title: Single cell sequencing data on ileum and mesentery tissue from Crohn's disease patients

city: New York

first: Emma

last: Erlich

state: NY

address: 417 E 68th St

institute: Memorial Sloan Kettering

summary: B lymphocytes may facilitate chronic inflammation through antibody production or secretion of cytokines, including lymphotoxin (LT)-a and -b associated with development of lymphoid tissue. Tertiary lymphoid structures (TLS) characterize human and murine ileitis by suppressing outflow from the ileum. Here, we unraveled disparate roles for B cells in chronic ileitis driven by the cytokine TNF. B cell-derived secretory IgA protected against ileal inflammation, whereas B cell-derived LTa guarded against ileitis-associated loss of body mass. This protection was not due to formation of TLS, as we initially hypothesized, because enhanced weight loss did not emerge when TLS were eliminated during ileitis due to B cell-selective deletion of LTb. Instead, weight loss driven by the cachectic cytokine TNF was exacerbated when LTa3, another ligand for TNF receptors, was selectively neutralized. Thus, B cells’ multi-faceted impact on ileitis includes generating secretory IgA, expressing LTa1b2 to drive formation of TLS, and producing LTa3 to protect against weight loss in the presence of TNF.

overall_design: Ileum and the attached mesentery was collected from consenting patients undergoing medically necessary surgical resection of their ileum. We used single cell RNA sequencing to compare the immune cells in paired inflamed ileal-draining mesentery surgical samples and non-inflamed ileal-draining mesentery surgical samples of Crohn's disease patients as well as to the corresponding paired ileum lamina propria regions from those same patients. As a control, ileum and the associated mesentery was also collected from gastrointestinal cancer patients from regions of their small intestine upstream of their disease.

first: Quazim

last: Alayo

first: Ayoung

last: Kim

first: Jichang

last: Han

first: Rachel

middle: L

last: Mintz

first: Christopher

middle: G

last: Huckstep

first: Heather

last: Ruiz

first: Rachael

last: Field

first: Taylor

middle: J

last: Dunning

first: Leila

last: Saleh

first: Mark

last: Hoofnagle

first: Alexei

last: Tumanov

first: Farshid

last: Guilak

first: Jonathan

last: Brestoff

first: Rafael

last: Czepielewski

first: Gwendalyn

last: Randolph


title: Derivation of Embryonic Stem Cells Across Avian Species

status: Public on Jul 31 2025

city: Pasadena

first: Xi

last: Chen

state: California

address: 1200 E. California Blvd

country: USA

institute: California Institute of Technology

type: Expression profiling by high throughput sequencing

summary: Germline-competent embryonic stem cells (ESCs) have been derived from mice and rats, but not from other species. Here, we report the development of conditions for the derivation of ESCs from chickens and several other avian species. Chicken ESCs express core pluripotency markers and can efficiently differentiate into cells of all three germ layers. Furthermore, chicken ESCs can form high rates of chimerism when injected into chicken embryos both ex ovo and in ovo. More importantly, chicken ESCs can give rise to germ cells both in vitro and in ovo, indicating that chicken ESCs are germline competent. Interspecies chimeras can also be generated by injecting other avian ESCs into chicken embryos. Establishment of germline competent avian ESCs opens up a new avenue for producing genetically engineered avian species.

overall_design: We derived novel chicken embryonic stem cell lines using primary cells from EGK.X stage embryos. We then performed gene expression profilling analysis using data obtained from RNA-seq of chicken ES cell lines and primary EGK.X chick embryos for comparison. Each type of sample was prepared in triplicate.

first: Qi-Long

last: Ying


title: A single cell framework identifies functionally and molecularly distinct multipotent progenitors in adult human hematopoiesis

city: Stanford

first: Asiri

last: Ediriwickrema

address: 265 Campus Dr

department: Institute for Stem Cell Biology and Regenerative Medicine

institute: Stanford University

summary: Hematopoietic multipotent progenitors (MPPs) regulate blood cell production to appropriately meet the biological demands of the human body. Human MPPs remain ill-defined whereas mouse MPPs have been well characterized with distinct immunophenotypes and lineage potencies. Using multiomic single cell analyses and complementary functional assays, we identified new human MPPs and oligopotent progenitor populations within Lin-CD34+CD38dim/lo adult bone marrow with distinct biomolecular and functional properties. These populations were prospectively isolated based on expression of CD69, CLL1, and CD2 in addition to classical markers like CD90 and CD45RA. We show that within the canonical Lin-CD34+CD38dim/loCD90-CD45RA- MPP population, there is a CD69+ MPP with long-term engraftment and multilineage differentiation potential, a CLL1+ myeloid-biased MPP, and a CLL1-CD69- erythroid-biased MPP. We also show that the canonical Lin-CD34+CD38dim/loCD90-CD45RA+ LMPP population can be separated into a CD2+ LMPP with lymphoid and myeloid potential, a CD2- LMPP with high lymphoid potential, and a CLL1+ GMP with minimal lymphoid potential. We used these new HSPC profiles to study human and mouse bone marrow cells and observe limited cell type specific homology between humans and mice and cell type specific changes associated with aging. By identifying and functionally characterizing new adult MPP sub-populations, we provide an updated reference and framework for future studies in human hematopoiesis.

overall_design: scRNA-seq and scADT-seq performed on healthy bone marrow. Raw data available through dbGAP.

first: A

first: R

last: Majeti


title: Select chromatin complexes are essential drivers of pathogenic enhancer activity and gene expression in Ewing sarcoma [RNA-seq]

city: Boston

first: Scott

last: Armstrong

state: MA

address: 450 Brookline Ave

department: pediatric oncology

institute: Dana Farber Cancer Institute

summary: Using RNA-seq we assessed the EWS:FLI1 MEDIATED gene expression changes occuring following perturbation of EWS::FLI1, MLL3/4 and p300/CBP.

overall_design: Using previously described EWS::FLI1 degrader cell lines (A673-dHALO and EWS::502 dTAG) we assessed the EWS::FLI1 driven gene expression changes compared to MLL3/4 genetic deletion and p300/CBP perturbation using small molecule inhibitor A485 and degrader dCBP1.

first: Laura

last: Godfrey

first: Charlie

last: Hatton


title: Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells [hTh17_RNAseq]

city: Kyoto

first: Koichi

last: Ikuta

state: Kyoto

address: 53 Shogoin-Kawaharamacho, Sakyo-ku

department: Department of Virus Research

country: Japan

institute: Institute for Frontier Life and Medical Sciences, Kyoto University

summary: Stress elicits inflammatory and autoimmune diseases while concurrently triggering the production of glucocorticoids (GCs), renowned for their anti-inflammatory effects. In addition, IL-17-producing helper T (Th17) cells are pivotal in initiating inflammation and certain autoimmune disorders. However, whether stress-induced GCs exacerbate inflammatory and autoimmune diseases through Th17 cells remains elusive. Here, we show that GCs facilitate the differentiation and survival of Th17 cells in mice. GCs inhibit the expression of TCF1, a negative regulator of Th17 cell differentiation, thereby increasing pathogenic TCF1low Th17 cells characterized by high glycolytic activity. Remarkably, mice lacking the glucocorticoid receptor (GR), specifically in  T cells, manifest less severe experimental autoimmune encephalomyelitis (EAE) and inflammatory colitis. Moreover, stress-induced GCs augment the population of Th17 cells, intensify their IL-17 production, and provoke neutrophil recruitment, resulting in severe inflammation and substantial weight loss in the colitis model. This study demonstrates that stress-induced GCs exacerbate inflammation and autoimmunity by fostering Th17 cell differentiation.

overall_design: Transcriptional profiling of CCR6+ CD4 T cells isolated from human CD4 T cells cultured under Th17-differentiation condition (IL-6+TGFb+IL-23)

first: Akihiro

last: Shimba


title: Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells [mTh17_RNAseq]

overall_design: Transcriptional profiling of IL-17-GFP positive CD4 T cells of small intestine from CD4-Cre GR flox/+ (Control) and CD4-Cre GR flox/flox (GRcKO) mice subjected to stress.


title: Altered translation elongation contributes to key hallmarks of aging in killifish brain

first: Jae Ho

last: Lee

state: CA

address: 318 Campus Drive E200

department: Biology

summary:
Aging is a major risk factor for neurodegeneration and is characterized by diverse cellular and molecular
hallmarks. To understand their origin, we studied the effects of aging on the transcriptome, translatome,
and proteome in the brain of short-lived killifish. We identified a cascade of events in which aberrant
translation pausing led to altered abundance of proteins independently of transcriptional regulation. In
particular, aging caused increased ribosome stalling and widespread depletion of proteins enriched in
basic amino acids. These findings uncover a potential vulnerable point in the aging brain's biology –
the biogenesis of basic DNA- and RNA-binding proteins. This vulnerability may represent a unifying
principle that connects various aging hallmarks, encompassing genome integrity, proteostasis and the
biosynthesis of macromolecules.

overall_design: Comparative analysis of transcriptome (RNA-seq) and translatome (Ribosome profiling) of Nothobranchius furzeri brain and liver from three age groups (5wph, 12wph, and 39wph). tRNA quantification of the brain from two age groups (5wph, 39wph).

first: Domenico

last: Di Fraia

first: Antonio

last: Marino

first: Jae

middle: H

first: Judith

last: Frydman

first: Alessandro

last: Cellerino

last: Ori


title: Neuronal Necroptosis Drives Neuroinflammation and Cognitive Decline Independent of Neuronal Cell Death

status: Public on Jul 30 2025

city: Oklahoma City

first: Willard

last: Freeman

address: 825 NE 13th St

institute: Oklahoma Medical Research Foundation

summary: This study investigates transcriptomic changes in a novel neuron-specific Mlkl knockin (nMlkl-KI) mouse model following tamoxifen-induced MLKL expression in neurons. Mlkl-KI mice were generated on a C57BL/6J background using a transgene construct containing 3xFLAG-tagged Mlkl cDNA inserted into the Rosa26 locus with a loxP-flanked stop cassette. Hemizygous Mlkl-KI females were crossed with homozygous Slick-H-Cre (Thy1-CreERT2-EYFP) males to produce mice expressing MLKL selectively in neurons upon tamoxifen induction. At 45 days of age, mice were treated with tamoxifen (60 mg/kg, intraperitoneally) or corn oil for 5 consecutive days. Brain cortex tissue was collected and RNA was extracted for sequencing. At 12-months of age, nMlkl-KI mice exhibited significant cognitive impairment compared to control mice as measured by a continuous homecage discrimination learning with the Noldus PhenoTyper. Unbiased stereological analysis revealed no loss in neuronal number in the cortex and hippocampus, suggesting neuronal dysfunction rather than neuronal death was responsible for the reduced cognition observed in the nMlkl-KI mice. Transcriptomic analysis of the cortex revealed an upregulation of pathways associated with age-related neurodegenerative diseases  as well as chemokine and TNF signaling in the nMlkl-KI mice.

