

last: Angelin

first: Kierstin

last: Keller

first: Peiran

first: Joeseph

first: Gabrielle

last: Widjaja

first: Rasheed

last: Sule

first: Kevin

last: Janssen

first: Arnold

last: Olali

first: Valeria

last: Carosi

first: Maina

last: Beauplan

first: Deborah

last: Murdock

first: Prasanth

last: Potluri

first: Zimu

last: Cen


title: Human Myelinated Brain Assembloids: A Novel Platform for Investigating Mechanisms and Enhancement of Remyelination

city: Basel

first: Roland

last: Schmucki

address: Grenzacherstrase

institute: F. Hoffmann - La Roche AG

summary: We created a human brain model to study the breakdown and repair of myelin, a process critical in neurological disorders. This system allows for the investigation of myelin dynamics and the testing of potential treatments.

overall_design: Myelinated brain organoids with and without integrated microglia which were either untreated, or demyelinated or remyelination

first: Simona

last: Lange

first: Martin

last: Ebeling

first: Gabin

last: Pierlot

first: Kerstin

last: Oelkers

first: Kim

last: Schneider


title: A targeted vector for brain endothelial cell gene delivery and cerebrovascular malformation modelling II

status: Public on Apr 29 2025

city: Beijing

first: Xing-jun

last: Chen

address: Bldg.3, NO.9, YIKE Rd, Zhongguancun Life Science Park, Changping District

institute: Chinese Institute for Brain Research, Beijing(CIBR)

summary: In-depth analysis of the molecular mechanisms underlying the initiation and development of bAVM was conducted through single-nucleus RNA sequencing of cells from bAVM lesions in Braf-CAfl/fl mice locally injected with AAV-miniBEND.

overall_design: Differential expression analysis and Gene Set Enrichment Analysis of single-nucleus RNA sequencing data. We performed differential expression analysis of RNA seq data and Gene Set Enrichment Analysis obtained from bAVM lesions in Braf-CAfl/fl mice and normal brain region samples from the contralateral hemisphere of the same mice served as a control group.

first: Jun-Liszt

last: Li

first: Zhanying

last: Bi

first: Tianyue

last: Ming

first: Woo-ping

last: Ge