overall_design: RNA Seq analysis of 12 months cortex from old Control and MLKL over expressed neurons

first: Nidheesh

last: Thadathil

first: Arlan

last: Richardson


title: Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells [ChIP-seq]

type: Genome binding/occupancy profiling by high throughput sequencing

overall_design: Chromatin immunoprecipitation and sequencing (ChIP-seq) in lymph nodes CD4 T cells isolated from WT mice at ZT16 using antibodiy against GR


title: Loss of Elmsan1 in Cardiomyocytes Leads to Age-Dependent Cardiac Dysfunction and Reduced Lifespan

city: Birmingham

first: Yang

last: Zhou

state: AL

address: 1825 University Blvd

department: Department of Biomedical Engineering

institute: University of Alabama at Birmingham

summary: Histone deacetylase (HDAC) complexes regulate pathological gene programs during heart disease progression. The recently identified mitotic deacetylase complex (MiDAC), which includes DNTTIP1, ELMSAN1, and HDAC1/2, remains the least characterized among these complexes. ELMSAN1 has been implicated in left ventricular remodeling, and its global deletion in mice leads to heart malformation. To investigate its role in mouse heart, we generated cardiomyocyte-specific Elmsan1 knockout (ELM cKO) using αMHC driven Cre recombinase. We analyzed both male and female animals across three experimental groups: αMHC-Cre (Cre control), ELM fl/fl (floxed control) and ELM cKO. In male ELM cKO mice, ejection fraction (EF) was significantly reduced by 12 weeks (45.64±3.12%), compared to αMHC-Cre (55.91±1.29%) and ELM fl/fl (59.16±3.70%) controls. By 24 weeks, EF declined further to 20.79%±4.52, representing a reduction of 46.4% (p<0.01) and 62.1% (p<0.0001) compared to αMHC-Cre and ELM fl/fl mice respectively. The heart failure phenotype in ELM cKO mice was supported by cardiomyocyte hypertrophy morphology, ventricular dilation, and shortened lifespan. Female ELM cKO mice exhibited similar defects with delayed onset. To investigate early molecular changes, we performed RNA sequencing on pre-symptomatic hearts from 8-week-old mice. A total of 1055 genes were differentially expressed in ELM ckO hearts, with 460 upregulated and 595 downregulated. Gene enrichment analysis revealed suppression of tricarboxylic acid cycle and key cardiac genes. These transcriptional changes were accompanied by decreased mitochondrial respiratory chain complex proteins, ultrastructural mitochondrial abnormalities, and impaired calcium handling. Our study demonstrates that Elmsan1 is pivotal for maintaining the heart function and hemostasis with advanced age.

overall_design: RNA sequencing (RNA-seq) analysis on hearts collected from 8-week-old ELM fl/fl (n=2), αMHC-Cre (n=2), and ELM cKO (n=4) mice.

first: Meimei

last: Wang


title: Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells [Visium]

city: Mainz

first: Matthias

last: Klein

address: Langenbeckstrasse 1

department: Inst. for Immunology

country: Germany

institute: University Medical Center Mainz

summary: In cancer, metabolic changes and uncontrolled tumor growth alter nutrient availability, impacting antitumor immune responses. Regulatory T (Treg) cells are a subset of T cells with immunosuppressive properties that has been found to additionally possess the ability to control tissue homeostasis and repair. However, it is not known how these functions are molecularly controlled and if they are influenced by tumor metabolism. Here, we report that excessive release of polyamines in the tumor microenvironment directs the functional polarization of Treg cells towards immunosuppression in a protein kinase CK2 (CK2)-dependent manner. Polyamine deprivation as well as genetic or pharmacological inhibition of CK2 activity in Treg cells induced tissue reparative properties in Treg cells that orchestrated efficient antitumor type 2 immune responses, and coordinated tissue repair mechanisms to support tumor eradication. These findings suggest the potential for targeted modulation of Treg cell functions, offering new avenues for cancer therapy.

overall_design: 2x105 B16.F10 cells were inoculated in wild-type mice (WT; Csnk2bfl/fl)  and Foxp3-Cre × CK2b-fl/fl (KO; Csnk2bTreg-/-) mice (8–16 weeks old). B16.F10 tumors of comparable size were isolated on day 15 after inoculation B16.F10 tumors of comparable size were isolated on day 15 after inoculation, fixed in formalin and embedded in paraffin. Tissue sections were analyzed using spatial transcriptomics.

first: Bündgen

last: Georg

first: Bopp

last: Tobias

first: Klein

last: Matthias


title: Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells [scRNA-Seq]

summary: In cancer, metabolic changes and uncontrolled tumor growth alter nutrient availability, impacting antitumor immune responses. Regulatory T (Treg) cells are a subset of T cells with immunosuppressive properties that has been found to additionally possess the ability to control tissue homeostasis and repair. However, it is not known how these functions are molecularly controlled and if they are influenced by tumor metabolism. Here, we report that excessive release of polyamines in the tumor microenvironment directs the functional polarization of Treg cells towards immunosuppression in a protein kinase CK2 (CK2)-dependent manner. Polyamine deprivation as well as genetic or pharmacological inhibition of CK2 activity in Treg cells induced tissue reparative properties in Treg cells that orchestrated efficient antitumor type 2 immune responses, and coordinated tissue repair mechanisms to support tumor eradication. These findings suggest the potential for targeted modulation of Treg cell functions, offering new avenues for cancer therapy. This dataset is intended to investigate the effect of the CK2b-deficiency in Treg cells on the composition of the T cell compartment in B16.F10 melanomas.

overall_design: 2x105 B16.F10 cells were inoculated in wild-type mice (WT; Csnk2bfl/fl)  and Foxp3-Cre × CK2b-fl/fl (KO; Csnk2bTreg-/-) mice (8–16 weeks old). B16.F10 tumors were isolated on day 21 after inoculation.


title: Polyamines regulate adaptive antitumor immunity by functional specialization of regulatory T cells

summary: In cancer, metabolic changes and uncontrolled tumor growth alter nutrient availability, impacting antitumor immune responses. Regulatory T (Treg) cells are a subset of T cells with immunosuppressive properties that has been found to additionally possess the ability to control tissue homeostasis and repair. However, it is not known how these functions are molecularly controlled and if they are influenced by tumor metabolism. Here, we report that excessive release of polyamines in the tumor microenvironment directs the functional polarization of Treg cells towards immunosuppression in a protein kinase CK2 (CK2)-dependent manner. Polyamine deprivation as well as genetic or pharmacological inhibition of CK2 activity in Treg cells induced tissue reparative properties in Treg cells that orchestrated efficient antitumor type 2 immune responses, and coordinated tissue repair mechanisms to support tumor eradication. These findings suggest the potential for targeted modulation of Treg cell functions, offering new avenues for cancer therapy. This dataset is intended to investigate the effect of DFMO on gene expression depending on the presence of CK2β, the beta subunit of protein kinase CK2.

overall_design: Spleens from wild-type mice (WT; Csnk2bfl/fl) (8–12 weeks old) and Foxp3-Cre × CK2b-fl/fl (KO; Csnk2bTreg-/-) mice were mechanically disrupted and filtered through a 40 µm cell strainer to remove debris. Red blood cells were lysed using Gey’s lysis buffer, followed by a second filtration through a 40 µm cell strainer. CD25+ CD4+ Regulatory T cells (Tregs) were isolated using the CD4+ CD25+ Regulatory T Cell Isolation Kit, mouse (Miltenyi Biotec; 130-091-041), according to the manufacturer’s instructions, using magnetic-activated cell sorting (MACS). A total of 2x10e5 isolated Tregs were stimulated in culture medium (Iscove’s Modified Dulbecco’s Medium (IMDM) supplemented with 10% (v/v) fetal calf serum (FCS), 0.1% (v/v) penicillin-streptomycin, 2 mM L-glutamine, 1 mM sodium pyruvate, and 50 µM β-mercaptoethanol). Cells were cultured in the presence of 250 ng/ml recombinant murine IL-2 (mrIL-2), anti-CD3/CD28 T-Cell Expander Beads (Gibco; 11452D) at a 2:1 bead-to-cell ratio, and 1 mM DFMO (difluoromethylornithine; MedChemExpress HY-B0744B). Cultures were maintained for 72 hours at 37 °C with 5% CO₂ in flat-bottom 96-well plates.


title: Genome accessibility profile at single cell level for conventional dendritic cells in human metastatic melanoma samples [snATAC-Seq]

first: Jiekun

last: Yang

address: 32 Vassar Street

institute: MIT

summary: Conventional dendritic cells (cDCs) has been shown to mediate immune checkpoint inhibitor responses in cancer patients. We used single nucleus ATAC sequencing (snATAC-seq) to analyze the epigenome of heterogeneous cDCs obtained from 14 human metastatic melanoma samples.

overall_design: We enzymatically digested and dissociated fresh tumor samples and analyzed using snATAC-seq.

first: Genevieve

middle: M

last: Boland

first: Manolis

last: Kellis


title: Stress-Induced Glucocorticoids Exacerbate Inflammation and Autoimmunity by Promoting the Differentiation and Function of Th17 Cells

first: Koichi

last: Ikuta

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

sample_organism:
Homo sapiens
Mus musculus

platform_organism:
Homo sapiens
Mus musculus

overall_design: Refer to individual Series


title: Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2 [ChIP-seq]

city: Jinan

first: Chunyan

last: Ji

address: Wenhua West Road

country: China

institute: Qilu Hospital

summary: Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma (B-NHL), is characterized by strong aggression, high heterogeneity and poor prognosis. Consequently, there is an urgent need to identify crucial therapeutic targets. Here, we found that the transcription factor Zinc-finger and homeoboxes 2 (ZHX2) is highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cells proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 binds to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activates its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles Zhx2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumor in vivo. In summary, our study indicated that LLPS of ZHX2 protects DLBCL against ferroptosis through induction of SLC3A2, and disturbing it with Zhx2-siRNA@LNP could significantly repress DLBCL, providing a promising therapeutic strategy for DLBCL.

overall_design: ChIP-seq was used to identify the downstream differential molecules that might be regulated between DB-ZHX2 and DB-ZHX2-Mut4

first: Juan

last: Zhang

first: Dongmei

first: Jingjing

last: Ye

first: Fei

last: Lu


title: Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2 [RNA-seq]

overall_design: RNA-seq was performed on SU-DHL-4-CON and SU-DHL-4-KD to identify the pathways that might be enriched


title: Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2

overall_design: RNA-seq was performed on DB-ZHX2 and DB-ZHX2-Mut4 to identify the pathways that might be enriched


title: Bidirectional interplay between SUMOylation and the tumor suppressor p14ARF

city: Santiago de Compostela

first: Carmen

last: Rivas

address: Avda Barcelona

department: CIMUS

country: Spain

institute: Universidad de Santiago de Compostela

summary: Tumor suppressor p14ARF is a lysine-less protein that suppresses tumorigenesis through different mechanisms, including enhancing the SUMOylation of its interactors. Although p14ARF is known to interact with the SUMO conjugating enzyme UBC9, the link between ARF and SUMOylation is poorly understood and the potential impact of SUMOylation on p14ARF is unknown. Herein, we show that p14ARF is modified by SUMO2 in vitro, both in transfected cells and under endogenous conditions. SUMO conjugates to the N-terminal part of the tumor suppressor protein increasing its stability. Degradation of p14ARF protein is induced by UBC9 downmodulation or the inhibition of SUMOylation, and is rescued by the NEDDylation inhibitor MLN4924. Treatment with MLN4924 also promotes p14ARF SUMOylation and the transcriptional transactivation of the SUMOylation machinery components SUMO1, SUMO2 and UBC9. This causes a global increase in SUMOylation that contributesto the upregulation of p14ARF levels. Importantly, p14ARF is required for the global increase in SUMOylation induced by MLN4924, and it plays an important role in the cytotoxic effect of the NEDDylation inhibitor on prostate cancer cells. Our results provide evidence that lysine-independent SUMOylation of p14ARF is a new post-translational mechanism regulating p14ARF stability and establishes a new link between inhibition of NEDDylation and SUMOylation.

overall_design: Our goal was to identify the genes involved in the response of PC3 cells to MLN4924, specifically those that depend on the expression of p14ARF. To achieve this, we generated PC3 cells with a knockout of the p14ARF gene (PC3-Sh-P14ARF KO). We then treated both the control PC3 cells and the P14 KO cells with either 1 mM MLN4924 or a vehicle for 3 days. Finally we compared the gene expression from RNA-seq data for PC3 cells and its derivatives (P14ARF-KO and/or MLN4924-treated).

first: Ahmed

middle: E

last: Motiam

first: Yanis

last: Bouzaher

first: Haifen

last: Chen

first: Rocío

last: Seoane

first: Santiago

last: Vidal

first: María

last: Blanquer

last: Tolosa

first: Anxo

first: Ignacio

last: Palmero

first: Manuel

middle: S

last: Rodríguez

first: James

middle: D

last: Sutherland

first: Rosa

last: Barrio

first: Dimitris

last: Xirodimas

last: Collado

first: Rod

last: Bremner


title: Pathogenic variants in TMEM184B cause a neurodevelopmental syndrome associated with alteration of metabolic signaling

city: Tucson

first: Martha

last: Bhattacharya

state: AZ

address: 1040 E 4th Street

department: Neuroscience

institute: University of Arizona

summary: Transmembrane protein 184B (TMEM184B) is an endosomal 7-pass transmembrane protein with evolutionarily conserved roles in synaptic structure and axon degeneration. We report six pediatric cases who have de novo heterozygous variants in TMEM184B. All individuals harbor rare missense or mRNA splicing changes and have neurodevelopmental deficits including developmental delay, corpus callosum hypoplasia, seizures, and/or microcephaly. TMEM184B is predicted to contain a pore domain, wherein many human disease-associated variants cluster. Structural modeling suggests that all missense variants alter TMEM184B protein stability. To understand the contribution of TMEM184B to neural development in vivo, we suppressed the TMEM184B ortholog in zebrafish and observed microcephaly and reduced anterior commissural neurons, aligning with symptoms of affected individuals. Ectopic TMEM184B expression resulted in dominant effects for Lys184Glu and Gly162Arg. However, in vivo complementation studies demonstrate that all other variants tested result in diminished protein function and indicate a haploinsufficiency basis for disease. Human induced pluripotent stem cells (iPSC) with monoallelic expression of Lys184Glu show mRNA disruptions in key metabolic pathways and molecules including those controlling mechanistic target of rapamycin (mTOR) activity. Expression of Lys184Glu and other variants increased apoptosis in cell lines and altered nuclear localization of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, further supporting disruptions to nutrient signaling pathways. Together, our data indicate that TMEM184B variants cause cellular metabolic disruption likely through divergent molecular effects that all result in abnormal neural development.

overall_design: RNAseq profiling of induced pluripotent stem cells (iPSCs) to determine mRNA levels of TMEM184b and expression of transcripts related to metabolism and cellular pH. The assessed cell lines belonged to one of three conditions, each containing four biological replicates: wild type (WT), Lys184Glu/+, or Lys184Glu/Lys184Glu. Non-WT samples exhibited either a heterozygous or homozygous mutation to TMEM184b that mimic mutations observed in human patients.

first: Kimberly

middle: A

last: Chapman

first: Farid

last: Ullah

first: Zachary

last: Yahiku

first: Sri Varsha

last: Kodiparthi

first: Georgios

last: Kellaris

first: Hazel

last: White

first: Andrew

middle: T

last: Powell

first: Sandrina

middle: P

last: Correia

first: Tommy

last: Stödberg

first: Christalena

last: Sofokleous

first: Nikolaos

last: Marinakis

first: Helena

last: Fryssira

first: Eirini

last: Tsoutsou

first: Jan

last: Traeger-Synodinos

first: Andrea

last: Accogli

first: Vittorio

last: Sciruicchio

first: Vincenzo

last: Salpietro

first: Pasquale

last: Striano

first: Candace

last: Muss

first: Boris

last: Keren

first: Delphine

last: Heron

first: Seth

middle: I

last: Berger

first: Kelvin

middle: W

last: Pond

first: Suman

last: Sirimulla

first: Erica

last: Davis

middle: R


title: SnoBIRD: A tool to identify C/D box snoRNAs and refine their annotation across all eukaryotes

city: Sherbrooke

first: Michelle

last: Scott

state: QC

address: 3201 Jean-Mignault

country: Canada

institute: Université de Sherbrooke

summary: Small nucleolar RNAs (snoRNAs), a group of noncoding RNAs present amongst all eukaryotes, are known for their regulation of ribosome biogenesis and splicing. Despite their central cellular roles, current snoRNA annotations remain incomplete. Indeed, several eukaryote annotations contain few or no snoRNAs, and none distinguishes expressed snoRNAs from their pseudogenes—a recently characterized snoRNA subclass with distinct features and expression levels. To address this, we developed SnoBIRD, a BERT-based C/D box snoRNA predictor trained on snoRNAs spanning all eukaryote kingdoms. We show that SnoBIRD outperforms existing tools in a test set environment and is the only predictor capable of identifying snoRNA pseudogenes using biologically relevant signal. Applied on the fission yeast and human genomes, we demonstrate that only SnoBIRD scales well with genome size in terms of runtime, and we identify and experimentally validate several new SnoBIRD-predicted C/D box snoRNAs. By running SnoBIRD on multiple eukaryote genomes, we identify hundreds of novel C/D box snoRNA candidates and highlight SnoBIRD’s usefulness to determine the evolutionary paths of snoRNAs that share a common host locus but are distributed across different species. Overall, SnoBIRD represents a user‑friendly and efficient tool for reliably predicting C/D box snoRNAs and their pseudogenes across any eukaryote kingdom.

sample_organism:
Schizosaccharomyces pombe
Saccharomyces cerevisiae
Gallus gallus
Macaca mulatta
Mus musculus

overall_design: TGIRT-Seq performed on ribodepleted samples from three wild-type (WT) S. cerevisiae replicates and three mouse brain samples, as well as TGIRT-Seq performed on size-selected RNAs (<300 nt) in two G. gallus universal reference samples, two M. mulatta universal reference samples and 3 size-selected (<150 nt) WT S. pombe replicates.

first: Étienne

last: Fafard-Couture

first: Cédric

last: Boulanger

first: Laurence

last: Faucher-Giguère

first: Vanessa

last: Sinagoga

first: Mélodie

last: Berthoumieux

first: Jordan

last: Hedjam

first: Virginie

last: Marcel

first: Sébastien

last: Durand

first: Mark

last: Bayfield

first: François

last: Bachand

first: Sherif

last: Abou Elela

first: Pierre-Étienne

last: Jacques


title: Genetic background and oncogenic driver determines the genomic evolution and transcriptomics of mammary tumor metastasis

city: Bethesda

first: Kent

last: Hunter

state: MD

address: 37/4048 37 Convent Drive

department: Center for Cancer Research

institute: National Cancer Institute

summary: Total RNA was isolated from matched primary mammary tumors and lung metastases from MMTV-Myc, MMTV-Her2 and C3TAg mouse models on homozygous FVB backgrounds.  Primary tumors and lung metastases were also isolated from MMTV-PyMT on (AKR/J x FVB/NJ0, (BALB/cJ x FVB/NJ) and (SEA/GnJ x FVB/NJ)F1 animals.  RNA-sequencing was performed to examine the expression differences of the primary tumors and lung metastases.

overall_design: Rna-seq analysis of paired primary and metastatic tumors from mouse genetically engineered models of breast cancer

first: Christina

last: Ross


title: Toxoplasma gondii infection and chronic IL-1 elevation drive hippocampal DNA double-strand break signaling, leading to cognitive deficits

city: Toulouse Cedex 3

first: Nicolas

last: Blanchard

address: CHU Purpan BP3028

department: Inserm UMR1291

country: France

institute: Toulouse Institute for Infectious and Inflammatory Diseases (Infinity)

summary: Chronic inflammation, resulting from infections, is characterized by increased levels of cytokines including interleukin-1 (IL-1), but little is known about how IL-1 contributes to cognitive impairment, potentially via epigenetic processes. Here we demonstrate that mice chronically infected with the parasite Toxoplasma gondii exhibit impaired spatial memory, which is dependent on neuronal IL-1 signaling and mimicked by chronic exposure to IL-1beta. Both T. gondii infection and chronic IL-1beta drive H2A.X-dependent DNA double-strand break signaling in hippocampal neurons and invalidating neuronal H2A.X-dependent signaling blocks memory impairments caused by either exposure. Our results highlight the instrumental role of cytokine-induced double-strand-break-dependent signaling in spatial memory defects, which may be relevant to multiple brain diseases.

overall_design: H2axfl/flCre- (neuronWT) or H2axfl/flCre+ (neuronKO) were implanted with osmotic minipumps containing saline or IL-1beta solutions for 35 days.  Hippocampi were microdissected and pooled from 2 mice of the same condition.  Neuronal nuclei from pooled hippocampi were isolated by FANS as described in Fernandez-Albert et al. (PMID 31501571).  After sorting, neuronal nuclei were centrifuged at 1000 g for 7 min at 4°C and pellet was resuspended in RLT buffer (Qiagen) supplemented with 1% (vol/vol) β-mercaptoethanol (final concentration 143mM, Sigma). Samples were homogenized through QiaShredder columns (Qiagen) and stored at -80°C until processing. Bulk nuclear RNA extraction was performed using RNeasy Micro Kit (Qiagen) following manufacturer’s instructions.

first: Marcy

last: Belloy

first: Amel

last: Aïda

first: Adeline

last: Chaubet

first: Margot

last: Zahm


overall_design: Commercial C57BL/6 male mice were acclimated for one week in the experimental BSL2 facility, prior to intraperitoneal (i.p.) injection with 200 Pru-derived tachyzoites (Pru.SAG1-OVA leading to encephalitis, or Pru.GRA6-OVAleading to latency) in 200 µL of PBS, or with 200 µL of PBS only for the uninfected group.


title: Single nucleus RNA sequencing of the cerebral cortex from genetically diverse inbred mouse strains reveals differences in pericyte and endothelial cell composition

city: Chapel Hill

last: Zylka

state: North Carolina

address: 116 Manning Drive, CB 7250, Unive7008B Mary Ellen Jones Building

institute: University of North Carolina at Chapel Hill

summary: Genetic background influences animal behavior and susceptibility to brain diseases. To evaluate how genetic background influences the relative number and/or types of cells in the brain, we performed single nucleus RNA sequencing on 14 genetically distinct collaborative cross (CC) inbred mouse strains. These data comprise over 287,000 nuclei derived from 92 samples across each of the strains. We identified 11 principal cell types and 59 refined cell types in each of the strains.

overall_design: We isolated nuclei from the right cortical hemisphere from 92 animals of 14 different CC inbred mouse strains. We performed Split Pool Ligation-based Transcriptome sequencing (SPLiT-seq) using these samples. After processing the data, we had over 287,000 nuclei derived from 92 samples acorss each of the strains.

first: Jieun

last: Park

first: James

last: Krantz


title: Gene expression profiling of Treg subsets based on ILT3 expression

first: Matthias

last: Klein

summary: Comparison of gene expression ex vivo isolated ILT3+ respectively ILT3- Treg cells

overall_design: 10-16-week-old syngeneic male and female mice were euthanized via CO2 inhalation. Spleens and mesenteric lymph nodes were mechanically disrupted and filtered through a 40 µm cell strainer to remove cell debris. Erythrocytes of spleen suspension were removed through the use of Gey’s lysis buffer and filtered again through a 40µM cell strainer. Live cells were counted microscopically by exclusion of dead cells with trypan blue staining. CD25+ CD4+ T cells were pre-enriched via magentic columns. ILT3+ respectively ILT3- CD4+ CD25+ T cells were sorted with a FACSAria III (BD Biosciences).

first: G

last: Bündgen

first: T

last: Bopp

first: M


title: Regnase-1 contributes to the cancer stem-like phenotype and post-tumorigenic growth in non-small cell lung cancer

city: Sendai

first: Hozumi

last: Motohashi

address: 2-1 Seiryo-machi, Aoba-ku

department: Medical Biochemistry

institute: Tohoku University

summary: To examine the function of Regnase-1 in non-small cell lung cancer, we compared mRNA expression between WT and ZC3H12A knockout cells using two different non-small cell lung cancer cell lines.

overall_design: ZC3H12A knockout cells were constructed in A549 and H2023 cells. Cells were grown in normal culture condition for 3days (Parent) or stem cell enriched culture condtion for 7days (Oncosphere), and then cells were harvested for RNA purification.

first: Keito

last: Okazaki

first: Haruna

last: Takeda


title: Diet-Induced Obesity Disrupts Sexually Dimorphic Gene Expression in Liver and Adipose Tissue in Mice

city: Barcelona

first: Vicent

last: Ribas

state: Choose a State or Province

address: Rosselló 149, 5th floor, Centre Esther Koplowitz

department: Pathogenesis and prevention of diabetes

institute: IDIBAPS

summary: Biological sex impacts on the prevalence, incidence, and severity of metabolic disorders associated to obesity, particularly type 2 diabetes. To elucidate the influence of sex on metabolic diseases during obesity progression, we conducted a comprehensive metabolic and transcriptomic analysis aiming to unravel the dynamics of metabolic adaptations to an obesogenic diet in both female and male mice.Males fed high-fat diet (HFD) displayed a progressive increase in glucose intolerance, fasting hyperglycemia, hyperinsulinemia, and impaired glucose-dependent insulin secretion, concomitant with increased adiposity and liver steatosis. Interestingly, females displayed a comparable increase in relative adiposity, but exhibited milder glucose intolerance, hyperglycemia, and lower insulin levels, which remained responsive to glucose even at advanced stages.These phenotypic disparities were mirrored by divergent gene expression profiles in liver and visceral white adipose tissue in males and females in response to HFD. Notably, variations in the regulation of diverse pathways and gene categories were observed between sexes in response to HFD, including differential regulation of genes within the same categories. Intriguingly, genes exhibiting sex dimorphism under regular dietary conditions were proportionally highly regulated in response to HFD. Indeed, a substantial part of the liver genes with sex dimorphism in regular diet lost their sex bias in animals in HFD, and this effect was even more pronounced in white adipose tissue, uncovering a substantial loss of sex dimorphism in the gene profile in liver and visceral white adipose tissue in response to HFD. These results indicate that there are different gene sets regulated in a sex-specific manner in response to metabolic perturbations, and metabolic disturbances are associated with a loss of sexually dimorphic gene expression in liver and adipose tissue in mice. These findings suggest that the sex bias gene expression profile is pivotal for maintaining metabolic homeostasis in both sexes, which may have broad implications in metabolic disturbances. Moreover, these sex-specific divergences highlight the importance of considering sex as a crucial factor when interpreting data related to metabolic disturbances.

overall_design: C57BL6/J male and female mice were obtained from Charles River Laboratories. At 8 weeks of age, mice were kept on regular diet (RD, control groups) (standard rodent chow, Teklad #2014) or fed with high-fat diet (HFD, 45% calories from fat, Research diets Inc. #D12451) for the periods indicated. 2 cohorts of animals (with male and female subgroups within) were fed for 2 or 12 (RD or HFD), and sacrificed for analysis at these time points. RNA from liver and visceral WAT from animals at early (2 weeks) or advanced HFD feeding (12) were used for RNA-seq transcriptomic analysis.

first: Joan-Marc

last: Servitja


title: Expression profiling of tumor-infiltrating CD4+ FOXP3- conventional T cells from tumors of wildtype and Foxp3-Cre x CK2b-fl/fl mice

summary: Analysis of tumor-infiltrating CD4+ FOXP3- conventional T cells from tumors of Rosa26-RFP x Csnk2bfl/fl mice (wildtype) and Rosa26-RFP x Csnk2bfl/fl x Foxp3-Cre mice.

overall_design: B16.F10 melanoma cells (2x10e5 in 100 µl PBS) were injected subcutaneously (s.c.) into the right flank of 10-16-week-old syngeneic male and female Rosa26-RFP x Csnk2bfl/fl and Rosa26-RFP x Csnk2bfl/fl x Foxp3-Cre mice. 21 days post-injection the mice were euthanized via CO2 inhalation. By using a scalpel, the tumors were carefully separated from the inside of the skin. Excised tumors were cut into small pieces (2-4mm), transferred into gentleMACS™ C tubes (Miltenyi Biotec; 130-093-237) and digested with the Tumor Dissocation Kit, mouse (Miltenyi Biotec; 130-096-730) according to the manufacturer's instructions using the gentleMACS™ Octo Dissociator with Heaters (Miltenyi Biotec; 130-096-427). For subsequent cell sorting, the cell suspensions were strained two subsequent times using a 70 µm and then a 40 µm cell strainer and resuspended in FACS buffer (PBS + 0.5% BSA + 0.01% sodium azide + 5 mM EDTA). Tumor-infiltrating CD4+ Tconv (TCRb+ CD4+ RFP-) cells were sorted with a FACSAria III (BD Biosciences).


title: scRNA sequencing analysis of neutrophils and sphingolipid pathway during virus persistence

status: Public on Jul 29 2025

city: Columbia

first: Bumsuk

last: Hahm

state: MO

address: NW301C Medical Sciences Building

department: Surgery-Research

institute: University of Missouri

summary: During lymphocytic choriomeningitis virus (LCMV) persistence, neutrophils were shown to be regulated, but the underlying mechanisms remain unclear. In this study, we have employed a scRNA analysis using bone marrow cells during LCMV infection. The experiment was conducted to define the possible role of sphingosine kinase 2 (SphK2) in neutrophil regulation upon LCMV infection. The findings may increase our understanding of viral mechanisms to regulate the host immunity and virus persistence.

overall_design: WT and Sphk2-/- knockout C57BL/6 mice (n=3 mice/group) were infected with LCMV Cl 13. Bone marrows cells were collected from uninfected WT and LCMV Cl 13-infected WT and Sphk2–/– mice at 3 dpi and analyzed using scRNA-seq.

first: Vijayamahantesh

last: Vijayamahantesh

first: Ying

last: He

first: Lei

last: Jiang

first: Hailey

last: Huerter

first: Kwang

last: Jung

first: Savannah

last: McKenna

first: Caleb

last: Studstill

first: Dong

last: Xu


title: Spatial transcriptomic data of salivary gland tumors in AFAP family

city: Montreal

first: Fiona

last: Chan Pak Choon

address: 3755 Côte-Sainte-Catherine

department: Human Genetics

institute: McGill University

summary: Intercalated duct hyperplasia, basal cell adenoma and basal cell adenocarcinomas of the proband were analyzed by spatial transcriptomics and demonstrated a stepwise increase in WNT activation from benign to malignant lesions

overall_design: Formalin-fixed, paraffin-embedded (FFPE) tissue samples from the proband's multiple salivary gland lesions were analyzed. These included intercalated duct hyperplasia, basal cell adenoma, and basal cell adenocarcinoma involving both the parotid and submandibular glands.

last: Chan-Pak-Choon

first: Catherine

last: Beaumont

first: José

last: Camacho Valenzuela

first: Josianne

last: Leblanc

first: Sonja

last: Dahlum

first: Reiner

last: Siebert

first: François

last: Thuot

first: Marc

last: Pusztaszeri

first: Jacinthe

last: Chênevert

first: Paz

last: Polak

first: Tania

last: Cruz Marino

first: Barbara

last: Rivera

first: William

last: Foulkes


title: Chemogenetic tuning reveals optimal MAPK signaling for cell-fate programming

city: Cambridge

first: Brittany

last: Lende-Dorn

address: 25 Ames St

department: Chemical Engineering

institute: Massachusetts Institute of Technology

summary: Cell states evolve through the combined activity of signaling pathways and gene regulatory networks. While transcription factors can direct cell fate, these factors rely on a cell state that is receptive to transitions in cell identity. How signaling levels contribute to the emergence of receptive cell states remains poorly defined in primary cells. Using a well-defined model of direct conversion, we examined how levels of the MAPK-activating oncogene HRASG12V influence direct conversion of primary fibroblasts to induced motor neurons. We demonstrate that an optimal ‘Goldilocks’ level of MAPK signaling efficiently drives cell-fate programming. Rates of direct conversion respond biphasically to increasing HRASG12V levels. While intermediate HRASG12V levels increase the rate of conversion, high levels of HRASG12V induce senescence. Through chemogenetic tuning, we set optimal MAPK activity for high rates of conversion in the absence of HRAS mutants. In addition to proliferation, MAPK signaling influences conversion by regulating Ngn2 activity, offering two distinct mechanisms of MAPK-mediated control in direct conversion. As MAPK pathways influence cell-fate transitions in development and disease, our results highlight the need to tune therapeutic interventions within a non-monotonic landscape that is shaped by genetics and levels of gene expression.

overall_design: Transcriptional profiling of cells during the process of direct conversion of primary mouse embryonic fibroblasts (MEFs) to induced motor neurons (iMNs). MEFs were infected with NIL, NIL + SDD, NIL + SDDIR, NIL + RISDD (NIL is Ngn2-2A-Isl1-2A-Lhx3; SDD is SNAP-p53DD, SDDIR is SDD-IRES-HRAS(G12V); RISDD is HRAS(G12V)-IRES-SDD). Samples were collected at 4 days post infection (dpi) were sorted by fluorescence-activated cell sorting (FACS) for live, single cells for conditions with only NIL, and on SNAP+ for cells expressing SDD.

first: Kate

last: Galloway


title: Ectopic expression of BEX genes in T-cell Acute Lymphoblastic Leukemia [RNA-Seq]

city: Marseille

first: Delphine

last: Potier

address: 27 boulevard Lei Roure

institute: CRCM

summary: T-cell acute lymphoblastic leukemia (T-ALL) is a malignant proliferation of T-cell progenitors originating in the thymus. T-ALL is a heterogenous disease involving the dysregulation of various oncogenes/tumour suppressor (TS) genes. Loss of the TS gene PTEN, is a recurrent alteration, which is often associated to mature T-ALL sub-group expressing a T-cell receptor (TCR). Herein, we used single-cell RNA sequencing approach to investigate the impact of the absence of PTEN on pathological development of mouse thymocytes. First, our differential gene expression analysis of tumour cells versus physiologic cells uncovers an ectopic expression, in leukemic cells, of the gene encoding Bex1. Then, to determine the relevance of our observation in Human, we queried public RNAseq database from the TARGET-TCGA project. We show that BEX1, BEX2 and BEX5 genes are ectopically expressed in T-ALL samples and we further found that ectopic BEX expression is mainly restricted to the T-ALL subgroup over-expressing TAL1 oncogene. Proximity ligation assays demonstrated the nuclear colocalization of BEX1/2 proteins with TAL1 in T-ALL cells. To investigate their functional role, we generated Jurkat cells with a triple knockout of BEX1, BEX2, and BEX5 using CRISPR-Cas9. This genetic inactivation led to reduced cell proliferation, a loss of H3K4me1 marks notably at genomic regions enriched for E-box motifs, and dysregulation of several TAL1 target genes. Collectively, our findings suggest that BEX1 and BEX2 may contribute to human T-ALL oncogenesis by acting as cofactors within the TAL1 complex.

overall_design: Bulk Rna-seq on Jurkat cells and edited Jurkat cells (triple KO of BEX1, BEX2 and BEX5).

first: Julie

last: Quessada

first: Mathis

last: Nozais

first: Clemence

last: Grosjean

first: Charlotte

last: Savey

first: Saran

last: Pankaew

first: Sara

last: Allelova

first: Marie

last: Loosveld

first: Dominique

last: Payet-Bornet


title: Ectopic expression of BEX genes in T-cell Acute Lymphoblastic Leukemia [CUT&Tag]

overall_design: CUT&Tag on Jurkat cells and edited Jurkat cells (triple KO of BEX1, BEX2 and BEX5).


title: Exploiting collateral sensitivity in the evolution of resistance to tyrosine kinase inhibitors in soft tissue sarcomas.

city: Sutton

first: Paul

last: Huang

address: 15 Cotswold Road

country: United Kingdom

institute: The Institute of Cancer Research

summary: Broad-spectrum multi-target tyrosine kinase inhibitors (mTKIs) are clinically approved for the treatment of soft tissue sarcomas (STS). However, acquired resistance inevitably arises in the  majority of STS patients. There is therefore an urgent need to identify new strategies to overcome resistance and achieve durable treatment responses. Here we show that STS cells that acquire resistance to clinically relevant mTKIs are cross-resistant to one another and sequential treatment does not delay the acquisition of drug resistance. Instead, we find that en route to acquiring drug resistance, STS cells develop collateral sensitivities to alternative drugs. We demonstrate that the mTKI sitravatinib rapidly induces collateral sensitivity to the FGFR inhibitor infigratinib which can be exploited for adaptive therapy to suppress STS cell growth. This study provides proof-of-principle that collateral sensitivity may be an effective strategy for overcoming resistance to mTKIs and this novel approach should be explored in the design of future trials.

overall_design: RNAseq profiling of A204 and G402 parental cell lines and sub-lines with acquired resistance to pazopanib, regorafenib, sitravatinib and anlotinib. Samples were collected without the presence of drug, 96 hours after seeding.

first: Mark

last: Elms

first: Andrew

last: Jenks

first: Avirup

last: Chowdhury

first: Lukas

last: Krasny

first: Madhumeeta

last: Chadha

first: Kaan

last: Low

first: Peter

last: Harrison

last: Kerrinson

first: Robin

last: Jones


title: Injection of Vocal Fold Lamina Propria-Derived Hydrogels Modulates Fibrosis in Injured Vocal Folds

city: Raleigh

first: Xinxia

last: Peng

address: 1060 William Moore Drive

institute: North Carolina State University

summary: Vocal fold (VF) fibrosis, often caused by phonosurgery, radiation, or trauma, leads to irreversible voice dysfunction due to excessive ECM deposition and increased tissue stiffness. VF fibrosis, a significant cause of chronic dysphonia, lacks FDA-approved treatments, highlighting the critical need for novel antifibrotic therapeutic. TGF-β1 is a major driver in the pathological transformation of fibroblasts into contractile myofibroblasts in VF fibrosis via SMAD3, YAP1, and integrin signaling pathways. These pathways lead to increased ACTA2 expression, excessive collagen production, and progressive tissue stiffening. Leveraging the principle that local cells respond to tissue-specific signals, our ECM hydrogel derived from decellularized vocal fold lamina propria (VFLP-ECM) reduced ACTA2 expression in TGF-β1 stimulated vocal fold fibroblasts, showcasing antifibrotic potential. In this study, we evaluated the therapeutic potential of VFLP-ECM hydrogel in a rabbit VF injury model—treatment involved VFLP-ECM or bovine type I collagen injections into VFs 7 days after injury, with evaluations at 28 days post-injury. We compared two VFLP-ECM formulations: a manual process (VFLP (man)) and an accelerated automated method (VFLP (au)). VFLP (man) showed more modulated fibrosis-associated gene expressions when compared to VFLP (au) and collagen. Proteomic analysis revealed that VFLP (man) preserves a broader array of bioactive proteins, such as vitronectin, crucial in TGF-β1 signaling and ECM remodeling. The transcriptomic analysis uncovered a downregulation of key fibrotic markers and potential inhibition of regulators such as SMAD3, YAP1, and MRTFA, alongside the upregulation of SMAD7, an inhibitor of TGF-β signaling. Notably, treatment with VFLP (man) resulted in vocal folds with similar stiffness as uninjured controls, whereas tissues treated with collagen or VFLP (au) remained stiffer, indicating incomplete mechanical recovery. These data provide the first in vivo evidence that VFLP-ECM hydrogel—mainly when produced via manual decellularization—attenuates fibrosis by disrupting biochemical and biomechanical drivers of myofibroblast activation.

overall_design: RNA-seq profiling of vocal fold tissue from New Zeland white rabbits. Rabbits were randomly assigned to five experimental groups. Four groups of animals had induced vocal fold injury with the following treatments: 1) collagen type 1 (‘Col1’); 2) VFLP (man), 3) VFLP (au), and 4) no treatments (‘Injury only’). An additional group was used as a “no injury, no injection” control. For each animal, paired samples were collected from both left and right vocal folds.

first: Camilo

last: Mora

first: Ethan

last: Smith

first: Ziyu

last: Wang

first: Maria

last: Ramos-Alamo

first: Leonard

last: Collins

first: Nour

last: Awad

first: Denzel

last: Cruz

first: Tammy

last: Tollison

first: Ian

last: Huntress

first: Gary

last: Gartling

first: Ryosuke

last: Nakamura

first: Greg

last: Dion

first: Ryan

middle: C

last: Branski

first: Donald

middle: O

last: Freytes


title: Pathogenic variants in the splicing factor SF1 lead to a new neurodevelopmental disorder.

city: Paris

first: Pierre

last: de la Grange

address: 29, rue du Faubourg Saint-Jacques

department: Paris Biotech Santé

institute: GenoSplice technology

summary: Alternative splicing is highly prevalent in the brain, orchestrating key processes like neurogenesis and synaptogenesis, which are critical for generating the nervous system's complexity and plasticity. Dysregulation of splicing mechanisms has been increasingly implicated in neurodevelopmental disorders. Splicing factor 1 (SF1) is integral to pre-mRNA processing, facilitating early spliceosome assembly at the 3′ splice site and contributing to the regulation of alternative splicing. Here, we report a newly identified neurodevelopmental disorder associated with de novo heterozygous variants in SF1, characterized by intellectual disability, dysmorphic features, and structural brain anomalies in 15 affected individuals. Functional studies in neural progenitor cells demonstrate that SF1 inhibition alters alternative splicing programs, with pronounced effects on genes involved in neuronal differentiation, synaptic transmission, and axonal guidance, processes fundamental to brain development. These findings establish SF1-related dysfunction as a novel spliceosomopathy and highlight its critical importance in neurodevelopment and human disease.

overall_design: High-depth RNAseq capturing splicing events in Neural Progenitor Cells (NPCs) transfected with siSF1 or siCTRL, originating from two iPSC backgrounds (WTSli21-B (NPC 1) and WTSli008-A (NPC 2)).

first: Johnny

last: Bou-Rouphael

first: Auriane

last: Cospain

first: Laila

last: El-Khattabi

first: Cyril

last: Mignot


title: Accelerated Midlife Endocrine and Bioenergetic Brain Aging in APOE4 Female Mice

city: TUCSON

first: Roberta

last: Brinton

state: Arizona

address: 1230 N Cherry Ave, PO Box 210242

department: The Center for Innovation in Brain Science

summary: Age, female sex and APOE4 genotype are top Alzheimer’s risk factors. Using a translational perimenopause mouse model based on STRAW criteria, we investigated APOE genotype impact on female midlife endocrine aging.

overall_design: Hippocampal gene expression data of APOE3 and APOE4 female mice across different chronological and endocrinological aging groups.

first: Tian

last: Wang

first: Zisu

last: Mao

first: Yuan

last: Shang

first: Jean-Paul

last: Wiegand

last: D. Brinton


title: Repetitive head impacts induce neuroinflammation and neuronal loss in young athletes

city: Boston

first: Single Cell

last: Sequencing Core

address: 72 E. Concord St

institute: BU Single Cell Sequencing Core

summary: Repetitive head impacts (RHI) sustained from contact sports are the largest risk factor for chronic traumatic encephalopathy (CTE). Currently, CTE can only be diagnosed after death and the multicellular cascade of events that trigger initial p-tau deposition remain unclear. Further, the symptoms endorsed by young individuals with early disease are not fully explained by the extent of p-tau deposition, severely hampering development of therapeutic interventions. Here, we show that RHI exposure associates with a multicellular response in young individuals (<51 years old) prior to the onset of CTE p-tau pathology that correlates with number of years of RHI exposure. Leveraging single nucleus RNA sequencing of tissue from 8 control, 9 RHI-exposed, and 11 early CTE individuals, we identify SPP1+ inflammatory microglia, angiogenic and inflamed endothelial cell profiles, reactive astrocytes, and altered synaptic gene expression in excitatory and inhibitory neurons. Surprisingly, we observe a significant loss of cortical sulcus layer 2/3 neurons in contact sport athletes compared to controls independent of p-tau pathology. These results provide robust evidence that multiple years of RHI exposure is sufficient to induce lasting cellular alterations that may underlie p-tau deposition and help explain the early clinical symptoms observed in young former contact sport athletes. Furthermore, these data identify specific cellular responses to repetitive head impacts that may direct future identification of diagnostic and therapeutic strategies for CTE.

overall_design: To investigate the early effects of RHI on the human brain, dorsolateral frontal cortex of young individuals were sampled across control individuals, individuals with RHI exposure and no CTE and with a CTE diagnosis and compared.

first: Morgane

last: Butler

first: Nida

last: Pervaiz

first: Jonathan

last: Cherry


title: Transgene-free generation of mouse post-gastrulation whole embryo models solely from naive ESCs and iPSCs

city: Rehovot

first: Noa

last: Novershtern

address: Weizmann Institute

department: Molecular Genetics

country: Israel

institute: Weizmann Institute of Science

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

overall_design: Refer to individual Series

first: Alperen

last: Yilmaz

first: Gulben

last: Gurhan

first: Alejandro

last: Aguilera-Castrejon

first: Bernardo

last: Oldak

first: Jacob

last: Hanna


title: Effect of USP10 knockout using CRISPR on gene expression in MCF7 breast cancer cells

status: Public on Jul 28 2025

city: Perth

first: Pieter

last: Eichhorn

state: WA

address: Kent Street

department: Medical School

country: Australia

institute: Curtin University

summary: Using a genome wide shRNa screen we identified the deubiqutinating enzyme USP10 as a potent regualtor of AKT activity. To validate our findings we performed RNA-Seq on MCF7 cells with or without USP10 depletion. In line with our previous observations we demonstrate that PI3k-AKT-mTOR pathway activation is downregualted in our USP10 knockout cells. Our later work shows that this function is mediated through a USP10-GSK3B mediated mechanism resulting in PTEN inactivation. Taken together this work demonstrates the imprtance of USP10 in PI3K pathway regualtion.

overall_design: RNA-Seq profiling of wildtype MCF7 cells and their USP10 knockout counterparts. Cells were taken from 5 sequential replicates.

first: Melissa

last: Eccles

first: Alex

last: Garnham


title: Neuronal-Activity Dependent Mechanisms of Small Cell Lung Cancer Pathogenesis

first: Carlos Alberto

middle: Oliveira de

last: Biagi Junior

address: 360 Longwood Ave

department: Pediatric Oncology

institute: Dana Farber Cancer Institute

summary: Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth both through paracrine mechanisms and through electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses. Outside of the CNS, innervation of tumors such as prostate, breast, pancreatic and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression. However, the extent to which the nervous system regulates lung cancer progression, either in the lung or when metastatic to brain, is less well understood. Small cell lung cancer (SCLC) is a lethal high-grade neuroendocrine tumor that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that SCLC cells in the brain co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. Glutamatergic and GABAergic cortical neuronal activity each drive proliferation of SCLC in the brain through both paracrine and synaptic neuron-cancer interactions. In the brain, SCLC cells form bona fide neuron-to-SCLC synapses and exhibit depolarizing currents with consequent calcium transients in response to neuronal activity. SCLC cell membrane depolarization is sufficient to promote the growth of intracranial tumors. In the lung, vagus nerve transection markedly inhibits primary lung tumor formation and development, highlighting a critical role for innervation in overall SCLC growth. Taken together, these studies illustrate that neuronal activity plays a crucial role in dictating SCLC pathogenesis in both the lung and the brain.

overall_design: Single cell transcriptomic profiling of the SCLC cells using co-culture systems in which cortically derived murine neurons, representing a mixture of glutamatergic and GABA-ergic subpopulations, were cultured together with murine 16T line of SCLC cells. In both cases, the presence of active neurons significantly increased the rate of proliferation of SCLC cells in co-culture. This effect was abrogated with the addition of tetrodotoxin (TTX), a voltage-gated sodium channel blocker that silences neuronal action potentials.

first: Solomiia

last: Savchuk

first: Wengang

last: Wang

first: Kaylee

last: Gentry

first: Elana

last: Carleton

first: Carlos

last: Biagi-Junior

first: Belgin

last: Yalçın

first: Lijun

last: Ni

first: Hannah

last: Farnsworth

first: Rachel

last: Davis

first: Yin

last: Liu

first: Lehi

last: Acosta-Alvarez

first: Griffin

last: Hartmann

first: Elisa

last: Pavarino

first: Jenna

last: LaBelle

first: Angus

last: Toland

first: Pamelyn

last: Woo

first: Fangfei

last: Qu

first: Mariella

last: Filbin

first: Mark

last: Krasnow

first: Keith

last: Ligon

first: Julien

last: Sage

last: Sabatini

first: Michelle

last: Monje

first: Humsa

last: Venkatesh


title: Senataxin regulates cisplatin resistance through an R-loop mediated mechanism in HPV-associated Head and Neck Cancer

city: Sheffield

last: Crane

address: Western Bank

institute: University of Sheffield

summary: Resistance to cisplatin is a key clinical concern in HPV-independent (HPV-) and HPV-associated (HPV+) head and neck cancer. Upregulation of DNA repair is known to contribute to cisplatin resistance and a major source of endogenous DNA damage are DNA/RNA hybrids, known as R-loops. Following creation of HPV+ and HPV- cisplatin resistant cell lines, RNA-Sequencing revealed alterations in the expression of known R-loop regulators. Resistant cells had elevated global R-loop levels and in HPV+ resistant cells there was a corresponding upregulation of the R-loop resolving protein, senataxin. Depletion of senataxin led to increased sensitivity to cisplatin, an increase in DNA damage and elevated R-loops at specific genomic loci. In summary, using an in vitro model of cisplatin resistance, we identified that senataxin modulates sensitivity to cisplatin through an R-loop mediated mechanism in HPV+ cells. R-loops may represent a potential therapeutic target and warrant further investigation.

overall_design: To investigate cisplatin resistance in HPV+ and HPV- cells, cisplatin resitance clones were developed and RNA-Sequencing was carried out on the parental clones and their resistant counterparts.

first: Ian

last: Carr

last: Hunter

first: Sherif

last: El-Khamisy


title: Inflammatory, transcriptomic and cell fate responses underlying the mammalian transmission of avian influenza viruses

city: Hong Kong

last: Zanin

state: Pokfulam

address: 7 Sassoon Road

department: School of Public Health

country: Hong Kong

institute: The University of Hong Kong

summary: Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component to their pandemic risk. While several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinant of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, here we describe host responses that segregate with AT phenotypes (DE300 and DE256 were AT and DE558 and DE213 were not AT). AIV infection upregulated interferon alpha and gamma responses, IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation. Single cell transcriptomics revealed that cellular genotoxic stress, NF-kB, interferon and cell fate pathways differentiated host responses to AIVs with different transmissibility. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100 and CXCL10 transcription in infected epithelia were a hallmark of AT viruses. Overall, our study reveals host responses associated with AIV infection and transmission in the nasal epithelium, the determinant anatomical site of influenza virus transmission.

overall_design: RNAseq data from the upper respiratory tract of ferrets inoculated with avian influenza viruses at two days post inoculation (n=4 ferrets per virus and PBS mock inoculated)

first: Kristine

last: Piza

first: Timothy

last: Flerlage


title: Inflammatory, transcriptomic and cell fate responses underlying the mammalian transmission of avian influenza viruses, bulk RNAseq.

summary: Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component to their pandemic risk. While several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinant of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, here we describe host responses that segregate with AT phenotypes. AIV infection upregulated interferon alpha and gamma responses, IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation. Single cell transcriptomics revealed that cellular genotoxic stress, NF-kB, interferon and cell fate pathways differentiated host responses to AIVs with different transmissibility. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100 and CXCL10 transcription in infected epithelia were a hallmark of AT viruses. Overall, our study reveals host responses associated with AIV infection and transmission in the nasal epithelium, the determinant anatomical site of influenza virus transmission.


title: Prenatal nicotine exposure induces epigenetic alterations in the Notch signaling genes in the proximal colon in rats [RNA-seq]

city: Rennes

first: Fatima

last: SMAGULOVA

address: 9 av. Prof. Léon Bernard

institute: Irset - U1085

summary: Background. Prenatal nicotine exposure (PNE) has been shown to significantly impact fetal development, leading to various pathologies in adulthood, including those affecting the digestive system. Despite considerable attention from the scientific community on the health effects of nicotine consumption, the epigenetic effects of nicotine on the colon remain poorly understood.  Objective, in this study, we analyzed the epigenetic effects of nicotine on the proximal colon.

overall_design: Methods. Sprague-Dawley rats were exposed to nicotine during gestation with dose 6mg/kg/bw. The proximal colon of male progeny was analyzed at 11 weeks of age.  RNA was extracted using a RNeasy plus kit and treated with a DNAse kit from Qiagen directly on the column. 1000 ng of RNA were used for library preparation using NEBNext® Ultra™ II DNA Library Prep Kit for Illumina and indexed primers. Transcriptomics analysis of the proximal colon was carried out by paired-end RNA sequencing.

last: Smagulova


title: Fetal Response to Maternal Exposures to Environmental Chemicals: Utility of a Four-Cell Human Feto-Maternal Interface Organ-on-Chip

city: College Station

first: Ivan

last: Rusyn

state: TX

address: VIDI(Veterinary Medicine 2), 2, 402 Raymond Stotzer Pkwy

department: Interdisciplinary Faculty of Toxicology

institute: Texas A&M University

summary: Epidemiological studies suggest that maternal exposures to environmental chemicals may be linked to spontaneous preterm birth. Mechanistic studies are needed to provide support to these hypotheses; however, existing in vitro models do not replicate the human feto-maternal barriers beyond placenta. The recently developed four-cell (human immortalized maternal decidua, chorion trophoblast, amnion mesenchymal, and amnion epithelial cells) Feto-Maternal interface Organ-On-Chip (FMi-OOC) enables studies of chemical effects on the decidua, chorion and amnion, maternal and fetal tissues that are critically important for maintaining full-term pregnancy. We tested four environmental compounds that have been associated with preterm birth – dichlorodiphenyltrichloroethane (DDT-o,p’), bisphenol A (BPA), 2,2'4,4'-tetrabromodiphenyl ether (PBDE-47), and perfluorooctanoic acid (PFOA). First, concentration-response effects of these chemicals were tested on maternal decidua cells in 96-well plates. Then, experiments were performed in FMi-OOC containing four fetal-maternal cell types arranged into four concentric chambers, mimicking the in utero cell topology. Compounds were added to the maternal (i.e., decidua) chambers, and chemical propagation, cell viability and proinflammatory cytokines (IL-6, IL-8, GM-CSF, TNF-α) were measured in decidua, chorion trophoblast, amnion mesenchymal, and amnion epithelial cells for up to 72 hrs. Minimal propagation of test compounds to fetal chambers was observed and tested concentrations were non-cytotoxic. Treatment-associated increase in cytokine production was observed for all compounds, with PFOA and BPA showing the strongest effects and amnion epithelial cells being the most responsive. We demonstrate how the multi-cellular FMi-OOC model can be used to study paracrine signaling in complex human tissues such as fetal-maternal interface. In addition, these studies provide mechanistic support for the plausibility of the epidemiological associations between maternal exposures to tested compounds and preterm birth. We show that upon maternal exposure, albeit at concentrations exceeding reported human blood levels by 1 to 2 orders of magnitude, fetal membranes attain a pro-inflammatory state, a potential trigger for preterm birth.

overall_design: Comparative gene expression profiling analysis of TempO-Seq data for immortalization of human maternal decidua (DEC), amnion mesenchymal (AMC) cells, and amnion epithelial (AEC) cells, genes that are over-expressed in certain cell types, and how these cells compared with the published dataset.

first: Haley

last: Moyer

first: Sungjin

last: Kim

first: Bowie

last: Lam

first: Lauren

last: Richardson

first: Han-Hsuan

last: Tsai

first: Lucie

last: Ford

first: Ramkumar

last: Menon

first: Arum

last: Han


title: Prenatal nicotine exposure induces epigenetic alterations in the Notch signaling genes in the proximal colon in rats [MeDIP-seq]

type: Methylation profiling by high throughput sequencing

summary: Background. Prenatal nicotine exposure (PNE) has been shown to significantly impact fetal development, leading to various pathologies in adulthood, including those affecting the digestive system. Despite considerable attention from the scientific community on the health effects of nicotine consumption, the epigenetic effects of nicotine on the colon remain poorly understood.  Objective,  in this study, we analyzed the epigenetic effects of nicotine on the proximal colon.

overall_design: Sprague-Dawley rats were exposed to nicotine during pregnancy and male progeny was analyzed at age of 11 weeks. A genome-wide DNA methylation was analyzed using MeDIP-seq.


title: Transcriptome analysis in brown adipose tissue of mice lacking ATF4 in thermogenic adipocytes

city: Iowa City

first: Renata

last: Pereira

state: Iowa

address: 169 Newton Rd

department: Internal Medicine

institute: University of Iowa

summary: mRNA expression profiles from interscapular brown adipose (iBAT) tissue male ATF4 BAT KO mice and their WT counterparts after 12 weeks of high fat diet.

overall_design: Samples were collected from ad libitum fed ATF4 BAT KO male mice and their WT counterparts after 12 weeks of 60% high fat diet.

first: Eric

last: Weatherford


title: Multiplex base editing of BCL11A regulatory elements to treat sickle cell disease

city: Padova

first: Oriana

last: Romano

address: Via U. Bassi 58/B

department: Molecular Medicine

country: Italy

institute: University of Padova

summary: Sickle cell disease (SCD) is a genetic anemia caused by the production of an abnormal adult hemoglobin. The clinical severity is lessened by elevated fetal hemoglobin (HbF) production in adulthood. A promising therapy is the transplantation of autologous, hematopoietic stem/progenitor cells (HSPCs) treated with CRISPR/Cas9 to downregulate the HbF repressor BCL11A via generation of double strand breaks (DSBs) in the +58-kb erythroid-specific enhancer. Here, to further enhance HbF production without increasing the mutagenic load, we targeted both +58-kb and +55-kb BCL11A erythroid-specific enhancers using base editors. We systematically dissected DNA motifs recognized by the key transcriptional activators within these regions and identified the critical nucleotides required for activator binding. Multiplex base editing of these residues was efficient and safe and generated no or little DSBs and genomic rearrangements. We observed substantial HbF reactivation, exceeding the levels achieved using the CRISPR/Cas9 nuclease-based strategy, thus efficiently rescuing the sickling phenotype. Multiplex base editing was efficient in long-term repopulating HSPCs and resulted in potent HbF reactivation in vivo. In summary, these results show that multiplex base editing of BCL11A erythroid-specific enhancers is a safe and potent strategy for treating sickle cell disease.

overall_design: We performed RNA-seq analysis in SCD CD34+ HSPCs (3 donors) that were preactivated for 2 days, then electroporated with a combination of base editors mRNA or Cas9 nuclease RNP and sgRNA targeting the +58-kb and +55-kb BCL11A enhancers, and then cultured for 2 additional days. Cells electroporated with TE buffer only or with epigenome editors mRNA only were used as controls.

first: Letizia

last: Fontana

last: Romana

first: Annarita

last: Miccio

first: Panagiotis

last: Antoniou


title: Role of HPV E5 in promoting resistance towards conventional chemotherapy and radiation in Head and neck squamous cell carcinoma (HNSCC)

city: La Jolla

first: Souvick

last: Roy

address: 3855 Health Sciences Dr

institute: University of California San Diego

summary: In this study, we used empty vector (EV), HPV16 E5- transduced and HPV16 E6E7-transduced CAL-27 cells to perform RNA-seq analysis. The data obtained from RNA-seq analysis was further used for differential gene expression and pathway enrichment analysis.

overall_design: Differential gene expression profiling of RNA-seq data for empty vector, CAL-27 E5 and CAL-27 E6E7 cells.

first: Sayuri

last: Miyauchi

first: Andrew

middle: B

last: Sharabi


title: Fruit surface topography, timely transcriptional responses, and reduced susceptibility factors enhance anthracnose resistance in papaya

city: Davis

first: Barbara

last: Blanco-Ulate

address: One Shields Ave

department: Plant Sciences

institute: University of California Davis

summary: Anthracnose disease, caused by Colletotrichum spp., leads to significant postharvest losses in papaya fruit. In this study, we identified a papaya genotype with quantitative resistance to anthracnose and investigated the mechanisms underlying this resistance using microscopy, fruit physicochemical analyses, and transcriptomics. The resistant genotype exhibited several beneficial traits compared to a susceptible genotype, including a thicker cuticular layer, lower stomatal density, greater firmness, and lower total soluble sugars. These characteristics can be considered preformed barriers or constitutive defenses or correlate with reduced susceptibility factors. We also found that the resistant genotype responds more rapidly to fungal presence by synthesizing components that maintain surface and cell wall integrity, such as cutin and cuticular elements, and by depositing callose. In contrast, the susceptible genotype had accumulated more susceptibility factors, including elevated sugar content and activation of CW-degrading enzymes. While the susceptible genotype had a more robust immune response at the later stages of infection, the combination of susceptibility factors and a delayed response to the pathogen was insufficient to control the disease. This study highlights the need to characterize potential susceptibility factors and physicochemical traits to better understand fruit-pathogen interactions. Such knowledge can provide breeding programs with strong targets for developing crop varieties that are less susceptible to fungal diseases yet maintain quality traits that consumers expect.

overall_design: Comparative transcriptomic analysis of natural anthracnose infections (Colletotrichum gloeosporioides, Colletotrichum truncatum) of Carica papaya at 5 and 6 days post harvest.

first: David

last: Perez-Leyva

first: Saskia

last: Mesquida-Pesci

first: Flor

middle: F

last: Rosas-Cardenas

first: Maria

last: Perea-Flores

first: Norma

last: Leyva-Lopez

last: Santos-Cervantes


title: Single-cell epigenetic, transcriptional, protein, and TCR states of HIV-1-infected cells in gut

status: Public on Jul 27 2025

city: New Haven

first: Yulong

last: Wei

state: CT

address: 295 Congress Avenue

department: Microbial Pathogenesis

institute: Yale University

summary: Tissue resident memory T cells (TRMs) are essential to mucosal immunity. We postulate that their long-lived tissue residency and restricted effector function promote HIV-1 persistence in human gut. We coupled single-cell-DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptor, HIV-1 DNA, and HIV-1 RNA in gut CD4+ and CD8+ T cells from ten aviremic HIV-1+ individuals and five HIV-1- donors. We found that BACH2, a transcription repressor that establishes long-lived memory in T cells, is the leading transcription factor that shapes gut TRMs into long-lived memory and restrains interferon-driven effector function.

overall_design: Colon primary cells from 10 PLWH and five HIV-1 negative donors were processed for DOGMA-seq. For each sample, cells were split into two aliquots, one for CD3+ T cell enrichment (_CD3) and the other for whole gut primary cell sequencing (_whole). Colon cells were processed through  dead-cell removal by negative selection. For the whole gut aliquots, cells from each participant  were stained by uniquely barcoded TotalSeq-A hashing antibodies and pooled. Cells were then stained with a panel of 154 cell surface proteins and 9 isotype controls included in TotalSeq-A Human Universal Cocktail and with TotalSeq-A CCR7. After staining, cells were permeabilized with 0.01% digitonin. Cells were then loaded into the 10x Genomics Chromium Controller for DOGMA-seq (3’ Single Cell 10x Multiome (ATAC + GEX) with feature barcoding). This resulted in libraries for the single cell epigenome, transcriptome, and surface proteome. Leftover cell-barcoded cDNA libraries were used to perform TREK-seq to enrich and sequence for TCR sequences.

first: Haocong Katherine

last: Ma

first: Michelle E.

last: Wong

first: Hyein

last: Back

first: Emmanouil

last: Papasavvas

first: Karam

last: Mounzer

first: Fatema

last: Aberra

first: Ricardo

last: Morgenstern

first: Pablo

last: Tebas

first: Liza

last: Konnikova

first: Luis J.

last: Montaner

first: Ya-Chi

last: Ho


title: Matrix directs trophoblast differentiation in a bioprinted organoid model of early placental development

city: Sydney

first: Hao

last: Chen

state: NSW

address: 745 Harris St

department: Faculty of Science

institute: University of Technology Sydney

summary: Trophoblast organoids can provide crucial insights into mechanisms of placentation, however their potential is limited by highly variable extracellular matrices unable to reflect in vivo tissues. Here, we present a bioprinted placental organoid model, generated using the first trimester trophoblast cell line, ACH-3P, and a synthetic polyethylene glycol (PEG) matrix. Bioprinted or Matrigel-embedded organoids differentiate spontaneously from cytotrophoblasts into two major subtypes: extravillous trophoblasts (EVTs) and syncytiotrophoblasts (STBs). Bioprinted organoids are driven towards EVT differentiation and show close similarity with early human placenta or primary trophoblast organoids. Inflammation inhibits proliferation and STBs within bioprinted organoids, which aspirin or metformin (0.5 mM) cannot rescue. We reverse the inside-out architecture of ACH-3P organoids by suspension culture with STBs forming on the outer layer of organoids, reflecting placental tissue. Our bioprinted methodology is applicable to trophoblast stem cells. We present a high-throughput, automated, and tuneable trophoblast organoid model that reproducibly mimics the placental microenvironment in health and disease.

overall_design: ACH-3P first trimester trophoblast cell line was cultured as organoids in a tranditional Matrigel and was in bioprinted as organoids using RASTRUM bioprinter (Inventia Life Science). Bioprinted and matrigel-embedded organoids were dissociated to single cells by accutase. Single-cell RNA sequencing was performed on the single cells extracted from approximately 700 organoids in total.

first: Claire

last: Richards

first: Matthew

last: O’Rourke

first: Grace

last: Owen

first: Alexander

last: Volkerling

first: Arnab

last: Ghosh

first: Catherine

last: Gorrie

first: David

middle: G

last: Ortega

first: Amy

last: Bottomley

first: Louise

last: Cole

first: Kristine

last: McGrath

last: Padula

first: Philip

last: Hansbro

first: Lana

last: McClements


title: Rocker or Pump? Transcriptomic Response of Endothelial Cells Exposed to Peristaltic Pump-Based Unidirectional Flow vs. Rocker-Induced Bidirectional Flow

city: Bern

first: Olivier

middle: Thierry

last: Guenat

address: Murtenstrasse 50

department: ARTORG Center for Biomedical Engineering Research

country: Switzerland

institute: University of Bern

summary: Rocking-platform perfusion systems rely on hydrostatic pressure differences to perfuse cells in organ-on-chip devices. These systems are popular due to their tubing-free design, which facilitates parallelization, an essential feature for drug discovery, precision medicine, and academic research. However, most of these systems generate bidirectional flow, which does not accurately replicate the physiological conditions experienced by endothelial cells (ECs) in the microvasculature. To address this limitation, pump-based systems are often employed to generate unidirectional flow, though they require external tubing, thereby limiting scalability compared to rocking platforms. In this study, we compared the transcriptomic responses of endothelial cells exposed to flow generated either by a rocking platform or a peristaltic pump, under matched average flow rates. Our results revealed distinct transcriptomic profiles induced by the two flow modalities, with hundreds of genes differentially expressed between the two conditions. After 4 hours of flow exposure, we observed an enrichment in signaling pathways including NF-κB, ERK, BMP and MAPK. Furthermore, after 24 hours of flow exposure, we identified significant changes in the genes involved in biological processes such as immune cell migration, angiogenesis and vascular and extracellular matrix remodeling, highlighting how different flow generated by pump or rokcer can shape endothelial cell behavior at the molecular level.

overall_design: Human umbilical vein endothelial cells between passage 4 and 6 were exposed to either pump-based unidirectional or rocker-induced bidirectional flow for 4h and 24h in three replicates. Bulk RNA-seq was performed to study the effect of flow type on the gene expression profile of the endothelial cells.

first: Negar

last: Vahdani

first: Prateek

last: Arora

first: Lisette

last: Van Os

first: Denise

last: Ackermann

first: Nadia

last: Mercader


title: Direct circMAN1A2(2,3,4,5)-CENPB mRNA interaction regulates cell proliferation and cancer progression

city: Shanghai

first: Li

last: Yang

address: 131 Dong-An Road

department: Institutes of Biological Sciences

institute: Fudan University

summary: A large number of covalently closed circular RNAs (circRNAs), produced from back-splicing of eukaryotic exons, have been identified among different cell lines/tissues. Interestingly, multiple circRNAs could be produced from a single gene locus through alternative circularization (AC), expanding the complexity and diversity of circRNAs. However, functions of most AC circRNAs remains poorly understood. Here, we profiled the landscape of AC across multiple cell lines and colorectal cancer (CRC) tissues, identifying predominantly expressed circRNAs (pe-circRNA) in each AC gene loci. While the expression of top pe-circRNAs exhibits a cell-type-specific manner, circMAN1A2(2,3,4,5), a pe-circRNA that is universally expressed in examined cells and CRC samples, was shown to play an important role in cell proliferation and CRC progression. Mechanistically, circMAN1A2(2,3,4,5) directly interacted with the 3' untranslated region of Centromere Protein B (CENPB) mRNA via its characteristic back-splicing junction site, which enhanced IGF2BP2-mediated CENPB mRNA stability. Inhibition of circMAN1A2(2,3,4,5) expression with specific shRNAs and locked nucleic acids (LNAs) resulted in repressed cell proliferation and tumor progression in the subcutaneous mouse CRC model. These results together uncover the prevalence of AC and the regulatory role of a specific AC circRNA, circMAN1A2(2,3,4,5), in cell proliferation and tumor progression.

overall_design: Total RNA-seq (rRNA depletion) of circMAN1A2(2,3,4,5) KD cells are used for circMAN1A2(2,3,4,5) function analysis.

first: Ling-Ling

last: Chen

first: Mei

last: Cao

first: Guo-Hua

last: Yuan

first: Shi-Meng


title: Glioma-associated microglia and macrophages as a potential target for mTOR inhibition in glioblastoma

city: Freiburg

first: Michael

last: Schulz

address: Breisacher Straße 64

department: Institute for Neuropathology

institute: University Hospital Freiburg

summary: Introduction: Glioma-associated microglia/macrophages (GAM) constitute the predominant immune cell population in glioblastoma (GB). Both GB cells and GAM exhibit upregulated mTOR signaling. This study aimed to investigate the effects of pharmacological mTOR inhibition (mTORi) specifically on GAM.Materials and Methods: We conducted a comprehensive analysis of the GAM phenotype, including whole transcriptome analyses and cytokine profiling. Effects were investigated in a tumor cell/GAM co-culture model under mTORi with rapamycin or torin2 or under treatment with temozolomide, the standard chemotherapy agent for GB patients.Results: In our in vitro model, mTORi had significant effects on central biological functions of GAM, resulting in reduced proliferation and oxygen consumption. Additionally, treatment with mTORi induced a pro-inflammatory phenotype in microglial cells.Conclusions: Our findings demonstrate the profound relevance of mTOR signaling on GAM biology. Moreover, they provide rationales for therapeutic interventions targeting mTOR signaling specifically in GAM as a potential novel treatment strategy.

overall_design: bulk RNA-Seq (each in triplicate per condition) data of tumor-cell stimulated and treated (rapamycin, temozolomide, control)  two different (C20 and HMC3) human microglia cell lines

first: Pia

last: Zeiner

last: Ronnellenfitsch


title: Chemical stimuli override a temperature-dependent morphological program by reprogramming the transcriptome

city: San Francisco

first: Mark

last: Voorhies

address: 513 Parnassus, S472

department: Microbiology and Immunology

institute: University of California

summary: The human fungal pathogen Histoplasma changes its morphology in response to temperature. At 37°C it grows as a budding yeast whereas at room temperature it transitions to hyphal growth. Prior work has demonstrated that 15-20% of transcripts are temperature-regulated, and that transcription factors Ryp1-4 are necessary to establish yeast growth. However, little is known about transcriptional regulators of the hyphal program. To identify TFs that regulate filamentation, we utilize chemical inducers of hyphal growth. We show that addition of cAMP analogs or an inhibitor of cAMP breakdown overrides yeast morphology, yielding inappropriate hyphal growth at 37°C. Additionally, butyrate supplementation triggers hyphal growth at 37°C. Transcriptional profiling of cultures filamenting in response to cAMP or butyrate reveals that a limited set of genes respond to cAMP while butyrate dysregulates a larger set.  Comparison of these profiles to previous temperature- or morphology-regulated gene sets identifies a small set of morphology-specific transcripts. This set contains 9 TFs of which we characterized three, STU1, FBC1, and PAC2, whose orthologs regulate development in other fungi. We found that each of these TFs is individually dispensable for room-temperature (RT) induced filamentation but each is required for other aspects of RT development. FBC1 and PAC2, but not STU1, are necessary for filamentation in response to cAMP . Ectopic expression of each of these TFs is sufficient to induce filamentation at 37°C. Finally, PAC2 induction of filamentation at 37°C is dependent on STU1, suggesting these TFs form a regulatory circuit that, when activated at RT, promotes the hyphal program.

overall_design: Expression profiling by RNA-seq of Histoplasma yeast cells treated with cAMP analogs or butyrate with three bioreps per treatment.

first: Dror

last: Assa

first: Anita

last: Sil


title: The B Cell Subtypes and VDJ Repertoire of Young Adult Rhesus Macaques

status: Public on Jul 26 2025

city: Baltimore

first: Andy Kwan Pui

last: Chan

address: 615 N Wolfe Street

department: Molecular Microbiology and Immunology

institute: Johns Hopkins University

summary: Rhesus macaques (RMs) are widely employed as a pre-clinical model in vaccination and infectious disease studies, yet their B cell immunobiology and immunogenetics remain ill-characterized. In this study, single-cell RNA/VDJ-seq (scRNA/VDJ-seq) was conducted on peripheral blood mononuclear cell (PBMC) samples from six RMs to describe the transcriptomic and V(D)JC repertoires of B cells and subtypes. 12 RM B cell clusters of distinct transcriptional states were identified, including  IgM+ memory B cells (MBC), class-switched MBC, CD11c+ MBC and activated B cells. Novel gene signatures were also characterized for each B cell subtype, such as FCRL2 and CD24 for circulating marginal-zone-like B cells. In addition, VDJ repertoire properties of the global B cell population and each B cell subtype were elucidated, including IGH/K/L-V(D)JC gene family and subtype usage, class-switch recombination (CSR) status, somatic hypermutation (SHM) rate and levels, complementarity-determining region heavy chain (CDRH3) amino acid (AA) length and CDRH3 AA hydrophobicity scores. Interesting insights included the 1:1 ratio of kappa and lambda light chain usage and a preferential decreased IGHV3 but increased IGHV1 and 5 gene family usage in IGHG1 than IGHM-bearing B cells. Altogether, this study through comprehensive transcriptomic analyses identifies 12 distinct RM B cell subtypes paired with their respective V(D)JC repertoire, unraveling the complexity of B cell heterogeneity and improving future pre-clinical studies that can translate insights from this important non-human primate model to the understanding of human immunobiology.

overall_design: 6 peripheral blood mononuclear cells (PBMCs) samples from healthy juvenile Indian-origin rhesus macaques (RMs), 2 male and 4 female, 2-3 years old, Macaca mulatta, were collected for single-cell RNA and VDJ sequencing.

first: Andy K.P.

first: Diane E.

last: Griffin


title: p52:ETS1: a transcriptional complex essential for germinal center formation [ChIP-seq]

city: Singapore

first: Vinay

last: Tergaonkar

address: 61 Biopolis Drive, Proteos

department: Institute of Molecular and Cell Biology (IMCB)

country: Singapore

institute: Agency for Science, Technology and Research (A*STAR)

summary: It is well-established that the five transcription factors of the NFκB family form homo/hetero dimers amongst themselves to regulate gene expression by binding DNA. Our study challenges this paradigm by showing that p52 activates transcription without directly binding DNA but as part of a hetero-tetrameric partnership with ETS1, a transcription factor outside the NFκB family. By generating a knock-in mouse model (p52ki/ki) with three mutated residues on p52 required for its interactions with ETS1 but not with RelB, we demonstrate that the p52:ETS1 complex is the hitherto undiscovered regulator of transcription factors, OCT1 and OBF1, known to be critical for the germinal centre (GC) program. Consequently B cell-intrinsic expression of p52:ETS1 complex is indispensable for splenic GC B cell formation and T cell-dependent antibody responses. Functionally, loss of p52:ETS1 interaction led to diminished antigen-specific IgE thereby protecting mice from allergic responses. Collectively, our expand our current knowledge of NFkB signalling and provide new therapeutic targets for the treatment of allergic diseases.

overall_design: ChIP-Seq of OCI-LY3 human cell lines

first: Dhakshayini

last: Morgan

first: Biyan

last: Zhang

first: Kerem

last: Fidan


title: p52:ETS1: a transcriptional complex essential for germinal center formation [RNA_Seq_GCB]

overall_design: RNA-Seq profiling of WT and p52 knock-in mouse spleen pre-GC and GC B cells.


title: mRNA sequencing of human AC16 cells expressing PCBP1, PCBP2, or both

status: Public on Jul 25 2025

city: Aurora

first: Edward

last: Lau

state: CO

address: 12700 E19th Av RCII Rm 8004

department: Medicine/Cardiology

institute: University of Colorado

summary: To explore potential functional implications of isoform usage shifts, we examined the effect of PCBP1/PCBP2 expression in human AC16 cardiac cells. PCBP1/PCBP2 are KH-domain-containing RNA-binding proteins (RBP)  that have been implicated in transcriptional, post-transcriptional and translational regulations. How PCBP1 and PCBP2 are functionally differentiated remains a subject of interest and few reports have outlined their function in cardiac cells. The two paralogs share close homology (~85% identical sequences) and partially overlapping RNA binding targets, suggesting they may form mutually regulatory relationships. Human and mouse PCBP1 sequences share 100.0% identity, whereas human and mouse PCBP2 are identical except in 5 positions; therefore we expressed the human/mouse PCBP1 and human PCBP2 coding sequences in human AC16 cardiac cells. Immunofluorescence imaging confirms broad cytonuclear localization of both paralogs under overexpression. The cells were then subjected to RNA sequencing to determine the effects of PCBP1/2 on gene expression.

overall_design: RNA sequencing of human AC16 cardiac cells (Millipore) expressing human PCBP1::Halo plasmid, PCBP2::Halo plasmid, both, or neither, 3 replicates each.

first: Maggie

last: Lam

first: Shaonil

last: Binti